Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 7149 

DEPARTMENT OF HOMELAND 

SECURITY 

6 CFR Part 46 

DEPARTMENT OF AGRICULTURE 

7 CFR Part 1c 

DEPARTMENT OF ENERGY 

10 CFR Part 745 

NATIONAL AERONAUTICS AND 

SPACE ADMINISTRATION 

14 CFR Part 1230 

DEPARTMENT OF COMMERCE 

15 CFR Part 27 

SOCIAL SECURITY ADMINISTRATION 

20 CFR Part 431 

AGENCY FOR INTERNATIONAL 

DEVELOPMENT 

22 CFR Part 225 

DEPARTMENT OF HOUSING AND 

URBAN DEVELOPMENT 

24 CFR Part 60 

DEPARTMENT OF LABOR 

29 CFR Part 21 

DEPARTMENT OF DEFENSE 

32 CFR Part 219 

DEPARTMENT OF EDUCATION 

34 CFR Part 97 

DEPARTMENT OF VETERANS 

AFFAIRS 

38 CFR Part 16 

ENVIRONMENTAL PROTECTION 

AGENCY 

40 CFR Part 26 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

45 CFR Part 46 

RIN 0937–AA02 

NATIONAL SCIENCE FOUNDATION 

45 CFR Part 690 

DEPARTMENT OF TRANSPORTATION 

49 CFR Part 11 

Federal Policy for the Protection of 

Human Subjects 

AGENCY: Department of Homeland 

Security; Department of Agriculture; 

Department of Energy; National 

Aeronautics and Space Administration; 

Department of Commerce; Social 

Security Administration; Agency for 

International Development; Department 

of Housing and Urban Development; 

Department of Labor; Department of 

Defense; Department of Education; 

Department of Veterans Affairs; 

Environmental Protection Agency; 

Department of Health and Human 

Services; National Science Foundation; 

and Department of Transportation. 

ACTION: Final rule. 

SUMMARY: The departments and agencies 

listed in this document announce 

revisions to modernize, strengthen, and 

make more effective the Federal Policy 

for the Protection of Human Subjects 

that was originally promulgated as a 

Common Rule in 1991. This final rule 

is intended to better protect human 

subjects involved in research, while 

facilitating valuable research and 

reducing burden, delay, and ambiguity 

for investigators. These revisions are an 

effort to modernize, simplify, and 

enhance the current system of oversight. 

DATES: This rule is effective on January 

19, 2018. The compliance date for this 

rule, except for §ll.114(b) 

(cooperative research), is January 19, 

2018. The compliance date for 

§ ll.114(b) (cooperative research) is 

January 20, 2020. 

ADDRESSES: Jerry Menikoff, M.D., J.D., 

OHRP, 1101 Wootton Parkway, Suite 

200, Rockville, MD 20852. 

FOR FURTHER INFORMATION CONTACT: Jerry 

Menikoff, M.D., J.D., Office for Human 

Research Protections (OHRP), 

Department of Health and Human 

Services, 1101 Wootton Parkway, Suite 

200, Rockville, MD 20852; telephone: 

240–453–6900 or 1–866–447–4777; 

facsimile: 301–402–2071; email: 

jerry.menikoff@hhs.gov. 

SUPPLEMENTARY INFORMATION: 

Preamble 

Executive Summary 

I. The Rationale for Modernizing the 

Common Rule 

II. To What Does This Policy Apply? Scope 

and Applicability of the Regulations 

III. Definitions for Purposes of this Policy 

(§ll.102) 

IV. Ensuring Compliance with this Policy 

(§ll.103) 

V. Exempt Research (§ll.104) 

VI. Protection of Identifiable Private 

Information and Identifiable 

Biospecimens 

VII. IRB Membership and Modification to 

References to Vulnerability 

(§§ll.107(a), ll.111(a)(3), and 

ll.111(b)) 

VIII. IRB Functions and Operations 

(§ll.108) 

IX. IRB Review of Research (§ll.109) 

X. Expedited Review Procedures (§ll.110) 

XI. Criteria for IRB Approval of Research 

(§ll.111) 

XII. Cooperative Research (§ll.114) 

XIII. IRB Records (§ll.115) 

XIV. General Requirements for Informed 

Consent (§ll.116) 

XV. Documentation of Informed Consent 

(§ll.117) 

XVI. Applications and Proposals Lacking 

Definite Plans for Involvement of Human 

Subjects (§ll.118) 

XVII. Research Undertaken Without the 

Intention of Involving Human Subjects 

(§ll.119) 

XVIII. Conditions (§ll.124) 

XIX. Regulatory Impact Analyses 

XX. Environmental Impact 

XXI. Paperwork Reduction Analysis 

XXII. Tribal Consultation Statement 

Final Regulatory Text 

Executive Summary 

Purpose of the Regulatory Action 

Individuals who are the subjects of 

research may be asked to contribute 

their time and assume risk to advance 

the research enterprise, which benefits 

society at large. U.S. federal regulations 

governing the protection of human 

subjects in research have been in 

existence for more than three decades. 

The Department of Health, Education, 

and Welfare first published regulations 

for the protection of human subjects in 

1974, and the Department of Health and 

Human Services (HHS) revised them in 

the early 1980s. During the 1980s, HHS 

began a process that eventually led to 

the adoption of a revised version of the 

regulations by 15 U.S. federal 

departments and agencies in 1991. The 

purpose of this effort was to promote 

uniformity, understanding, and 

compliance with human subject 

protections as well as to create a 

uniform body of regulations across 

federal departments and agencies 

(subpart A of 45 Code of Federal 

Regulations [CFR] part 46), often 

referred to as the ‘‘Common Rule’’ or 

‘‘Protection of Human Subjects 

Regulations.’’ Those regulations were 

last amended in 2005, and have 

remained unchanged until the issuance 

of this final rule. 

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7150 Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 

1HHS. Human Subjects Research Protections: 

Enhancing Protections for Research Subjects and 

Reducing Burden, Delay, and Ambiguity for 

Investigators. 76 FR 44512 (Jul. 26, 2011). Retrieved 

from https://www.gpo.gov/fdsys/pkg/FR-2011-07- 

26/pdf/2011-18792.pdf 

2HHS. Federal Policy for the Protection of 

Human Subjects. 80 FR 53931 (Sept. 8, 2015). 

Retrieved from https://www.federalregister.gov/ 

documents/2015/09/08/2015-21756/federal-policyfor-the-protection-of-human-subjects 

Since the Common Rule was 

promulgated, the volume and landscape 

of research involving human subjects 

have changed considerably. Research 

with human subjects has grown in scale 

and become more diverse. Examples of 

developments include: an expansion in 

the number and types of clinical trials, 

as well as observational studies and 

cohort studies; a diversification of the 

types of social and behavioral research 

being used in human subjects research; 

increased use of sophisticated analytic 

techniques to study human 

biospecimens; and the growing use of 

electronic health data and other digital 

records to enable very large datasets to 

be rapidly analyzed and combined in 

novel ways. Yet these developments 

have not been accompanied by major 

change in the human subjects research 

oversight system, which has remained 

largely unaltered over the past two 

decades. 

On July 26, 2011, the Office of the 

Secretary of HHS, in coordination with 

the Executive Office of the President’s 

Office of Science and Technology Policy 

(OSTP), published an advance notice of 

proposed rulemaking (ANPRM) to 

request comment on how current 

regulations for protecting those who 

participate in research might be 

modernized and revised to be more 

effective.1

On September 8, 2015, HHS and 15 

other federal departments and agencies 

published a Notice of Proposed 

Rulemaking (NPRM) proposing 

revisions to the regulations for 

protection of human subjects in 

research.2 Like the ANPRM, the NPRM 

sought comment on how to better 

protect research subjects while 

facilitating valuable research and 

reducing burden, delay, and ambiguity 

for investigators. Public comments on 

both the ANPRM and the NPRM have 

informed the final rule that is now being 

promulgated. 

The final rule is designed to more 

thoroughly address the broader types of 

research conducted or otherwise 

supported by all of the Common Rule 

departments and agencies such as 

behavioral and social science research. 

It also benefits from continuing efforts 

to harmonize human subjects policies 

across federal departments and 

agencies. 

Summary of the Major Changes in the 

Final Rule 

The final rule differs in important 

ways from the NPRM. Most 

significantly, several proposals are not 

being adopted: 

• The final rule does not adopt the 

proposal to require that research 

involving nonidentified biospecimens 

be subject to the Common Rule, and that 

consent would need to be obtained in 

order to conduct such research. 

• To the extent some of the NPRM 

proposals relied on standards that had 

not yet been proposed, the final rule 

either does not adopt those proposals or 

includes revisions to eliminate such 

reliance. 

• The final rule does not expand the 

policy to cover clinical trials that are not 

federally funded. 

• The final rule does not adopt the 

proposed new concept of ‘‘excluded’’ 

activities. Generally, activities proposed 

to be excluded are now either described 

as not satisfying the definition of what 

constitutes research under the 

regulations or are classified as exempt. 

• The proposed revisions to the 

exemption categories have been 

modified to better align with the longstanding ordering in the final rule. The 

final rule does not include the proposed 

requirement that exemption 

determinations need to be made in 

specified ways. 

• The final rule does not include the 

proposed standardized privacy 

safeguards for identifiable private 

information and identifiable 

biospecimens. Aspects of proposals that 

relied on those safeguards have been 

modified or are not being adopted. 

• The final rule does not adopt the 

most restrictive proposed criteria for 

obtaining a waiver of the consent 

requirements relating to research with 

identifiable biospecimens. 

The final rule makes the following 

significant changes to the Common 

Rule: 

• Establishes new requirements 

regarding the information that must be 

given to prospective research subjects as 

part of the informed consent process. 

• Allows the use of broad consent 

(i.e., seeking prospective consent to 

unspecified future research) from a 

subject for storage, maintenance, and 

secondary research use of identifiable 

private information and identifiable 

biospecimens. Broad consent will be an 

optional alternative that an investigator 

may choose instead of, for example, 

conducting the research on 

nonidentified information and 

nonidentified biospecimens, having an 

institutional review board (IRB) waive 

the requirement for informed consent, 

or obtaining consent for a specific study. 

• Establishes new exempt categories 

of research based on their risk profile. 

Under some of the new categories, 

exempt research would be required to 

undergo limited IRB review to ensure 

that there are adequate privacy 

safeguards for identifiable private 

information and identifiable 

biospecimens. 

• Creates a requirement for U.S.- 

based institutions engaged in 

cooperative research to use a single IRB 

for that portion of the research that takes 

place within the United States, with 

certain exceptions. This requirement 

becomes effective 3 years after 

publication of the final rule. 

• Removes the requirement to 

conduct continuing review of ongoing 

research for studies that undergo 

expedited review and for studies that 

have completed study interventions and 

are merely analyzing study data or 

involve only observational follow up in 

conjunction with standard clinical care. 

Other minor changes have been to 

improve the rule and for purposes of 

clarity and accuracy. 

Estimated Costs and Benefits 

Table 1 summarizes the quantified 

and nonquantified benefits and costs of 

all changes to the Common Rule. Over 

the 2017–2026 period, present value 

benefits of $1,904 million and 

annualized benefits of $223 million are 

estimated using a 3 percent discount 

rate; present value benefits of $1,494 

million and annualized benefits of $213 

million are estimated using a 7 percent 

discount rate. Present value costs of 

$528 million and annualized costs of 

$62.0 million are estimated using a 3 

percent discount rate; present value 

costs of $474 million and annualized 

costs of $67.0 million are estimated 

using a 7 percent discount rate. 

Nonquantified benefits include 

improved human subjects protections in 

research; enhanced oversight of research 

reviewed by IRBs not operated by a 

Federalwide Assurance (FWA)-holding 

institution; and increased uniformity in 

regulatory requirements among 

Common Rule departments and 

agencies. Nonquantified costs include 

the time needed for consultation among 

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Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 7151 

3National Commission for the Protection of 

Human Subjects of Biomedical and Behavioral 

Research. Belmont Report. Washington, DC: U.S. 

Department of Health and Human Services. 1979. 

Retrieved from http://www.hhs.gov/ohrp/ 

humansubjects/guidance/belmont.html. 4National Research Council of the National 

Academies. Proposed Revisions to the Common 

Rule for the Protection of Human Subjects in the 

Behavioral and Social Sciences. Washington, DC: 

The National Academies Press; 2014. 13–168. 

Retrieved from http://www.nap.edu/catalog/18614/ 

proposed-revisions-to-the-common-rule-for-theContinued 

Common Rule agencies before federal 

guidance is issued. 

TABLE 1—ACCOUNTING TABLE OF BENEFITS AND COSTS OF ALL CHANGES

Present value of 10 years by 

discount rate 

(millions of 2015 dollars) 

Annualized value over 10 

years by discount rate 

(millions of 2015 dollars) 

3 percent 7 percent 3 percent 7 percent 

Benefits: 

Quantified Benefits ................................................................................... 1,904 1,493 223 213 

Nonquantified Benefits: 

Improved human subjects protections in research; enhanced oversight in research reviewed by IRBs not operated by an FWA-holding institution; and increased uniformity in regulatory requirements among Common Rule departments and agencies. 

Costs: 

Quantified Costs ....................................................................................... 528 474 62.0 67.0 

Nonquantified Benefits: 

Time for consultation among Common Rule agencies before federal guidance is issued. 

I. The Rationale for Modernizing the 

Common Rule 

A. The Changing Nature of Research 

This final rule recognizes that in the 

past two decades a paradigm shift has 

occurred in how research is conducted. 

Evolving technologies—including 

imaging, mobile technologies, and the 

growth in computing power—have 

changed the scale and nature of 

information collected in many 

disciplines. Computer scientists, 

engineers, and social scientists are 

developing techniques to integrate 

different types of data so they can be 

combined, mined, analyzed, and shared. 

The advent of sophisticated computer 

software programs, the Internet, and 

mobile technology has created new 

areas of research activity, particularly 

within the social and behavioral 

sciences. In biomedical science, the 

Human Genome Project laid the 

foundation for precision medicine and 

promoted an environment of data 

sharing and innovation in analytics and 

technology, and drew attention to the 

need for policies that support a 

changing research landscape. New 

technologies, including genomic 

sequencing, have quickly led to 

exponential growth in the data to which 

investigators have access. The sheer 

volume of data that can be generated in 

research, the ease with which it can be 

shared, and the ways in which it can be 

used to identify individuals were 

simply not possible, or even imaginable, 

when the Common Rule was first 

adopted. 

Research settings are also shifting. 

Although much biomedical research 

continues to be conducted in academic 

medical centers, more research is being 

conducted in clinical care settings, thus 

combining research and medical data. 

Biospecimen repositories and large 

databases have made it easier to do 

research on existing (stored) 

biospecimens and data. Clinical 

research networks connected through 

electronic health records have 

developed methods for extracting 

clinical data for research purposes and 

are working toward integration of 

research data into electronic health 

records in a meaningful way. The 

scientific community recognizes the 

value of data sharing and open-source 

resources and understands that pooling 

intellectual resources and capitalizing 

on efficient uses of data and technology 

represent the best ways to advance 

knowledge. 

At the same time, the level of public 

engagement in the research enterprise 

has changed. More people want to play 

an active role in research, particularly 

related to health. 

As technology evolves, so does the 

nature of the risks and benefits of 

participating in certain types of 

research. Many studies do not involve 

interaction with research subjects, but 

instead involve secondary analysis of 

data or biospecimens. Risks related to 

these types of research studies are 

largely informational, not physical; that 

is, harms could result primarily from 

the inappropriate disclosure of 

information and not from the research 

interventions themselves. Nonetheless, 

those harms can be significant. 

Because of these shifts in science, 

technology, and public engagement and 

expectations, a wide range of 

stakeholders have raised concerns about 

the limitations of the existing regulatory 

framework, arguing for a re-evaluation 

of how the fundamental principles of 

the 1979 Belmont Report 3 that underlie 

the Common Rule—respect for persons, 

beneficence, and justice—are applied in 

practice to the myriad new contexts in 

which U.S. research is conducted in the 

21st century. The changes that are being 

implemented in the final rule continue 

to be shaped by those principles (a 

detailed background discussion of 

which was provided in the NPRM). 

Finally, it is important to note that, to 

the extent appropriate, the intent is to 

eventually amend the other subparts of 

the HHS human subjects protection 

regulations in 45 CFR part 46 (subparts 

B, C, D, and E), and consider the need 

for updates to FDA regulations and 

other relevant federal departmental or 

agency regulations with overlapping 

scope. 

B. Public Comments, Expert Advice, 

Stakeholder Dialogue 

The revisions to the Common Rule are 

based on a variety of sources of public, 

stakeholder, and expert comments and 

advice, including comments received on 

the 2011 ANPRM and the 2015 NPRM. 

They also benefit from guidance 

provided by a 2014 National Research 

Council consensus report, Proposed 

Revisions to the Common Rule for the 

Protection of Human Subjects in the 

Behavioral and Social Sciences,4 and 

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7152 Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 

protection-of-human-subjects-in-the-behavioraland-social-sciences. 5National Academies of Sciences, Engineering, 

and Medicine. Optimizing the Nation’s Investment 

in Academic Research: A New Regulatory 

Framework for the 21st Century. Washington, DC: 

The National Academies Press; 2016. Retrieved 

from https://www.nap.edu/read/21824/chapter/1. 6National Institutes of Health. Final NIH Policy 

on the Use of a Single Institutional Review Board 

for Multi-Site Research. June 21, 2016. Notice 

Number: NOT–OD–16–094. Retrieved from https:// 

grants.nih.gov/grants/guide/notice-files/NOT-OD16-094.html. 

7HHS. Draft Guidance on Disclosing Reasonably 

Foreseeable Risks in Research Evaluating Standards 

of Care. 79 FR 63630 (Oct. 24, 2014). Retrieved from 

https://www.gpo.gov/fdsys/pkg/FR-2014-10-24/pdf/ 

2014-25318.pdf. 

8 Information about the NIH Genomic Data 

Sharing policy is available at https://gds.nih.gov/ 

03policy2.html. 

9The White House, Office of the Press Secretary. 

Fact Sheets: President Obama’s Precision Medicine 

Initiative. January 30, 2015. Retrieved from https:// 

www.whitehouse.gov/the-press-office/2015/01/30/ 

fact-sheet-president-obama-s-precision-medicineinitiative. 

10Collins FS, Varmus H. A New Initiative on 

Precision Medicine. The New England Journal of 

Medicine 2015 Feb; 372:793–795. 

11For more information on the Precision 

Medicine Initiative Cohort Program see https:// 

www.nih.gov/sites/default/files/research-training/ 

initiatives/pmi/pmi-working-group-report20150917-2.pdf. 

the National Academies of Science, 

Engineering, and Medicine 2016 report 

Optimizing the Nation’s Investment in 

Academic Research: A New Regulatory 

Framework for the 21st Century.5

Since the publication of the 2011 

ANPRM, HHS has continued to solicit 

public comment on a variety of policy 

issues related to human subjects 

protections, including consent, the use 

of a single IRB for multi-institutional 

studies, and sharing of genomic data. 

Although these policies were more 

specific than the issues raised in the 

ANPRM, the responses received from 

public comments provide insight for 

refining the proposals initially put 

forward in the ANPRM. Of particular 

relevance are the National Institutes of 

Health’s (NIH’s) recently issued policy 

on the use of a single IRB for multiinstitutional research,6 the Office for 

Human Research Protection’s (OHRP’s) 

draft guidance on the required content 

of consent language for research 

conducted within the standard of care,7

and NIH’s policy to promote sharing of 

large-scale human genomic data 

generated from studies funded or 

conducted by NIH.8

Other developments include the 

enactment of the Newborn Screening 

Saves Lives Reauthorization Act of 2014 

(Pub. L. 113–240) in December 2014. 

The law made a number of changes 

relevant to the HHS regulations for 

protecting research subjects, including 

asserting that research with newborn 

dried blood spots (DBS) that is federally 

funded pursuant to the Public Health 

Service Act is to be considered research 

with human subjects, and that the 

provisions allowing IRBs to waive 

consent would not apply. By statute, the 

changes made by this law applied only 

until changes to the Common Rule are 

promulgated. Thus, the changes made 

by this statute will no longer apply after 

the effective date of this rule, January 

19, 2018. In addition, in April 2015, the 

Medicare Access and Children’s Health 

Insurance Program Reauthorization Act 

of 2015 (Pub. L. 114–10) was passed. 

That law requires HHS to issue a 

clarification or modification of the 

Common Rule with regard to how the 

regulatory requirements should be 

applied to activities involving clinical 

data registries. In addition, in December 

2016 the 21st Century Cures Act (Pub. 

L. 114–255) was enacted. 

Finally, as a result of conducting a 

variety of public discussions associated 

with the President’s Precision Medicine 

Initiative,9 10 11 many perspectives were 

heard, with much alignment around the 

central tenet that participants should be 

active partners in such research and not 

merely passive subjects of research 

studies. 

1. Summary of Public Comments on 

Structural, Conceptual, and Policy 

Implications of the Proposed Rule 

The NPRM received more than 2,100 

public comments, the majority of which 

were from people writing in their 

individual capacity. The remaining 

comments were submitted by 

institutions, professional organizations 

and societies, and membership 

organizations. The proposals receiving 

the most comments were those related 

to biospecimens (expanded definition of 

human subject, broad consent, and 

tightened criteria for waiver of consent). 

Here we summarize comments on the 

overall structural, conceptual, and 

policy implications of the proposed 

rule. Comments regarding the specific 

provisions of the rule appear throughout 

this preamble. 

The NPRM asked for public comment 

on whether the proposed changes will 

achieve the objectives of: (1) decreasing 

administrative burden, delay, and 

ambiguity for investigators, institutions, 

and institutional review boards (IRBs); 

and (2) strengthening, modernizing, and 

making the regulations more effective in 

protecting research subjects. In 

response, many public commenters 

expressed concern about the overall 

complexity and length of the NPRM, the 

unavailability of key deliverables, 

proposals being internally inconsistent, 

and proposals giving investigators too 

much leeway to determine if their 

research is exempt or falls outside the 

scope of the rule. 

Several commenters expressed 

concerns that they were unable to 

adequately or meaningfully comment on 

particular provisions proposed in the 

NPRM because an underlying 

document, tool, or list had not been 

developed or shared with the public at 

the time the NPRM was published, 

specifically: (1) the proposed broad 

consent templates; (2) the proposed 

standards for privacy protection; (3) the 

proposed list of eligible expedited 

procedures; and (4) the proposed 

exemption decision tool. Several 

commenters suggested that these items 

should be removed from the final rule 

and developed independently, urging 

government personnel to work 

collaboratively with representatives 

from the research community and 

funding agencies in the development of 

such documents, tools, and lists. 

Some commenters suggested issuing a 

new NPRM that would be more 

complete and would include details on 

the privacy protection standards, 

exemption decision tool, and broad 

consent templates. Another commenter 

recommended that only the fully 

developed, less controversial provisions 

of the NPRM should be adopted into a 

final rule. Another commenter urged the 

Common Rule departments and 

agencies to reissue the NPRM to solicit 

comment on several of these documents, 

tools, and lists, arguing that it would be 

unlawful for a final rule to be issued 

until such an action were taken. This 

commenter noted that for members of 

the public to reasonably participate in 

rulemaking, agencies must provide 

enough factual detail and rationale to 

allow interested parties to comment 

meaningfully on the rule. This 

commenter also argued that the NPRM 

did not satisfy the requirement set forth 

in the Administrative Procedure Act 

that the notice provided to the public in 

rulemaking include either the terms or 

substance of the proposed rule or a 

description of the subjects and issues 

involved. In sum, the commenter argued 

that the NPRM sought comments on 

numerous provisions without providing 

the ‘‘terms or substance’’ of the specific 

proposals. 

Some commenters encouraged 

dropping the proposal to require 

consent for research use of 

nonidentified biospecimens and instead 

exploring a system of public notification 

and opportunity to opt out of such 

research through issuance of a new 

NPRM following widespread 

consultation. A few commenters 

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12For purposes of this preamble, the terms ‘‘pre2018 requirements’’ or ‘‘pre-2018 rule’’ refer to the 

Common Rule as published in the 2016 edition of 

the Code of Federal Regulations (i.e., the Federal 

Policy for the Protection of Human Subjects, 

originally published on June 18, 1991 and 

subsequently amended on June 23, 2005). In 

addition, the term ‘‘this rule’’ or ‘‘final rule’’ refers 

to the 2018 requirements as presented in this 

issuance. 

13Federal Regulations Amending Basic HHS 

Policy for the Protection of Human Research 

Subjects; Final Rule, 46 FR8366 (January 26, 1981). 

Retrieved from https://wayback.archive-it.org/all/ 

20160202182914/http://archive.hhs.gov/ohrp/ 

documents/19810126.pdf. 

14Federal Policy for the Protection of Human 

Subjects; Notices and Rules. 56 FR 28002. (June 18, 

1981). Retrieved from https://www.hhs.gov/ohrp/ 

sites/default/files/ohrp/policy/frcomrul.pdf. 

suggested that Common Rule 

departments and agencies fund pilot 

studies to better understand how such a 

system might work. Additional 

commenters focused on the importance 

of public education about the research 

enterprise regardless of the policy 

choices pursued in a final rule. 

Commenters, including state health 

departments and other health entities 

involved in newborn screening 

activities, raised concerns that several of 

the NPRM proposals represented 

unfunded mandates, specifically the 

expansion of the definition of human 

subject to include all biospecimens 

regardless of identifiability, expansion 

of the policy to apply to all clinical 

trials that meet certain conditions, and 

mandatory single IRB review of 

cooperative research. Several 

institutions and disease advocacy 

groups noted that statewide newborn 

screening programs are often modestly 

funded, and the NPRM proposals would 

impose processes that could cost 

millions of dollars each year. 

In addition, commenters raised 

concerns that HHS and other Common 

Rule departments and agencies are not 

authorized under 42 U.S.C. 289 to 

regulate humanities and social science 

research. 

Public comments also discussed 

several ideas for consideration in a final 

rule that were not otherwise proposed 

in the NPRM, including: 

• Develop or strengthen sanctions 

and penalties for investigators or 

institutions that re-identify subjects 

without proper authorization or review, 

rather than focusing solely on obtaining 

consent as the way to protect subjects. 

To this end, several commenters 

suggested that a separate section be 

added to the Common Rule focused on 

investigator responsibilities. 

• Develop an IRB efficiency rating 

system. 

• Deem research about IRB operations 

as an excluded, exempt, or expeditable 

activity to foster research into IRB 

operations. 

• Include provisions about 

compensation for research-related 

injuries. 

• More fully review and address how 

the rule should or should not apply to 

prisoners, children, and pregnant 

women and fetuses. 

• Include provisions about U.S.- 

funded studies in developing countries 

with regard to defining standards of care 

and addressing post-trial access to 

proven therapies. 

2. Response to Public Comments on 

Structural, Conceptual, and Policy 

Implications of the Proposed Rule 

The final rule differs in numerous, 

major ways from what was proposed in 

the NPRM. Most significantly, the 

provisions relating to making 

nonidentified biospecimens subject to 

the Common Rule are not being 

implemented. That change alone 

addresses many of the public comments 

on the NPRM. Eliminating that proposal 

is intended to address concerns about 

the complexity of and lack of 

justification for the proposed changes in 

the rule, as well as concerns about 

embarking on significant changes 

without evidence that they would 

improve the system. Responses to 

public comments on specific provisions 

appear throughout this preamble. Below 

we summarize our responses to 

comments that addressed major 

structural or organizational issues or 

perceived insufficiencies in the NPRM 

proposals and their presentation. 

Concerns about the overall 

complexity of the proposed changes 

have been addressed in several ways. 

For example, concerns about creating a 

new category of ‘‘excluded’’ activities 

have been addressed by not adopting 

that concept in the final rule. Instead, 

the goal of clarifying what is covered by 

the rule has been accomplished by 

modifying the definition of what 

constitutes research, and by adding or 

modifying exemptions that were already 

in the pre-2018 rule.12 And, even where 

existing concepts are modified, we have 

attempted to make those modifications 

in ways that minimize the extent of the 

change (such as largely preserving much 

of the core structure of the previous 

exemption categories). 

To reduce public concerns about the 

aspects of the proposal that were not yet 

developed, we chose not to implement 

most of those provisions. For example, 

given the changes made to the proposals 

regarding broad consent, the final rule 

does not reference or include the 

concept of broad consent templates. The 

requirement that the Secretary of HHS 

develop a list of proposed privacy 

safeguards has been eliminated, as has 

the proposed exemption decision tool. 

In addition, we have dropped the 

regulatory requirement for the Secretary 

of HHS to publish a list of activities that 

are minimal risk (as was proposed in the 

NPRM in the definition of minimal 

risk). The final rule retains the 

requirement at § ll.110(a) that the 

Secretary of HHS will establish and 

publish for public comment a list of 

categories of research that may be 

reviewed by an IRB through the 

expedited review procedure, consistent 

with the pre-2018 rule. 

Some of the ‘‘new ideas’’ for altering 

the system for protecting research 

subjects that were presented by 

commenters—for example, addressing 

compensation for research-related 

injuries or the meaning of equivalent 

protections when research is conducted 

in foreign countries—were either very 

innovative or not yet widely discussed. 

This made it difficult to adopt them at 

this point without further study and 

additional notice and opportunity for 

public comment. Therefore, the fact that 

one or another of these ideas was not 

incorporated into the final rule should 

not be viewed as a rejection of their 

possible merits, or an indication that 

they might not be explored in some 

future revision of the Common Rule or 

in guidance. 

a. Process Issues 

We carefully considered concerns 

voiced by commenters about the process 

that led to this final rule, and other legal 

concerns about the adequacy of that 

process. We concluded that the 

approach proposed in the NPRM and 

the approach adopted in this final rule 

are consistent with the Federal 

Government’s obligations under the 

Administrative Procedure Act. 

Regarding the concerns expressed that 

the Common Rule departments and 

agencies are not authorized to regulate 

humanities and social science research, 

this challenge had been asserted 

previously against the 1981 HHS 

protection of human subjects 

regulations,13 as well as the 1991 

Common Rule,14 and in each case the 

regulatory agencies concluded that the 

regulation of humanities and social 

science research is justified. We 

continue to assert the authority to 

regulate humanities and social science 

research that falls within the scope of 

the final rule. 

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C. Signatories to the Common Rule 

This section provides information 

about where each Common Rule 

department or agency’s statutory 

authority for enacting and revising 

human subjects research protection 

regulation lies, and provides additional 

information about new signatories to the 

Common Rule. 

The regulations are codified in each 

department or agency’s title or chapter 

of the CFR. The Common Rule was 

based on HHS’s regulations, 45 CFR part 

46, subpart A, and includes identical 

language in the separate regulations of 

each department and agency. 

Although they did not previously 

issue the Common Rule in regulations, 

four departments and agencies have 

historically complied with all subparts 

of the HHS protection of human subjects 

regulations at 45 CFR part 46. These are 

the Central Intelligence Agency (CIA), 

the Office of the Director of National 

Intelligence (ODNI), the Department of 

Homeland Security (DHS), and the 

Social Security Administration (SSA). 

Pursuant to Executive Order 12333 of 

December 4, 1981, as amended, 

elements of the Intelligence Community 

must comply with the guidelines issued 

by HHS regarding research on human 

subjects found in 45 CFR part 46. This 

final rule does not supersede the 

Executive Order. The CIA will continue 

to adhere to the HHS regulations at 45 

CFR part 46, pursuant to the Executive 

Order. 

Through this rulemaking, DHS is 

codifying the final rule into its own 

agency regulations. DHS, which was 

created after issuance of the pre-2018 

rule, has been required by statute (Pub. 

L. 108–458, title VIII, section 8306) to 

comply with 45 CFR part 46, or with 

equivalent regulations promulgated by 

the Secretary of Homeland Security or 

his designee. Through this rulemaking, 

DHS is issuing equivalent regulations, 

consistent with statute, and will comply 

with the DHS regulations as the 

requirements will be equivalent to 

compliance with HHS regulations at 45 

CFR part 46, subpart A. 

Through this rulemaking, SSA is 

codifying the final rule into its own 

agency regulations. SSA was separated 

from HHS in 1995 and, pursuant to the 

transition rules provided in Section 106 

of title 1 of Pub. L. 103–296, has been 

required to apply regulations that 

applied to SSA before the separation, 

absent action by the Commissioner. 

With this rulemaking, SSA will follow 

the SSA regulations (adopting the 

provisions of this final rule) instead of 

HHS regulations at 45 CFR part 46, 

subpart A. (See Pub. L. 103–296 §106(b), 

108 Stat. 1464, 1476.) 

The Department of Labor (DOL), 

which was not a signatory to the pre2018 rule, is now a signatory to this 

rulemaking and is codifying the final 

rule in DOL regulations for human 

subjects research that DOL conducts or 

supports. 

The Consumer Product Safety 

Commission (CPSC), subject to 

Commission vote, intends to adopt this 

rule through a separate rulemaking. 

The legal authority for the 

departments and agencies that are 

signatories to this action is as follows: 

Department of Homeland Security, 5 

U.S.C. 301; Pub. L. 107–296, sec. 102, 

306(c); Pub. L. 108–458, sec. 8306. 

Department of Agriculture, 5 U.S.C. 301; 

42 U.S.C. 300v–1(b). Department of 

Energy, 5 U.S.C. 301; 42 U.S.C. 7254; 42 

U.S.C. 300v–1(b). National Aeronautics 

and Space Administration, 5 U.S.C. 301; 

42 U.S.C. 300v–1(b). Department of 

Commerce, 5 U.S.C. 301; 42 U.S.C. 

300v–1(b). Social Security 

Administration, 5 U.S.C. 301; 42 U.S.C. 

289(a). Agency for International 

Development, 5 U.S.C. 301; 42 U.S.C. 

300v–1(b), unless otherwise noted. 

Department of Housing and Urban 

Development, 5 U.S.C. 301; 42 U.S.C. 

300v–1(b) and 3535(d). Department of 

Labor, 5 U.S.C. 301; 29 U.S.C. 551. 

Department of Defense, 5 U.S.C. 301. 

Department of Education, 5 U.S.C. 301; 

20 U.S.C. 1221e–3, 3474; 42 U.S.C. 

300v–1(b). Department of Veterans 

Affairs, 5 U.S.C. 301; 38 U.S.C. 501, 

7331, 7334; 42 U.S.C. 300v–1(b). 

Environmental Protection Agency, 5 

U.S.C. 301; 7 U.S.C. 136a(a) and 

136w(a)(1); 21 U.S.C. 346a(e)(1)(C); sec. 

201, Pub. L. 109–54, 119 Stat. 531; and 

42 U.S.C. 300v–1(b). Department of 

Health and Human Services, 5 U.S.C. 

301; 42 U.S.C. 289(a); 42 U.S.C. 300v– 

1(b). National Science Foundation, 5 

U.S.C. 301; 42 U.S.C. 300v–1(b). 

Department of Transportation, 5 U.S.C. 

301; 42 U.S.C. 300v–1(b). 

II. To what does this policy apply? 

Scope and Applicability of the 

Regulations 

This section of the preamble describes 

changes made in the final rule with 

regard to its scope and applicability. 

Specifically, it addresses which entities 

are subject to the rule; coverage of 

clinical trials; department and agency 

discretion in applying the rule; the 

relevance of state and local laws; 

coverage of research conducted in 

foreign countries; the goal of 

harmonizing guidance across the federal 

entities; effective and compliance dates; 

and severability. 

A. IRBs Not Operated by an Institution 

Holding a Federalwide Assurance 

(§ ll.101(a)(1)) 

1. Background and Pre-2018 

Requirements 

Before this final rule, IRBs not 

operated by an institution holding an 

FWA were not directly subject to 

oversight for compliance with the 

Common Rule. In situations in which an 

institution relied on an IRB not operated 

by the institution, OHRP’s practice was 

to hold the institution engaged in 

human subjects research accountable for 

compliance violations, even in 

circumstances in which the regulatory 

violation was directly related to the 

responsibilities of the IRB. 

An institution might rely on an IRB 

not operated by that institution to 

review cooperative research, that is, 

research conducted at more than one 

institution. However, for some, such 

reliance has been considered 

problematic due to lack of direct 

regulatory accountability for these IRBs. 

Previously, the choice to have 

cooperative research reviewed by a 

single IRB was voluntary and, for 

federally funded research, most 

institutions have been reluctant to 

replace review by their own IRB with 

review by a single IRB not operated by 

that institution. 

2. NPRM Proposal To Cover IRBs not 

Operated by an Institution Holding an 

FWA 

For the reasons outlined above, and 

based on comments to OHRP’s 2011 

ANPRM, the NPRM proposed adding a 

new provision at §ll.101(a) that 

would explicitly give Common Rule 

departments and agencies the authority 

to enforce compliance directly against 

IRBs that are not operated by an FWAholding institution (sometimes referred 

to as ‘‘independent IRBs’’). Under the 

pre-2018 rule, even if an institution 

engaged in research relied on an IRB 

operated by another FWA-holding 

institution, OHRP’s practice has been to 

enforce compliance through the engaged 

institution and not the reviewing IRB. 

Relatedly, another NPRM proposal 

would require single IRB review of 

multi-institution studies (see Section XII 

of this preamble). This proposal would 

place responsibility for meeting the 

relevant regulatory requirements on the 

IRB of record in a multi-institutional 

study, rather than on the institution 

engaged in the research. 

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15Federman DD, Hanna KE, Rodriguez LL, eds. 

Responsible Research: A Systems Approach to 

Protecting Research Participants. Washington, DC: 

National Academies Press; 2002. 

16National Bioethics Advisory Commission. 

Ethical and Policy Issues in Research Involving 

Human Participants. Bethesda, MD; 2001. 

3. Public Comments 

Approximately 50 comments 

addressed this proposal, largely in 

support, because it would encourage 

institutions to rely on IRBs not operated 

by an FWA-holding institution when 

necessary and would place 

responsibility on the IRB and its 

decisions rather than on the institution 

relying on the IRB’s determination. 

Commenters stated that this change 

could increase IRB accountability and 

protect institutions relying on IRBs that 

they do not operate. However, a few 

commenters supported the proposal 

only if the mandate for a single IRB of 

record in multi-institutional research 

was not implemented. That is, they 

supported the concept of holding IRBs 

not operated by the institution engaged 

in research accountable for compliance, 

but did not support it if it was intended 

solely to facilitate mandatory single IRB 

review for cooperative research, because 

they opposed that mandate. One 

organization that advocates for human 

subjects protections opposed the 

proposal because it did not believe that 

any research should be reviewed by an 

independent IRB, and feared this 

practice would become more frequent 

with this change. Several academic 

institutions opposed the proposal, as 

did a large trade organization, stating 

that this extension of the rule was not 

necessary. 

4. Response to Comments and 

Explanation of the Final Rule: Authority 

To Enforce Compliance Directly Against 

IRBs Not Operated by an FWA-Holding 

Institution 

New language at §ll.101(a) is 

adopted that gives Common Rule 

departments and agencies the authority 

to enforce compliance directly against 

IRBs that are not operated by an assured 

institution. This authority will allow 

Common Rule departments and 

agencies to avoid involving other 

engaged institutions in enforcement 

activities related to the responsibilities 

of the designated IRB. It is anticipated 

that this change will reassure 

institutions using an IRB that they do 

not operate because compliance actions 

could be taken directly against the IRB 

responsible for the regulatory 

noncompliance, rather than against the 

institutions that relied on that review. 

B. Coverage of Clinical Trials 

1. Background and Pre-2018 

Requirements 

The Common Rule has historically 

applied to human subjects research that 

is conducted or supported by a Common 

Rule department or agency. Research 

that is not federally conducted or 

supported has not been subject to the 

Common Rule’s requirements unless the 

U.S. institution receiving federal 

funding for research voluntarily 

extended the Common Rule to all 

research conducted at that institution, 

regardless of funding source. 

The Institute of Medicine,15 the 

National Bioethics Advisory 

Commission,16 and others have stated 

that human subjects would be best 

protected by applying consistent ethical 

standards and a uniform system of 

regulatory oversight to all human 

subjects research conducted in the 

United States. Common Rule 

departments and agencies do not have 

statutory authority to directly apply the 

Common Rule to all human subjects 

research conducted in the United States. 

However, departments and agencies can 

require U.S. institutions that receive 

some federal funding from a Common 

Rule department or agency for research 

with human subjects to extend 

regulatory protections to all research 

studies conducted at the institution as a 

condition of funding. The 2011 ANPRM 

sought comment on this approach. 

2. NPRM Proposal 

The NPRM proposed changes in the 

regulatory language to extend the rule to 

all clinical trials, irrespective of funding 

source, that met three conditions: (1) 

The clinical trials are conducted at an 

institution that receives support from a 

federal department or agency for human 

subjects research that was not proposed 

to be excluded under the NPRM and 

was not exempt; (2) the clinical trials 

are not subject to FDA regulation; and 

(3) the clinical trials are conducted at an 

institution located within the United 

States. 

The purpose of the proposed clinical 

trials extension was to ensure that 

clinical trials involving significant risks 

that would otherwise not be covered be 

subject to federal oversight. It was for 

that reason that the proposed extension 

excluded clinical trials subject to FDA 

oversight. The proposed extension also 

was based on whether an institution 

received funding specifically for other 

human subjects research that had to 

comply with the substantive 

requirements of the Common Rule. The 

Common Rule departments and 

agencies have a more substantial 

relationship with institutions that 

receive federal support to conduct 

research subject to the regulatory 

requirements than they do with 

institutions that receive such support 

for only exempt human subjects 

research. 

The NPRM proposed that a clinical 

trial be defined as a research study in 

which one or more human subjects are 

prospectively assigned to one or more 

interventions (which may include 

placebo or other control) to evaluate the 

effects of the interventions on 

biomedical or behavioral health-related 

outcomes. By the term ‘‘behavioral 

health-related outcomes,’’ the NPRM 

recognized that clinical trials may occur 

outside of the biomedical context, and 

further stated that the studies addressed 

in the proposed definition of clinical 

trial are more likely to present more 

than minimal risk to subjects, and, 

therefore, require the highest level of 

oversight. 

3. Public Comments 

Approximately 70 comments 

discussed the proposal to extend the 

Common Rule to cover certain clinical 

trials. Opinion was mixed, with a slim 

majority opposing the proposed change. 

Universities and medical centers 

providing comments largely opposed 

the proposed measure, while 

professional associations and advocacy 

groups largely supported the proposal. 

We note that some of those who 

opposed the clinical trial extension did 

so because they felt that the proposal 

did not go far enough to include 

additional types of research. 

Those supporting the proposed 

change indicated that it had the 

potential to ensure greater consistency 

of rules and protections for research 

subjects, thereby aiding efficiency and 

speeding the review process of study 

protocols. However, even those 

commenters who supported the 

proposal indicated that such an 

extension must fulfill the intent of a 

risk-based, streamlined approach to 

human subject protection, considering 

the effects of this extension on certain 

minimal risk research activities, such as 

student research, and social, behavioral, 

and educational research. 

Those expressing opposition to this 

expansion of coverage noted concerns 

that: (1) Because the research 

institutions likely to engage in clinical 

trials already require IRB review of such 

research, the expansion would only 

increase administrative burdens (such 

as federal reporting requirements) for 

this type of research without a 

meaningful increase in protections to 

human subjects; (2) the regulatory 

extension to nonfederally funded 

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clinical trials would encompass many 

minimal-risk social and behavioral 

research activities and currently 

unregulated institutional activities that 

involve randomization (such as 

nonfederally funded quality 

improvement or quality assurance 

activities); and (3) because an 

institution’s funding status may change, 

implementation of this proposal would 

be complicated. Several commenters 

expressed concern about the lack of 

detail in the NPRM regarding the 

planned implementation of the 

proposed requirement. 

Several commenters also expressed 

concern that the unfunded clinical trials 

encompassed by this proposal would be 

subject to the single IRB mandate 

without a corresponding provision of 

federal funds to implement that 

requirement. 

Some commenters suggested that the 

proposed change in the NPRM will not 

address the real gap in human subjects 

protections—facilities that receive no 

federal funding—and that if broad 

concern exists that some subjects are not 

being adequately protected in research 

that is not federally funded, then 

Congress would be the appropriate body 

to address any such deficiency through 

legislation. Further, some commenters 

expressed concern that extending the 

Common Rule to nonfederally funded 

clinical trials might have an overall 

effect of decreasing human subject 

protections by discouraging some 

smaller organizations from accepting 

any federal funding, thus removing 

federal oversight of their work. 

One research institution noted that, if 

finalized, the proposed clinical trials 

extension would be implemented at the 

same time the ability of institutions to 

formally extend the application of the 

rule to all research conducted at the 

institution is being eliminated. Some 

states, such as Virginia, have state 

human subjects regulations that must be 

applied to research when federal 

regulations are not required. The 

commenter noted that removing the 

option to voluntarily extend the FWA 

would have the effect of reducing 

uniform application of the federal 

standards, as nonfederally funded 

research that does not meet the 

proposed definition of a clinical trial 

would by default be subject to state law. 

A few commenters challenged 

whether the legal authority provided by 

the Public Health Service Act was 

sufficient to extend the Common Rule to 

nonfederally funded clinical trials. 

Commenters also suggested that this 

proposal is an unfunded mandate from 

the Federal Government with no benefit 

accruing to subjects or the research 

enterprise. 

4. Response to Comments and 

Explanation of the Final Rule: Coverage 

of Certain Clinical Trials 

The final rule does not adopt the 

NPRM proposal. Although we continue 

to maintain the position that increased 

harmonization of appropriate standards 

for ethical oversight of human subjects 

research is an important and desirable 

endpoint, we agree with the concerns 

expressed by commenters suggesting 

that our proposal for extending the 

Common Rule to currently unregulated 

clinical trials would benefit from further 

deliberation. Some commenters asserted 

that, in our attempt to close the 

perceived ‘‘gap’’ in oversight, the NPRM 

created a structure that would be both 

confusing and complicated for 

institutions to implement. We received 

multiple comments objecting to the 

administrative complexity involved in 

applying a regulatory extension 

triggered by the receipt of Common Rule 

department or agency funding for other 

nonexempt research, and asserting that 

the administrative burden is not offset 

by a corresponding increase in the 

meaningful protection of human 

subjects. Additionally, it is apparent 

from the public comments received that 

our intention to apply the Common Rule 

to cover the most risky types of 

research—clinical trials—was not 

accomplished through the NPRM 

proposal, given the definition of 

‘‘clinical trial’’ included in the NPRM, 

as that definition encompassed research 

that would pose no more than minimal 

risk to subjects. Commenters were 

further concerned that an unintended 

consequence might be that the proposed 

extension would apply to low-risk 

student research and social, behavioral, 

or educational research, and would 

cause currently unregulated 

institutional activities, such as certain 

quality improvement or quality 

assurance activities, to fall within 

regulatory oversight. Upon reflection on 

the perspectives expressed by these 

commenters, we are persuaded that the 

proposed extension of the Common 

Rule is not appropriate to include in a 

final rule at this time. We will continue 

to carefully consider the related issues. 

As an alternative, we contemplated 

explicitly limiting the extension of this 

policy to clinical trials that present 

greater than minimal risk to subjects in 

order to better align with the intent of 

this extension, as described in the 

preamble to the NPRM. However, such 

an alteration of the rule would itself 

introduce a variety of complexities, 

including the question of how a 

determination would be made that a 

particular activity involves more than 

minimal risk. Thus, there would be a 

very real possibility that such a rule 

would lead to an administrative burden 

on substantially more activities than the 

rule itself would be targeting (such as 

many minimal risk quality improvement 

activities). 

We also considered the alternative of 

maintaining the pre-2018 standard of 

allowing institutions to voluntarily 

extend their FWAs to nonfederally 

funded research. We concluded that this 

alternative would not further the 

expressed goal of increasing the 

application of consistent protections to 

clinical trials, regardless of the source of 

support, because the extension of the 

FWA would be optional. We therefore 

plan to implement the proposed 

nonregulatory change to the assurance 

mechanism to eliminate the voluntary 

extension of the FWA to nonfederally 

funded research. 

We note the concern expressed by 

commenters that a gap in federal 

oversight will remain for nonfederally 

funded research, and the comment that 

Congress would be the appropriate body 

to address any such deficiency through 

legislation. We recognize that 

institutions may choose to establish an 

institutional policy that would require 

IRB review of research that is not 

funded by a Common Rule department 

or agency (and indeed, as commenters 

noted, almost all institutions already do 

this), and nothing in this final rule 

precludes institutions from providing 

protections to human subjects in this 

way. As a result, the final rule continues 

to allow institutions the same wide 

degree of flexibility that they currently 

have with regard to making other 

similar determinations regarding ethical 

oversight of research not regulated by 

the Common Rule. 

Although we are not implementing 

the proposed extension of the Common 

Rule to ‘‘clinical trials’’ (as defined by 

this policy), the proposed definition of 

‘‘clinical trial’’ is still relevant to the 

final rule provision requiring posting of 

one IRB-approved consent form used to 

enroll subjects for a clinical trial 

conducted or supported by a federal 

department or agency, at §ll.116(h). 

The definition of clinical trial is 

unaltered from the NPRM proposal and 

appears at § ll.102(b). 

C. Activities Deemed Not To Be 

Research Appear at §ll.102(l) and 

Research Exempt From This Policy 

Appears at § ll.104 

In response to the public comments, 

the NPRM’s general approach of 

designating various categories of 

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activities as excluded is not included in 

the final rule. The final rule reverts to 

the general structure of the pre-2018 

rule and integrates some of the 

categories proposed for exclusion in the 

NPRM into that structure. Some changes 

to the categories are also included in the 

final rule. 

In the final rule, some of the proposed 

exclusions from the requirements of the 

Common Rule are addressed in the 

definition of research, which includes a 

provision identifying ‘‘activities that are 

deemed not to be research’’ (see Section 

III). In addition, some of the proposed 

exclusions are included as exemptions 

in the final rule. Under § ll.101(b) of 

the pre-2018 rule, six categories of 

research were considered exempt from 

this policy unless otherwise required by 

department or agency heads. In the final 

rule, exempt research is now described 

at §ll.104 and eight categories are 

included (see Section V). 

D. Department or Agency Discretion in 

Applying the Policy (§ll.101(c), (d), 

(i)) 

1. Background and Pre-2018 

Requirements 

The pre-2018 requirements included 

provisions at § ll.101 that allowed 

federal department or agency heads to 

determine which specific activities or 

classes of activities are covered by the 

rule and whether certain requirements 

could be waived. This flexibility was 

allowed in recognition of the varying 

missions of the federal departments and 

agencies, the possibility that there may 

be superseding or alternative statutes or 

regulations governing their activities, 

and the possibility that a given situation 

requires either more stringent oversight 

(e.g., ‘‘sensitive research’’) or reduced 

requirements (e.g., a public health 

emergency). 

2. NPRM Proposals 

The NPRM proposed to retain the 

Common Rule’s pre-2018 requirement 

that federal department or agency heads 

retain final judgment about the coverage 

of particular research activities under 

the Common Rule (§ll.101(c)) and 

proposed an additional requirement that 

federal department or agency heads 

exercise their authority consistent with 

the principles of the Belmont Report. 

The NPRM also proposed at 

§ ll.101(d) that a department or 

agency may require additional 

protections for specific types of research 

it supports or conducts, or that is 

otherwise subject to regulation by the 

federal department or agency but not 

otherwise covered by the Common Rule. 

However, advance public notice would 

be required when those additional 

requirements apply to entities outside of 

the federal department or agency itself. 

This latter requirement was intended to 

promote harmonization among federal 

agencies or departments, to the extent 

possible, and to ensure transparency 

between funding entities and the 

regulated community. 

Finally, at § ll.101(i) the NPRM 

proposed to amend the criteria for a 

department or agency waiving the 

applicability of some or all of the 

provisions of the policy, by stating that 

the alternative procedures to be 

followed must be consistent with the 

principles of the Belmont Report. The 

addition of this provision was to make 

explicit the ethical basis underpinning 

how waiver decisions have and must be 

considered. The NPRM also proposed 

that such waivers be posted on a 

publicly accessible federal Web site. 

3. Public Comments 

Approximately 25 comments related 

to the NPRM proposals at § ll.101(c) 

and (i) and none on § ll.101(d). 

Comments received on these proposals 

generally expressed opposition to ever 

granting the authority to department or 

agency heads to retain final judgment as 

to whether a particular activity is 

covered by this policy, or to waive 

certain requirements, even though these 

provisions existed in the pre-2018 rule. 

These commenters were concerned 

about the potential for Common Rule 

departments and agencies to exclude 

certain activities for political purposes 

or for expediency, such as certain 

activities that might involve 

surveillance or criminal investigative 

aims. With regard to §ll.101(i), some 

commenters stated that reference to the 

ethical principles of the Belmont Report 

was too narrow. That is, one might rely 

on additional ethical considerations to 

evaluate the applicability of the 

regulations. 

4. Response to Public Comments and 

Explanation of the Final Rule: 

Department or Agency Discretion About 

Applicability of the Policy 

The final rule adopts the NPRM 

proposals in § ll.101(c). Thus, under 

§ ll.101(c), department or agency 

heads retain final judgment as to 

whether a particular activity is covered 

by the Common Rule, and this judgment 

should be exercised consistent with the 

ethical principles of the Belmont Report. 

We note that under the pre-2018 

requirements Common Rule 

departments and agencies retained final 

authority as to whether a particular 

human subjects research study 

conducted or supported by that 

department or agency is covered by the 

Common Rule (§ ll.101(c)) and that 

authority continues under the final 

regulations, but with the new limitation 

that this judgment must be consistent 

with the ethical principles of the 

Belmont Report. This discretion 

provides important flexibility given the 

varying missions and policies of the 

many departments and agencies. 

Although some commenters were 

opposed to ever granting departments or 

agencies the authority permitted by 

§ ll.101(c), we believe requiring that 

these decisions be consistent with the 

principles of the Belmont Report is an 

approach that promotes accountability 

while still giving federal departments 

and agencies the necessary flexibility to 

achieve their respective missions. 

The final rule in §ll.101(d) does 

not adopt the NPRM proposals, and 

instead retains the pre-2018 language. 

The NPRM proposed to modify 

§ ll.101(d) to say that department or 

agency heads could require additional 

protections to research activities 

conducted or supported by federal 

departments or agencies, but that were 

not otherwise covered by the Common 

Rule. This language was intended as a 

clarification to the pre-2018 language. 

However, we determined that the term 

‘‘additional protections’’ could 

potentially be confusing in that the 

activities at issue in this provision are 

those for which no Common Rule 

protections are required; thus the 

protections imposed by department or 

agency heads might be the only 

protections to which these activities are 

subject. We also note that departments 

or agencies conducting or supporting an 

activity subject to the Common Rule 

may require additional protections for 

human subjects. 

The final rule also does not 

incorporate the NPRM proposal in 

§ ll.101(d) that advance public notice 

must be provided when a department or 

agency head requires that the Common 

Rule, or part of it, be applied to research 

activities not otherwise subject to the 

rule. Upon further assessment, we 

decided that such a requirement could 

hinder the ability of a department or 

agency to move quickly in cases where 

the department or agency determined 

that additional protections are 

warranted. 

Section ll.101(i) of the final rule 

adopts a majority of the NPRM 

proposals. As proposed in the NPRM, 

§ ll.101(i) is modified to require that 

any alternative procedures adopted by 

departments or agency heads are 

consistent with the principles of the 

Belmont Report. Also as proposed in the 

NPRM, §ll.101(i) is modified to state 

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that, unless otherwise required by 

statute or executive order, notice of 

these alternative procedures must be 

forwarded to OHRP (or any successor 

office), or to the equivalent office within 

the appropriate federal department or 

agency. The pre-2018 rule only listed 

OHRP (or any successor office) as the 

office to which notices must be sent. 

This final rule modification is intended 

to ensure that if a non-HHS department 

or agency allows for alternative 

procedures, the appropriate office 

within that same department or agency 

receives notification. The final rule 

retains the pre-2018 requirement for the 

notice to also be published in the 

Federal Register or in such other 

manner provided for in department or 

agency procedures. 

The final rule also adopts in 

§ ll.101(i) the NPRM proposal to 

require that the waiver notice include a 

statement that identifies the conditions 

under which the waiver will be applied 

and a justification as to why the waiver 

is appropriate for the research, 

including how the decision is consistent 

with the principles in the Belmont 

Report. 

Section ll.101(i) of the final rule 

does not include the NPRM proposal 

that would have required each federal 

department or agency conducting or 

supporting the research to establish on 

a publicly accessible federal Web site a 

list of the research for which a waiver 

has been issued. We decided that the 

rule’s requirement to publish the waiver 

notice in the Federal Register, or in 

such other manner as provided in 

department or agency procedures, 

adequately ensures that the waiver 

notice will be available to the public 

without also requiring that such notices 

be listed on a federal Web site. We note 

that some departments, such as HHS, 

currently post such notices on their Web 

sites. 

The final rule thus formally codifies 

in §ll.101(c) and (i) the general 

practice that the ethical standards 

articulated in the Belmont Report are 

the ethical standards that Common Rule 

departments or agencies will use in 

determining whether an activity is 

covered under this policy or whether to 

grant a waiver of the applicability of 

some or all of the provisions (unless 

otherwise required by law). The 

addition of the reference to the Belmont 

Report makes explicit the ethical basis 

underpinning how waiver decisions 

have and must be considered. 

E. State and Local Laws That Provide 

Additional Protections for Human 

Subjects (§ll.101(f)) 

1. Background and Pre-2018 

Requirements 

The pre-2018 rule specified that the 

policy does not affect any state or local 

laws or regulations that may otherwise 

be applicable and that provide 

additional protections for human 

subjects. The NPRM did not propose 

any changes to this statement. However, 

questions raised by public comments, as 

described below, led to some 

clarifications to the final rule. 

1. Public Comments 

Several public comments raised 

questions and concerns about the ability 

of tribal nations to require additional 

protections that might be needed for 

research involving American Indian/ 

Alaska Native (AI/AN) populations. 

One tribal government noted the 

documented mistrust of research by AI/ 

AN people and communities, and 

advocated for specific provisions 

acknowledging the authority and role of 

tribal nations in overseeing research that 

happens on their lands and with their 

citizens. Additionally, this entity noted 

that tribal nations do not always have 

their own regulatory bodies for human 

subject research protections, expressing 

concern about external groups deciding 

what constitute risks and benefits for 

the community. 

Other AI/AN Population concerns of 

commenters included: 

• Tribal (i.e., group) and individual 

consent for secondary research with 

biospecimens: Commenters noted that 

group consent can occur and should 

inform the proposed changes in the rule. 

They also noted that broad consent for 

future, unspecified research use of 

biospecimens presents a challenge to 

the ongoing ability of both tribes and 

individuals to choose to remove their 

data from research, or to understand 

how their information is being used to 

benefit, or put at risk, themselves or 

others. 

• Tribal and individual consent for 

research with biospecimens or other 

data from people who are no longer 

alive: AI/AN groups noted the need to 

address protections for biospecimens 

initially collected from living humans 

after those humans pass away. 

• Research oversight by tribal IRBs 

and other tribal regulatory bodies: AI/ 

AN groups raised concerns about the 

use of a single IRB in cooperative and 

multi-institutional research, which does 

not foster community-based governance 

and oversight of research that has the 

potential to improve outcomes for tribal 

and minority populations. 

• Research oversight for categories of 

research and activities important in 

tribal contexts: Commenters noted 

concerns about the proposed changes 

related to the exclusion of certain 

categories of activities (e.g., oral history, 

biography), addition of exempt 

categories of research (e.g., educational 

tests, surveys, interviews), and 

elimination of continuing review 

requirements for some studies because 

tribal research review often extends the 

scope of examination beyond 

individual-level protections to enact 

community-level protections important 

for maintaining the integrity of 

culturally significant information and 

practices. Changes to excluded and 

exempt categories of research and 

eliminating some continuing review 

requirements, especially where no clear 

mechanism for additional tribal 

oversight and input has been 

established, are a cause for concern for 

the AI/AN community. 

2. Response to Public Comments and 

Explanation of the Final Rule: State and 

Local Laws That Provide Additional 

Protections 

Consistent with the pre-2018 rule, this 

final rule retains the language in 

§ ll.101(f)) providing that the 

Common Rule does not affect any state 

or local laws or regulations that may 

otherwise be applicable and that 

provide additional protections for 

human subjects. However, the final rule 

adds clarifying language providing that 

the referenced state or local laws or 

regulations include tribal laws passed 

by the official governing body of an AI/ 

AN tribe. Thus, if the official governing 

body of a tribe passes a tribal law that 

provides additional protections for 

human subjects, the Common Rule does 

not affect or alter the applicability of 

such tribal law. (Note that a similar 

change was also made to § ll.116(i) 

and (j) to provide the same 

clarification.) In addition, for purposes 

of the exception to the single IRB review 

requirement for cooperative research, 

relating to circumstances where review 

by more than a single IRB is required by 

law, §ll.114(b)(2)(i) specifies that 

tribal law is to be considered in 

assessing whether more than single IRB 

review is required by law. 

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F. Research Covered by This Policy 

Conducted in Foreign Countries 

(§ ll.101(h)) 

1. Background and Pre-2018 

Requirements 

The pre-2018 requirements at 

§ ll.101(h) stated that when research 

covered by this policy takes place in 

foreign countries, procedures normally 

followed in those countries to protect 

human subjects may differ from those 

set forth in this policy. The previous 

rule cited the Declaration of Helsinki, as 

amended in 1989, as an example of 

internationally recognized ethical 

standards that a foreign country might 

use as its ethical standard. The rule 

provided that if a department or agency 

head determined that procedures 

prescribed by the institution in the 

foreign country afforded protections that 

are at least equivalent to those provided 

in this policy, the department or agency 

head may approve the substitution of 

the foreign procedures in lieu of the 

procedural requirements provided in 

this policy. 

2. NPRM Proposal 

The NPRM proposed to remove the 

specific reference to the Declaration of 

Helsinki in this provision. A concern 

with providing a specific example of an 

internationally recognized ethical 

document is that such a document is 

subject to change independent of 

Common Rule departments and 

agencies, and therefore could be 

modified to contain provisions that are 

inconsistent with future U.S. laws and 

regulations. 

3. Public Comments 

A few comments addressed the 

removal of the reference to the 

Declaration of Helsinki. These 

comments were equally divided 

between those opposed and those 

supportive or generally supportive. 

Those opposed feared that the removal 

of the reference would suggest that the 

Declaration of Helsinki does not apply 

and that it was cited in the pre-2018 

requirements as an example, not as an 

equivalent replacement for the Common 

Rule. These commenters also noted that 

the United States had refused to sign on 

to some recent revisions to the 

Declaration. One organization 

commented that it would have been 

useful for the NPRM to address the issue 

of equivalent protections for U.S.- 

funded research conducted in foreign 

countries, as that might have addressed 

ongoing concerns about the use of 

alternative systems of protections when 

research is conducted outside the 

United States. Those supportive of 

removing the reference to the 

Declaration of Helsinki agreed with the 

arguments laid out in the NPRM and felt 

that it was judicious to not align U.S. 

regulations with other standards 

because those standards are likely to 

change, perhaps in ways inconsistent 

with U.S. policy. 

4. Response to Public Comments and 

Explanation of Final Rule: Removing the 

Reference to the Declaration of Helsinki 

The final rule adopts the NPRM 

proposal. Although the pre-2018 

requirements cited the Declaration of 

Helsinki as an example of 

internationally recognized ethical 

standards that a foreign country might 

use as its ethical base, we note that 

providing a specific example of an 

internationally recognized ethical 

document is concerning because such a 

document is subject to change 

independent of Common Rule 

department or agency policies, and 

therefore might be modified in ways 

that create standards that are 

inconsistent with U.S. laws and 

regulations. 

G. Harmonization of Department and 

Agency Guidance (§ ll.101(j)) 

1. Background and Pre-2018 

Requirements 

Each Common Rule department and 

agency and the Food and Drug 

Administration (FDA) are authorized to 

issue its own guidance with regard to 

interpreting and implementing the 

regulations protecting human subjects. 

That guidance may differ substantially 

across entities. Currently, multiple 

efforts are underway to address 

variation in guidance across the Federal 

Government, but no regulatory 

requirement exists for departments and 

agencies to consult with other 

departments before issuing a policy, to 

the extent appropriate. As a result, 

interdepartmental communication has 

been at times uneven, leading to 

potentially avoidable inconsistencies. 

The Common Rule departments and 

agencies have procedures for sharing 

proposed guidance before it is adopted, 

and these procedures have generally 

been successful. Additionally, FDA and 

OHRP have worked closely to ensure 

harmonization of guidance to the extent 

possible, given the differing statutory 

authorities and regulatory missions. 

Also, as mentioned earlier in section 

I.B., the 21st Century Cures Act was 

enacted in December 2016. Among other 

things, it requires that the Secretary of 

HHS, to the extent practicable and 

consistent with other statutory 

provisions, harmonize the differences 

between 45 CFR part 46, subpart A, and 

FDA’s human subject regulations. 

2. NPRM Proposal 

Responses to questions in the 2011 

ANPRM about the need for 

harmonization of guidance across 

Common Rule departments and 

agencies reflected widespread support 

for such efforts. Several commenters 

acknowledged the difficulty of getting 

all Common Rule departments and 

agencies to agree on all issues, as each 

has a different mission and research 

portfolio. However, they encouraged 

seeking harmonized guidance whenever 

possible. Thus the NPRM proposed that 

the regulations contain language 

requiring consultation among the 

Common Rule departments and 

agencies for the purpose of 

harmonization of guidance, to the extent 

appropriate, before guidance on the 

Common Rule is issued, unless such 

consultation is not feasible. The NPRM 

requested public comment on whether 

the proposed language would be 

effective in achieving greater 

harmonization of department and 

agency guidance, and if not, how it 

should be modified. 

3. Public Comments 

Approximately 60 comments were 

received regarding this proposal, and 

they were almost equally divided for 

and against it, although some of those 

opposed thought it did not go far 

enough to achieve the intended goal. 

Those who supported the proposal, 

either fully or partially, cited concerns 

they have as institutions, investigators, 

or IRBs in navigating different sets of 

regulations and different department or 

agency guidance documents. As noted 

above, among those who opposed the 

proposal, some expressed concern that 

the proposed language about 

harmonization did not go far enough. 

That is, they thought the language 

should mandate harmonization in 

guidance across Common Rule 

departments and agencies. These 

commenters felt that without a 

requirement to harmonize, federal 

departments and agencies will continue 

with business as usual and policy and 

guidance will continue to differ, 

creating complexity in the research 

environment. For example, one large 

research university emphasized the 

importance of harmonization across 

federal departments and agencies 

regarding guidance on the protections of 

human subjects for investigators, IRB 

administrators, and human subjects, and 

felt that the proposed language in the 

Common Rule NPRM might be 

ineffective in harmonizing agency 

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guidance. Several commenters 

emphasized the need, in particular, for 

greater harmonization between the 

Common Rule and FDA requirements, 

and between the Common Rule and the 

requirements of the Health Insurance 

Portability and Accountability Act of 

1996 (HIPAA; Pub. L. 104–191). 

Others were concerned that this 

provision would, in effect, mean that 

Common Rule departments and 

agencies issue fewer guidance 

documents because of lengthy internal 

government review and approval 

processes. 

4. Response to Public Comments and 

Explanation of the Final Rule: 

Harmonization of Guidance 

We believe there is a compelling case 

for as much consistency as is possible 

regarding guidance on the protections of 

human subjects. As such, the final rule 

implements the NPRM proposal at 

§ ll.101(j). The final rule creates a 

requirement that guidance should be 

issued only after consultation among the 

Common Rule departments and 

agencies, while also permitting 

guidance to be issued without such 

consultation when it is not feasible. The 

proposal recognizes that harmonization 

will not always be possible or desirable 

given the varied missions of the 

departments and agencies that oversee 

the protection of human subjects and 

differences in their statutory authorities. 

We note that some public comments 

expressed concern about the acceptable 

degree of variability among departments 

and agencies and encouraged attention 

to these concerns when diverging on 

guidance. The departments and agencies 

that oversee the protection of human 

subjects have a variety of missions and 

functions, including regulatory agencies 

and agencies that conduct and support 

research. In addition, in some cases, 

statutory differences among the 

departments and agencies have resulted 

in different regulatory requirements and 

guidance. They also oversee very 

different types and phases of research 

and thus may have reasonable 

justifications for differences in 

guidance. However, we agree that efforts 

should be made to issue collective 

guidance when possible and feasible 

and in a timely manner. We do not 

believe that this provision will result in 

the issuance of less guidance, because it 

largely codifies what has been the 

working practice among Common Rule 

departments and agencies up to this 

point. 

H. Compliance Dates and Transition 

Provisions of the Final Rule 

(§ ll.101(l)) 

1. NPRM Proposal 

In the NPRM, we shared the 

expectation that both the effective date 

of the final rule (meaning the date that 

the regulatory text is published in the 

Code of Federal Regulations) and the 

general compliance date of the final rule 

(meaning the date after which, as a 

general matter, regulated entities must 

comply with this rule) would be 1 year 

after publication of the final rule in the 

Federal Register. The NPRM also 

proposed two exceptions that would 

provide different compliance dates for 

two provisions. The first proposed 

exception pertained to the NPRM’s 

proposal that the Common Rule be 

extended to cover all biospecimens 

regardless of identifiability. The second 

proposed exception pertained to the 

NPRM’s proposal that a single IRB 

would be responsible for certain multiinstitutional clinical trials, also 

described as cooperative research. The 

NPRM proposed that both of these 

provisions would have compliance 

dates of 3 years after publication of the 

final rule in the Federal Register. The 

intent behind this proposed delay was 

to enable institutions to develop 

institutional policies and procedures 

necessary to implement these new 

requirements. The NPRM sought public 

comments about the advisability of this 

proposed approach as well as possible 

alternatives. 

The preamble to the NPRM also 

discussed the option for institutions or 

investigators to implement provisions of 

the final rule anticipated to provide 

additional regulatory flexibilities 

voluntarily 90 days after publication of 

the final rule in the Federal Register. 

This proposed approach was intended 

to enable institutions or investigators to 

gain the benefit of revisions to the 

Common Rule as soon as possible. The 

NPRM proposed a 90-day timeframe for 

this flexibility to enable the Common 

Rule departments and agencies time to 

develop the documents and tools 

needed to assist institutions in 

implementing the rule’s regulatory 

flexibilities (e.g., the Secretary’s broad 

consent templates) and the Secretary’s 

list of privacy safeguards. 

The NPRM also explained that the 

proposed extension of the Common 

Rule to clinical trials that are not 

directly funded by a Common Rule 

department or agency, but that are 

conducted at an institution that receives 

funding from a Common Rule 

department or agency for other human 

subjects research, would not apply to an 

institution until the institution had 

received federal funding for nonexempt 

research in an award made after the 

effective date of the final rule. 

The NPRM also proposed that 

ongoing human subjects research 

initiated before the effective date of the 

final rule would not need to comply 

with particular regulatory requirements. 

In addition, the NPRM proposed a 

grandfather clause for research 

involving the use of biospecimens 

collected before the compliance date. 

This clause applied to the provision that 

would extend the Common Rule to 

cover all biospecimens, regardless of 

identifiability. Specifically, the NPRM 

proposed that such research would not 

need to comply with the final rule if any 

research uses of the biospecimens 

occurred only after removal of any 

individually identifiable information. 

2. Public Comments 

A majority of comments received on 

the effective dates opposed the NPRM’s 

proposal that only nonidentified 

biospecimens would be grandfathered. 

Others commented on the proposed 3- 

year compliance date for the proposed 

expansion of the definition of human 

subjects to all biospecimens, regardless 

of their identifiability. In Section III, we 

discuss the determination not to finalize 

the biospecimen provisions, which 

addresses these comments. Some 

commenters expressed support for the 

general compliance date, as well as the 

delayed compliance date for the 

cooperative research provision. 

Many commenters expressed the 

viewpoint that regulated entities would 

need to invest significant time and 

resources before they would be able to 

comply with the changes to the 

Common Rule proposed in the NPRM. 

Some commenters (including an 

academic institution and a hospital 

association) noted that such investments 

would have implications not only for 

research operations, but also for clinical 

care. Some commenters also noted their 

concern that 1 year was not enough time 

for institutions to comply with the large 

number of new and different regulatory 

requirements proposed in the NPRM 

and that such changes would necessitate 

significant modifications to their 

research and clinical enterprises and 

might impose hardships on IRBs, IRB 

staff, institutional leadership, and the 

regulated research community. Several 

commenters explained that the 

proposed 1-year general compliance 

period would not provide enough time 

to update written IRB procedures 

(which are required under the Common 

Rule), disseminate such procedures, 

update related documents (e.g., forms), 

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and develop appropriate training 

materials. One of these commenters 

explained that accredited institutions 

will need time for accrediting bodies to 

align their accreditation standards with 

the revised regulatory standards or risk 

conflicts between meeting proposed 

regulatory standards and losing 

accreditations. 

Other commenters recommended 2- 

year or 3-year general compliance dates 

(including some that recommended 

permitting institutions to comply 

earlier), noting that compliance would 

be particularly challenging for 

institutions with smaller research 

programs. At least one commenter 

argued that the 3-year compliance date 

for the proposed cooperative research 

provision was inadequate given the 

significant costs and time that would be 

associated with establishing reliance 

agreements between collaborating 

research sites, maintaining required 

documents at the reviewing IRB, and 

ensuring that applicable laws were 

followed. At least one commenter 

argued that the proposed effective and 

compliance provisions left institutions 

with the discretion to remove studies 

from the oversight of the Common Rule 

without establishing any protective 

standards for doing so. 

One group representing multiple 

professional societies stated that the 

efficiencies achieved by eliminating 

protracted negotiations concerning 

consent forms and institutional 

responsibilities will far outweigh any 

upfront costs incurred through 

implementation of this policy, and 

advocated for a faster timeframe for 

compliance than the proposed 3 years 

from the time of final publication: 1 year 

for clinical trials and 2 years for 

research studies. Another commenter 

echoed these views. 

We did not receive many comments 

concerning the proposal to allow 

institutions to implement provisions 

offering regulatory flexibilities before 

the compliance date. 

3. Response to Comments and 

Explanation of the Final Rule: 

Compliance Dates and Transition 

Provisions 

The effective date and compliance 

dates included in this final rule are 

intended to meet the same general 

objectives as those described in the 

NPRM. Nonetheless, the approach 

adopted in the final rule is different in 

certain respects from the approach 

proposed in the NPRM. 

As a general matter, none of the 

proposed dates in the NPRM related to 

research with biospecimens will be 

implemented because the proposal 

included to extend the Common Rule to 

research with all biospecimens, 

regardless of identifiability, is not being 

implemented. 

The final rule adopts an effective date 

and a general compliance date of 1 year 

from publication of this final rule in the 

Federal Register. During this 1-year 

timeframe, institutions will be able to 

revise forms, documents, and practices 

for consistency with the revisions 

reflected in this regulation. Although we 

recognize the work associated with 

compliance, we concluded that 1 year is 

a reasonable and adequate timeframe. 

We note that ongoing research studies 

that were initially approved by an IRB, 

waived pursuant to §ll.101(i), or 

determined to be exempt before January 

19, 2018 will not be required to comply 

with the changes reflected in this final 

rule. 

Section 101(l) describes the regulatory 

requirements that will apply to specific 

categories of research once the final rule 

goes into effect. For clarity, § ll.101(l) 

begins by defining two sets of 

requirements. First, as set forth in 

§ ll.101(l)(1), the pre-2018 rule is 

described as the ‘‘pre-2018 

Requirements’’, which refers to the 

Common Rule as published in the 2016 

edition of the Code of Federal 

Regulations. As described below, certain 

ongoing research may be subject to these 

requirements. 

Section 101(l)(3)–(4) describes the 

different regulatory requirements that 

apply to different categories of research. 

For clarity and in order to have an easyto-implement standard, these categories 

are generally based upon the date the 

research was initially approved by an 

IRB, waived pursuant to §ll.101(i), or 

determined to be exempt. 

The first category of research, 

described in § ll.101(l)(3), applies to 

research initially approved by an IRB, 

waived pursuant to §ll.101(i), or 

determined to be exempt before January 

19, 2018. We believe that such research 

(e.g., research for which an initial 

determination was made before the 

effective date of this final rule) should, 

as a general rule, be able to follow the 

same set of standards throughout the 

entire course of the research. The intent 

is to minimize burdens associated with 

research conducted over a period of 

time and to avoid a requirement that 

such research be subject to two sets of 

rules during the lifetime of the research. 

For that reason, this regulation adopts as 

a default rule, set forth in 

§ ll.101(l)(3), that research initially 

approved by an IRB, waived pursuant to 

§ ll.101(i), or determined to be 

exempted before January 19, 2018 (the 

effective date of this final rule) will not 

be subject to this final rule but will 

continue to be subject to the 

requirements of the Common Rule in 

place before January 19, 2018. 

However, we also recognize that 

institutions may prefer, for a particular 

study initiated before to January 19, 

2018, to comply with this final rule 

given the benefits that it offers and for 

administrative simplicity such as 

common regulatory requirements across 

an institution. Thus, §ll.101(l)(3) 

permits institutions engaged in ongoing 

research that was initially approved by 

an IRB, waived pursuant to 

§ ll.101(i), or determined to be 

exempted before January 19, 2018, to 

choose, on a study-by-study basis, 

whether such research will be subject to 

the pre-2018 requirements (the rule in 

place before January 19, 2018, or the 

final rule. This is an exception and is 

offered as an additional flexibility to 

regulated entities. If an institution 

engaged in such research determines 

that it prefers to comply with the final 

rule for a particular research study, such 

research will be subject to the final rule 

if the institution formally makes a 

determination that the final rule will 

apply to such research and an IRB 

documents the decision made by the 

institution. If these requirements are not 

met or if the institution makes no 

decision, the pre-2018 requirements will 

apply to such research. 

The second category of research, 

described in § ll.101(l)(4), applies to 

research initially approved by an IRB, 

waived pursuant to §ll.101(i), or 

determined to be exempted on or after 

January 19, 2018. Because such research 

does not begin and is not conducted 

until after the general compliance date 

of this final rule, this category of 

research is subject to the final rule 

throughout its lifetime. 

A single IRB requirement for 

cooperative research has been adopted 

in §ll.114(b) of this final rule. As set 

forth in § ll.101(l)(2), this final rule 

adopts the proposed 3-year compliance 

date for this requirement to afford 

affected institutions sufficient time to 

prepare for and implement this 

requirement (e.g., developing 

institutional policies and procedures). 

Although we understand the concerns 

expressed concerning the complexities 

that will be involved in establishing 

reliance agreements to satisfy the 

cooperative research provision adopted 

in this final rule, this final rule reflects 

the conclusion that a 3-year compliance 

date is adequate for this provision, 

based on our belief that this provision 

will offer significant benefits to 

institutions, particularly as the 

regulated community becomes 

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accustomed to this requirement. In 

addition, we believe it is likely that the 

institutional policies, procedures, and 

standard documents needed to 

implement this regulatory provision 

will, over time, become increasingly 

standardized, which will significantly 

minimize the burden on institutions 

associated with this requirement. So 

long as all other regulatory requirements 

are satisfied, institutions may use a 

single IRB to oversee cooperative 

research even before this compliance 

date occurs with respect to any research 

that institutions believe may benefit 

from this approach. 

This final rule does not adopt the 

proposal mentioned in the preamble to 

the NPRM to permit institutions and 

investigators to voluntarily implement 

provisions in the final rule that allow 

additional flexibilities 90 days after 

publication of the final rule. We 

determined that the approach adopted 

at §ll.101(l)(3), and described above, 

offers institutions and investigators 

similar advantages with respect to the 

conduct of ongoing research, while 

providing greater clarity and more 

simplicity concerning which set of 

regulatory requirements apply to 

particular studies. 

We disagree with the comment that 

the proposed timelines enable 

institutions to remove their studies from 

the oversight of the Common Rule 

without establishing appropriate 

standards for doing so. The final rule 

does not enable institutions to opt out 

of compliance with the Common Rule. 

The effective dates do afford institutions 

the discretion to choose, on a studyspecific basis whether existing research 

should comply with the Common Rule 

in place when the research was initiated 

(the pre-2018 requirements) or this final 

rule (the 2018 requirements). This 

flexibility is offered only for certain 

ongoing research studies that were 

initially approved, determined to be 

exempt, or subject to a § ll.101(i) 

waiver before the effective date of this 

final rule. 

To explain the approach adopted in 

this final rule, the following chart 

describes the standards that apply to 

different categories of research: 

Research Study Initiation Date Standards 

Research initially approved by an IRB, waived pursuant to §ll.101(i), 

or determined to be exempt before January 19, 2018.

These studies are by default subject to the pre-2018 rule (the Common 

Rule as published in the 2016 edition of the Code of Federal Regulations). 

However, an institution engaged in such research may choose to comply with the final rule (2018 requirements) for such a study if the institution makes a determination to apply the final rule to the study 

and an IRB documents this determination. 

Research initially approved by an IRB, waived pursuant to §ll.101(i), 

or determined to be exempt on or after January 19, 2018.

These studies are subject to the final rule (2018 requirements). 

I. Severability (§ ll.101(m)) 

A severability clause has been added 

as §ll.101(m), providing that if any 

provision of this final rule is held to be 

unenforceable in one set of 

circumstances, it should be construed to 

give maximum effect to the provision as 

applied to other persons or 

circumstances. Similarly, if a provision 

is held to be invalid or unenforceable, 

that provision should be severable from, 

and have no impact on the application 

of, the remainder of the rule. This 

provision reflects our intention 

regarding the way that this final rule, 

and the pre-2018 rule, should be 

construed and interpreted and is meant 

as a clarification. 

III. Definitions for Purposes of this 

Policy (§ll.102) 

The final rule revises and adds new 

definitions of key terms for the purposes 

of this policy, as summarized below. 

Some of the changes are made to clarify 

new provisions that appear elsewhere in 

the final rule. In addition, the 

definitions have been placed in 

alphabetical order to facilitate searching 

by the reader. The definitions of 

institution, IRB, and IRB approval are 

unchanged but appear in a different 

place in the regulatory language. 

A. Certification (§ ll.102(a)) 

Although ‘‘certification’’ was defined 

in the pre-2018 requirements, as was 

proposed in the NPRM, the final rule 

clarifies that notification by the 

institution that a proposed research 

study has been reviewed and approved 

is made to the supporting ‘‘federal’’ 

department or agency and that it might 

be a component of the agency or 

department that is notified rather than 

the entity as a whole. This clarification 

relates to the change included in the 

final rule at §ll.102(d) regarding the 

definition of ‘‘federal department or 

agency’’ that clarifies that this phrase 

refers to the department or agency itself, 

not its bureaus, offices, or divisions. 

There were no public comments on this 

clarification. 

B. Clinical Trial (§ll.102(b)) 

1. Background and Pre-2018 

Requirements 

The pre-2018 rule did not include a 

definition of ‘‘clinical trial.’’ 

2. NPRM Proposal 

The NPRM proposed defining 

‘‘clinical trial,’’ for purposes of this 

policy, as a research study in which one 

or more human subjects are 

prospectively assigned to one or more 

interventions (which may include 

placebo or other control) to evaluate the 

effects of the interventions on 

biomedical or behavioral health-related 

outcomes. In addition, the NPRM 

requested public comment on whether 

the proposed definition should include 

additional explanation of what is 

encompassed by the term behavioral 

health-related outcomes. 

3. Public Comments 

Approximately 20 comments 

explicitly addressed the definition of 

‘‘clinical trial’’ included in the NPRM. 

All expressed concern that the proposed 

definition encompassed more activities 

than intended, given the NPRM 

discussion that the definition was 

intended to cover the riskiest research. 

Commenters who responded asked for 

some type of clarification, either in 

guidance or in the regulatory language 

itself about the term ‘‘behavioral healthrelated outcomes.’’ One commenter 

noted that clinical trials involving 

activities such as behavioral 

interventions, psychotherapy, or skills 

training, for example, should be 

included in the proposed regulations of 

clinical trials in a risk-based manner, as 

for nonbehavioral studies. That is, 

greater oversight would be required for 

trials with a higher potential degree of 

risk, regardless of what type of trial. The 

commenter noted that certain 

populations for whom behavioral health 

research is conducted are high risk by 

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17HHS. Clinical Trials Registration and Results 

Information Submission. 81 FR 64981. (Sept. 21, 

2016). Retrieved from https:// 

www.federalregister.gov/documents/2016/09/21/ 

2016-22129/clinical-trials-registration-and-resultsinformation-submission 

nature, such as chronically suicidal 

individuals. Another commenter asked 

that the regulatory language include 

additional explanation of what is 

encompassed by the term ‘‘behavioral 

health-related outcomes’’ because 

practitioners and researchers 

conceptualize the term differently. 

4. Response to Comments and 

Explanation of the Final Rule Definition 

of Clinical Trial 

The final rule at §ll.102(b) adopts 

the NPRM definition of ‘‘clinical trial,’’ 

which is a research study in which one 

or more human subjects are 

prospectively assigned to one or more 

interventions (which may include 

placebo or other control) to evaluate the 

effects of the interventions on 

biomedical or behavioral health-related 

outcomes. We generally expect that this 

definition will be applied harmoniously 

with the definition of clinical trial 

recently promulgated in the 

ClinicalTrials.gov final rule.17

In response to public concerns about 

an overly expansive definition of 

‘‘clinical trial’’ given the importance of 

that definition to the proposed 

extension of the rule to clinical trials 

previously not covered by the rule, we 

have eliminated that proposed 

expansion of coverage in this final rule. 

As such, the definition that appears in 

the final rule will only be relevant to the 

requirement for posting of consent 

forms for clinical trials conducted or 

supported by Federal departments or 

agencies (§ll.116(h)). It should be 

appropriate for that relatively narrow 

regulatory purpose. 

C. Department or Agency Head and 

Federal Department or Agency/ 

Institutions (§ll.102(c) (d) and (f)) 

1. Background and Pre-2018 

Requirements 

The pre-2018 rule provided a 

definition of ‘‘department or agency 

head.’’ The phrase appeared repeatedly 

throughout the regulations. 

2. NPRM Proposals 

New definitions of ‘‘department or 

agency head’’ and ‘‘federal department 

or agency’’ were proposed in the NPRM 

to clarify requirements related to federal 

department and agency discretion in 

applying the policy to their funded or 

conducted research. 

3. Public Comments 

There were no comments directly 

related to these proposed revisions. 

4. Explanation of the Final Rule: 

Definition of Department or Agency 

Head, Federal Department or Agency, 

and Institution 

The final rule adopts the NPRM 

proposals to provide new definitions of 

‘‘department or agency head’’ and 

‘‘federal department or agency,’’ which 

appear at § ll.102(c) and (d). 

‘‘Department or agency head’’ at 

§ ll.102(c) refers to the head of any 

federal department or agency, for 

example, the Secretary of HHS, and any 

other officer or employee of any federal 

department or agency to whom 

authority has been delegated. To add 

clarity to the definition found in the 

pre-2018 regulations, the example of the 

Secretary of HHS was inserted. 

The final rule provides at 

§ ll.102(d) a definition of ‘‘federal 

department or agency’’ in order to avoid 

confusion as to whether this phrase 

encompasses federal departments and 

agencies that do not follow the Common 

Rule. The definition also clarifies that 

this phrase refers to the department or 

agency itself, not its bureaus, offices, or 

divisions. This is consistent with the 

historical interpretation of the Common 

Rule. Related to this, the definition of 

‘‘institution’’ was changed at 

§ ll.102(f) in the final rule to clarify 

that departments can be considered 

institutions for the purposes of this 

policy. The final rule provides examples 

of what is intended by this definition: 

HHS, the Department of Defense, and 

the Central Intelligence Agency. 

D. Human Subject (§ll.102(e)) 

1. Background and Pre-2018 

Requirements 

The pre-2018 rule defined ‘‘human 

subject’’ as a living individual about 

whom an investigator (whether 

professional or student) conducting 

research obtains (1) data through 

intervention or interaction with the 

individual, or (2) identifiable private 

information. Further, the pre-2018 rule 

asserted that ‘‘private information’’ was 

considered individually identifiable if 

the identity of the subject is or may 

readily be ascertained by the 

investigator or is associated with the 

information. 

Thus, in cases where no intervention 

or interaction with an individual 

occurred, determining the meaning of 

‘‘identifiable’’ and ‘‘readily 

ascertainable’’ was central to 

determining whether human subjects 

were involved in a research activity 

covered by the pre-2018 rule. Under the 

pre-2018 rule, provided the data were 

collected for purposes other than the 

currently proposed research, it was 

permissible for investigators to conduct 

research on biospecimens and data that 

had been stripped of all identifiers or 

coded without obtaining consent 

because the nonidentified biospecimens 

and data did not meet the regulatory 

definition of a human subject. 

Moreover, ‘‘private information’’ was 

not considered to be identifiable under 

the pre-2018 rule if the identity of the 

subject is not or may not be ‘‘readily 

ascertained’’ by the investigator from 

the information or associated with the 

information. 

If the definition of ‘‘human subject’’ 

was met, together with the other 

significant requirements, the pre-2018 

rule required IRB review and approval 

unless the study was exempt. IRB 

waiver of informed consent was 

allowable under the Common Rule, if 

the research study satisfied the criteria 

for waiver of informed consent. 

2. NPRM Proposal 

The NPRM proposed to revise the 

definition of ‘‘human subject’’ to 

include research in which an 

investigator obtains, uses, studies, or 

analyzes biospecimens, regardless of 

identifiability. Thus, the focus of this 

proposal was to require informed 

consent for research involving 

biospecimens in all but a limited 

number of circumstances. In addition, 

the NPRM proposal would have still 

permitted IRBs to waive the requirement 

for informed consent for research use of 

biospecimens, but the requirements for 

approval of such waivers would have 

been very strict, and such waivers 

would have occurred only in rare 

circumstances (see Section XIV on 

waiver of informed consent). This 

expansion of the definition of ‘‘human 

subject’’ would also have triggered other 

provisions of the NPRM relating to the 

use of biospecimens, including security 

measures. Thus, it was a complex and 

far-reaching proposal. 

The NPRM also offered two 

alternative proposals to altering the 

definition of ‘‘human subject,’’ both of 

which maintained ‘‘identifiability’’ as a 

major aspect of determining 

applicability of the Common Rule to 

biospecimens. The public was asked to 

comment on which of the three 

proposals achieved the most reasonable 

tradeoff between the principles of 

autonomy and beneficence. 

Alternative Proposal A would have 

expanded the definition of ‘‘human 

subject’’ to include whole genome 

sequencing (WGS). Under this 

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7164 Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 

18CIRCULAR NO. A–130 Memorandum to: The 

Heads of Executive Departments and Agencies 

Subject: ‘‘Managing Information as a Strategic 

Resource’’. July 7, 2016. See especially, Appendix 

II: Responsibilities for Managing Personally 

Identifiable Information. Retrieved from https://

www.federalregister.gov/documents/2016/07/28/ 

2016-17872/revision-of-omb-circular-no-a-130- 

managing-information-as-a-strategic-resource 

alternative, WGS would have been 

considered to be the sequencing of a 

human germline or somatic 

biospecimen with the intent to generate 

the genome or exome sequence of that 

biospecimen. 

Alternative Proposal B would have 

expanded the definition of ‘‘human 

subject’’ to include the research use of 

information that was produced using a 

technology applied to a biospecimen 

that generated information unique to an 

individual. In such a case, it was 

foreseeable that, when used in 

combination with publicly available 

information, the individual could have 

been identified. Information that met 

this standard would have been referred 

to as ‘‘bio-unique information.’’ 

The NPRM also asked the public to 

comment on whether the rule should 

include a definition of ‘‘biospecimen’’ 

and whether the rule should be clearer 

and more direct about the definition of 

‘‘identifiable private information.’’ 

The NPRM also proposed some minor 

changes to the wording of the definition 

of ‘‘human subject’’ merely to clarify 

how the word ‘‘obtains’’ has been 

interpreted. 

The NPRM did not propose any major 

substantive modifications to the 

descriptions of ‘‘private information’’ 

and ‘‘identifiable private information’’ 

found in the pre-2018 rule. However, 

the NPRM proposed clarifying language 

with regard to ‘‘private information’’ 

and ‘‘identifiable private information.’’ 

The pre-2018 rule used the example of 

a medical record as constituting private 

information. The NPRM added the 

example of a biospecimen in keeping 

with the proposal to expand the 

definition of ‘‘human subject’’ to 

include all biospecimens. In addition, 

the NPRM proposed adding the words 

‘‘shared or’’ to the description of what 

constitutes ‘‘private information,’’ for 

the purpose of expanding the scope of 

the information that would be described 

by that term. 

In addition, the NPRM asked for 

public comment about whether a 

different identifiability standard would 

be appropriate. One alternative 

discussed was to adopt the term 

‘‘identifiable private information’’ with 

the term used across the Federal 

Government: ‘‘personally identifiable 

information’’ (PII). PII refers to 

information that can be used to 

distinguish or trace an individual’s 

identity (such as name, social security 

number, biometric records) alone, or 

when combined with other personal or 

identifying information that is linked or 

linkable to a specific individual, such as 

date and place of birth, or mother’s 

maiden name. It acknowledged that 

replacing ‘‘identifiable private 

information’’ with ‘‘PII’’ would increase 

the scope of what is subject to the 

Common Rule. Subsequent to the 

release of the NPRM, the Office of 

Management and Budget (OMB) 

updated government-wide guidance for 

managing personally identifiable 

information.18

Related to this issue, the NPRM noted 

new legislative developments, 

specifically the Newborn Screening 

Saves Lives Reauthorization Act of 2014 

(Pub. L. 113–240), signed into law in 

December 2014. The law required 

consent for federally funded research 

with newborn dried blood spots and 

prohibits IRBs from waiving consent. 

These changes were to be effective until 

updates to the Common Rule were 

promulgated, and applied whether or 

not the newborn dried blood spots 

would be considered ‘‘identifiable 

private information’’ under the 

regulatory definition. 

3. Public Comments 

a. Public Comments on the Primary 

NPRM Proposal 

The proposal regarding revising the 

definition of ‘‘human subject’’ to 

include biospecimens regardless of 

identifiability was commented on by 

almost 50 percent of the commenters. 

Others commented on the effects such 

an expansion would have on consent 

requirements, the ability to waive 

consent, and the applicability of 

exemptions and exclusions. The vast 

majority of commenters who addressed 

this expansion (80 percent) were 

opposed to it for a variety of reasons, 

particularly because of the implications 

of this change for requiring consent for 

most research uses of biospecimens that 

were collected as part of clinical care. 

A majority of these commenters 

responded as members of the general 

public (that is, not explicitly affiliated 

with a specific organization or 

institution) or as patients (including 

family members of patients). Patients 

tended to oppose these proposals, 

focusing on the additional and more 

stringent criteria for waiver of informed 

consent because they believed the 

effects of the proposals would be that 

many people would not provide 

consent, thus restricting access by 

investigators to biospecimens, which 

would in turn slow research. 

Investigators also expressed concerns 

about the negative impact on research. 

Organizations and institutions with 

some affiliation with the research 

enterprise expressed opposition to this 

suite of proposals as well, but for 

different reasons, as discussed further 

below. 

Most support for the expansion of the 

definition of ‘‘human subject’’ to 

encompass all biospecimens and its 

implications for consent, waiver of 

consent, and exempt research came 

from members of the public who argued 

that they wanted to always be consulted 

before their biospecimens were used in 

research, without exception. Within this 

group, a strong majority opposed the 

comprehensive biospecimen-related 

proposals because they were 

uncomfortable with the concept of 

broad consent (as discussed in Section 

IIV of this preamble) to any future 

research use of those biospecimens and 

the existence of any type of over-ride by 

an IRB of the requirement to obtain 

informed consent. 

Many of the commenters supporting 

the expansion stated that it would 

respect autonomy by requiring that 

nearly all research with biospecimens 

be subject to IRB review and informed 

consent requirements. Others expressed 

distrust of the medical and scientific 

enterprises. One member of the public 

felt that consent should be required for 

government research seeking to use an 

individual’s biospecimens, and that 

researchers should be required to inform 

the individual of the ‘‘who, what, how, 

and why’’ of the desired research. 

Many of those who expressed support 

for this proposal also indicated that they 

felt it important for their biospecimens 

to be anonymized in research activities. 

For example, a member of the public 

with experience in biobanking 

expressed a willingness to consent to 

the use of his biospecimens to advance 

science, but called for a mechanism to 

inform the public about such research 

use even if some individuals might 

decline to participate. The commenter 

stressed the importance of respecting 

the individual’s right to know and 

refuse, citing privacy concerns and 

stressing the importance of anonymity 

of biospecimens to protect individuals 

from potential negative consequences. 

Still others supported the expansion 

of the definition of ‘‘human subject’’ to 

include all biospecimens because of a 

desire to receive research results or to 

financially profit from discoveries, 

implying that retaining identifying 

information with biospecimens would 

enable both of these possibilities. Some 

who felt there is an entitlement to 

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financially profit from discoveries 

described biospecimens as personal 

property. For example, one commenter 

compared the use of an individual’s 

biospecimens without consent to one 

party illegally taking another’s property 

such as land, a house, or an arm. 

Several commenters noted that 

medical services should not be allowed 

to be contingent upon a person’s 

consent to use of their leftover 

biospecimens for research despite the 

fact that this was not proposed in the 

NPRM. In fact, the pre-2018 rule states 

that informed consent must include a 

statement that ‘‘refusal to participate 

will involve no penalty or loss of 

benefits to which the subject is 

otherwise entitled’’ and that element 

appears in the final rule as well. 

For example, one commenter 

indicated that patients should be 

informed and be given the opportunity 

to consent to the use of their body 

tissues, and if one declines consent, the 

individual should not be denied 

treatment or receive diminished care. In 

other words, they felt that consent 

should never be a condition of 

treatment. 

The reasons for opposing the 

expansion of the definition of ‘‘human 

subject’’ to include all biospecimens 

were numerous, including: the 

feasibility of obtaining broad consent in 

a clinical setting; the costs of obtaining, 

tagging, and tracking consents given the 

low risk nature of the research in 

question; allowing autonomy to trump 

beneficence and justice; insufficient 

evidence of risk or public concern about 

the issue; the fact that it would result in 

fewer specimens collected from fewer 

sources, with adverse implications for 

rare diseases and for justice; the idea 

that requiring all biospecimens to 

remain identified poses greater privacy 

and confidentiality risks than the 

current system; and overall negative 

impacts on research. 

Many expressed concern about the 

number of biospecimens that might no 

longer be available for research, not out 

of concern that individuals would 

decline to have their leftover tissue used 

in research, but rather because many 

hospitals and medical providers might 

decline to enact the expensive consent 

and tracking system that the NPRM 

envisioned. Some commenters were 

concerned that this would then limit the 

heterogeneity of biospecimens obtained 

and stored, as community hospitals and 

clinics might opt out of participating in 

such collections. 

Several comments suggested that for 

academic medical centers where a large 

amount of research is conducted, 

research activities often do not result in 

profits, and that the proposed policies 

would come at great costs to institutions 

already struggling to financially sustain 

a healthy research enterprise. For 

example, one commenter noted that the 

NPRM proposal would require 

additional resources to obtain consent, 

which would hinder smaller institutions 

with fewer staff or resources available in 

their ability to contribute to scientific 

and medical research, and limit the 

opportunities for patients at these 

facilities to participate in research. The 

commenter also pointed out that 

academic institutions rarely receive 

significant financial gain from their 

research, and institutions sometimes 

share biospecimens, which can be 

valuable in research, especially in the 

case of uncommon and poorly 

understood diseases. Thus, this 

commenter expressed concern that 

biospecimens might not be available for 

research given the requirements of the 

proposed policy. 

Many members of the public with rare 

diseases commented on how research 

into their specific diseases might be 

affected should the NPRM proposal be 

finalized. For example, several 

commenters expressed interest in the 

proposed rule because they or a family 

member had been diagnosed with a 

desmoid tumor, which are often limb 

threatening and sometimes life 

threatening. Research using tissue 

blocks is critical to determine how to 

treat these tumors, which are rare and 

can vary among patients. The 

commenter felt that the proposed rule 

would make desmoid tumor research 

virtually impossible by reducing access 

to the already low number of tissue 

blocks available for research. 

More than one academic medical 

center asserted that there was a lack of 

evidence that patients value their 

autonomy over the potential for 

innovative diagnostics, treatments, 

cures, or preventative interventions that 

could result from research with leftover 

biospecimens, and called for empirical 

research on whether patients, patient 

advocacy groups, and the general public 

value autonomy (in the form of written 

consent for research use of 

nonidentified biospecimens) above 

other values when explained in light of 

potential impact on medical advances. 

Some public commenters pointed out 

the illogic of treating biospecimens 

differently from information for the 

purposes of defining what constitutes a 

human subject. For instance, one 

professional organization composed of 

investigative pathologists and dozens of 

individual pathologists around the 

country noted that there are several 

areas in which the NPRM proposes 

treating biospecimens differently from 

identifiable information unjustifiably 

since both create the potential for 

identification of the donor and a 

potential negative impact on the 

individual and their family, such as 

employment or insurance 

discrimination, embarrassment, or 

stigmatization. That organization noted 

that no empirical evidence has been 

provided to indicate either that 

biospecimens pose a risk greater than 

that posed for identifiable information 

or that the public is more concerned 

about the use of biospecimens compared 

to the use of identifiable private 

information. 

One member of the public asserted 

that the research use of leftover 

biospecimens in medical research poses 

less of a privacy risk to individuals than 

market research that analyzes one’s 

attitudes, words, and behaviors and is 

used to generate commercial profit. 

Several commenters noted that the 

proposed expansion of the definition of 

‘‘human subject’’ creates a cascade of 

consequences throughout the rule that 

are overly complex and unnecessary 

given the minimal risk of such research. 

Other commenters suggested that the 

NPRM proposals would have negative 

impacts on the advancement of 

precision medicine. For example, a 

research university felt that mandating 

consent for de-identified biospecimens 

would impair the ability to achieve 

precision medicine for all. The 

commenter asserted that to offer care 

tailored to the needs of each individual 

based on understanding how each 

person is affected by disease requires 

understanding differences in the origins 

and manifestations of disease in 

individual patients who differ in 

genetics and environmental exposures. 

The commenter felt that restricting 

access to nonidentified biospecimens 

would violate the principles of justice 

and beneficence because many health 

care facilities serving under-represented 

minorities and economicallydisadvantaged individuals, particularly 

those in rural settings, might not have 

the financial resources to obtain and 

track consent. As a result, medical 

research therefore might represent a 

skewed population of individuals 

receiving care at large, research 

intensive referral centers. In addition, 

the commenter felt that compliance 

would impose an onerous and 

expensive bureaucratic burden that 

would result in many institutions no 

longer collecting and using these 

critically important specimens with the 

net effect of thwarting efforts to provide 

precision medicine for all citizens. 

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19 Kwok P, et al. Harder Than You Think: A Case 

Study of Re-Identification Risk of HIPAACompliant Records. NORC at The University of 

Chicago and Office of the National Coordinator for 

Health Information Technology. 2011. Retrieved 

from http://www.amstat.org/meetings/jsm/2011/ 

onlineprogram/AbstractDetails.cfm?

abstractid=302255. 

20NCI defines ‘‘biospecimen’’ as, ‘‘A quantity of 

tissue, blood, urine, or other human-derived 

material. A single biopsy may generate several 

biospecimens, including multiple paraffin blocks or 

frozen biospecimens. A biospecimen can comprise 

subcellular structures, cells, tissue (e.g., bone, 

muscle, connective tissue, and skin), organs (e.g., 

liver, bladder, heart, and kidney), blood, gametes 

(sperm and ova), embryos, fetal tissue, and waste 

(urine, feces, sweat, hair and nail clippings, shed 

epithelial cells, and placenta). Portions or aliquots 

of a biospecimen are referred to as samples (NCI 

Best Practices working definition).’’ Retrieved from 

http://biospecimens.cancer.gov/bestpractices/got/ 

#B. Last modified March 16, 2016. 

21The Commission had previously addressed 

related issues in its October 2012 report, Privacy 

and Progress in Whole Genome Sequencing. 

Washington, DC: Presidential Advisory Commission 

for the Study of Bioethical Issues. Retrieved from 

http://bioethics.gov/sites/default/files/ 

PrivacyProgress508l1.pdf. 

Many commenters expressed the 

opinion that the existing regulatory 

framework is adequate and that current 

practices should be maintained, 

stressing that the research use of 

nonidentified data or biospecimens 

involves minimal or low risk to the 

research subject. Furthermore, several 

commenters noted that, although it is 

theoretically plausible to identify a 

person based on their biospecimen, the 

likelihood remains remote enough to 

argue against the presumption that the 

sources of all biospecimens are 

identifiable and cited a study showing 

that the risk of re-identification from a 

system intrusion of databases was only 

0.22 percent.19 Other commenters noted 

that the existing definition of human 

subject is sufficient because once a 

biospecimen becomes identifiable in 

research, such research is considered to 

involve human subjects and therefore 

IRB review and consent or waiver of 

consent would be required. They argued 

that the current policy works and there 

has been no evidence provided that it 

needs to be fixed. 

The NPRM specifically asked whether 

the final rule should include a 

definition of ‘‘biospecimen’’ to assist the 

regulated community in understanding 

what types of activities might fall under 

the rule. Approximately 100 comments 

answered this question. A majority of 

these comments did not provide a 

suggestion for how biospecimen should 

be defined, but suggested that the 

Federal Government convene panels 

and solicit input from governmental and 

nongovernmental experts. 

One university emergency medical 

department suggested including in this 

definition biological samples from 

human subjects which contain DNA and 

are being obtained for the purpose of 

medical analysis and provided 

examples of biospecimens which would 

fall under this definition, including 

excised tissue (fresh, fixed, or paraffin 

embedded), whole blood, urine (when 

hematuria is known to exist), and saliva 

among others. The commenter also 

provided examples of biospecimens 

which would not fit in this definition, 

including serum or plasma, urine (when 

no hematuria is known to exist), and 

processed tissues where the DNA has 

been removed as a part of the 

processing. 

Others indicated that the definition of 

biospecimen used by the National 

Cancer Institute 20 seemed appropriate 

and workable for this rule. 

A majority of comments on the 

definition of ‘‘biospecimen’’ asked for 

explicit clarification on how certain 

biospecimens would be treated under 

the rule. Several comments asked 

whether microbiology biospecimens 

would be considered covered under the 

NPRM proposal. One research 

university requested specification that 

biologic material of organisms that use 

human biospecimens merely as a host 

(e.g., bacteria, viruses, fungi) not be 

considered to involve human subjects. 

The NPRM also asked whether 

covering only biospecimens that include 

nucleic acids would be a reasonable 

definition. A majority of those who 

responded to this said it would not be 

a good line to draw. One commenter 

specifically noted that the presence of 

nucleic acids does not guarantee reidentification. 

b. Public Comments on Alternative 

NPRM Proposals A and B 

Some of the alternative NPRM 

proposals were partly based on the 

premise that biospecimens could at 

some point become readily identifiable 

as a result of increasingly sophisticated 

technology. Many public commenters 

stated that a better approach to 

protecting privacy than requiring 

consent is to impose sanctions against 

investigators who aim to or do reidentify biospecimens without 

authorization by an IRB or other body. 

Such an approach, they said, would be 

less onerous for the entire enterprise, 

and if accompanied by clear guidance 

from funding agencies, would do more 

to protect privacy and guard against 

potential harms to subject rights and 

welfare. 

Few commenters, approximately 20, 

explicitly supported Alternative A or B 

over the NPRM proposal or the pre-2018 

rule. 

The Presidential Commission for the 

Study of Bioethical Issues explicitly 

supported Alternative B, noting that it is 

the most forward-looking of all three 

proposals, using ‘‘bio-unique’’ data as 

human subjects research with a focus on 

the technology and its ability to identify 

donors using small amounts of data, as 

opposed to tying the definition of 

human subjects research to a particular 

kind of data.21 Another commenter 

identified alternative B as the best 

proposal to keep pace with advances in 

technology (including technologies 

driving personalized medicine), protect 

research participants, respect autonomy, 

increase trust, and close the gap in 

protection in the current regulations. 

Those who supported the primary 

NPRM proposal—to expand the 

definition of ‘‘human subject’’ to 

include all biospecimens—indicated 

that Alternatives A and B would not 

give individuals who wanted to control 

the use of their biospecimens the 

opportunity to do so. 

Approximately 250 commenters 

(about 12 percent of the total comments 

received) said that they endorsed the 

pre-2018 policy, but that if the Federal 

Government must do something other 

than maintain the current definition of 

human subject, Alternative A would be 

preferable to the NPRM proposal or to 

Alternative B. These comments argued 

that Alternative A would be the least 

disruptive to the research enterprise, but 

that the pre-2018 policy would be 

better. 

However, the majority of those 

commenters addressing the alternative 

proposals indicated that neither struck 

an appropriate balance among the 

Belmont Report principles. A research 

university concluded that both 

alternatives lack balance, emphasizing 

respect for persons with little regard for 

the principles of beneficence and 

justice. 

Additional concerns about Alternative 

A included the fact that while limiting 

the expansion of the scope of activities 

covered by the rule to whole genome 

sequencing may be a reasonable line for 

inclusion today, that line might not be 

inclusive enough in the future. 

Additional concerns about Alternative 

B included that by requiring continual 

re-review of technologies and databases 

by the federal government, there would 

be an ‘‘inevitable lag’’ between when a 

technology might be identified and 

when it would be added to the list. 

Thus, these commenters argued that the 

list might end up being useless. 

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c. Alternative Proposals Offered by 

Public Commenters 

Many commenters proposed or 

endorsed alternatives to the NPRM 

proposals. Generally, these alternatives 

involved maintaining the existing 

schema, developing a system of notice 

and opt out, engaging in a public 

education campaign about how the 

research enterprise works, and 

developing penalties and sanctions for 

re-identification of biospecimens and 

information. A policy that requires 

notice, opt out, and public education 

were generally endorsed or discussed 

together. 

The Secretary’s Advisory Committee 

on Human Research Protections 

(SACHRP) offered one of the most 

detailed alternative proposals. SACHRP 

indicated that existing practices of 

research with biospecimens and data 

that have been collected for nonresearch 

uses (most often in the course of clinical 

care) should be revised to better protect 

subjects through greater transparency, 

public education about research with 

biospecimens, more exacting standards 

for protecting against dignity harms, 

allowing individuals to opt out, 

requiring IRB or institutional review 

and approval of specific research uses of 

identified biospecimens and identified 

data, and through strict legal 

consequences for re-identification of deidentified biospecimens and data that 

have been shared for research purposes. 

SACHRP also proposed that data 

security protections be developed to 

safeguard biospecimen-associated data 

and identified data against unauthorized 

release or access, and focused review of 

the storage, maintenance, or secondary 

research use of identified biospecimens 

and identified data to determine 

whether the proposed activity is likely 

to be objectionable. 

A professional organization of 

investigative pathologists urged 

consideration of opt-out broad consent 

models for nonidentified biospecimens 

collected in research and nonresearch 

settings, and suggested that this model 

would bring consent for the broad use 

of nonidentified biospecimens in line 

with HIPAA privacy practices, 

preserving the ability for an individual 

to decide not to participate in research 

efforts. This organization asserted that 

this option would be less burdensome 

and an inclusive, respectful, and 

functional way to promote ethically 

conducted biomedical research on 

biospecimens. 

d. Public Comments on Identifiability 

Approximately 40 comments were 

received in response to the request to 

comment on the definition of 

identifiable private information. 

Comments were mixed. The largest 

proportion of those comments 

(approximately 13) supported the 

definition in the pre-2018 rule. Others 

felt that the pre-2018 definition of 

identifiable private information was 

sufficient, but that additional guidance 

would be needed to implement it. 

Another group of commenters 

supported adopting a different 

identifiability standard in the final rule 

(such as the federal government’s 

personally identifiable information 

standard, or the HIPAA identifiability 

standard). 

Several public comments claimed that 

the meaning of ‘‘identifiable’’ with 

regard to information and biospecimens 

will change as technology advances. 

They indicated that the technique of 

whole genome sequencing altered the 

conversations about the identifiability of 

biospecimens and future technological 

advances using advanced computing 

and large databases could provide 

methods for easily aggregating disparate 

data for the purposes of identifying an 

individual. 

Public comments received from a 

large professional association related to 

the definition of identifiable private 

information noted that the modifier 

‘‘may be readily ascertained’’ that was 

included in the definition of identifiable 

private information within the 

definition of human subject allows for 

changes in scientific technology and 

data sharing over time since what was 

readily ascertainable 10 years ago has 

changed and will be different 10 years 

from now. The commenter noted that 

this allows IRBs and investigators to 

assess identifiability based on current 

technology, data sharing and computing 

capabilities, rather than comparing it to 

an enumerated list of identifiers or 

scientific technologies. 

Some commenters expressed a desire 

for guidance to be issued on these 

definitions or for the definitions to be 

better clarified and explained in the 

regulatory text. Several comments 

specifically suggested a need for a 

definition of or guidance on the term 

‘‘readily ascertainable.’’ 

Approximately 10 comments 

endorsed replacing the Common Rule’s 

identifiability standard with either the 

Federal Government’s concept of 

personally identifiable information (PII) 

or HIPAA’s concept of protected health 

information (PHI). 

One academic medical center felt that 

the concept of PII would unnecessarily 

broaden the scope of the Common Rule 

and create a larger administrative 

burden due to the vagueness of the PII 

definition without providing substantial 

added protection to human subjects, 

and suggested replacing the term 

‘‘identifiable private information’’ with 

the definition of ‘‘protected health 

information,’’ which can be found at 45 

CFR 160.103. 

Those who supported the use of the 

PII concept noted that it would 

harmonize other definitions of 

identifiability used in other Federal 

Government regulations. One state 

department of health and human 

services noted that adopting PII would 

be consistent with other confidentiality 

laws, policies, and industry standards 

that require organizations to protect the 

privacy and security of PII, achieving 

consistency across standards and 

helping organizations comply with the 

various privacy and security 

requirements. The commenter felt that 

replacing the identifiable private 

information standard with the concept 

of PII should not be overly burdensome 

on the research community since 

exemptions and waivers of informed 

consent would likely apply in many 

contexts. 

A few commenters also noted that 

regardless of how identifiability might 

be defined, some concerns about group 

harms still were not addressed in the 

NPRM. 

Several other commenters noted that 

a change to the definition of PII would 

not increase public trust or 

understanding of the system, nor would 

it likely clarify for investigators whether 

biospecimens or private information are 

identifiable. 

A majority of the commenters noted 

that whatever direction the final rule 

takes; additional guidance will be 

necessary to reduce ambiguity within 

the regulated community. 

e. Public Comments on Newborn Dried 

Blood Spots 

Approximately 50 comments 

discussed how issues related to research 

use of residual newborn dried blood 

spots (DBS) were addressed by the 

proposal to expand the definition of 

human subject. Of those comments, 35 

supported the idea of parental consent 

for research with DBS. Thirty-two 

comments stated that specific consent 

should be required for all research uses, 

in other words, that the exemptions and 

exclusion categories should not apply to 

research involving DBS. Those who felt 

that parental consent should always be 

required for the research use of DBS 

expressed the need to respect autonomy 

and parents’ rights, and frequently 

conveyed a distrust of medicine and 

scientists. These individuals generally 

supported the spirit of the main NPRM 

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proposal, but objected to any 

exemptions, exclusions, and waivers of 

informed consent. 

Fifteen comments expressed concerns 

that the biospecimen proposals in the 

NPRM would impede research 

involving DBS, which could negatively 

affect the expansion and improvement 

of newborn screening programs due to, 

among other things, a possible lack of 

resources for obtaining consent. In this 

regard, an employee of a California state 

health department described the health 

department’s experience of seeking and 

obtaining consent for the research use of 

DBS. This individual noted that 52 

percent of new parents were offered the 

opportunity to consent. Of those offered 

the opportunity, 90 percent said yes. 

This employee was thus concerned that 

due to staffing constraints, the majority 

of new parents simply would not be 

asked to provide consent to future 

research uses of DBS. 

Others indicated that some kind of 

notice and opt-out process would be 

acceptable, but that as a general matter 

the research community would benefit 

from guidance on the extent to which 

the exemptions and exclusions apply to 

this type of work. 

4. Response to Comments and 

Explanation of the Final Rule: 

Definition of Human Subject 

The final rule does not implement the 

proposed expansion of the definition of 

‘‘human subject’’ to include all 

biospecimens regardless of 

identifiability. It is clear from the 

comments received that the public has 

significant and appropriate concern 

about both the need for obtaining 

consent before using such biospecimens 

for research, and the potential negative 

impacts of implementing that proposal 

on the ability to conduct research. And, 

while it does not substantially change 

the definition of ‘‘identifiable private 

information,’’ the final rule includes a 

new process by which Common Rule 

departments and agencies can regularly 

assess the scientific and technological 

landscape to determine whether new 

developments merit reconsideration of 

how identifiability of either information 

or biospecimens is interpreted in the 

context of research. Because the final 

rule does not implement the NPRM’s 

proposed expansion to the definition of 

‘‘human subject,’’ it also does not 

implement the NPRM proposal to 

exclude certain research activities 

involving nonidentified biospecimens. 

With regard to changing the definition 

of ‘‘human subject’’ to include all 

biospecimens, the majority of 

commenters who addressed this 

expansion opposed it for a variety of 

reasons, as described above. As 

explained in the NPRM, one of the core 

reasons for proposing that the rule be 

broadened to cover all biospecimens, 

regardless of identifiability, was based 

on the premise that continuing to allow 

secondary research with biospecimens 

collected without consent for research 

places the publicly funded research 

enterprise in an increasingly untenable 

position because it is not consistent 

with the majority of the public’s wishes, 

which reflect legitimate autonomy 

interests. However, the public 

comments on this proposal raise 

sufficient questions about this premise 

such that we have determined that the 

proposal should not be adopted in this 

final rule. 

Further, the current regulatory policy 

appears to sufficiently protect against 

the unauthorized research use of 

identifiable biospecimens. Under the 

pre-2018 rule, if an investigator funded 

by a Common Rule department or 

agency uses nonidentified biospecimens 

and manages to re-identify them, that 

investigator would then be conducting 

human subjects research without IRB 

approval, in violation of the rules. It 

should also be noted that the position 

adopted in the final rule does not 

eliminate any authority, separate and 

apart from the Common Rule, that 

Common Rule departments and 

agencies have to establish policies with 

additional requirements related to 

consent for research involving 

nonidentifiable biospecimens or 

nonidentifiable private information, or 

preclude them from exercising such 

authority. 

Nonetheless, we acknowledge the 

need to also appropriately respect and 

promote autonomy interests. Any future 

proposals aimed at promoting autonomy 

should jointly evaluate the importance 

of the autonomy interests at issue, as 

well as explicitly quantify the potential 

negative impacts the proposal might 

have on the ability to conduct research, 

including such consequences on the 

representativeness of biospecimens 

available for research. 

In the final rule, we have added 

requirements to the informed consent 

process to increase transparency so that 

potential subjects will have more 

information about how their 

biospecimens or private information 

might be used. Specifically, prospective 

subjects will be told that identifiers 

might be removed from their 

biospecimens or private information 

and used for future research, if this 

might be a possibility. Finally, as some 

public comments addressed the desire 

to share in any profits that might accrue 

as a result of research use of their 

biospecimens, an additional element of 

consent will require, as appropriate, a 

statement that the subject’s 

biospecimens may be used for 

commercial profit and whether the 

subject will or will not share in this 

commercial profit. We believe that this 

increased attention to transparency in 

the consent process will allow 

individuals to make informed choices 

about whether they want to consent to 

current or future research uses of their 

biospecimens. A few clarifying changes 

are made in the final rule pertaining to 

the definition of ‘‘human subject’’ and 

the components within that definition, 

particularly referring to both 

information and biospecimens as key 

determinants of whether a human 

subject is involved in research. 

With respect to the definition of 

‘‘identifiable private information,’’ 

although the pre-2018 definition of 

‘‘identifiable’’ did not incorporate a 

specific process for considering the 

growing volume of information being 

generated and shared in research 

(including from biospecimens), or 

consider how evolving technology can 

ease and speed the ability to re-identify 

information or biospecimens previously 

considered nonidentifiable, we 

appreciate that a change in that 

definition could have collateral 

implications with respect to imposing 

unwarranted consent requirements on 

activities that were not subject to the 

regulations. We appreciate the 

commenter requests for more guidance 

on how they should interpret the 

definition of identifiable private 

information. Thus, although the final 

rule only makes minor changes to the 

existing definition of ‘‘identifiable 

private information,’’ it sets in place a 

process (§ll.102(e)(7), discussed 

below) that will help facilitate any 

necessary future updates to the 

understanding of that term. 

In the final rule the language at 

§ ll.102(e)(1)(i) relating to 

information obtained through 

intervention or interaction with an 

individual was adopted and modified 

by replacing the reference to data, as 

proposed in the NPRM, with a reference 

to information or biospecimens, and by 

adding the NPRM-proposed language 

relating to using, studying, or analyzing 

the information or biospecimens. The 

explicit reference to biospecimens in 

this context is intended as a mere 

clarification of the previous 

understanding of how the pre-2018 rule 

operated. 

Likewise, the final rule adopts the 

NPRM-proposed language at 

§ ll.102(e)(1)(ii) relating to obtaining 

identifiable private information, but 

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modifies it by adding an explicit 

reference to ‘‘identifiable 

biospecimens.’’ This is also intended as 

a mere clarification of the previous 

understanding of how the pre-2018 rule 

operated as applied to biospecimens. 

Similarly, the definition of intervention 

has been modified to clarify that 

information or biospecimens might be 

gathered, replacing the former reference 

only to data. This, too, is merely a 

clarification of the existing 

understanding of that concept. 

A definition of ‘‘identifiable 

biospecimen’’ has been added at 

§ ll.102(e)(6). This new definition 

was not added as a result of any 

substantive change, but rather to enable 

greater clarity in other provisions of 

these regulations in explaining when a 

particular provision relates to either 

identifiable private information alone 

(not including biospecimens), or 

identifiable biospecimens alone, or 

both. The pre-2018 rule’s concept of 

‘‘identifiable private information’’ had 

encompassed the concept of an 

identifiable biospecimen, whereas 

under the final rule that concept has 

been ‘‘cleaved off’’ from that definition 

and given its own definition. Note that 

a biospecimen is deemed to include 

private information (consistent with the 

understanding of this concept under the 

pre-2018 rule), so there is no need to 

add the adjective ‘‘private’’ in the 

definition of an ‘‘identifiable 

biospecimen.’’ In effect, once a 

biospecimen becomes identifiable (for 

example, by being tagged with the name 

or other information that indicates the 

person from whom the biospecimen was 

obtained), then an investigator using 

that biospecimen is already using 

something to which §ll.102(e)(1)(ii) 

would apply. There is no need to make 

any additional determination about the 

‘‘private’’ aspects of what is taking 

place. 

In addition, the minor clarifying 

change in the language for the concept 

of ‘‘private information’’ that was 

proposed in the NPRM, namely adding 

the phrase ‘‘shared or,’’ was not 

adopted. It was decided that because 

any information that should not be 

shared would always meet the standard 

of being information that should not be 

made public, this change would not 

actually expand the amount of 

information that is considered private 

information. 

Although the description of when 

private information is identifiable was 

not significantly changed, a new 

provision has been added at 

§ ll.102(e)(7) requiring federal 

departments and agencies that 

implement the Common Rule to 

regularly, upon consultation with 

appropriate experts, reexamine the 

meaning of the terms ‘‘identifiable 

private information,’’ as defined in 

§ ll.102(e)(5), and ‘‘identifiable 

biospecimen,’’ as defined in 

§ ll.102(e)(6). Such reexamination 

shall take place at least every 4 years. 

This new provision specifically requires 

that the federal departments and 

agencies implementing this policy 

collaborate on this process to avoid a 

duplication of efforts and in order to 

have a consistent interpretation of these 

terms. 

This new process responds to the 

growing volume of information being 

generated and shared in research 

(including from biospecimens), and 

evolving technology that can ease and 

speed the ability to re-identify 

information or biospecimens previously 

considered nonidentifiable. With an 

increase in the number of exemptions 

included in this final rule, it will be 

important to reconsider the potential 

identifiability of information and 

biospecimens and facilitate uniform 

interpretation to ensure adequate 

privacy and security measures are in 

place. 

Section 102(e)(7) also provides that, 

after conducting this process, if it is 

determined to be appropriate and 

permitted by law, Common Rule 

departments and agencies could alter 

the interpretation of identifiable private 

information or identifiable 

biospecimens, including through the 

use of guidance. 

In addition, there will occur, also at 

least every 4 years and as a collaborative 

process among those federal 

departments and agencies, upon 

consultation with appropriate experts, 

an assessment as to whether there are 

analytic technologies and techniques 

that should be considered by 

investigators to generate identifiable 

private information or identifiable 

biospecimens. The ultimate goal is to 

implement the Common Rule in a way 

that is aligned with the evolving 

understanding of the concept of 

identifiability while protecting subjects 

and encouraging and facilitating 

valuable research. 

To the extent that this process leads 

to a determination that particular 

analytic technologies or techniques, 

when applied to information or 

biospecimens that are not identified, do 

lead to the generation of identifiable 

private information or identifiable 

biospecimens, those technologies or 

techniques will be placed on a list of 

technologies and techniques satisfying 

that determination, and 

recommendations might accordingly be 

made with regard to relevant issues 

relating to consent and privacy and data 

security protections. The result may be 

that such technologies and techniques 

could therefore only be used in 

instances where the person has 

provided their consent (broad or studyspecific) which meets the requirements 

of the Common Rule, or where an IRB 

has waived the requirement for consent. 

Notice and the opportunity for public 

comment would take place before a 

technology or technique could be placed 

on this list. The expectation is that 

whole genome sequencing will be one of 

the first technologies to be evaluated to 

determine whether it should be placed 

on this list. 

It is important to note that an 

investigator who possesses information 

or biospecimens to which such a 

technology or technique might be 

applied is not to be considered in 

possession of identifiable private 

information or identifiable 

biospecimens merely as a result of such 

a circumstance: that would only be true 

were the investigator to actually apply 

the technology or technique to generate 

identifiable private information or 

identifiable biospecimens. 

This new provision is not being added 

as a result of any pre-conceived 

determination that there is indeed a 

need to change, whether by guidance or 

otherwise, the interpretation of 

‘‘individually identifiable’’ as that 

concept is currently interpreted. 

Consistent with a core theme 

underpinning the process that led to 

this final rule, it would be inappropriate 

to expand the scope of coverage of the 

Common Rule with regard to activities 

that usually involve very little risk 

absent good reason to think that there is 

a problem that the added administrative 

burden will be correcting. The public 

comments on both the ANPRM and the 

NPRM do not identify a specific 

problem, but clarification from the 

regulatory agencies might be useful. 

Thus, apart from the consequences of 

placing technologies and techniques on 

the new list, the most significant effect 

of §ll.102(e)(7) may be the issuance 

of guidance from time to time that 

facilitates understanding of and 

compliance with existing 

interpretations. 

Finally, with regard to the use of 

newborn DBS, retaining the pre-2018 

approach toward nonidentified 

biospecimens resolves many of the 

concerns expressed by commenters who 

felt that important research involving 

newborn screening would be halted or 

inhibited under the NPRM. The 

Newborn Screening Saves Lives 

Reauthorization Act of 2014 (Pub. L. 

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7170 Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 

22Presidential Commission for the Study of 

Bioethical Issues. Gray Matters: Topics at the 

Intersection of Neuroscience, Ethics, and Society 

(Volume 2). Washington, DC: Presidential 

Commission for the Study of Bioethical Issues, 

2015. Retrieved from http://bioethics.gov/sites/ 

default/files/GrayMatterlV2l508.pdf 

113–240) will no longer be effective 

following the effective date of this final 

rule, given that its changes applied only 

until changes to the Common Rule were 

promulgated. As a result, under the final 

rule, secondary research with 

nonidentified newborn DBS would be 

treated in the same way as secondary 

research with any other type of 

nonidentified biospecimen. Such 

research would not be considered 

research with human subjects under the 

final rule, and thus would not be subject 

to the rule. 

E. Legally Authorized Representative 

(§ ll.102(i)) 

1. Background and Pre-2018 

Requirements 

The Common Rule contains a 

definition of legally authorized 

representative to clarify who can 

consent on behalf of a prospective 

subject who is unable to consent to 

research participation on his or her own 

behalf. Under the pre-2018 rule, a 

legally authorized representative was 

defined as an individual or judicial or 

other body authorized under applicable 

law to consent on behalf of a 

prospective subject to the subject’s 

participation in the procedure(s) 

involved in the research. 

As there is no federal legal standard 

as to who, or what entity, is authorized 

to serve as a legally authorized 

representative to provide consent to a 

subject’s research participation, the 

issue of who can serve as a legally 

authorized representative has been 

determined by the laws of the 

jurisdiction in which the research will 

be conducted. Within the United States, 

this generally means state or local law. 

‘‘Applicable law’’ could be a state 

statute or regulation, case law on point, 

an opinion of a State Attorney General, 

or a combination of these. 

Some states and jurisdictions have 

statutes, regulations, or common law 

that specifically address consent by 

someone other than the subject for 

participation in research. Most states 

and jurisdictions have no law 

specifically addressing the issue of 

consent in the research context. In these 

states and jurisdictions, law that 

addresses who is authorized to give 

consent on behalf of another person to 

specific medical procedures or generally 

to clinical care may be relevant if those 

types of procedures are the procedures 

involved in the research. The longstanding interpretation by OHRP has 

been that such laws relating to surrogate 

consent in the clinical context can be 

used for purposes of the Common Rule. 

In every state, a legally authorized 

representative can be authorized 

through an advance directive or by a 

court through guardianship 

proceedings. However some states have 

no law specifically addressing the issue 

of consent by a surrogate in the research 

setting, and some states have no 

applicable statutes, regulations, or 

common law specifying when an 

individual can provide consent for 

another to medical treatment. In the 

absence of such law, it is usually the 

case that community or other standards 

(such as institutional policies) define 

hierarchies or identify individuals who 

are allowed to provide consent, for 

medical treatment purposes, on behalf 

of others who cannot consent for 

themselves. 

SACHRP and the Presidential 

Commission for the Study of Bioethical 

Issues have raised concerns that the 

definition of legally authorized 

representative may be inappropriately 

hindering the conduct of research with 

subjects who lack capacity to consent. 

In the second part of its report on 

neuroscience and ethics, Gray Matters: 

Topics at the Intersection of 

Neuroscience, Ethics, and Society 

(Volume 2), the Commission 

recommended that federal regulatory 

agencies establish clear requirements to 

identify who can serve as legally 

authorized representatives for 

individuals with impaired decisionmaking capacity to support their 

responsible inclusion in research.22

2. NPRM Proposal 

Although the NPRM did not propose 

regulatory text that would change the 

definition of ‘‘legally authorized 

representative,’’ it requested public 

comment on whether we should modify 

the definition in light of the definition’s 

reference to persons or entities 

‘‘authorized under applicable law.’’ 

The NPRM sought comment on 

whether expansion of the current 

definition to permit a legally authorized 

representative to be defined by an 

accepted common practice standard 

within a state or jurisdiction that lacks 

applicable state law for determining 

who can legally consent to clinical care 

would be consistent with the ethical 

principles underlying the Common 

Rule. The NPRM proposed to allow use 

of this alternative standard only in 

jurisdictions in which there is also no 

applicable law affirmatively authorizing 

a legally authorized representative to 

provide consent to the subject’s research 

participation. 

3. Public Comments 

Approximately 60 commenters 

discussed the Common Rule’s definition 

of ‘‘legally authorized representative.’’ A 

clear majority supported the goal of 

addressing the barrier that the 

regulatory definition of ‘‘legally 

authorized representative’’ poses in 

jurisdictions that have no applicable 

law affirmatively authorizing an 

individual to provide consent for 

another. Commenters also favored the 

suggested approach and responded that 

including the allowance of an accepted 

common practice standard would still 

appropriately protect subjects. About 

one-third of the commenters responding 

to this question, including disability 

rights organizations, advocacy 

organizations, and academic 

institutions, did not agree with the 

direction of the contemplated 

modification or whether this issue 

should be addressed through regulatory 

change. 

Those supporting a modified 

definition generally agreed that 

broadening the definition to cover 

anyone considered acceptable to 

provide consent for another individual 

in the clinical setting would be 

appropriate, would represent an 

alignment with accepted common 

practice, and would bring consistency to 

the consent process for the jurisdictions 

that are silent on both who may provide 

consent for clinical care and who may 

provide consent for research. A number 

of commenters who supported the 

proposal for modification noted that 

state law authorizing individuals to 

provide consent would continue to 

apply. 

Among the commenters who opposed 

the modification, several said state law 

provides sufficient guidance regarding 

the hierarchy of those who can consent 

for an adult incapable of consenting on 

his or her own behalf, and reduces the 

institution’s liability in the event that an 

inappropriate person consents for the 

subject. A research institution 

recommended that we reassess this 

proposal and include more specific 

requirements and details as to the role 

and authority of the legally authorized 

representative. A disability rights 

organization, while recognizing that the 

pre-2018 standard is not acceptable, 

commented that the problem is not 

solved by incorporating broad discretion 

among different jurisdictions. The 

organization also opined that a common 

practice standard does not provide 

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sufficient guidance to assess and 

balance reasonable risk, considering that 

a legally authorized representative’s 

consent is not equivalent to an 

autonomous decision by the subject. A 

research subject advocacy organization 

expressed concern that such a change 

would not provide sufficient oversight 

of investigators, who might use this 

standard in a way that would violate 

local law. Another commenter stated 

that certain individuals may be 

considered able to give consent for 

participation in clinical procedures for 

individuals unable to do so for 

themselves, but may not have the best 

interests of the individual in mind. 

Commenters responded specifically to 

the solicitation of comment on the 

proposed standard of ‘‘accepted 

common practice’’ and indicated that 

practices for surrogate consent should 

be those used in clinical settings. 

Several commenters provided ideas for 

a more specific approach to interpreting 

the terms ‘‘accepted’’ and ‘‘common.’’ A 

researchers’ association commented that 

interpretation of these terms should 

include standards that define 

hierarchies or identify individuals who 

may provide legally acceptable consent, 

for clinical purposes, on behalf of others 

who cannot consent for themselves. One 

commenter supporting the modification 

suggested that the terms could be 

defined to refer to the historically used 

form of governing and familial decision 

making within the group of subjects. A 

research institution commented that an 

IRB’s careful review and documentation 

of who may serve as a legally authorized 

representative would be preferable to an 

accepted common practice standard, as 

that standard is vague. A research 

institution commenting in support of 

broadening the definition to those who 

are allowed to consent to clinical 

procedures advised that this would 

reduce confusion between physicians 

and researchers as to who can consent 

for whom in research situations, and 

suggested that the terms ‘‘accepted’’ and 

‘‘common’’ should refer to the 

conducting institution’s own policies on 

who can provide consent to clinical 

procedures. 

4. Responses to Comments and 

Explanation of the Final Rule: 

Definition of Legally Authorized 

Representative 

The definition of legally authorized 

representative in the final rule at 

§ ll.102(i) has been modified to 

address jurisdictions in which no 

applicable law authorizes a legally 

authorized representative to provide 

consent on behalf of a prospective 

research subject. In these jurisdictions, 

an individual recognized by 

institutional policy as acceptable for 

providing consent in the nonresearch 

context to the subject’s participation in 

the procedures involved in the research, 

will now be considered a legally 

authorized representative for purposes 

of this rule. 

The change made from the NPRM 

discussion that ‘‘accepted common 

practice’’ could be used to identify a 

legally authorized representative is in 

response to objections to the vagueness 

of these terms and the potential for 

confusion in implementation, which 

was expressed by the majority of 

commenters opposed to the proposal. 

We agree with the commenters’ 

suggestion that an institution’s own 

policies as to surrogate consent may be 

a better touchstone than ‘‘accepted 

common practice,’’ as a standard 

referencing institutional policy will 

provide additional clarity as to who may 

serve as a legally authorized 

representative at that particular 

institution. 

The final rule also differs from the 

NPRM discussion in that it allows 

institutional policies applicable to 

surrogate consent in either the clinical 

context, or other nonresearch contexts, 

to authorize a legally authorized 

representative. We expect that 

implementation of this aspect of the 

final rule definition will in large part 

rely on institutional policies for 

determining surrogates for clinical 

decision making. In those instances, 

there is relatively little risk that this rule 

will have inappropriate consequences, 

as far more significant considerations, 

not related to the Common Rule, play a 

role in shaping and constraining an 

institution’s policies relating to 

surrogate decision making in the 

clinical context. 

However, we recognize that some 

studies could be taking place that do not 

relate to the types of decisions that are 

involved in clinical care, or that do not 

involve procedures utilized in the 

clinical context. If the institution has a 

policy relating to who acts as a surrogate 

outside of the research context for those 

types of decisions, then such a policy 

could be employed in the research 

context. Similar to our assessment of 

policies relating to surrogate decision 

making in the clinical context, we 

expect that considerations not related to 

the Common Rule would constrain the 

institution’s design and implementation 

of policies in other nonresearch 

contexts, and thus see relatively little 

risk that this added regulatory flexibility 

will have inappropriate consequences. 

Maintaining the pre-2018 standard 

would have continued to allow 

disparate results in terms of when 

research can take place in those states 

that have specific laws governing either 

surrogate clinical consent or research 

consent, and those that do not. 

Accepting that the Common Rule has 

been interpreted to allow the use of laws 

governing surrogate consent in the 

clinical context to be applied to 

surrogate decision making in the 

research context, it is difficult to see 

why there should be different outcomes 

in terms of what research is allowable 

based on whether the standards for 

surrogate consent in the clinical context 

in a state are based on specific laws or 

some other accepted regime. 

This outcome also appears 

inconsistent with the Belmont Report 

principle of justice. Individuals who 

lack the capacity to consent to research 

ought not be inappropriately excluded 

from research participation based solely 

on these circumstances. Research that 

an IRB has approved as ethical to 

conduct with the participation of 

subjects with impaired decision-making 

capacity ought not be prohibited in the 

few states and jurisdictions in which no 

affirmative law authorizing a legally 

authorized representative exists, while 

being allowed to proceed in the vast 

majority of states and jurisdictions that 

have laws specifically authorizing 

consent by a legally authorized 

representative in the clinical or research 

context. 

Reduced ambiguity in the 

interpretation of the regulatory 

requirements will facilitate research that 

may offer the promise of improved 

medical treatment for this subject 

population, thus increasing beneficence. 

This approach reflects the calls for 

increased clarity in the regulatory 

requirements regarding who may serve 

as a legally authorized representative, 

which will serve to facilitate the 

responsible inclusion of subjects who 

cannot consent on their own behalf to 

research participation. 

F. Minimal Risk (§ll.102(j)) 

1. Background and Pre-2018 

Requirements 

The concept of ‘‘minimal risk’’ is 

central to numerous aspects of the 

Common Rule, as it affects the type of 

review required, the permissibility of 

waiver of informed consent, 

considerations for IRBs in the review 

process, and the frequency of review. In 

sum, the review process has been 

calibrated, for the most part, to the risk 

of the research. For example, under the 

pre-2018 rule at §ll.110, a research 

study could receive expedited review if 

the research activities to be conducted 

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23HHS. Office for Human Research Protections . 

Categories of Research That May Be Reviewed by 

the Institutional Review Board (IRB) through an 

Expedited Review Procedure. November 9, 1998. 

Retrieved from http://www.hhs.gov/ohrp/policy/ 

expedited98.html. 

24Consistent with 45 CFR 164.501 in the Privacy 

Rule. 

appeared on the list of activities 

published by the Secretary of HHS that 

are eligible for such review,23 and found 

by the reviewer(s) to involve no more 

than minimal risk. Under an expedited 

review procedure, the review could be 

carried out by the IRB chairperson or by 

one or more experienced reviewers 

designated by the chairperson. 

The definition of ‘‘minimal risk’’ in 

the pre-2018 rule at §ll.102(i) 

encompassed research activities where 

the probability and magnitude of harm 

or discomfort anticipated in the research 

are not greater in and of themselves than 

those ordinarily encountered in daily 

life or during the performance of routine 

physical or psychological examinations 

or tests. IRBs report challenges in 

assessing the level of risk presented by 

some studies in order to make the 

critical minimal risk determination. 

This is, in part, due to the difficulties in 

applying the definition of minimal risk 

under the pre-2018 rule, particularly 

because the terms ‘‘ordinarily 

encountered in daily life’’ and ‘‘routine 

physical or psychological examinations 

or tests’’ are not clarified. 

2. NPRM Proposal 

The NPRM did not propose to modify 

the definition of ‘‘minimal risk,’’ but 

rather proposed adding to the definition 

a requirement that the Secretary of HHS 

create and publish a list of activities that 

qualify as ‘‘minimal risk.’’ This list 

would be re-evaluated periodically, but 

at least every 8 years, based on 

recommendations from federal 

departments and agencies and the 

public. This would not be an exhaustive 

list of all activities that should be 

considered minimal risk under the 

Common Rule, but would allow IRBs to 

rely on the determination of minimal 

risk for activities appearing on the list. 

IRBs would still need to make minimal 

risk determinations about activities that 

do not appear on this list. The public 

was asked to comment on whether 8 

years was a reasonable time period for 

updating the list and whether advice 

should be solicited from outside parties 

when updating the list. The public was 

also asked to comment on whether the 

Secretary’s list would be a useful tool 

for the research community, and 

whether it would represent a loss of IRB 

flexibility in risk determinations. 

3. Public Comments 

Approximately 100 comments were 

received on this proposal. A strong 

majority supported the proposal, stating 

that it would be useful to have such a 

list, and some even suggested that the 

list of minimal risk activities should be 

reviewed more often than once every 8 

years. One research university suggested 

that it is impossible to determine the 

future direction of human research and 

therefore a list of minimal risk activities 

would need to be updated at least 

yearly. 

Several commenters, including those 

who supported this proposal generally, 

stated that even though this list of 

minimal risk activities was a good idea 

in theory, it should be developed 

separately from a final rule to allow for 

more time to work collaboratively with 

other Common Rule departments and 

agencies and with members of the 

regulated community. Some of those 

who supported the proposal asked that 

there be widely solicited public input 

on the list. Others who supported the 

proposal noted the list does not 

represent a loss of flexibility because the 

IRB can still override the presumption 

of minimal risk as long as the rationale 

is documented. One large research 

university felt that the Secretary’s list 

should not replace the IRB’s discretion 

to review a study, particularly if it will 

only be updated periodically. One 

commenter was opposed to the NPRM 

proposal that the list be further codified, 

suggesting that it should instead be 

eliminated as a regulatory yardstick to 

simplify the regulations and remove 

added administrative burden. 

4. Response to Comments and 

Explanation of the Final Rule: 

Definition of Minimal Risk 

Although this proposal received 

significant support, several commenters 

expressed concern that the Secretary’s 

list was another NPRM deliverable that 

the public did not have a chance to see 

and comment on during the NPRM 

public comment period. These 

commenters suggested that this proposal 

be removed from a final rule and 

developed on a separate track. We agree 

that this list should be developed as a 

separate process from the final rule 

promulgation, and thus this proposal 

has not been included in the final rule. 

Thus, no change is made to the 

definition of ‘‘minimal risk’’ in the final 

rule at § ll.102(j). We still intend to 

publish guidance on this issue and 

could still pursue publication of such a 

list in the future. 

G. Public Health Authority 

(§ ll.102(k)) 

The pre-2018 rule did not provide a 

definition of ‘‘public health authority.’’ 

As proposed in the NPRM, the final rule 

now defines the term so that references 

to it in the definition of research are 

understood. Specifically, because the 

definition of ‘‘research’’ 

(§ ll.102(l)(2)) removes from that 

definition public health surveillance 

activities that are conducted, supported, 

requested, ordered, required, or 

authorized by a public health authority, 

this definition of ‘‘public health 

authority’’ clarifies the scope of the 

activities removed from the definition of 

‘‘research’’ for the purposes of this final 

rule. 

In the final rule, as in the NPRM, the 

term ‘‘public health authority’’ 24 means 

an agency or authority of the United 

States, a state, a territory, a political 

subdivision of a state or territory, an 

Indian tribe, or a foreign government, or 

a person or entity acting under a grant 

of authority from or contract with such 

public agency, including the employees 

or agents of such public agency or its 

contractors or persons or entities to 

whom it has granted authority, that is 

responsible for public health matters as 

part of its official mandate. We received 

no public comments on this definition. 

H. Research (§ ll.102(l)) 

1. Background and Pre-2018 

Requirements 

The pre-2018 rule defined ‘‘research’’ 

as a systematic investigation, including 

research development, testing, and 

evaluation, designed to develop or 

contribute to generalizable knowledge. 

Activities that met this definition 

constituted research for the purposes of 

that rule. An activity was only subject 

to that rule if it met this definition (in 

addition to meeting various other 

criteria). The pre-2018 rule also 

included categories of research 

involving human subjects that would be 

considered exempt from the rule. 

The pre-2018 rule was criticized for 

not being clear about how to interpret 

which activities were covered by the 

rule and which were not. Some 

commenters also criticized the pre-2018 

rule for extending to activities that 

should not be covered and for inhibiting 

the conduct of certain activities. 

According to some, the definition of 

‘‘research’’ did not provide a sufficiently 

clear and precise way to distinguish 

between similar activities in a way that 

made it immediately obvious which 

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activities fell under the definition and 

which did not. 

2. NPRM Proposals 

The NPRM proposed creating a new 

section in the regulations referred to as 

‘‘exclusions.’’ By proposing exclusion 

categories, the NPRM intended to make 

clear that these activities would not 

have to satisfy the regulatory 

requirements of the Common Rule. That 

is, the proposed excluded activities 

would have been outside the scope of 

the Common Rule. 

Three of the proposed exclusions 

sought to reduce uncertainty about 

whether certain internal program 

improvement activities, historical or 

journalistic inquiries, or quality 

assurance or improvement activities 

satisfied the Common Rule’s definition 

of research. 

Another three proposed exclusions 

pertained to activities that are part of 

inherently governmental functions with 

purposes other than research, such as 

responsibilities to protect public health 

and welfare (i.e., criminal 

investigations, public health 

surveillance, and national security 

missions). It was proposed that these 

activities promote recognized specific 

goods that are crucial to the public 

welfare. 

An additional four categories of 

proposed exclusions included human 

subjects research activities that were 

either considered low risk, or for which 

there were appropriate safeguards 

already in place independent of the 

Common Rule. These four categories 

pertained to: (1) Research that involves 

the use of educational tests, survey 

procedures, interview procedures, or 

observation of public behavior 

uninfluenced by the investigators; (2) 

research involving the collection or 

study of information that has been or 

will be acquired solely for non-research 

activities or were acquired for research 

studies other than the proposed research 

study; (3) research conducted by a 

federal government agency using federal 

government-generated non-research 

information when certain criteria are 

met; and (4) research regulated as 

‘‘health care operations,’’ ‘‘public health 

activities,’’ or ‘‘research’’ under HIPAA. 

As noted in the NPRM, in these 

categories the principle of beneficence 

alone could support the conduct of 

these activities after considering the 

level of risk, potential benefits, and 

nature of human participation in these 

activities, without the need to add the 

protections of the Common Rule. 

A final proposed exclusion would 

have applied to research involving the 

secondary use of nonidentified 

biospecimens when the research was 

limited to generating information about 

the subject that is already known by the 

subject (e.g., disease diagnosis). As 

such, this research would not need any 

additional protections provided by these 

regulations. This proposed exclusion 

was directly related to the proposed 

changes in the definition of ‘‘human 

subject’’ to include all biospecimens, 

regardless of whether they are 

identifiable (as discussed above in 

Section III, that proposal has not been 

adopted). 

3. Public Comments, Response to 

Comments, and Description of the Final 

Rule: Definition of Research 

a. Overview 

Approximately 375 public comments 

discussed at least one aspect of the 

proposed NPRM exclusions. General 

concerns about the exclusions included 

that they added a layer of unnecessary 

complexity in determining what studies 

fall under the Common Rule, and that 

overlapping categories of exclusions and 

exemptions were proposed. Comments 

also expressed the concern about the 

lack of requirements on who would 

decide whether an activity met the 

criteria for an exclusion, including 

investigators, or whether those 

decisions would be documented in any 

way. 

In response to the public comments, 

the NPRM’s general approach of 

designating various categories of 

activities as excluded has not been 

adopted. Instead, the final rule reverts to 

the general structure of the pre-2018 

rule and integrates some of the 

categories proposed for exclusion in the 

NPRM into that structure, with some 

changes to the categories. 

The final rule retains the wording of 

the pre-2018 definition of research, and 

explicitly removes four categories of 

activities from activities that would 

meet that definition. These revisions are 

intended to make the rule simpler, more 

familiar to readers who are aware of the 

pre-2018 rule and its definition of 

research, and easier to understand. 

The four categories of activities 

removed from the definition of research 

are set out in order to make clear that 

they are not within the jurisdiction of 

the rule. The four categories pertain to 

certain scholarly and journalistic 

activities, public health surveillance 

activities, criminal justice activities, and 

authorized operational activities in 

support of national security missions. 

These categories were proposed as 

exclusions in the NPRM; the final rule 

retains these categories, with some 

changes made in the wording for clarity, 

in response to public comments. 

The category of certain scholarly or 

journalistic activities is removed from 

the definition in order to resolve longstanding debate and uncertainty about 

whether these activities are considered 

research in the sense of the regulatory 

definition. We believe that these 

activities should not be considered 

research in the context of the Common 

Rule, and that making this explicit in 

the final rule will help to resolve the 

uncertainty. 

The final rule includes a simpler 

definition of national security missions 

not considered to be human subject 

research, as a response to concern that 

the earlier draft language in the NPRM 

could be interpreted too broadly or too 

narrowly due to the specific activities 

listed, such as surveys, interviews, 

surveillance activities and related 

analyses, and the collection and use of 

biospecimens. These authorized 

operational activities, as determined by 

each agency, do not include research 

activities as defined by the Common 

Rule, nor have they ever in the past 

been considered regulated by the 

Common Rule. This category of activity 

is removed from the definition of 

research to make explicit that the 

requirements of the final rule do not 

apply to authorized operational 

activities in support of national security 

missions. 

The other two categories of activities 

deemed not to be research under the 

final rule (pertaining to public health 

surveillance activities and criminal 

justice activities) include many 

activities that under the pre-2018 rule 

do not fit the definition of research, and 

some activities that otherwise might. 

These categories are included in the 

final rule in order to make it explicit 

that the requirements of the final rule do 

not apply to them. 

Three categories of activities proposed 

as exclusions have been eliminated from 

the final rule. The proposed exclusion 

for certain quality assurance/quality 

improvement (QA/QI) activities has 

been dropped because it could create 

more confusion than it resolved, and it 

might have inadvertently created 

inappropriate obstacles to those QA/QI 

activities that should not fall under the 

rule. The proposed exclusion for 

internal program improvement activities 

has been dropped due to similar 

considerations. The category regarding 

secondary research involving 

nonidentified biospecimens designed 

only to generate information about an 

individual that is already known has 

been dropped because it is no longer 

necessary given that the NPRM proposal 

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7174 Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 

to modify the definition of human 

subject to include all biospecimens 

regardless of identifiability is not 

included in the final rule. The 

discussion of the proposed exclusion for 

certain research activities with 

nonidentified biospecimens appears in 

additional detail in Section III.D. 

The four exclusions proposed in the 

NPRM that are incorporated into the 

exemptions in the final rule are: (1) The 

proposed exclusion for certain 

educational tests, survey or interview 

procedures or observation of public 

behavior; (2) the proposed exclusion for 

secondary research use of information 

that is publicly available or recorded 

without identifiers; (3) the proposed 

exclusion regarding secondary research 

use of information collected by the 

Federal Government for other purposes 

and subject to certain privacy laws; and 

(4) the proposed exclusion regarding 

secondary research use of information 

covered by HIPAA protections. 

b. Scholarly and Journalistic Activities 

(e.g., Oral History, Journalism, 

Biography, Literary Criticism, Legal 

Research, and Historical Scholarship) 

(§ ll.102(l)(1)) 

i. Public Comments 

Approximately 50 comments 

discussed the NPRM proposal to 

exclude scholarly and journalistic 

articles from coverage by the rule. The 

majority of these comments supported 

the intent of the exclusion, although 

several comments suggested possible 

changes. The minority of the comments 

expressed concerns. Those who 

opposed this exclusion generally 

opposed all exclusions, arguing that 

investigators should be required to get 

permission from subjects before 

engaging in these activities. 

One commenter expressed concern 

about an exclusion that would permit 

oral history activities with tribal nations 

without oversight. This commenter 

noted that some oral history with tribal 

nations is tantamount to cultural 

appropriation, and the concern of tribal 

nations might not be adequately 

protected by the ethical standards of 

various professions. 

Several commenters discussed that 

the wording of the NPRM regulatory text 

here might be more restrictive than 

necessary. Specifically, several 

commenters noted that in calling out 

specific disciplines and methodologies, 

the regulatory text seems counter to the 

NPRM policy goal of allowing this type 

of research (as opposed to research in 

these specific fields) to occur. 

A few commenters discussed the need 

for ethnographic research to be 

explicitly called out in this exclusion. 

One commenter also raised cultural 

anthropology as another academic 

discipline that should be referenced in 

this exclusion. 

Several commenters, including 

academic discipline advocacy groups, 

noted that the exclusion conflated broad 

disciplines (journalism) with 

methodologies (oral history), which 

could be confusing to those attempting 

to implement the exclusion. 

Several commenters also questioned 

whether the provision ‘‘that focus 

directly on the specific individuals 

about whom the information is 

collected’’ applied only to historical 

scholarship activities or to all of the 

activities and disciplines noted in the 

exclusion. Several other commenters 

indicated that they supported a full 

exclusion of all oral history, journalism, 

biographical, and historical scholarship 

activities, suggesting that those several 

individuals do not presume that the 

provision ‘‘that focus directly on the 

specific individuals about whom the 

information is collected’’ served as a 

limitation on what activities were 

covered under this exclusion. 

A minority of commenters—including 

accreditation bodies, human research 

protection experts, and research 

universities—suggested that an 

exclusion for these activities was not 

needed, and that this topic could be 

addressed through guidance. These 

comments also indicated that 

addressing this topic in guidance might 

be clearer to the regulated community as 

well. Others indicated that the 

exclusion is not warranted because the 

excluded activities are those that would 

not contribute to generalizable 

knowledge and thus already would not 

fall under the rule. 

The NPRM also asked whether 

biospecimens should be included in this 

exclusion. Very few individuals 

answered this question, and those that 

did indicated that biospecimens should 

not be included. 

One research university indicated that 

with respect to oral history, the 

exclusion should make a distinction 

between oral history projects that meet 

the definition of research and those that 

do not, suggesting that the exclusion 

should not exempt all projects that 

might fall under the ‘‘oral history’’ 

banner. One commenter noted that oral 

history should be defined in order to 

distinguish that activity from 

interviews. 

ii. Response to Comments and 

Explanation of the Final Rule: Scholarly 

and Journalistic Activities 

The final rule explicitly removes a 

category of activities consisting of 

certain scholarly and journalistic 

activities from the definition of research 

and the scope of the regulations. This 

category of activities concerns certain 

activities in various fields that focus 

directly on the specific individuals 

about whom information are collected. 

As described above, this category is 

removed from the definition in order to 

resolve long-standing debate and 

uncertainty about whether these 

activities are considered research in the 

sense of the regulatory definition. We 

believe that these activities should not 

be considered research in the context of 

the Common Rule, and that making this 

explicit in the final rule will help to 

resolve the uncertainty. 

In these activities, the ethical 

requirement is to provide an accurate 

and evidence-based portrayal of the 

individuals involved, and not 

necessarily to protect them from public 

scrutiny. For example, a biographer 

might collect and present factual 

information to support the biographer’s 

opinion about the character of an 

individual to show that the individual 

does not deserve the positive reputation 

he or she enjoys in society. These fields 

of research have their own codes of 

ethics, according to which, for example, 

consent is obtained for oral histories. 

We note that this consent standard 

should address the issue of oral 

histories of tribal members. For these 

reasons, we have determined that it is 

appropriate to remove these activities 

from the definition of research and from 

the scope of the Common Rule. 

In response to public comments, 

§ ll.102(l)(1) refers to more fields and 

methodological traditions than were 

proposed in the NPRM. The final rule 

also explicitly cites those fields and 

traditions as examples, in order to 

clarify that the focus is on the specific 

activities that collect and use 

information about specific individuals 

themselves, and not generalizing to 

other individuals, and that such 

activities occur in various fields of 

inquiry and methodological traditions. 

Literary criticism has been added as an 

example because while a piece of 

literary criticism might focus on 

information about the author(s), it 

would typically focus on the specific 

author(s) in view. Legal research has 

been added as an example because it 

would often focus on the circumstances 

of specific plaintiffs or parties involved 

in a case. It is not the particular field 

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25The Tuskegee Syphilis study ‘‘initially 

involved 600 black men—399 with syphilis, 201 

who did not have the disease. The study was 

conducted without the benefit of patients’ informed 

consent. Researchers told the men they were being 

treated for ‘bad blood,’ a local term used to describe 

several ailments, including syphilis, anemia, and 

fatigue. In truth, they did not receive the proper 

treatment needed to cure their illness. In exchange 

for taking part in the study, the men received free 

medical exams, free meals, and burial insurance. 

Although originally projected to last 6 months, the 

study actually went on for 40 years. 

The [federal government panel investigating this 

study] found that the men had agreed freely to be 

examined and treated. However, there was no 

evidence that researchers had informed them of the 

study or its real purpose. In fact, the men had been 

misled and had not been given all the facts required 

to provide informed consent . . . The men were 

never given adequate treatment for their disease. 

Even when penicillin became the drug of choice for 

syphilis in 1947, researchers did not offer it to the 

subjects. The advisory panel [investigating this 

study] found nothing to show that subjects were 

ever given the choice of quitting the study, even 

when this new, highly effective treatment became 

widely used.’’ Source: ‘‘The Tuskegee Timeline.’’ 

Centers for Disease Control and Prevention, last 

updated 19 Feb 2016. Retrieved from http:// 

www.cdc.gov/tuskegee/timeline.htm.) 

that removes the activity from the 

definition, but rather the particular 

activity’s focus on specific individuals. 

Activities described in §ll.102(l)(1) 

may sometimes be performed in the 

fields of anthropology or sociology, but 

not all activities characteristic of these 

fields are outside of the rule. Studies 

using methods such as participant 

observation and ethnographic studies, 

in which investigators gather 

information from individuals in order to 

understand their beliefs, customs, and 

practices, and the findings apply to the 

studied community or group, and not 

just the individuals from whom the 

information was obtained, fall within 

the scope of the definition of research of 

the final rule. 

c. Public Health Surveillance 

(§ ll.102(l)(2)) 

i. Public Comments 

Approximately 80 comments 

discussed the proposed exclusion for 

certain public health surveillance 

activities. Public comments were 

generally mixed with many comments 

suggesting that the regulated community 

will need to see additional examples of 

activities that satisfy this exclusion and 

activities that fall outside its scope. 

Those who supported this exclusion 

generally said that this would 

streamline important public health 

surveillance activities. 

Several comments discussed the 

importance of this exclusion with 

respect to residual newborn DBS 

screening programs. These comments 

generally expressed the opinion that 

most state mandated public health 

reporting of such program activities 

would fall under this exclusion. 

Commenters requested additional 

explanation of what aspects of these 

state newborn screening programs 

would be covered under this exclusion, 

and listed components of the program 

that should be covered, including 

validity testing and test development. 

Others suggested that this exclusion 

should also exclude minimal risk efforts 

to evaluate surveillance methods. 

Others suggested that this exclusion 

should also exclude minimal risk efforts 

to evaluate surveillance methods. 

Another comment suggested that a final 

rule address, in this exclusion or 

elsewhere, the issue of research that 

must be conducted during public health 

emergencies, citing the example of 

HHS’s emergency use provision with a 

waiver of informed consent, which 

describes limited circumstances in 

which a patient is physically 

incapacitated or otherwise unable to 

give consent. 

Those who opposed excluding these 

activities argued that in some cases, 

research activities for which informed 

consent should be sought and obtained 

are sometimes conducted under the 

auspices of public health surveillance; 

the importance of the activity itself 

should not be an argument to avoid 

seeking and obtaining consent. Others 

argued that consent should always be 

sought and obtained for research 

activities and that all of the exemptions 

and exclusions discussed in the NPRM 

should be covered activities. One 

institution indicated that this exclusion 

was simply not needed because the 

activities described did not meet the 

definition of ‘‘research’’ and thus were 

not subject to the Common Rule. 

Another commenter indicated that 

while the intent of the exclusion seemed 

reasonable, implementation of the 

regulatory intent would be difficult, and 

there are many examples of modern 

public health surveillance activities 

where informed consent would have 

been appropriate. 

A few comments that opposed the 

exclusion indicated concern that it 

might be abused, and cited the Tuskegee 

Syphilis study 25 as an example of what 

they feared might be included under 

this exclusion category. We do not think 

that study would fall within this 

category, because it involved research 

interventions with the subjects, 

including the provision of substandard 

treatment and efforts to prevent subjects 

from obtaining effective treatment, 

which under no circumstances could be 

considered surveillance about a 

condition of public health importance. 

The NPRM asked whether the 

parameters of this exclusion were 

sufficiently clear, and if not, how the 

exclusion could be clarified. In 

response, one private organization 

conducting public health research stated 

that it was unclear if this only applies 

to governmental entities like the Centers 

for Disease Control and Prevention 

(CDC), or if it applies to other 

organizations as well. Another 

institution suggested that the 

community needed additional 

clarification of what types of activities 

fall under this exclusion. One research 

university requested clarification on 

whether public health surveillance 

activities falling under this exclusion is 

subject to subpart B and C, that is, 

research involving pregnant women or 

prisoners, respectively. One 

organization indicated that it would be 

helpful for the examples used in the 

NPRM preamble to be published as a 

separate guidance document. 

Another comment noted that the 

examples included in the preamble only 

addressed acute infectious disease 

surveillance and no other types of 

public health surveillance activities, 

specifically, chronic disease 

surveillance and biomonitoring for toxic 

chemical compounds and metabolites, 

which should be covered under this 

exclusion. 

Another research organization noted 

that the regulatory text and examples 

provided might be too narrow, 

suggesting the exclusion be broadened 

to clarify that it applies to public health 

monitoring aimed at evaluating the 

degree to which affected individuals 

seek and obtain treatment, barriers to 

care, quality of care, treatment 

outcomes, and health disparities. 

Commenters also requested additional 

explanation of what aspects of state 

newborn screening programs would be 

covered under this exclusion, and listed 

a variety of components of the program, 

including validity testing and 

development of new tests, that should 

be covered by the exclusion. 

Commenters asked that clarification of 

the parameters of the public health 

exclusion be provided so that state 

newborn screening programs can 

undertake the activities necessary for 

new test development. They added that 

if the parameters are not clarified, given 

the past controversies associated with 

the retention and secondary use of 

newborn DBS, many programs may not 

undertake activities for which they have 

not been given express permission to 

pursue. 

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26See http://www.fda.gov/Drugs/ 

InformationOnDrugs/ucm135151.htm. 27See https://vaers.hhs.gov/index. 28See http://www.fda.gov/MedicalDevices/ 

DeviceRegulationandGuidance/ 

PostmarketRequirements/ReportingAdverseEvents/ 

ucm127891.htm. 29See http://www.fda.gov/MedicalDevices/Safety/ 

MedSunMedicalProductSafetyNetwork/. 30See http://www.fda.gov/Safety/FDAsSentinel

Initiative/ucm2007250.htm. 

ii. Response to Comments and 

Explanation of the Final Rule: Public 

Health Surveillance 

The final rule adopts the NPRM 

proposal related to deeming certain 

public health surveillance activities as 

explicitly outside of the scope of the 

Common Rule. Several editorial 

modifications have been made to this 

category to improve readability. 

Additionally, the final rule explicitly 

specifies that the collection of 

information is permitted under this 

category of activities. 

The final rule codifies the current 

interpretation that the definition of 

research does not include a category of 

activities that solely involve public 

health surveillance, including collecting 

and testing information or biospecimens 

in activities that are conducted, 

supported, requested, ordered, required, 

or authorized by a public health 

authority and that are limited to those 

necessary to allow the public health 

authority to identify, monitor, assess, or 

investigate potential public health 

signals, onsets of disease outbreaks, or 

conditions of public health importance. 

Such surveillance activities can include 

collecting information about trends, 

signals, risk factors, patterns in diseases, 

or increases in injuries from using 

consumer products. Such activities 

include those associated with providing 

timely situational awareness and 

priority-setting during the course of an 

event or crisis that threatens public 

health, including natural or man-made 

disasters. 

This codification of public health 

surveillance activities as outside the 

definition of research is designed to 

remove uncertainty, but is not intended 

to change the scope of activities subject 

to or not subject to the Common Rule. 

When a public health authority 

conducts public health surveillance 

activities to fulfill its legal mandate to 

protect and maintain the health and 

welfare of the populations it oversees, 

the regulatory protections of the 

Common Rule should not impede that 

authority’s ability to accomplish its 

mandated mission of promoting this 

recognized public good, in keeping with 

the principle of beneficence. Other 

protections independent of the Common 

Rule exist that serve to protect the rights 

and welfare of individuals participating 

in such activities, including federal and 

state policies to protect privacy, 

confidentiality, and security safeguards 

for the information collected. 

Public health surveillance refers to 

collecting, analyzing, and using data to 

target public health and disease 

prevention. It is the foundation of 

public health practice. Surveillance uses 

data from a variety of sources, including 

mandatory reporting of certain 

conditions, routine monitoring, vital 

records, medical billing records, and 

public health investigations. The line 

between public health surveillance and 

epidemiological research can be 

difficult to draw, as the same 

epidemiological techniques may be used 

in both. Generally, the difference 

between the activities is the purpose or 

context in which the investigation is 

being conducted and the role of the 

public health authority. 

The following are examples of public 

health surveillance activities being 

codified as outside of the definition of 

research in this regulation: 

• Safety and injury surveillance 

activities designed to enable a public 

health authority to identify, monitor, 

assess, and investigate potential safety 

signals for a specific product or class of 

products (for example, the surveillance 

activities of the FDA’s Adverse Event 

Reporting System,26 the Vaccine 

Adverse Event Reporting System,27

Manufacturer and User Facility Device 

Experience database,28 the Medical 

Product Safety Network,29 and the 

Sentinel Initiative); 30

• Surveillance activities designed to 

enable a public health authority to 

identify unexpected changes in the 

incidence or prevalence of a certain 

disease in a defined geographic region 

where specific public health concerns 

have been raised (e.g., the U.S. influenza 

surveillance system, which allows CDC 

to find out when and where influenza 

activity is occurring, track influenzarelated illness, determine what strains 

of influenza virus are circulating, detect 

changes in influenza viruses, and 

measure the impact influenza is having 

on hospitalizations and deaths in the 

United States); 

• Surveillance activities designed to 

enable a public health authority to 

identify the prevalence of known risk 

factors associated with a health problem 

in the context of a domestic or 

international public health emergency; 

• Surveillance activities designed to 

enable a public health authority to 

locate the range and source of a disease 

outbreak or to identify cases of a disease 

outbreak; 

• Surveillance activities designed to 

enable a public health authority to 

detect the onset of disease outbreaks or 

provide timely situational awareness 

during the course of an event or crisis 

that threatens the public health, such as 

a natural or man-made disaster; and, 

• Surveillance activities designed to 

enable a public health authority to 

identify the prevalence of a condition of 

public health importance, known risk 

factors associated with a condition of 

public health importance, or behaviors 

or medical practices related to 

prevalence of a known condition of 

public health importance (e.g., 

surveillance of the prevalence of: 

tobacco use, exposure to secondhand 

smoke, lung cancer, or use of smoking 

cessation treatments). 

On the other hand, subsequent 

research using information collected 

during a public health surveillance 

activity, for instance, genetic analysis of 

biospecimens, would not be removed 

from the definition. 

This clarification of current 

interpretation would not remove the 

following activities from the definition 

of ‘‘research’’: exploratory studies 

designed to better understand risk 

factors for chronic diseases, including 

genetic predisposition, for chronic 

diseases; exploratory studies designed 

to elucidate the relationships between 

biomarkers of exposure and biomarkers 

of disease; and exploratory studies of 

potential relationships between 

behavioral factors (e.g., diet) and 

indicators of environmental exposures. 

These types of activities would be 

considered research because they would 

not be conducted solely for the purposes 

described in § ll.102(l)(2), and thus 

would be covered by the Common Rule 

if they involved human subjects, even if 

conducted by a federal agency with a 

public health mandate. Again, they 

might fall within an exemption, 

depending on how they are carried out. 

We note that this provision does 

apply to some activities responding to 

emergencies, and that various 

department or agency activities, not just 

those of HHS, will be affected. Research 

evaluations of public health 

surveillance activities are not included 

in this category because the nature of 

such evaluations is to create 

generalizable knowledge. We also 

recognize that in some public health 

surveillance activities, it may be 

appropriate to obtain consent from the 

individuals from whom information or 

biospecimens are collected. 

We recognize the public comments 

stating that the boundaries of public 

health surveillance activities being 

removed from the definition of research 

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31Memorandum of March 27, 1997. Strengthened 

Protections for Human Subjects of Classified 

Research. 62 FR 26367 (May 13, 1997). Retrieved 

from http://www.fas.org/sgp/clinton/humexp.html. 

are not entirely clear. We recognize that 

some of the activities in this category 

are not research, but believe that the 

inclusion of this provision will help to 

resolve uncertainty in some 

circumstances about whether the rule 

applies. We believe that developing 

guidance in this area will be useful. 

Finally, to clarify what public health 

surveillance activities are being 

removed from the definition of research, 

the final rule contains a new definition 

of ‘‘public health authority’’ at 

§ ll.102(k). 

d. Criminal Justice Activities 

(§ ll.102(l)(3)) and Authorized 

Operational Activities in Support of 

National Security Missions 

(§ ll.102(l)(4)) 

i. Public Comments 

Approximately 60 comments 

discussed the exclusion for certain 

criminal justice activities, the exclusion 

for intelligence surveillance activities, 

or both. The majority of commenters 

opposed these provisions. 

Several commenters stated that the 

two exclusions seemed to contradict 

President Clinton’s Memorandum of 

1997, which stated that classified 

research activities are subject to the 

Common Rule and directed that the 

regulations be revised to include certain 

protections specific to classified 

research activities.31

The majority of commenters 

discussing these provisions also 

expressed concern about what appeared 

to be an expansion of activities not 

covered by the Common Rule. These 

commenters also discussed concerns 

about how this exclusion would affect 

human subjects protections in classified 

research activities. 

Those who supported these 

exclusions generally did not provide the 

rationale for why they supported them. 

One research organization noted that 

additional clarification on the exclusion 

for certain criminal justice activities 

would be needed, and noted that such 

activities should continue to be subject 

to the Common Rule because this type 

of research often includes the collection 

of sensitive, identifiable information, 

which, if disclosed could present risks 

to the subjects. 

ii. Response to Comments and 

Explanation of the Final Rule: Criminal 

Justice Activities 

The final rule clarifies that, consistent 

with current practice, data collection 

and analysis that enables the conduct of 

certain activities carried out as part of 

the criminal justice system is not 

research. The scope of these activities is 

collection and analysis of information, 

biospecimens, or records by or for a 

criminal justice agency for activities 

authorized by law or court order solely 

for criminal justice or criminal 

investigative purposes. The activities 

are necessary for the operation and 

implementation of the criminal justice 

system. The final rule changes the 

wording of the category from that 

proposed in the NPRM only by 

substituting the word ‘‘information’’ for 

‘‘data,’’ for consistency with other parts 

of the rule. 

The provision essentially codifies 

current federal interpretation that such 

activities are not considered to be 

research under the Common Rule. 

Revising the regulations to explicitly 

remove such activities from the scope of 

research subject to the rule is designed 

to avoid the imposition of disparate 

requirements by IRBs with overlapping 

jurisdictions when information 

collection or analysis encompasses the 

development of methods required by 

law or court order for criminal justice or 

criminal investigative purposes. For 

example, the Federal Bureau of 

Investigation (FBI) is charged by law 

with setting standards governing the 

collection and processing of DNA 

biospecimens and information taken 

(forcibly if necessary) from certain 

federal and state criminal suspects or 

offenders incident to their arrest or 

conviction for prescribed offenses under 

the National DNA Identification Act of 

1994 and other acts. Similarly, the FBI 

is charged by law with setting standards 

governing the collection and processing 

of fingerprints and related biographical 

information taken from federal and state 

criminal suspects or offenders and 

certain sensitive civil employment 

applicants. Many criminal law 

enforcement agencies routinely collect 

human biospecimens at crime scenes 

from or relating to victims, suspects, 

and offenders both known and 

unknown. Incident to these activities, 

the FBI is also charged with 

maintaining, and authenticating through 

identification processes, the criminal 

record history of criminal offenders for 

federal government agencies and for the 

overwhelming majority of state 

governments that elect to participate 

and share information through those 

systems. We have determined that this 

category of activities does not meet the 

definition of research in the final rule, 

so that these activities can be conducted 

in accordance with the legitimate goals 

of the criminal justice system. 

We do not believe that this provision 

contradicts President Clinton’s 1997 

memorandum, which addressed the 

regulatory requirements for certain 

activities that are considered research 

under the regulations. This category 

pertains to activities that are outside of 

the regulatory requirements. 

This category is also not intended to 

include social and behavioral studies of 

the causes of criminal behavior. Such 

studies would be considered research 

under the final rule. 

iii. Response to Comments and 

Explanation of the Final Rule: 

Authorized Operational Activities in 

Support of National Security Missions 

The final rule clarifies current federal 

practice that the definition of research 

does not include authorized operational 

activities (as determined by each 

agency) in support of intelligence, 

homeland security, defense, or other 

national security missions. This 

clarification codifies the interpretation 

of the pre-2018 Common Rule. 

As described above, the final rule 

includes a simpler reference to 

authorized operational activities in 

support of national security missions 

not considered to be human subject 

research, as a response to concern that 

the NPRM proposal could be interpreted 

too broadly or too narrowly due to the 

specific activities listed, such as 

surveys, interviews, surveillance 

activities and related analyses, and the 

collection and use of biospecimens. 

These authorized operational activities, 

as determined by each agency, do not 

include research activities as defined by 

the Common Rule, nor have they ever in 

the past been considered regulated by 

the Common Rule. This category of 

activity is removed from the definition 

of research to make explicit that the 

requirements of the final rule do not 

apply to authorized operational 

activities in support of national security 

missions. This clarification is not 

intended to narrow the scope of the 

Common Rule. 

We do not believe that this category 

contradicts President Clinton’s 

Memorandum of 1997 regarding 

classified research, because this 

category is merely clarifying what 

activities are not considered to meet the 

definition of research. The Clinton 

Memorandum calls for a number of 

requirements to be added to protections 

for classified research activities, but it 

does not address activities that are not 

considered research. 

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7178 Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 

4. NPRM Exclusions Not Included in the 

Final Rule 

a. Certain Quality Assurance and 

Quality Improvement Activities 

i. Public Comments 

Approximately 90 comments 

discussed the proposed exclusion for 

certain QA/QI activities in the NPRM 

involving the implementation of an 

accepted practice. A majority of 

comments supported the concept of 

excluding some QA/QI activities from 

the Common Rule, although some stated 

that the QA/QI exclusion proposed in 

the NPRM was too narrow to cover what 

has evolved as current practice. 

These commenters expressed 

concerns that: (1) The NPRM proposed 

to exclude only the QA/QI activities that 

met the exclusion, and that all other 

QA/QI activities would fall under the 

rule; or (2) the exclusion would be 

interpreted to mean that the activities 

described in the exclusion were the only 

QA/QI activities that could be 

considered not covered by the rule. 

The most commonly discussed 

suggestions for expanding the scope of 

this exclusion included: 

• Expanding the exclusion beyond 

‘‘accepted practices’’ 

• Permitting the collection of 

outcome measures in the category of 

activities proposed to be excluded by 

the NPRM 

One hospital noted that QA/QI is not 

limited to implementation of an 

‘‘accepted practice’’ and that limiting 

the exclusion in this way might impede 

innovation, for example, accessing an 

electronic medical record system for 

QA/QI to test incorporating clinical 

information to analyze and test bestpractice pop-up alerts that signal 

important information for healthcare 

providers in caring for a patient. This 

commenter asserted that there is no 

current ‘‘accepted practice’’ for 

activities like this, yet they should be 

excluded from the definition of research 

to avoid confusion and to support 

ongoing innovation and care 

improvement activities. This commenter 

also suggested that any QA/QI exclusion 

should permit activities that allow 

medical centers to analyze how they 

deliver care, improve outcomes, and 

modify processes to achieve healthcare 

reform goals. 

One commenter also noted that the 

‘‘accepted practice’’ limitation would 

also be problematic in the social 

sciences. This commenter disagreed that 

the proposed exclusion for quality 

improvement or assurance practices 

should be limited to ‘‘an accepted 

practice,’’ and felt that it should apply 

to the evaluation of alternative 

practices. In social sciences research an 

‘‘accepted practice’’ is generally not as 

well defined, can evolve rapidly, and 

vary by considerations such as timing, 

culture, geography, and nature of 

service. In social science research, this 

limitation could severely limit the use 

of this exclusion for research that is 

equally low in risk and therefore does 

not require review. 

A few commenters explicitly 

referenced the importance of QA/QI 

activities in the context of a learning 

health care system, and discussed the 

need for a broader exclusion in order to 

achieve the goals of a learning health 

system. 

A professional organization focused 

on advancing the fields of health 

services research and health policy 

noted that a basic tenet of the learning 

health system is the expectation of 

continuous learning from routine care, 

which often is accomplished by 

evaluating health outcomes. The 

intentional assessment of the outcomes 

related to a QI activity by itself should 

not make the activity subject to the 

Common Rule. 

A medical education membership 

organization felt that routine evaluation 

of practices and continuous 

incorporation of knowledge learned into 

patient care is fundamental to a learning 

health system and should not be 

impeded by the regulatory framework. It 

stated that the current Common Rule 

provides insufficient guidance to 

distinguish research and improvement 

in care delivery in a consistent manner. 

The organization indicated that the 

revised Common Rule explicitly 

recognizes that efforts to improve care 

by evaluating an accepted practice and 

the resulting effects are not research that 

should be regulated under the Common 

Rule. 

Commenters suggested many other 

QA/QI activities that should be 

explicitly excluded or exempted from 

the Common Rule, such as: 

• Activities mandated by the Clinical 

Laboratory Improvement Amendments 

(CLIA) 

• Evaluations of systems-level 

interventions to improve quality and 

safety 

• Comparative assessment of 

alternative practices to determine 

relative effectiveness 

• All QA/QI research for the purpose 

of health care operations, including 

patient-centered comparative 

effectiveness research 

• Evaluation of competing QA/QI 

strategies for implementation of 

accepted medical practices, which 

should not be subject to IRB review 

• Evaluation of competing low-risk 

interventions that would typically be 

implemented in a QA/QI framework 

without further research: these typically 

are not direct medical treatments but 

ancillary aspects of care. 

• The use of other analytic 

assessment methods, such as 

interrupted time series analysis, or 

randomization of clusters (including 

stepped wedge designs) 

• Dissemination of QA/QI results, or 

the intention to disseminate results, 

including by publication, which should 

not by itself make the activity subject to 

IRB review (consistent with current 

OHRP guidance) 

• Multi-institution collaborations of 

otherwise routine QA/QI activities 

• Public health-related QA/QI 

activities 

• Comparative benchmarking 

Others expressed approval for the 

proposed exclusion, but suggested that 

substantial guidance would be 

necessary for the regulated community 

to apply this exclusion appropriately. 

Specifically, several commenters asked 

about the extent to which OHRP’s 

current guidance on QA/QI activities 

would still apply. Others asked for 

clarification about the extent to which 

the NPRM proposal would apply in 

situations where a hospital system with 

several hospitals implemented different 

accepted practices at different hospitals 

within the system, and compared 

outcomes to determine which accepted 

practice would be best for that hospital 

system. 

Several comments did not support the 

NPRM’s QA/QI proposal. Reasons 

included: believing that the activities 

excluded by the NPRM already did not 

meet the definition of research and thus 

did not need to be explicitly excluded; 

believing that these activities should be 

subject to some type of review because 

of concerns about investigator selfdetermination; and, believing that even 

in QA/QI activities, human subjects 

should be offered the opportunity to 

know that they are subjects in a research 

activity and should be offered the 

option to consent. 

One patient advocacy group noted 

that because much research is done in 

the guise of administration or QI, this 

proposed exclusion might encourage 

researchers to evade human subjects 

protections while the projects may put 

primary subjects and third parties at 

risk. It stated that although some 

hospital-based projects might incur 

minimal risk to primary subjects, they 

might pose greater risk to other parties, 

for example, patients. Thus, the group 

argued that this exclusion should be 

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stricken and that if personal information 

and biospecimens are to be collected 

and analyzed for purposes other than 

the individual patient’s care, then that 

activity should be subject to the 

Common Rule. 

One research institution felt that the 

proposed change suggests that patient 

consent will be necessary for many 

activities designed to ensure QA/QI in 

health care settings, and could interfere 

with the imperative to design and 

evaluate new approaches to enhance 

patient safety and clinical outcomes. 

The commenter added that the 

implications of this provision should be 

assessed by clinical practitioners and 

hospital administrators in addition to 

researchers and research institutions. 

Another commenter noted that the 

proposed exclusion of QA/QI activities 

fails to exclude important activities that 

are considered ‘‘not research’’ under the 

current Common Rule, arguing that the 

new NPRM exclusion is more in line 

with evidence-based practice than with 

QI. Institutions are required under The 

Joint Commission to perform 

continuous QI activities, which 

typically are small, iterative changes to 

improve clinical care; these activities 

are seen as part of hospital operations 

rather than research. The commenter 

stated that the proposed limitations 

would make certain QI activities subject 

to IRB review and possible informed 

consent requirements, which could 

result in overregulating an activity that 

is currently not subject to the Common 

Rule. 

Several of these commenters generally 

indicated that they interpreted the 

proposed exclusion as providing a 

definition of QA/QI, as opposed to 

excluding a specific type of QA/QI 

activity. Several of these commenters 

suggested deleting a QA/QI exclusion 

from the rule so that IRBs and 

investigators would not be confused. 

One hospital suggested eliminating 

quality activities from the NPRM since 

by specifying that certain quality 

activities are not research, the NPRM 

seems to designate all other quality 

activities as research by default. 

ii. Response to Comments and 

Explanation of the Final Rule: Certain 

Quality Assurance and Quality 

Improvement Activities 

The proposed exclusion for QA/QI 

activities is not included in the final 

rule. The degree of concern expressed 

by the public comments on this topic is 

significant. We recognize that human 

subject protections would be 

meaningful and appropriate for some 

QA/QI research activities, but not for 

others. However, to avoid increasing 

confusion and unnecessary obstacles to 

innovation, the final rule does not single 

out certain QA/QI activities as meeting 

or not meeting the definition of 

research. 

b. Program Improvement Activities 

i. Public Comments 

Approximately 20 comments were 

received on this proposed exclusion 

regarding data collection and analysis 

for internal operational monitoring and 

program improvement purposes, with a 

strong majority in support. Commenters 

indicated that the proposed exclusion 

would require significant guidance 

because it was unclear what types of 

activities it might include and when. 

Several commenters supported the 

proposed exclusion, but noted that the 

exclusion should specifically reference 

QI activities instead of just program 

improvement activities. One commenter 

suggested that activities defined as 

‘‘health care operations’’ under HIPAA 

also be included in this exclusion. One 

commenter opposed this exclusion 

because of the lack of specific reference 

to QI. Another opposed this exclusion 

because they felt it was too narrowly 

written. 

One large private research firm 

indicated opposition to this proposal 

because it was too confusing. Further, 

this group questioned the need for an 

exclusion that seemed to only reference 

activities that would not be considered 

to fall under the rule because these 

activities would not satisfy the 

definition of research (specifically, these 

activities would not be designed to 

contribute to generalizable knowledge). 

Of those who opposed this proposal, 

a minority suggested that the proposed 

exclusion could be abused by 

investigators, especially given that the 

NPRM did not propose to require any 

institutional oversight of exclusion 

determinations. One commenter noted 

that because many research activities 

might be conducted under the guise of 

internal improvement activities, this 

exclusion seemed to be giving 

investigators significant opportunities to 

conduct human research activities 

outside the confines of the rule. 

One commenter who supported this 

provision suggested that it could be 

merged with the QA/QI exclusion 

proposed in the NPRM. This commenter 

also suggested that a definition of 

program improvement and operational 

monitoring be provided. 

The NPRM asked whether the use of 

biospecimens should be permitted in 

this exclusion. Of those who answered 

this question, a majority indicated yes. 

This majority generally referenced a 

belief that many activities with residual 

newborn DBS (see Section III.D) would 

fall under this exclusion. One 

commenter who opposed the inclusion 

of biospecimens in this excluded 

category indicated that if the goal of the 

NPRM was to cover all nonidentified 

biospecimens, then this exclusion 

should not include the research use of 

biospecimens. 

ii. Response to Comments and 

Explanation of the Final Rule: Program 

Improvement Activities 

The proposed exclusion for program 

improvement activities is not included 

in the final rule. Based on the public 

comments it does not seem useful for 

this category of activities to be singled 

out as not meeting the definition of 

research. As with the NPRM proposed 

exclusion regarding QI/QA activities 

implementing accepted practices, public 

commenters raised concerns that this 

exclusion would have created more 

misunderstanding and confusion than it 

would have resolved. As with QI/QA 

activities, some program improvement 

activities involve research and deserve 

the protections of the rule, while others 

are not research and are not under the 

rule. We believe that this topic would be 

better addressed through other means. 

I. Written or in Writing (§ ll.102(m)) 

The final rule includes a definition 

that was not included in the NPRM nor 

in the pre-2018 rule. The definition of 

‘‘written or in writing’’ is included at 

§ ll.102(m) to clarify that, in 

accordance with the longstanding 

interpretation of the pre-2018 rule, these 

terms include electronic formats, which 

are increasingly used to fulfill many of 

the documentation requirements that 

appear throughout the rule. 

Although public comments did not 

directly address this issue, we are aware 

that some in the regulated community 

are uncertain of whether, for example, 

consent forms may be in electronic 

formats. This definition is intended to 

address this concern. Note that the 

definition of ‘‘written or in writing’’ 

does not preclude the possibility that 

consent forms could be in media other 

than paper or electronic formats and 

still meet the requirements of the 

Common Rule. 

IV. Ensuring Compliance With This 

Policy (§ll.103) 

A. Background and Pre-2018 

Requirements 

Requirements in the pre-2018 rule at 

§ ll.103 delineated procedural 

requirements for institutions and IRBs 

to follow to comply with the rule. The 

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requirements pertained to written 

assurances (through FWAs) that 

institutions engaged in research are in 

compliance with the regulations and 

that the content of such assurances 

include: a statement of principles 

governing the institution in the 

discharge of its responsibilities to 

protect research subjects; designation of 

one or more IRBs; a detailed IRB 

membership roster; and written 

procedures for IRBs and reporting of 

unanticipated problems. A U.S. 

institution also was able to voluntarily 

pledge to conduct all of its nonexempt 

human subjects research, regardless of 

funding source, in compliance with the 

Common Rule or the Common Rule and 

subparts B, C, and D of 45 CFR part 46— 

often referred to as ‘‘checking the box’’ 

on the assurance form. 

The pre-2018 rule also stated who 

will execute and evaluate assurances. 

Finally, the rule described the process 

by which institutions certify that 

nonexempt research has been reviewed 

and approved by an IRB. There has been 

concern expressed by some that the 

assurance process may have been 

unduly burdensome for institutions and 

did not provide meaningful protections 

for human subjects. 

B. NPRM Proposals 

The NPRM proposed a number of 

substantive and procedural 

modifications to § ll.103 of the 

Common Rule. First, the NPRM 

proposed to move several requirements 

from §ll.103 to § ll.108, which 

pertains to IRB functions and 

operations: (1) The IRB recordkeeping 

requirements; (2) the requirement in the 

pre-2018 rule that IRBs have sufficient 

meeting space and staff to support IRB 

reviews and record keeping 

requirements; and (3) the pre-2018 

requirement that an up-to-date list of the 

IRB members and their qualifications be 

included in an institution’s assurance. 

The NPRM also proposed to modify the 

IRB membership requirement such that 

this up-to-date list would no longer be 

required as part of an institution’s 

assurance. Instead, an IRB or an 

institution would be required to prepare 

and maintain a current list of IRB 

members. 

The NPRM proposed to delete several 

requirements found in the pre-2018 

rule: (1) The requirement that an 

institution provide a statement of 

ethical principles by which the 

institution will abide, as part of the 

assurance process; (2) the pre-2018 rule 

requirement that an institution 

designate one or more IRBs on its FWA; 

(3) the provision found in the pre-2018 

rule that a department or agency head’s 

evaluation of an assurance will take into 

consideration the adequacy of the 

proposed IRB(s) designated under the 

assurance, in light of the anticipated 

scope of the institution’s activities and 

the types of subject populations likely to 

be involved, the appropriateness of the 

proposed initial and continuing review 

procedures in light of the probable risks, 

and the size and complexity of the 

institution; and (4) the requirement that 

grant applications undergo IRB review 

and approval for the purposes of 

certification. 

Note that under the NPRM federal 

departments or agencies would retain 

the ability to ask for information about 

which IRBs review research conducted 

at an institution as part of the assurance 

process, even if providing this 

information is not explicitly mandated. 

According to the NPRM, an 

additional, nonregulatory change was 

proposed for the assurance mechanism. 

The current option of ‘‘checking the 

box’’ on an FWA (described in section 

IV.A above) would be eliminated. 

To further strengthen the proposed 

new provision at §ll.101(a), giving 

Common Rule departments and 

agencies explicit authority to enforce 

compliance directly against IRBs that 

are not operated by an assured 

institution, language was proposed 

requiring that for nonexempt research 

involving human subjects that is 

covered by this policy and takes place 

at an institution in which IRB oversight 

is conducted by an IRB that is not 

operated by the institution, the 

institution and the organization 

operating the IRB shall establish and 

follow procedures for documenting the 

institution’s reliance on the IRB for 

oversight of the research and the 

responsibilities that each entity will 

undertake to ensure compliance with 

the requirements of this policy (e.g., a 

written agreement between the 

institution and the IRB, or by 

implementation of an institution-wide 

policy directive providing the allocation 

of responsibilities between the 

institution and an IRB that is not 

operated by the institution). 

The NPRM requested public comment 

on whether protection for human 

subjects in research would be enhanced 

if OHRP conducted routine periodic 

inspections to ensure that the 

membership of IRBs designated under 

FWAs satisfy the requirements of 

§ ll.107. 

C. Public Comments 

Very few comments were received on 

the proposals at §ll.103. Four 

commenters expressed their views on 

the proposal to delete the requirement 

that an institution provide a statement 

of ethical principles as part of the 

assurance process, with three 

supporting the proposal and one 

opposing it. 

Four commenters supported the 

proposal to eliminate the requirement 

that an institution designate one or more 

IRBs on its FWA. 

Two comments were received, one in 

support and one opposed, on the 

proposed elimination of the requirement 

that an up-to-date list of the IRB 

members and their qualifications be 

included in an institution’s assurance. 

Two comments, one for and one against, 

were received on the proposal to remove 

the requirement that a department or 

agency head’s evaluation of an 

assurance take into consideration the 

adequacy of the proposed IRBs. 

Responses to the question about 

periodic inspections to ensure IRBs 

were compliant were mixed, with most 

commenters saying that it is not clear 

that ensuring IRBs are compliant would 

enhance human subjects protections. 

Others questioned the need for this 

requirement, given other incentives 

institutions have to ensure they have a 

duly constituted IRB, and still others 

asked what was meant by ‘‘periodic.’’ 

Approximately 30 commenters 

supported the proposal to delete the 

requirement that the IRB review grant 

applications, with only one commenter 

opposed to the proposal. 

D. Response to Comments and 

Explanation of the Final Rule: Assuring 

Compliance With the Policy 

As proposed in the NPRM, the final 

rule eliminates the pre-2018 rule 

requirement that an institution provide 

a statement of ethical principles by 

which an institution will abide as part 

of the assurance process. We believe 

this requirement is unnecessary. 

Further, for international institutions 

that may receive federal funding for 

research activities, it creates the 

impression that these international 

institutions must modify their internal 

procedures to comport with the set of 

principles designated on the FWA for 

activities conducted at those institutions 

that receive no federal funding. OHRP 

has received many questions about the 

extent to which international 

institutions must adhere to the ethical 

principles designated as part of the 

assurance process for research activities 

conducted by the institution that receive 

no Common Rule department or agency 

funding. That such measures are not 

required will be made clear by deletion 

of this requirement in the final rule. 

Additionally, as proposed in the 

NPRM, the final rule eliminates the 

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requirement that appeared in the pre2018 rule that an up-to-date list of the 

IRB members and their qualifications be 

included in an institution’s assurance. 

Instead, §§ll.108(a)(2) and 

ll.115(a)(5) in the final rule require 

that an IRB or the institution prepare 

and maintain a current list of IRB 

members. This eliminates the previous 

requirement that changes in IRB 

membership be reported to the 

department or agency head, or to OHRP 

when the existence of an assurance 

approved by HHS for federal-wide use 

is accepted. Of note, SACHRP 

recommended in March, 2008 that 

OHRP pursue harmonizing the Common 

Rule with FDA’s human subjects 

protection regulations by eliminating 

the requirement to submit IRB 

membership lists. 

The final rule, as proposed in the 

NPRM, also eliminates the requirement 

that appeared in the pre-2018 rule that 

an institution designate one or more 

IRBs on its FWA. Federal departments 

or agencies retain the ability to ask for 

information about which IRBs review 

research conducted at an institution as 

part of the assurance process, even if 

that requirement is not explicitly 

mandated in the regulations. 

An additional, a nonregulatory change 

that was described in the NPRM will be 

made to the assurance mechanism. The 

prior option that enabled institutions 

with an active FWA to ‘‘check the box’’ 

(described in section IV.A above) is 

being eliminated. Importantly, 

institutions could, if they so desire, 

continue for purposes of their own 

internal rules to voluntarily extend the 

regulations to all research conducted by 

the institution, but this voluntary 

extension will no longer be part of the 

assurance process and such research 

will not be subject to OHRP oversight. 

We expect this change to have the 

beneficial effect of encouraging some 

institutions to explore a variety of 

flexible approaches to overseeing lowrisk research that is not funded by a 

Common Rule department or agency, 

without reducing protection of human 

subjects, thus furthering the goal to 

decrease inappropriate administrative 

burdens. 

In addition, as proposed in the NPRM, 

the final rule removes the provision 

found in the pre-2018 rule that a 

department or agency head’s evaluation 

of an assurance will take into 

consideration the adequacy of the 

proposed IRB(s) designated under the 

assurance in light of the anticipated 

scope of the institution’s activities and 

the types of subject populations likely to 

be involved, the appropriateness of the 

proposed initial and continuing review 

procedures in light of the probable risks, 

and the size and complexity of the 

institution. We believe this deletion 

aligns the regulations with changes 

made in December 2000 to OHRP’s 

implementation of the FWA process. 

Those changes streamlined and 

simplified the assurance process and 

eliminated OHRP’s institution-specific 

evaluation of the adequacy of each IRB 

designated under the assurance. 

Each FWA-holding institution 

continues to have responsibility for 

ensuring that the IRBs on which it relies 

are registered with OHRP and are 

appropriately constituted to review and 

approve the institution’s human 

subjects research, as required under 

§§ ll.107 and ll.108 of the final 

rule. 

The final rule contains language at 

§ ll.103(e) requiring that for 

nonexempt research involving human 

subjects (or exempt research that 

requires limited IRB review) that takes 

place at an institution for which an IRB 

not operated by that institution 

exercises oversight, the institution and 

the organization operating the IRB must 

document the institution’s reliance on 

the IRB for its research oversight. The 

final rule also requires that this 

documentation include the 

responsibilities of each entity to ensure 

compliance with the requirements of the 

rule. 

The requirement included in the final 

rule for documenting an institution’s 

reliance on an IRB that it does not 

operate is more flexible than what was 

proposed in the NPRM. The final rule 

only requires that the reliance 

agreement between the institution and 

the organization operating the IRB be 

documented. It does not include the 

NPRM proposal that the institution and 

the organization operating the IRB 

establish and follow procedures for 

documenting the institution’s reliance 

on the IRB for oversight of the research 

and delineating the responsibilities that 

each entity would assume to ensure 

compliance with the requirements of the 

rule. 

In considering the public comments, 

we determined that it was unnecessary 

to require that such reliance 

relationships be described in 

institutional procedures. Under the final 

rule, compliance with this provision 

could be achieved in a variety of flexible 

ways, for example, through a written 

agreement between the institution and a 

specific IRB, through language 

contained in a protocol of a multiinstitutional study, or more broadly, by 

implementation of an institution-wide 

policy directive providing the allocation 

of responsibilities between the 

institution and all IRBs that are not 

operated by the institution. 

Documenting the responsibilities of the 

institution and the IRB is already a 

requirement under the terms of an FWA, 

but is now a regulatory requirement. An 

additional requirement has been added 

at §ll.115(a)(9) that such 

documentation be part of the IRB 

records. 

We acknowledge that the new 

requirement could increase 

administrative burden for some 

institutions, but believe that the 

examples cited above reflecting the 

various options an institution may use 

to document reliance on an IRB not 

operated by that institution are 

generally already standard practice in 

the regulated community. 

Finally, the final rule eliminates the 

requirement in the pre-2018 rule at 

§ ll.103(f) that grant applications 

undergo IRB review and approval for 

the purposes of certification. The grant 

application is often outdated by the time 

the research study is submitted for IRB 

review and contains detailed 

information about the costs of a study, 

personnel, and administrative issues 

that go beyond the mission of the IRB 

to protect human subjects. Therefore, 

experience suggests that review and 

approval of the grant application is not 

a productive use of IRB time. 

V. Exempt Research (§ll.104) 

A. Applicability of Exemptions to 

Subparts B, C, and D 

1. Background and Pre-2018 

Requirements 

In the pre-2018 rule, the application 

of the exemptions to research under 

subparts B, C, and D was specified 

through footnote 1, which stated that 

the exemptions do not apply to research 

involving prisoners, and are also limited 

in their application to research 

involving children. Regarding the latter 

issue, the pre-2018 exemption at 

§ ll.101(b)(2) for research involving 

educational tests, survey or interview 

procedures or observations of public 

behavior did not apply to subpart D (i.e., 

such research did not qualify for this 

exemption), except for research 

involving educational tests, or 

observations of public behavior when 

the investigator does not participate in 

the activities being observed. The pre2018 exemptions did apply to subpart B. 

2. NPRM Proposals 

Although some of the exemptions 

proposed in the NPRM were based 

largely on exemptions in the pre-2018 

rule, not all would have applied to 

subparts B, C, and D. Language in the 

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32HHS. Waiver of the Applicability of Certain 

Provisions of Department of Health and Human 

Services Regulations for Protection of Human 

Research Subjects for Department of Health and 

Human Services Conducted or Supported 

Epidemiologic Research Involving Prisoners as 

Subjects. FR 68(119):36929 (June 20, 2003). 

Retrieved from https://www.gpo.gov/fdsys/pkg/FR2003-06-20/pdf/03-15580.pdf. 

NPRM explained how the proposed 

exemptions may have applied to the 

subparts. The NPRM proposed that all 

of the exemptions be applied to research 

conducted under subpart B, and that 

none of the exemptions may be applied 

to research conducted under subpart C, 

except for research aimed at a broader 

population that consists mostly of 

nonprisoners but that incidentally 

includes some number of prisoners. The 

NPRM proposed that some of the 

exemptions may be applied to research 

conducted under subpart D. Under the 

NPRM, the exemption at proposed 

§ ll.104(e)(1) (Research Involving 

Educational Tests, Surveys, Interviews, 

or Observation of Public Behavior if the 

Information is Recorded with Identifiers 

and even if the Information is Sensitive) 

could not be applied to research 

involving children under subpart D. 

This was because protections including 

IRB review and parental permission are 

appropriate for research involving 

educational tests, surveys or interview 

procedures, or observation of public 

behavior when the information 

collected may be individually identified 

and sensitive in nature. 

Although the NPRM did not propose 

changes to the HHS regulations at 45 

CFR part 46, subparts B, C and D, 

consideration was given to whether the 

proposed exemption categories should 

apply to research involving prisoners 

under subpart C, either if the research 

consists mostly of nonprisoners and 

only incidentally includes some number 

of prisoners, or if the research intends 

to involve prisoners as research 

subjects. Public comment was requested 

on whether the revised exemption 

categories should be permitted to apply 

to research involving prisoners. The 

NPRM explained considerations 

including the following: The history of 

HHS subpart C research certifications to 

date; the preponderance of low-risk, 

sociobehavioral research focused on 

prisoner welfare, substance abuse 

treatment, community reintegration, and 

services utilization; the occurrence of 

prisoner-subjects in databases or 

registries; and the broad interpretation 

of the subpart C ‘‘prisoner’’ definition 

that includes, for example, subjects in 

court-mandated residential substance 

abuse treatment. 

The NPRM posed a question asking 

whether language in the final rule 

should resemble the 2003 waiver of the 

applicability of certain provisions of the 

rule for HHS-conducted or -supported 

epidemiologic research involving 

prisoners and state that the exemptions 

apply except for research where 

prisoners are a particular focus of the 

research.32 The language of the 2003 

waiver criteria are broader than what 

was proposed in the NPRM, and already 

familiar to the research community. 

They apply to epidemiological research 

that presents no more than minimal risk 

and no more than inconvenience to the 

prisoner/subjects. A question was also 

asked whether the proposed application 

of the exemptions to subparts B and D 

was appropriate. 

3. Public Comments 

Approximately 50 comments were 

received on the applicability of the 

proposed exclusions and exemptions to 

the subparts of the rule. Eight comments 

addressed the applicability of the 

exemptions to subparts B and D. 

However, responses to the question, ‘‘Is 

the proposed application of the 

exemptions to subparts B and D 

appropriate?’’ uniformly agreed with the 

proposal. A strong majority of the 

comments addressed the applicability of 

the exemptions to subpart C. 

The NPRM sought comment on the 

proposal to allow the exemptions to 

apply in research that only incidentally 

involves prisoners, but that is enrolling 

a primarily nonprisoner population. 

This would represent a policy shift in 

how the exemptions historically have 

been applied to subpart C. Comments 

regarding this proposal were mixed. 

Some responses claimed that the 

proposal expanded the application of 

the exemptions to all research under 

subpart C, rather than a small subset of 

subpart C research. Other comments 

opposed the proposal, pointing to the 

troubled history of research with 

prisoners, and suggesting that research 

involving prisoners, regardless of the 

risk level, should always go through 

subpart C IRB review. A narrow 

majority of comments responded that 

the exemptions should be permitted to 

apply to subpart C in a limited way. 

However, responses regarding the 

proposed language or which exemptions 

should be applicable to subpart C 

prisoners varied. Some felt a study 

should be exempted only if it offered 

some benefit to the prison population. 

Others felt it could be exempt so long 

as there was no identifiable sensitive 

information or biospecimens involved. 

Some who supported the proposal 

indicated that because the NPRM did 

not propose to expand the applicability 

of the exemptions to research targeting 

prisoners, the proposal seemed to be a 

reasonable expansion. One comment 

noted that permitting a broader 

interpretation might enable more 

prisoner-subjects to participate in 

potentially low-risk beneficial research. 

A few commenters addressed whether 

the language describing the applicability 

of the subparts to research involving 

subpart C should resemble the 2003 

epidemiological waiver criteria. Of 

these, comments were mixed, with some 

indicating that the 2003 epidemiological 

waiver criteria would be too ambiguous, 

others indicating that it would be 

appropriate language to use, and a final 

minority reiterating their opinion that 

the exemptions should never be 

permitted in research conducted under 

subpart C. 

4. Response to Comments and 

Explanation of the Final Rule: 

Applicability of Exemptions to Subparts 

The NPRM proposal regarding how 

the proposed exemptions may be 

applied to the subparts is largely 

unchanged in the final rule. The 

language at § ll.104(b)(2) regarding 

subpart C has been modified slightly to 

reduce ambiguity and potential 

administrative burden, and in response 

to public comment, to narrow the scope 

of exemption application. The final rule 

does not adopt the 2003 epidemiological 

waiver language due to concerns from 

public comments that such language 

would be ambiguous and difficult to 

interpret. 

The final rule sectionll.104(b)(1) 

states that all of the exemptions at 

§ ll.104 may be applied to research 

conducted under subpart B if the 

conditions of the exemption are met. 

Language at § ll.104(b)(2) states that 

none of the §ll.104 exemptions may 

be applied to research conducted under 

subpart C, except for research aimed at 

involving a broader subject population 

that only incidentally includes 

prisoners. This is a modification of the 

NPRM language, which proposed that 

the exemptions could apply if research 

consisted ‘‘mostly of nonprisoners and 

only incidentally’’ included some 

number of prisoners. The language was 

changed in order to avoid the implied 

need (‘‘mostly’’) for institutions to 

project and track the percentage of 

prisoners participating in nonexempt 

research. The revision also more clearly 

describes and limits the circumstances 

in which exempt research may include 

prisoners. The language at 

§ ll.104(b)(3) relevant to subpart D 

has been modified to reflect the revised 

structure of the final rule, and now 

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states that the exemptions at paragraphs 

(d)(1), and (d)(4)–(8) of this section may 

be applied to research that is subject to 

subpart D if the conditions of the 

exemption are met. Paragraphs (d)(2)(i) 

and (ii) of this section may apply only 

to research activities that are subject to 

subpart D involving educational tests or 

the observation of public behavior when 

the investigator(s) do not participate in 

the activities being observed. Paragraph 

(d)(2)(iii) of this section may not be 

applied to research that is subject to 

subpart D, because protections, 

including IRB review and parental 

permission, are appropriate for research 

involving children and educational 

tests, surveys or interview procedures, 

or observation of public behavior when 

the information collected may be 

individually identified and sensitive in 

nature. 

The final rule does not make revisions 

to the HHS regulations at 45 CFR part 

46, subparts B, C, and D. Throughout 

this rulemaking process, the intent has 

been to revise subpart A, and to address 

revisions to subparts B, C, and D at a 

later time. However, particular 

consideration has been given to the 

specific issue of whether the proposed 

exemption categories should apply in 

the context of research that is aimed at 

a broad population and only 

incidentally includes prisoners. We 

concur with the comments expressing 

support for this change. 

In such instances, the specific 

protections required by subpart C are 

frequently not relevant to the research 

subjects. The permitted inclusion of this 

subset of prisoners under the 

exemptions at § ll.104 is intended to 

allow an appropriate reduction in IRB 

administrative burden while preventing 

IRBs from necessarily prohibiting the 

participation of this group in exempt 

research activities, assuming the 

conditions of the exemptions are fully 

satisfied. 

We believe this subpart C change is 

narrow in scope, affecting only a small 

subset of subjects who are prisoners. 

This change will permit, for example, 

the exempt secondary research use of 

information or biospecimens from 

subjects who are prisoners, if that 

analysis is not seeking to examine 

prisoners as a population and only 

incidentally includes prisoners in the 

broader study. Such inclusion would 

previously have required IRB review 

under subpart C, including review by an 

IRB prisoner representative, followed by 

certification to and authorization by 

OHRP. In addition, if the research did 

not fit into a § 46.306(a)(2) subpart C 

category of permissible research, 

prisoners could not be included as 

subjects in the study, thereby causing 

problems involving identifying and 

removing these subjects from the 

analysis of repositories and databases. 

Similarly, the narrow expansion 

would allow a subject to continue 

participation in exempt research if he or 

she became a prisoner during the course 

of an exempt study, assuming the study 

was aimed at a broad nonprisoner 

population, without the need for 

subpart C IRB review and certification 

to OHRP. For example, an exempt study 

that recruited subjects from a local 

community center to participate in a 

comparison of HIV educational 

materials would continue to be exempt, 

and would not trigger the need for 

review under subpart C, even if some of 

the subjects became prisoners after 

enrollment. On the other hand, a study 

that recruited subjects from a jail or 

prison to participate in a comparison of 

HIV educational materials would 

continue to be nonexempt under the 

final rule and require both subpart A 

and subpart C review, including 

certification to OHRP. 

B. Exemption Determination 

1. Background and Pre-2018 

Requirements 

The pre-2018 rule did not specify who 

at an institution may determine that 

research is exempt. However, in the 

past, OHRP has recommended that 

because of the potential for conflict of 

interest, investigators not be given the 

authority to make an independent 

determination that their human subjects 

research is exempt. OHRP has 

recommended that institutions 

implement exemption policies that most 

effectively address the local setting and 

programs of research. OHRP has 

recognized that this may result in a 

variety of configurations of exemption 

authority, any of which were acceptable 

assuming compliance with the pre-2018 

regulations. In addition, OHRP guidance 

provided that institutional policies and 

procedures should identify clearly who 

is responsible for making exemption 

decisions. We note that under the pre2018 and final rule a Common Rule 

department or agency retains final 

authority as to whether a particular 

human subjects research study 

conducted or supported by that 

department or agency is exempt from 

the Common Rule. 

2. NPRM Proposals 

The NPRM proposed to adopt a 

requirement that exemption 

determinations be documented, and that 

such determinations could be made 

only in two specified ways. To assist 

investigators and institutions in making 

a timely and accurate determination of 

exemption status the NPRM proposed 

that federal departments or agencies 

would develop one or more exemption 

determination tools (the use of which 

would constitute one of the ways in 

which determinations could be made). 

Federal departments or agencies would 

create their own tool, or rely on a tool 

created by another department or 

agency (including a web-based tool 

created by HHS). Institutions would 

have discretion as to whether or not to 

implement such a tool. As proposed in 

the NPRM, it would be designed in such 

a way that if the person using the tool 

inputs accurate information about the 

study, the tool would produce a 

determination of whether the study is 

exempt. Institutions could rely on the 

use of the federally developed tool by 

investigators as a ‘‘safe harbor’’ for this 

determination. Use of the tool would be 

voluntary, and each institution and 

agency would decide whether to rely on 

the decision tool for their 

determinations, and if so, who would be 

allowed to use it. Institutions that chose 

not to use the tool for particular 

determinations would be required to 

have such determinations made by an 

individual who is knowledgeable about 

the exemption categories and who has 

access to sufficient information to make 

an informed and reasonable 

determination. In general, as envisioned 

in the NPRM, it was expected that 

investigators would not be allowed to 

make exemption determinations for 

themselves without the use of the 

decision tool, due to considerations of a 

conflict of interest. 

The NPRM requested public comment 

on several aspects of the proposal to 

develop a decision tool: (1) The 

likelihood of an institution allowing 

investigators to use the tool; (2) the ease 

of investigators contriving answers in 

using the tool; (3) whether use of the 

tool should be restricted to certain 

exempt categories of research; (4) 

whether deployment of such a tool 

would erode public trust in research; 

and (5) what additional information 

should be required to be kept as a record 

other than the information submitted 

into the decision tool. 

The NPRM also proposed that the 

institution or IRB be required to 

maintain records of exemption 

determinations, which records must 

include, at a minimum, the name of the 

research study, the name of the 

investigator, and the exemption category 

applied to the research study. As 

described in the NPRM, maintenance of 

the output of the completed decision 

tool would fulfill this recordkeeping 

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requirement. Although the NPRM did 

not propose an auditing requirement for 

assessing the accuracy of exemption 

determinations, it sought public 

comment about the need for one. 

3. Public Comments 

This was one of the more commentedon provisions of the NPRM, receiving 

approximately 280 comments. Public 

comment was generally mixed, with 

approximately half supporting and half 

opposing this proposal. A large majority 

noted that they felt unable to adequately 

respond to this proposal without seeing 

the decision tool first. Many of those 

who indicated general support for this 

proposal noted substantial 

qualifications to their support, such as 

the need to see the tool before deciding. 

Some requested that this proposal not 

be included in a final rule, and that a 

separate NPRM be issued specific to this 

proposal. Many commenters said that 

for simplicity and consistency, one tool 

should be agreed on by all of the 

sponsoring departments and agencies 

and that the departments and agencies 

should involve research administration 

professionals in developing such a tool 

so that it would have field-friendly 

workability and produces trustworthy 

results. Further, they thought that the 

tool should be pilot tested and validated 

by institutions and investigators before 

being deployed. For those who 

supported the concept of a decision 

tool, they felt that its use would speed 

the review process for exempt research. 

Some cited long wait times to receive an 

exemption determination from their 

institution’s IRB. 

Some commenters stated that the tool 

should clearly indicate that although it 

determines exemption from federal 

regulations, state restrictions still apply. 

A large academic center argued that 

though the tool could be useful, for 

institutions that provide services, 

treatment, and care for vulnerable 

populations it might be prudent to have 

someone with expertise in human 

research protections independently 

review research proposals to determine 

whether they are exempt or excluded 

from IRB review, rather than rely on the 

tool. 

One large research university 

questioned the need for such a tool, 

asserting that properly designed 

oversight and review of exempt research 

should take minimal time and ensure 

that only exempt research is conducted 

without IRB approval. This commenter 

preferred comprehensive guidance on 

exempt research to support IRBs in 

making efficient and expeditious 

exemption determinations. A large 

academic/research organization 

concurred, pointing out confusion 

among investigators about exempt 

categories, which requires careful 

conversation with IRB officers to 

understand how their project fits into 

the human protection framework. This 

organization believed that these 

conversations promote safe and effective 

research decision making and argued 

that use of the tool could fail to properly 

educate investigators about the 

complexities of exempt research 

determinations. 

Some commenters noted that the 

decisions produced by the tool would 

be only as good as the tool and the 

materials and guidance that accompany 

it. Some commenters added that it is 

unlikely, however, that the use of a 

federal decision tool would shield the 

institution or investigator from liability 

in third-party actions. Still others went 

so far as to say that they doubted their 

institution would allow its use, at least 

for some time after which it was proven. 

To the extent institutions are not 

engaged in the exemption determination 

process through the tool, some argued 

that institutions should not be held 

accountable for any unintended 

outcomes. 

Of those who commented on whether 

investigators should be allowed and 

trusted to use the exemption 

determination tool, some noted that it 

seemed inappropriate and a conflict of 

interest for investigators to be allowed 

to use the tool to generate exemption 

determinations for their own research 

activities. Others noted that an 

investigator might be able to use the 

tool, but that the proposed exemptions 

categories were so nuanced that 

experienced IRB staff might have 

difficulty determining what qualifies for 

an exemption. To that end, these 

comments noted that the tool would 

need to be accompanied with 

substantial guidance for an investigator 

to be able to accurately input 

information into it. Finally, some 

commenters expressed concern about 

the possibility that investigators might 

enter inaccurate or misleading 

information into the tool to ‘‘game the 

system,’’ while others noted that that 

possibility, although remote, exists in 

the current protocol submission process 

and that a well-developed tool could 

include a means for validating certain 

types of inputs to assess accuracy. 

4. Response to Comments and 

Explanation of the Final Rule: 

Exemption Determination 

The final rule does not adopt the 

NPRM proposal at this time. Therefore, 

the final rule does not require that 

exemption determinations be 

documented, as had been proposed in 

the NPRM, and continues to permit 

flexibility in how exemption 

determinations are made. We recognize 

it was difficult to provide detailed 

feedback in the absence of an exemption 

decision tool to evaluate. However, we 

continue to believe that a well-designed, 

tested, and validated exemption 

decision tool could offer an expedient 

mechanism for determining whether 

research studies are exempt. Thus, we 

will continue to explore development of 

an exemption decision tool. If and when 

an exemption decision tool is 

developed, we would issue a 

subsequent (separate) Federal Register 

notice for public comment. The notice 

would also give the public the 

opportunity to comment on whether the 

use of the tool would be appropriate in 

making exemption determinations 

under this final rule. Thus, members of 

the public would be afforded a 

sufficient opportunity to provide 

meaningful comments on such a 

proposed decision tool. 

C. Categories of Exempt Research 

The following sections describe the 

categories of exempt research found in 

the final rule. Note that several 

categories of activities proposed in the 

NPRM as exclusions appear in the final 

rule as exemptions. 

1. Background and Pre-2018 Rule 

Under the pre-2018 rule, a research 

activity qualified for exemption from 

the Common Rule if it fell into one or 

more of six categories at 

§ ll.101(b)(1)–(6). Such studies were 

fully exempt from the regulations. That 

is, so long as a study did indeed fall 

within a category, it did not need to 

satisfy any other regulatory 

requirements that it needed to satisfy 

under the pre-2018 rule. 

2. NPRM Proposals 

The NPRM proposed that all 

exemption language would be found at 

§ ll.104. The NPRM proposed 

retaining all of the exemption categories 

in the pre-2018 rule in one form or 

another except for the exemption 

pertaining to research involving the use 

of educational tests, survey or interview 

procedures or observation of public 

behavior if the subjects are elected or 

appointed officials, or if the 

confidentiality of the information were 

protected by statute. However, the 

NPRM proposed re-classifying some of 

the pre-2018 rule’s exemptions as 

exclusions under the NPRM (and thus 

they would not have been subject to 

administrative or IRB review), while 

retaining some of the pre-2018 rule’s 

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33The legislative language can be found at 

https://www.healthit.gov/sites/default/files/hitech_

act_excerpt_from_arra_with_index.pdf. 

exemptions as exemptions (versus 

exclusions). 

The NPRM proposed eight 

exemptions divided into three 

categories: (1) Low-risk interventions for 

which there would have been no other 

requirement (e.g., informed consent and 

privacy safeguards) other than the 

determination and recording 

requirements; (2) research activities that 

would have required application of 

privacy safeguards; and (3) secondary 

research involving biospecimens and 

identifiable private information that 

would have required application of 

privacy safeguards, broad consent, and 

limited IRB review. The NPRM 

proposed to have some exempt studies 

meet certain other regulatory 

requirements while not having to meet 

other requirements, making them not 

‘‘fully exempt’’ in the sense of the pre2018 rule. 

The NPRM proposed retaining 

exemption categories § ll.101(b)(1), 

(5), and (6) from the pre-2018 rule. The 

NPRM proposed clarifying the 

exemption for research on public benefit 

programs or demonstration projects in 

the pre-2018 rule and explained that 

OHRP’s guidance would be changed to 

include the applicability of the 

exemption to cover research on public 

benefit and service programs that an 

agency does not itself administer 

through its own employees or agents. 

The NPRM proposed requiring federal 

departments or agencies conducting 

such studies to publish a list of studies 

under this exemption. 

The NPRM proposed that new 

exemptions would be created for: 

• Certain research involving benign 

interventions; 

• Certain research involving 

educational tests, survey or interview 

procedures, or observation of public 

behavior where identifiable private 

information was recorded, so long as 

data protection standards are met; 

• Secondary research use of 

identifiable private information 

originally collected for nonresearch 

purposes; 

• Activities relating to storing and 

maintaining biospecimens and 

identifiable private information for 

secondary research use, if subjects 

provided broad consent; 

• Secondary research studies that 

would use the biospecimens and 

identifiable private information stored 

or maintained under the above 

exemption. 

The NPRM asked for public comment 

on several aspects of these proposals, as 

they appeared as either exemptions or 

exclusions and whether their placement 

in the NPRM was appropriate with 

regard to protecting human subjects in 

research. Comment was requested on 

whether guidance would be needed to 

help make exemption determinations 

and whether the scopes of the proposed 

exemptions or proposed exclusions 

were appropriate. That is, whether 

particular exclusions or exemptions 

were either too narrow or too broad. For 

example, several questions were posed 

about whether research should be 

exempt if it involved psychological 

risks. The NPRM asked about whether 

notice should be given to subjects for 

any of the activities. The public was 

asked to comment on whether and how 

exempt activities could comply with the 

NPRM’s proposed privacy safeguards. 

The NPRM also inquired whether the 

exemption category related to research 

conducted in established or commonly 

accepted educational settings should 

apply only to research activities in 

which notice is given to prospective 

subjects or their legally authorized 

representatives as a regulatory 

requirement, when not already required 

under the Privacy Act of 1974. If so, 

comment was sought on the type of 

information to include in the notice and 

on how such notice should be delivered. 

The NPRM asked for feedback on 

whether the proposed privacy 

safeguards should apply to research 

included in the proposed exempt 

category related to research conducted 

in established or commonly accepted 

educational setting, given that such 

research may involve risk of disclosing 

identifiable private information. The 

public was also asked to comment on 

whether the protections provided by the 

HIPAA Rules for identifiable health 

information used for health care 

operations, public health activities, and 

research activities are sufficient to 

protect human subjects involved in such 

activities, and whether the current 

process of seeking IRB approval 

meaningfully adds to the protection of 

subjects involved in such research 

studies. 

The NPRM asked about the extent to 

which the HIPAA Rules and the Health 

Information Technology for Economic 

and Clinical Health (HITECH) Act 33

adequately address the beneficence, 

autonomy, and justice considerations 

related to collecting new information 

and whether any exemption for such 

collection should be limited to data 

collected or generated in the course of 

clinical practice. 

With regard to the proposed 

exemption related to research and 

demonstration projects conducted or 

supported by a federal department or 

agency, the public was asked to 

comment on: (1) Whether notice should 

be given to prospective subjects and the 

nature of such notice; (2) whether such 

activities can involve greater than 

minimal risk and whether they are 

appropriate as exemptions; and (3) 

whether existing privacy safeguards for 

such activities were sufficient. 

A proposed new exemption category 

was intended to facilitate secondary 

research using identifiable private 

information that would have been or 

would be collected or generated for 

nonresearch purposes, when prior 

notice had been given and privacy 

safeguards and prohibitions on re-use of 

the information were in place. The 

public was asked to comment on what 

types of research should fall under this 

proposed exemption, whether it should 

be limited to research in which 

individuals have been informed of the 

potential for future research use of their 

information and given the opportunity 

to opt out, and whether the exemption 

would be appropriate for clinical data 

registries. 

Finally, public comment was sought 

on two related proposed exemptions for 

research involving the use of 

biospecimens or identifiable private 

information that would have been 

stored or maintained for secondary 

research use, if consent for the storage 

and maintenance of the information and 

biospecimens had been obtained using a 

broad consent template that the NPRM 

proposed would be developed by the 

Secretary of HHS. 

3. Public Comments, Response to 

Comments, and Explanation of the Final 

Rule: Exemption Categories 

All exemption categories, of which 

there are eight, appear at § ll.104 in 

the final rule. Four of the exemption 

categories were proposed as exclusions 

under the NPRM. In addition, the 

proposed exclusion concerning certain 

research involving educational tests, 

survey or interview procedures, or 

observation of public behavior has been 

combined with the exemption regarding 

additional research activities using the 

same research methods. The rule 

includes four exemptions for research 

involving normal educational practices, 

research involving benign behavioral 

interventions, research involving public 

benefit or service programs, and 

research involving taste and food 

quality, all of which were also proposed 

in the NPRM. 

Three exemptions pertain to 

secondary research uses of identifiable 

private information or identifiable 

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biospecimens. One exemption, at 

§ ll.104(d)(4), which concerns 

secondary research for which consent is 

not required, which consists of three of 

the proposals for exclusions in the 

NPRM. A second exemption, at 

§ ll.104(d)(7), pertains to storage or 

maintenance of identifiable private 

information or identifiable 

biospecimens for which broad consent 

is required, and a third exemption, at 

§ ll.104(d)(8), concerns secondary use 

of identifiable private information or 

identifiable biospecimens for which 

broad consent is required. As will be 

discussed in more detail below, some of 

the conditions associated with the 

finalized exemptions differ from what 

was proposed in the NPRM. 

In the final rule, similar to what was 

proposed in the NPRM, ‘‘exempt’’ does 

not always mean exempt from all of the 

requirements of the Common Rule; the 

activity must fit the description of the 

exempt category and not include 

nonexempt research activities. For 

example, the exemption categories in 

the final rule at §ll.104(d)(7) and (8) 

identify specific regulatory 

requirements that must be met (e.g., 

limited IRB review, the use of broad 

consent) as a condition of being exempt 

from other regulatory requirements. 

Public comments, responses to 

comments, and explanations of the final 

rule for each exemption category follow. 

a. Research Conducted in Established or 

Commonly Accepted Educational 

Settings When It Specifically Involves 

Normal Educational Practices 

(§ ll.104(d)(1)) 

i. Public Comments 

Approximately 50 comments 

discussed this exemption, which was a 

slight modification of an exemption that 

existed in the pre-2018 rule. The NPRM 

asked two questions about this 

exemption: (1) whether it should require 

some type of notice and if so, how 

notice should be delivered; and (2) 

whether the proposed privacy 

safeguards should apply to this 

exemption. 

One commenter (a research dean from 

a university) suggested that the wording 

of the exemption be modified from 

‘‘research conducted in established or 

commonly accepted educational 

settings’’ to ‘‘research conducted in 

established or commonly accepted 

educational or other settings’’ in order 

to allow more flexibility in how this 

exemption could be applied. 

Other commenters noted a need for 

guidance on how this exemption should 

be interpreted. For example, one 

comment suggested that a wide array of 

‘‘normal’’ educational practices exists, 

and the intention of this language was 

difficult to discern. Another comment 

noted that clarification was needed 

about permissible data collection 

methods under this exemption. 

One commenter discussing the 

addition of the limitation that the study 

should not be likely to adversely affect 

students’ opportunity to learn noted that 

it might be difficult to predict ahead of 

time if the research contemplated under 

this exemption might have this adverse 

impact. 

Several commenters discussed 

whether notice should be required. The 

majority of these comments indicated 

that some type of notice should be 

required. A few specifically discussed 

the importance of notifying subjects of 

these activities (with one commenter 

stating that parental consent should be 

required), stating that lack of notice 

could erode public trust in research. 

Groups representing AI/AN tribal 

interests argued that notice for this type 

of research should be required. 

Specifically, they asserted that 

transparency around research-related 

activities and policies, especially in 

school settings, can build trust among 

AI/AN populations and ensure that 

individual and community benefits of 

participation in research are achieved. 

They also noted that tribal consultation 

facilitates decisions about appropriate 

ways to implement such notices, and 

observed that the rural nature of many 

AI/AN communities requires the use of 

multiple modes of communication and 

more time spent reaching the intended 

audience. The commenter also noted 

that potential subjects should be given 

the opportunity to opt out of research 

activities. 

One commenter argued that notice is 

generally an insufficient standard for 

this type of research and is not a 

suitable substitute for informed consent. 

Approximately 20 comments 

discussed whether the proposed privacy 

safeguards that appeared at §ll.105 in 

the NPRM should apply to this 

exclusion. Comments were generally 

mixed about whether this would be 

appropriate, with a small majority 

indicating that the privacy safeguards 

should not apply. These comments 

generally argued that if an activity is 

exempt, no additional requirements 

should be placed on that research 

activity. 

A privacy advocacy organization that 

supported both notice and attaching the 

proposed privacy safeguards to this 

provision, stated that notice in this 

context is also important because other 

federal standards (e.g., Family 

Educational Rights and Privacy Act 

[FERPA; 20 U.S.C. 1232g; 34 CFR part 

99], Protection of Pupil Rights 

Amendment [PPRA; 20 U.S.C. 1232h; 34 

CFR part 98]) are not acceptable proxies 

for privacy protection. This commenter 

indicated that the notice should be 

robust with detailed information 

presented to parents directly. As 

justification for providing additional 

protections in this context, this group 

noted that the consequences for misuse 

of data are greater for children; that is, 

lost, misused, or leaked information 

about children could have lifelong 

consequences. The commenter argued 

that if an exemption is proposed for this 

class of research, then the lack of IRB 

oversight should require that 

researchers must comply with 

appropriate privacy safeguards. 

ii. Response to Comments and 

Explanation of the Final Rule: 

Exemption for Certain Research 

Conducted in Certain Educational 

Settings 

The final rule includes an exemption 

at §ll.104(d)(1) for research 

conducted in established or commonly 

accepted educational settings that 

specifically involves normal educational 

practices, so long as the research is not 

likely to adversely affect students’ 

opportunity to learn required 

educational content or the assessment of 

educators who provide instruction. This 

includes most research on regular and 

special education instructional 

strategies, and research on the 

effectiveness of, or the comparison 

among, instructional techniques, 

curricula, or classroom management 

methods. 

This exemption is a revised version of 

the first exemption in the pre-2018 rule 

and a modified version of the exemption 

as proposed in the NPRM. This change 

is based on concerns about whether the 

conduct of some research projects of 

this type might draw enough time and 

attention away from the delivery of the 

regular educational curriculum that they 

could have a detrimental effect on 

student achievement. The wording of 

the exemption has been modified to 

include a condition that the research is 

not likely to have these adverse impacts. 

This was the original intent of the 

NPRM proposal, and it is an important 

qualification that should apply to any 

research activity that is exempt under 

this provision. It also drops the phrase 

‘‘in that educational setting,’’ because 

that phrase is redundant. 

The exemption is retained to allow for 

the conduct of education research that 

may contribute to the important public 

good of improving education, consistent 

with the principle of beneficence. The 

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exemption retains the condition that the 

research activity takes place in 

established or commonly accepted 

educational settings, because otherwise 

IRB review would be warranted for such 

research activities being conducted in 

unconventional settings. 

We recognize that providing notice for 

this type of research could involve a 

significant administrative burden and 

that it is not always appropriate, and 

therefore have decided not to include it 

as a regulatory requirement at this time. 

We note that making these activities 

exempt does not mean that there ought 

not to be tribal consultation about the 

research activities, and that such 

consultation may lead to a notice 

requirement. Where appropriate or 

mandated by tribal law, tribal 

consultation should take place 

irrespective of whether the activity has 

to meet the requirements of this final 

rule. Such consultation would represent 

a free-standing legal obligation, as is 

referred to in §ll.101(f).When 

appropriate, investigators may provide 

notice in a manner that is appropriate to 

the research activity and the cultural 

context in which it occurs. 

This exemption is largely unchanged 

from the pre-2018 rule, and does not 

add requirements for safeguarding 

privacy at this time. 

b. Research That Includes Only 

Interactions Involving Educational Tests 

(Cognitive, Diagnostic, Aptitude, 

Achievement), Survey Procedures, 

Interview Procedures, or Observation of 

Public Behavior (Including Visual or 

Auditory Recording), If at Least One of 

Three Criteria Is Met (§ll.104(d)(2)) 

This exemption in the final rule is a 

revised version of an exemption in the 

pre-2018 rule, and is a combination of 

a provision proposed as an exclusion in 

the NPRM, and a provision proposed as 

an exemption in the NPRM. Thus, 

public comments on both of these 

proposals follow here. 

i. Public Comments 

Approximately 80 comments 

discussed this proposed exclusion, 

which was an exemption in the pre2018 rule. Public comments were 

mixed. Some felt that moving these 

activities from the exemption to 

exclusion category would streamline 

this type of low-risk, common research 

activity and allow IRBs to focus time 

and attention on more complicated and 

higher risk activities. Others, including 

SACHRP and many research 

universities, argued that based on their 

experience, investigators have difficulty 

making the assessments required to 

determine whether an activity falls 

under this exemption. For example, 

investigators have a difficult time 

determining whether disclosure outside 

of the research context might put 

someone at risk of criminal or civil 

liability. 

Commenters also expressed concern 

about whether the three statutes cited in 

the third prong of the proposed 

exclusion would provide a comparable 

level of protections to human subjects as 

does the Common Rule. Many of these 

commenters noted that they simply 

were not sure what types of protections 

would be afforded to subjects under the 

Privacy Act, the Paperwork Reduction 

Act, and the E-Government Act of 2002. 

Others noted that the main protections 

provided by these statutes involved 

notice and not ethics review. 

The NPRM requested comment on the 

extent to which covering educational 

tests, survey procedures, interview 

procedures, or observation of public 

behavior under the Common Rule 

would substantially add to the 

protections provided to human subjects. 

Public comment was mixed, but the 

majority of commenters felt that these 

activities should be exempt rather than 

excluded. One commenter indicated 

that contrary to the primary justification 

for excluding these categories of 

research, these activities cannot always 

be considered to be low risk and could 

pose significant risks depending on the 

nature of the research and sensitivity of 

the data collected. 

One commenter expressed strong 

opposition to excluding these activities 

from Common Rule protections, 

indicating that excluding them would 

compromise the rights and welfare of 

research subjects. The commenter 

emphasized that consent cannot be 

inherent to participation in the activity 

because researchers cannot know with 

certainty that participants are familiar 

with common forms of educational 

tests, surveys, and interview procedures 

and the potential risks inherent to 

information disclosure. In addition, the 

commenter pointed out, assuming that 

even vulnerable subjects know the risks 

associated with participation in surveys 

and interviews is contrary to the 

Belmont Report’s assertion that 

vulnerable subjects need additional 

protection. 

Some comments were mixed, for 

example, suggesting that observation of 

public behavior might be an acceptable 

exclusion, whereas surveys and 

interviews ought to remain exempt. One 

commenter indicated that it might be 

reasonable for these activities to be 

excluded if an exclusion determination 

tool was available to help investigators 

make the decision. Another commenter 

suggested that whether the activities are 

exempt or excluded, notice should be 

required, to indicate the purpose of the 

activity, describe privacy safeguards, 

state that participation is voluntary, and 

provide information on opting out. 

Other commenters expressed concern 

that investigators might not be able to 

effectively make these determinations, 

and pointed out that IRBs, with a broad 

range of experience and expertise in 

data identifiability, provide a check for 

researchers’ judgment and are better 

placed to make consistent and informed 

decisions about exemptions. 

Even so, some other commenters felt 

that Common Rule protections do not 

substantially add to the protection of 

human subjects in these categories of 

activities. Thus, categorizing them as an 

exemption just adds administrative 

burden. 

The NPRM asked whether this 

exclusion should apply only to research 

activities in which notice is given to 

prospective subjects or their legally 

authorized representatives as a 

regulatory requirement, and if so, what 

information should be included in the 

notice. Some commenters supported a 

requirement for notice or at a minimum, 

some sort of tracking system for these 

activities. One emphasized that the 

ethical principle of respect for persons 

demands some sort of notice. Some 

indicated that requiring notice prevents 

these activities from being excluded and 

might necessitate including them on the 

list of activities for expedited review 

rather than deeming them exempt 

activities. 

Other commenters expressed concern 

about the proposed exclusion. For 

example, one indicated that it might not 

be correct to assume that people agree 

to participate, and understand that they 

can opt out, by virtue of their 

participation, and another reiterated 

concern about assuming that these 

activities are inherently low risk and 

expressed a desire to keep these 

activities in the exempt category to 

maintain a level of IRB oversight. 

The NPRM asked whether it is 

reasonable to rely on investigators to 

make self-determinations for the types 

of research activities covered in this 

particular exclusion category, and if so, 

whether documentation of any kind 

should be generated and retained. One 

commenter expressed a strong opinion 

that investigators should be allowed 

make these self-determinations. 

However, the majority of comments 

responding to this question felt that 

investigators should not be solely 

responsible for making these 

determinations. 

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Some commenters felt that selfdetermination might work in certain 

cases or with certain groups but that 

there would be too much variability to 

allow it generally. One suggested a 

screening system that might check 

whether determinations were being 

made correctly. 

Many commenters pointed out that it 

is unreasonable to expect investigators 

to be able to reliably discern levels of 

risk inherent to disclosure of 

information, and that what might seem 

innocuous to researchers could cause 

real harm to others. Other commenters 

expressed concern about conflicts of 

interest, and that investigators might be 

more likely to make a determination to 

not delay their research. Another 

commenter emphasized that oversight is 

necessary to avoid situations in which 

investigators inaccurately assume that 

subjects understand that they are 

participating in research, or that they 

are being recorded, for example. 

The NPRM requested comment on 

whether some or all of these activities 

should be exemptions rather than 

exclusions. Response to this question 

was mixed. Some commenters felt that 

these activities should be excluded. 

Others felt that surveys and interview 

should be considered exempt while 

educational tests and observation of 

public behavior should be excluded. 

Still others felt that all should be 

exemptions except for observations of 

public behavior, which could be 

excluded. 

The NPRM asked whether these 

exclusions should be narrowed such 

that studies with the potential for 

psychological risk are not included and 

whether certain topics that involve 

sensitive information should not be 

covered by this exclusion. There was 

general agreement among responses to 

this question that the exclusions should 

be narrowed so that studies with the 

potential for psychological risk were not 

included in the exclusion. Some 

commenters, however, indicated that it 

would be unrealistic to expect 

investigators to make this determination 

reliably, that it might be challenging to 

implement such a policy, and that 

guidance would be required from 

regulatory bodies. 

Commenters felt that these activities 

should be exemptions rather than 

exclusions, to preserve a level of IRB 

oversight. One commenter pointed out 

that circumstances that occur in 

research for which psychological risks 

are possible are fairly common in this 

category of activities and that excluding 

them would leave the risk unaddressed. 

One professional organization 

emphasized that the ‘‘potential for 

serious psychological harms that may be 

associated with participation in 

nonbiological research . . . [is] not 

merely the result of inappropriate 

disclosure of information.’’ It also 

indicated that ‘‘the probability and 

magnitude of this risk may vary by 

characteristics of individual 

participants, clinical expertise of the 

interviewer(s), as well as the riskminimizing protections that are in 

place.’’ 

The NPRM requested comment on 

whether for activities captured under 

the third element of this exclusion, the 

statutory, regulatory, and other policy 

requirements cited provide enough 

oversight and protection that being 

subject to expedited review under the 

Common Rule would produce minimal 

additional subject protections. If so, the 

NPRM asked whether the exclusion 

should be broadened to also cover 

secondary analysis of information 

collected pursuant to such activities. Of 

the few responses to this question, one 

commenter felt that existing protections 

are sufficient if information is stored in 

a secure information technology (IT) 

infrastructure. 

Other organizations expressed strong 

sentiments that neither the Paperwork 

Reduction Act nor the Privacy Act were 

protective in the research context and 

that current privacy protections are 

inadequate. They stressed the 

importance of safeguarding IT and cyber 

infrastructure and provided examples of 

large data breaches. 

The NPRM asked about the extent to 

which excluding any of these research 

activities from the Common Rule could 

result in an actual or perceived 

reduction or alteration of existing rights 

or protections provided to human 

subjects. That is, does excluding these 

research activities from the Common 

Rule pose any risks to scientific 

integrity or public trust? Commenters 

who responded to this question 

generally felt that excluding any of these 

research activities could result in an 

actual or perceived reduction or 

alteration of existing rights or 

protections provided to human subjects. 

One indicated that reduction in 

oversight would lead to subjects being 

exposed to unintended risks that 

otherwise would be preventable. Other 

commenters felt that improper 

assumptions about low levels of risk in 

these activities and allowing for selfdetermination could lead to a reduction 

in protections for human subjects. 

ii. Public Comments on the Proposed 

Exemption for Research Involving 

Educational Tests, Surveys, Interviews, 

or Observation of Public Behavior If the 

Information Is Recorded With 

Identifiers, and Even If the Information 

Is Sensitive 

Approximately 50 comments 

discussed the proposal to exempt 

educational tests, surveys, interviews, or 

observation of public behavior if the 

information is recorded with identifiers 

and even if the information is sensitive. 

Public comment here was mixed, with 

some agreeing that by mandating 

privacy safeguards, the proposal 

effectively addresses the primary risk 

that occurs in this type of research. 

Others argued that this type of research 

still benefits from some type of IRB 

review and thus should be considered 

covered rather than exempted research. 

Yet other comments noted that it was 

impossible to make a determination 

about this proposed exemption without 

seeing the proposed privacy safeguards 

that were proposed in the NPRM. 

Several commenters noted that the 

parameters of this exclusion might be 

acceptable if it excluded sensitive topics 

or if it excluded research studies that 

posed psychological harm to potential 

subjects. One comment by a 

professional organization of psychology 

professionals noted that IRBs often 

misunderstand and overstate 

psychological risks in research. Because 

of this, this group argued that the rule 

should not include a limitation based on 

psychological risks because IRBs are not 

able to effectively assess psychological 

risks. 

The NPRM also asked whether this 

exemption should be extended to 

research involving children. The 

majority of those who responded to this 

question were opposed to such an 

extension. 

iii. Response to Comments and 

Explanation of the Final Rule: 

Exemption for Certain Research 

Involving Educational Tests, Surveys, 

Interviews, or Observation of Public 

Behavior Under Specific Conditions 

The final rule includes an exemption 

at §ll.104(d)(2) that is a revised 

version of an exemption in the pre-2018 

rule. The exemption applies to research 

that only includes interactions 

involving educational tests (cognitive, 

diagnostic, aptitude, achievement), 

survey procedures, interview 

procedures, or observation of public 

behavior (including visual or auditory 

recording) uninfluenced by the 

investigator if at least one of three 

criteria is met: 

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Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 7189 

• The information obtained is 

recorded by the investigator in such a 

manner that the identity of the human 

subject cannot readily be ascertained, 

directly or through identifiers linked to 

the subjects; 

• Any disclosure of the human 

subjects’ responses outside the research 

would not reasonably place the subjects 

at risk of criminal or civil liability or be 

damaging to the subjects’ financial 

standing, employability, educational 

advancement, or reputation; or 

• The information obtained is 

recorded by the investigator in such a 

manner that the identity of human 

subjects can readily be ascertained, 

directly or through identifiers linked to 

the subjects, and an IRB conducts a 

limited IRB review to make the 

determination required by 

§ ll.111(a)(7) (which relate to there 

being adequate provisions for protecting 

privacy and maintaining 

confidentiality). 

The final rule does not include the 

language proposed in the NPRM that 

offered as one prong of the exemption 

(proposed as an exclusion) that the 

research be subject to the Privacy Act, 

the Paperwork Reduction Act, or the EGovernment Act of 2002. The final rule 

simply includes § ll.104(d)(2)(iii), 

which requires limited IRB review as 

described at § ll.111(a)(7) if 

identifiable private information will be 

obtained and recorded in such a way 

that the identity of human subjects can 

readily be ascertained, either directly or 

through identifiers linked to the subject. 

This exemption is based on the 

assumption that the potential risks 

raised by this category are largely 

informational and that subjects are 

aware of them, and thus the most 

important role that an IRB might play 

with respect to reducing potential harms 

is to ensure the application of privacy 

safeguards. Under this assumption, the 

exemption is consistent with the 

principle of respect for persons and the 

preservation of autonomy. In the case of 

observation of public behavior, even if 

the subject does not know that an 

investigator is watching his or her 

actions, the subject’s behavior is public 

and could be observed by others, and 

thus the research observation is not 

inappropriately intrusive. 

The term ‘‘survey’’ as used here refers 

to information collected about 

individuals through questionnaires or 

similar procedures (e.g., the Current 

Population Survey conducted by the 

U.S. Census). ‘‘Human subjects’’ do not 

include organizations or businesses. 

‘‘Survey,’’ as used here, does not 

include the collection of biospecimens. 

Thus, an activity that included the 

collection of a biospecimen (e.g., a 

cheek swab), in addition to collecting 

verbal or written responses to questions, 

could not qualify for this exemption. 

This exemption includes the research 

activities that appeared at 

§ ll.101(b)(2) in the pre-2018 rule, as 

well as some additional information 

collection research activities using the 

same methods. As in the pre-2018 rule, 

this exemption includes research 

studies whose methods consist of the 

use of educational tests, survey or 

interview procedures, or observation of 

public behavior that does not involve an 

intervention, if the data are recorded 

anonymously, or the information is 

recorded with identifiers, but is not 

sensitive such that its disclosure could 

result in harm to the subjects. The 

exemption provides a list of the specific 

harms that must be considered, as did 

the pre-2018 rule, with the addition of 

the specific harm of potential damage to 

the subjects’ educational advancement. 

This potential harm has been added 

because of the obvious relevance to the 

effects of the disclosure of responses in 

research involving educational tests. 

This exemption has been expanded to 

include research using the same 

methods involving identifiable private 

information that might be sensitive or 

potentially harmful if disclosed, so long 

as the investigators adhere to the limited 

IRB requirements outlined in 

§ ll.111(a)(7), and the research is not 

subject to Subpart D. The limited IRB 

review requirements are designed to 

provide privacy safeguards to reduce the 

chances that the disclosure of 

identifiable private information will 

occur and lead to harm. 

The wording of the exemption is 

clarified to indicate (consistent with the 

interpretation of § ll.101(b)(2) in the 

pre-2018 rule) that the research cannot 

include interventions in addition to the 

educational tests, survey or interview 

procedures, or observation of public 

behavior. Research involving 

interventions that are distinct from 

those information collection methods 

allowable under this exemption do not 

satisfy the conditions of this exemption. 

For example, if a research study were to 

randomly assign students to take an 

educational test in a quiet room or in a 

room with a moderate level of noise, or 

to consume a snack (or not) before 

taking the test, this research would not 

be exempt under this exemption. It 

should be noted, however, that 

educational tests may include exposing 

test takers to certain materials as part of 

the test, and that such materials do not 

constitute interventions distinct from 

the test. For example, reading 

comprehension tests may direct test 

takers to read a passage, and a 

geography test may present test takers 

with a map, and ask them to draw 

information from that map. Likewise, 

survey procedures may contain some 

information that the respondents are 

asked questions about, which would not 

be considered distinct interventions. 

However, research in which the purpose 

of the research is to see whether 

respondents answer survey questions 

differently depending on the gender of 

the interviewer would not satisfy the 

conditions of the exemption, because 

the manipulation of the interviewer 

would be a distinct intervention. 

Research involving observation of 

public behavior does not qualify for this 

exemption if the investigator intervenes 

with subjects, for example, by offering 

them an ostensibly lost wallet to see if 

they will accept it. 

Part of the rationale for exempting the 

research activities at §ll.104(d)(2) 

from the Common Rule, even when the 

research is not otherwise subject to 

additional federal controls, is that for 

education tests, survey or interview 

procedures, agreement to participate is 

inherent in participation and that for 

much of this research the risks most 

likely to be experienced by subjects are 

related to disclosure of anonymous, 

nonsensitive information and are thus 

categorized as ‘‘low.’’ In general, it is 

reasonable to expect that individuals, 

including vulnerable populations (other 

than children), would understand that 

actively providing responses to 

educational tests, surveys, or interview 

procedures constitutes agreement to 

participate and that the risks associated 

with such participation would be 

related to disclosure of the information 

they provided. The exemption of this 

type of activity rests in large part on the 

idea that all individuals, regardless of 

the setting or context in which the 

activity will take place, are generally 

familiar with common forms of 

educational tests and survey and 

interview procedures that they 

experience in their daily lives, and do 

not need additional measures to protect 

themselves and their privacy from 

investigators who seek their 

involvement in research activities 

involving these procedures. They can 

decline to participate, or to answer some 

questions. In addition, if the 

information collected is both 

identifiable and sensitive or potentially 

harmful, the safeguards offered by the 

limited IRB review requirements at 

§ ll.111(a)(7) apply. This is 

accomplished through the added 

provision at § ll.104(d)(2)(iii). 

Concerns have also been raised about 

psychological risks of participating in 

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7190 Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 

34Milgram S. Behavioral Study of Obedience. The 

Journal of Abnormal and Social Psychology, 1963; 

67(4):371–378. Retrieved from http://

www.columbia.edu/cu/psychology/terrace/w1001/ 

readings/milgram.pdf. 

35Haney C, Banks WC, and Zimbardo PG. A study 

of prisoners and guards in a simulated prison. 

Naval Research Review, 1973, 30:4–17. Retrieved 

from http://www.simplypsychology.org/zimbardopaper.pdf. 

surveys or interviews, and of situational 

risks where the simple awareness that 

someone was surveyed or interviewed 

poses a risk. We recognize that this is 

possible, but believe that this is rare 

enough that it does not warrant adding 

additional conditions to the exemption 

category. 

With respect to applying this 

exemption to research with children, 

two subcategories of this exemption— 

concerning information recorded so that 

subjects cannot be identified 

(§ ll.104(d)(2)(i)), and concerning 

disclosures of the subjects’ responses 

that would not place them at certain 

kinds of risk or create certain kinds of 

damage (§ll.104(d)(2)(ii))—may 

apply to research involving children 

under subpart D if the research involves 

educational tests or observation of 

public behavior and the investigator 

does not participate in the activities 

being observed. The final subcategory of 

this exemption (§ ll.104(d)(2)(iii)), 

which allows for obtaining and 

recording identifiable private 

information, may not be applied to 

research involving children under 

subpart D. 

c. Research Involving Benign Behavioral 

Interventions in Conjunction With the 

Collection of Information From an Adult 

Subject (§ll.104(d)(3)) 

i. Public Comments 

Approximately 50 comments 

discussed the NPRM proposed 

exemption involving benign 

interventions in conjunction with 

collecting information from an adult 

subject. Public comments here were 

mixed, with a majority favoring this 

exemption, and with the majority of 

commenters indicating that guidance 

will be needed for this exemption to be 

implemented properly. For example, 

one large research university stated, 

‘‘The proposed category involving 

benign interventions needs further 

revision. While we are supportive of 

this category in general, the words 

‘benign intervention’ without definition 

leaves too much room for different 

interpretations and these terms are not 

easily applicable to social science 

research, a context in which these types 

of activities are likely to occur.’’ Those 

that favored this exemption generally 

agreed with the argument put forth in 

the NPRM that these activities were low 

in risk and IRB review did not provide 

subjects meaningful additional 

protections in this context. 

Several comments requested 

clarification on the extent to which 

medical interventions might be covered 

under this exemption. For example, to 

what extent could proven diagnostic 

methods that introduce energy but are 

not invasive (e.g., magnetic resonance 

imaging, ultrasound, computerized 

tomography scan) be considered a 

‘‘benign intervention’’ for the purpose of 

this exemption? Another comment 

asked whether the provision included 

the use of medical devices, such as 

blood pressure monitors or 

thermometers. 

Those who did not support this 

exemption offered a variety of reasons. 

One comment from a research 

university indicated that it did not 

support this exemption because it could 

cause studies like the ‘‘Milgram 

Obedience Experiment’’ 34 and the 

‘‘Stanford Prison Study’’ 35 to occur 

without IRB review. Another comment 

reiterated the general stance that all 

research activities should require IRB 

review and informed consent. 

One comment from a research ethics, 

public education, and professional 

organization noted that if the final rule 

includes an expansion of exemption 

categories such as the proposed benign 

intervention exemption in the NPRM, 

then investigator education on human 

subjects protection should be mandated. 

Another comment noted that it should 

be clarified in the regulatory text that 

withholding the investigator’s 

hypothesis from subjects is not 

deception. 

The majority of commenters indicated 

that no additional requirements, be it 

notice or the proposed privacy 

safeguards, should be applied to this 

exemption category. A minority of 

comments indicated that some kind of 

notice should be required with this 

provision, generally asking for that 

notice to include the purpose of the 

study, the privacy and confidentiality 

protections in place, a statement that 

participation is voluntary, information 

on how to opt out of the study, and 

information about who to contact for 

more information. Comments that 

favored notice suggested that the notice 

should be study-specific. 

Although commenters generally felt 

the examples of activities that would 

satisfy this exemption included in the 

regulatory text were sufficient, 

commenters also indicated that many of 

the terms used in this exemption 

needed additional explanation, for 

example, ‘‘brief in duration,’’ 

‘‘painless,’’ and ‘‘physically invasive.’’ 

A large research university noted that 

the proposed language raised questions 

about what sorts of impact are 

significant and how long is ‘‘lasting.’’ 

One large professional organization 

representing research universities and 

organizations noted that the term 

‘‘benign intervention’’ did not seem to 

encapsulate the types of activities that 

the NPRM contemplated. Specifically, 

this organization argued that ‘‘benign 

intervention’’ connotes a medical 

procedure, when the NPRM preamble 

suggested that this exemption 

encompasses nonmedical ‘‘benign 

interventions’’ generally. This 

organization also suggested that the 

activities contemplated by this 

exemption are more like interactions 

than interventions. 

In response to a question about 

whether the decision tool could be 

relied on for making this exemption 

determination, a majority of those who 

responded indicated that it would be 

impossible to answer this question 

without first seeing the decision tool. 

Others indicated that without better 

definition of terms like ‘‘benign 

intervention,’’ ‘‘prospectively agree,’’ 

‘‘long lasting,’’ and ‘‘significant impact,’’ 

it would be impossible for a tool to 

provide accurate determinations for this 

exemption. 

ii. Response to Comments and 

Explanation of the Final Rule: 

Exemption for Certain Research 

Involving Benign Behavioral 

Interventions in Adults 

This exemption at §ll.104(d)(3) 

was not in the pre-2018 rule, but was 

proposed in the NPRM. In response to 

public comments that expressed 

concern over the need to further clarify 

the term ‘‘benign interventions,’’ the 

word ‘‘behavioral’’ has been inserted to 

modify the type of intervention which 

may be included. The intent of this 

change is to exclude the use of medical 

interventions (including medical tests, 

procedures and devices). The exemption 

being finalized is specifically for 

research involving benign ‘‘behavioral’’ 

interventions in conjunction with the 

collection of information from an adult 

subject through verbal or written 

responses (including data entry) or 

audiovisual recording if the subject 

prospectively agrees to the intervention 

and information collection and at least 

one of the following is met: 

• The information obtained is 

recorded by the investigator in such a 

manner that the identity of the human 

subjects cannot readily be ascertained 

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directly or through identifiers linked to 

the subjects; 

• Any disclosure of the human 

subjects’ responses outside the research 

would not reasonably place the subjects 

at risk of criminal or civil liability or be 

damaging to the subjects’ financial 

standing, employability, educational 

advancement, or reputation; or 

• The information obtained is 

recorded by the investigator in such a 

manner that the identity of the human 

subjects can readily be ascertained, 

directly or through identifiers linked to 

the subject, and an IRB conducts a 

limited IRB review to make the 

determination required by 

§ ll.111(a)(7). 

For the purpose of this provision, the 

exemption describes benign behavioral 

interventions as being brief in duration, 

harmless, painless, not physically 

invasive, not likely to have a significant 

adverse lasting impact on the subjects, 

and the investigator has no reason to 

think the subjects will find the 

interventions offensive or embarrassing. 

Provided all such criteria are met, 

examples of such benign behavioral 

interventions include having the 

subjects play an online game, solve 

puzzles under various noise conditions, 

or decide how to allocate a nominal 

amount of received cash between 

themselves and someone else. 

Unlike the exemption at 

§ ll.104(d)(2), this exemption allows 

for the intervention to be distinct from 

the data collection method; for example, 

a research study comparing test 

performance of test takers in quiet or 

noisy surroundings would qualify for 

this exemption. Also subjects could be 

asked to perform cognitive tasks, and 

audiovisual recording could be used to 

collect the data, without any 

educational test, survey or interview 

procedure occurring, and this research 

would qualify for this exemption. 

If the research involves deceiving the 

subjects about the nature or purposes of 

the research, this exemption would not 

be applicable unless the subject 

authorizes the deception. For the 

purpose of this provision, authorized 

deception would be prospective 

agreement by the subject to participate 

in research where the subject is 

informed that he or she will be unaware 

of or misled regarding the nature or 

purposes of the research. The final rule 

allows this type of research to occur 

without the requirements of informed 

consent because the intervention is not 

likely to result in harm or offense to the 

subject, and the subject must 

prospectively agree to the intervention 

and the data collection. 

Subjects must be adults, but the 

provision does not specify that they 

must be competent, and therefore tests 

of competency are not necessary. 

However, the presumption is that, in 

keeping with the principle of respect for 

persons, such subjects will not be 

exploited. 

This new exemption category is 

added because respect for persons is 

accomplished through the prospective 

subject’s forthcoming agreement or 

authorization to participate, the research 

activities pose little risk to subjects, and 

the use of this exemption for many 

social or behavioral studies will enable 

IRBs to devote more time and attention 

to research studies involving greater 

risks or ethical challenges. We note that 

the requirement for the agreement of the 

subject effectively serves as a kind of 

notice, because the subject is asked to 

agree to participate in the research, and 

the request will be tailored to the nature 

of the specific research study. 

The final rule includes another 

condition that was not included in the 

NPRM, which broadens the type of 

research that may meet this exemption. 

The final rule at §ll.104(d)(3)(i)(C) 

permits investigators to obtain and 

record information in such a manner 

that the identity of the human subjects 

can readily be ascertained, directly or 

through identifiers linked to the subject, 

provided the research has undergone 

limited IRB review in accord with 

§ ll.111(a)(7). This alternative 

condition was added to the final rule for 

reasons similar to the exemption at 

§ ll.104(d)(2), as a way of providing 

additional protections when 

investigators obtain and record 

information in such a manner that 

human subjects can be identified 

directly or through identifiers linked to 

the subject. Because the risk associated 

with enabling investigators to obtain 

and record identifiable private 

information can be addressed by 

requiring adherence to the privacy 

safeguards provided through limited 

IRB review, we believe it is appropriate 

to allow such research to be exempt. 

In addition, the final rule permits the 

collection of data through audiovisual 

recording, not just video recording, as 

was proposed in the NPRM. We believe 

that broadening the exemption in this 

way provides more flexibility to the 

permissible data collection methods 

without creating greater risk of harm to 

research subjects. 

We acknowledge that guidance may 

be useful for interpreting some of the 

terms in this exemption, and that some 

cases will be debatable. However, we 

also believe that a substantial number of 

research activities will plainly fit this 

exemption, and should be allowed to 

proceed without IRB review. We agree 

that investigator education is often 

desirable, but that the provisions of the 

exemption are not difficult to 

understand. We believe that Milgram’s 

obedience experiments and the Stanford 

Prison Experiment would obviously not 

qualify for this exemption, because 

investigators had reason to think some 

subjects would find the interventions 

offensive or embarrassing. We 

acknowledge that in this exemption the 

word ‘‘deception’’ is used to include 

withholding the purpose of the research, 

which is consistent with how the term 

is often used in this context. 

d. Secondary Research Use of 

Identifiable Private Information and 

Identifiable Biospecimens for Which 

Consent Is Not Required 

(§ ll.104(d)(4)) 

i. Overview 

The final rule exemption at 

§ ll.104(d)(4) is for secondary 

research use of identifiable private 

information and identifiable 

biospecimens for which consent is not 

required. This particular exemption 

combines several NPRM exclusion 

proposals. It exempts secondary 

research use of identifiable private 

information and identifiable 

biospecimens when: 

• The identifiable private information 

or identifiable biospecimens are 

publicly available; 

• The information is recorded by the 

investigator in such a way that the 

identity of subjects cannot readily be 

ascertained, and the investigator does 

not contact subjects or try to re-identify 

subjects; 

• The secondary research activity is 

regulated under HIPAA; or 

• The secondary research activity is 

conducted by or on behalf of a federal 

entity and involves the use of federally 

generated nonresearch information 

provided that the original collection was 

subject to specific federal privacy 

protections and continues to be 

protected. 

By ‘‘secondary research,’’ this 

exemption is referring to re-using 

identifiable information and identifiable 

biospecimens that are collected for some 

other ‘‘primary’’ or ‘‘initial’’ activity. 

The information or biospecimens that 

are covered by this exemption would 

generally be found by the investigator in 

some type of records (in the case of 

information) or some type of tissue 

repository (such as a hospital’s 

department for storing clinical 

pathology specimens). 

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It is important to recognize that this 

exemption does not cover any primary 

collections of either information or 

biospecimens. For example, if an 

investigator wants to collect information 

directly from research subjects by asking 

them to complete a questionnaire, that 

would not be covered by this 

exemption. If an investigator wants to 

collect biospecimens by having subjects 

swab their cheek, that would similarly 

not be covered by this exemption. On 

the other hand, an investigator who 

wants to use information that is in some 

databank, or use biospecimens that are 

in a pathology laboratory, or use the 

‘‘excess’’ portion of blood that was 

drawn for clinical purposes, could use 

this exemption assuming all of the 

relevant conditions are met. 

Also, note that unlike the pre-2018 

rule’s exemption relating to certain 

secondary uses of information and 

biospecimens, the final rule has no 

requirement that the information and 

biospecimens must be pre-existing at 

the time that the investigator begins a 

particular research study. For example, 

an investigator could start a study that 

involves using biospecimens from 

clinical pathology laboratories, and 

could include specimens that are added 

to the laboratories during the course of 

the study (again assuming that the other 

conditions of the exemption are met). 

Public comments on each of the 

exclusions proposed in the NPRM and 

combined in this exemption follow. 

(1) Public Comments on the Proposed 

Exclusion for Research Involving the 

Collection or Study of Identifiable 

Private Information or Identifiable 

Biospecimens That Are Publicly 

Available or Recorded by the 

Investigator Without Identifiers 

Approximately 50 commenters 

discussed this proposed exclusion about 

identifiable private information or 

identifiable biospecimens that are 

publicly available or recorded by the 

investigator without identifiers. Public 

comments were mixed, with many 

indicating that investigators should not 

themselves be allowed to determine 

whether their research fits under this 

exclusion, and many indicating that this 

should be an exemption rather than an 

exclusion. A majority supported the 

clarifying language that this category of 

activities could include information that 

will be collected. 

One commenter indicated that the 

prohibition on re-identification should 

apply to activities in publicly available 

data sets. This commenter also 

indicated that any research involving reidentification should undergo IRB 

oversight. Another commenter 

suggested that there should also be a 

prohibition in this category against the 

release or publication of information 

that would lead to re-identification. 

One commenter indicated that the 

terminology used in this provision 

needed clarification. Specifically, the 

commenter wondered how one should 

interpret the term ‘‘recorded by the 

investigator’’ with respect to electronic 

data? 

In response to a question posed in the 

NPRM about whether any of the 

exclusion categories should include 

biospecimens, a majority of those who 

responded to the question indicated that 

biospecimens should be included in this 

category. 

The NPRM also asked whether this 

exclusion should apply to activities 

involving prisoners. Of those who 

responded to this question, responses 

were mixed with some indicating that 

this exclusion should apply to research 

with prisoners and others indicating 

that it would be inappropriate for 

research with prisoners to be allowed. 

One commenter indicated that allowing 

prisoners in this type of research would 

be a weakening of protections in 

activities involving vulnerable 

populations. 

(2) Public Comments on the Proposed 

Exclusion for Certain Activities Covered 

by HIPAA 

Approximately 50 comments 

discussed the NPRM proposal to 

exclude certain activities subject to 

HIPAA. Public comments were mixed, 

with many indicating that the 

protections required under HIPAA for 

‘‘health care operations,’’ ‘‘research,’’ 

and ‘‘public health activities,’’ were 

sufficient, and that for the types of 

activities identified by the exclusion, 

review under the Common Rule did not 

provide meaningful protections. In 

contrast, others argued that because the 

scope of a privacy review board is 

narrower than for an IRB, these 

activities should not receive a blanket 

exclusion from the Common Rule. 

Under the HIPAA Privacy Rule, 

health information is de-identified and 

thus exempt from that rule only if it 

neither identifies nor provides a 

reasonable basis to believe that the 

information can be used to identify an 

individual. The HIPAA Privacy Rule 

provides two ways to de-identify 

information: (1) A formal determination 

by a qualified expert that the risk is very 

small that an individual could be 

identified; or (2) the removal of all 18 

specified identifiers of the individual 

and of the individual’s relatives, 

household members, and employers, as 

long as the covered entity has no actual 

knowledge that the remaining 

information could be used to identify 

the individual (45 CFR 164.514(b)). 

Otherwise, the HIPAA Privacy Rule 

addresses some informational risks by 

imposing restrictions on how 

individually identifiable health 

information collected by health plans, 

health care clearinghouses, and most 

health care providers (‘‘covered 

entities’’) may be used and disclosed, 

including for research. In addition, the 

HIPAA Security Rule (45 CFR parts 160 

and subparts A and C of part 164) 

requires that these entities implement 

certain administrative, physical, and 

technical safeguards to protect this 

information, when in electronic form, 

from unauthorized use or disclosure. 

However, the HIPAA Rules apply only 

to covered entities (and in certain 

situations to their business associates). 

Not all investigators are part of a 

covered entity and thus some 

investigators are not required to comply 

with those rules. Moreover, the HIPAA 

Rules do not apply specifically to 

biospecimens in and of themselves. 

One commenter proposed that the 

exclusion be expanded so that 

investigators from noncovered entities 

(as defined in the HIPAA Rules) would 

be eligible for the exclusion as well. 

Another commenter suggested that the 

HIPAA exclusion should be expanded 

to cover business associates and 

researchers that comply with HIPAA. 

The NPRM asked whether the 

protections provided by the HIPAA 

Rules for identifiable health information 

used for health care operations, public 

health activities, and research activities 

are sufficient to protect human subjects 

involved in such activities, and whether 

the current process of seeking IRB 

approval meaningfully adds to the 

protection of human subjects involved 

in such research studies. Approximately 

half of the comments that addressed this 

question suggested that HIPAA 

protections are sufficient and that no 

additional safeguards were needed. 

Others expressed concern, and 

suggested that in some, if not all, of the 

categories in the HIPAA exclusion, 

HIPAA protections would not be 

sufficient. 

One commenter suggested that this 

exclusion might be appropriate for 

health care operations or public health 

activities, but that the HIPAA rules were 

not sufficiently protective for research 

activities. Specifically, one commenter 

expressed concern that excluding from 

the Common Rule the use of PHI for 

research activities in HIPAA-covered 

entities would weaken protections for 

patients, because HIPAA’s privacy 

safeguards were never intended to 

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replace human subject protections and 

associated ethical and scientific review. 

One commenter also noted that other 

HHS preambles to rules have discussed 

the differences between the Common 

Rule and HIPAA, and these preambles 

noted that HIPAA was not intended to 

replace the Common Rule. This 

commenter suggested that given the 

language included in previous HHS 

preambles, additional justification for 

this exclusion would be needed before 

being included in a final rule. 

One commenter felt that the HIPAA 

rules and HITECH adequately address 

the Belmont Report principles with 

respect to these exclusions from the 

Common Rule, but felt the exclusion 

should not be limited to covered 

entities. The commenter suggested that 

the exclusion be extended to 

noncovered entities that receive PHI and 

are required to apply HIPAA safeguards 

in addition to institutions with 

equivalent protections. Others suggested 

that the HIPAA and HITECH standards 

are too protective for much research. 

Other commenters felt that this set of 

exclusions violates the protective 

mandate because HIPAA’s provisions 

are narrow and do not reflect research 

ethics concerns. They noted that 

HITECH addresses technical data 

security for covered PHI for health care 

use but not for research use, especially 

if the data are sent elsewhere. 

Commenters felt that data used for 

research should be subject to HITECH 

data security standards and should not 

be excluded from Common Rule 

coverage. 

Few commented on whether 

additional collections (i.e., collections 

beyond what would ordinarily be 

collected through routine medical care) 

should be covered by this exclusion, 

and those that did suggested that they 

should be subject to the Common Rule 

unless those additional collections are 

covered by another exemption and 

exclusion. 

The NPRM asked whether additional 

or fewer activities regulated under the 

HIPAA Privacy Rule should be included 

in this exclusion. One commenter 

expressed concern that the HIPAA 

Privacy Rule was not appropriate 

because it both underregulates and 

overregulates research. Another 

commenter felt that the exclusion 

creates confusion because HHS has, in 

other contexts, discussed the differences 

between the Common Rule and HIPAA 

and the differing needs in separate 

contexts. 

(3) Public Comments on Research 

Conducted by a Government Agency 

Using Government-Generated or 

Government-Collected Data Obtained 

for Nonresearch Activities 

Approximately 20 comments 

discussed this proposed exclusion. 

Public comment was mixed, with 

several commenters suggesting that they 

did not understand the full scope of the 

information generated or collected by 

the government that would fall under 

this exclusion. A minority of comments 

indicated that this category of activities 

should be exempt rather than excluded. 

The NPRM also asked whether this or 

a separate exclusion should also include 

research involving information collected 

for nonresearch purposes by nonfederal 

entities where comparable privacy 

safeguards have been established by 

state law or regulation. Few responded 

to this question. Of these, several 

indicated that this exclusion should not 

be expanded to cover nonresearch data, 

and should not be expanded to cover 

activities conducted by 

nongovernmental investigators using 

government-generated or -collected 

data. Several comments indicated that 

this category was acceptable as an 

exclusion, with a few commenters 

suggesting that the category could be 

further broadened. 

One commenter suggested that this 

provision should apply to nonfederal 

entities if state laws are as protective as 

the federal laws cited. This commenter 

indicated that for these types of 

activities, the Common Rule protections 

did not provide meaningful additional 

protections to subjects. In contrast, 

several other commenters expressed 

concern that the privacy safeguards 

identified in this exclusion were not as 

protective of subjects as the Common 

Rule. One commenter indicated that 

clarifying what constitutes appropriate 

nonfederal use of this exclusion would 

be needed. 

One commenter suggested that this 

exclusion might be reasonable as an 

exclusion if there were a public posting 

requirement for activities conducted 

under this exclusion. If this were the 

case, this commenter indicated that 

investigator self-determination of 

whether an activity fit under this 

exclusion would be reasonable. 

In response generally to the question 

of whether any of the exclusions should 

apply to activities involving prisoners, a 

small number of comments addressed 

this question in the context of this 

exclusion. Of these responses, 

comments were mixed. 

ii. Response to Public Comments and 

Explanation of the Final Rule: 

Exemption for Secondary Research for 

Which Consent Is Not Required 

This exemption at §ll.104(d)(4) is 

for secondary research uses of 

identifiable private information or 

identifiable biospecimens when consent 

is not required, if at least one of the 

following criteria is met: 

• The identifiable private information 

or identifiable biospecimens are 

publicly available; 

• Information, which may include 

information about the biospecimens, is 

recorded by the investigator in such a 

manner that the identity of human 

subjects cannot readily be ascertained 

directly or through identifiers linked to 

the subjects, the investigator does not 

contact the subjects, and the investigator 

will not re-identify subjects; 

• The research involves only 

information collection and analysis 

involving the investigator’s use of 

identifiable health information when 

that use is regulated under 45 CFR parts 

160 and 164, subparts A and E, for the 

purposes of ‘‘health care operations’’ or 

‘‘research’’ as those terms are defined at 

45 CFR 164.501 or for ‘‘public health 

activities and purposes’’ as described 

under 45 CFR 164.512(b); or 

• The research is conducted by, or on 

behalf of, a federal department or 

agency using government-generated or 

government-collected information 

obtained for nonresearch activities, if 

the research generates identifiable 

private information that is or will be 

maintained on information technology 

that is subject to and in compliance 

with section 208(b) of the E-Government 

Act of 2002, 44 U.S.C. 3501 note, if all 

of the identifiable private information 

collected, used, or generated as part of 

the activity will be maintained in 

systems of records subject to the Privacy 

Act of 1974, 5 U.S.C. 552a, and, if 

applicable, the information used in the 

research was collected subject to the 

Paperwork Reduction Act of 1995, 44 

U.S.C. 3501 et seq. 

The criteria for this exemption were 

proposed in the NPRM as three 

exclusions. The final rule modifies the 

NPRM proposal to allow this exemption 

to apply to secondary research involving 

identifiable biospecimens, provided that 

the exemption’s conditions are met. 

Note that because the NPRM proposal to 

alter the definition of a human subject 

to extend to research involving 

nonidentified biospecimens was not 

adopted, an exemption for research with 

such biospecimens is not needed. 

Accordingly, this exemption is only 

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relevant to secondary research use of 

identifiable biospecimens. 

The goal of the exemption at 

§ ll.104(d)(4) is to facilitate secondary 

research using identifiable private 

information or identifiable 

biospecimens that have been or will be 

collected or generated for nonresearch 

purposes or from research studies other 

than the proposed research study. 

Unlike two other new exemptions that 

also relate to secondary research (the 

ones at § ll.104(d)(7) and 

§ ll.104(d)(8), discussed below), this 

exemption does not depend on any 

consent requirements imposed by the 

Common Rule being met. 

The first two provisions of this 

exemption (§ll.104(d)(4)(i) and (ii)) 

are a modified version of the fourth 

exemption under the pre-2018 rule. The 

modified provisions allow the 

exemption to include research with 

information and biospecimens that do 

not yet exist when the research study is 

proposed for exemption (i.e., that could 

be collected, for purposes not related to 

the proposed research study, in the 

future). 

The third and fourth provisions of the 

exemption have no precursors in the 

pre-2018 rule. The third provision 

applies the exemption to secondary 

research using identifiable private 

information covered under HIPAA, and 

the fourth provision applies the 

exemption to secondary research using 

identifiable private information 

collected for nonresearch purposes by 

the Federal Government, if compliant 

with the three cited federal statutes. 

These new rules will allow investigators 

to see identifiable private information, 

and also allow them to retain and record 

that information (including the 

identifiers) as part of their research 

records. 

We also note that, according to new 

language at § ll.104(b)(2) adopted as 

part of this final rule, this exemption 

permits the secondary research use of 

identifiable private information or 

identifiable biospecimens obtained from 

subjects who are prisoners, if the 

research is not designed in a way that 

seeks to recruit prisoners as a 

population but rather only incidentally 

(i.e., not intentionally) includes 

prisoners. 

(1) Response to Public Comments and 

Explanation of the Final Rule: Research 

Involving the Collection or Study of 

Identifiable Private Information or 

Identifiable Biospecimens That Are 

Publicly Available 

The exemption criterion at 

§ ll.104(d)(4)(i) is for secondary 

research if the identifiable private 

information or identifiable 

biospecimens are publicly available. 

This would apply to secondary research 

use of archives in a public library, for 

example, or to government or other 

institutional records where public 

access is provided on request, or from 

a commercial entity if the information is 

provided to members of the public on 

request or if the only requirement for 

obtaining the information is paying a 

user fee, registering or signing in as a 

visitor to an archive. It would also apply 

if a commercial entity made identifiable 

biospecimens publicly available to 

anyone on request or for a fee. This 

exemption effectively acknowledges 

that for secondary research with 

publicly available information or 

biospecimens, IRB review would not 

reduce the risk. 

(2) Response to Public Comments and 

Explanation of the Final Rule: Research 

Involving the Collection or Study of 

Information (Which May Include 

Information About Biospecimens) That 

Has Been or Will Be Collected and Is 

Recorded Without Identifiers 

The provision at §ll.104(d)(4)(ii) 

exempts research involving identifiable 

private information, which may include 

information about biospecimens, if 

information is recorded by the 

investigator in such a manner that the 

identity of human subjects cannot 

readily be ascertained directly or 

through identifiers linked to the 

subjects, the investigator does not 

contact the subjects, and the investigator 

will not re-identify subjects. As with the 

provision at § ll.104(d)(4)(i), this 

provision is related to an exemption that 

existed in the pre-2018 rule. In this 

instance, that prior exemption is being 

extended to now also cover research 

with information for which identifiers 

have been removed when the original 

collection of information or 

biospecimens occurs in the future. 

(3) Response to Public Comments and 

Explanation of the Final Rule: The 

HIPAA Exclusion 

The provision at §ll.104(d)(4)(iii) 

permits the secondary research use of 

identifiable private information or 

identifiable biospecimens when the 

research involves only information 

collection and analysis involving the 

investigator’s use of identifiable health 

information when that use is regulated 

under 45 CFR parts 160 and 164 (the 

HIPAA Privacy Rule), subparts A and E, 

for the purposes of ‘‘health care 

operations’’ or ‘‘research’’ as those terms 

are defined at 45 CFR 164.501, or for 

‘‘public health activities’’ as described 

under 45 CFR 164.512(b). 

With regard to the criterion at 

§ ll.104(d)(4)(iii), HIPAA also 

provides protections in the research 

context for the information that would 

be subject to this exemption (e.g., 

clinical records), such that additional 

Common Rule requirements for consent 

should be unnecessary in those 

contexts. Under HIPAA, these 

protections include, where appropriate, 

requirements to obtain the individual’s 

authorization for future, secondary 

research uses of protected health 

information, or waiver of that 

authorization by an IRB or HIPAA 

Privacy Board. This provision 

introduces a clearer distinction between 

when the Common Rule and the HIPAA 

Privacy Rule apply to research in order 

to avoid duplication of regulatory 

burden. We believe that the HIPAA 

protections are adequate for this type of 

research, and that it is unduly 

burdensome and confusing to require 

applying the protections of both HIPAA 

and an additional set of protections. 

This provision was not part of the pre2018 rule, and was proposed as an 

exclusion in the NPRM. It is included as 

a component of an exemption in the 

final rule, consistent with public 

comments supporting the proposal. 

(4) Response to Public Comments and 

Explanation of the Final Rule: Research 

Conducted by a Government Agency 

Using Government Generated or 

Government Collected Data Obtained for 

Nonresearch Activities 

The provision at §ll.104(d)(4)(iv) 

did not exist in the pre-2018 rule and 

was proposed as an exclusion in the 

NPRM. It appears as a component of an 

exemption in the final rule. The 

exemption permits the use of 

identifiable private information or 

identifiable biospecimens for secondary 

research conducted by, or on behalf of, 

a federal department or agency using 

government-generated or governmentcollected information obtained for 

nonresearch activities, if the 

information originally involved a 

collection that adheres to the federal 

standards for safeguarding privacy as 

described in this part of the exemption. 

We believe that the privacy 

protections are adequate for this type of 

research, and that it is unduly 

burdensome and confusing to require 

these protections and an additional set 

of protections. This provision has been 

modified to apply the federal statutory 

privacy safeguards identified in the 

exemption provision to both the original 

collection of the information, and to the 

secondary research use of the 

information to which the exemption 

applies. 

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e. Research and Demonstration Projects 

Conducted or Supported by a Federal 

Department or Agency (§ ll.104(d)(5)) 

i. Public Comments 

Approximately 35 comments 

discussed the changes proposed in the 

public benefit or service program 

exemption. Few of the comments 

discussed the proposed expansion in 

OHRP’s interpretation of this exemption 

to include the applicability of the 

exemption to cover research on public 

benefit and service programs that an 

agency does not itself administer 

through its own employees or agents, 

with a majority supporting the NPRM 

proposed expansion. One research 

university indicated that OHRP should 

not expand its interpretation of this 

exemption, and that it should be limited 

to ‘‘federally funded studies evaluating 

federal programs.’’ This institution did 

not offer justification for its comment. 

Few comments were received about 

the proposed requirement for exemption 

designation of research or 

demonstration projects to be posted to a 

publicly available federal Web site. The 

comments discussing this proposed 

requirement supported it. 

The majority of comments indicated 

that no additional requirements or 

limitations should be imposed on this 

exemption. These institutions argued 

that because this exemption represented 

a mechanism through which the Federal 

Government evaluated its own 

programs, additional limitations and 

restrictions in the Common Rule did not 

seem appropriate. 

Specifically, with respect to whether 

or not some sort of notice should be 

required here, several commenters 

noted that any notice would need to be 

meaningful. One commenter indicated 

that because meaningful notice would 

be difficult, a notice requirement should 

not be imposed. One comment 

suggested that notice should only be 

required if opt-out would be permitted, 

and if not, no notice requirement should 

be imposed. Groups representing AI/AN 

populations supported the notice 

requirement and indicated that it should 

be required at a minimum. 

ii. Response to Comments and 

Explanation of the Final Rule: 

Exemption for Certain Research and 

Demonstration Projects Conducted or 

Supported by a Federal Department or 

Agency 

The final rule includes this exemption 

as a modified version of an exemption 

proposed in the NPRM. The exemption 

at §ll.104(d)(5) in the final rule 

applies to research and demonstration 

projects involving public benefit or 

service programs, and is a slightly 

revised version of the exemption in the 

pre-2018 rule. This revision is designed 

to clarify the scope of the exemption so 

that more research studies would be 

eligible, and to make the exemption 

easier to apply. It is also designed to 

allow the Federal Government to carry 

out important evaluations of its public 

benefit and service programs to ensure 

that those programs are cost effective 

and provide the intended benefits or 

services, consistent with the principle of 

beneficence. The wording of the 

exemption has added ‘‘improve’’ to the 

purposes of these activities, to make 

more explicit the idea that the Federal 

Government conducts these activities in 

order to enable them to make the public 

benefit and service programs better, and 

not just to gauge their current quality. 

This exemption is for research and 

demonstration projects that are 

conducted or supported by a federal 

department or agency, or otherwise 

subject to the approval of department or 

agency heads. It applies to activities that 

are designed to study, evaluate, 

improve, or otherwise examine public 

benefit or service programs, including, 

but not limited to: Procedures for 

obtaining benefits or services under 

those programs; possible changes in or 

alternatives to those programs or 

procedures; or possible changes in 

methods or levels of payment for 

benefits or services under those 

programs. 

In addition, the final rule clarifies the 

language of the exemption to conform to 

OHRP’s previous interpretation of 

public benefit and service programs that 

are being evaluated as part of the 

research. This interpretation includes 

public benefit or service programs that 

a Common Rule department or agency 

does not itself administer or conduct 

through its own employees or agents, 

but rather supports through a grant or 

contract program. Therefore, the 

exemption applies to research and 

demonstration projects supported 

through, for example, federal grants or 

cooperative agreements. These changes 

would bring the regulatory language 

into conformance with other provisions 

of the rule that refer to research 

‘‘conducted or supported’’ by federal 

departments and agencies. These 

methods of administration are, of 

course, always subject to department or 

agency head approval, either directly or 

by delegation. In addition, some of these 

research and demonstration projects are 

conducted through waivers, interagency 

agreements, or other methods that also 

require agency head approval. 

Accordingly, both the previous and 

revised language allow for the full 

panoply of methods by which research 

and demonstration projects on public 

benefit or service programs can be 

carried out. 

The wording of the exemption also is 

clarified to specifically include projects 

involving waivers of otherwise 

mandatory requirements using 

authorities such as sections 1115 and 

1115A of the Social Security Act, in 

order to make it plain that such research 

projects on public benefit or service 

programs qualify for the exemption. The 

relevant sections of the Social Security 

Act were also cited when this 

exemption was published in 1983. 

In the interest of transparency, as was 

proposed in the NPRM, the final rule 

requires that each federal department or 

agency conducting or supporting the 

research and demonstration projects 

must establish, on a publicly accessible 

federal Web site or in such other 

manner as the department or agency 

head may determine, a list of the 

research and demonstration projects the 

federal department or agency conducts 

or supports under this provision. The 

research or demonstration project must 

be published on this list before 

beginning the research involving human 

subjects. The department or agency 

head can determine what sort of 

information will be included on this list 

and maintains its oversight. 

Departments and agencies that already 

publish research and demonstration 

projects on a publicly accessible Web 

site could satisfy this proposed 

requirement if the existing Web site 

includes a statement indicating which 

of the studies were determined to meet 

this exemption. 

The goal of this proposed requirement 

is to promote transparency of federally 

conducted or supported activities 

affecting the public that are not subject 

to oversight under the Common Rule. It 

should not cause any delay to the 

research. HHS will develop a resource 

that all Common Rule departments and 

agencies may use to satisfy the 

requirement at § ll.104(d)(5)(i). 

Alternatively, an agency can create or 

modify its own Web site for this 

purpose. 

The exemption is not modified to 

require notice, to apply only to minimal 

risk research activities, or to require the 

privacy safeguards, for reasons reflected 

in the public comments. We agree with 

the public comments that argued that in 

many cases notice would be difficult or 

impossible to achieve effectively, and 

that this exemption enables the Federal 

Government to conduct important 

evaluations of its own programs that 

provide significant benefits to the 

public. In addition, federal departments 

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and agencies are already subject to other 

laws and policies that protect the 

interests of research subjects (e.g., the 

Privacy Act). 

f. Taste and Food Quality Evaluation 

and Consumer Acceptance Studies 

(§ ll.104(d)(6)) 

i. Public Comments 

Approximately 20 comments 

discussed this exemption for taste and 

food quality evaluation and consumer 

acceptance studies. The NPRM did not 

propose changes to this exemption from 

what appeared in the pre-2018 rule. 

However, it did ask whether this 

exemption should be narrowed to apply 

only to activities for which prospective 

subjects have been given prior notice, 

and if so, how that notice should be 

issued. The NPRM further asked 

whether subjects should be allowed to 

opt out of exempt research. 

A majority of comments received 

indicated that the final rule should 

maintain this exemption without any 

additional requirements. Commenters 

generally did not include explanation of 

this position. A small minority of 

commenters indicated that subjects 

should explicitly be provided the 

opportunity to opt out of this type of 

activity. In addition, a small minority of 

commenters indicated that subjects 

should be given notice before 

participation. One comment suggested 

that this exemption include ‘‘odor’’ 

evaluations as well. 

ii. Response to Comments and 

Explanation of the Final Rule: 

Exemption for Taste and Food Quality 

Evaluation and Consumer Acceptance 

Studies 

The final rule retains the exemption 

from the pre-2018 rule, which was 

proposed in the NPRM without any 

change, for taste and food quality 

evaluation and consumer acceptance 

studies. This exemption applies if 

wholesome foods without additives are 

consumed, or if a food is consumed that 

contains a food ingredient at or below 

the level and for a use found to be safe, 

or agricultural, chemical or 

environmental contaminant at or below 

the level found to be safe by FDA or 

approved by the Environmental 

Protection Agency or the Food Safety 

and Inspection Service of the U.S. 

Department of Agriculture. This 

exemption is retained unchanged from 

the pre-2018 rule. 

g. Secondary Research Use of 

Identifiable Private Information or 

Identifiable Biospecimens (or Storage or 

Maintenance for Such Secondary 

Research Use) for Which Broad Consent 

Is Required (§ ll.104(d)(7) and (8)) 

The final rule includes two 

exemptions related to the secondary 

research use (including storage or 

maintenance for such use) of 

identifiable private information and 

identifiable biospecimens that require a 

subject’s broad consent. 

The first of these exemptions is in the 

final rule at §ll.104(d)(7), and applies 

to storing and maintaining identifiable 

private information or identifiable 

biospecimens for secondary research 

use. 

The second of these exemptions is in 

the final rule at §ll.104(d)(8) and 

applies to the secondary research use of 

identifiable private information and 

identifiable biospecimens for specific 

secondary research studies. Secondary 

research under this exemption would 

generally be conducted with the 

information or biospecimens stored and 

maintained under the exemption at 

§ ll.104(d)(7). 

Both of these exemptions for the 

secondary use of identifiable private 

information and identifiable 

biospecimens require broad consent and 

are discussed in detail below. As with 

the secondary use exemptions that do 

not require the subject’s broad consent 

(discussed above in Section V.3.d. of the 

preamble), the two exemptions at 

§ ll.104(d)(7) and (8) are also limited 

to ‘‘secondary research.’’ These 

exemptions pertain only to research that 

involves re-using information or 

biospecimens that were or will be 

collected for some other ‘‘primary’’ or 

‘‘initial’’ activity distinct from using 

them in secondary research. These 

exemptions do not cover any primary 

collections of either information or 

biospecimens. In other words, if an 

investigator wants to collect information 

directly from research subjects, for 

example, by asking them to complete a 

questionnaire, that would not be 

covered by these exemptions. Or if an 

investigator wants to collect 

biospecimens by having subjects swab 

their cheeks, that collection would 

similarly not be covered by these 

exemptions. On the other hand, an 

investigator who wants to use 

information that is in some databank, or 

to use biospecimens that are in a 

pathology laboratory, could use these 

exemptions, assuming all of the relevant 

conditions of the exemptions were met. 

i. Public Comments on the Proposed 

Exemptions for Secondary Research Use 

of Identifiable Private Information or 

Identifiable Biospecimens (or Storage or 

Maintenance for Such Secondary 

Research Use) for Which Broad Consent 

Is Required 

In combination, approximately 150 

comments discussed these proposals. 

Although commenters generally 

supported creating a pathway for lowrisk research with biospecimens to 

occur without IRB review, a majority 

opposed the overarching proposal that 

these exemptions would, for the most 

part, be the only way (besides studyspecific consent) for research with 

biospecimens to occur. Many of the 

arguments for and against these 

exemptions were outlined in section 

III.D, summarizing public comments 

received on the proposal to define 

‘‘human subject’’ as including all 

biospecimens used in research, 

regardless of identifiability. 

Many commenters opposed the idea 

that the exemption should allow 

specific secondary studies involving 

biospecimens retained with identifiers 

to occur without IRB review. These 

commenters noted that IRBs are 

required to assess more than privacy 

and confidentiality protections, and 

whether informed consent was sought 

and obtained. Other commenters noted 

that by effectively encouraging the 

retention of identifiers with 

biospecimens (which would likely be 

required to track which specimens 

could be used in research at an 

institution), the NPRM proposals 

effectively introduced new privacy and 

confidentiality risks to subjects that did 

not exist under the pre-2018 rule. 

Some commenters who supported the 

expanded definition of human subject to 

include all biospecimens did not 

support these exemptions. These 

comments were mostly from members of 

the public and they generally argued 

that study-specific consent should be 

sought and obtained from subjects for 

every study involving that person’s 

biospecimens. These comments 

expressed concern that, with broad 

consent, investigators could still engage 

in research activities without the 

individuals’ knowledge. 

Several commenters expressed 

opposition to the NPRM proposal that 

the exemption could not be used if the 

investigator intended to return research 

results to subjects. These commenters 

saw this as a disincentive to return 

research results and also noted that it 

seemed at odds with existing law (e.g., 

HIPAA) and policy. Specifically, they 

argued, because patients are entitled 

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under HIPAA to the contents of their 

medical records, investigators must 

always be ready to return research 

results to subjects enrolled in their 

studies. 

The NPRM inquired about whether 

the proposed exemption was the best 

option, or whether there is a better way 

to balance respect for persons with 

facilitating research. Responses to this 

question were mixed, with a majority 

indicating that the proposed exemptions 

were not the best option. One comment 

indicated that broad consent would be 

reasonable if the consent was 

meaningful. 

Other commenters opposed the 

proposal as written. One felt it provided 

too little information and another found 

the language too complex and subject to 

misinterpretation. One institution 

asserted that the exemption would pose 

a burden on the research enterprise, 

would make a significant subset of 

studies impracticable, and would 

increase costs. 

Still other commenters indicated that 

consent should not be required for 

secondary research with biospecimens, 

noting that it was contradictory to 

determine that a type of research was 

exempt but still require consent, or that 

this exemption should not apply to 

state-mandated newborn DBS programs. 

One commenter suggested, ‘‘A far better 

option would be to include an 

exemption for the secondary research 

use of de-identified or nonidentified 

biospecimens, without the caveat of 

requiring a broad consent.’’ 

The NPRM requested public comment 

on whether and how the provision 

regarding the return of research results 

should be revised. Public comment was 

mixed in response to this question. 

Several comments indicated that the 

provision was too complex to follow. 

Comments that supported the 

provision about the return of research 

results in the proposed exemption 

stressed the complexity of decisions 

around returning results and many 

indicated support for required IRB 

review of investigators’ plans for 

returning research results. One 

professional organization also 

emphasized the need to communicate to 

potential participants during the 

informed consent process the policies 

concerning the return of individual 

research results. Many commenters also 

called for detailed OHRP guidance on 

this provision. 

One commenter suggested that the 

broad consent required when 

biospecimens are collected for storage 

for future research use include an 

indication as to whether potential 

subjects would like to be re-contacted 

with individual research results if 

applicable. 

Other commenters were opposed to 

the provision as written. One large 

health system indicated that the 

provision discourages researchers from 

returning research results to participants 

and from providing participants with 

easy access to their individual research 

data. The commenter emphasized that 

‘‘Respecting research participants as 

partners obligates us to avoid the 

assumptions that researchers, an IRB, or 

even a panel of experts . . . know best.’’ 

The commenter went on to say: ‘‘While 

the NPRM suggests researchers cannot 

use the Common Rule as a shield from 

a request to deliver a designated record 

set upon request, the policy seems to 

discourage equitable research practices 

and allows informational disparities to 

continue. This does not serve the 

interest of justice.’’ 

In addition, one professional 

organization indicated concern that the 

provision might be interpreted by some 

to say that IRBs should not allow return 

of results, which it felt would create a 

bad situation. 

The NPRM sought comment on 

whether there should be an additional 

exemption that would permit the 

collection of biospecimens through 

minimally invasive procedures (e.g., 

cheek swab, saliva). A strong majority of 

commenters indicated no need for an 

additional exemption to permit the 

collection of biospecimens through 

minimally invasive procedures. One 

professional organization asserted that 

specimens should not be treated 

differently based on how they were 

collected. Other commenters indicated 

that obtaining specimens through 

minimally invasive procedures is 

similar to data collection and should be 

treated the same way. 

ii. Explanation of the Final Rule: 

Exemptions for Secondary Research Use 

of Identifiable Private Information or 

Identifiable Biospecimens (or Storage or 

Maintenance for Such Secondary 

Research Use) for Which Broad Consent 

Is Required 

(1) Exemption for the Storage or 

Maintenance for Secondary Use of 

Identifiable Private Information or 

Identifiable Biospecimens for Which 

Broad Consent is Required 

(§ ll.104(d)(7)) 

Section ll.104(d)(7) is an 

exemption for the storage or 

maintenance for secondary research use 

of identifiable private information or 

identifiable biospecimens. It requires 

that an IRB conduct limited IRB review 

to make the following determinations 

(required by § ll.111(a)(8)): 

• Broad consent for storage, 

maintenance, and secondary research 

use of identifiable private information 

or identifiable biospecimens is obtained 

in accordance with the requirements of 

§ ll.116(a)(1)–(4), and (a)(6), and (d); 

• Broad consent is appropriately 

documented or waiver of 

documentation is appropriate, in 

accordance with § ll.117; and 

• If a change is made for research 

purposes in the way the identifiable 

private information or identifiable 

biospecimens are stored or maintained, 

adequate provisions must be in place to 

protect the privacy of subjects and to 

maintain the confidentiality of data. 

This exemption is similar to the 

exemption proposed in the NPRM at 

§ ll.104(f)(1), but it has been modified 

in some respects, and the operation of 

this exemption is also affected by other 

changes in the final rule that are 

different from the NPRM. Namely, the 

exemption has been modified to apply 

only to storage or maintenance for 

secondary research use of identifiable 

private information or identifiable 

biospecimens, because the final rule 

does not incorporate the NPRM 

proposal to alter the definition of a 

human subject to extend to research 

involving biospecimens regardless of 

their identifiability. This exemption was 

also modified given the decision not to 

adopt the privacy safeguards proposed 

in the NPRM at §ll.105. 

In addition, the Secretary’s template 

for broad consent is not being finalized 

for this exemption. Instead, institutions 

will have the flexibility to create their 

own consent forms that satisfy 

requirements at § ll.116(a)(1)–(4), 

(a)(6) and (d) (see Section XIV). The 

consent form may be electronic. 

Given these changes from the NPRM 

proposal, the limited IRB review 

requirement for this exemption 

provided at § ll.111(a)(8) has been 

expanded in the final rule to require 

that the IRB make the following 

determinations, some of which are 

similar to those proposed in the NPRM. 

The final rule requires that for the 

exemption to apply, the IRB must 

determine that broad consent for 

storage, maintenance, and secondary 

research use of identifiable private 

information or identifiable 

biospecimens is obtained in accordance 

with the requirements of 

§ ll.116(a)(1)–(4), (a)(6), and (d); This 

includes the requirement proposed in 

the NPRM that there be IRB review of 

the process through which broad 

consent will be obtained. 

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Also, given that we are not finalizing 

the proposed requirement to use the 

Secretary’s template for broad consent, 

the final rule includes in this 

requirement that an IRB determine that 

the broad consent includes the 

requirements and elements of consent in 

accordance with § ll.116(a)(1)–4), 

(a)(6), and (d). 

The final rule also requires that the 

IRB determine that broad consent is 

appropriately documented or waived in 

accordance with § ll.117. Although 

written broad consent generally will be 

required for this exemption to apply, the 

final rule also permits the exemption to 

apply when broad consent is obtained 

and an IRB has waived the 

documentation requirement for written 

informed consent under § ll.117(c)(1). 

And because the proposed privacy 

safeguards proposed in the NPRM at 

§ ll.105 are not included in the final 

rule, if a change will be made for 

research purposes in the way the 

identifiable private information or 

identifiable biospecimens are stored or 

maintained, the IRB must determine 

that when appropriate, adequate 

provisions are in place to protect the 

privacy of subjects and to maintain the 

confidentiality of data. This is the same 

IRB determination related to privacy 

and confidentiality that is required for 

nonexempt research. Importantly, this 

IRB determination is required only 

when a change is made for research 

purposes in the way the identifiable 

private information or identifiable 

biospecimens are stored or maintained, 

and only pertains to the aspects of 

storage and maintenance that are 

changed for research purposes. In this 

circumstance, the investigators are 

assuming responsibility for the manner 

in which the information and 

biospecimens are stored and 

maintained, and the IRB should be 

required to ensure that appropriate 

protections for the subjects are place 

with regard to the aspects of storage or 

maintenance that were changed for 

research purposes. 

If, on the other hand, no changes are 

being made for research purposes to the 

storage or maintenance, then this IRB 

determination does not apply. The 

institution storing and maintaining the 

information or biospecimens of course 

still has its responsibility to determine 

what protections distinct from those 

required by the Common Rule are 

appropriate, which may include other 

legal or regulatory safeguards or 

institutional policies. In light of 

application of such additional 

safeguards, it appears unnecessary to 

require additional protections through a 

requirement of this final rule simply 

because the individuals providing broad 

consent have agreed that their 

biospecimens or information could be 

used for research at some point in the 

future. And of course this provision 

regarding changes made for research 

purposes applies only when a Common 

Rule department or agency supports or 

conducts the research activity. 

Note that in many instances the only 

change that results from a person having 

signed a broad consent form for research 

relating to storing and maintaining that 

person’s biospecimens or information is 

that the institution that is already 

holding the biospecimens or 

information (for clinical purposes, for 

example) merely creates a record 

indicating that this person has signed 

such a consent form. The biospecimens 

and information could remain stored in 

whatever way (and for whatever period 

of time) that the institution had 

previously been storing them, based on 

the legitimate nonresearch or researchrelated reasons that the institution has 

used for initially collecting and storing 

those biospecimens and information. 

Any privacy and security protections 

(outside of the Common Rule) that 

already may apply to the institution’s 

information record-keeping or 

biospecimen preservation activities 

would continue to apply. The Common 

Rule’s protections would not apply 

before a change in storage or 

maintenance occurs for research 

purposes, but rather the institution 

would continue to operate in 

accordance with its pre-existing 

legitimate reasons for having and storing 

the biospecimens and information. The 

fact that the broad consent form has 

been signed does not by itself mean that 

there needs to be any alteration of what 

the institution is already doing with the 

biospecimens or information. 

Examples of changed aspects of 

storage or maintenance for research 

purposes that would require the IRB to 

find, before those changes go into effect, 

whether there are adequate provisions 

to protect the privacy of subjects and 

maintain the confidentiality of data 

include the following: If information or 

biospecimens are moved from one 

electronic or physical storage location to 

another due to considerations related to 

research plans; if information or 

biospecimens will be stored for longer 

than they otherwise would have been 

for the original purpose; if information 

or biospecimens are placed in a research 

registry or repository created to serve as 

a resource for investigators; or 

investigators are given electronic or 

physical access to the information or 

biospecimens. The relevant changes do 

not necessarily involve moving 

information or biospecimens from one 

location to another. Rather, the relevant 

changes include any change for research 

purposes that introduces or alters risks 

to the privacy or security of the stored 

information or biospecimens, including 

giving access to or transferring 

information or biospecimens for 

research purposes to someone who 

otherwise would not have access. 

The rationale for this exemption is 

that with the requirement for limited 

IRB review and the specified required 

IRB determinations, including subjects’ 

broad consent, this exemption respects 

subjects’ autonomy and provides 

appropriate privacy safeguards. More 

specifically, we believe that broad 

consent provides some measure of 

autonomy for individuals to decide 

whether to allow the research use of 

their identifiable private information or 

identifiable biospecimens, without 

imposing the kind of burden on 

investigators that would result from a 

requirement for specific informed 

consent for each secondary research 

study. We believe that it is appropriate 

to create a mechanism for broad consent 

for secondary research use, even if it 

involves the potential risk of having 

identifiers associated with the 

identifiable private information or 

identifiable biospecimens. We believe 

the administrative burden is also 

acceptable in order to allow for broad 

consent for secondary research use. 

(2) Exemption for Research Involving 

the Use of Identifiable Private 

Information or Identifable Biospecimens 

for Which Broad Consent is Required 

(§ ll.104(d)(8)) 

Section ll.104(d)(8) is an 

exemption that also requires that broad 

consent has been obtained, and is for 

research involving the use of 

identifiable private information or 

identifiable biospecimens. This 

exemption will frequently be paired 

with the exemption at §ll.104(d)(7), 

which permits the storage and 

maintenance of identifiable private 

information and identifiable 

biospecimens for secondary research 

use. The exemption at §ll.104(d)(8) 

would apply to a specific secondary 

research study, provided that the 

following criteria are met: 

• Broad consent for the storage, 

maintenance, and secondary research 

use of the identifiable private 

information or identifiable 

biospecimens was obtained in 

accordance with § ll.116(a)(1)–(4), 

(a)(6), and (d); 

• Documentation of informed consent 

or waiver of documentation of consent 

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was obtained in accordance with 

§ ll.117; 

• An IRB conducts a limited IRB 

review to make the determination 

required by § ll.111(a)(7), and to 

make the determination that the 

research to be conducted is within the 

scope of the broad consent; and 

• The investigator does not include 

returning individual research results to 

subjects as part of the study plan. 

However, it is permissible under this 

exemption to return individual research 

results when required by law regardless 

of whether or not such return is 

described in the study plan. 

This exemption could also apply if 

the investigator obtains appropriate 

broad consent from the subject in 

addition to the consent to an original 

specific study, and then proceeds to use 

the information or biospecimen in a 

secondary study. 

The exemption at §ll.104(d)(8) is 

similar to the exemption proposed in 

the NPRM, but it has been modified in 

some respects. As with the exemption at 

§ ll.104(d)(7), the operation of the 

exemption at § ll.104(d)(8) is also 

affected by other provisions in the final 

rule that are different from what was 

proposed in the NPRM. Namely, the 

exemption has been modified to apply 

only to storage or maintenance for 

secondary research use of identifiable 

private information or identifiable 

biospecimens because the final rule 

does not incorporate the NPRM 

proposal to alter the definition of a 

human subject to extend to research 

involving biospecimens regardless of 

their identifiability. 

Due to the decision not to adopt the 

proposed privacy and security 

safeguards proposed in the NPRM at 

§ ll.105, this exemption was also 

modified to require that limited IRB 

review include an IRB determination 

that, when appropriate, adequate 

provisions are in place to protect the 

privacy of subjects and the 

confidentiality of data (§ll.111(a)(7)). 

This is the same IRB approval criteria 

related to privacy and confidentiality 

that is required for nonexempt human 

subjects research. 

In addition, because the final rule 

does not include a broad consent 

template when a specific study has been 

proposed, it is required that the study be 

reviewed by an IRB to determine 

whether the proposed secondary 

analysis fits within the parameters of 

the broad consent that was obtained for 

secondary research use. 

We believe that the final rule’s 

requirement for limited IRB review of 

the privacy and confidentiality 

protections and the adequacy of the 

broad consent is responsive to 

commenters who believe that IRB 

oversight should be retained for the 

secondary research use of identifiable 

private information and identifiable 

biospecimens. 

We recognize commenters’ point that 

this exemption does not provide an 

incentive to investigators to provide 

individual research results to subjects, 

but we believe that the challenges of 

how and when to return such results 

warrant consultation with the IRB. We 

note that with the other revisions to the 

NPRM proposals, other options for 

research involving identifiable private 

information and identifiable 

biospecimens exist, which would be 

consistent with having plans for 

returning individual results. Although 

broad consent may include a statement 

that clinically relevant research results 

might be returned to subjects, we 

believe that when specific secondary 

studies include such a plan to return 

research results, it would almost always 

be appropriate for the study to be 

reviewed by an IRB, in part to better 

ensure that research results are 

disclosed to subjects in an appropriate 

manner. The only exceptions would be 

if the research qualified for another 

exemption, an IRB waived informed 

consent under § ll.116(e) or (f), or the 

research was carried out under a 

Secretarial waiver at §ll.101(i). We 

expect that as part of the IRB’s review, 

the IRB would consider what subjects 

were told in the broad consent regarding 

the return of research results. 

It should be noted that the two 

exemptions in the final rule at 

§ ll.104(d)(7) and (8) create additional 

options for investigators to conduct 

secondary research studies with 

identifiable private information. The 

final rule retains, largely unchanged, the 

options previously available to 

investigators in the pre-2018 rule. For 

instance, the final rule retains the pre2018 criteria for requesting a waiver of 

consent in order to carry out those 

studies without obtaining consent. 

Moreover, secondary research using 

nonidentified biospecimens would not 

have to meet these requirements, 

because the final rule does not finalize 

the NPRM proposal to alter the 

definition of a human subject to include 

research involving nonidentified 

biospecimens under the rule. 

h. NPRM Proposal To Delete the Pre2018 Rule’s Exemption for Surveys and 

Interviews of Public Officials 

The NPRM proposed to delete 

language found in the pre-2018 rule that 

exempted surveys and interviews with 

public officials. Approximately 100 

comments discussed this proposed 

deletion and it was almost universally 

opposed. Political science professors, 

students, researchers, and academics 

from other disciplines generally 

addressed this deletion. 

Comments argued that this deletion 

would have a chilling effect on political 

science research and might make 

political science researchers more 

vulnerable to law suits. Other comments 

noted that public officials are generally 

treated differently in numerous laws, 

and it is in fact appropriate for the 

Common Rule to have a different 

standard for surveys and interviews 

with public officials. Comments also 

suggested that this deletion could 

negatively affect the public’s ability to 

hold public officials accountable for 

their actions. One commenter suggested 

that instead of deleting this exemption, 

a final rule might consider explicitly 

limiting this exemption to studies that 

relate to the public officials in their 

official capacity. 

The final rule removes the exemption 

category in the pre-2018 rule at 

§ ll.101(b)(3)(i), which pertained to 

research involving the use of 

educational tests, survey procedures, 

interview procedures, or observation of 

public behavior, if the human subjects 

are elected or appointed public officials 

or candidates for public office, or if 

federal statute requires without 

exception that the confidentiality of the 

personally identifiable information will 

be maintained throughout the research 

and thereafter. We note that many of the 

public comment concerns are addressed 

by other provisions in the final rule. 

Almost all of the research activities in 

this category would already be 

exempted under the final rule at 

§ ll.104(d)(2), without needing to 

single out elected or appointed officials 

as being treated differently in this way. 

If the research is designed to provide 

sensitive generalizable knowledge about 

officials, then the identifiable private 

information obtained should be kept 

confidential as required by this final 

rule. If the purpose of the activity is in 

fact designed to hold specific elected or 

appointed officials up for public 

scrutiny, and not keep the information 

confidential, such an activity is not 

considered research under the provision 

at §ll.102(l)(2). 

Thus, the final rule adopts the NPRM 

proposal. 

i. NPRM Proposal To Exempt Secondary 

Research Use of Identifiable Private 

Information Where Notice Was Given 

One exemption proposed in the 

NPRM is not included in the final rule. 

Note that exclusions proposed in the 

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NPRM and not included in the final rule 

also are described in Section III.I.4 of 

this preamble. 

The NPRM proposed to exempt 

certain secondary research activities 

involving identifiable private 

information where notice of such use 

had been given. The proposed 

exemption was included, in part, to be 

responsive to section 511 of the 

Medicare Access and CHIP 

Reauthorization Act of 2015 (MACRA), 

which requires the Secretary to issue a 

clarification or modification with 

respect to the application of these 

regulations to certain activities 

involving clinical data registries. The 

preamble for the Common Rule NPRM 

noted ‘‘. . . this exemption category 

might allow certain research activities of 

these clinical data registries not 

otherwise covered by the proposed 

HIPAA-related exclusion (i.e., when the 

clinical data registries are not part of a 

HIPAA covered entity or acting as a 

business associate), such as when a 

clinical data registry may receive 

information from a health care entity for 

research purposes.’’ 

Approximately 70 comments 

discussed this proposal, with the vast 

majority from institutions. A minority of 

commenters (14) supported the NPRM 

proposal as drafted. In addition, 11 

commenters who did not indicate 

whether they supported the inclusion of 

this proposal in a final rule asked 

questions about implementation and the 

meaning of ‘‘notice’’ under this 

proposal. 

A majority of commenters (41) 

opposed the proposal as drafted in the 

NPRM, citing a variety of conflicting 

reasons: 

• Sixteen commenters felt that the 

NPRM proposal was too permissive as 

drafted, and that it would not provide 

adequate protections to prospective 

subjects. Many of these commenters also 

suggested that the proposal as drafted 

did not respect subject autonomy 

interests sufficiently in not providing 

subjects with an ability to opt out. They 

indicated that the exemption might be 

acceptable if additional requirements 

(such as subject opt out), or additional 

limitations (such as limiting the 

nonresearch information to which this 

exemption applies to data governed by 

certain privacy-oriented laws) were 

implemented. 

• Fourteen commenters felt that the 

NPRM proposal was too restrictive, and 

that as drafted it would not achieve the 

stated goal of reducing administrative 

burden on IRBs. These commenters 

specifically discussed the 

implementation burdens involved in 

providing notice to prospective subjects. 

These commenters also noted that 

providing an option to opt out would be 

very burdensome to IRBs and 

investigators, an outcome that seemed 

counter to the justifications the NPRM 

provided for this exemption. 

• Five commenters felt that the type 

of research encompassed by this 

proposal should not be exempted from 

the Common Rule, and that IRB review 

or informed consent should be required 

instead. 

Approximately 25 comments 

discussed whether the NPRM proposal 

was necessary to enable activities 

involving qualified clinical data 

registries. A majority of these comments 

indicated that because the activities 

would be subject to the HIPAA 

regulations, protection of subjects 

would not be enhanced by the proposed 

NPRM exemption. Several commenters 

pointed out that qualified clinical data 

registries also might qualify for 

exclusion under the NPRM proposal at 

101(b)(2)(ii). Additional comments 

suggested that other NPRM exemptions 

and exclusions would cover activities 

with qualified clinical data registries 

without commenting on which 

exemptions and exclusions applied. 

The NPRM included the exemption at 

§ ll.104(e)(2), in part, to be responsive 

to section 511 of MACRA, but 

commenters expressed little support for 

this exemption, even for activities 

carried out by clinical data registries. 

Section 511 of MACRA has directed the 

Secretary of HHS to issue a clarification 

or modification with respect to the 

application of the Common Rule to 

activities involving clinical data 

registries, including quality 

improvement activities. With this final 

rule, the Secretary of HHS is providing 

that clarification here. Because clinical 

data registries are created for a variety 

of purposes, and are designed and used 

in different ways, there is no simple, 

single answer regarding how the 

Common Rule applies to clinical data 

registries. The Secretary of HHS has 

received advice from SACHRP on this 

topic, and SACHRP recommended that 

the pre-2018 rule was adequate to apply 

to clinical data registries without those 

registries being given any distinctive 

status. The Secretary of HHS believes 

that the same is true for the final rule, 

and so has not created a specific 

provision for clinical data registries. 

The final rule does not impose any 

requirements on a large portion of the 

activities related to clinical data 

registries. The following points are 

important: First, the rule does not apply 

to clinical data registry activities not 

conducted or supported by a Common 

Rule department or agency. Second, 

many clinical data registry activities, 

including many quality improvement 

activities, do not meet the definition of 

research, and so the Common Rule does 

not apply. For example, the creation of 

a clinical data registry designed to 

provide information about the 

performance quality of institutional care 

providers, and whose design is not 

influenced or altered to facilitate 

research, is not covered by this rule 

even if it is known that the registry will 

be used for research studies. Third, the 

Common Rule does not apply to a 

clinical data registry research study that 

only involves obtaining and analyzing 

nonidentified information because that 

activity would not involve a ‘‘human 

subject’’ as defined by the rule. Fourth, 

some clinical data registry research 

activities may qualify for exemption 

under the proposed provision at 

§ ll.104(d). Fifth, if an institution 

solely releases identifiable private 

information that was obtained in the 

course of patient clinical care to a 

clinical data registry for research, that 

institution is considered to be not 

engaged in human subjects research, 

and no requirements of the rule apply 

to that institution. 

In contrast, if investigators receive 

funding from a Common Rule 

department or agency to design a 

clinical data registry for research 

purposes and the registry includes 

identifiable private information, or 

involves interacting with individuals 

(e.g., a research survey), then such an 

activity involves human subjects 

research, but may be exempt if it meets 

one or more of the exemption categories 

under §ll.104(d)(7). Similarly, if 

investigators use federal support to 

obtain identifiable private information 

from a clinical data registry to conduct 

a research study, then such secondary 

research use of clinical registry 

information would involve human 

subjects research and the requirements 

of the rule would apply, although the 

research may qualify for exemption 

under §ll.104(d)(8). This is 

comparable to how the rule applies to 

a research study that involves chart 

review of identifiable private 

information drawn directly from 

hospital medical records. 

VI. Protection of Identifiable Private 

Information and Identifiable 

Biospecimens 

A. Background and Pre-2018 

Requirements 

Increasing research use of genetic 

information, information obtained from 

analysis of biospecimens, and the ability 

to more easily merge multiple sources of 

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administrative and survey datasets (e.g., 

medical records, claims data, vital 

records, and information about lifestyle 

behaviors from surveys) are some 

examples of how advances in research 

have increased the risks of data breaches 

that reveal identifiable private 

information. For example, the 

unauthorized release or use of 

information about subjects such as the 

disclosure of Social Security or 

Medicare numbers may pose financial 

risks, and disclosure of illegal behavior, 

substance abuse, or chronic illness 

might jeopardize subjects’ current or 

future employment, or cause emotional 

or social harm. 

Based on questions from and 

conversations with members of the 

regulated community, we are aware that 

IRBs are not always equipped with the 

expertise needed to evaluate risks to 

privacy and confidentiality, specifically 

regarding sophisticated IT security. 

However, we note that no data suggest 

that IRBs are currently approving 

research without requiring appropriate 

privacy and confidentiality safeguards. 

Despite this, we recognized that setting 

standards could assure appropriate 

privacy and confidentiality 

consideration and consequent 

protections to all research subjects, 

without the administrative burden of 

needing a specific committee review of 

the privacy and confidentiality 

protections of each study. To that end, 

the 2011 ANPRM suggested establishing 

mandatory data security and 

information protection standards for all 

studies that involve the collection, 

generation, storage, or use of identifiable 

or potentially identifiable information 

that might exist electronically or in 

paper form or be contained in a 

biospecimen. It put forward the idea 

that these standards might adopt the 

categories used in the HIPAA Rules and 

asked a series of questions about how 

best to protect private information. 

B. NPRM Proposal 

A goal of the NPRM was to ensure 

that researchers protect the privacy of 

their participants and the security of the 

data, calibrated to the likelihood of 

identifiability and sensitivity of the 

information being collected. The NPRM 

proposed to require that investigators 

and institutions conducting research 

subject to the Common Rule implement 

reasonable safeguards for protecting 

against risks to the security or integrity 

of biospecimens or identifiable private 

information. Given the significant 

concerns of public commenters about an 

idea discussed in the 2011 ANPRM of 

adopting the standards solely modeled 

on certain standards of the HIPAA 

Rules, the NPRM proposed several sets 

of standards, and allowed a choice 

about which set to use. 

First, the NPRM proposed that the 

Secretary of HHS could publish a list of 

specific measures that an institution or 

investigator could use to meet the 

security requirements. The list would be 

evaluated and amended, as appropriate, 

after consultation with other Common 

Rule departments and agencies. The 

proposed list would be published in the 

Federal Register, and public comment 

on the proposed list would be sought 

before the list was finalized. 

The specific safeguards that would be 

identified by the Secretary would be 

designed so that they could be readily 

implemented by the individual 

investigator, and could build on existing 

safeguards already in place to protect 

research data. These standards would 

include security safeguards to assure 

that access to physical biospecimens or 

data is limited only to those who need 

access for research purposes. The 

standards would also assure that access 

to electronic information is authorized 

only for appropriate use. Finally, the 

safeguards, collectively referred to as 

‘‘privacy safeguards,’’ would assure that 

information and biospecimens posing 

informational risks to subjects would be 

protected according to appropriate 

standards. 

Second, the NPRM proposed that if an 

institution or investigator is currently 

required to comply with the HIPAA 

rules, then the safeguards required by 

the Common Rule would be satisfied. 

No additional requirements were 

proposed to protect information subject 

to the HIPAA Rules. The NPRM also 

proposed to clarify that the proposed 

provisions would not amend or repeal 

the requirements of 45 CFR parts 160 

and 164 for the institutions or 

investigators to which these regulations 

apply pursuant to 45 CFR 160.102. 

Institutions or investigators that are not 

required to follow HIPAA could 

voluntarily implement the HIPAA Rules 

and be considered as satisfying the 

proposed requirements. The NPRM also 

proposed that for federal departments 

and agencies that conduct research 

activities that are or will be maintained 

on information technology that is 

subject to and in compliance with 

section 208(b) of the E-Government Act 

of 2002, 44 U.S.C. 3501 note, if all of the 

information collected, used, or 

generated as part of the activity will be 

maintained in systems of records subject 

to the Privacy Act of 1974, 5 U.S.C. 

552a, and the research will involve a 

collection of information subject to the 

Paperwork Reduction Act of 1995, 44 

U.S.C. 3501 et seq., the requirements 

would be satisfied. 

For purposes of informing the 

development of the proposed privacy 

safeguards, the NPRM sought comment 

on the types of safeguards that would be 

appropriate for the Secretary’s list. The 

NPRM also noted that additional 

statutes or acts mandate the protection 

of privacy and confidentiality of 

identifiable private information. It might 

be reasonable to include these as 

additional standards that would meet 

the proposed requirement if they were 

met in research that is subject to those 

standards or for which an investigator or 

institution has voluntarily elected to 

comply. Public comment was sought on 

whether any of these existing statutes or 

acts would serve the goals of proposed 

privacy safeguards. 

The NPRM also included conditions 

for use and disclosure of research 

information to other entities. It required 

that protections be in place when a 

biospecimen or identifiable private 

information is shared for appropriate 

research or other purposes. Unless 

required by law, the NPRM proposed to 

limit the re-disclosure of identifiable 

private information or release of 

biospecimens obtained for research. 

The NPRM asked for feedback on 

whether limiting re-disclosure to four 

specific circumstances unless such a 

disclosure was ‘‘required by law’’ would 

be too restrictive, or whether more 

permissive standards would better 

facilitate the NPRM goal of fostering the 

secondary research use of information. 

The NPRM also whether the proposed 

limitations on re-disclosure were more 

or less restrictive than necessary and 

whether there should be additional 

purposes for which release of 

biospecimens or re-disclosure of 

identifiable private information would 

be permitted should be allowed. 

The NPRM justified this change by 

arguing that its benefit would be that 

IRBs would not be required to review 

the individual plans for safeguarding 

information and biospecimens for each 

research study. Although the NPRM 

presumed that the proposed privacy 

safeguards would be sufficient, an IRB 

could determine that a particular 

activity would require more than what 

was proposed. Once IRBs became 

familiar with standard institutional and 

investigator-adopted protections, the 

NPRM anticipated that they would 

become more comfortable with the fact 

that they need not review every protocol 

for privacy safeguards. In addition, it 

was expected that if the proposed 

privacy safeguards were adopted, 

overall reduction in regulatory burden 

would occur because IRBs would not 

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have to review security provisions on a 

case-by-case basis. 

Finally, as discussed in Section V, the 

NPRM contained proposed exemptions 

that would have permitted a larger 

number of protocols to proceed without 

IRB review if specific conditions were 

met, conditioned on investigators and 

institutions also meeting the proposed 

privacy and security requirements. Note 

that there was no requirement for an IRB 

to determine whether investigators were 

adhering to the privacy safeguards for 

such exempt research. 

C. Public Comments 

Approximately 130 comments 

addressed the privacy safeguards, with 

a majority generally supporting the 

proposal. Both those who supported the 

proposal and those who opposed it 

indicated that it was difficult to 

comment on the adequacy of privacy 

standards that had yet to be developed. 

Those who supported the proposal 

stated that having standardized, 

minimum safeguards would create more 

consistency across IRBs in how 

biospecimens and identifiable private 

information are protected. Those who 

were opposed to the proposal stated that 

patient information is already covered 

by HIPAA security standards and 

student records are already covered by 

FERPA, arguing that these plus an array 

of other standards cover financial and 

various other types of sensitive 

information, making inclusion in the 

Common Rule redundant. 

However, several comments asserted 

that the HIPAA standards, while 

appropriate for health information, 

would not be appropriate for other types 

of research data. Others noted that the 

wide range and nature of research 

makes it too challenging to develop a 

blanket standard. With regard to 

applying the standards to exempt 

research, one large association of 

research universities, medical centers, 

and independent research institutes 

argued that research covered by the 

proposed exempt or excluded categories 

should be low risk and therefore third 

party evaluation of privacy safeguards 

was not needed. Several academic 

research institutions urged that if the 

security and privacy requirements were 

included in the final rule, then the 

measures should be as simple as 

possible. For example, they suggested 

developing a single set of standards for 

all identifiable data rather than 

calibrating the safeguards to the 

sensitivity of the information to be 

collected. 

A few comments addressed the 

proposed re-disclosure criteria. Of these, 

a majority indicated concerns with the 

NPRM redisclosure provision. Most of 

the opposition was specifically aimed at 

imposing the sharing criteria for 

nonidentified biospecimens. These 

commenters indicated that for sharing 

nonidentified biospecimens, imposing 

HIPAA-like privacy safeguards was 

unnecessary and would be extremely 

burdensome. Several comments 

suggested that the Common Rule adopt 

the same permissible uses and 

disclosures of information without 

authorization that exists under HIPAA. 

One scientific professional 

organization and more than 60 

institutions endorsing its comments 

noted that specific redisclosure 

considerations should exist for 

identifiable biospecimens, stating that 

redisclosure of the identity of the source 

of a biospecimen is appropriate in rare 

situations in which a confirmed 

research finding may have a significant 

impact on the health of the donor of the 

specimen. A large, private higher 

education institution noted that the 

limitations on use, release, and 

disclosure as proposed seemed at odds 

with the permissible uses and 

disclosures allowed under HIPAA. 

Others suggested that the language 

stating that biospecimens or identifiable 

private information could be released 

for any lawful purpose with the consent 

of the subject was too open-ended and 

permissive. One data privacy and 

security advocacy group also noted that 

the introductory language to the 

proposed safeguards could be read as 

requiring an investigator to release 

research biospecimens or disclose 

identifiable private information upon 

receipt of a valid request, as opposed to 

simply permitting an institution to do 

so. One academic research organization 

suggested an alternative approach—that 

the Federal Government clarify that 

institutions and networks may designate 

specialized privacy and security boards 

to review safeguards. 

D. Response to Comments and 

Explanation of the Final Rule: Privacy 

and Security Protections 

The final rule does not adopt the 

privacy and security protections 

proposed in the NPRM, but rather 

retains and acknowledges the IRB’s role 

in ensuring that privacy safeguards are 

appropriate for the research studies that 

require IRB review. To better ensure that 

appropriate privacy protections are 

required by IRBs, the final rule includes 

a new provision in the IRB review and 

approval criteria at §ll.111(a)(7)(i) 

that requires the Secretary of HHS in 

consultation with OMB and the 

Common Rule departments and 

agencies to issue guidance o assist IRBs 

in assessing what provisions are 

adequate to protect the privacy of 

subjects and to maintain the 

confidentiality of data. This requirement 

is discussed in more detail in Section 

XI. 

Although we continue to believe that 

appropriately protecting the privacy of 

human subjects who provide 

identifiable private information and 

identifiable biospecimens as well as 

preventing security breaches is critically 

important, we agree with the public’s 

concerns about requiring adherence to 

privacy and security standards when the 

safeguards to be issued by the Secretary 

of HHS have yet to be developed. The 

federal privacy and security laws would 

apply only to certain federally 

conducted research. Rather than 

promulgate a regulation that lacked 

sufficient specificity, we determined it 

would be preferable to maintain the 

requirement that IRBs review research 

studies to ensure that appropriate 

privacy and security safeguards are in 

place to protect research subjects, but 

include a commitment that the 

Secretary of HHS will issue guidance to 

assist IRBs in appropriately protecting 

subjects’ privacy and confidentiality. 

This guidance would take into 

consideration, among other things, the 

level of identifiability and sensitivity of 

the information being collected. 

Although IRBs were not specifically 

designed to evaluate risk to privacy and 

confidentiality and the adequacy of 

safeguards to protect against those risks, 

IRBs have been responsible for 

evaluating such risks under the pre2018 rule. We believe that guidance in 

this complex and evolving area will 

assist IRBs to identify appropriate 

protections, and may be better able than 

standardized protections, to address the 

variety of privacy and confidentiality 

concerns that arise in the broad range of 

research studies that are being carried 

out now and those that will be 

conducted in the years to come. 

As discussed in Section V, certain 

NPRM exemption proposals required 

the application of the NPRM’s proposed 

safeguards in whole or in part. To 

accommodate the fact that the final rule 

does not include the privacy safeguards, 

exemption categories in the final rule 

that are predicated on the need for some 

type of privacy safeguards will instead 

require that an IRB conduct a limited 

review to ensure that adequate 

provisions are in place to protect the 

privacy of subjects and to maintain the 

confidentiality of data. 

The final rule exemptions subject to 

this limited IRB review requirement are: 

• The exemption for research that 

includes only interactions involving 

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educational tests, survey procedures, 

interview procedures, or observations of 

public behavior regardless of the 

identifiability or sensitivity of the 

information collected/recorded 

(§ ll.104(d)(2)(iii)); 

• The exemption for research 

involving benign behavioral 

interventions in conjunction with the 

collection of information from an adult 

subject through verbal or written 

responses or video recording (regardless 

of the identifiability or sensitivity of the 

information collected/recorded 

(§ ll.104(d)(3)(i)(C)); 

• The exemption for the storage or 

maintenance of identifiable private 

information or identifiable 

biospecimens for which broad consent 

is required, when there is a change 

specific to the research activity in how 

the identifiable private information or 

identifiable biospecimens are stored and 

maintained (§ll.104(d)(7)); and 

• The exemption for the secondary 

research use of identifiable private 

information or identified biospecimens 

for which broad consent is required 

(§ ll.104(d)(8)) 

VII. IRB Membership and Modification 

to References to Vulnerability 

(§§ ll.107(a), ll.111(a)(3), and 

ll.111(b)) 

A. Background and Pre-2018 

Requirements 

The pre-2018 rule stipulated a 

condition of IRB membership at 

§ ll.107(a) stating that IRBs should 

aim for membership that does not 

consist entirely of individuals of one 

gender, race, or cultural background. It 

referred again to the characteristics of 

IRB members at §ll.107(b), stating 

that efforts should be made to ensure 

that no IRB consists entirely of members 

of one gender or one profession. 

The pre-2018 rule also referred to the 

concept of vulnerability and 

consideration of vulnerable populations 

in three provisions, one of which 

pertained to IRB membership 

(§ ll.107(a)), one with regard to 

selection of subjects (§ll.111(a)(3)), 

and one with regard to additional 

protections needed for subjects 

vulnerable to coercion or undue 

influence (at § ll.111(b)). Under the 

pre-2018 rule, only §ll.111(b) of the 

three provisions specifically referred to 

vulnerability to coercion or undue 

influence as the type of vulnerability 

that should be considered. In addition, 

of these same three provisions in the 

pre-2018 rule, only §ll.107(a) 

identified ‘‘handicapped’’ individuals as 

a vulnerable category of subjects. 

B. NPRM Proposal 

The NPRM proposed eliminating the 

pre-2018 rule stipulation that IRBs 

should aim for membership that does 

not consist entirely of individuals of one 

gender or profession because the 

requirement that IRB membership 

reflect members of varying backgrounds 

and diversity, including gender, 

accomplishes the same goal. 

Further, the NPRM proposed that the 

criterion at § ll.111(a)(3) be revised to 

align with the language of § ll.111(b) 

to reflect that the vulnerability of the 

populations in these research studies 

should be considered to be a function of 

the possibility of coercion or undue 

influence, and that this vulnerability 

alone should be the IRB focus of 

concern with respect to this criterion. 

The proposed change was intended to 

provide greater consistency and clarity 

in IRB consideration of vulnerability of 

subject populations in research 

activities and appropriate protections. A 

comparable change was also proposed at 

§ ll.107(a), pertaining to IRB 

membership. 

In addition, the NPRM proposed that 

the term ‘‘handicapped’’ be changed to 

‘‘physically disabled’’ individuals. 

Therefore, to enhance consistency and 

clarity among these three provisions, it 

was proposed that the term ‘‘physically 

disabled’’ be inserted at §ll.111(a)(3) 

and (b). This would mean that 

physically disabled persons would be 

among the individuals that the IRB may 

consider in determining that the 

selection of subjects is equitable 

(§ ll.111(a)(3)), and that the IRB may 

consider to be vulnerable to coercion or 

undue influence (§ ll.111(b)). Public 

comment was sought on whether 

pregnant women and those with 

physical disabilities should be 

characterized as vulnerable to coercion 

or undue influence. Whether or not 

these subpopulations are considered 

vulnerable to coercion or undue 

influence would not affect the 

applicability of subpart B. 

Finally, the NPRM proposed a change 

in §ll.107(a), involving the insertion 

of ‘‘economically or educationally 

disadvantaged persons’’ as an example 

of a vulnerable population, and 

requiring an IRB to give consideration to 

membership expertise in this area. This 

language was already included in the 

pre-2018 rule at §ll.111(a)(3) and 

§ ll.111(b). Adding this category of 

individuals to those who may be 

considered vulnerable to coercion or 

undue influence at §ll.107(a) was 

intended to create greater consistency 

among these three provisions. 

C. Public Comments 

Between 40 and 50 NPRM comments 

discussed the language describing 

vulnerable populations found in 

§§ ll.107(a), ll.111(a)(3), and (b). A 

majority of these comments only 

discussed the inclusion of pregnant 

women as an example of a population 

that might be vulnerable. Typically, 

comments addressed only one of the 

three questions posed in the NPRM 

about these provisions. The questions 

asked whether the §ll.111(a)(3) and 

(b) focus on issues related to coercion or 

undue influence in research with 

vulnerable populations, and no other 

considerations related to vulnerability, 

was appropriate; whether pregnant 

women and those with physical 

disabilities should be included in the 

category of subpopulations that may be 

vulnerable to coercion or undue 

influence; and, whether populations 

should be considered vulnerable for 

reasons other than vulnerability to 

coercion or undue influence. 

A majority of the comments stated 

that the inclusion of pregnant women as 

an example of a group that might be 

vulnerable to coercion or undue 

influence was inappropriate. These 

commenters noted that to suggest that 

noncognitive limitations make 

individuals inherently vulnerable is 

insulting to those populations. Of those 

comments that addressed these 

proposals, a minority discussed whether 

individuals with physical disabilities 

should be included as an example of a 

group that might be vulnerable to 

coercion and undue influence. As with 

pregnant women, these commenters 

stated that the insinuation that groups 

with physical disabilities might be 

inherently vulnerable to coercion and 

undue influence was insulting. One 

commenter noted that a physical 

condition might make one vulnerable to 

coercion or undue influence in the 

research context, but typically only 

when the research activity targets that 

vulnerability (as opposed to those 

populations always being vulnerable). 

In terms of whether other types of 

vulnerabilities should be considered by 

IRBs, public comment was mixed. Some 

commenters indicated that in the 

research context, the specific concerns 

with respect to vulnerable populations 

are limited to vulnerability to coercion 

and undue influence, while others 

noted that the regulations do not 

preclude an IRB from considering other 

types of vulnerability and that because 

of this flexibility, additional regulatory 

text was not necessarily needed. Groups 

specifically concerned with issues 

related to research involving Native 

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36HHS. SACHRP. Attachment: Recommendations 

Regarding Research Involving Individuals with 

Impaired Decision-making (2008, 2009). Retrieved 

from http://www.hhs.gov/ohrp/sachrp-committee/ 

recommendations/2009-july-15-letter-attachment/#. 

American populations noted that there 

are issues broader than vulnerability to 

coercion and undue influence that 

should be considered, such as 

vulnerability to group harms; one 

commenter recommended that 

populations be considered vulnerable as 

a result of being historically 

marginalized, such as native/tribal 

communities; lesbian, gay, bisexual, and 

transgender (LGBT) individuals; and 

racial and ethnic groups. 

Commenters who disagreed with this 

change generally felt that a history of 

societal marginalization, such as that 

experienced by LGBT groups or AI/AN 

tribes, should be a basis for determining 

vulnerability, and that a focus on only 

coercion or undue influence may be 

insufficient for IRB consideration. 

Several comments discussed the fact 

that using the term mentally disabled is 

potentially patronizing. One commenter 

suggested that instead of listing 

mentally disabled individuals as a 

group that might be vulnerable to 

coercion and undue influence, the 

regulations should use the term 

‘‘populations with impaired decision 

making ability.’’ This suggestion echoes 

a recommendation made by SACHRP in 

2009 as well.36

Another commenter stated that 

vulnerability status should be based on 

situational context, not on membership 

in a population, which potentially 

promotes stigmatization. Rather, focus 

should be more on the risk of the 

research and the situation of each 

subject when asked to participate in 

research. Finally, it was suggested that 

terminally ill patients who have 

exhausted all standard therapies, and 

possibly other research interventions, 

should be considered vulnerable. 

D. Response to Comments and 

Explanation of the Final Rule: 

References to Vulnerability 

A majority of comments agreed that 

the focus on issues related to coercion 

or undue influence, and no other 

considerations related to vulnerability, 

was appropriate. We agree with this 

assessment, and have retained this 

language in the final rule. We believe 

this change will help guide IRBs when 

assessing the type of vulnerability that 

should be the focus of review. We note 

that the § ll.111(a)(3) approval 

criterion retains the reference to the 

purposes of the research and the setting 

in which it is conducted because these 

considerations are also relevant to the 

assessment of the equitable selection of 

subjects, and may include factors such 

as societal marginalization or 

discrimination. 

The language at the three provisions 

(§ ll.107(a), §ll.111(a)(3), and 

§ ll.111(b)) has been made identical 

in referring to vulnerability as meaning 

vulnerability to coercion and undue 

influence, in recognition that coercion 

or undue influence refers to the ability 

to make an informed decision about 

participating in research. 

We agree with comments that said 

that the list of example vulnerable 

populations listed in the pre-2018 rule 

is out of date. 

In agreement with the majority of 

comments, the final rule no longer 

includes pregnant women or 

‘‘handicapped’’ or physically disabled 

individuals as examples of populations 

that are potentially vulnerable to 

coercion or undue influence. Adopting 

a suggestion from public comment and 

SACHRP, the final rule uses the term 

‘‘individuals with impaired decisionmaking ability’’ to replace the term 

‘‘mentally disabled persons.’’ 

VIII. IRB Functions and Operations 

(§ ll.108) 

A. Background and Pre-2018 

Requirements 

The pre-2018 rule outlined IRB 

functions and operations at §§ll.103 

and ll.108. 

B. NPRM Proposals 

The NPRM contained several 

proposals for changes in IRB functions 

and operations. Of relevance here, the 

requirements for recordkeeping by IRBs 

would no longer appear in § ll.103 of 

the rule but in §ll.108. Much of the 

discussion related to these changes 

appears in Section IV regarding the 

assurance process. The issues are 

summarized here. 

The NPRM proposed that the 

requirement that a written assurance 

include a list of IRB members for each 

IRB designated under the assurance 

process be replaced. In its place, the 

NPRM proposed that the assurance 

include a statement for each designated 

IRB, prepared and maintained by the 

institution, or when appropriate the 

IRB, with a current detailed list of the 

IRB members including information 

sufficient to describe each member’s 

chief anticipated contributions to IRB 

deliberation; and any employment or 

other relationship between each 

member and the institution. The 

regulatory requirement at 

§ ll.103(b)(3) that changes in IRB 

membership be reported to the 

department or agency head, or to OHRP 

when the existence of an HHS-approved 

assurance is accepted, would be deleted, 

eliminating the requirement. Instead, an 

institution would be required under 

proposed §ll.108(a)(2) to maintain a 

current IRB roster, but such a roster 

would not need to be submitted to 

OHRP or other agency managing the 

assurance of compliance process. 

The NPRM also proposed to eliminate 

the requirement in §ll.103(b)(2) that 

an institution designate one or more 

IRBs on its FWA established in 

accordance with the Common Rule. The 

requirement in the pre-2018 Common 

Rule at § ll.103(b)(2) that IRBs have 

sufficient meeting space and staff to 

support IRB reviews and record keeping 

requirements was moved in the NPRM 

to §ll.108(a)(1). Note that under this 

proposal federal departments or 

agencies would retain the ability to ask 

for information about which IRBs 

review research conducted at an 

institution as part of the assurance 

process. 

C. Public Comments 

Approximately 10 comments were 

received on these proposals. Of those, 

all supported the NPRM proposal that 

changes in IRB membership no longer 

needed to be reported to the funding 

department or agency. All commenters 

supported the proposal that IRBs would 

simply need to prepare and maintain a 

current list of IRB members. 

Commenters agreed that the proposed 

changes to the IRB roster requirement 

would reduce administrative burden 

without having any significant impact 

on the protection of human subjects. 

Those who commented on the proposed 

deletion of the requirement to designate 

one or more IRBs on an institution’s 

FWA generally supported the proposal. 

No comments were received on the 

proposed movement of IRB policy and 

recordkeeping requirements from 

§ ll.103 to § ll.108. 

D. Explanation of the Final Rule: IRB 

Functions and Operations 

The final rule adopts the NPRM 

proposals to move the IRB 

recordkeeping requirements from 

§ ll.103(b)(3), (4), and (5) to 

§ ll.108(a)(2), (3), and (4). (See 

Section IV regarding changes to 

§ ll.103 as well.) The final rule also 

adopts the NPRM proposal that IRBs 

must maintain an accurate list of IRB 

members but are not required to submit 

changes to that roster to the funding 

department or agency. The final rule 

also adopts the NPRM proposal to delete 

the requirement in the pre-2018 rule 

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37Office for Human Research Protections. 

Categories of Research That May Be Reviewed by 

the Institutional Review Board (IRB) through an 

Expedited Review Procedure. November 9, 1998. 

Retrieved from http://www.hhs.gov/ohrp/policy/ 

expedited98.html. 

that institutions designate one or more 

IRBs on that institution’s FWA. 

IX. IRB Review of Research (§ ll.109) 

A. Background and Pre-2018 

Requirements 

The pre-2018 rule listed four areas of 

responsibility for IRBs in the review 

process concerning their authority to 

approve, request modification, or 

disapprove research activities; ensure 

informed consent requirements are met 

(including documentation or waiver, as 

relevant); notify investigators of their 

determinations; and conduct continuing 

review of research. The rule at 

§ ll.109(a) stated that IRBs have the 

authority to carry out these 

responsibilities for all research activities 

covered by the policy. 

In particular, the pre-2018 rule at 

§ ll.109(e) required that IRBs conduct 

continuing review of research covered 

by this policy at intervals appropriate to 

the degree of risk, but not less than once 

per year. Except when an expedited 

review procedure was used, continuing 

review of research was to occur at 

convened meetings at which a majority 

of the IRB members are present, 

including at least one member whose 

primary concerns are in nonscientific 

areas. 

An IRB could use an expedited review 

procedure to conduct continuing review 

of research for some or all of the 

research appearing on the list of 

research eligible for expedited review 37

and found by the reviewer(s) to involve 

no more than minimal risk. The 

Common Rule departments and 

agencies could restrict, suspend, 

terminate, or choose not to authorize an 

IRB’s use of the expedited review 

procedure (§ll.110(d)). 

B. NPRM Proposals 

The NPRM proposed clarifying that 

the Common Rule does not give IRBs 

the authority to review or approve, 

require modification in or disapprove 

research that qualifies for the 

exemptions proposed in the NPRM. 

The NPRM also proposed to eliminate 

continuing review for many minimal 

risk studies (namely those that qualify 

for expedited review), unless the 

reviewer documents why continuing 

review should take place, which would 

be required according to the NPRM. 

Moreover, for studies initially reviewed 

by a convened IRB, continuing review 

would not be required, unless 

specifically mandated by the IRB, after 

the study reaches the stage where it 

involves only one or both of the 

following: (1) Analyzing data (even if it 

is identifiable private information); or 

(2) accessing follow-up clinical data 

from procedures that subjects would 

undergo as part of standard care for 

their medical condition or disease. 

In addition, the NPRM proposed that 

continuing review would not be 

required for research involving certain 

secondary research using information 

and biospecimens that requires limited 

IRB review in order to qualify for an 

exemption proposed in the NPRM. 

Further, the NPRM proposed that an 

IRB must receive annual confirmation 

that research is ongoing and that no 

changes have been made that would 

require the IRB to conduct continuing 

review (that is, the study still qualifies 

for expedited review because it still 

meets the criteria listed above and still 

involves no greater than minimal risk). 

The NPRM also proposed a new 

requirement for IRBs to maintain 

records of continuing reviews. Because 

the NPRM proposed a new provision 

that eliminates the need for continuing 

review under specific circumstances, it 

also proposed that IRBs need to justify 

the need for continuing review in cases 

where it was not required. If an IRB 

chooses to conduct continuing review 

even when these conditions are met, the 

NPRM stated that the rationale for doing 

so must be documented. 

C. Public Comments 

Approximately four comments 

addressed the clarification proposed in 

the NPRM that IRBs were not authorized 

by this policy to review exempt 

research. All who commented opposed 

the proposed modification. Those who 

commented were concerned that IRBs 

and institutions would interpret the 

modifications to mean that IRBs were 

precluded from ever reviewing such 

research and pointed to the possibility, 

although rare, that there might be a need 

to do so, particularly if the initial 

exemption determination was flawed. 

With regard to continuing review, 

approximately 120 comments discussed 

this proposal. A strong majority of 

comments (approximately 95) supported 

this proposal and approximately 15 

opposed it. Other comments were 

mixed. Those who supported the 

proposal said that it would indeed 

alleviate IRB administrative burden 

without diminishing the protections 

afforded to human subjects. Those who 

did not support this proposal believed 

the continuing review process served an 

important role in allowing an institution 

to periodically re-evaluate the benefits, 

risks, methods, and procedures used in 

research activities, and whether the 

research had been modified without 

approval. Some commenters who 

supported the proposal were opposed to 

the requirement for annual confirmation 

to the IRB that such research is ongoing 

and that no changes have been made 

that would require the IRB to conduct 

continuing review. They stated that the 

burden alleviated by eliminating the 

need for continuing review was offset by 

the requirement to submit an annual 

confirmation. 

D. Response to Comments and 

Explanation of the Final Rule: Review of 

Research 

The final rule at §ll.109(a) 

modifies the language of the pre-2018 

rule to state that IRBs review and have 

the authority to approve, require 

modifications in, or disapprove all 

research activities covered by this 

policy, including exempt research 

activities under § ll.104 for which 

limited IRB review is a condition of 

exemption (§ll.104(d)(2)(iii), 

§ ll.104(d)(3)(i)(C), §ll.104(d)(7), 

and §ll.104(d)(8)). Since the final 

rule requires limited IRB review for 

certain categories of exempt research, 

the provision at §ll.109(a) has been 

modified to clarify that IRBs have the 

authority needed to conduct limited IRB 

review. 

As proposed in the NPRM, and as 

generally supported in public 

comments, continuing review is 

eliminated for all studies that undergo 

expedited review, unless the reviewer 

explicitly justifies why continuing 

review would enhance protection of 

research subjects (§ ll.109(f)(1)(i) and 

§ ll.115(a)(3)). For studies initially 

reviewed by a convened IRB, once 

certain specified procedures are all that 

remain for the study, continuing review 

would not be required, unless 

specifically mandated by the IRB. These 

activities include: (1) Research eligible 

for expedited review in accordance with 

§ ll.110; or (2) Research that has 

progressed to the point that it involves 

only one or both of the following, which 

are part of the IRB-approved study: (a) 

Data analysis, including analysis of 

identifiable private information or 

identifiable biospecimens, or (b) 

Accessing follow-up clinical data from 

procedures that subjects would undergo 

as part of clinical care (at §ll.109(f)). 

In addition, the final rule states at 

§ ll.109(f)(1)(ii) that continuing 

review is not required for research 

reviewed in accordance with the limited 

IRB review procedure described in 

§ ll.104(d)(2)(iii), 

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38HHS. OHRP. Categories of Research That May 

Be Reviewed by the Institutional Review Board 

(IRB) through an Expedited Review Procedure. 

November 9, 1998. Retrieved from http://

www.hhs.gov/ohrp/policy/expedited98.html. 

§ ll.104(d)(3)(i)(C), §ll.104(d)(7), 

or §ll.104(d)(8). 

The final rule does not require 

investigators to provide annual 

confirmation to the IRB that such 

research is ongoing and that no changes 

have been made that would require the 

IRB to conduct continuing review. 

Institutions that choose to require some 

accounting of ongoing research not 

subject to continuing review have 

significant flexibility in how they 

implement their own requirements. 

Note that under the final rule, 

investigators would still have the 

current obligations to report various 

developments (such as unanticipated 

problems or proposed changes to the 

study) to the IRB. 

X. Expedited Review Procedures 

(§ ll.110) 

A. Background and Pre-2018 

Requirements 

Under the pre-2018 rule, a research 

study could receive expedited review if 

the research activities to be conducted 

appear on the list of activities published 

by the Secretary of HHS that are eligible 

for such review,38 and was found by the 

reviewer(s) to involve no more than 

minimal risk. Under an expedited 

review procedure, the review could be 

carried out by the IRB chairperson or by 

one or more experienced reviewers 

designated by the chairperson from 

among the members of the IRB. 

Research that was eligible for expedited 

review required continuing review at 

least annually. 

B. NPRM Proposals 

The NPRM proposed changes 

regarding expedited review, to allow 

expedited review to occur for studies on 

the Secretary’s list unless the 

reviewer(s) determine(s) that the study 

involves more than minimal risk. This 

was in contrast to the pre-2018 

regulations, which required that an IRB 

use the expedited review procedure 

only if the reviewer determines (and 

documents) that the research involves 

no more than minimal risk. In addition, 

OHRP has indicated that the activities 

on the current list should not be deemed 

to be of minimal risk simply because 

they are included on the list. In a related 

change, the NPRM contained a 

requirement that IRBs document the 

rationale for an expedited reviewer’s 

determination that research appearing 

on the expedited review list is more 

than minimal risk (i.e., an override of 

the presumption that studies on the 

Secretary’s list are minimal risk). 

The NPRM proposed that IRBs 

reviewing the consent process (and, 

when required, the privacy safeguards) 

for studies eligible for the proposed 

exemption at § ll.104(f)(1) could use 

the expedited review procedure. 

As discussed in Section III of this 

preamble, the NPRM did not propose to 

modify the definition of minimal risk, 

but rather proposed adding to the 

definition a requirement that the 

Secretary of HHS create and publish a 

list of activities that qualify as ‘‘minimal 

risk’’. This Secretary’s list would be reevaluated periodically, but at least every 

8 years, based on recommendations 

from federal departments and agencies 

and the public. Note that this would not 

be an exhaustive list of all activities that 

would be considered minimal risk 

under the Common Rule, but would 

allow IRBs to rely on the determination 

of minimal risk for activities appearing 

on the list. IRBs would still need to 

make minimal risk determinations about 

activities that do not appear on this list. 

In addition, the NPRM proposed to 

eliminate the parenthetical phrase ‘‘of 

one year or less’’ when referring to the 

IRB approval period, since annual 

continuing review of research eligible 

for expedited review would no longer be 

required. 

The NPRM also proposed that the 

regulations be revised to require 

evaluation of the list of expedited 

review categories every 8 years, 

followed by publication in the Federal 

Register and solicitation of public 

comment. A revised list would be 

prepared for public comment outside 

the scope of the NPRM. 

C. Public Comments 

Approximately 50 comments were 

received regarding the proposal to 

update the Secretary’s list of expedited 

review categories every 8 years. A strong 

majority supported this proposal 

although some recommended that the 

mandatory period of review occur more 

frequently than every 8 years. 

Approximately 10 comments 

discussed the NPRM proposal that an 

IRB may use the expedited review 

procedure to satisfy limited IRB review 

of the consent process as required under 

the proposed NPRM exemption. A 

strong majority of these comments 

supported this proposal. 

D. Response to Comments and 

Explanation of the Final Rule: 

Expedited Review Procedures 

Under the final rule, a study is 

deemed to be minimal risk and thus 

eligible for expedited review if the study 

only involves activities on the 

Secretary’s list, unless the reviewer 

determines and documents that the 

study involves more than minimal risk 

(§ ll.110(a) and (b)(1)). Thus, we 

anticipate that more studies that involve 

no more than minimal risk will undergo 

expedited review, rather than full 

review, which will relieve burden on 

IRBs. 

Further, IRBs will be required to 

document their rationale when they 

override the presumption that studies 

on the Secretary’s expedited review list 

involve greater than minimal risk (at 

§ ll.115(a)(8)). Although public 

comments argued that this 

documentation represented an 

unjustified burden on IRBs, we believe 

that such documentation could provide 

a basis for the Secretary’s future 

determinations about the 

appropriateness of the list, and allow for 

greater consistency across institutions, 

and thus make the Common Rule more 

just. 

At §ll.110(b)(1)(iii) the final rule 

adopts the NPRM proposal that an IRB 

may use the expedited review process 

when conducting limited IRB review as 

required by the exemptions at 

§ ll.104(d)(2)(iii), 

§ ll.104(d)(3)(i)(C), §ll.104(d)(7), 

and §ll.104(d)(8). 

Finally, as proposed in the NRPM, 

evaluation of the list of expedited 

review categories will occur every 8 

years, followed by publication in the 

Federal Register and solicitation of 

public comment. 

XI. Criteria for IRB Approval of 

Research (§ll.111) 

A. Background and the Pre-2018 

Requirements 

The determinations that an IRB must 

make before it can approve a study were 

spelled out in the pre-2018 rule at 

§ ll.111. These relate, among other 

things, to minimizing risks to subjects, 

determining that an appropriate 

relationship exists between risks and 

benefits, and ensuring the equitable 

selection of subjects. The regulations 

generally required all of these 

determinations to be made for any study 

that must undergo IRB review. 

B. NPRM Proposals 

The NPRM proposed a number of 

changes regarding the criteria for IRB 

approval of research, including (1) 

creating a new form of IRB review for 

activities relating to storing or 

maintaining data and biospecimens for 

later secondary use; (2) revising two of 

the existing criteria for approval of 

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39http://www.hhs.gov/ohrp/sachrp-committee/ 

recommendations/attachment-b-return-individualresearch-results/index.html. 

research that have special 

considerations related to the 

involvement of vulnerable populations 

and for privacy and confidentiality of 

data provisions; and (3) adding a 

provision about plans to review the 

return of individual results to 

participants. 

The first set of changes concerned 

updating the IRB review criteria for 

research activities relating to storing or 

maintaining information and 

biospecimens, and to the secondary use 

of such information and biospecimens. 

Paragraph (a)(9)(i) of proposed 

§ ll.111 would have applied to a 

proposed exemption at §ll.104(f)(1) 

for storing or maintaining biospecimens 

or identifiable private information for 

use in secondary research. This 

provision would have eliminated the 

need for an IRB to make the usual 

determinations about such an activity. 

Instead, the IRB would have been 

required to determine that the 

procedures for obtaining broad consent 

to storing or maintaining the 

biospecimens or information were 

appropriate, and met the standards 

included in the introductory paragraph 

of §ll.116. In addition, if these 

storage and maintenance activities 

involved a change for research purposes 

from the way the biospecimens or 

information had been stored or 

maintained, then the IRB would have 

needed to determine that the proposed 

biospecimen and privacy safeguards at 

§ ll.105 were satisfied for the creation 

of any related storage database or 

repository. 

The second proposed change was 

related to the NPRM privacy safeguard 

proposal and clarified that it would not 

be an IRB responsibility to review the 

security plans for biospecimens and 

identifiable private information for 

every protocol (i.e., on a case-by-case 

basis). Also, as discussed in Section VII, 

the NPRM proposed changing how 

vulnerable populations are referred to in 

the regulatory language at 

§ ll.111(a)(3). 

The third proposed change was the 

addition of section (a)(8) to § ll.111 

clarifying that if an investigator submits 

as part of the protocol a plan for 

returning clinically relevant research 

results to subjects, the IRB would have 

to evaluate the appropriateness of the 

plan. This criterion was proposed in 

response to public discussions, 

including SACHRP, recommending that 

IRBs consider returning individual 

results to subjects.39

C. Public Comments 

Approximately 20 comments 

discussed the proposed modifications in 

§ ll.111 related to the criteria for IRB 

approval of research. Of these 

comments, a majority discussed the 

proposal that an IRB be required to 

review the adequacy of plans to return 

research results, should a proposed 

study include such a plan. Comments 

on this proposal were mixed, with both 

those opposing and supporting the 

proposal indicating that HHS and other 

Common Rule departments and 

agencies would need to issue detailed 

guidance addressing what is considered 

an adequate plan in this context. Several 

commenters suggested deleting this 

provision due to the lack of clarity 

surrounding the IRB’s role in such a 

review. 

D. Response to Comments and 

Explanation of the Final Rule: Criteria 

for IRB Approval of Research 

The final rule does not adopt all of the 

NPRM proposals. It does not include the 

NPRM proposal regarding IRB review of 

plans to review the return of clinically 

relevant results to subjects. This 

proposal was deleted due to concern 

over the criteria that would be required 

for an IRB to appropriately consider this 

area, the need for particular IRB 

expertise to appropriately assess the 

return of results, and ambiguity over the 

meaning of ‘‘clinically relevant.’’ 

The final rule does, however, revise 

two of the existing criteria for approval 

of research: (1) Special considerations 

related to the involvement of vulnerable 

populations, and (2) privacy and 

confidentiality of data provisions. 

As discussed in more detail in Section 

VII, the language regarding vulnerable 

populations at § ll.111(a)(3) and (b) 

has been revised to reflect the current 

understanding of which populations 

should receive special consideration 

due to potential vulnerabilities specific 

to the purposes and context of human 

subjects studies and to parallel other 

references to vulnerable populations 

found at § ll.107(a). 

Section ll.111(a)(7) in the final rule 

retains the pre-2018 language, but also 

adds an additional requirement, thereby 

serving a dual function as both the 

primary regulatory provision requiring 

IRB review of the adequacy of 

protections for the privacy of subjects 

and confidentiality of identifiable 

private information (including that 

obtained from the analysis of 

biospecimens), and as the primary 

limited IRB review requirement needed 

to satisfy certain exemption 

determinations in § ll.104(d). 

In §ll.111(a)(7)(i) the Secretary of 

HHS commits to issuing guidance to 

assist IRBs in assessing what provisions 

are adequate to protect the privacy of 

subjects and to maintain the 

confidentiality of information, after 

consultation with OMB’s privacy office 

and other federal departments and 

agencies that have adopted this policy. 

This modification is intended to serve a 

similar function as the privacy 

safeguards proposed in the NPRM (but 

not adopted in the final rule). The 

guidance might address the following 

considerations such as: 

• The extent to which identifiable 

private information is or has been deidentified and the risk that such deidentified information can be reidentified; 

• The use of the information; 

• The extent to which the information 

will be shared or transferred to a third 

party or otherwise disclosed or released; 

• The likely retention period or life of 

the information; 

• The security controls that are in 

place to protect the confidentiality and 

integrity of the information; and 

• The potential risk of harm to 

individuals should the information be 

lost, stolen, compromised, or otherwise 

used in a way contrary to the contours 

of the research under the exemption. 

The final rule at §ll.111(a)(8) 

modifies the NPRM proposal on the 

limited IRB review required by 

§ ll.104(d)(7). Section ll.111(a)(8) 

specifies that for the purposes of 

conducting the limited IRB review 

required by § ll.104(d)(7), the IRB 

must determine that broad consent for 

storage, maintenance, and secondary 

research use of identifiable 

biospecimens or identifiable private 

information is obtained in accordance 

with the requirements of 

§ ll.116(a)(1)–(4), (a)(6), and (d). As 

part of its review of these requirements 

for broad consent, the IRB would review 

the appropriateness of the process 

proposed for obtaining broad consent, 

and ensure that the required elements of 

broad consent were appropriately 

included in the broad consent form (or 

process, if broad consent is to be 

obtained orally). Additionally, the IRB 

must determine that consent is 

appropriately documented, or that a 

waiver of documentation is appropriate, 

in accordance with §ll.117. Finally, 

if a change is made for research 

purposes in the way identifiable private 

information or identifiable 

biospecimens are stored or maintained, 

the IRB must determine that adequate 

provisions are in place to protect the 

privacy of subjects and to maintain the 

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40SACHRP’s public comment to the NPRM is 

available here: https://www.hhs.gov/ohrp/sachrpcommittee/recommendations/2016-january-5- 

recommendation-nprm-attachment-a/index.html. 

confidentiality of data. It is expected 

that the guidance to be developed by the 

Secretary of HHS about protecting the 

privacy of subjects and maintaining the 

confidentiality of data will also be 

applicable to the privacy and 

confidentiality considerations included 

in this limited IRB review requirement. 

XII. Cooperative Research (§ ll.114) 

A. Background and Pre-2018 

Requirements 

The pre-2018 rule required that each 

institution engaged in a cooperative 

research study obtain IRB approval of 

the study, although it did not require 

that a separate local IRB at each 

institution conduct such review. In 

many cases, however, a local IRB for 

each institution would independently 

review the research protocol, and 

informed consent forms and other 

materials, often resulting in multiple 

reviews for one study. When any one of 

these IRBs would require changes to the 

research protocol that are adopted for 

the entire study, investigators would 

have to re-submit the revised protocol to 

all of the reviewing IRBs. This process 

could take many months and 

significantly delay the initiation of 

research projects and recruitment of 

subjects into studies. More importantly, 

little evidence has suggested that the 

time and effort put into these activities 

by investigators (in providing materials 

to IRBs) and IRBs have significantly 

increased the well-being of research 

subjects. 

B. NPRM Proposals 

Taking into consideration the history 

of public debate on this topic and 

various sources of public comments, the 

NPRM proposed a requirement 

mandating that all institutions located 

in the United States engaged in 

cooperative research rely on a single IRB 

as their reviewing IRB for that study. 

Under this proposal, this requirement 

would not apply to: (1) Cooperative 

research for which more than single IRB 

review is required by law; or (2) 

research for which the federal 

department or agency supporting or 

conducting the research determines and 

documents that the use of a single IRB 

is not appropriate for the particular 

study. Public comment was sought on 

whether it would be useful for this 

requirement to include criteria that 

federal departments or agencies would 

need to apply in determining whether to 

make exceptions to the use of a single 

IRB requirement and what those criteria 

might be. Further the public was asked 

whether the exceptions proposed were 

appropriate and sufficient, or whether 

this mandate should have additional 

exceptions for single IRB review than 

those proposed in the NPRM. 

The change proposed by the NPRM 

would apply only to U.S.-conducted 

portions of studies because the 

flexibility to make use of local IRB 

reviews at international sites should be 

maintained. It might be difficult for an 

IRB in the United States to adequately 

evaluate local conditions in a foreign 

country that could play an important 

role in the ethical evaluation of the 

study. 

This policy would apply regardless of 

whether the study underwent convened 

review or expedited review. Under the 

NPRM, the IRB of record would be 

expected to be selected either by the 

funding agency or, if there is no funding 

agency, by the lead institution 

conducting the study. An agency may, 

but is not required, to solicit input 

regarding which IRB would be most 

appropriate to designate as the IRB of 

record. Public comment was sought on 

how this would work in practice. 

This policy would not relieve any site 

of its other obligations under the 

regulations to protect human subjects. 

Nor would it prohibit institutions from 

choosing, for their own purposes, to 

conduct additional IRB or other 

administrative reviews, though such 

reviews would no longer have any 

regulatory status in terms of compliance 

with the Common Rule. 

Some concerns about a mandated 

single IRB review for cooperative 

research point to implementation 

logistics, and the time necessary to 

establish new policies, procedures, and 

agreements. Recognizing this concern, 

the proposed compliance date was 3 

years from the publication of the final 

rule. Public comment was sought on 

whether this was a realistic timeframe. 

The public was asked to comment on 

whether mandated single IRB review for 

all cooperative research was a realistic 

option, and what the likely costs and 

benefits to institutions might be. 

Further, the public was asked to 

comment on whether additional 

resources would be necessary to meet 

this requirement in the short term and 

whether savings might be anticipated in 

the long run. Finally, public comment 

was sought regarding in what areas 

guidance would be needed for 

institutions to comply with this 

requirement and whether the Common 

Rule departments and agencies could 

take actions to address concerns about 

institutional liability, such as 

developing model written agreements. 

C. Public Comments 

This proposal was one of the most 

commented on in the NPRM, receiving 

more than 300 comments. Public 

comment was divided on whether a 

final rule should implement the 

proposal to mandate one IRB of record 

in domestic cooperative research 

studies. Of those who commented on 

this proposal, approximately 130 

supported the proposal, and 

approximately 140 opposed it. Others 

had mixed views. 

Research institutions tended to 

oppose this proposal, while individuals 

(i.e., those who were not providing 

comment in an official institutional 

capacity) and scientific organizations 

tended to support the proposal. A strong 

majority of those who opposed the 

proposal indicated that the final rule 

should encourage, rather than mandate, 

a single IRB of record in cooperative 

research studies. Arguments against the 

proposal cited the need for local review 

and potential loss of accountability, as 

well as operational issues such as the 

increased administrative capacity and 

technological systems required for a site 

to function effectively as a single IRB. 

One comment stated that mandated 

single IRB review would not eliminate 

the challenges associated with multiinstitutional trials. The commenter 

argued that it would shift the burden 

from sponsors to investigators and at the 

institutional level, centralized systems 

would have to be developed and 

sustained in order to manage single IRB 

reviews. 

Some who supported the proposal 

stated that it would decrease 

administrative burdens and 

inefficiencies for investigators and 

institutions. Conversely, some 

commenters stated that the proposal 

should not be implemented because it 

would ultimately increase burdens and 

inefficiencies for investigators and 

institutions. 

In addition to the broad themes for 

and against this proposal, some 

commenters such as SACHRP noted that 

the proposed requirement seems 

premature at this time and suggested 

that more data are needed before such 

a provision could be implemented. 

Others said the scope of the proposal 

seemed overly broad. Many cited the 

alternative, narrower approach 

discussed in SACHRP’s public comment 

as a reasonable option.40 Further 

commenters stated that the lead 

institution likely would experience 

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increased costs if this proposal were 

implemented because of the obligations 

it would have to assume. In addition, 

some commenters said that the proposal 

does not address risk of liability to 

institutions and IRBs that are not 

considered the lead. 

Commenters also noted that long 

review times for prospective research 

studies are not solely related to the IRB 

review and approval itself. Rather, 

commenters noted that long review 

times are caused by the sum total of the 

many different types of reviews either 

mandated by other regulations or by 

institutional policy (e.g., radiation safety 

board review, privacy board review, 

departmental scientific review) that 

must be completed. These other reviews 

would likely not be affected by the 

NPRM proposal. 

Several commenters expressed 

concern that according to the NPRM 

proposal, the supporting federal 

department or agency would select the 

IRB of record as required by the 

provision. These commenters were 

concerned that the provisions did not 

seem to allow for grantee or awardee 

input on what IRB should be the IRB of 

record nor did they seem to suggest that 

funding departments or agencies should 

consult with the institutions receiving 

funding about the IRB of record. Several 

public comments also expressed 

concern about the burden this provision 

would place on nonfederally supported 

studies subject to the rule solely based 

on the clinical trials expansion 

proposed in the NPRM. 

Representatives of AI/AN tribes also 

provided comments emphasizing the 

sovereign status of their governments, 

and stating that nonlocal review would 

be inappropriate for their communities. 

D. Response to Public Comments and 

Explanation of the Final Rule: 

Cooperative Research 

The final rule adopts the NPRM 

proposal with modifications that are 

responsive to public comment. We agree 

with commenters who speculated that 

mandated single IRB review would 

ultimately decrease administrative 

burdens and inefficiencies for 

investigators and institutions, while 

acknowledging that the transition to this 

model would require significant time 

and an adjustment to institutional 

structures and policies. We concur that, 

rather than offering additional 

protections, in many cases multiple IRB 

approvals increase burden and 

frequently delay the implementation of 

studies, increasing the costs of clinical 

trials and potentially stalling access to 

new therapies. We note comments that 

expressed frustration with the frequent 

occurrence of central IRB participating 

sites insisting on separate institutional 

reviews. One comment noted that these 

additional IRB reviews generally reach 

the same conclusions, or conclusions 

with minor changes, that are then 

imposed solely on that site. When 

working optimally, we expect the 

central IRB model will work more 

efficiently and require less personnel 

time and fewer resources for tracking 

and implementing IRB changes and 

approvals, thereby eliminating the 

potential for unnecessarily duplicative 

reviews. 

Although a large number of comments 

believed that single IRB review should 

be encouraged rather than mandated, we 

feel that this incentivized approach 

would ultimately fail to yield 

substantive positive change in the 

system. Rather, systematic efficiencies 

have the best chance of occurring if 

single IRB review is required for all 

review in domestic research involving 

more than one institution. We 

acknowledge that further guidance for 

this requirement will need to be 

developed and that initial cost 

projections may have been low. 

However, we feel this change supports 

the best interests of the research 

infrastructure through increasing 

efficiency. Note that the final rule 

permits appropriate flexibilities that 

will assist in implementation. 

Institutions may still choose to conduct 

additional internal IRB reviews for their 

own purposes, though such reviews 

would no longer have any regulatory 

status in terms of compliance with the 

Common Rule. 

We agree with comments 

recommending that a greater role should 

be provided for grantee input on 

choosing the IRB of record, and have 

modified the language accordingly. The 

language at § ll.114(b)(1) now states 

that the reviewing IRB (i.e., the IRB of 

record) will be identified by the federal 

department or agency supporting or 

conducting the research, yet allows lead 

institutions to propose the reviewing 

IRB, subject to the acceptance of the 

federal department or agency supporting 

the research. This provision is 

consistent with the NIH single IRB 

policy, which was published on June 

21, 2016. 

This final rule adopts (in 

§ ll.114(b)(2)(i)) the NPRM’s proposal 

that cooperative research for which 

more than single IRB review is required 

by law is not subject to the requirements 

of §ll.114. The rule also adds 

clarifying language providing that this 

provision extends to tribal laws passed 

by the official governing body of an AI/ 

AN tribe. Thus, if the official governing 

body of an AI/AN tribe passes a tribal 

law that requires more than single IRB 

review for certain cooperative research, 

the requirement for single IRB review 

does not apply to such cooperative 

research. In addition, we highlight that 

§ ll.114(b)(2)(ii) allows a federal 

department or agency the flexibility to 

determine that the use of a single IRB is 

not appropriate for certain contexts, 

thereby permitting additional IRB 

review and consideration of local and 

regional variations in some 

circumstances. 

Finally, the final rule adopts the 

NPRM proposal for this provision to 

have a delayed compliance date of 3- 

years from the date the final rule is 

published in the Federal Register. This 

transition period is intended to allow 

the regulated community appropriate 

time and flexibility in adjusting to this 

new model. 

XIII. IRB Records (§ll.115) 

A. Background and Pre-2018 

Requirements 

The pre-2018 rule at §ll.115 

outlined requirements for IRBs in 

preparing and documenting its activities 

and for maintaining records. 

B. NPRM Proposals 

As discussed in Section IV, the NPRM 

proposed to revise the pre-2018 

requirement that an up-to-date list of the 

IRB members and their qualifications be 

included in an institution’s assurance. 

Instead, the NPRM proposed the 

requirement that an IRB or the 

institution prepare and maintain a 

current list of IRB members. 

As discussed in Section IX, the NPRM 

proposed a new requirement for IRBs to 

maintain, as part of their records of 

continuing reviews, the rationale for 

conducting continuing review of 

research that was deemed eligible for 

elimination of continuing review per 

proposed changes at §ll.109(f)(1)(ii). 

Specifically, this would apply to 

research that had progressed to the 

point that it involves only one or both 

of the following, which are part of the 

IRB-approved study: (1) Conducting 

data analysis, including analysis of 

identifiable private information, or (2) 

accessing follow-up clinical data from 

procedures that subjects would undergo 

as part of standard care for their medical 

condition. 

Also, as discussed in Section IX, the 

NPRM proposed eliminating continuing 

review for many minimal risk studies 

(namely those that qualify for expedited 

review), unless the reviewer finds and 

documents why continuing review 

should take place for the study. Finally, 

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the NPRM contained a requirement that 

IRBs document the rationale for an 

expedited reviewer’s determination that 

research appearing on the expedited 

review list is more than minimal risk 

(i.e., overturning the presumption that 

studies on the Secretary’s list are 

minimal risk). 

New in the NPRM was a proposal to 

require that an IRB maintain records of 

exemption determinations. 

Additionally, the NPRM proposed that 

the use of the proposed exemption 

determination tool would satisfy the 

proposed documentation requirement. 

In addition, a new provision was 

proposed to require that the institution 

or IRB that retains IRB records should 

safeguard, if relevant, individually 

identifiable private information 

contained in those records in 

compliance with the proposed privacy 

safeguards. 

Finally, the NPRM proposed a 

modification of the pre-2018 rule 

clarifying that IRB records may be 

maintained in print or electronic form. 

C. Public Comment 

The proposed modifications to 

§ ll.115 received approximately 25 

comments. A majority focused on three 

proposed revisions. The NPRM 

proposed to require that reviewers 

document why an IRB required 

continuing review when continuing 

review was not required as proposed in 

the NPRM. The majority of commenters 

opposed this requirement stating that it 

merely shifted administrative burden 

from one activity to another with no 

increase in protections. 

The NPRM also proposed to require 

that a reviewer document why a 

research activity appearing on the 

expedited review list is more than 

minimal risk, and thus should be 

subject to full IRB review. This was 

opposed by the majority of commenters 

who indicated that this proposal was an 

unjustified administrative burden. 

One commenter stated that the 

proposed documentation requirements 

would be punitive to IRBs. Several 

others suggested that this requirement 

served as a disincentive to institutions 

who wanted to implement additional 

protections than those required by the 

Common Rule. These commenters noted 

that this seemed in contrast to the 

longstanding policy articulation that the 

Common Rule served as a ‘‘floor’’ for 

protections and that institutions could 

require additional protections for 

research conducted at their institutions. 

D. Response to Comments and 

Explanation of the Final Rule: IRB 

Records 

A majority of the changes proposed in 

the NPRM in §ll.115 have been 

retained in the final rule without 

alteration. However, the final rule 

differs from the NPRM in a few ways. 

First, the NPRM included two 

provisions requiring documentation of 

continuing review activities; these have 

been merged into one provision in the 

final rule at §ll.115(a)(3). Second, the 

NPRM required that the IRB keep 

records of the IRB reliance agreements 

between an institution and the IRBs not 

operated by that institution that review 

said institution’s nonexempt research 

activities. Instead, the final rule 

includes language at §ll.115(a)(9) 

that requires each institution to 

maintain adequate documentation of the 

responsibilities that each entity will 

undertake to ensure compliance with 

this policy. This provision differs from 

the NPRM proposal to correspond to the 

more flexible provision included at 

§ ll.103(e), which does not require 

the creation of a written agreement 

between an institution and a reviewing 

IRB that said institution does not 

operate. 

Because the final rule does not 

include an exemption determination 

requirement, the exemption 

documentation requirement proposed in 

the NPRM is not included in the final 

rule. Additionally, because the final rule 

does not include specified privacy 

safeguards, the NPRM proposal for an 

IRB to safeguard records as required by 

the proposed privacy safeguards is not 

included. 

The final rule includes the NPRM 

proposal that IRBs document decisions 

to require continuing review or full 

board review even in circumstances 

when such review is not required 

because we believe it is important to 

document why an IRB is making a 

determination that differs from the 

regulatory baseline. This also helps to 

promote the principle of justice (as 

applied to IRB operations). Note that 

nothing in these regulations prevents an 

institution from authorizing an IRB to 

apply standards that exceed those in the 

regulations, if indeed the institution has 

chosen to do so. 

In addition, while the NPRM 

proposed to require that IRB records 

that contain identifiable private 

information be safeguarded through 

compliance with the proposed privacy 

safeguards, the final rule does not 

require such safeguards. Although no 

public comments were received on this 

provision, in deciding not to include the 

NPRM’s proposed privacy safeguard 

requirements in the final rule, we 

determined that it was unnecessary for 

the Common Rule to impose additional 

privacy requirements on IRB records as 

we are unaware of instances in which 

IRB records were breached. In addition, 

IRB records are not the regulatory 

equivalent of research records, which 

should be adequately secured or 

safeguarded against inappropriate uses 

or disclosures of identifiable private 

information. IRB records will generally 

be secured for a variety of reasons. 

These include not only protecting 

identifiable private information, but 

also, for example, protecting discrete 

information and intellectual property 

that might be included in a protocol. 

There are other means for ensuring 

institutions and IRBs protect their 

records beyond what is required by the 

Common Rule. 

XIV. General Requirements for 

Informed Consent (§ ll.116) 

The final rule contains several major 

revisions to the requirements for 

informed consent, specifically with 

respect to: (1) New requirements 

relating to the content, organization, and 

presentation of information included in 

the consent form and process to 

facilitate a prospective subject’s 

decision about whether to participate in 

research; (2) the basic and additional 

elements of consent; (3) the elements of 

broad consent for the storage, 

maintenance, or secondary research use 

of identifiable private information and 

identifiable biospecimens; (4) attendant 

changes in the waiver or alteration 

criteria for consent; (5) a new provision 

that allows IRBs to approve a research 

proposal for which investigators obtain 

information or biospecimens without 

individuals’ informed consent for the 

purpose of screening, recruiting, or 

determining the eligibility of 

prospective human subjects of research, 

provided certain conditions are met; 

and, (6) a new requirement to post to a 

federal Web site a copy of an IRBapproved version of the consent form 

that was used for enrollment purposes 

for each clinical trial conducted or 

supported by a federal department or 

agency. Each of the final rule provisions 

are discussed separately below. 

A. General Requirements for Informed 

Consent (§ll.116(a)) 

1. Background and Pre-2018 

Requirements 

Under the pre-2018 rule, many 

fundamental requirements applicable to 

all informed consents were set forth in 

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Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 7211 

41Levine RJ. Informed consent: Some challenges 

to the universal validity of the western model. J Law 

Med Ethics 1991;19(3–4):207–213. 

42Menikoff J., Richards E. What the Doctor Didn’t 

Say: The Hidden Truth about Medical Research. 

New York, NY: Oxford University Press; 2006:113– 

123. 

43Beardsley E. et al. Longer Consent Forms for 

Clinical Trials Compromise Patient Understanding: 

So Why Are They Lengthening? Journal of Clinical 

Oncology. 2007 Mar 20;25(9):e13–4. 

44Section ll.109(b) of the pre-2018 rule states 

that an IRB shall require that information given to 

subjects as part of informed consent is in 

accordance with §ll.116. The IRB may require 

that information, in addition to that specifically 

mentioned in §ll.116, be given to the subjects 

when in the IRB’s judgment the information would 

Continued 

an introductory (and unnumbered) 

paragraph at the beginning of § ll.116. 

In considering changes to the general 

requirements set forth in §ll.116(a), 

we considered arguments put forth by 

some that consent forms have evolved to 

protect institutions rather than to 

provide potential research subjects with 

the most important pieces of 

information that a person would need in 

order to make an informed decision 

about whether to enroll in a research 

study.41 Instead of presenting the 

information in a way that is most 

helpful to prospective subjects—such as 

explaining why someone might want to 

choose not to enroll—these individuals 

argued the forms may function more as 

sales documents or as a means to protect 

against institutional liability.42 We also 

considered a growing body of literature 

that suggests informed consent forms 

have grown too lengthy and complex, 

adversely affecting their ability to 

effectively convey the information 

needed for prospective participants to 

make an informed decision about 

participating in research.43

2. NPRM Proposals 

The NPRM proposed adding new 

language to the introductory text of 

§ ll.116 to emphasize the need to first 

provide essential information that a 

reasonable person would want to know 

in order to make an informed decision 

about whether to participate in research, 

and to provide an opportunity to 

discuss that information. Furthermore, 

in recognition of complaints that 

consent forms are too often complicated 

documents primarily used to protect 

sponsors from legal liability, the NPRM 

proposed requiring that the information 

in these forms be organized and 

presented in a way that does not merely 

provide lists of isolated facts, but rather 

facilitated the prospective subject’s or 

representative’s understanding of the 

reasons why one might or might not 

want to participate in the research. 

The NPRM also proposed that an 

investigator seeking to obtain informed 

consent be required to present first the 

information required by § ll.116, 

which has been recognized by the 

Common Rule departments and 

agencies as the most fundamental and 

required content of informed consent, 

before providing other information, if 

any, to the subject. As proposed under 

the NPRM, the main portion of a 

consent document could include only 

the elements of informed consent that 

were required by the Common Rule, 

with any other information included in 

an appendix. This change was intended 

to lead to substantially shorter ‘‘core’’ 

sections of consent forms, with 

prospective subjects receiving the most 

important information in the body of 

these relatively short forms, instead of 

that key information being buried in 

long and overly complex documents. As 

proposed, additional information could 

be set forth in appendices to consent 

forms. 

Given the consensus that informed 

consent forms should be written in 

appropriate language, this proposal 

reinforced the need to include 

information using language 

understandable to the subject. This goal 

was consistent with Federal Plain 

Language guidelines and the Federal 

Plain Writing Act of 2010. The NPRM 

proposed that the Secretary publish 

guidance at a later time to explain how 

consent forms could be written to 

comply with this regulatory 

requirement. Public comments were 

sought on what topics should be 

addressed in future guidance on 

improving the understandability of 

informed consents. As explained in the 

NPRM, it was not envisioned that the 

revised Common Rule would require a 

formal assessment to evaluate an 

individual’s competency, but we 

acknowledged that such a practice 

might be appropriate for certain 

populations or studies. 

In addition, the NPRM proposed to 

clarify in the introductory language at 

§ ll.116 that if a HIPAA authorization 

is combined with a consent form, the 

authorization elements required by 45 

CFR 164.508 (part of the HIPAA Privacy 

regulations) must be included in the 

consent document and not the 

appendices. In other words, when 

informed consent for research under the 

Common Rule is combined with a 

HIPAA authorization, the NPRM 

proposed that the authorization 

elements would be considered to 

constitute one of the required elements 

of informed consent. 

3. Public Comments 

Approximately 200 comments 

discussed the proposal to include 

information required by the Common 

Rule in the consent form and place 

other information in appendices. A 

majority of those (approximately 140) 

supported the proposal and 

approximately 35 commenters opposed 

this proposal. Those who expressed 

support for this proposal generally 

noted agreement with the NPRM’s 

rationale for the proposed revisions. 

Even those who supported the proposal 

stated that guidance would be needed 

for the proposal to be implemented and 

for the proposal to have the desired 

effect. Among those who opposed this 

proposal, all indicated support for the 

intention behind it. Reasons for 

opposing this proposal included: 

• Concern that having a ‘‘dual 

document’’ system (with a primary 

consent form and appendices) would 

not actually improve subjects’ 

understanding specifically and the 

informed consent process generally. 

• Concerns that in some 

circumstances, the information that one 

might require to make an informed 

decision about research participation 

may not always be information required 

under the Common Rule when seeking 

and obtaining informed consent. 

• Concern that the proposed language 

for the § ll.116 introductory 

paragraph should not be promulgated as 

regulatory text (and would be more 

appropriate as guidance). 

• Concern that because the proposed 

language does not include specific 

standards and specific criteria, the 

provision would ultimately be 

impossible to implement and enforce. 

• Concern that the language as 

proposed would not reduce the 

complexity and length of consent forms 

because much of the information 

generally contained in an informed 

consent document is required by 

various regulatory agencies. To this end, 

several commenters noted that the 

NPRM proposed an additional four 

required elements of consent, which 

would add to the quantity of 

information that is required to be 

discussed in an informed consent 

document. 

Some comments noted that although 

they liked the general idea of the 

proposal for the introductory paragraph 

of §ll.116, they felt that the proposal 

should not focus on the length of a 

consent form, but rather on clarity and 

understandability. One comment 

expressed a need for guidance on how 

to implement the proposed language in 

the introductory paragraph of §ll.116 

and the requirement at §ll.109(b) of 

the pre-2018 rule.44 The NPRM did not 

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7212 Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 

meaningfully add to the protection of the rights and 

welfare of subjects. 

propose changing the latter item, which 

mandated that IRBs require that 

information given to subjects as part of 

informed consent conform with the 

requirement. However, the NPRM also 

permitted IRBs to require additional 

information if it would meaningfully 

add to the protection of the rights and 

welfare of subjects. This comment was 

made in light of the NPRM’s proposal 

that information not required as an 

element of consent at §ll.116 must be 

provided after providing the required 

elements of consent. 

The NPRM asked about what topics 

should be addressed in future guidance 

on improving the understandability of 

informed consent. Approximately 35 

commenters answered this question, a 

majority of which were universities and 

research institutions. Several 

commenters questioned whether the 

proposals in the introductory paragraph 

of §ll.116 would be enforceable, and 

how Common Rule departments and 

agencies would assess and enforce 

compliance. 

Several commenters indicated that 

mandating the order in which the 

content of consent forms should be 

presented may not always facilitate 

increased understanding by potential 

subjects because the best way to 

facilitate understanding is likely to be 

study specific. In other words, the order 

of importance of issues could be 

dependent on unique aspects of a given 

study. Others noted that most 

information in consent forms is there 

because the regulations require it to be 

included. Thus, the proposal to include 

the information required by the 

regulations up front, with all other 

information included as an appendix, is 

not a requirement that will inherently 

improve consent forms. Some 

commenters suggested that more 

research was needed on the informed 

consent process before prescribing 

specific approaches. 

Many commenters asked that future 

guidance be developed to assist in 

drafting consent forms that addresses 

language level, literacy, risk 

communication, and best practices in 

use of alternative media in the informed 

consent process (e.g., interactive 

presentation on a tablet, comic strips for 

pediatric populations). In this regard, 

some comments objected to the singular 

focus on a ‘‘form’’ in the proposed 

language, stating that this sends the 

message that alternative and innovative 

approaches to improving the informed 

consent process would be discouraged. 

Others noted that future guidance 

should include topics of interest to 

tribal groups, such as acknowledgement 

of community-level implications of 

research and clarification about the 

handling of biospecimens in a study. 

Several commenters noted that 

guidance should focus on how to foster 

understanding rather than focusing on 

mandatory length limitations on consent 

forms. However, a few comments 

endorsed a recommended page length 

maximum, citing it as perhaps the only 

way to force investigators and 

institutions to be brief and concise in 

the presentation of relevant information. 

4. Response to Comments and 

Explanation of the Final Rule: General 

Requirements for Informed Consent 

Before addressing how the general 

requirements for informed consent 

proposed in the NPRM have been 

adopted and altered in the final rule, it 

is important to note that the structure 

for this regulatory text has been altered. 

In the pre-2018 rule, the general 

requirements were included in an 

unnumbered introductory paragraph. 

The NPRM proposed the same 

approach. To emphasize the fact that 

this paragraph includes multiple 

independent and important regulatory 

requirements, and to enable 

stakeholders and Common Rule 

departments and agencies to more easily 

reference particular requirements, these 

general requirements have been 

redesignated into a new §ll.116(a). In 

addition, the general requirement for 

consent in the final rule at 

§ ll.116(a)(6) removes the reference to 

oral or written consent that was in the 

pre-2018 rule. This is the provision that 

addresses the prohibition on including 

exculpatory language through which the 

subject or the legally authorized 

representative is made to waive or 

appear to waive any of the subject’s 

legal rights, or releases or appears to 

release the investigator, the sponsor, the 

institution, or its agents from liability 

for negligence. The reference to oral or 

written consent was removed from this 

provision in the final rule. In its place, 

a similar reference was included in to 

§ ll.116(a) to clarify that all the 

requirements set forth in §ll.116(a) 

apply to written and oral consent. 

Another change made in the final 

rule, as compared with the pre-2018 

rule and the language proposed in the 

NPRM, is that §ll.116(a) contains 

introductory language summarizing 

each paragraph of §ll.116 and the 

relationship between those paragraphs. 

Given that the framework for informed 

consent has been altered and 

reorganized through this regulation, this 

introductory language is intended to 

explain the overall approach set forth in 

revised §ll.116, as well as the 

significance of each paragraph. This 

introductory language is also intended 

to explain the role of broad consent 

under revised § ll.116. The 

introductory paragraph explains that the 

general requirements for informed 

consent are now set forth in 

§ ll.116(a) and that these general 

requirements apply with respect to 

informed consent obtained pursuant to 

§ ll.116(b), (c), and (d) (except, as 

described later, § ll.116(a)(5) does not 

apply to broad consent obtained under 

§ ll.116(d)). This introductory 

language also explains that the basic 

elements of informed consent (which 

were described in §ll.116(a) of the 

pre-2018 rule) are included in 

§ ll.116(b) of this final rule and that 

additional elements of informed consent 

that pertain only to certain studies 

(which were described in §ll.116(b) 

of the pre-2018 rule) are included in 

§ ll.116(c) of this final rule. 

In addition, this introductory 

language explains that the requirements 

for broad consent (a concept not 

specifically addressed in the pre-2018 

rule) are described in §ll.116(d) of 

this final rule. As discussed below, 

broad consent under this final rule 

differs from the broad consent approach 

proposed for § ll.116(c) in the NPRM. 

The introductory language of 

§ ll.116(a) explains that broad 

consent may be obtained in lieu of 

informed consent obtained under 

§ ll.116(b) and § ll.116(c) (which 

describe basic elements of informed 

consent as a general matter and 

additional elements of informed consent 

that apply only to certain studies, 

respectively) for certain purposes. 

Specifically, in lieu of obtaining studyspecific informed consent in accordance 

with §ll.116(b) and (c), broad 

consent may be obtained under 

§ ll.116(d) for the use of identifiable 

private information or identifiable 

biospecimens collected for either 

research studies other than the proposed 

research or nonresearch purposes for: 

(1) storage and maintenance for 

secondary research use; and (2) 

secondary research. For those purposes 

(and no others), broad consent under 

§ ll.116(d) may be obtained instead of 

specific consent under § ll.116(b) and 

(c). 

New introductory language at 

§ ll.116(a) also summarizes the 

provisions describing circumstances in 

which waiver or alteration of the 

requirements of informed consent are 

permitted. These circumstances pertain 

to research involving public benefit and 

service programs conducted by or 

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subject to the approval of state or local 

officials at § ll.116(e), and to research 

more generally at §ll.116(f) (see 

below). 

Another change reflected in the final 

rule is that specific requirements for 

informed consent have been included in 

subparagraphs for clarity and emphasis. 

For example, the requirement that 

information that is given to the subject 

or the legally authorized representative 

shall be in language understandable to 

such subject or representative is no 

longer included as part of a general 

introductory paragraph and is instead 

included as § ll.116(a)(3). Except as 

noted here, these requirements remain 

the same as they were under the pre2018 rule. 

The final rule adopts, almost 

verbatim, all of the proposals made in 

the NPRM to improve and clarify the 

general requirements for informed 

consent. For example, the final rule 

adopts the proposed requirement 

specifying that the information provided 

in an informed consent form must be 

presented in sufficient detail relating to 

the research, and must be organized and 

presented in a way that does not merely 

provide lists of isolated facts, but rather 

facilitates the prospective subject’s or 

legally authorized representative’s 

understanding of the reasons why one 

might or might not want to participate. 

The final rule also adopts new language 

clarifying that this requirement applies 

to the informed consent as a whole. In 

addition, the final rule adopts the 

NPRM’s proposal that prospective 

subjects or legally authorized 

representative must be provided with 

key information that is most likely to 

assist a prospective subject or legally 

authorized representative in making a 

decision about participating in research, 

and to provide an opportunity to 

discuss that information. Moreover, the 

final rule adopts an approach, 

consistent with many public comments, 

emphasizing efforts to foster 

understanding overall rather than 

imposing specific length limitations on 

the entire consent forms. 

The final rule also includes language 

slightly different from that proposed in 

the NPRM for clarity or for conformance 

with other language in the final rule. For 

example, the final rule replaces 

references to a subject’s representative 

with references to a subject’s legally 

authorized representative (a term 

defined in § ll.102) for clarity. 

As discussed above, a significant 

proposal in the NPRM was that in 

obtaining informed consent, 

investigators would first have to present 

the information required by §ll.116, 

before presenting any other information, 

if any. In addition, the NPRM proposed 

mandating that consent forms must 

include only the required information 

under §ll.116 and that any other 

information be included in appendices. 

The final rule does not adopt a 

requirement that certain information be 

included only in appendices. This 

approach is responsive to public 

comments expressing concerns that 

such a mandate might sometimes 

undermine the informed consent 

process. The final rule adopts a slight 

variation of that approach in response to 

public comments about perceived lack 

of flexibility in the proposed language. 

Whereas the NPRM referred to the 

‘‘body’’ of the consent form as opposed 

to appendices to the consent form, the 

final rule replaces those concepts with 

references to material that must be at the 

beginning of the consent form, versus 

material that can appear after that 

beginning section. The final rule does 

not limit the information that can be 

provided in the beginning of a consent 

form to only the §ll.116 

requirements, but instead offers a more 

flexible and meaningful approach in 

response to public concerns that the 

NPRM proposal was too prescriptive. 

Moreover, the approach recognizes 

public comments that expressed 

concerns about creating a ‘‘dual 

document’’ system. As such, the final 

rule does not address appendices to the 

informed consent. However, the 

NPRM’s references to the appendices of 

the consent form have in general been 

conceptually replaced by references to 

the material in a consent form that 

follows the ‘‘beginning’’ section. 

In particular, the final rule imposes a 

new requirement (set forth in 

§ ll.116(a)(5)(i)) that the informed 

consent begin with a concise and 

focused presentation of the key 

information that is most likely to assist 

a prospective subject or legally 

authorized representative in 

understanding the reasons why one 

might or might not want to participate 

in the research. This provision further 

requires that this beginning portion of 

the informed consent must be organized 

and presented in a way that facilitates 

comprehension. This requirement 

applies to all informed consents, except 

for broad consents obtained pursuant to 

§ ll.116(d), which may warrant a 

different presentation. 

This new requirement included at 

§ ll.116(a)(5)(i) is somewhat similar 

to the proposal advanced in the NPRM 

insofar as both emphasize the 

importance of presenting the 

information that would be most 

important to a subject (or a legally 

authorized representative) before 

presenting other information. However, 

the requirement included in 

§ ll.116(a)(5)(i) is more specific, 

detailed, and flexible. First, this 

provision requires that key information 

be included in the beginning of the 

informed consent in a concise and 

focused presentation. We recognize that 

how this requirement applies will 

depend on the nature of the specific 

research study and the information 

presented in the informed consent and 

believe that this requirement strikes an 

appropriate balance between facilitating 

the comprehension of subjects of key 

issues and allowing study-specific 

flexibilities. In general, our expectation 

is that this initial presentation of the key 

pieces of information will be relatively 

short. This section of the consent could, 

in appropriate circumstances, include a 

summary of relevant pieces of 

information that are explained in greater 

detail later in the consent form. 

The requirement that key information 

be presented in a concise and focused 

way will require an assessment that is 

specific to a study and its informed 

consent. For example, for most 

complicated clinical trials involving 

cancer patients with long (e.g., 20- to 25- 

page) consent documents, our 

expectation would be that the concise 

and focused presentation referred to in 

§ ll.116(a)(5)(i) would be no more 

than a few pages, and would provide the 

key pieces of information about the trial 

in such a manner that facilitates a 

person’s comprehension of why they 

might or might not want to participate 

in the research. 

In such cases, for example, we would 

not consider a 10-page description of 

elements such as potential risks, 

accompanied by lengthy and complex 

charts and graphs, to satisfy the 

‘‘concise and focused’’ requirement of 

§ ll.116(a)(5)(i). With regard to risks 

in the type of cancer trial mentioned 

above, for example, instead of needing 

to mention every reasonably foreseeable 

risk, which would be required by 

§ ll.116(b)(2), this beginning section 

of the consent form should identify the 

most important risks, similar to the 

information that a doctor might deliver 

in the clinical context in telling a 

patient how sick the chemotherapy 

drugs will make them, but with a 

particular emphasis on how those risks 

are changed by participating in the 

study. 

We recognize the advantages of 

allowing institutions to design informed 

consents, consistent with 

§ ll.116(a)(5)(i), that are tailored to 

particular research studies to assist 

prospective subjects in understanding 

the most fundamental aspects of the 

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45For general requirements for informed consent 

see §ll.116 in the pre-2018 Rule, and 21 CFR 

50.20, .25 in FDA’s comparable requirements. There 

are provisions under the Common Rule, that allow 

for the waiver of some or all of the elements of 

informed consent (see §ll.116(e) and (f)). The 

Federal Food, Drug, and Cosmetic Act limits the 

circumstances under which informed consent can 

be waived. See, e.g., section 520(g) (21 U.S.C. 

360j(g)). Currently, FDA regulations contain only 

two exceptions from informed consent in certain 

life-threatening and emergency situations under 21 

CFR 50.23–24. However, the 21st Century Cures Act 

recently amended the Federal Food, Drug and 

Cosmetic Act to allow waiver of informed consent 

for certain FDA-regulated minimal risk 

investigations. 

informed consent. For this reason, the 

final rule does not strictly specify the 

types of information that should or 

should not be included to satisfy 

§ ll.116(a)(5)(i), or the length of such 

concise and focused presentations. This 

flexibility is responsive to public 

comments recommending against a rigid 

approach to enable institutions and 

individuals to tailor informed consents 

to the circumstances of particular 

studies. A discussion of the key 

information to be included in the 

beginning section of the consent form, 

and how it will operate in practice, may 

be further clarified in future guidance. 

We also recognize that for some 

relatively simple research studies with 

limited risks or benefits, the entire 

informed consent document may be 

relatively brief and still satisfy 

§ ll.116. In such circumstances, an 

institution may determine that virtually 

all of the information required by 

§ ll.116 would also satisfy 

§ ll.116(a)(5)(i). In such cases, the 

informed consent document could 

include the concise and focused 

presentation of § ll.116(a)(5)(i) at the 

beginning of the informed consent 

document, followed by limited 

additional information required to 

satisfy §ll.116. 

In all circumstances (those involving 

lengthy and complex informed consents 

as well as short and relatively simple 

informed consents), if information 

included at the beginning of the 

informed consent satisfies both 

§ ll.116(a)(5)(i) and the elements of 

informed consent under § ll.116(b) 

and §ll.116(c) more generally, the 

information included at the beginning 

need not be repeated later in the body 

of the informed consent. Thus, with 

respect to the example provided above 

concerning a clinical trial with cancer 

patients, the most important reasonably 

foreseeable risks to subjects would be 

summarized at the beginning of the 

informed consent as part of 

§ ll.116(a)(5)(i)’s concise and focused 

presentation, but that a more 

comprehensive and detailed description 

of reasonably foreseeable risks to 

subjects would be included later in the 

body of the informed consent. In 

contrast, with respect to a relatively 

simple research study with limited 

risks, we would expect that all of the 

information provided to potential 

subjects concerning such risks might 

satisfy both § ll.116(a)(5)(i) (as part of 

a concise and focused presentation of 

key information) and §ll.116(b)(2) (a 

description of any reasonably 

foreseeable risks or discomforts to the 

subject). In such circumstances, the 

information provided at the beginning 

of the informed consent would not need 

to be repeated or further detailed in the 

informed consent and the entire 

informed consent could be relatively 

short. 

In general, we would expect that to 

satisfy §ll.116(a)(5)(i), the beginning 

of an informed consent would include 

a concise explanation of the following: 

(1) the fact that consent is being sought 

for research and that participation is 

voluntary; (2) the purposes of the 

research, the expected duration of the 

prospective subject’s participation, and 

the procedures to be followed in the 

research; (3) the reasonably foreseeable 

risks or discomforts to the prospective 

subject; (4) the benefits to the 

prospective subject or to others that may 

reasonably be expected from the 

research; and (5) appropriate alternative 

procedures or courses of treatment, if 

any, that might be advantageous to the 

prospective subject. As a general matter, 

a brief description of these five factors 

would encompass the key information 

most likely to assist a reasonable person 

(or legally authorized representative) in 

understanding the reasons why one 

might or might not want to participate 

in research, as required by 

§ ll.116(a)(5)(i) and § ll.116(a)(4). 

However, we recognize that this 

determination is necessarily factspecific and that IRBs and institutions 

may require that somewhat different (or 

additional) information be presented at 

the beginning of an informed consent to 

satisfy §ll.116(a)(5)(i). 

The NPRM also proposed adding a 

new requirement to the general 

introductory paragraph of § ll.116, 

which would provide that if an 

authorization required by 45 CFR parts 

160 and 164 (parts of the HIPAA Privacy 

Rule) is combined with a consent form, 

the authorization elements required by 

45 CFR 164.508 must be included in the 

consent form (and not the appendices). 

Because this final rule does not 

incorporate the distinction proposed in 

the NPRM between the informed 

consent and appendices, the final rule 

does not incorporate this language. 

We are satisfied that the approach 

adopted in this final rule will enable 

regulated entities and individuals to 

pursue different and innovative 

approaches to obtaining informed 

consent, as recommended in some 

public comments, while ensuring that 

the important aspects of informed 

consent are clearly communicated to 

prospective subjects and subjects. 

B. Basic Elements of Informed Consent 

(§ ll.116(b)) 

1. Background and Pre-2018 

Requirements 

Under the pre-2018 rule, investigators 

were generally required to obtain the 

subjects’ informed consent to participate 

in research.45 The regulations required 

that the consent form include at least 

eight specific items of information, 

including: (1) an explanation of the 

purposes of the research, its duration, 

and procedures involved, and 

identification of any procedures which 

are experimental; (2) a description of the 

reasonably foreseeable risks; (3) a 

description of any potential benefits; (4) 

a disclosure of appropriate alternative 

procedures or courses of treatment, as 

relevant; (5) information about 

confidentiality of records, 

compensation, and treatments if injury 

occurs; (6) for research involving more 

than minimal risk, an explanation as to 

whether any compensation or medical 

treatments are available if injury occurs; 

(7) contact information; and (8) a 

statement that participation is 

voluntary, and that refusal to participate 

or decision to withdraw will involve no 

penalty or loss of benefits to which the 

subject is otherwise entitled. 

2. NPRM Proposals 

In the NPRM it was proposed that 

research with nonidentified data 

continue to be considered not to involve 

‘‘human subjects.’’ However, to better 

ensure that subjects are informed of the 

possibility that identifiers collected as 

part of a research study could be 

removed from the data and then be used 

for secondary research studies without 

the protections provided by this policy, 

it was proposed that a new element of 

informed consent be required. The new 

basic element of consent proposed in 

the NPRM at §ll.116(a)(9) would 

apply to all research collecting 

identifiable private information. Based 

on the investigator’s plans, the informed 

consent form and process would need to 

inform subjects either that: (1) 

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identifiers might be removed from the 

data and that the nonidentified data 

could be used for future research studies 

or distributed to another investigator for 

future research studies without 

additional informed consent from the 

subject or the representative, if this 

might be a possibility; or (2) the 

subject’s data collected as part of the 

research, from which identifiers are 

removed, would not be used or 

distributed for future research studies. 

3. Public Comments 

Approximately 40 public comments 

were received on the proposed new 

required element of informed consent 

found in the NPRM at proposed 

§ ll.116(a)(9). A large majority 

favored this proposal. Those who 

supported this proposal indicated that it 

provided useful information to 

prospective subjects about how private 

information obtained from a study 

might be used in the future. They also 

commented that it enhanced 

transparency in research, providing 

potential subjects with the information 

they need to decide whether to 

participate. Those who opposed this 

proposal suggested that it would 

increase the length of consent forms 

without appreciably improving 

potential subjects’ understanding of a 

specific research activity. 

4. Response to Comments and 

Explanation of the Final Rule: Basic 

Elements of Informed Consent 

The final rule, at §ll.116(b)(9), 

adopts the NPRM proposal to inform 

potential subjects about the possible use 

of their identifiable private information 

with two clarifying changes. First, 

because the final rule at § ll.102(e)(1) 

now states that the definition of human 

subject, in part, includes research in 

which an investigator obtains, uses, 

studies, analyzes, or generates 

identifiable biospecimens or identifiable 

private information, this new element of 

informed consent has been clarified to 

specifically apply to any research that 

involves the collection of identifiable 

biospecimens, rather than all 

biospecimens, in addition to research 

that involves the collection of 

identifiable private information. In 

addition, a change to what was 

proposed in the NPRM has been made 

to the new element of consent in the 

final rule at §ll.116(b)(9)(ii), to 

clarify that it is intended to inform 

subjects that their information or 

biospecimens collected as part of the 

research will not be used or distributed 

for future research, even if identifiers 

are removed. 

We agree with the public comments 

that indicated this new element of 

consent will provide useful information 

to prospective subjects about whether 

their identifiable private information or 

identifiable biospecimens might be 

stripped of identifiers and used for 

future research studies or distributed to 

another investigator for future research 

studies without additional informed 

consent from the subject or the legally 

authorized representative. 

We expect that this information can 

usually be provided in a brief statement, 

and disagree with the commenters that 

suggested that this new basic element of 

consent would increase the length of 

consent forms without appreciably 

improving potential subjects’ 

understanding of a specific research 

activity. This new requirement is 

intended to give the potential subject a 

right to know that identifiers might be 

removed from information or 

biospecimens and be used for future 

research without additional consent, 

when such a possibility exists, so he or 

she can make a fully informed decision 

about whether to participate in the 

research. If subjects’ identifiable private 

information or identifiable 

biospecimens will not be used for future 

research studies, even if identifiers are 

removed, this new element of consent 

requires that subjects be informed of 

this as well. Finally, if a specific 

technology or technique determined to 

be capable of generating identifiable 

private information or identifiable 

biospecimens through the consultative 

process described at §ll.102(e)(7) 

will be used, that information should be 

included in the description of the 

research at § ll.116(b)(1). 

C. Additional Elements of Informed 

Consent (§ll.116(c)) 

1. Background and Pre-2018 

Requirements 

The pre-2018 rule contained six 

additional elements of consent required 

when appropriate: (1) A statement that 

the particular treatment or procedure 

may involve risks to the subject (or to 

the embryo or fetus, if the subject is or 

may become pregnant) which are 

currently unforeseeable; (2) anticipated 

circumstances under which the subject’s 

participation may be terminated by the 

investigator without regard to the 

subject’s consent; (3) any additional 

costs to the subject that may result from 

participation in the research; (4) the 

consequences of a subject’s decision to 

withdraw from the research and 

procedures for orderly termination of 

participation by the subject; (5) a 

statement that significant new findings 

developed during the course of the 

research which may relate to the 

subject’s willingness to continue 

participation will be provided to the 

subject; and (6) the approximate number 

of subjects involved in the study. 

2. NPRM Proposals 

The NPRM proposed adding three 

additional elements of consent that, 

when appropriate, would be required to 

be included in the informed consent 

form and process. These proposed 

additional elements of consent pertain 

to issues that have become more 

relevant in recent years as science has 

advanced and the nature of research has 

changed. One proposed new element 

would require that prospective subjects 

be informed that their biospecimens 

may be used for commercial profit and 

whether the subject will or will not 

share in this commercial profit. A 

second proposed element would require 

that prospective subjects be informed of 

whether clinically relevant research 

results, including individual research 

results, will be disclosed to subjects, 

and if so, under what conditions. A 

third proposed new element would 

provide subjects or their legally 

authorized representatives with an 

option to consent, or refuse to consent, 

to investigators re-contacting the 

research subject to obtain additional 

information or biospecimens, or for 

future research. 

3. Public Comments 

Each of the proposed additional 

elements of informed consent found in 

the NPRM at §ll.116(b)(7)–(9) 

received approximately 50 comments. 

All three proposals were generally 

favored by the public. With respect to 

the proposed element of consent at 

§ ll.116(b)(7), requiring that 

prospective subjects be informed that 

their biospecimens may be used for 

commercial profit and whether the 

subject will or will not share in this 

commercial profit, comments, especially 

from individual members of the public 

not identified with any institution or 

organization, indicated that the extent to 

which an investigator might profit from 

information or biospecimens collected 

or used during a study was an important 

decision point as to whether a 

prospective subject would want to 

participate in a study. In response to 

proposed element § ll.116(b)(8)— 

requiring that prospective subjects be 

informed of whether clinically relevant 

research results, including individual 

research results, will be disclosed to 

subjects, and if so, under what 

conditions—several public comments 

stated that knowing whether or not 

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research results would be returned to 

them was an important piece of 

information for them to know and 

understand in deciding whether to 

participate in a study. 

Finally, comments discussing 

§ ll.116(b)(9) regarding the potential 

to be contacted for future studies noted 

that allowing an individual to indicate 

whether or not he or she might be 

contacted for future research studies 

respected subject autonomy. Those who 

opposed the provision noted that while 

the intent of the provision was laudable, 

the ensuing tracking system that would 

need to be developed by institutions to 

track who had said ‘‘yes’’ or ‘‘no’’ to 

being re-contacted, and in what 

circumstances, would be difficult to 

develop and maintain, and would also 

represent significant costs to institutions 

without a corresponding tangible 

increase in the protections afforded to 

human subjects. 

4. Response to Comments and 

Explanation of the Final Rule: 

Additional Elements of Consent 

The final rule contains two of the 

three proposed additional elements of 

consent. The final rule does not include 

the additional element proposed in the 

NPRM relating to providing subjects or 

their legally authorized representatives 

the option to consent or refuse to 

consent to being re-contacted to obtain 

additional information or biospecimens, 

or for future research. 

New additional elements included in 

the final rule are: (1) A statement that 

the subject’s biospecimens (even if 

identifiers are removed) may be used for 

commercial profit and whether the 

subject will or will not share in this 

commercial profit (§ ll.116(c)(7)); and 

(2) a statement regarding whether 

clinically relevant research results, 

including individual research results, 

will be disclosed to subjects, and if so, 

under what conditions 

(§ ll.116(c)(8)). Because many public 

comments addressed a desire to share in 

the profits of successful products 

developed using their biospecimens, we 

believe that investigators, when 

appropriate, should inform prospective 

subjects about whether they might or 

might not benefit commercially from 

future products resulting from the 

research, should that possibility be 

important in their decision making 

process. Also, several comments 

received from individuals who reported 

participation in research studies 

described disappointment that research 

results were not returned to them. We 

believe that potential subjects should be 

aware of the possibility that they might 

not receive research results, as well as 

the possibility that they might, so that 

they can factor that information into 

their decision about whether to consent 

to research. This provision is intended 

to pertain to all clinically relevant 

research results, including general or 

aggregate research findings and 

individual research results. 

We are also including in the final rule 

an additional element that when 

appropriate for research involving 

biospecimens, subjects be informed of 

whether the research will (if known) or 

might include whole genome 

sequencing (WGS) (§ ll.116(c)(9)). 

This provision of the final rule describes 

WGS as the sequencing of a human 

germline or somatic specimen with the 

intent to generate the genome or exome 

sequence of that specimen. WGS 

generates an extremely large amount of 

information about people, including 

factors that will contribute to their 

future medical conditions. As was 

recognized in the NPRM’s Alternative 

Proposal A to expand the definition of 

‘‘human subject’’ to include WGS 

(discussed in Section III), data obtained 

through WGS can provide important 

insights into the health of individuals as 

well as their biological family. It is also 

possible that WGS data gathered for one 

purpose may reveal important 

information, perhaps unanticipated and 

unplanned for, years later. Given the 

unique implications of the information 

that can be developed through WGS, if 

it is either known that a specific 

research study will include this 

technique, or might include it, we 

believe that this aspect of the research 

must be disclosed to prospective 

subjects as part of the informed consent 

process. It is recognized that under the 

pre-2018 rule, if a research study were 

to involve WGS, this research procedure 

would have almost always been 

included in the description of the 

research. However, to remove any 

ambiguity about whether such 

information would need to be included 

in the informed consent, the final rule 

makes this requirement explicit through 

this new element of consent. 

The information that would have to 

be disclosed under these additional 

elements of consent is often relevant to 

an individual’s decision of whether to 

participate in a research study. Such 

information may have been included in 

informed consent forms under the pre2018 rule. However, the final rule now 

requires inclusion of these additional 

elements, when appropriate. 

The additional element of consent 

proposed in the NPRM that was not 

included in the final rule would have 

required providing subjects or their 

legally authorized representatives with 

an option to consent, or refuse to 

consent, to investigators re-contacting 

the subject to seek additional 

information or biospecimens or to 

discuss participation in another 

research study. Although for some 

research studies, it will be desirable to 

inform prospective subjects about 

investigators’ plan to re-contact subjects 

for certain purposes, and give them the 

option to agree or disagree to such recontact, we agree with the public 

comments that questioned the 

importance of requiring that such 

information be included in the consent 

form. Although the final rule does not 

include this additional element of 

consent, this information can be 

included in the consent form. 

D. Elements of Broad Consent for the 

Storage, Maintenance, and Secondary 

Research Use of Identifiable Private 

Information or Identifiable 

Biospecimens (§ll.116(d)) 

1. Background and Pre-2018 

Requirements 

Under the pre-2018 rule, if identifiers 

are removed from information and 

biospecimens such that the identity of 

the subject could not be readily 

ascertained by an investigator or 

associated with the information or 

biospecimens, then such information 

and biospecimens that have been 

collected for purposes other than the 

proposed research could be used 

without any requirement for informed 

consent. Similarly, under the HIPAA 

Privacy Rule, if data are de-identified or 

HIPAA identifiers do not accompany 

biospecimens, then the Privacy Rule 

does not apply. When identifiers have 

not been removed, under the pre-2018 

rule investigators were allowed in 

certain situations to obtain a consent 

that is broader than for a specific 

research study, such as for creating a 

research repository that involves 

obtaining biospecimens from living 

individuals for use in future research 

studies. In these cases, an IRB could 

determine that the original consent for 

the creation of the research repository 

satisfied the requirements of the 

Common Rule for the conduct of the 

future research, provided that the 

elements of consent continue to be 

satisfied for the future research. Despite 

this flexibility in the Common Rule, 

stakeholders and the Common Rule 

departments and agencies believe that 

the elements of consent required under 

§ ll.116 of the pre-2018 rule often 

were not satisfied in the case of broad 

consent for future unspecified research 

use of identifiable private information 

or identifiable biospecimens. 

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46HHS. Modifications to the HIPAA Privacy, 

Security, Enforcement, and Breach Notification 

Rules Under the Health Information Technology for 

Economic and Clinical Health Act and the Genetic 

Information Nondiscrimination Act; Other 

Modifications to the HIPAA Rules. 78 FR 5611 (Jan. 

25, 2013). Retrieved from https://www.gpo.gov// 

fdsys/pkg/FR-2013-01-25/pdf/2013-01073.pdf. 

With respect to HIPAA, HHS’s pre2013 interpretation of the HIPAA 

Privacy Rule was that authorizations for 

research needed to be study-specific, 

and thus, that such authorizations could 

not authorize certain future unspecified 

research. However, in January 2013, the 

Office for Civil Rights modified its prior 

interpretation.46 Under the new 

interpretation, an authorization now 

may be obtained from an individual for 

uses and disclosures of protected health 

information for future research 

purposes, so long as the authorization 

adequately describes the future research 

such that it would be reasonable for the 

individual to expect that his or her 

protected health information could be 

used or disclosed for the future research 

purposes. 

Because biospecimens and 

information that have been collected for 

clinical use or purposes other than for 

the proposed research are often an 

important source of information and 

material for investigators, and the re-use 

of existing information and materials 

can be an efficient mechanism for 

conducting research without presenting 

additional physical or psychological 

risks to the individual, it seemed 

prudent to consider changes to current 

regulations relating to those issues. 

2. NPRM Proposals 

The NPRM proposed to allow broad 

consent to cover the storage or 

maintenance for secondary research use 

of all biospecimens (regardless of 

identifiability) and identifiable private 

information. Broad consent would be 

permissible for the storage or 

maintenance for secondary research of 

such information and biospecimens that 

were originally collected for either 

research studies other than the proposed 

research or nonresearch purposes. The 

broad consent document would also 

meet the consent requirement for the 

use of such stored biospecimens and 

information for individual research 

studies. The NPRM made a separate 

case for nonidentified private 

information than it did for 

biospecimens, stating that consent 

would not be required for the secondary 

research use of nonidentified private 

information, such as the research use of 

medical records that have had all 

identifiers removed. Because the NPRM 

proposed that the definition of human 

subject be expanded to include all 

biospecimens, it also proposed to 

facilitate research using biospecimens 

by permitting broad consent to be 

obtained for their storage or 

maintenance for secondary research. 

It was envisioned that the proposed 

broad consent provision would be used 

by institutions and investigators to give 

individuals the choice to either allow or 

disallow the use of their biospecimens 

and identifiable private information for 

secondary research. In some cases, 

institutions would be expected to seek 

broad consent as part of a research 

protocol to create a research repository 

of biospecimens or information. 

However, in other cases it was expected 

that institutions, particularly those that 

do not typically conduct human 

subjects research, might not develop a 

research protocol to create a research 

repository, but still choose to seek broad 

consent from individuals for the 

research use of their biospecimens or 

identifiable private information. In such 

cases, these institutions might simply 

‘‘tag’’ biospecimens and information as 

either available or not available for 

secondary research. 

Because broad consent is a different 

form of consent than the consent that is 

obtained for a specific research study, 

the NPRM proposed required elements 

for broad consent that would include 

several of the basic and additional 

elements of informed consent, but not 

all, and would include several 

additional required elements. The 

NPRM proposed to require that the 

information included in broad consent 

describe the biospecimens and 

identifiable private information that 

would be covered by the consent, 

recognizing that the biospecimens and 

information to be used in future 

research studies might be collected after 

the consent was obtained. Further, the 

NPRM proposed that broad consent for 

the research use of biospecimens or 

identifiable private information 

obtained for nonresearch purposes 

would be limited to covering either or 

both of the following: (1) Biospecimens 

or identifiable private information that 

exist at the time at which broad consent 

is sought; and (2) biospecimens or 

identifiable private information that will 

be collected up to 10 years after broad 

consent is obtained for adult subjects, 

and, for research involving children as 

subjects, biospecimens or identifiable 

private information that will be 

collected up to 10 years after broad 

consent is obtained or until the child 

reaches the legal age of consent to the 

treatments or procedures involved in 

the research, whichever comes first. 

The NPRM proposed to include the 

standard concerning who is a child 

based upon the definition of ‘‘children’’ 

as defined at 45 CFR 46.402(a). At the 

time the child becomes an adult, the 

broad consent or permission would no 

longer be valid and either broad consent 

would need to be sought from the childturned-adult, or the investigator would 

need to seek a waiver of informed 

consent in order to use the individual’s 

biospecimens or identifiable private 

information for research, unless one of 

the exclusions or exemptions were 

applicable. 

A proposed element of broad consent 

in the NPRM included a requirement 

that subjects be informed that they may 

withdraw consent, if feasible, for 

research use or distribution of the 

subject’s information or biospecimens at 

any time without penalty or loss of 

benefits to which the subject is 

otherwise entitled. However, 

information that has been stripped of 

identifiers might not be traceable. Thus, 

it might not be feasible to withdraw 

consent for future use or distribution in 

this case. If, however, an investigator 

committed to permitting a subject to 

discontinue the use of such information, 

it was expected that the investigator 

would honor this commitment by not 

stripping identifiers and using the 

information or biospecimens in 

research. The proposed regulations 

would not require investigators to make 

such a commitment. 

Another proposed element of broad 

consent in the NPRM related to the 

public posting of nonidentified data 

about a subject. This proposed element 

of broad consent would include an 

option, when relevant, for an adult 

subject or the subject’s legally 

authorized representative to consent or 

refuse to consent to the inclusion of the 

subject’s data with removal of the 

identifiers listed in the HIPAA Privacy 

Rule at 45 CFR 164.514(b)(2)(i)(A) 

through (Q), in a database that is 

publicly available and openly accessible 

to anyone. This provision was proposed 

in the context of increasing interest in 

inviting study participants to allow their 

study data, in some cases including 

genomic data, to be made publicly 

available in order to maximize the 

potential for research that spurs 

increased understanding of disease 

processes. Under this provision, the 

consent document would be required to 

prominently note the option for the 

participant to allow the investigator to 

publically post (e.g., on a Web site) the 

participant’s genomic or other 

potentially identifiable sensitive 

information, and to include a 

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description of the risks associated with 

public access to the data. 

To facilitate the use of broad consent, 

the NPRM proposed that the Secretary 

of HHS would publish in the Federal 

Register templates for broad consent 

that would contain all of the required 

elements of consent in these situations. 

It was envisioned that at least two broad 

consent templates would be developed: 

one for information and biospecimens 

originally collected in the research 

context, and another for information 

and biospecimens originally collected in 

the nonresearch context. 

Public comment was sought on 

whether broad consent to secondary 

research use of information and 

biospecimens collected for nonresearch 

purposes should be permissible without 

a boundary, or whether a time limitation 

or some other type of limitation should 

be imposed on information and 

biospecimens collected in the future 

that could be included in the broad 

consent as proposed in the NPRM. If a 

time limit should be required, public 

comment was sought on whether the 

NPRM proposal of up to 10 years was 

a reasonable limitation and whether a 

limitation related to an identified 

clinical encounter would better inform 

individuals of the clinical information 

and biospecimens that would be 

covered by a broad consent. Public 

comment was also sought on whether 

all of the elements of broad consent 

proposed in the NPRM should be 

required for the secondary use of 

biospecimens or identifiable private 

information originally collected as part 

of a research study that was conducted 

without consent because (1) either the 

original research study met an exclusion 

or exempt category of research, or (2) a 

waiver of consent was approved by an 

IRB. 

Public comment was sought on how 

likely investigators are to seek broad 

consent for the use of identifiable 

private information (as contrasted with 

biospecimens), given that provisions 

within the NPRM would make it easier 

to do such research without consent. In 

this regard, the NPRM proposal to 

prohibit waiver of consent by an IRB if 

a person has been asked for broad 

consent and refused to provide it could 

create a disincentive on the part of 

investigators from choosing to seek 

broad consent for research involving 

secondary use of identifiable private 

information. Given the costs and time 

and effort involved in implementing the 

system for obtaining broad consent for 

the use of identifiable private 

information and tracking when people 

provide consent or refuse to do so, the 

public was asked to comment on 

whether the benefits to the system were 

likely to outweigh the costs, and if so, 

whether the broad consent provisions 

should be limited to obtaining broad 

consent for research use of 

biospecimens. 

3. Public Comments 

Approximately 475 comments 

addressed broad consent, a majority of 

which expressed opposition to broad 

consent as proposed and discussed in 

the NPRM. The basis of this opposition 

was largely related to the NPRM 

proposal that some type of consent 

(broad or specific) would be required for 

research with nonidentified 

biospecimens. A smaller number of 

comments (approximately 150) 

addressed the adequacy or inadequacy 

of broad consent as a concept, or the 

proposed broad consent templates to be 

created by HHS. 

Public comment on the proposed, but 

not yet developed, broad consent 

templates was mixed, with a majority of 

comments stating that it was impossible 

to comment on a template that had not 

yet been created. Even among those who 

supported the use of broad consent, 

some had questions about whether 

broad consent provided at one 

institution would be sufficient for 

research ultimately conducted at 

another institution. Many comments 

further noted that the entire regulatory 

schema around broad consent (e.g., 

exemptions dependent on broad 

consent, prohibition on an IRB waiving 

broad consent if broad consent had been 

sought and someone declined) required 

additional study and discussion and 

recommended that the department issue 

another NPRM on these issues following 

some form of systematic analysis and 

broader public consultation. A 

professional investigative pathology 

association and many of its members 

endorsed the concept of broad consent 

and the development of templates by 

the Federal Government, writing that 

they would be less burdensome but still 

a functional way of promoting ethically 

conducted biomedical research with 

biospecimens. 

Several commenters suggested that 

institutions needed to retain the ability 

to create and amend broad consent 

forms tailored to a variety of situations 

rather than rely on a federal template. 

These comments also generally stressed 

the importance of retaining an IRB’s 

active role in reviewing the broad 

consent process and specific secondary 

research studies to ensure that interests 

other than autonomy and concerns other 

than those related to privacy were 

considered in a proposed study. A 

minority of commenters additionally 

expressed concern with the Federal 

Government’s ability to develop broad 

consent templates that the regulated 

community might feel were sufficiently 

informative. 

Public comments were also mixed on 

whether or not broad consent as 

proposed in the NPRM would constitute 

meaningful consent. Many comments 

noted that a consent form sufficiently 

broad to cover all potential future 

secondary research uses of 

biospecimens or identifiable private 

information might be so broad and 

vague as to be not meaningful or 

informative to prospective research 

subjects. Others doubted the 

meaningfulness of broad consent 

obtained in the clinical setting. One 

academic research institution 

questioned whether it was really 

consent at all, but rather an agreement 

or permission, and another commenter 

questioned whether broad consent 

would increase subjects’ autonomy. 

Many of the commenters who 

opposed broad consent also argued 

against any requirement to obtain 

consent for the use of nonidentified 

biospecimens. One academic research 

institution raised serious concerns about 

obtaining meaningful broad consent, 

which undermines existing privacy and 

other protections for subjects in 

research. Others noted that requiring 

broad consent for all secondary use of 

all biospecimens would require that 

there always be a link or code between 

the biospecimen and the subject’s 

identity, which ultimately would result 

in an overall increase in privacy risks. 

Many commenters favored an opt-out 

system for broad consent (especially 

with respect to broad consent for use of 

nonidentified biospecimens). An AI/AN 

organization expressed overall concern 

about the concept of broad consent, 

noting that many AI/AN people believe 

that specimens and blood are 

considered sacred and recommending 

that all secondary uses of collected 

specimens and data should require an 

additional consent process, including 

tribal consent when specimens and data 

are obtained from AI/AN populations. 

Few comments were received on the 

actual proposed elements of broad 

consent. Of these, a majority expressed 

confusion with the proposals related to 

the duration of the consent and the 

scope of the biospecimens and 

identifiable information that could be 

collected. 

The NPRM also asked whether broad 

consent to secondary research use of 

information and biospecimens collected 

for nonresearch purposes should be 

permissible without a boundary, or 

whether a time limitation or some other 

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type of limitation should be imposed on 

information and biospecimens collected 

in the future that could be included in 

the broad consent. If a time limit should 

be required, the NPRM asked whether 

up to 10 years was a reasonable 

limitation. It also asked whether a 

limitation related to an identified 

clinical encounter would better inform 

individuals of the clinical information 

and biospecimens that would be 

covered by a broad consent document. 

Approximately 65 commenters 

specifically answered this question. 

Most who commented were opposed 

to the 10-year limitation on the period 

of time that an institution could collect 

biospecimens and information from an 

individual once broad consent had been 

sought and obtained. They stated that 

the limitation was arbitrary, not 

supportable by anything discussed in 

the NPRM, and presented an 

administrative burden for institutions 

and investigators to time stamp and 

track the 10-year limit for each subject. 

A few commenters stated that a 10-year 

limit is a reasonable boundary, but were 

concerned about the need to re-consent 

people once they reach the legal age of 

consent. In large data sets, identifying 

such people could be very challenging 

as people often move locations during 

such lengths of time, which would 

create an administrative barrier. A few 

commenters suggested that 10-year 

boundary was too long and one research 

institution commented that in its 

experience individuals seem to prefer 

shorter time limits tied to specific 

periods (e.g., a series of clinical 

encounters, participation in an ongoing 

study). 

A few comments stated that any time 

limit could have a negative effect on 

rare disease research as the numbers of 

affected people are so small and, as 

discoveries are made, there is often a 

need to go back to years’ worth of 

information or stored biospecimens to 

search for markers, mutations, or 

clinical information that is related to the 

new discovery. Such commenters 

expressed concern that this could be 

deleterious to individuals with rare 

disease seeking a diagnosis. 

Some commenters were confused 

about how the 10-year boundary 

proposed in the NPRM was supposed to 

function. Some comments assumed that 

one could only use the biospecimens or 

data for a 10-year period and after that 

period one would be required to get 

consent again for the use of those items. 

Others assumed that investigators 

would have to re-consent people every 

10 years, but the information and 

biospecimens could be used 

indefinitely. For these reasons, many 

comments on the 10-year boundary said 

it was unreasonable and unworkable 

operationally. Some suggested that 

instead of 10-year boundary, patients 

could be routinely reminded that they 

gave consent and can be reminded that 

they can opt out at any time. Several 

large research institutions commented 

that the time limit would necessitate a 

lot of tracking for institutions and could 

lead to smaller health care institutions 

ceasing their collection of biospecimens 

for research, which would ultimately 

have a negative impact on research. 

The NPRM also asked whether all of 

the elements of consent proposed at 

§ ll.116(c) should be required for the 

secondary use of biospecimens or 

identifiable private information 

originally collected as part of a research 

study that was conducted without 

consent because either the original 

research study met an exclusion or 

exempt category of research, or a waiver 

of consent was approved by an IRB. 

Approximately 30 comments answered 

this question. Responses ranged from 

those saying the elements are not as 

relevant as the burden of having to seek 

consent every 10 years. Many stated that 

the elements of consent appeared to be 

growing in the proposed rule at the 

same time that the rule was requiring 

simpler and shorter consent forms. As 

such, efforts should not be made to 

include all of the elements required in 

specific consent to broad consent; 

otherwise the intent of broad consent 

would be lost. 

The NPRM also asked whether oral 

consent should be permissible in 

limited circumstances as proposed 

under the exemption for the storage and 

maintenance of biospecimens and 

identifiable private information. More 

than 60 pathologists, pathology 

departments, and pathology 

organizations suggested that oral 

consent should not be allowed in this 

context because it raises too many 

administrative challenges and may 

undermine public trust. A few 

commenters felt oral consent should be 

permitted but generally did not provide 

a rationale. 

Finally, some comments indicated 

that broad consent as a concept should 

not be included in a final rule, and that 

the standards that exist under the pre2018 rule for secondary research (i.e., 

either that an investigator obtains study 

specific consent or a waiver of informed 

consent from an IRB) should be 

maintained in a final rule. 

4. Response to Comments and 

Explanation of the Final Rule: Elements 

of Broad Consent 

The final rule includes an option to 

obtain broad consent for the storage, 

maintenance, and secondary research 

use of identifiable private information 

or identifiable biospecimens, as defined 

at §ll.102(e)(5) and (6), but several 

significant changes were made in 

response to public comments. Although 

in some ways the final rule’s broad 

consent provision resembles the 

provision that was proposed in the 

NPRM, it is important to recognize a 

very fundamental difference between 

the role that this provision will play 

under the final rule, as compared to the 

role it was intended to play under the 

NPRM. This key difference relates to the 

fact that the provisions in the NPRM 

that would have generally required 

consent for secondary research use of 

nonidentified biospecimens, including 

imposing narrow stringent criteria for 

IRB waiver of consent with respect to 

such research, are not being 

implemented because the NPRM’s 

proposal that all biospecimens, 

regardless of their identifiability, be 

covered under the Common Rule has 

not been adopted. Importantly, under 

the final rule, broad consent is 

permissible only for secondary research 

and no other types of research. 

Thus, had all of those NPRM 

provisions been implemented, 

investigators who wanted to conduct 

secondary research with biospecimens 

would in most instances have found 

themselves essentially forced to use the 

new broad consent provisions as their 

only practical option for conducting 

such research. This is because generally, 

under the NPRM proposals, they would 

no longer have had the option to deidentify information or biospecimens, or 

to use them in coded form, to avoid 

application of the Common Rule’s 

requirements. Under the NPRM’s 

proposals, had investigators not 

obtained broad consent, they would 

often not practicably be able to meet the 

informed consent requirements relating 

to such research (which would have 

been covered under the Common Rule). 

Therefore, it would generally have been 

the case that they would have had little 

choice but to obtain broad consent, 

assuming they did not want to 

undertake the alternative of obtaining 

study-specific consent from subjects 

each and every time they conducted a 

study involving secondary use of 

biospecimens. 

Given that we did not adopt the 

NPRM’s proposal to cover all 

biospecimens regardless of their 

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47HHS. Office for Human Research Protections. 

Coded Private Information or Specimens Use in 

Research, Guidance. October 16, 2008. Retrieved 

from https://www.hhs.gov/ohrp/regulations-andpolicy/guidance/research-involving-coded-privateinformation/index.html. 

identifiability under the Common Rule, 

the final rule also does not adopt 

proposed consent requirements for 

secondary research with nonidentified 

biospecimens. For this reason, the final 

rule’s provisions relating to broad 

consent now play a very different role 

from those proposed in the NPRM. In 

most instances, these provisions will be 

providing new options—that is, new 

flexibility—to an investigator, in 

addition to those options that an 

investigator would have had under the 

pre-2018 rule. An investigator wishing 

to do secondary research with 

biospecimens will continue to have the 

option of doing secondary research with 

nonidentifiable biospecimens, as was 

the case in the pre-2018 rule. An 

investigator also could continue to use 

biospecimens that are coded, thus 

allowing the collection of additional 

information about the subjects over 

time.47 In both of those instances, no 

additional consent would be required 

because the research would not involve 

human subjects as defined by the final 

rule. Furthermore, even if the 

investigator wanted to use the 

biospecimens with identifiers attached, 

he or she would still have the option of 

asking an IRB to waive the requirement 

to obtain informed consent: the waiver 

criteria are in most respects unchanged 

under the final rule. 

For these reasons, the broad consent 

provisions at § ll.116(d) afford 

investigators wishing to conduct 

secondary research on identifiable 

private information or identifiable 

biospecimens an additional alternative 

to obtaining an IRB waiver of consent or 

to obtaining study-specific consent. 

Given that these new broad consent 

provisions are essentially a new 

alternative to other options that are very 

similar to those that existed under the 

pre-2018 rule, these provisions are not 

increasing any regulatory burden or 

making it more difficult to do research. 

Indeed, just the opposite is the case. The 

changes made in the final rule are 

responsive to the significant criticisms 

expressed by many of the commenters 

about what the NPRM proposed, under 

which obtaining broad consent would 

have imposed substantial new burdens 

on a vast amount of secondary research 

with biospecimens. In contrast, when 

investigators choose to use the broad 

consent provisions under the final rule, 

they will presumably be doing so 

because this new option is less 

burdensome to them than their other 

(largely unchanged) options for 

conducting such research. 

Although we recognize public 

commenters’ concern that broad consent 

might not be as meaningful or 

informative as study-specific consent, it 

is also important to note that when an 

investigator chooses to use this new 

option, doing so will generally provide 

increased protection to the autonomy of 

research subjects. It will give them a 

choice to say no to such research, in 

contrast to most of the other routes by 

which an investigator might generally 

choose to conduct this type of research, 

such as with a waiver of informed 

consent, which allows research to take 

place regardless of the wishes of the 

person whose information or 

biospecimens are being studied, and 

without their knowledge. In addition, in 

response to the public’s concerns that 

broad consent would not be meaningful, 

some of the elements of broad consent 

have changed from what was proposed 

in the NPRM to require more specific 

information about the research that may 

be conducted. As discussed in the 

NPRM, one of the main purposes of the 

final rule is to facilitate the conduct of 

minimal risk research, while enhancing 

subjects’ autonomy. We believe that the 

option to obtain broad consent furthers 

this goal. 

It is important to recognize that broad 

consent is a permissible option only for 

secondary research. Secondary research 

is limited to research using identifiable 

private information or identifiable 

biospecimens that are collected for 

either research studies other than the 

proposed research or nonresearch 

purposes. It is not permissible to obtain 

broad consent for any other type of 

research (e.g., research involving the 

collection of information or 

biospecimens through a research 

interaction or intervention with a 

subject). The informed consent 

requirements in § ll.116(b) and (c) 

will be applicable to all human subjects 

research for which broad consent is not 

an option. However, it is envisioned 

that research requiring study-specific 

consent, such as research involving the 

collection of information or 

biospecimens through a research 

interaction or intervention with a 

subject, will sometimes also involve 

seeking subjects’ broad consent for the 

secondary research use of identifiable 

private information or identifiable 

biospecimens obtained as part of the 

original research study. 

When broad consent is obtained, the 

general requirements for informed 

consent in § ll.116(a) apply, except 

that the requirements at §ll.116(a)(5) 

(imposing certain requirements 

concerning the presentation of 

information for informed consent and 

prescribing the order in which consent 

information is presented) do not apply 

to broad consent. 

We expect that, given the different 

requirements set forth for study-specific 

consent and broad consent, some 

institutions and investigators may elect 

to pursue study-specific consents for the 

storage, maintenance, and secondary 

research uses of identifiable private 

information and identifiable 

biospecimens (or for some subset of 

such research) whereas other 

institutions and investigators may elect 

to pursue broad consent for the same 

types of research (or for some subset of 

such research). For instance, with regard 

to the public comments raising concern 

about broad consent being sought from 

AI/AN peoples, it is expected that 

institutions, investigators, and IRBs will 

consider these concerns when 

determining when it might be 

appropriate to seek study-specific 

consent for the secondary research use 

of identifiable biospecimens, as well as 

the need for tribal consent, when 

appropriate. 

Perhaps even more commonly, 

however, given that the NPRM proposal 

regarding generally requiring consent 

for research use of nonidentifiable 

biospecimens has not been adopted, 

many investigators may choose to use 

the routes that previously existed under 

the pre-2018 rule, and will continue to 

exist, for conducting such research 

without informed consent under the 

Common Rule. Those options include 

using nonidentifiable biospecimens, 

including perhaps having a code 

maintained that will allow the 

investigator to obtain additional 

information about the subjects, or 

obtaining a waiver from an IRB of the 

need to obtain informed consent. 

The broad consent provision in the 

final rule is different in three main ways 

from what was proposed in the NPRM. 

First, consistent with the decision not to 

revise the definition of human subject to 

include biospecimens regardless of 

identifiability, the broad consent 

provision in § ll.116(d) only applies 

to secondary research using identifiable 

private information and identifiable 

biospecimens. 

Second, the elements of broad consent 

have been strengthened and simplified 

in response to public comments. The 

final rule strengthens the element of 

broad consent proposed in the NPRM 

regarding the need to provide a general 

description of the types of research that 

may be conducted with identifiable 

private information and identifiable 

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biospecimens. It does this by requiring 

that this description must include 

sufficient information to allow a 

reasonable person to expect that the 

broad consent would permit the types of 

research conducted. This ‘‘reasonable 

person’’ standard is consistent with the 

interpretation that the Office for Civil 

Rights provided for authorization 

obtained from an individual for the use 

or disclosure of protected health 

information for future research 

purposes. In addition, the final rule has 

been strengthened to require that when 

subjects will not be informed about the 

details for any specific research studies 

that might be conducted using their 

identifiable private information or 

identifiable biospecimens, the broad 

consent must disclose this fact and 

inform subjects that they might have 

chosen not to consent to some of those 

specific research studies. It is 

envisioned that for certain types of 

research, such as research for which 

there is reason to believe some subjects 

will find the research controversial or 

objectionable, a more robust description 

of the research will be required in order 

to meet this ‘‘reasonable person’’ 

standard. This requirement has been 

included in the final rule in recognition 

of the concerns raised by some public 

commenters that broad consent would 

not be meaningful because it will not 

provide detailed information about 

specific research studies that might be 

conducted with the individual’s 

identifiable private information or 

identifiable biospecimens. 

As proposed in the NPRM, the final 

rule permits broad consent to be sought 

for either a narrow type of research to 

be conducted in the future (e.g., cancer 

research), or a broader scope of research. 

Given this flexibility, while the final 

rule includes an exemption for 

secondary research for which broad 

consent is required, the exemption is 

contingent on several criteria being 

satisfied, including that an IRB 

determines that the research to be 

conducted is within the scope of the 

broad consent (§ ll.104(d)(8)). This 

exemption is further discussed in 

Section V. For research that is not 

exempt, the IRB is expected to assess 

whether the description of the research 

included in the broad consent form is 

adequate to permit a reasonable person 

to expect that they were providing 

consent for the currently proposed 

secondary research study. 

While strengthening the broad 

consent requirements, the final rule also 

adopts simplified and more flexible 

elements of broad consent than what 

was proposed in the NPRM. For 

example, the final rule requires that the 

broad consent include a description of 

the identifiable private information or 

identifiable biospecimens that might be 

used in research, whether sharing of 

such information or biospecimens might 

occur, and the types of institutions or 

investigators that might conduct 

research with such information or 

biospecimens. However, the final rule 

does not adopt the NPRM’s proposed 

limitations on the research use of 

biospecimens or identifiable private 

information obtained for nonresearch 

purposes, that would have only 

permitted a broad consent to cover 

either or both of the following: (1) 

Biospecimens or identifiable private 

information that exist at the time at 

which broad consent is sought; and (2) 

biospecimens or identifiable private 

information that will be collected up to 

10 years after broad consent is obtained 

or until the child reaches the legal age 

of consent to the treatments or 

procedures involved in the research, 

whichever comes first. We were 

persuaded by the public comments that 

raised concerns about the complexity 

and tracking burden that such 

limitations would impose, without 

clearly offering individuals a more 

meaningful way to control the use of 

their information or biospecimens. 

In addition, the broad consent 

requirements have been simplified to 

avoid creating redundant requirements 

with the basic elements of informed 

consent under § ll.116(b) that must 

also be included in broad consent 

obtained under § ll.116(d). For 

example, in the final rule, it is required 

that broad consent include a statement 

that participation is voluntary, refusal to 

participate will involve no penalty or 

loss of benefits to which the subject is 

otherwise entitled, and the subject may 

discontinue participation at any time 

without loss of benefits to which the 

subject is otherwise entitled 

((§ ll.116(d)(1), incorporating 

§ ll.116(b)(8) for broad consent). 

Therefore, the comparable element of 

broad consent that was proposed in the 

NPRM is not included in the final rule. 

As discussed in the NPRM, we expect 

that, when appropriate, this element of 

broad consent will inform subjects that 

information that has been stripped of 

identifiers might not be traceable, and 

thus it might not be feasible to withdraw 

consent for future use or distribution in 

this case. However, if an investigator 

commits to permitting a subject to 

discontinue use of the subject’s 

identifiable private information or 

identifiable biospecimens, it is expected 

that the investigator will honor this 

commitment by not removing 

identifiers. 

Similarly, the final rule also does not 

include the element of broad consent 

proposed in the NPRM that, when 

relevant, would have required the broad 

consent to include an option for an 

adult subject or the representative to 

consent, or refuse to consent, to the 

inclusion of the subject’s data, with 

removal of the identifiers listed in 45 

CFR 164.514(b)(2)(i)(A) through (Q), in 

a database that is publicly and openly 

accessible to anyone, and that this 

option be prominently noted and 

include a description of the risks of 

public access to the data. We believe 

this proposed requirement is 

unnecessary because it overlaps with 

the broad consent elements included in 

the final rule requiring a statement 

describing the extent, if any, to which 

confidentiality of records identifying the 

subject will be maintained 

(§ ll.116(d)(1), incorporating 

§ ll.116(b)(5) for broad consent), and 

a description of any reasonably 

foreseeable risks or discomforts to the 

subject (§ll.116(d)(1), incorporating 

§ ll.116(b)(2) for broad consent). 

The final rule includes a slightly 

different provision relating to the return 

of research results than that proposed in 

the NPRM. As set forth in 

§ ll.116(d)(6) of the final rule, unless 

it is known that clinically relevant 

research results, including individual 

research results, will be disclosed to the 

subject in all circumstances, a statement 

that such results may not be disclosed 

to the subject must be included in the 

broad consent. This element of broad 

consent differs from the related 

requirement in § ll.116(c)(8) that 

pertains when an investigator is seeking 

consent for a specific study, since 

unlike the circumstances under which 

broad consent is likely to be sought, 

investigators seeking consent for a 

specific study will know if the study 

includes a plan to return research 

results to subjects. The NPRM proposed 

that a general element of informed 

consent be included as part of a broad 

consent, namely that the consent 

include a statement regarding whether 

clinically relevant research results, 

including individual research results, 

would be disclosed to subjects, and if 

so, under what conditions. The language 

adopted in the final rule is intended to 

provide transparency, but is tailored to 

the broad consent context as those 

seeking broad consent may not know 

whether clinically relevant research 

results, including individual research 

results, will always be disclosed to 

subjects, and if so, under what 

conditions. Nonetheless, unless 

investigators know that such results will 

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be disclosed to subjects in all 

circumstances, subjects will be 

informed through a broad consent of the 

possibility that such results will not be 

disclosed to them. This provision is 

intended to pertain to all clinically 

relevant research results, including 

general or aggregate research findings 

and individual research results. This 

element of broad consent will affect the 

applicability of the exemption set forth 

at §ll.104(d)(8), for secondary 

research for which broad consent is 

required. This exemption applies only if 

the investigator does not include 

returning individual research results to 

subjects as part of the study plan 

(noting, however, that this provision 

does not prevent an investigator from 

abiding by any legal requirements to 

return individual research results). 

Although it is envisioned that broad 

consent will often be sought with the 

expectation that specific secondary 

research studies using identifiable 

private information or identifiable 

biospecimens will be exempt under 

§ ll.104(d)(8), this will not always be 

the case. Broad consent can also be 

obtained for secondary research that 

will not qualify for this exemption, such 

as secondary research that will involve 

returning clinically relevant research 

results to subjects. In these cases, the 

specific secondary research study will 

need to undergo IRB review and 

approval under § ll.111, and we 

expect that the IRB would consider 

what subjects were told in the broad 

consent regarding the return of research 

results. The only exception to the 

requirement for IRB review of such 

research, if covered by this policy, is if 

the research qualifies for another 

exemption or the research is carried out 

under a Secretarial waiver at 

§ ll.101(i). 

Finally, the third main difference 

between the NPRM and final rule 

provision on broad consent is that the 

final rule does not include broad 

consent templates to be established by 

the Secretary of HHS. We agree with the 

public comments that favored allowing 

institutions to create their own broad 

consent forms that could be tailored to 

a variety of circumstances. Therefore, 

under the final rule, investigators and 

institutions may develop broad consent 

forms, which, provided specified 

conditions are satisfied, would meet the 

exemption for the storage and 

maintenance for secondary research use 

of identifiable biospecimens or 

identifiable private information 

(§ ll.104(d)(7)). This exemption is 

further discussed in Section V. At a later 

time, the Secretary of HHS expects to 

develop guidance on broad consent, 

which could include broad consent 

templates. 

In addition, we are also including in 

the final rule an element that for 

research involving biospecimens, when 

appropriate, the broad consent must 

state whether the research will (if 

known) or might include whole genome 

sequencing (WGS) (§ ll.116(d)(1), 

incorporating §ll.116(c)(9)). The 

reasons for requiring this element in the 

broad consent are similar to those 

discussed above regarding the addition 

of this requirement in the additional 

elements of consent at §ll.116(c)(9). 

WGS generates an extremely large 

amount of data, which when analyzed 

can yield information about an 

individual, including factors that could 

contribute to their future medical 

conditions. Therefore, given the 

implications of WGS information for an 

individual and his or her biological 

family, if it is known that the broad 

consent will or might permit the use of 

individuals’ biospecimens for WGS, we 

believe that this aspect of the research 

must be disclosed to prospective 

subjects as part of the broad consent 

process. The broad consent must 

include a general description of the 

types of research that may be conducted 

with the identifiable private information 

or identifiable biospecimens, with 

sufficient information to allow a 

reasonable person to expect that the 

broad consent would permit the types of 

research conducted (§ ll.116(d)(2)). 

Including an additional element of 

broad consent that specifically 

addresses WGS makes it clear that such 

information must be disclosed to 

prospective subjects. 

Under the final rule, if the subject or 

the subject’s legally authorized 

representative is asked to provide broad 

consent, the broad consent must satisfy 

the general informed consent 

requirements at § ll.116(a)(1)-(4), and 

(a)(6), and must include all of the 

following 12 elements that are 

applicable: 

• A description of any reasonably 

foreseeable risks or discomforts to the 

subjects (§ll.116(d)(1), incorporating 

basic elements of informed consent in 

§ ll.116(b)(2)); 

• A description of any benefits to the 

subject or to others that may reasonably 

be expected from the research 

((§ ll.116(d)(1), incorporating basic 

elements of informed consent in 

§ ll.116(b)(3); 

• A statement describing the extent, if 

any, to which confidentiality of records 

identifying the subject will be 

maintained ((§ll.116(d)(1), 

incorporating basic elements of 

informed consent in §ll.116(b)(5)); 

• A statement that participation is 

voluntary, refusal to participate will 

involve no penalty or loss of benefits to 

which the subject is otherwise entitled, 

and the subject may discontinue 

participation at any time without 

penalty or loss of benefits to which the 

subject is otherwise entitled 

((§ ll.116(d)(1), incorporating basic 

elements of informed consent in 

§ ll.116(b)(8)); 

• If applicable, a statement that the 

subject’s biospecimens (even if 

identifiers are removed) may be used for 

commercial profit and whether the 

subject will or will not share in this 

commercial profit ((§ ll.116(d)(1), 

incorporating additional elements of 

consent in § ll.116(c)(7)); 

• When appropriate, for research 

involving biospecimens, whether the 

research will (if known) or might 

include WGS (i.e., sequencing of a 

human germline or somatic specimen 

with the intent to generate the genome 

or exome sequence of that specimen.) 

((§ ll.116(d)(1), incorporating the 

additional element of consent in 

§ ll.116(c)(9)); 

• A general description of the types of 

research that may be conducted with 

identifiable private information or 

identifiable biospecimens. This 

description must include sufficient 

information to permit a reasonable 

person to expect that the broad consent 

would permit the types of research 

conducted (§ll.116(d)(2)); 

• A description of the identifiable 

private information or identifiable 

biospecimens that might be used in 

research, whether sharing of such 

information or biospecimens might 

occur, and the types of institutions or 

investigators that might conduct 

research with such information or 

biospecimens (§ll.116(d)(3)); 

• A description of the period of time 

allowed that the identifiable private 

information or identifiable 

biospecimens may be stored and 

maintained (which period of time could 

be indefinite), and a description of the 

period of time that such information or 

biospecimens may be used for research 

purposes (which period of time could be 

indefinite (§ll.116(d)(4)); 

• Unless the subject or legally 

authorized representative will be 

provided details about specific research 

studies, a statement that they will not be 

informed of the details of any specific 

research studies that might be 

conducted using the subject’s 

identifiable private information or 

identifiable biospecimens, including the 

purposes of the research and that they 

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might have chosen not to consent to 

some of those specific research studies 

(§ ll.116(d)(5)); 

• Unless it is known that clinically 

relevant research results, including 

individual research results, will be 

disclosed to the subject in all 

circumstances, a statement that such 

results may not be disclosed to the 

subject; (§ll.116(d)(6)); and 

• An explanation of whom to contact 

for answers to questions about the 

subject’s rights about storage and use of 

the subject’s identifiable private 

information or identifiable 

biospecimens, and whom to contact in 

the event of a research-related harm 

(§ ll.116(d)(7)). 

The elements of broad consent 

described in the first six bullet points 

above are not unique to broad consent, 

while the elements described in the last 

six bullet points are specific to the 

requirements of broad consent. 

E. Waiver or Alteration of Informed 

Consent Involving Public Benefit and 

Service Programs (§ ll.116(e)) 

1. Background and Pre-2018 

Requirements 

The pre-2018 rule permitted an IRB to 

waive the requirements for obtaining 

informed consent, or to alter such 

requirements, under two sets of 

circumstances described at § ll.116(c) 

or (d) of the pre-2018 rule. The first set 

of circumstances, described at 

§ ll.116(c) of the pre-2018 rule was 

more narrow and was limited to certain 

research or demonstration projects 

conducted by or subject to the approval 

of state or local government officials. 

These projects are similar in some ways 

to the projects identified in the 

exemption at § ll.104(d)(5) of this 

final rule. The broader provisions 

concerning waivers or alterations of the 

requirements of informed consent that 

apply beyond the circumstances 

described in § ll.116(c) of the pre2018 rule are discussed below in the 

section concerning § ll.116(f). 

2. NPRM Proposal 

The NPRM proposed retaining the 

waiver and alteration of informed 

consent provisions included in the pre2018 rule with respect to research 

involving public benefit and service 

programs conducted by or subject to the 

approval of state or local officials, with 

two exceptions. First, the NPRM 

proposed (for proposed § ll.116(e)(2)), 

additional criteria for waiver or 

alteration of consent for biospecimens. 

This was tied to the NPRM’s proposal 

that all biospecimens, regardless of their 

identifiability, be covered under the 

Common Rule. Under these proposed 

criteria, IRBs would be able to approve 

waivers or alterations of the required 

informed consent elements only if an 

IRB found and documented both that 

there were compelling scientific reasons 

to conduct the research and that the 

research could not be conducted with 

other biospecimens for which informed 

consent was obtained or could be 

obtained. Second, the NPRM proposed 

new language (for proposed 

§ ll.116(e)(3)), providing that if an 

individual was asked to consent to the 

storage or maintenance for secondary 

research use of biospecimens or 

identifiable private information in 

accordance with the proposed broad 

consent provisions and that individual 

refused to consent, the IRB would be 

prohibited from waiving consent for the 

storage, maintenance, or the secondary 

research use of the biospecimens or 

information. 

3. Response to Comments and 

Explanation of the Final Rule: Waiver or 

Alteration of Informed Consent 

Involving Public Benefit and Service 

Programs 

Public comments on this proposal are 

described in section F below because 

the comments submitted generally 

addressed the waiver and alteration 

criteria under both proposed 

§ ll.116(e) and § ll.116(f). 

The final rule adopts one of the two 

proposals made in the NPRM for 

proposed §ll.116(e). The final rule 

adopts (in § ll.116(e)(1)) the language 

proposed in the NPRM providing that if 

an individual was asked to consent to 

the storage or maintenance for 

secondary research use of identifiable 

private information or identifiable 

biospecimens in accordance with the 

proposed broad consent provisions and 

such individual refused to consent, the 

IRB would be prohibited from waiving 

consent for the storage, maintenance, or 

the secondary research use of such 

biospecimens or information. The 

references in this provision to 

biospecimens are changed to refer 

specifically to identifiable biospecimens 

as the final rule does not apply to the 

research use of nonidentifiable 

biospecimens. This change is intended 

to honor the autonomy of individuals 

and to further the Belmont Report 

principle of respect for persons, in that 

this provision will prevent an 

individual’s refusal to consent to 

additional research use of information 

or biospecimens from being overridden. 

The final rule does not incorporate 

the NPRM’s proposed additional waiver 

criterion to apply to research involving 

the use of biospecimens. This change is 

not necessary given that the proposal in 

the NPRM that the Common Rule 

extend to all biospecimens has not been 

adopted in the final rule. We 

determined that the waiver and 

alteration criteria included in the final 

rule are appropriately protective of 

identifiable biospecimens, as defined at 

§ ll.102(e)(6) and that an additional 

waiver criterion for such biospecimens 

is not warranted. For example, 

§ ll.116(e)(3)(ii) mandates that an IRB 

may not waive or alter the requirements 

of informed consent with respect to 

research under this category unless the 

research could not practicably be 

carried out without the waiver or 

alteration. 

The format and organization of 

§ ll.116(e) in the final rule is different 

from that included in the pre-2018 rule 

or proposed in the NPRM. These 

changes were implemented to be clearer 

about the effect of each requirement. 

Most significantly, § ll.116(e) in the 

final rule provides separate paragraphs 

concerning the applicable criteria for 

waiver and the applicable criteria for 

alteration of the requirements for 

informed consent. This differs from the 

approach proposed in the NPRM, and 

the approach included in the pre-2018 

rule, that did not separate those 

discussions. We concluded that 

separating the discussion of waiver and 

the discussion of alteration would help 

clarify the applicable criteria, 

particularly given that the final rule 

addresses broad consent. 

Section ll.116(e)(1) describes the 

general framework for an IRB to waive 

the requirements for informed consent. 

This paragraph explains that an IRB 

may waive the requirement to obtain 

informed consent under § ll.116(a) 

(general requirements for informed 

consent), §ll.116(b) (basic elements 

of informed consent), or §ll.116(c) 

(additional elements of informed 

consent that apply to certain research) if 

the IRB satisfies the criteria set forth at 

§ ll.116(e)(3) (discussed below). As 

explained above, the ability to satisfy 

the requirement to obtain informed 

consent of a subject or a subject’s legally 

authorized representative through use of 

a broad consent in particular 

circumstances is a flexibility offered to 

institutions, but institutions are never 

required to obtain informed consent 

through a broad consent process. For 

this reason, § ll.116(e)(1) does not 

provide that an IRB may waive the 

requirement to obtain informed consent 

under §ll.116(d) (broad consent) 

because use of broad consent is not a 

requirement. As noted above, and to 

honor the autonomy of individuals, 

§ ll.116(e)(1) prohibits an IRB from 

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waiving consent for the storage, 

maintenance, or secondary research 

uses of identifiable private 

biospecimens or identifiable private 

information if an individual was asked 

to provide broad consent for such 

purposes and refused to provide such 

consent. 

Section ll.116(e)(2) describes the 

general framework for an IRB to alter the 

requirements for informed consent. An 

IRB may omit or alter some or all of the 

elements of informed consent under 

§ ll.116(b) (basic elements of 

informed consent) or §ll.116(c) 

(additional elements of informed 

consent that apply to certain research) if 

the IRB satisfies the criteria set forth at 

§ ll.116(e)(3) (discussed below). This 

is consistent with the proposal made in 

the NPRM. This paragraph further 

explains that an IRB may not omit or 

alter any of the requirements described 

in §ll.116(a) (general requirements 

for informed consent). This is also 

consistent with the proposal made in 

the NPRM (which proposed permitting 

an IRB to omit or alter elements of 

informed consent, but did not propose 

permitting omissions or alterations of 

the general requirements of informed 

consent that were included in the 

unnumbered introductory paragraph in 

the pre-2018 rule at §ll.116). This 

paragraph also specifies that if a broad 

consent is used, an IRB may not omit or 

alter any of the elements required under 

§ ll.116(d). We determined that it 

would not be appropriate to permit the 

omission or alteration of any of the 

broad consent elements given the fact 

that the required elements of broad 

consent are limited and given our view 

that each of these elements (described at 

§ ll.116(d)) is critical for the purpose 

of soliciting broad consent that is both 

informed and ethically appropriate. 

This approach is different from what 

was proposed in the NPRM because of 

the NPRM’s different approach to broad 

consent than that adopted in the final 

rule. 

Section ll.116(e)(3) sets forth the 

specific criteria that an IRB must find 

and document to waive or alter the 

requirements for informed consent, 

consistent with the limitations set forth 

in §ll.116(e)(1) and § ll.116(e)(2). 

These criteria are the same as those 

proposed in the NPRM. First, the IRB 

must find and document that the 

research or demonstration project is to 

be conducted by or subject to the 

approval of state or local government 

officials and is designed to study, 

evaluate, or otherwise examine public 

benefit or service programs; procedures 

for obtaining benefits or services under 

those programs; possible changes in or 

alternatives to those programs or 

procedures; or possible changes in 

methods or levels of payment for 

benefits or services under those 

programs. Second, the IRB must find 

and document that the research could 

not practicably be carried out without 

the waiver or alteration. 

F. General Waiver or Alteration of 

Informed Consent (§ ll.116(f)) 

1. Background and Pre-2018 

Requirements 

Beyond the circumstances addressed 

in §ll.116(c) of the pre-2018 rule 

(which is limited to certain research 

conducted by or subject to the approval 

of state or local government officials), 

the pre-2018 rule includes a more 

general provision that is not limited to 

any particular type of research and that 

permits an IRB to either waive the 

requirements for obtaining informed 

consent, or to alter such requirements. 

Waiver or alteration of the requirements 

of informed consent under this general 

provision requires that the following 

four criteria be satisfied: (1) the research 

involves no more than minimal risk to 

the subjects; (2) the waiver or alteration 

will not adversely affect the rights and 

welfare of the subjects; (3) the research 

could not practicably be carried out 

without the waiver or alteration; and (4) 

whenever appropriate, the subjects will 

be provided with additional pertinent 

information after participation. 

Concerns have been expressed that 

requirements for obtaining waivers of 

informed consent or waivers of 

documentation of informed consent 

were confusing and inflexible, resulting 

in inconsistent application and a lack of 

uniformity in interpretation, which led 

to the proposals in the NPRM. 

2. NPRM Proposals 

The NPRM offered three substantive 

proposals related to the general waiver 

or alteration of informed consent 

provisions. First, the NPRM proposed to 

add a new waiver criterion that would 

require that for research involving 

access to or use of identifiable 

biospecimens or identifiable private 

information, the requirements of 

informed consent could only be waived 

or altered if the research could not 

practicably be carried out without 

accessing or using identifiers. This 

criterion was modeled on the 

comparable criterion in the HIPAA 

Privacy Rule, which requires as a 

condition of waiver of the requirement 

to obtain an individual’s authorization 

that the research could not practicably 

be conducted without access to and use 

of protected health information. The 

principle embodied in this additional 

proposed criterion was that 

nonidentified information should be 

used whenever possible in order to 

respect subjects’ interests in protecting 

the confidentiality of their data and 

biospecimens. 

Second, the NPRM proposed two 

additional waiver criteria for research 

involving the use of biospecimens. For 

such research, the NPRM proposed that 

the requirements of informed consent 

could only be waived or altered if an 

IRB found and documented that: (1) 

there were compelling scientific reasons 

for the research use of the biospecimens; 

and (2) the research could not be 

conducted with other biospecimens for 

which informed consent was or could 

be obtained. 

Third, the NPRM proposed that the 

Common Rule prohibit IRBs from 

waiving informed consent if individuals 

were asked and refused to provide broad 

consent to the storage and maintenance 

for secondary research use of 

biospecimens and identifiable private 

information. If a subject refused to 

provide broad consent, it was proposed 

that this refusal would need to be 

recorded by the investigator to better 

ensure that the subject’s wishes would 

be honored. 

3. Public Comments 

Approximately 975 public comments 

discussed the NPRM proposals found at 

§ ll.116(f) either directly, or as related 

to linked provisions related to the 

definition of human subject, the broad 

consent proposal, or proposed 

exemptions. A majority of these 

discussed the NPRM proposals related 

to the more stringent waiver criteria for 

research involving biospecimens. A 

majority of these comments were from 

patients (including family members of 

patients) and other individuals who 

commented anonymously. Patients 

tended to oppose these proposals 

because they believed they would 

severely restrict access to biospecimens, 

which would slow research. Some 

commenters were opposed to waiver of 

consent under any conditions, whether 

specific or broad consent. 

Approximately 40 comments were 

received on the NPRM’s proposal to 

prohibit an IRB from waiving consent 

for the storage, maintenance, or 

secondary research uses of identifiable 

biospecimens or identifiable private 

information if an individual was asked 

to provide broad consent for such 

purposes and refused to provide such 

consent. Public comment was mixed. 

Those who supported it indicated that 

this requirement made sense in order to 

respect subject autonomy. Those who 

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opposed the proposal indicated that it 

would be impossible for an IRB to know 

the reasons why an individual refused 

to sign a broad consent form. Thus, 

these individuals argued, the 

prohibition on waiver of consent did not 

seem appropriate given the difficulty in 

understanding why someone refused to 

sign a broad consent form. Several 

commenters noted that it would be 

reasonable to prohibit an IRB from 

waiving a subject’s refusal to provide 

consent to a specific study, but that 

such a prohibition in the context of 

broad consent seemed unduly 

burdensome. 

The NPRM sought comments 

concerning language in the pre-2018 

rule (that the NPRM proposed retaining) 

that waiver or alteration of informed 

consent only occur if the IRB finds that 

the research could not practicably be 

carried out without the requested 

waiver or alteration. Several 

commenters recommended further 

defining or clarifying the meaning of 

‘‘practicably.’’ Some members of the 

public felt that this criterion was too 

open-ended and that greater emphasis 

should be placed on respect for persons 

over other ethical concerns and 

scientific validity. Several commenters 

favored SACHRP’s recommendations on 

this topic, including that this 

requirement be interpreted to mean that 

it would be impracticable to perform the 

research, not impracticable to obtain 

consent due to financial or 

administrative burdens, without the 

waiver or alteration. Another 

commenter argued that because of a lack 

of clarity as to the meaning of terms 

including ‘‘minimal risk,’’ 

‘‘practicably,’’ and ‘‘the rights and 

welfare of subjects,’’ as well as the 

potential that IRBs may not apply the 

criteria uniformly, IRBs should not be 

able to waive or alter consent. The 

following suggestions were offered as 

replacement language: ‘‘reasonably done 

without excessive time or financial 

constraints to the researcher that would 

delay the project so significantly as to 

make it impossible to conduct the 

research,’’ ‘‘capable of being done or 

accomplished with available means or 

resources,’’ ‘‘reasonably feasible,’’ 

‘‘capable of being effective,’’ and ‘‘could 

practicably be obtained.’’ Several 

commenters favored retaining the term 

‘‘practicably’’ and were satisfied that it 

was clear. 

Other comments raised different 

issues about waiver or alteration. Many 

commenters who opposed all classified 

research conducted without consent 

recommended that waivers be 

prohibited with respect to classified 

research involving humans. One 

commenter recommended a 

reorganization of the waiver and 

alteration provisions to clarify the 

different standards that apply to waivers 

and alterations. Another commenter 

expressed concern that the NPRM’s 

proposed waiver provision would 

unreasonably limit the flexibility of 

IRBs. One commenter believed that the 

§ ll.116(f) alteration criteria were too 

rigid and that the final rule should 

incorporate a notion of risk adjustment. 

Another commenter (a professional 

medical organization) supported 

SACHRP’s proposed revisions to the 

waiver criteria at §ll.116(f) to allow 

an IRB to approve the storage, 

maintenance, and secondary research 

use of identified data. 

The NPRM sought public comment on 

the proposed differences between the 

criteria for waiving informed consent for 

the research use of biospecimens versus 

identifiable information. Approximately 

60 comments stated that no justification 

exists for treating biospecimens and 

information differently. Some also noted 

that the proposed criteria for waiver of 

consent for use of biospecimens is so 

high as to be virtually impossible to 

meet and asked why biospecimens 

should have a higher standard than 

information (which theoretically could 

be more easily identifiable). One 

commenter noted that the proposed 

waiver criteria promotes ‘‘biospecimen 

exceptionalism’’ and that data and 

biospecimens should be treated the 

same. 

A request in the NPRM for public 

comment on whether the proposal to 

permit an IRB to waive consent for 

research involving the use of 

biospecimens should be included in the 

regulations received few comments. One 

commenter noted that it seemed 

incongruous to include biospecimens in 

the definition of ‘‘human subject,’’ but 

then allow waiver based on different 

criteria. Others stated that IRBs should 

continue to have the ability to waive 

consent. 

The NPRM sought public comment 

regarding how likely investigators are to 

seek broad consent for the use of 

identifiable private information (as 

contrasted with biospecimens), given 

that the NPRM contains provisions that 

would make it easier to do such 

research without consent (such as the 

new exemption proposed for 

§ ll.104(e)(2)). Approximately 30 

commenters responded to this question. 

A majority said they would not use the 

broad consent mechanism for secondary 

use of information if other options were 

available. Some said that they suspected 

that investigators would continue to 

seek consent waivers for secondary use 

of identifiable private information 

instead of seeking broad consent. 

The NPRM also sought public 

comment on several aspects of the 

proposed prohibition on waiving 

consent when an individual has been 

asked to provide broad consent and 

refused, including the following 

questions: In particular, how would this 

prohibition on waiving consent affect 

the secondary research use of 

identifiable private information? If an 

individual was asked to provide such 

consent, should the absence of a signed 

secondary use consent be considered a 

refusal? Does this prohibition on 

waiving consent for the secondary use 

of identifiable private information create 

a disincentive for institutions to seek 

broad consent for secondary use and 

instead seek a waiver of consent from an 

IRB? Under what circumstances, if any, 

would it be justified to permit an IRB to 

waive consent even if an individual 

declined or refused to consent? 

Approximately 35 comments were 

received on this set of questions. 

Approximately half of these stated that 

‘‘no means no.’’ If someone was asked 

to give broad consent and the person 

specifically said no, researchers should 

not be allowed to obtain a waiver of 

consent. Those who opposed the idea of 

a prohibition on waiver argued that it 

would be very difficult for institutions 

to understand why someone said no to 

providing broad consent. In other 

words, a blanket prohibition does not 

accurately address all the issues that can 

occur in this situation. 

A majority of the responses did not 

address the questions of how a broad 

consent form with no indication either 

way should be treated. The responses 

we received to this question suggested 

that absence of a signed form should not 

be treated as if the individual explicitly 

said no to broad consent (i.e., that in 

those situations, waiver should be 

permitted). 

A majority of the responses that we 

received on the question of whether the 

prohibition on waiver in the broad 

consent context created a disincentive 

for the use of broad consent with 

identifiable private information 

answered in the affirmative. 

4. Response to Comments and 

Explanation of the Final Rule: General 

Waiver of Alteration of Consent 

Overall, two of the three proposals 

made in the NPRM for proposed 

§ ll.116(f) have been retained. The 

final rule adopts (in §ll.116(f)(3)(iii)) 

a new waiver criterion very similar to 

that proposed in the NPRM, which now 

mandates that for research involving 

access to or use of identifiable private 

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7226 Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 

information or identifiable 

biospecimens, the requirements of 

informed consent can be waived or 

altered only if the research could not 

practicably be carried out without using 

such information or biospecimens in an 

identifiable format. The minor wording 

change made in the language of this 

provision, as compared with that 

proposed in the NPRM, is intended for 

clarity. This change is intended to 

protect the privacy of individuals, while 

not unduly inhibiting research. After 

considering the diversity of opinions 

expressed in the public comments on 

this issue, including many comments 

seeking further guidance concerning the 

proper interpretation of the 

‘‘practicably’’ language, the final rule 

does not define this language (which 

was also included in the pre-2018 rule). 

We have concluded that the 

requirements for waiver and alteration 

in §ll.116(e) and (f) appropriately 

honor respect for persons and balances 

this with other ethical principles. 

The final rule also adopts (in 

§ ll.116(f)(1)) the language proposed 

in the NPRM (for §ll.116(f)(3)) 

prohibiting IRBs from waiving informed 

consent if individuals were asked and 

declined to provide broad consent to the 

storage and maintenance for secondary 

research use of identifiable private 

information or identifiable 

biospecimens (except that the final 

rule’s formulation is limited to 

identifiable biospecimens, consistent 

with changes made in the final rule). We 

considered public comments that 

opposed this prohibition and 

understand that IRBs may not always 

understand the reason that individuals 

refused to sign a consent form and that 

the effects of this broad prohibition 

could be significant in the context of 

broad consent (given the broad scope of 

research that such a broad consent 

could potentially extend to). 

Nonetheless, we determined that it is 

important to prevent an individual’s 

refusal to consent to additional research 

use of such information or biospecimens 

from being overridden. This change to 

the Common Rule is intended to honor 

the autonomy of individuals and to 

further the Belmont Report principle of 

respect for persons. 

The final rule does not incorporate 

the NPRM’s proposed additional waiver 

criteria (proposed for §ll.116(f)(2)) to 

apply to research involving the use of 

biospecimens. This change is not 

necessary given that the proposal in the 

NPRM that the Common Rule extend to 

all biospecimens regardless of their 

identifiability has not been adopted in 

the final rule. We determined that the 

waiver and alteration criteria included 

in the final rule are appropriately 

protective of identifiable biospecimens 

and that an additional waiver criterion 

for such biospecimens is not warranted. 

For example, § ll.116(f)(3)(iii) in the 

final rule is a research criterion specific 

to research that involves using 

identifiable private information or 

identifiable biospecimens. Under this 

criterion, an IRB may not waive or alter 

requirements of informed consent with 

respect to such research unless the IRB 

finds and documents that the research 

could not practicably be carried out 

without using such information or 

biospecimens in an identifiable format. 

The format and organization of 

§ ll.116(f) in the final rule are 

different from the proposed §ll.116(f) 

described in the NPRM. We made these 

changes in an effort to be clear about the 

effect of each requirement. Most 

significantly, §ll.116(f) in the final 

rule provides separate paragraphs 

concerning the applicable criteria for 

waiver and the applicable criteria for 

alteration of the requirements for 

informed consent. This differs from the 

approach proposed in the NPRM, and 

the approach included in the pre-2018 

rule that did not separate those 

discussions. We conclude that 

separating the discussion of waiver and 

alteration will help clarify the 

applicable criteria, particularly given 

that the final rule addresses the 

application of the waiver and alteration 

provisions in the context of broad 

consent. 

Section ll.116(f)(1) describes the 

general framework for an IRB to waive 

the requirements for informed consent. 

This paragraph explains that an IRB 

may waive the requirement to obtain 

informed consent under § ll.116(a) 

(general requirements for informed 

consent), §ll.116(b) (basic elements 

of informed consent), or §ll.116(c) 

(additional elements of informed 

consent that apply to certain research) if 

the research satisfies the criteria set 

forth at § ll.116(f)(3) (discussed 

below). As explained above, the ability 

to satisfy the requirement to obtain 

informed consent of a subject or a 

subject’s legally authorized 

representative through use of a broad 

consent in particular circumstances is a 

flexibility offered to institutions, but 

institutions are never required to obtain 

informed consent through a broad 

consent process. For this reason, 

§ ll.116(f)(1) does not provide that an 

IRB may waive the requirement to 

obtain informed consent under 

§ ll.116(d) (broad consent) because 

use of broad consent is a regulatory 

flexibility, and not a requirement. 

Consistent with the proposal made in 

the NPRM (proposed §ll.116(f)(3)), 

§ ll.116(f)(1) provides that if an 

individual was asked to provide broad 

consent for the storage, maintenance, 

and secondary research use of 

identifiable private information or 

identifiable biospecimens and refused to 

consent, an IRB cannot waive consent 

for either the storage, maintenance, or 

secondary research use of such 

biospecimens or information. 

Sectionll.116(f)(2) describes the 

general framework for an IRB to alter the 

requirements for informed consent. This 

paragraph explains that an IRB may 

omit or alter some or all of the elements 

of informed consent under §ll.116(b) 

(basic elements of informed consent) or 

§ ll.116(c) (additional elements of 

informed consent that apply to certain 

research) if the IRB satisfies the criteria 

set forth at §ll.116(f)(3) (discussed 

below). This is consistent with the 

proposal made in the NPRM. This 

paragraph further explains that an IRB 

may not omit or alter any of the 

requirements described in § ll.116(a) 

(general requirements for informed 

consent). This is also consistent with 

the proposal made in the NPRM (which 

proposed permitting an IRB to omit or 

alter elements of informed consent, but 

did not propose permitting omissions or 

alterations of the general requirements 

of informed consent that were included 

in the unnumbered introductory 

paragraph in the pre-2018 rule at 

§ ll.116). This paragraph also 

specifies that when reviewing a broad 

consent, an IRB may not omit or alter 

any of the elements required under 

§ ll.116(d). As with §ll.116(e)(2), 

we determined that it would not be 

appropriate to permit the omission or 

alteration of any of the broad consent 

elements in § ll.116(f). The elements 

of broad consent reflected in this NPRM 

are limited. We have concluded that 

each of these elements (which are 

included at § ll.116(d)) is critical to 

the solicitation of an informed and 

ethically appropriate broad consent. For 

that reason, none of the elements of 

broad consent may be omitted or altered 

if broad consent is solicited. This 

prohibition is different than the NPRM’s 

proposal given the different formulation 

of broad consent represented in this 

final rule. 

Section 116(f)(3) sets forth the specific 

criteria that an IRB must find and 

document in order to waive or alter the 

requirements for informed consent. 

These criteria are the same as those 

proposed in the NPRM, except that the 

third criterion includes minor wording 

changes that were made for clarity: (1) 

the research involves no more than 

minimal risk to the subjects; (2) the 

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Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 7227 

48See Secretary’s Advisory Committee on Human 

Research Protections (SACHRP). Attachment C: 

Approved by SACHRP July 20, 2011. SACHRP 

Recommendation regarding application of 45 CFR 

46 and 21 CFR 56 to early processes in research, 

such as identifying potential subjects, contacting 

subjects and recruiting subjects. (July 20, 2011). 

Retrieved from http://www.hhs.gov/ohrp/sachrpcommittee/recommendations/2011-october-13- 

letter-attachment-c/index.html. 

research could not practicably be 

carried out without the requested 

waiver or alteration; (3) if the research 

involves using identifiable private 

information or identifiable 

biospecimens, the research could not 

practicably be carried out without using 

such information or biospecimens in an 

identifiable format; (4) the waiver or 

alteration will not adversely affect the 

rights and welfare of the subjects; and 

(5) whenever appropriate, the subjects 

will be provided with additional 

pertinent information after 

participation. 

G. IRB Approval of Research Involving 

Screening, Recruiting, or Determining 

Eligibility of Prospective Subjects 

(§ ll.116(g)) 

1. Background and Pre-2018 

Requirements 

The pre-2018 rule required an IRB to 

determine that informed consent can be 

waived under § ll.116(d) before 

investigators could record identifiable 

private information for the purpose of 

identifying and contacting prospective 

subjects for a research study. This 

requirement to waive informed consent 

has been viewed as burdensome and 

unnecessary for protecting subjects, and 

is not consistent with FDA’s regulations, 

which do not require informed consent 

or a waiver of informed consent for such 

activities. 

2. NPRM Proposal 

The NPRM proposed a new provision 

at §ll.116(g) that would authorize an 

IRB to approve a research proposal in 

which investigators obtain identifiable 

private information without individuals’ 

informed consent for the purpose of 

screening, recruiting, or determining the 

eligibility of prospective human subjects 

of research. The IRB would be permitted 

to approve a research proposal only in 

such circumstances if the proposal 

included an assurance that the 

investigator would implement standards 

for protecting the information obtained, 

in accordance with and to the extent 

required by proposed §ll.105. This 

proposal was intended to address 

concerns that the pre-2018 rule required 

an IRB to determine that informed 

consent can be waived before 

investigators could record identifiable 

private information for the purpose of 

identifying and contacting prospective 

subjects for a research study. 

3. Public Comments 

Few comments were received 

regarding this proposal. All were 

generally supportive. One academic 

institution noted that ‘‘This review is 

unnecessary considering the low 

potential risk to subjects and will 

expedite research endeavors and ensure 

harmonization between FDA‘s 

expectations and the Common Rule.’’ 

However, one commenter thought that 

prospective subjects should be notified 

that this might be a possibility. Another 

commenter said that it should be clear 

that this is not an IRB waiver of consent, 

but rather it is an exception to the 

consent requirement. 

4. Response to Comments and 

Explanation of the Final Rule: Approval 

of Research Involving Screening, 

Recruiting, or Determining Eligibility of 

Prospective Subjects 

The final rule adopts the NPRM 

proposal at § ll.116(g), with minor 

changes made for clarity, and without a 

requirement that investigators adhere to 

the proposed privacy safeguards at 

§ ll.105, since this provision is not 

included in the final rule. The provision 

at §ll.116(g) addresses concerns that 

the pre-2018 regulations required an IRB 

to determine that informed consent can 

be waived before investigators may 

record identifiable private information 

for the purpose of identifying and 

contacting prospective subjects for a 

research study. This change is intended 

to address these concerns by eliminating 

the requirement for the IRB to waive 

informed consent for these activities. In 

response to public comments, we are 

clarifying that this is not a waiver of the 

consent requirement but rather an 

exception to the requirement. This 

change is also responsive to SACHRP’s 

recommendation regarding how the 

Common Rule should apply to activities 

that are conducted before subjects 

provide consent to participate in 

research, such as identifying potential 

subjects, contacting subjects, and 

recruiting subjects.48

The final rule includes some minor 

changes from the NPRM proposal, to 

clarify the circumstances in which the 

IRB may approve the investigator’s 

proposal to obtain information directly 

from a prospective subject, or to obtain 

already collected identifiable private 

information or identifiable 

biospecimens by accessing records or 

stored biospecimens, for purposes of 

screening, recruiting, or eligibility 

assessment, without the informed 

consent of the prospective subject or the 

subject’s legally authorized 

representative. The final rule also adds 

a reference to the subject’s legally 

authorized representative at 

§ ll.116(g)(1) to clarify that this 

exception to informed consent will also 

apply in circumstances in which the 

prospective subject has a legally 

authorized representative who will 

provide information about the 

prospective subject through oral or 

written communication with the 

investigator. 

We note that in approving this 

exception to informed consent for the 

purpose of screening, recruiting, or 

determining the eligibility of 

prospective subjects, the IRB will be 

reviewing and approving the entire 

research proposal. Therefore, all of the 

IRB approval criteria at §ll.111 will 

need to be satisfied, including that 

when appropriate, there are adequate 

provisions to protect the privacy of 

subjects and to maintain the 

confidentiality of data (§ ll.111(a)(7)). 

Thus, as part of its review and approval 

of the research, the IRB must determine 

that there are adequate privacy and 

confidentiality safeguards for 

information obtained by investigators 

for these preparatory-to-research 

activities. 

We believe that these preparatory-toresearch activities are critical means by 

which to identify subjects that do not 

involve additional risks, given their 

limited nature. If prospective subjects 

are identified through these ‘‘screening’’ 

activities, then all other relevant 

requirements of this rule must be met if 

they are subsequently recruited to 

participate in the research. 

H. Posting of Consent Forms 

(§ ll.116(h)) 

1. Background and Pre-2018 

Requirements 

The pre-2018 rule did not have a 

requirement to post consent forms from 

clinical trials. 

2. NPRM Proposal 

The NPRM proposed a new provision 

that would require that a copy of the 

final version of the consent form (absent 

any signatures) for each clinical trial 

conducted or supported by a Common 

Rule department or agency be posted on 

a publicly available federal Web site 

that will be established as a repository 

for such consent forms. The name of the 

protocol and contact information would 

be required to be included with the 

submission of the consent form. Under 

the NPRM proposal, the consent form 

would have to be published on the Web 

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site within 60 days after the trial is 

closed for recruitment. 

3. Public Comments 

The NPRM proposal received 

approximately 130 comments, most of 

which opposed the proposal in whole or 

in part. Many commenters expressed 

concern that the proposal represented 

administrative burden without a 

corresponding increase in protections to 

human subjects or benefit to the 

research community. Some commenters 

felt that the proposal represented a 

waste of resources that would not 

increase compliance with the 

regulations, and might result in longer 

consent forms if researchers felt the 

need to include an abundance of 

additional information to protect against 

perceived regulatory noncompliance or 

legal challenge. These commenters 

expressed concern that the repository of 

posted consent forms might be used to 

seek out instances of noncompliance. 

For example, one large medical school 

indicated that the posting requirement 

creates a rich environment for litigation 

and represents an effort to publicly 

shame investigators to improve quality 

of documents that will not work. 

Other commenters, including some 

private research firms, were concerned 

that the proposal as drafted would not 

allow for the redaction of proprietary or 

institutionally sensitive information 

from consent forms before they would 

be posted to the Web site, and allow 

competing research entities access to 

detailed information about 

investigational drug or research 

programs beyond what is publicly 

available already. Additional concern 

was expressed about the proposed 

timeframe in which consent forms 

needed to be posted. Some felt that 

more time was needed. Other 

commenters felt it would be more 

beneficial to research participants if 

consent forms were posted before or 

during recruitment. In addition, some 

commenters felt that researchers should 

be allowed or encouraged to update 

posted consent forms if they are 

updated for the study. Others felt that 

requiring that consent forms be posted 

once (even if the forms were updated 

after being posted) would lead to 

potential confusion among research 

participants. For example, several 

commenters noted that should a subject 

participating in a trial see a consent 

form for a particular study that differed 

from the form that he or she originally 

signed, that discrepancy could cause 

unnecessary concern and confusion. 

Still other commenters expressed 

concern that the high volume of consent 

forms that would be posted as a result 

of this requirement would make the 

collection cumbersome and difficult to 

use, negating any potential benefit 

gained by increased transparency. 

Others expressed a concern that 

requiring all studies to post consent 

forms might lead to the perpetuation of 

poorly written forms, as researchers 

might use poor examples from the 

database to write their own informed 

consent documents in addition to 

excellent ones. A few major research 

universities suggested that guidance, 

best practices, or exemplary informed 

consent forms should be selected and 

shared publicly, rather than all 

informed consent forms. Some 

commenters suggested limiting the 

posting requirement to a subset of 

research studies, for example, to only 

high risk or large multi-institution 

studies. 

Those who supported the proposal 

agreed that it would help increase 

accountability and promote 

transparency in informed consent forms. 

To that end, a minority of commenters 

said that this proposal should be 

extended to all research that is subject 

to the Common Rule, not just to studies 

meeting the definition of a clinical trial. 

Some commenters supported the idea of 

publicly sharing informed consent 

documents but felt it would be best 

accomplished through guidance or 

optional posting. One federal level 

advisory committee supported the 

proposal and recommended the creation 

of robust guidance with the goal of 

minimizing confusion and misuse of the 

posted documents, and facilitating the 

use of the posted forms to educate 

investigators, institutions, and 

regulators to improve future informed 

consent documents and the informed 

consent process generally. Others felt it 

would be helpful to post additional 

information and documents along with 

consent forms. For example, one 

investigator suggested that copies of IRB 

proposals and decisions be made public 

along with approved informed consent 

documents to provide additional 

transparency and accountability. 

Another commenter suggested that 

investigators be given the option to post 

assessment tools for evaluating 

prospective subjects’ understanding of 

important study information. 

Both those who supported and 

opposed the proposal indicated that in 

terms of implementing this proposal, 

consent forms should be posted to 

ClinicalTrials.gov as opposed to creating 

a new federal Web site in order to limit 

the additional administrative burden 

that this proposal would impose. 

4. Response to Comments and 

Explanation of the Final Rule: Posting of 

Consent Forms 

The final rule adopts the NPRM 

proposal with some modifications and 

clarifications. The primary purpose of 

this provision is to improve the quality 

of consent forms in federally funded 

research by assuring that—contrary to 

current practices, under which it is 

often very difficult to ever obtain a copy 

of these documents—they eventually 

would become subject to public scrutiny 

and that they will provide useful 

models for others. The consent form 

plays a key role in making sure that 

someone asked to enter a clinical trial 

receives the information they need to be 

making an informed decision about 

whether to enroll in that trial. 

Accordingly, it also plays a key role in 

supporting and justifying the public’s 

trust in the integrity of our clinical trial 

enterprise. 

We are not persuaded by the 

arguments of those commenters who 

suggest that potential negative 

consequences of this proposal outweigh 

its benefits. Fundamentally, this 

proposal is about increasing the 

transparency of one of the most 

important aspects of our human subjects 

protection system. Increased 

transparency is in general a good thing, 

and in this instance, as in many others, 

it offers multiple benefits—including 

increased trust—at very low cost. This 

provision is not a form of shaming, but 

rather an effort to ask people to work 

together to create a system that will 

improve the quality of informed 

consent. Moreover, the new standards 

for determining the acceptable content 

of a consent form—including 

§ ll.116(a)(5), which will require a 

concise presentation of key information 

at the beginning of the consent form— 

should counter any consequences of 

attempts to pad consent forms with 

additional information as a response to 

the posting requirement. 

We agree with the conclusions of 

SACHRP that implementing this 

proposal will indeed result in better 

consent forms. Having a repository of 

such forms freely available for analysis 

and public discussion will create 

multiple opportunities for improving 

these forms. In an era in which we have 

previously unheard of capabilities for 

analyzing textual material and 

processing large amounts of data, the 

fact that there will be a high volume of 

consent forms posted should be a minor 

impediment, if any, to the ability to 

learn from the content of this database. 

With regard to those who suggested 

that it would indeed be desirable to 

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make consent forms more public, but 

that posting should be optional, we note 

that nothing in the pre-2018 rule 

prevents the people in charge of 

research from making their consent 

forms public, yet that is rarely done. In 

order to significantly increase the 

transparency of this portion of our 

system for protecting subjects, we are 

finalizing this proposal. 

With regard to the commenters who 

were concerned that posting consent 

forms would create a rich environment 

for litigation, it is noteworthy that the 

existing evidence fails to suggest that 

there has been much of a problem with 

regard to inappropriate litigation over 

clinical trials. Whatever disincentives 

currently exist for such litigation, it 

seems unlikely that the mere fact that 

consent forms would now be more 

available will dramatically alter such 

disincentives. With regard to the 

commenters who were concerned about 

the added regulatory burden, we note 

that this change, compared to the 

traditional costs of clinical trials, will 

add a relatively small amount of 

additional burden, one that is well 

justified in comparison to the likely 

increase in transparency. This new 

provision has specifically been designed 

to minimize that burden. And the final 

rule has been modified in a number of 

respects from the NPRM proposal in 

response to public comments. As 

discussed below in detail, the time by 

which a consent form must be posted 

has been greatly extended. That change 

would also address the concerns of 

some commenters that the posted 

consent forms might create confusion 

among research subjects. Furthermore, 

provisions have been added that allow 

for redaction, as necessary, of portions 

of consent forms. 

As a means of increasing transparency 

and facilitating the development of 

more informative consent forms, the 

final rule accordingly requires at 

§ ll.116(h)(1) that for clinical trials 

conducted or supported by a Common 

Rule department or agency, a copy of an 

IRB-approved version of a consent form 

that was used to enroll subjects would 

need to be posted by the awardee or the 

federal department or agency 

conducting the trial on a publicly 

available federal Web site that will be 

established as a repository for such 

forms. Unlike the NPRM, which 

required that the ‘‘final version’’ of the 

consent form be posted, the final rule 

adds flexibility in merely requiring that 

it be an IRB-approved consent form that 

was used for enrollment purposes. 

There is accordingly no further 

restriction as to which version of a 

consent form (which might have been 

subject to many modifications over the 

course of time) must be posted. The 

final rule also gives greater flexibility 

than the NPRM proposal in terms of 

when that posting needs to be done. It 

can take place any time after the trial is 

closed to recruitment, so long as the 

posting is no later than 60 days after the 

last study visit by any subject (as 

required by the protocol). If the federal 

department or agency supporting or 

conducting the clinical trial determines 

that certain information should not be 

made publicly available on a federal 

Web site (e.g., confidential commercial 

information), the department or agency 

may permit appropriate redactions to 

the information posted. In rare 

instances, it could be the case that the 

federal department or agency would 

determine that the very existence of a 

particular clinical trial should not be 

publicly disclosed, in which case no 

posting relating to such a trial would be 

required. 

The final rule differs from the NPRM 

proposal in that it no longer specifies 

that certain information needs to be 

posted in addition to the consent form. 

This change eliminates the need for 

mandatory posting of information that 

might not be justified by the purposes 

of this provision. 

Only one posting would be required 

for each multi-institution study. There 

is accordingly no expectation that a 

version would need to be posted for 

each class of subjects in the study (for 

example, a posting both for adults and 

for minors), nor for each study site. 

We also note that this provision 

applies only to those clinical trials that 

are conducted or supported by a federal 

department or agency. 

A Web site will be developed by HHS, 

which could be used by other federal 

departments or agencies, or the other 

federal departments or agencies could 

create their own Web sites for the 

posting of these consent forms. Public 

posting of consent forms is intended to 

increase transparency, enhance 

confidence in the research enterprise, 

increase accountability, and inform the 

development of future consent forms. It 

is anticipated that the Web site will be 

searchable. With regard to the 

comments suggesting that 

ClinicalTrials.gov might be an 

appropriate choice as the Web site, we 

agree that such a choice has the 

possibility of minimizing administrative 

burdens. Using ClinicalTrials.gov has 

another advantage, in addition to what 

some of the commenters said. Many 

clinical trials funded by HHS have 

records in ClincialTrials.gov due to 

requirements that certain clinical trials 

register and submit results information 

to that database (section 402(j) of the 

Public Health Service Act and 42 CFR 

part 11, and other policies that 

incentivize trial registration and results 

submission, such as the NIH Policy on 

Dissemination of NIH-Funded Clinical 

Trial Information). The fact that these 

trials already have a record in the 

database will mean that the burden of 

submission of the informed consent 

document will be substantially lower. 

Accordingly, we will take these points 

into consideration as we determine 

what federal Web site will be used to 

implement this provision. 

XV. Documentation of Informed 

Consent (§ll.117) 

A. Background and Pre-2018 

Requirements 

The pre-2018 rule at §ll.117 

described the requirements for 

documenting informed consent and 

when the waiver for obtaining a written 

and signed consent form was allowable. 

B. NPRM Proposals 

The NPRM proposed to alter the 

language at § ll.117(b)(1) to specify 

that the consent document should 

include only the language required by 

§ ll.116, with appendices included to 

cover any additional information. 

In addition, the NPRM would make it 

explicit in the regulatory language at 

proposed §ll.117(c)(1)(iii) that if the 

subjects are members of a distinct 

cultural group or community for whom 

signing documents is not the norm, so 

long as the research presents no more 

than minimal risk of harm to subjects 

and provided there is an appropriate 

alternative mechanism for documenting 

that informed consent was obtained, the 

requirement to obtain a signed consent 

form may be waived. Documentation 

must include a description as to why 

signing forms is not the norm for the 

distinct cultural group or community. 

Additionally, to facilitate the tracking 

of broad consent to storage or 

maintenance for secondary research use 

of biospecimens or identifiable private 

information, and to provide information 

to IRBs should IRB review be required, 

the NPRM proposed that waiver of 

documentation of consent for the 

research use of such biospecimens 

would not be allowed based upon a new 

provision at § ll.117(c)(3). 

The NPRM also introduced the term 

‘‘oral consent’’ in the context of the 

various provisions related to the broad 

consent for the storage, maintenance, 

and secondary use of biospecimens and 

identifiable private information. As a 

general matter, under the pre-2018 rule, 

individuals wanting to obtain oral 

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consent from subjects in a nonexempt 

research activity needed to seek a 

waiver of documentation of informed 

consent under § ll.117(c). Therefore, 

the NPRM proposed to permit 

investigators to obtain oral broad 

consent for the storage, maintenance, 

and secondary research use in limited 

circumstances. Specifically, the NPRM 

proposals would allow an investigator 

to obtain oral broad consent if: 

• An investigator used the proposed 

broad consent template; 

• Investigators only sought oral broad 

consent only for the storage, 

maintenance, and secondary research 

use context for the use of identifiable 

private information, not for 

biospecimens; 

• If broad consent for the storage, 

maintenance, and secondary research 

use was obtained only as part of a 

separate, primary research study; and 

• The oral broad consent was sought 

as part of the consent process in a study 

eligible for one specific exclusion or 

three specific exemptions related to the 

collection of identifiable information. 

Finally, the regulatory language 

proposed at § ll.117(c)(4) was 

intended to clarify that waivers of 

documentation may not be permitted for 

research subject to regulation by FDA. 

C. Public Comments 

Approximately 15 comments were 

received on the proposals found in the 

NPRM at § ll.117. Several 

commenters discussing the proposed 

requirement at § ll.117(b)(1) 

indicated that even if consent forms are 

split into a primary document and 

appendices, there should be an 

expectation that the content included in 

the appendices are discussed with 

prospective subjects as part of the 

informed consent process. Although 

very few comments discussed the 

requirements of proposed 

§ ll.117(b)(1) specifically, many of the 

comments discussing the NPRM 

proposal found in the introductory 

paragraph of § ll.116 discussed the 

concept of including only the required 

information in the main body of a 

consent form, and all additional 

information in appendices. 

Few comments were received on the 

proposal found in §ll.117(c)(1)(iii) 

that documentation of informed consent 

may be waived if consent is being 

sought amongst subjects who are 

members of a distinct cultural group or 

community in which signing forms is 

not the norm. Comments received on 

this proposal were generally favorable. 

Those who commented on the 

proposals related to oral broad consent 

indicated that the provisions were 

confusing and difficult to understand. 

We note that these proposals were 

found in the NPRM through a series of 

interrelated cross references in 

§§ ll.116(d), ll.117(c), and 

ll.104(f)(1)–(2). 

Several commenters discussed the 

statement found in §ll.117(c)(4) that 

waiver of documentation of consent is 

generally not permitted for research 

subject to regulation by the FDA. These 

commenters noted that this would be 

true regardless of whether this was 

included in the Common Rule. 

Additionally, commenters noted that if 

the FDA regulations ever permitted 

waiver of documentation of consent, the 

existence of this provision in the 

Common Rule might result in confusion 

and contradictory requirements for 

dually regulated research. 

D. Response to Comments and 

Explanation of the Final Rule: 

Documentation of Informed Consent 

The language at §ll.117(b)(1) and 

(2) are altered in the final rule to 

conform to the requirements included at 

§ ll.116, which are discussed above. 

The goal in §§ll.116 and ll.117 of 

the final rule is to facilitate a 

prospective subject’s or legally 

authorized representative’s 

understanding of the reasons why one 

might or might not want to participate 

in the research, in part by requiring that 

only the key information essential to 

decision making receive priority by 

appearing at the beginning of the 

consent document. In the final rule, 

these requirements also apply when a 

short form written informed consent 

process is used, or the requirement for 

written informed consent is waived. 

We agree with the majority of public 

comments that favored adding a new 

provision allowing a waiver of the 

requirement for a signed consent form if 

the subjects are members of a distinct 

cultural group or community for whom 

signing documents is not the norm, 

provided that the research presents no 

more than minimal risk of harm to 

subjects and there is an appropriate 

alternative method for documenting that 

informed consent was obtained. 

Therefore, this new provision is added 

at §ll.117(c)(1)(iii). The final rule 

includes a reference to the subject’s 

legally authorized representative to 

clarify that this provision applies when 

a subject has a legally authorized 

representative who is a member of a 

distinct cultural group or community in 

which signing forms is not the norm. 

The final rule does not include the 

NPRM’s proposal at §ll.117(c)(3) to 

prohibit a waiver of documentation of 

broad consent for the storage, 

maintenance, or secondary research use 

of biospecimens. 

Some of those who commented on the 

NPRM proposals related to oral broad 

consent found it to be unnecessarily 

confusing. In response to these 

comments, the final rule permits waiver 

of documentation of informed consent 

under §ll.117(c) when a broad 

consent procedure is used. No 

additional criteria or special restrictions 

apply. Additionally, the final rule 

removes all NPRM references to ‘‘oral 

consent’’ to reduce confusion. 

However, we expect that it will rarely 

be permissible to waive documentation 

of broad consent for the secondary 

research use of medical records or 

stored biospecimens because there will 

likely be a need to track which 

individuals have provided broad 

consent and which have not, so the 

informed consent would not be the only 

record linking the subject and the 

research as required for a waiver under 

§ ll.117(c)(1)(i). Additionally, when 

identifiable information and identifiable 

biospecimens are shared for a 

nonresearch purposes, the person’s 

consent is usually required, so we 

expect that documentation of consent 

often could not be waived under 

§ ll.117(c)(1)(ii), which requires that 

the research involves only procedures 

for which written consent is not 

normally required outside of the 

research context. 

One instance when we believe it may 

be appropriate for the IRB to waive the 

requirement for a signed broad consent 

form is when the initial activity 

involved obtaining information from a 

person through oral communication, 

such as a phone survey, because there 

might not be an opportunity to obtain 

written broad consent from such 

individuals for the secondary research 

use of their information. In this 

scenario, documentation of broad 

consent could be waived under 

§ ll.117(c)(1)(ii) if the research 

presents no more than minimal risk of 

harm to subjects and involves no 

procedures for which written consent is 

normally required outside of the 

research context. In addition, it might be 

appropriate for an IRB to waive the 

requirement for a signed broad consent 

document under the provision included 

in the final rule related to when the 

subjects or their legally authorized 

representatives are members of a 

distinct cultural group or community for 

whom signing documents is not the 

norm, provided that the research 

presents no more than minimal risk of 

harm to subjects and an appropriate 

alternative method is available for 

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Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 7231 

49 5 U.S.C. 603. 

50 5 U.S.C. 601. 

51 2 U.S.C. 1532. 

documenting that informed consent was 

obtained (§ll.117(c)(1)(iii)). 

The final rule also does not include 

the NPRM’s proposed clarification that 

waivers of documentation may not be 

permitted for research subject to 

regulation by FDA. Because this is not 

the only difference between what is 

permitted under the Common Rule and 

the FDA regulations, we determined 

that clarifying only this specific 

difference in the final rule is likely to 

create more confusion rather than 

provide clarification. 

XVI. Applications and Proposals 

Lacking Definite Plans for Involvement 

of Human Subjects (§ll.118) 

A. Background and Pre-2018 

Requirements 

This provision of the pre-2018 rule 

stated that while an award or grant may 

be made for a project with indefinite 

plans to involve human subjects, that 

project must be reviewed by an IRB 

before human subjects may be involved. 

B. NPRM Proposals 

The NPRM language clarified that IRB 

review and approval was required 

before human subjects could be 

involved in a study unless the study 

was excluded under §ll.101(b), 

waived under § ll.101(i), or exempted 

under §ll.104(d), (e) or (f)(2). 

C. Public Comments 

No comments were received. 

D. Explanation of the Final Rule 

The final rule adopts the language of 

the NPRM, with updated citations. This 

provision makes explicit that it applies 

only to nonexempt human subjects 

research. 

XVII. Research Undertaken Without the 

Intention of Involving Human Subjects 

(§ ll.119) 

A. Background and Pre-2018 

Requirements 

This provision of the regulations 

outlines the process that an institution 

must undergo when a federally funded 

research project that was designed 

without the intention of involving 

human subjects later involves human 

subjects as defined by this policy. 

B. NPRM Proposals 

The NPRM proposed to add language 

to make clear that this provision applies 

only to nonexempt human subjects 

research. It also clarifies its reference to 

department or agency to mean a federal 

department or agency component 

supporting the research. 

C. Public Comments 

No comments were received. 

D. Explanation of the Final Rule 

The final rule adopts the language of 

the NPRM, with updated citations. This 

provision makes explicit that it applies 

only to nonexempt human subjects 

research, and clarifies the reference to 

department or agency to be a federal 

department or agency component 

supporting the research. 

XVIII. Conditions (§ ll.124) 

A. Background and Pre-2018 

Requirements 

This provision of the regulations 

allows departments and agencies to 

impose additional requirements on 

human subjects research when such 

requirements are deemed necessary for 

the protection of human subjects. 

B. NPRM Proposals 

The NPRM provided more specific 

language at § ll.124, stating that with 

respect to any research project or any 

class of research projects the department 

or agency head of either the conducting 

or the supporting federal department or 

agency may impose additional 

conditions prior to or at the time of 

approval when in the judgment of the 

department or agency additional 

conditions are necessary for the 

protection of human subjects. 

C. Public Comments 

One commenter discussed this NPRM 

proposal, arguing that this would 

increase variance in implementation of 

the Common Rule, rather than promote 

harmonization as the NPRM suggested. 

D. Explanation of the Final Rule 

The final rule adopts the NPRM 

language, which clarifies the pre-2018 

rule by stating that the head of either the 

conducting or the supporting federal 

department or agency may impose 

additional conditions on research, when 

necessary for the protection of human 

subjects. 

XIX. Regulatory Impact Analyses 

A. Introduction 

HHS has examined the impacts of this 

final rule under Executive Order 12866 

on Regulatory Planning and Review 

(September 30, 1993); Executive Order 

13563 on Improving Regulation and 

Regulatory Review (January 18, 2011); 

the Regulatory Flexibility Act of 1980, 

Pub. L. 96–354 (September 19, 1980); 

the Unfunded Mandates Reform Act of 

1995, Pub. L. 104–4 (March 22, 1995); 

and Executive Order 13132 on 

Federalism (August 4, 1999). 

Executive Order 12866 directs 

agencies to assess all costs and benefits 

of available regulatory alternatives and, 

if regulation is necessary, to select 

regulatory approaches that maximize 

net benefits (including potential 

economic, environmental, public health 

and safety effects; distributive impacts; 

and equity). Executive Order 13563 is 

supplemental to and reaffirms the 

principles, structures, and definitions 

governing regulatory review as 

established in Executive Order 12866. 

HHS expects that this rule will have an 

annual effect on the economy of $100 

million or more in any one year and 

therefore is a significant regulatory 

action as defined by Executive Order 

12866. 

The Regulatory Flexibility Act (RFA) 

requires agencies that issue a regulation 

to analyze options for regulatory relief 

for small businesses if a rule has a 

significant impact on a substantial 

number of small entities.49 The RFA 

generally defines a ‘‘small entity’’ as (1) 

a proprietary firm meeting the size 

standards of the Small Business 

Administration (SBA); (2) a nonprofit 

organization that is not dominant in its 

field; or (3) a small government 

jurisdiction with a population of less 

than 50,000 (states and individuals are 

not included in the definition of ‘‘small 

entity’’).50 HHS considers a rule to have 

a significant economic impact on a 

substantial number of small entities if at 

least 5 percent of small entities 

experience an impact of more than 3 

percent of revenue. HHS anticipates that 

the rule will not have a significant 

economic impact on a substantial 

number of small entities. Supporting 

analysis is provided in Section XIX.F 

below. 

Section 202(a) of the Unfunded 

Mandates Reform Act of 1995 51 requires 

that agencies prepare a written 

statement, including an assessment of 

anticipated costs and benefits, before 

proposing ‘‘any rule that includes any 

Federal mandate that may result in the 

expenditure by State, local, and tribal 

governments, in the aggregate, or by the 

private sector, of $100,000,000 or more 

(adjusted annually for inflation) in any 

one year.’’ The current threshold after 

adjustment for inflation is $146 million, 

using the most current (2015) implicit 

price deflator for the gross domestic 

product. HHS expects this rule to result 

in expenditures that will exceed this 

amount. 

Executive Order 13132 establishes 

certain requirements that an agency 

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7232 Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 

must meet when it promulgates a rule 

that imposes substantial direct 

requirement costs on state and local 

governments or has federalism 

implications. HHS has determined that 

the rule will not contain policies that 

would have substantial direct effects on 

the States, on the relationship between 

the Federal Government and the States, 

or on the distribution of power and 

responsibilities among the various 

levels of government. The changes in 

the rule represent the Federal 

Government regulating its own program. 

Accordingly, HHS concludes that the 

rule does not contain policies that have 

federalism implications as defined in 

Executive Order 13132 and, 

consequently, a federalism summary 

impact statement is not required. 

B. Need for the Final Rule and Summary 

This final rule is being issued to 

modernize, strengthen, and make more 

effective the regulations for protecting 

human subjects in research. Although 

professional organizations have codes of 

conduct and guidelines for members 

conducting research, only the Federal 

Government has the authority to 

regulate the activities of institutions 

using public funds for human subjects 

research. Since the Common Rule was 

developed, the volume of research has 

increased, evolved, and diversified. 

Thus, the final rule includes a number 

of measures to address the issues 

described above. Provisions that 

strengthen the requirements for 

informed consent and promote 

transparency in the informed consent 

process include: (1) Requiring that the 

informed consent form be designed and 

presented in such a way that facilitates 

a prospective subject’s understanding of 

why one would want to participate in a 

research study or not; (2) revising and 

adding to the required elements of 

consent; (3) requiring for certain clinical 

trials the posting of a copy of at least 

one version of a consent form on a 

publicly available federal Web site; and 

(4) clarifying the conditions and 

requirements for waiver or alteration of 

consent to remove ambiguity, including 

a new provision that, under specific 

conditions, an IRB may approve a 

research proposal in which investigators 

obtain information without individuals’ 

informed consent for the purpose of 

screening, recruiting, or determining 

eligibility of prospective human subjects 

of research. 

Provisions that strengthen the extent 

to which regulations promotes the 

principle of respect for persons include: 

(1) Requiring that informed consent 

forms present the key information to 

potential subjects at the beginning of a 

consent process; (2) allowing 

investigators the option of obtaining 

broad consent from a potential subject 

for future, unspecified research use of 

identifiable private information and 

identifiable biospecimens; and (3) 

adding a provision that would prohibit 

a waiver of consent if someone has been 

asked to provide their broad consent for 

the storage, maintenance, and secondary 

research use of identifiable 

biospecimens or identifiable private 

information and refused to do so. 

New provisions that would allow 

IRBs greater flexibility to focus 

resources on higher-risk research 

include: (1) Distinguishing categories of 

activities that are deemed not to be 

research; and (2) expanding and 

clarifying categories of exempt research. 

Provisions that streamline or reduce 

burden for IRBs or institutions include: 

(1) Requiring consultation among the 

Common Rule agencies for the purpose 

of harmonizing guidance (to the extent 

appropriate); (2) eliminating an 

administrative requirement for reporting 

IRB membership; (3) removing the 

requirement that IRBs must review and 

approve grant applications; (4) 

eliminating, under certain 

circumstances, continuing review; (5) 

mandating the use of a single IRB for 

multi-institutional studies; and (6) 

holding IRBs not operated by an FWAholding institution directly responsible 

for compliance when appropriate. 

1. Accounting Table 

Table 1 summarizes the quantified 

and nonquantified benefits and costs of 

all changes to the Common Rule. Over 

the 2017–2026 period, present value 

benefits of $1,904 million and 

annualized benefits of $223 million are 

estimated using a 3 percent discount 

rate; present value benefits of $1,494 

million and annualized benefits of $213 

million are estimated using a 7 percent 

discount rate. Present value costs of 

$528 million and annualized costs of 

$62.0 million are estimated using a 3 

percent discount rate; present value 

costs of $474 million and annualized 

costs of $67.0 million are estimated 

using a 7 percent discount rate. 

Nonquantified benefits include 

improved human subjects protections in 

research; enhanced oversight of research 

reviewed by IRBs not operated by an 

FWA-holding institution; and increased 

uniformity in regulatory requirements 

among Common Rule departments and 

agencies. Nonquantified costs include 

the time needed for consultation among 

Common Rule agencies before federal 

guidance is issued. 

TABLE 1—ACCOUNTING TABLE OF BENEFITS AND COSTS OF ALL CHANGES

Present value of 10 years 

by discount rate 

(millions of 2015 dollars) 

Annualized value over 10 

years by discount rate 

(millions of 2015 dollars) 

3 percent 7 percent 3 percent 7 percent 

Benefits: 

Quantified Benefits ................................................................................... 1,904 1,494 223 213 

Nonquantified Benefits: 

Improved human subjects protections in research; enhanced oversight in research reviewed by IRBs not operated by an FWA-holding institution; and increased uniformity in regulatory requirements among Common Rule departments and agencies. 

Costs: 

Quantified Costs: ...................................................................................... 528 474 62.0 67.0 

Nonquantified Costs: 

Time for consultation among Common Rule agencies before federal guidance is issued. 

Table 2 summarizes the quantified 

present value benefits and costs of each 

change to the Common Rule using a 3 

percent discount rate. 

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Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 7233 

TABLE 2—ACCOUNTING TABLE OF QUANTIFIED BENEFITS AND COSTS OF EACH CHANGE

Change 

Present value of 10 years 

at a 3 percent discount rate 

(millions of 2015 dollars) 

Benefits Costs 

Costs to Learn New Requirements and Develop Training Materials; OHRP Costs to Develop Training and 

Guidance Materials, and to Implement the Rule ................................................................................................. ........................ 213 

Extending Oversight to IRBs Unaffiliated with an Institution Holding an FWA (impact to IRBs not operated by 

an FWA-holding institution) .................................................................................................................................. ........................ 85.6 

Excluding Activities from the Requirements of the Common Rule because They are not Research .................... 36.2 ........................

Clarifying and Harmonizing Regulatory Requirements and Agency Guidance ...................................................... ........................ ........................

Modifying the Assurance Requirements .................................................................................................................. 5.93 ........................

Requirement for Written Procedures and Agreements for Reliance on IRBs Not Operated by the Engaged Institution (impact to FWA-holding institutions) ...................................................................................................... ........................ 11.4 

Eliminating the Requirement that the Grant Application Undergo IRB Review and Approval ............................... 326 ........................

Expansion of Research Activities Exempt from Full IRB Review ........................................................................... 798 0.37 

Elimination of Continuing Review of Research Under Specific Conditions ............................................................ 148 41.0 

Amending the Expedited Review Procedures ......................................................................................................... 51.0 ........................

Cooperative Research (single IRB mandate in multi-institutional research) .......................................................... 538 157 

Changes in the Basic Elements of Consent, Including Documentation ................................................................. ........................ 4.62 

Obtaining Consent to Secondary Use of Identifiable biospecimens and Identifiable private information .............. ........................ ........................

Elimination of Pre-2018 Rule Requirement to Waive Consent in Certain Subject Recruitment Activities ............. 1.25 ........................

Requirement for Posting of Consent Forms for Clinical Trials Conducted or supported by Common Rule Department or Agencies ........................................................................................................................................... ........................ 15.4 

Alteration in Waiver for Documentation of Informed Consent in Certain Circumstances ....................................... ........................ ........................

C. Public Comments and Response to 

Public Comments 

1. General Comments 

Approximately 50 comments 

discussed the specific cost estimates 

provided in the NPRM’s Regulatory 

Impact Analyses (RIA). Several 

commenters strongly suggested that the 

final rule eliminate the proposals 

related to biospecimens, cooperative 

research, and expanding coverage to 

nonfederally funded clinical research 

because the NPRM failed to appreciate 

the cost and burden that would result 

from implementing these proposals. 

Although a majority of the comments 

received on the RIA suggested that 

several of the cost estimates were 

significantly underestimated, few 

commenters described specific changes 

to the cost and benefit estimates 

included in the NPRM RIA. 

One commenter noted that the NPRM 

cost estimates are derived from a 1998 

NIH-sponsored evaluation of the 

implementation of Section 491 of the 

Public Health Service Act and ‘‘because 

of the lack of available data about IRB 

effectiveness and how IRBs function 

operationally, many of the estimations 

in this analysis are based on anecdotal 

evidence.’’ This commenter stated that 

reliance on outdated and anecdotal 

‘‘evidence’’ means that the NPRM 

assumptions seriously underestimate 

predictable costs, such as those derived 

from current salary data for health care 

workers who would have at least some 

background sufficient to explain 

consent, and the time needed to obtain 

consent. They also claimed that the 

NPRM analysis also seriously 

overestimates cost savings because 

excluding an activity from the Common 

Rule does not necessarily remove it 

from the purview of the IRB pursuant to 

other laws, such as the HIPAA 

regulations, and may simply shift the 

economic burden of responsible 

oversight to personnel elsewhere within 

the organization. This commenter also 

noted that the initial transition costs 

estimated in the NPRM are staggering, 

mostly due to costs related to 

biospecimen provisions. 

One commenter stated that a review 

of the tables indicates that the costs 

used for hourly wages of individuals 

affected by the proposed changes may 

be underestimated by as much as 12 to 

139 percent. Similarly, the hours 

associated with the proposed changes 

are substantially underestimated. 

One commenter stated that an 

institutional official must be 

administratively high enough to insist 

on any necessary institutional changes, 

most likely a Vice President or higher, 

and felt that such an official would 

make at least $250 per hour. This 

commenter stated that the $48.20 

estimate in the proposed rules may 

apply to liberal arts colleges, but the 

proportion of medical research 

conducted at such institutions is small 

and strongly recommends that salary 

data from medical institutions 

(published for public institutions) be 

used to generate a revised cost estimate. 

One commenter stated that the estimates 

of the salary rates presented in the 

NPRM for institutional officials, IRB 

members and staff, and investigators are 

far below the national average for these 

roles. Likewise, they state that the 

anticipated benefits of the new 

proposed rule appear to be grossly 

overstated. 

One commenter stated that the rule as 

proposed was officially estimated to add 

$1.4 billion a year to the cost of the 

current system, but the true cost 

increase will be at least triple that due 

to egregious underestimates of wage 

costs, substantial underestimates of time 

spent on red tape by investigators, and 

many underestimated or omitted costs, 

as well as some estimates that 

misrepresent the effects of the rule. 

They claim that the rule is likely to 

impose about $5 billion a year in 

needless costs, while reducing rather 

than improving protection of human 

subjects. One commenter stated that, at 

their institution, analysts average far 

greater pay levels than $15 per hour, 

and many of the tasks will have to be 

borne by faculty whose salaries exceed 

what is identified in the current cost 

analyses. 

One commenter proposed to mandate 

instead that institutions sufficiently 

resource their IRBs so as to protect 10 

percent of their IRBs’ and IRB 

administrators’ time (about 1 meeting/

year for an IRB that meets monthly; 

about 200 hours/year for a full-time 

equivalent IRB administrator with 2 

weeks’ vacation and 40-hour work 

weeks) to devote to finding efficiencies 

and innovations in the IRB review 

process. 

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52See, e.g., Abbott L, Grady C. A Systematic 

Review of the Empirical Literature Evaluating IRBs: 

What We Know and What We Still Need to Learn. 

Retrieved from http://www.ncbi.nlm.nih.gov/pmc/ 

articles/PMC3235475/. 

a. Response to General Comments 

We note that the NPRM discussed the 

fact that data about IRB effectiveness 

and how IRBs function operationally 52

is generally unavailable. The NPRM 

further noted that many of the NPRM 

RIA assumptions were based on 

anecdotal evidence; the NPRM 

requested comment on the accuracy of 

the assumptions presented and on 

whether better data sources might be 

available to support the analyses. RIA 

comments did not provide the evidence 

necessary to improve our estimates, and 

thus, limited changes have been made. 

We note that the NPRM RIA used a 

national average for the salary estimates. 

We received no compelling evidence to 

change cost estimates because we must 

account for the fact that personnel and 

salaries in affected categories vary 

widely. 

2. Extension of the Common Rule to 

Certain Nonfederally Funded Clinical 

Trials 

One commenter stated that coverage 

of this subset of projects will extend 

requirements, such as the single IRB 

requirement, without any consideration 

or mechanism for how to implement or 

fund this requirement and they do not 

believe that they should be required to 

accept added cost and burdens without 

any meaningful or measureable benefit 

to the welfare of human subjects. 

One commenter stated that the 

inclusion of nonregulated, unfunded 

trials under the regulations for the 

subset of organizations that receive 

federal grants would lead to a 

significant increase in burden, delay, 

ambiguity, and cost, and a loss of 

valuable research without increasing 

protections for human subjects. 

One commenter stated that an 

unintended burden would be the 

increased administrative costs of 

requiring reporting of all clinical trial 

Unanticipated Problems Involving Risks 

to Subjects or Others (unanticipated 

problems) to OHRP. They estimated 

requiring all unanticipated problems to 

be reported would increase their 

institution’s necessary reporting by 25 

percent. 

a. Response to Comments on Extension 

of the Common Rule to Certain 

Nonfederally Funded Clinical Trials 

The final rule does not adopt this 

proposal. 

3. Biospecimens 

With respect to expanding the 

definition of human subject to include 

nonidentifiable biospecimens and 

creating an exemption for secondary 

research on these specimens and 

identifiable information, many 

commenters claimed the NPRM 

significantly underestimated the cost of 

including nonidentified biospecimens 

under human subjects regulations and 

the consequent requirement for 

informed consent. Comments of a 

professional association, which were 

endorsed by numerous other 

commenters, stated that the NPRM has 

underestimated the financial impact of 

the Common Rule changes by a factor of 

at least 10, failing to account for the 

significant volume of specimens 

gathered outside of the federally funded 

environment, vastly underestimating the 

required time commitment and the 

requirements of administering a 

database to track consents, failing to 

include the expense incurred should an 

individual withdraw his or her consent 

for future research, and not including 

the potential expenditures required to 

develop a robust database that may be 

queried by researchers to identify 

biospecimens for use in future research 

projects. This association, and the 

numerous commenters who endorsed 

their comments, also felt that the 

increased administrative and cost 

burden to obtain informed consent for 

nonidentified biospecimens will 

disproportionately affect departments of 

pathology and laboratory medicine and 

will further increase indirect costs, 

which will eventually be built into the 

cost recovery rate from NIH, thereby 

reducing funds available for research 

when the NIH budget is fixed. One 

commenter stated that a major 

operations issue, and the one most 

necessary to ensure compliance with 

such a change, is the appropriate 

cataloging of biospecimens. Inherent in 

this new process are costs that will vary 

greatly based on the size of the stock of 

biospecimens held. Another commenter 

stated that the estimate for these costs 

was not plausible given the costs of 

developing or re-designing electronic 

systems. 

a. Response to Comments on 

Biospecimens Proposals 

As noted above in the preamble, the 

provisions relating to making 

nonidentified biospecimens subject to 

the Common Rule have been entirely 

eliminated. The final rule RIA does 

include impact estimates related to this 

proposal in Section XIX.E of this 

preamble, discussing the impact of 

regulatory alternatives considered. 

4. Broad Consent 

One commenter wrote that the NPRM 

stated that institutions would need to 

obtain broad consent from only a third 

of the 30 million individuals who are 

estimated to provide research and 

clinical biospecimens each year. 

Several commenters stated that this 

assertion fails to recognize that broad 

consent would need to be obtained from 

most individuals, not just those 

identified as research subjects, and 

underestimates the amount of time 

needed to revise consent processes and 

obtain such consent. For one institution, 

assuming staff time to obtain broad 

consent averages 20 minutes and the 

minimal staff salary is $25 per hour, this 

cost alone would be $2.54 million per 

year. Several commenters noted that the 

NPRM estimates that, per subject, the 

investigator or dedicated health care 

professional will spend 5 to 10 minutes 

obtaining broad consent, but this 

institution believes that a more 

appropriate standard for obtaining broad 

consents, particularly in the initial 

years, would be 20 to 30 minutes. One 

commenter stated that literally 

hundreds of employees would need 

extensive training and periodic 

retraining in research ethics to obtain 

broad consent, and they calculate that 

every procedure that involves any tissue 

collection should take a minimum of 10 

to 15 minutes of additional staff time to 

be able to even attempt to make the 

process meaningful. 

Many other commenters stated that 

tracking broad consent would impose 

significant costs, and require significant 

resources and infrastructure 

restructuring, given the complicated 

framework proposed by the NPRM. 

One of these commenters also stated 

that a significant cost absent from the 

NPRM analysis is the potential need for 

rebuilding existing biorepositories and 

databanks that may be invalidated 

under the NPRM because: (1) The 

samples were collected without initial 

broad consent; (2) the samples are coded 

and thus not eligible for the transition 

provisions; (3) consenting all human 

sources would not be feasible; and (4) 

the revised and limited waiver 

mechanism would not be available. One 

commenter estimated that it will require 

millions of dollars to build and support 

the necessary IT and infrastructure 

required to keep track of the consents. 

One commenter stated that, if the 

NPRM’s concern for ‘‘respect for 

persons’’ is really sincere, then the cost 

estimates involved should be increased 

by a factor of 4 to 10 times what is 

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estimated in the NPRM. One commenter 

stated estimates that the biospecimen 

changes alone will cost their institution 

close to half a million U.S. dollars just 

in system changes to allow for the 

added administrative consent processes 

followed by the tracking mechanisms 

that will have to be put into place to 

accommodate the regulatory changes. 

a. Response to Comments on Broad 

Consent 

As noted above in the preamble, the 

provisions relating to making 

nonidentified biospecimens subject to 

the Common Rule have been entirely 

eliminated. Eliminating that proposal 

largely addresses the concerns regarding 

costs of the Broad Consent proposal. 

Note that in response to public 

comments, we have modified our 

estimates of the time it would take to 

seek, obtain, and document broad 

consent under the regulatory 

alternatives section of the RIA. 

5. Exemptions 

One commenter stated that even if a 

decision tool is used, IRBs will likely 

still need to review protocols to confirm 

the exempt classification, which will 

therefore not result in any cost savings. 

a. Response to Comments on 

Exemptions 

The final rule does not include the 

exemption determination and 

documentation requirement proposed in 

the NPRM. 

6. Privacy Safeguards 

One commenter stated that mandatory 

use of HIPAA or alternative, but yet-tobe determined, data security provisions 

would lead to a significant increase in 

burden, delay, ambiguity, and cost; this 

commenter also asserted that these 

safeguards might result in a loss of 

valuable research without increasing 

protections for human subjects. 

One commenter noted that a large 

component of the data security 

safeguards is only necessary because of 

the 10-fold increase in the number of 

identified biospecimens due to tracking 

informed consent and that this adds 

significantly to the cost of this 

requirement, well beyond what was 

represented in the NPRM RIA. 

a. Response to Comments on Privacy 

Safeguards 

The final rule does not adopt the 

NPRM’s proposal to implement 

standardized privacy safeguards. 

7. Continuing Review 

One commenter applauded the NPRM 

for recognizing the cost-benefit value of 

eliminating continuing review for many 

studies. This will have a positive impact 

on the workload of investigators and 

IRBs. 

8. Single IRB Review 

Several commenters stated that 

mandated single IRB review would not 

decrease the burden for investigators but 

would, in fact, increase the burden in 

both the long and short term. They 

stated that investigators who currently 

work only with a single IRB (their 

institution’s IRB) will now have to work 

with multiple IRBs, adding to burden. 

Further, the resources needed to use a 

commercial IRB would be beyond the 

capacity of small trials, which often 

have limited resources. One of these 

commenters estimated that, an 

investigator who has 50 protocols and 

currently two IRBs of record, would 

have a minimum of 10 different IRBs of 

record under the regulations proposed 

in the NPRM. As a result, the 

investigator would need to work with at 

least an additional 8 IRBs (10 in total), 

each with unique and complex 

requirements. 

One commenter stated that the NPRM 

grossly underestimates in its 

assumption that a central IRB 

administrator would cost $15 per hour. 

One commenter stated that 

developing the infrastructure to support 

this effort will involve significant 

financial costs. Although using single 

IRBs for multi-institutional studies has 

the potential for long-term cost savings 

and reduction of burden when 

implemented well, reaching that point 

requires a substantial initial investment. 

Many other commenters agreed that the 

NPRM underestimated these initial 

costs. They stated that these ‘‘start-up 

costs’’ include but are not limited to: 

The creation of electronic management 

systems that are interoperable among 

institutions; the adaptation of 

automated processes to multiple 

institutions; the communications tools 

necessary to link investigators and IRBs; 

the staff time necessary to develop 

agreements, consensus documents, or 

standard operating procedures; and the 

interaction necessary to build and 

maintain trusting relationships among 

institutional officials. One university 

received an estimate from the vendor of 

such a system that costs to 

accommodate this change would be in 

excess of $220,000 for the initial 

changes, with increased maintenance 

costs thereafter. In addition, the 

university would need to hire at least 

one full-time-equivalent (FTE) to handle 

the interface with all of the potential 

central IRBs and this position has a 

salary mid-point of $54,000, to which 

would be applied fringe benefits costs of 

$19,500. Several commenters noted that, 

even for institutions not serving as the 

IRB of record, there are real financial 

implications of participating in the 

centralized process in terms of adapting 

existing software systems and protocols. 

One commenter noted that the RIA 

section of the NPRM assigned nearly 

one-third of the total financial benefit of 

the revised Common Rule to savings 

achieved by the use of single IRBs for 

cooperative research. The RIA arrived at 

its estimate by assuming that when a 

single IRB of record reviews a protocol, 

all institutional costs are eliminated. 

The commenting institution uses 

numerous single IRBs, and they say they 

know from experience that the 

assumptions in the RIA are erroneous 

and no net savings accrue for IRB staff 

when using single IRBs of record. This 

same commenter noted that the NPRM 

states that its authors believe that, over 

time, standardization of agreements will 

occur so that all issues that currently 

take weeks or months to negotiate will 

be resolved. This commenter stated that 

no data to support this assumption and 

that, with each new single IRB required 

by NIH, they find a new set of 

requirements that requires the 

negotiation of hundreds of agreements 

with other institutions. They believe 

that study initiation will often be 

delayed because of this requirement and 

will result in additional software system 

needs and costs that are not even 

contemplated in the NPRM. They also 

stated that the vast majority of researchintensive universities are already over 

the federal mandated 26 percent 

facilities and administrative cap. 

Therefore, the commenter noted, the 

universities have no mechanism for 

funding the additional costs of serving 

as a central IRB because IRB costs are 

included in the portion of the facilities 

and administrative costs. 

One commenter estimated the costs of 

ensuring an appropriate data flow 

between an institution and each new 

IRB of record, with respect to research 

studies conducted, to require an extra 

200 hours of IRB administrator time, in 

addition to software customization, 

configuration, and development costs. 

This commenter estimated the true costs 

far exceed those included in the NPRM 

by a factor of 1433 percent (2150 hours 

required in total for 10 IRBs of record, 

versus 150 hours). Even splitting the 

difference to only a factor of 767 percent 

(1150 hours required in total for 10 IRBs 

of record versus 150 hours), the true 

costs of this approach virtually eclipse 

any possible quantified benefits 

estimated in the NPRM. 

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53Bell J., Whiton J., and Connelly S., Final 

Report: Evaluation of NIH Implementation of 

Section 491 of the Public Health Service Act, 

Mandating a Program of Protection for Research 

Subjects, 1998. 

Two commenters cautioned that the 

costs to implement single IRB review in 

multi-institutional studies should not be 

factored into the overall cost breakdown 

of a contract or grant. In other words, 

federal departments and agencies 

supporting research should make 

additional funds available to cover the 

costs associated with implementing 

§ ll.114. 

a. Response to Comments on Single IRB 

Review 

We agree with commenters who felt 

that mandated single IRB review will 

ultimately decrease administrative 

burdens and inefficiencies for 

investigators and institutions, while 

acknowledging that the transition to this 

model will require time and an 

adjustment to institutional structures 

and policies. To incorporate this into 

our estimates, we assume that 

investigators for which multiinstitutional reviews are eliminated will 

face a reduction in burden associated 

with the elimination of the site-specific 

protocol review, but will face increased 

burden in the form of coordination with 

investigators at other sites, for example 

to ensure that the results of the IRB 

review are effectively communicated. 

Specifically, we assume that the 

elimination of multi-institutional 

reviews will result in investigators 

spending half as much time engaging 

with the review process as they would 

have if IRB review had taken place at all 

sites. As a result, the estimated 

quantified benefits associated with the 

elimination of multi-institutional review 

have been revised downward by 27 

percent. 

9. Posting of Clinical Trial Informed 

Consent Forms 

Several commenters stated that they 

do not see the utility of the proposed 

provision to publish consent forms to a 

public Web site as it creates a new 

administrative burden without 

providing any clear additional 

protection for research subjects or 

benefit to the public at large. One 

commenter stated that the cost estimates 

that the NPRM attaches to this proposed 

requirement are unrealistically low. One 

commenter stated that if the site is 

either ClinicalTrials.gov or some future 

site that is of equal difficulty to use, the 

cost estimates for investigators and 

institutions to upload to the site are 

greatly underestimated. This institution 

has found that their investigators have 

found ClinicalTrials.gov sufficiently 

difficult that they have had to add and 

train staff devoted solely to meet this 

requirement. 

a. Response to Comments on Posting of 

Consent Forms 

We note that this change, compared to 

the huge costs of clinical trials, will add 

a relatively small amount of additional 

burden. The time by which a consent 

form must be posted has been greatly 

extended. Furthermore, provisions have 

been added that allow for redaction of 

certain portions of consent forms, 

including the entire form in appropriate 

instances. We estimate that the revised 

rule will not affect the quantified and 

nonquantified costs summarized in the 

NPRM. 

D. Analysis of Benefits and Costs 

In this section, we present the 

analysis of the quantified and 

nonquantified benefits and costs of the 

changes to the Common Rule. First, we 

discuss the common assumptions of the 

analysis. Then we present the estimated 

quantified and nonquantified benefits 

and costs of the specific changes. As 

discussed above and in the NPRM, 

because of the lack of available data 

about IRB effectiveness and how IRBs 

function operationally, many of the 

estimations in this analysis are based on 

anecdotal evidence. 

1. Analytic Assumptions 

The analysis relies on common data 

elements and assumptions, detailed 

below, concerning the domestic entities, 

individuals, and IRB reviews affected by 

the changes to the Common Rule. Many 

of the estimates are derived from a 1998 

NIH-sponsored evaluation of the 

implementation of Section 491 of the 

Public Health Service Act, which 

involved nationally representative 

surveys of IRBs, institutions, and 

investigators. Based on a review of the 

literature, this study contains the best 

available data on the time spent on 

protocol reviews as well as the 

characteristics of the reviews 

themselves. Additionally, OHRP 

processes the majority of FWAs and IRB 

registrations for all Common Rule 

departments or agencies. Thus, using 

information from the OHRP database of 

assured institutions and registered 

institutions or organizations and their 

IRBs is a reasonable way to estimate the 

number of institutions and IRBs 

regulated by all Common Rule 

departments or agencies that will be 

affected by these changes. OHRP’s IRB 

registration process requires institutions 

and organizations to provide 

information about the approximate 

number of active protocols reviewed by 

IRBs during the preceding 12 months. 

Thus, OHRP’s IRB database is the best 

source for determining the total number 

of protocols reviewed by IRBs at this 

time. 

According to the OHRP database of 

assured institutions and registered 

institutions or organizations and their 

IRBs, approximately 8,035 institutions 

in the United States have an FWA, of 

which 2,871 have an IRB. Some 

institutions have multiple IRBs and 

some IRBs are not affiliated with an 

institution with an FWA. In total, 3,499 

registered IRBs are in the United States. 

The OHRP database of assured 

institutions and registered institutions 

or organizations and their IRBs shows 

that 675,390 annual reviews of 

nonexempt protocols involving human 

subjects are conducted. It is estimated 

that of this total, 324,187 are initial 

protocol reviews (48 percent) and 

351,203 are continuing protocol reviews 

(52 percent) based on estimates reported 

in Bell et al.53 In each category, it is 

estimated that 69 percent of these 

reviews are convened and 31 percent 

are expedited based on estimates 

reported in Bell et al. 

It is estimated that 472,773 reviews of 

single-site protocols (70 percent) and 

202,617 reviews of multi-institutional 

protocols (30 percent) take place, based 

on estimates reported in Bell et al. This 

analysis also assumes that, on average, 

5 IRB reviews take place per multiplesite protocol. This implies 472,773 

single-site protocols and 40,523 multiinstitutional protocols, for a total of 

513,296 protocols. The above also 

implies approximately 246,382 new 

protocols each year. 

Based on queries of ClinicalTrials.gov, 

we estimated that HHS supports 909 

new clinical trials annually, of which 

575 are regulated by FDA. In addition, 

based on queries of ClinicalTrials.gov, 

non-HHS Common Rule departments 

and agencies support approximately 

5,270 studies. 

Many individuals in various 

occupations would be affected by the 

changes to the Common Rule. We 

estimated that an average of one 

institution official at each institution 

with an FWA would be affected by these 

changes, for a total of 2,871 institution 

officials. The OHRP database of 

registered IRBs shows that IRBs have 

10,197 full-time equivalents (FTEs) staff 

persons working as administrators or 

administrative staff, and that 89.8 

percent of IRBs have an administrator. 

It is assumed that these individuals 

work full-time, implying a total of 3,193 

IRB administrators and 7,004 IRB 

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54To derive this estimate, the number of new 

protocols, estimated above, is divided by the 

average number of new protocol submissions 

reported per investigator. This is estimated to be 2.8 

based on Bell et al. This number is then multiplied 

by the average number of investigators working on 

each protocol (which is assumed to be 5). This 

allows for an accounting of investigators working 

on multiple protocols as well as protocols with 

multiple investigators. 

administrative staff. The OHRP database 

of IRB membership rosters contains 

3,359 individuals who serve as IRB 

chairs and an additional 32,518 voting 

members. The number of IRB chairs is 

less than the number of IRBs because 

some individuals chair multiple IRBs. It 

is assumed that 439,968 investigators 

conduct human subjects research in the 

United States.54

We estimated the hourly wages of 

individuals affected by the changes to 

the Common Rule using information on 

annual salaries provided by the U.S. 

Bureau of Labor Statistics and the U.S. 

Office of Personal Management. The 

salary of postsecondary education 

administrators is used as a proxy for the 

salary of institution officials; the salary 

of lawyers is used as a proxy for the 

salary of institution legal staff and IRB 

administrators; the salary of office and 

administrative support workers is used 

as a proxy for the salary of IRB 

administrative staff; the salary of 

postsecondary health teachers is used as 

a proxy for the salary of IRB chairs and 

IRB voting members; the salary of 

postsecondary teachers is used as a 

proxy for the salary of investigators; the 

salary of database and systems 

administrators and network architects is 

used as a proxy for the salary of 

database administrators; and the salary 

of all occupations, as a proxy for the 

salary of prospective human subjects. 

The federal employees affected by the 

changes to the Common Rule are 

assumed to be Step 5 within their GSlevel and earn locality pay for the 

District of Columbia, Baltimore, and 

Northern Virginia. Annual salaries are 

divided by 2,087 hours to derive hourly 

wages. To project wages over 2017– 

2026, wages are adjusted for growth 

over time using the average annual per 

capita growth in real wage income over 

1929–2012 reported by the U.S. Bureau 

of Economic Analysis, which is 2.1 

percent. The total dollar value of labor, 

which includes wages, benefits, and 

overhead, is assumed to be equal to 200 

percent of the wage rate. 

We calculated person-hours by 

occupation per initial protocol review 

and per continuing protocol review 

based on each occupation’s share of 

total person-hours reported in Bell et al. 

In particular, Bell et al. reports that 

institution officials account for 4 

percent, IRB administrators account for 

28 percent, IRB administrative staff 

account for 30 percent, IRB chairs 

account for 7 percent, and IRB voting 

members account for 31 percent of total 

person-hours. We assumed that the 

average number of person-hours spent 

per review equals the weighted average 

of the person-hours spent per convened 

review and the person-hours spent per 

expedited review. We further assumed 

that convened review requires twice as 

many person-hours as expedited review. 

Table 3 shows the number of entities 

affected by the changes to the Common 

Rule and other common assumptions of 

the analysis (described above). 

TABLE 3—NUMBER OF AFFECTED ENTITIES AND OTHER COMMON ASSUMPTIONS

Description Estimate 

U.S. Institutions and IRBs: 

Institutions with an FWA ............................................................................................................................................... 8,035 

FWA Institutions with an IRB ....................................................................................................................................... 2,871 

FWA Institutions without an IRB .................................................................................................................................. 5,164 

U.S. IRBs ...................................................................................................................................................................... 3,499 

Occupations: 

Institution officials ......................................................................................................................................................... 2,871 

IRB administrators ........................................................................................................................................................ 3,193 

IRB administrative staff ................................................................................................................................................ 7,004 

IRB chairs ..................................................................................................................................................................... 3,359 

IRB voting members ..................................................................................................................................................... 32,518 

Investigators ................................................................................................................................................................. 439,968 

Hourly Wages: 

Institution officials (2015) .............................................................................................................................................. $49.17 

Institution legal staff (2015) .......................................................................................................................................... $65.29 

IRB administrators (2015) ............................................................................................................................................ $65.29 

IRB administrative staff (2015) ..................................................................................................................................... $17.41 

IRB chairs (2015) ......................................................................................................................................................... $50.06 

IRB voting members (2015) ......................................................................................................................................... $50.06 

Investigators (2015) ...................................................................................................................................................... $37.13 

Database administrators (2015) ................................................................................................................................... $40.37 

Prospective Human Subjects (2015) ............................................................................................................................ $23.15 

Federal employees in the District of Columbia, Baltimore, and Northern Virginia (2015) .......................................... ........................................

GS–11 Step 5 ........................................................................................................................................................ $34.60 

GS–13 Step 5 ........................................................................................................................................................ $49.32 

GS–14 Step 5 ........................................................................................................................................................ $58.28 

GS–15 Step 5 ........................................................................................................................................................ $68.56 

Average annual per capita growth in real wage income ............................................................................................. 2.1% 

IRB Reviews of Human Subjects Research Protocols at U.S. Institutions: 

Annual reviews of nonexempt protocols ...................................................................................................................... 675,390 

Initial protocol reviews (48%) ................................................................................................................................ 324,187 

Convened reviews (69%) ............................................................................................................................... 223,689 

Expedited reviews (31%) ............................................................................................................................... 100,498 

Continuing protocol reviews (52%) ....................................................................................................................... 351,203 

Convened reviews (69%) ............................................................................................................................... 242,30 

Expedited reviews (31%) ............................................................................................................................... 108,873 

Annual reviews of single-site protocols (70%) ............................................................................................................. 472,773 

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TABLE 3—NUMBER OF AFFECTED ENTITIES AND OTHER COMMON ASSUMPTIONS—Continued 

Description Estimate 

Annual reviews of multi-institutional protocols (30%) .................................................................................................. 202,617 

Human Subjects Research Protocols at U.S. Institutions: 

Active protocols ............................................................................................................................................................ 513,296 

Single-site protocols .............................................................................................................................................. 472,773 

Multi-site protocols ................................................................................................................................................ 40,523 

New protocols (48%) .................................................................................................................................................... 246,382 

Average number of IRB reviews per active multi-institutional protocol ....................................................................... 5 

Clinical Trials: 

New clinical trials supported by HHS annually ............................................................................................................ 909 

Regulated by FDA ................................................................................................................................................. 575 

Clinical Trials supported by Common Rule Agencies .................................................................................................. 5,270 

Person-Hours per Protocol Reviewed by Occupation and Type of Review: 

Institution officials: 

Initial protocol reviews: 

Convened reviews .......................................................................................................................................... 0.52 

Expedited reviews .......................................................................................................................................... 0.26 

Continuing protocol reviews: 

Convened reviews .......................................................................................................................................... 0.10 

Expedited reviews .......................................................................................................................................... 0.05 

IRB administrators: 

Initial protocol reviews: 

Convened reviews .......................................................................................................................................... 3.64 

Expedited reviews .......................................................................................................................................... 1.82 

Continuing protocol reviews: 

Convened reviews .......................................................................................................................................... 0.68 

Expedited reviews .......................................................................................................................................... 0.34 

IRB administrative staff: 

Initial protocol reviews: 

Convened reviews .......................................................................................................................................... 3.91 

Expedited reviews .......................................................................................................................................... 1.95 

Continuing protocol reviews: 

Convened reviews .......................................................................................................................................... 0.73 

Expedited reviews .......................................................................................................................................... 0.36 

IRB chairs: 

Initial protocol reviews: 

Convened reviews .......................................................................................................................................... 0.91 

Expedited reviews .......................................................................................................................................... 0.46 

Continuing protocol reviews: 

Convened reviews .......................................................................................................................................... 0.17 

Expedited reviews .......................................................................................................................................... 0.08 

IRB voting members: 

Initial protocol reviews: 

Convened reviews .......................................................................................................................................... 2.70 

Expedited reviews .......................................................................................................................................... 1.35 

Exempt reviews .............................................................................................................................................. 0.50 

Continuing protocol reviews: 

Convened reviews .......................................................................................................................................... 0.75 

Expedited reviews .......................................................................................................................................... 0.38 

Investigators: 

Initial protocol reviews: 

Convened reviews .......................................................................................................................................... 13.65 

Expedited reviews .......................................................................................................................................... 7.15 

Exempt reviews .............................................................................................................................................. 0.50 

Continuing protocol reviews: 

Convened reviews .......................................................................................................................................... 6.83 

Expedited reviews .......................................................................................................................................... 3.58 

2. Analysis of Changes 

We present below an analysis of the 

quantified and nonquantified benefits 

and costs of the changes to the Common 

Rule. For each change, we describe the 

change, provide a qualitative summary 

of the anticipated benefits and costs, 

describe the methods we use to quantify 

benefits and costs, and then present 

estimates. 

a. Costs for the Regulated Community 

To Learn New Requirements and 

Develop Training Materials; Costs for 

OHRP To Develop Materials and 

Guidance 

Domestic institutions, IRBs, and 

investigators would need to spend time 

learning the changes to the Common 

Rule once training materials become 

available to them. In addition, IRBs and 

OHRP would need to update training 

materials for investigators. OHRP also 

would need to develop guidance, 

templates, and a number of electronic 

resources. 

We estimate that institution officials, 

IRB administrators, IRB administrative 

staff, IRB chairs, IRB voting members, 

and investigators would each spend 5 

hours to learn the changes to the 

Common Rule. We also estimate that 

institution officials would spend 2 

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hours to learn new procedures, IRB 

administrators would spend 20 hours, 

and administrative staff would spend 80 

hours. Based on the estimates presented 

in Table 3, the dollar value of their time 

is calculated by multiplying hours by 

their estimated 2016 wages and 

adjusting for overhead and benefits. For 

example, to calculate the dollar value of 

time spent by institution officials to 

learn the changes to the Common Rule 

in 2017, we multiply the number of 

institution officials (2,871) by the 

number of hours spent per institutional 

official (5), by the projected hourly wage 

of institution officials ($49.17), and by 

the adjustment factor for benefits and 

overhead (2). 

In order to develop the resources 

required by the final rule, we anticipate 

that OHRP would need: 

• Three staff people at the GS–14 

level and three staff people at the GS– 

13 level to: (1) Promote harmonization 

efforts to issue guidance across Common 

Rule agencies and departments; (2) 

develop guidance for the regulated 

community; (3) develop template 

agreements for use by the regulated 

community; (4) manage the 

administrative transition to the new 

processes in the final rule; and, (5) 

develop web-based posting portals. 

• One staff person at the GS–13 level 

to manage process changes in the final 

rule, and assist with implementation for 

the web-based portals. 

• One staff person at the GS–11 level 

to provide technical support for the 

web-based portals in the final rule. 

In addition, the first year after the 

final rule is published staffing resources 

beyond what is described above would 

be necessary: 

• Three staff people at the GS–14 

level to draft new guidance and revise 

old guidance. 

• One staff person at the GS–14 level 

to conduct educational seminars. 

OHRP also anticipates the following 

in nonpersonnel costs: 

• Technical development of two Webbased portals for investigators to post 

final consent forms for HHS-funded 

clinical trials, and for investigators who 

conduct certain types of demonstration 

projects to post information about said 

projects ($350,000) 

• Developing five educational 

seminars (including travel) to educate 

the public about the requirements of the 

new rule ($150,000) 

• Upgrading equipment for education 

activities ($50,000) 

We also note that additional staff time 

throughout the Common Rule 

departments and agencies will be 

needed to fulfill the consultation 

requirement found in §ll.102(e)(7). 

As we assume that this consultation will 

not involve the hiring of additional 

personnel to fulfill, we consider this a 

nonquantified cost. 

Present value costs of $214 million 

and annualized costs of $25.0 million 

are estimated using a 3 percent discount 

rate; present value costs of $204 million 

and annualized costs of $29.1 million 

are estimated using a 7 percent discount 

rate. Table 4 summarizes the quantified 

and nonquantified benefits and costs to 

learn new requirements and develop 

training materials. 

TABLE 4—SUMMARY OF ESTIMATED BENEFITS AND COSTS TO LEARN NEW REQUIREMENTS AND DEVELOP TRAINING

MATERIALS

Present value of 10 

years by discount rate 

(millions of 2015 dollars) 

Annualized value over 10 

years by discount rate 

(millions of 2015 dollars) 

3 percent 7 percent 3 percent 7 percent 

BENEFITS: 

Quantified Benefits: 

None ......................................................................................................... ........................ ........................ ........................ ........................

Nonquantified Benefits: 

None. 

COSTS: 

Quantified Costs: 

Time and money to learn new requirements, update training materials, 

develop tools and conduct consultations .............................................. 214 204 25.0 29.1 

Nonquantified Costs: 

Implementation of consultation requirements. 

b. Extending Oversight to IRBs 

Unaffiliated With an Institution Holding 

an FWA (§ ll.101(a)) 

As outlined in the NPRM, and as 

generally supported by public 

commenters, the final rule includes a 

new provision at §ll.101(a) that gives 

Common Rule departments and 

agencies the authority to enforce 

compliance directly against IRBs that 

are not operated by an assured 

institution. We anticipate that this 

change will encourage institutions to 

rely on IRBs not operated by an FWAholding institution more often and also 

will assist in the implementation of the 

requirements at § ll.114. Here, we 

estimate the impact that this proposal 

will have on IRBs that are not operated 

by an FWA- holding institution. The 

estimated impact of this and other 

related proposals on FWA- holding 

institutions is addressed in Section 

XIX.D.2.f of this RIA. 

The OHRP database of assured 

institutions and registered IRBs shows 

that approximately 449 IRBs not 

affiliated with an institution holding an 

FWA will now be subject to oversight. 

These IRBs will develop an estimated 

average of 10 written agreements with 

other institutions each year as a result 

of this rule. It is further estimated that 

each agreement will require an average 

of 10 hours of institution legal staff time 

and 5 hours of IRB administrator time 

to complete. 

The estimated costs to institution 

officials, IRB administrators, IRB 

administrative staff, IRB chairs, IRB 

voting members, and investigators of 

conducting these reviews are based on 

the estimates presented in Table 3. The 

dollar value of their time is calculated 

by multiplying hours by their estimated 

2017–2026 wages and adjusting for 

overhead and benefits. 

Present value costs of $85.6 million 

and annualized costs of $10.0 million 

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7240 Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 

are estimated using a 3 percent discount 

rate; present value costs of $70.0 million 

and annualized costs of $10.0 million 

are estimated using a 7 percent discount 

rate. Table 5 summarizes the quantified 

and nonquantified benefits and costs of 

extending oversight to IRBs unaffiliated 

with an institution holding an FWA. 

TABLE 5—SUMMARY OF ESTIMATED BENEFITS AND COSTS OF EXTENDING OVERSIGHT TO IRBS UNAFFILIATED WITH AN

INSTITUTION HOLDING AN FWA (§ ll.101(a)) 

Present value of 10 

years by discount rate 

(millions of 2015 dollars) 

Annualized value over 10 

years by discount rate 

(millions of 2015 dollars) 

3 percent 7 percent 3 percent 7 percent 

BENEFITS: 

Quantified Benefits: 

None ......................................................................................................... ........................ ........................ ........................ ........................

Nonquantified Benefits: 

Encouraging institutions to rely on single IRBs of record in multi-institutional studies when appropriate. 

COSTS: 

Quantified Costs: 

Developing IRB authorization agreements or other procedures .............. 85.6 70.0 10.0 10.0 

Nonquantified Costs: 

None. 

c. Explicit Carve-Outs of Activities From 

the Definition of Research (§ll.102(l)) 

The final rule includes four categories 

that are explicitly deemed to be not 

research (final rule at §ll.102(l)(1)– 

(4)). These categories include: (1) 

Scholarly and journalistic activities 

(e.g., oral history, journalism, biography, 

literary criticism, legal research and 

historical scholarship), including the 

collection and use of information that 

focuses directly on the specific 

individuals about whom the 

information is collected; (2) certain 

public health surveillance activities; (3) 

certain collection and analysis activities 

conducted by a criminal justice agency; 

and (4) certain activities conducted by 

a defense, national security, or 

homeland security authority. 

Institutions, investigators, and IRBs 

involved in supporting, conducting, or 

reviewing these activities will no longer 

incur the costs of IRB review and 

approval and continuing review. 

Activities that were not intended to be 

subject to the regulations will clearly be 

removed from the definition of research, 

allowing such activities to proceed 

without delays caused by the need for 

IRB submission, review, and approval. 

We estimate that 3,376 annual 

reviews of protocols (0.5 percent) will 

no longer be conducted as a result of the 

activities deemed not to be research in 

§ ll.102(l)(1)–(4). Of these reviews, 

1,118 will have undergone convened 

initial review, 502 will have undergone 

expedited initial review, 1,212 will have 

undergone convened continuing review, 

and 544 will have undergone expedited 

continuing review based on the 

distribution of reviews presented in 

Table 3. 

The estimated costs to institution 

officials, IRB administrators, IRB 

administrative staff, IRB chairs, IRB 

voting members, and investigators of 

conducting these reviews are based on 

the estimates presented in Table 3. The 

dollar value of their time is calculated 

by multiplying hours by their estimated 

2017–2026 wages and adjusting for 

overhead and benefits. 

Present value benefits of $36.2 million 

and annualized benefits of $4.24 million 

are estimated using a 3 percent discount 

rate, and present value benefits of $29.6 

million and annualized benefits of $4.22 

million are estimated using a 7 percent 

discount rate. Table 6 summarizes the 

quantified and nonquantified benefits 

and costs of excluding these activities 

from the requirements of the Common 

Rule. 

TABLE 6—SUMMARY OF ESTIMATED BENEFITS AND COSTS OF § ll.102(l) 

Present value of 10 

years by discount rate 

(millions of 2015 dollars) 

Annualized value over 10 

years by discount rate 

(millions of 2015 dollars) 

3 percent 7 percent 3 percent 7 percent 

BENEFITS: 

Quantified Benefits: 

Reduction in number of reviews ............................................................... 36.2 29.6 4.24 4.22 

Nonquantified Benefits: 

Increased clarity in what must be reviewed; ability for IRBs to focus efforts on reviews of higher-risk, more complex research activities. 

COSTS: 

Quantified Costs: 

None ......................................................................................................... ........................ ........................ ........................ ........................

Nonquantified Costs: 

None. 

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Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 7241 

d. Clarifying and Harmonizing 

Regulatory Requirements and Agency 

Guidance (§ll.101(j)) 

The final rule at §ll.101(j) requires 

consultation among the Common Rule 

departments and agencies for the 

purpose of harmonization of guidance 

(to the extent appropriate) before federal 

guidance on the Common Rule is 

issued, unless such consultation is not 

feasible. 

As this change likely will not affect 

staffing requirements in the Federal 

Government, no costs are quantified 

here. It is possible however, that the 

harmonization requirement could result 

in it taking longer for Common Rule 

department or agency guidance to be 

approved and issued to the public. 

Similarly, as the extent to which this 

change will reduce the time IRBs spend 

on reviewing protocols is unclear, 

benefits are also not quantified. Table 7 

summarizes the nonquantified benefits 

and costs of clarifying and harmonizing 

regulatory requirements and agency 

guidance. 

TABLE 7—SUMMARY OF ESTIMATED BENEFITS AND COSTS OF CLARIFYING AND HARMONIZING REGULATORY

REQUIREMENTS AND AGENCY GUIDANCE (§ ll.101(j)) 

Present value of 10 

years by discount rate 

(millions of 2015 dollars) 

Annualized value over 10 

years by discount rate 

(millions of 2015 dollars) 

3 percent 7 percent 3 percent 7 percent 

BENEFITS: 

Quantified Benefits: 

None ......................................................................................................... ........................ ........................ ........................ ........................

Nonquantified Benefits: 

Increased uniformity in regulatory requirements among Common Rule agencies; increased clarity to the regulated community about how 

regulations should be interpreted. 

COSTS: 

Quantified Costs: 

None ......................................................................................................... ........................ ........................ ........................ ........................

Nonquantified Costs: 

Time for consultation among Common Rule agencies before federal guidance is issued. 

e. Modifying the Assurance 

Requirements (§ll.103) 

The final rule modifies the 

requirements of the assurance process in 

the following ways. First, the final rule 

does not include the pre-2018 

requirement of identifying a statement 

of principles governing all research at 

an institution. The requirement for 

institutions to designate a set of ethical 

principles by which that institution will 

abide in all research activities was 

generally not enforced. Further, for 

international institutions that received 

U.S. Government funding for research 

activities, it created the impression that 

these international institutions must 

modify their internal procedures to 

comport with the set of principles 

designated on the FWA for activities 

conducted at those institutions that 

received no U.S. Government funding. 

This provision was deleted from the 

final rule to provide clarity to these 

international institutions that such 

measures are not required for activities 

that receive no Common Rule 

department or agency support. 

The requirement in the pre-2018 rule 

that a written assurance include a list of 

IRB members for each IRB designated 

under the assurance has been moved to 

§ ll.108(a)(2) and modified. The final 

rule requires that an institution, or 

when appropriate the IRB, prepare and 

maintain a current detailed list of the 

IRB members with information 

sufficient to describe each member’s 

chief anticipated contributions to IRB 

deliberation, and any employment or 

other relationship between each 

member and the institution. The final 

rule also deletes the pre-2018 

requirement that changes in IRB 

membership be reported to the 

department or agency head, or to OHRP 

when the existence of an HHS-approved 

assurance is accepted. 

The changes to the IRB roster 

requirement are expected to reduce 

administrative burden without having 

any significant impact on the protection 

of human subjects: 

Finally, the requirement in the pre2018 rule that a department or agency 

head’s evaluation of an assurance take 

certain factors into consideration has 

been deleted. These factors include the 

adequacy of the proposed IRB in light of 

the anticipated scope of the institution’s 

activities and the types of subject 

populations likely to be involved, the 

appropriateness of the proposed initial 

and continuing review procedures in 

light of the probable risks, and the size 

and complexity of the institution. 

Deletion of that provision eliminates an 

administrative process that was no 

longer meaningful given the purpose 

and design of the FWA and OHRP’s 

processes for reviewing IRB registrations 

and reviewing and approving FWAs. 

This change also harmonizes the 

Common Rule with FDA’s human 

subjects protection regulations by 

eliminating the requirement to submit 

IRB membership lists. 

We estimate that administrative staff 

at each IRB would spend 5 fewer hours 

complying with the assurance 

requirements. Based on the estimates 

presented in Table 3, the dollar value of 

their time is calculated by multiplying 

hours by their estimated 2017–2026 

wages and adjusting for overhead and 

benefits. 

Present value benefits of $5.93 million 

and annualized benefits of $0.69 million 

are estimated using a 3 percent discount 

rate; present value benefits of $4.18 

million and annualized benefits of $0.60 

million are estimated using a 7 percent 

discount rate. Table 8 summarizes the 

quantified and nonquantified benefits 

and costs of the proposed change to the 

IRB roster requirement. 

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TABLE 8—SUMMARY OF ESTIMATED BENEFITS AND COSTS OF CHANGES TO MODIFYING THE ASSURANCE REQUIREMENTS

(PRE-2018 RULE AT § ll.103(b)(1), (b)(3), (d)) 

Present value of 10 

years by discount rate 

(millions of 2015 dollars) 

Annualized value over 10 

years by discount rate 

(millions of 2015 dollars) 

3 percent 7 percent 3 percent 7 percent 

BENEFITS: 

Quantified Benefits: 

Reduction in time for IRB administrative staff and OHRP staff to submit, review, and process IRB membership lists ................................... 5.93 4.18 0.69 0.60 

Nonquantified Benefits: 

Reduction in volume of records created by an institution. 

COSTS: 

Quantified Costs: 

None ......................................................................................................... ........................ ........................ ........................ ........................

Nonquantified Costs: 

None. 

f. Requirement for Documenting 

Reliance on IRBs Not Operated by the 

FWA-Holding Institution (§§ ll.103(e) 

and ll.115(a)(9)) 

The final rule contains a requirement 

at §ll.103(e) that, to ensure 

compliance with the requirements of the 

Common Rule, nonexempt human 

subjects research subject to this policy 

that takes place at an institution in 

which IRB oversight is conducted by an 

IRB that is not operated by the 

institution, the institution and the 

organization operating the IRB shall 

document the institution’s reliance on 

the IRB for oversight of the research and 

the responsibilities that each entity will 

undertake. This requirement could be 

satisfied, for example, by: (1) 

Developing a written agreement 

between the institution and the IRB; (2) 

implementing an institution-wide 

policy directive providing the allocation 

of responsibilities between the 

institution and an IRB that is not 

affiliated with the institution; or (3) 

describing the allocation of 

responsibilities in a research protocol. 

In addition, a requirement is added at 

§ ll.115(a)(9) of the final rule that 

institutions or IRBs retain this written 

agreement or other procedures 

undertaken to ensure compliance with 

the requirements of this policy, as 

described in § ll.103(e). 

Initially, costs would be involved in 

drafting, revising, and conducting 

managerial review of agreements to 

ensure they satisfy these new 

requirements. Anticipated benefits 

include greater reliance on IRBs not 

operated by the institutions as the IRB 

of record for cooperative research. 

Table 3 shows that 5,164 FWAholding institutions do not have an IRB 

and 2,871 FWA-holding institutions 

have an IRB. We assume that the 5,164 

FWA-holding institutions without an 

IRB have an average of 1 IRB 

authorization agreement that will need 

to be modified as a result of the new 

requirements for agreements between 

institutions and IRBs not operated by 

the institutions in 2017. In addition, we 

assume that the 2,871 FWA-holding 

institutions with an IRB have an average 

of 0.20 IRB authorization agreements 

that would need to be modified in 2017. 

We estimate that each agreement will 

require an average of 10 hours of 

institution legal staff time and 5 hours 

of IRB administrator time to complete. 

The dollar value of their time is 

calculated by multiplying hours by their 

estimated 2017 wages and adjusting for 

overhead and benefits. 

Present value costs of $11.4 million 

and annualized costs of $1.33 million 

are estimated using a 3 percent discount 

rate; present value costs of $10.9 million 

and annualized costs of $1.56 million 

are estimated using a 7 percent discount 

rate. Table 9 summarizes the quantified 

and nonquantified benefits and costs of 

the requirement for written procedures 

and agreements for reliance on IRBs not 

operated by the FWA-holding 

institution (§§ll.103(e) and 

ll.115(a)(9) in the final rule). 

TABLE 9—SUMMARY OF REQUIREMENT FOR WRITTEN PROCEDURES AND AGREEMENTS FOR RELIANCE ON IRBS NOT

OPERATED BY THE FWA-HOLDING INSTITUTION (§§ ll.103(e) AND ll.115(a)(10)) 

Present value of 10 

years by discount rate 

(millions of 2015 dollars) 

Annualized value over 10 

years by discount rate 

(millions of 2015 dollars) 

3 percent 7 percent 3 percent 7 percent 

BENEFITS: 

Quantified Benefits: 

None ......................................................................................................... ........................ ........................ ........................ ........................

Nonquantified Benefits: 

None. 

COSTS: 

Quantified Costs: 

Time to modify written agreements between IRBs and institutions ......... 11.4 10.9 1.33 1.56 

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TABLE 9—SUMMARY OF REQUIREMENT FOR WRITTEN PROCEDURES AND AGREEMENTS FOR RELIANCE ON IRBS NOT

OPERATED BY THE FWA-HOLDING INSTITUTION (§§ ll.103(e) AND ll.115(a)(10))—Continued 

Present value of 10 

years by discount rate 

(millions of 2015 dollars) 

Annualized value over 10 

years by discount rate 

(millions of 2015 dollars) 

3 percent 7 percent 3 percent 7 percent 

Nonquantified Costs: 

None. 

g. Eliminating the Requirement That the 

Grant Application Undergo IRB Review 

and Approval (Pre-2018 Rule at 

§ ll.103(f)) 

The final rule eliminates the 

requirement in the pre-2018 rule that 

grant applications undergo IRB review 

and approval for the purposes of 

certification. The grant application is 

often outdated by the time the research 

study is submitted for IRB review and 

contains detailed information about the 

costs of a study, personnel, and 

administrative issues that go beyond the 

mission of the IRB to protect human 

subjects. Therefore, experience suggests 

that review and approval of the grant 

application is not a productive use of 

IRB time, and the change likely will not 

reduce protections for human subjects 

or impose other costs. 

We estimate that 324,187 initial 

reviews of protocols occur annually, of 

which 223,689 involve convened review 

and 100,498 involve expedited review 

based on the distribution of reviews 

presented in Table 3. For the purpose of 

this analysis, we assume that each 

protocol reviewed by an IRB is 

associated with one grant application or 

other funding proposal. We estimate 

that investigators spend an average of 15 

minutes compiling their grant 

applications when they submit a 

protocol for initial review. Further, we 

estimate that IRBs typically use two 

primary reviewers for convened review 

and one primary reviewer for expedited 

review, and that primary reviewers 

spend an average of 30 minutes 

reviewing the grant application. Based 

on the estimates in Table 3, the dollar 

value of their time is calculated by 

multiplying hours by their estimated 

2017–2026 wages and adjusting for 

overhead and benefits. 

Present value benefits of $326 million 

and annualized benefits of $38.2 million 

are estimated using a 3 percent discount 

rate and present value benefits of $230 

million and annualized benefits of $32.7 

million are estimated using a 7 percent 

discount rate. Table 10 below 

summarizes the quantified and 

nonquantified benefits and costs of 

eliminating the requirement that the 

grant application undergo IRB review 

and approval. 

TABLE 10—SUMMARY OF ESTIMATED BENEFITS AND COSTS OF ELIMINATING THE REQUIREMENT THAT THE GRANT

APPLICATION UNDERGO IRB REVIEW AND APPROVAL (PRE-2018 RULE AT § ll.103(f)) 

Present value of 10 

years by discount rate 

(millions of 2015 dollars) 

Annualized value over 10 

years by discount rate 

(millions of 2015 dollars) 

3 percent 7 percent 3 percent 7 percent 

BENEFITS: 

Quantified Benefits: 

Decreased time associated with reviewing grant applications ................. 326 230 38.2 32.7 

Nonquantified Benefits: 

None. 

COSTS: 

Quantified Costs: 

None ......................................................................................................... ........................ ........................ ........................ ........................

Nonquantified Costs: 

None. 

h. Expansion of Exemption Categories 

(§ ll.104(d)) 

The final rule includes eight 

exemption categories. Some of these 

categories include subcategories of 

exemptions. 

We note that one pre-2018 exemption 

does not appear in the final rule 

(exemption for educational tests, survey 

procedures, interview procedures, or 

observation of public behavior where a 

statute requires confidentiality of the 

information collected, or where the 

human subjects involved in the activity 

are public figures). We also note that 

several of the final rule exemptions 

were proposed in the NPRM as 

exclusions. Finally, we note that only 

one pre-2018 exemption has been 

unmodified in the final rule (the 

exemption for taste and food quality 

evaluations). 

The exemptions included in the final 

rule are: 

• Certain research involving normal 

educational practices 

• Certain research that involves the 

use of educational tests, survey 

procedures, interview procedures, or 

observation of public behavior 

• Research involving benign 

behavioral interventions in conjunction 

with the collection of information from 

an adult subject through verbal or 

written responses or video recording 

• Research involving the secondary 

use of identifiable private information 

or identifiable biospecimens provided 

that: 

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7244 Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 

55Estimates based on queries of ClinicalTrials.gov 

and a search of the CMS Web site. See e.g., http:// 

www.medicaid.gov/medicaid-chip-programinformation/by-topics/waivers/ 

waivers_faceted.html, and https://www.cms.gov/ 

Research-Statistics-Data-and-Systems/StatisticsTrends-and-Reports/ActiveProjectReports/ 

APR_2011_Edition.html. 

Æ The sources are publicly available 

Æ The information is recorded in such 

a manner that the identity of subjects is 

not readily ascertainable by the 

investigator 

Æ The research is regulated as ‘‘health 

care operations,’’ ‘‘public health 

activities,’’ or ‘‘research’’ under HIPAA 

Æ The research is conducted by or on 

behalf of a federal department or agency 

using government-generated or 

government-collected nonresearch 

information, provided that certain 

conditions are met 

• Research and demonstration 

projects conducted or supported by a 

federal department or agency 

Æ In addition to OHRP’s 

interpretation of this exemption 

expanding under the final rule, and 

language being modified in this 

exemption to reflect that expanded 

interpretation, the final rule also 

includes a requirement that federal 

departments or agencies conducting or 

supporting demonstration projects post 

information about these studies on a 

publicly accessible federal Web site 

• Taste and food quality evaluation 

and consumer acceptance studies 

• The storage and maintenance of 

identifiable biospecimens or identifiable 

private information for unspecified 

secondary research studies 

• The secondary research use of 

identifiable biospecimens or identifiable 

private information where broad 

consent has been sought and obtained 

The goal of the posting requirement in 

the exemption for research and 

demonstration projects (final rule at 

§ ll.104(d)(5)) is to promote 

transparency in federally conducted or 

supported activities affecting the public 

that are not subject to oversight under 

the Common Rule. It should not create 

any delay in research. HHS will develop 

a resource that all Common Rule 

departments and agencies may use to 

satisfy the posting requirement 

(accounted for in Section XIX.D.2.a of 

this RIA). Alternatively, an agency can 

create or modify its own Web site for 

this purpose. Thus, increased 

transparency in federally funded or 

supported demonstration projects is a 

non-quantified benefit of the final rule 

modifications. 

Other nonquantified benefits of the 

expansion to the modifications of 

exempt research include clearer 

instructions to the regulated community 

about the extent to which creating a 

system for storing and maintaining 

identifiable biospecimens and 

identifiable private information for 

future, unspecified secondary research 

activities is governed by this rule. 

Additionally, by reducing the IRB 

burden associated with approving this 

type of activity, the new exemption for 

storing and maintaining identifiable 

biospecimens and identifiable private 

information also incentivizes the 

creation of institution-wide, 

comprehensive systems for storing and 

maintaining such biospecimens and 

information. We anticipate that this 

will, in turn, foster research while also 

giving human subjects increased control 

over how their identifiable 

biospecimens and identifiable private 

information will be used (promoting the 

principle of respect for persons). 

Consistent with the NPRM, we 

estimate that 70,916 annual reviews of 

protocols (10.5 percent) would no 

longer be conducted as a result of the 

changes at § ll.104(d). Of these 

reviews, 23,487 will have undergone 

convened initial review, 10,552 will 

have undergone expedited initial 

review, 25,445 will have undergone 

convened continuing review, and 

11,432 will have undergone expedited 

continuing review based on the 

distribution of reviews presented in 

Table 3. 

Further, we estimate that that 1,000 

exempt research and demonstration 

studies are currently conducted each 

year.55 We further estimate that due to 

the change in OHRP’s interpretation of 

the research and demonstration project 

exemption at § ll.104(d)(5), an 

additional 3,376 annual reviews of 

protocols (0.5 percent) will no longer be 

conducted. Of these 3,376 reviews, 

1,118 would have undergone convened 

initial review, 502 would have 

undergone expedited initial review, 

1,212 would have undergone convened 

continuing review, and 544 would have 

undergone expedited continuing review 

based on the distribution of reviews 

presented in Table 3. The 4,376 

estimated annual studies conducted 

under this exemption will need to be 

posted on a federal Web site as required 

by §ll.104(d)(5)(i). We anticipate that 

it will take individuals at the IRB 

administrative staff level 15 minutes per 

study to post the study on the Web site. 

Present value benefits of $798 million 

and annualized benefits of $93.6 million 

are estimated using a 3 percent discount 

rate, and present value benefits of $653 

million and annualized benefits of $93.0 

million are estimated using a 7 percent 

discount rate. Present value costs of 

$0.37 million and annualized costs of 

$0.04 million are estimated using a 3 

percent discount rate; present value 

costs of $0.30 million and annualized 

costs of $0.04 million are estimated 

using a 7 percent discount rate. Table 11 

summarizes the quantified and 

nonquantified benefits and costs of 

amending an exempt category. 

TABLE 11—SUMMARY OF ESTIMATED BENEFITS AND COSTS OF EXPANDING THE EXEMPTION CATEGORIES (§ ll.104(d)) 

Present value of 10 

years by discount rate 

(millions of 2015 dollars) 

Annualized value over 10 

years by discount rate 

(millions of 2015 dollars) 

3 percent 7 percent 3 percent 7 percent 

BENEFITS: 

Quantified Benefits: 

Reduction in number of reviews ............................................................... 798 653 93.6 93.0 

Nonquantified Benefits: 

Clarity in what research activities must be reviewed; ability for IRBs to focus efforts on reviews of higher-risk, more complex, research activities; fostering research with biospecimens and identifiable private information. 

COSTS: 

Quantified Costs: 

None ......................................................................................................... 0.37 0.30 0.04 0.04 

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Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 7245 

TABLE 11—SUMMARY OF ESTIMATED BENEFITS AND COSTS OF EXPANDING THE EXEMPTION CATEGORIES (§ ll

.104(d))—Continued 

Present value of 10 

years by discount rate 

(millions of 2015 dollars) 

Annualized value over 10 

years by discount rate 

(millions of 2015 dollars) 

3 percent 7 percent 3 percent 7 percent 

Nonquantified Costs: 

None. 

i. Elimination of Continuing Review of 

Research Under Specific Conditions 

(§§ ll.109(f) and ll.115(a)(3)) 

The final rule eliminates continuing 

review for many minimal risk studies, 

as detailed at §ll.109(f). Unless an 

IRB determines otherwise, continuing 

review of research is not required if: (1) 

The research is eligible for expedited 

review in accordance with §ll.110; 

(2) the research is reviewed by the IRB 

in accordance with the limited IRB 

review procedure described in several of 

the exemption categories (specifically, 

§ ll.104(d)(2)(iii), 

§ ll.104(d)(3)(i)(C), §ll.104(d)(7), 

or §ll.104(d)(8)); or (3) the research 

has progressed to the point that it only 

involves data analysis (including 

analysis of identifiable information or 

identifiable biospecimens) or access to 

follow-up clinical data from procedures 

that subjects would undergo as part of 

clinical care. If an IRB chooses to 

conduct continuing review even when 

these conditions are met, the rationale 

for doing so must be documented 

according to a new provision at 

§ ll.115(a)(3). 

We estimate that 108,873 expedited 

continuing reviews of protocols occur 

annually, based on the distribution of 

reviews presented in Table 3. Of these 

reviews, we further estimate that 81,546 

reviews (75 percent) will not be 

eliminated by other changes to the 

Common Rule (such as the 

modifications at § ll.104(d)). It is 

estimated that 40,773 of these 81,546 

reviews (50 percent) will be 

discontinued under § ll.109(f), and 

the remaining 40,773 reviews (50 

percent) will still require 

documentation of the rationale for doing 

so (as required under §ll.115(a)(3)). 

We also estimate that IRB voting 

members will spend 1 hour per review 

providing the necessary documentation. 

In addition, administrative staff at each 

IRB will spend an estimated 10 hours in 

2017 updating their communication 

systems to no longer send continuing 

review reminders to affected 

investigators. 

The estimated costs to institution 

officials, IRB administrators, IRB 

administrative staff, IRB chairs, IRB 

voting members, and investigators of 

conducting these reviews are based on 

the estimates presented in Table 3. The 

dollar value of their time is calculated 

by multiplying hours by their estimated 

2017–2026 wages and adjusting for 

overhead and benefits. 

Present value benefits of $148 million 

and annualized benefits of $17.4 million 

are estimated using a 3 percent discount 

rate, and present value benefits of $121 

million and annualized benefits of $17.3 

million are estimated using a 7 percent 

discount rate. Present value costs of 

$41.0 million and annualized costs of 

$4.80 million are estimated using a 3 

percent discount rate; present value 

costs of $33.7 million and annualized 

costs of $4.80 million are estimated 

using a 7 percent discount rate. Table 12 

summarizes the quantified and 

nonquantified benefits and costs of the 

elimination of continuing review of 

research under specific conditions. 

TABLE 12—SUMMARY OF ESTIMATED BENEFITS AND COSTS OF THE ELIMINATION OF CONTINUING REVIEW OF RESEARCH

UNDER SPECIFIC CONDITIONS (§§ ll.109(f) AND ll.115(a)(3)) 

Present value of 10 years by 

discount rate 

(millions of 2015 dollars) 

Annualized value over 10 

years by discount rate 

(millions of 2015 dollars) 

3 percent 7 percent 3 percent 7 percent 

BENEFITS: 

Quantified Benefits: 

Reduction in number of continuing reviews ............................................. 148 121 17.4 17.3 

Nonquantified Benefits: 

None. 

3 Percent 7 Percent 3 Percent 7 Percent 

COSTS: 

Quantified Costs: 

Time to document rationale for conducting continuing review and update IRB communication systems ........................................................ 41.0 33.7 4.80 4.80 

Nonquantified Costs: 

None. 

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7246 Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 

j. Expedited Review Procedures 

(§§ ll.110 and ll.115(a)(8)) 

The final rule changes the default 

position such that any research activity 

appearing on the expedited review list 

is presumed to be minimal risk. 

Additionally, the final rule requires 

that, in consultation with other 

Common Rule departments or agencies, 

the expedited review categories be 

reviewed every 8 years and amended as 

appropriate, followed by publication in 

the Federal Register and solicitation of 

public comment. Finally, the final rule 

contains a new requirement at 

§ ll.115(a)(8) concerning IRB records, 

requiring that IRBs document the 

rationale for an expedited reviewer’s 

determination that research activities 

appearing on the expedited review list 

are more than minimal risk (i.e., an 

override of the presumption that studies 

on the Secretary’s list of expedited 

review activities are minimal risk). We 

note that because the final rule does not 

include a proposal to develop guidance 

with a list of activities presumed to be 

minimal risk, cost estimates in the final 

rule have been modified accordingly. 

Changes to the expedited review 

procedures are expected to reduce IRB 

workload by decreasing the amount of 

time IRB voting members spend making 

minimal risk determinations and 

documenting such determinations. 

Nonquantified benefits include a 

reduction in the number of studies that 

require full, convened IRB review 

should more categories of activities be 

added to the expedited review list. 

According to the estimates presented 

in Table 3, 209,371 protocols undergo 

expedited review each year. For these 

protocols, we estimate that, as a result 

of these changes, IRB voting members 

will spend an average of 15 fewer 

minutes per protocol developing and 

documenting a rationale for why certain 

activities that are permitted to be 

reviewed under the expedited review 

procedure are minimal risk. 

The dollar value of IRB voting 

member time is calculated by 

multiplying hours by their estimated 

2017–2026 wages and adjusting for 

overhead and benefits. 

Present value benefits of $51.0 million 

and annualized benefits of $5.98 million 

are estimated using a 3 percent discount 

rate, and present value benefits of $41.7 

million and annualized benefits of $5.94 

million are estimated using a 7 percent 

discount rate. Table 13 summarizes the 

quantified and nonquantified benefits 

and costs of amending expedited review 

procedures. 

TABLE 13—SUMMARY OF ESTIMATED BENEFITS AND COSTS OF AMENDING THE EXPEDITED REVIEW PROCEDURES

(§§ ll.110 AND ll.115(a)(8)) 

Present value of 10 years by 

discount rate 

(millions of 2015 dollars) 

Annualized value over 10 

years by discount rate 

(millions of 2015 dollars) 

3 percent 7 percent 3 percent 7 percent 

BENEFITS: 

Quantified Benefits: 

Reduction in time spent making and documenting minimal risk determinations and documenting such determinations ................................ 51.0 41.7 5.98 5.94 

Nonquantified Benefits: 

None. 

3 Percent 7 Percent 3 Percent 7 Percent 

COSTS: 

Quantified Costs: 

None ......................................................................................................... ........................ ........................ ........................ ........................

Nonquantified Costs: 

None. 

k. Cooperative Research (§ ll.114)) 

The final rule requires under 

§ ll.114 that any institution located in 

the United States that is engaged in 

cooperative research shall rely on 

approval by a single IRB for that portion 

of the research that is conducted in the 

United States. This policy has two 

exceptions (detailed in §ll.114(b)(2)): 

(1) Cooperative research for which more 

than single IRB review is required by 

law (including tribal law passed by the 

official governing body of a American 

Indian or Alaska Native tribe); and (2) 

research for which any federal 

department or agency supporting or 

conducting the research determines and 

documents that the use of a single IRB 

is not appropriate for the particular 

study. Nonquantified benefits of this 

change include standardization of 

human subjects protections in multiinstitutional studies. 

Ultimately, these revisions are 

expected to lower costs associated with 

multiple reviews for investigators, 

institutions, and IRBs. Some cost 

shifting may occur as certain IRBs 

assume the role of reviewing IRB. 

However, these will be offset by savings 

at other IRBs that are no longer required 

to conduct additional reviews of the 

same research study. Initially, IRBs and 

institutions will have to draft and revise 

their policies regarding their reliance on 

single IRBs. It is expected that, over 

time, reliance agreements and other 

methods of documenting external 

reliance will become standardized, 

which will result in reduced costs 

associated with multiple reviews and 

time savings for investigators who no 

longer must wait for multiple reviews. 

The OHRP database of registered 

institutions and IRBs shows that 8,035 

institutions have an FWA. We estimate 

that these institutions will develop an 

average of 10 written joint review 

agreements with other institutions in 

2019 before the first year of compliance. 

We further estimate that each agreement 

will require an average of 10 hours of 

institution legal staff time and 5 hours 

of IRB administrator time to complete. 

The dollar value of their time is 

calculated by multiplying hours by their 

estimated wages and adjusting for 

overhead and benefits. 

We estimate that 202,617 annual 

reviews of multi-institutional protocols 

take place, and an average of 5 reviews 

per multi-institutional protocol, 

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Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 7247 

56 Moral Science: Protecting Participants in 

Human Subjects Research. Washington, DC: 

Presidential Advisory Commission for the Study of 

Bioethical Issues. Retrieved from http://

bioethics.gov/sites/default/files/ 

Moral%20Science%20June%202012.pdf, p. 34. 

implying that 40,523 multi-institutional 

protocols are reviewed each year. We 

further estimate that 16,209 (40 percent) 

of these multi-institutional studies are 

funded by NIH 56 and thus will already 

be subject to NIH’s single IRB review 

policy. Accordingly, we estimate that 

approximately 97,256 annual reviews of 

protocols will no longer be conducted as 

a result of these proposed changes. Of 

these reviews, 32,211 would have 

undergone convened initial review, 

14,472 would have undergone 

expedited initial review, 34,896 would 

have undergone convened continuing 

review, and 15,678 would have 

undergone expedited continuing review 

based on the distribution of reviews 

presented in Table 3. 

In response to comments on the 

NPRM RIA, we have modified our 

assumptions of how much time would 

ultimately be saved by the 

implementation of this proposal (see 

Section XIX.C of this RIA). We assume 

that investigators for whom multiinstitutional reviews are eliminated will 

face a reduction in burden associated 

with the elimination of the site-specific 

protocol review, but will face increased 

burden in the form of coordination with 

investigators at other sites, for example, 

to ensure that the results of the IRB 

review are effectively communicated. 

Specifically, we assume that the 

elimination of multi-institutional 

reviews will result in investigators 

spending half as much time engaging 

with the review process as they would 

have if IRB review had taken place at all 

sites. 

The estimated costs to institution 

officials, IRB administrators, IRB 

administrative staff, IRB chairs, IRB 

voting members, and investigators of 

conducting these reviews are based on 

the estimates presented in Table 3, 

adjusted accordingly to account for our 

assumption that the time savings for 

these eliminated reviews is reduced by 

half for investigators. The dollar value 

of their time is calculated by 

multiplying hours by their estimated 

2020–2026 wages and adjusting for 

overhead and benefits. 

Present value benefits of $538 million 

and annualized benefits of $63.1 million 

are estimated using a 3 percent discount 

rate, and present value benefits of $414 

million and annualized benefits of $59.0 

million are estimated using a 7 percent 

discount rate. Present value costs of 

$157 million and annualized costs of 

$18.3 million are estimated using a 3 

percent discount rate; present value 

costs of $140 million and annualized 

costs of $19.9 million are estimated 

using a 7 percent discount rate. Table 14 

summarizes the quantified and 

nonquantified benefits and costs of 

cooperative research. 

TABLE 14—SUMMARY OF ESTIMATED BENEFITS AND COSTS OF COOPERATIVE RESEARCH (§ ll.114) 

Present value of 10 years by 

discount rate 

(millions of 2015 dollars) 

Annualized value over 10 

years by discount rate 

(millions of 2015 dollars) 

3 percent 7 percent 3 percent 7 percent 

BENEFITS: 

Quantified Benefits: 

Reduction in number of reviews ............................................................... 538 414 63.1 59.0 

Nonquantified Benefits: 

Standardization of human subjects protections in multi-institutional studies. 

3 Percent 7 Percent 3 Percent 7 Percent 

COSTS: 

Quantified Costs: 

Time required to develop model reliance agreement and written joint 

review agreements ................................................................................ 157 140 18.3 19.9 

Nonquantified Costs: 

None. 

l. Changes in the Elements of Consent, 

Including Documentation 

(§§ ll.116(a)(5), (b)(9), (c)(7)–(9), and 

ll.117(b)) 

The final rule imposes a new 

requirement at § ll.116(a)(5)(i) that 

informed consent must begin with a 

concise and focused presentation of the 

key information that is most likely to 

assist a prospective subject or legally 

authorized representative in 

understanding the reasons why one 

might or might not want to participate 

in the research. This provision further 

mandates that this part of the informed 

consent must be organized and 

presented in a way that facilitates 

comprehension. This requirement 

applies to all informed consent 

processes, except for broad consent 

obtained pursuant to §ll.116(d), 

which may warrant a different 

presentation. 

The final rule includes a new element 

of consent at §ll.116(b)(9) that 

requires one of the following statements 

be included for any research that 

involves the collection of identifiable 

private information or identifiable 

biospecimens: 

• A statement that identifiers might 

be removed from the identifiable private 

information or identifiable 

biospecimens and that, after such 

removal, the information or 

biospecimens could be used for future 

research studies or distributed to 

another investigator for future research 

studies without additional informed 

consent from the subject or the legally 

authorized representative, if this might 

be a possibility; or 

• A statement that the subject’s 

information or biospecimens collected 

as part of the research, even if 

identifiers are removed, will not be used 

or distributed for future research 

studies. 

This new requirement is intended to 

give the potential subject the knowledge 

that identifiers might be removed from 

information or biospecimens for their 

use in future research without 

additional consent, when such a 

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7248 Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 

possibility exists, so he or she can make 

a fully informed decision about whether 

to participate in the research. If subjects’ 

identifiable private information or 

identifiable biospecimens will not be 

used for future research studies, even if 

identifiers are removed, this new 

element of consent requires that subjects 

be informed of this as well. 

The final rule’s three additional 

elements of consent are in 

§ ll.116(c)(7), (8), and (9). These 

require that a subject be informed of the 

following, when appropriate: 

• That the subject’s biospecimens 

(even if identifiers are removed) may be 

used for commercial profit and whether 

the subject will or will not share in this 

commercial profit; 

• Whether clinically relevant research 

results, including individual research 

results, will be disclosed to subjects, 

and if so, under what conditions. 

• For research involving 

biospecimens, whether the research will 

(if known) or might include whole 

genome sequencing (i.e., sequencing of 

a human germline or somatic specimen 

with the intent to generate the genome 

or exome sequence of that specimen. 

These three additional elements of 

consent will promote respect for 

persons and greater transparency in the 

research enterprise. Additionally, 

including the information referenced in 

these provisions in a consent form will 

help ensure that prospective subjects are 

given information necessary for 

understanding why one might want to 

participate (or not) in a research study. 

The language at §ll.117(b)(1) in the 

final rule was modified to reference 

§ ll.116(a)(5)(i) and state that if a 

short form consent process is used, the 

key information required by 

§ ll.116(a)(5)(i) must be presented 

first to the prospective subject, before 

other information, if any, is provided. 

We estimate that 246,382 new 

protocols annually use identifiable 

information. For each protocol, we 

estimate that investigators will spend an 

average of 15 minutes in 2017 updating 

consent forms to comply with the new 

requirements found in the final rule at 

§ ll.116(a)(5), (b)(9), (c)(7), (c)(8), or 

(c)(9). Based on the estimates presented 

in Table 3, the dollar value of 

investigators’ time is calculated by 

multiplying hours by their estimated 

2017 wages and adjusting for overhead 

and benefits. 

We assume that few additional 

investigators will elect to offer the 

second option at §ll.116(b)(9), and 

that the investigators who currently 

offer equivalent options already track 

the permissible and impermissible uses 

of information in line with the 

requirements discussed above. As a 

result, we estimate that no additional 

costs are associated with tracking. 

Present value costs of $4.62 million 

and annualized costs of $0.54 million 

are estimated using a 3 percent discount 

rate; present value costs of $4.32 million 

and annualized costs of $0.62 million 

are estimated using a 7 percent discount 

rate. Table 15 summarizes the 

quantified and nonquantified benefits 

and costs of changes in the basic 

elements of consent, including 

documentation. 

TABLE 15—SUMMARY OF ESTIMATED BENEFITS AND COSTS OF CHANGES IN THE ELEMENTS OF CONSENT, INCLUDING

DOCUMENTATION (§§ ll.116(a)(5), (b)(9), (c)(7), (c)(8) AND ll.117(b)) 

Present value of 10 

years by discount rate 

(millions of 2015 dollars) 

Annualized value over 10 

years by discount rate 

(millions of 2015 dollars) 

3 percent 7 percent 3 percent 7 percent 

BENEFITS: 

Quantified Benefits: 

None ......................................................................................................... ........................ ........................ ........................ ........................

Nonquantified Benefits: 

Improved informed consent forms and processes; greater transparency in the research enterprise. 

COSTS: 

Quantified Costs: 

Time to update consent forms .................................................................. 4.62 4.32 0.54 0.62 

Nonquantified Costs: 

None. 

m. Obtaining Consent to Secondary Use 

of Identifiable Biospecimens and 

Identifiable Private Information 

(§ ll.116(d)) 

Because the final rule does not adopt 

the NPRM proposal to consider all 

biospecimens as human subjects 

regardless of identifiability, the costs 

associated with seeking, obtaining, and 

tracking broad consent are reduced 

significantly. As noted above, comments 

on the NPRM suggest that the costs 

associated with building systems to 

track broad consent are very 

burdensome. Therefore, we expect that 

broad consent and institution-wide 

tracking systems will be pursued only in 

situations where it generates net 

benefits. As a result, in the short term, 

we are unsure of the extent to which 

institutions will adopt institution-wide 

mechanisms to seek, obtain, and track 

broad consent. We anticipate in the 

short term that broad consent (and the 

attendant tracking and maintenance 

obligations) will be a system used and 

managed by investigators or teams of 

investigators in their research portfolios. 

However, we believe that it will be 

adopted more over time at an 

institutional level as IT systems evolve 

at research institutions through normal 

practice. We lack data to estimate the 

number of research studies for which 

this option will be adopted. Each of 

these studies will have some variable 

costs (e.g., consent, tracking) and fixed 

costs (IT infrastructure). Because this is 

optional, we believe that it will be 

pursued only if private benefits exceed 

private costs. Therefore, we anticipate 

benefits, in terms of improvements in 

the quality and efficiency of human 

subjects research, proportional to the 

adoption of broad consent. We note that 

the voluntary nature of adoption implies 

that broad consent may not be sought in 

some situations where its social benefit 

exceeds its social cost. 

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TABLE 16—SUMMARY OF ESTIMATED BENEFITS AND COSTS OF OBTAINING CONSENT TO SECONDARY USE OF

IDENTIFIABLE BIOSPECIMENS AND IDENTIFIABLE PRIVATE INFORMATION (§ ll.116(d)) 

Present value of 10 

years by discount rate 

(millions of 2015 dollars) 

Annualized value over 10 

years by discount rate 

(millions of 2015 dollars) 

3 percent 7 percent 3 percent 7 percent 

BENEFITS: 

Quantified Benefits: 

None ......................................................................................................... ........................ ........................ ........................ ........................

Nonquantified Benefits: 

Improvements in the quality and efficiency of human subjects research. 

COSTS: 

Quantified Costs: 

None ......................................................................................................... ........................ ........................ ........................ ........................

Nonquantified Costs: 

Time and infrastructure required to obtain and track broad consent. 

n. Allowing IRBs To Approve a 

Research Proposal for Subject 

Recruitment Activities Without 

Granting a Waiver of Consent 

(§ ll.116(g)) 

The final rule will allow an IRB to 

approve a research proposal in which 

investigators obtain information or 

biospecimens without individuals’ 

informed consent for the purpose of 

screening, recruiting, or determining the 

eligibility of prospective human subjects 

of research in certain circumstances. 

This addresses concerns that the pre2018 regulations required an IRB to 

determine that informed consent could 

be waived before investigators could 

record identifiable private information 

for the purpose of screening, recruiting, 

or determining the eligibility of 

prospective subjects for a research 

study. The pre-2018 rule requirement 

was viewed as burdensome without 

providing meaningful protections to 

subjects. 

The policy adopted in the final rule 

should result in time and cost savings 

for investigators and IRBs, but they 

likely will be small. The savings will 

come from IRBs no longer needing to 

consider whether informed consent can 

be waived for such preparatory-toresearch activities. Savings will accrue 

for investigators who can proceed with 

such activities in less time. 

We estimate that 1,620 annual initial 

reviews of protocols (0.5 percent) 

involve a waiver of consent for 

recruitment activities that will not be 

required as a result of these changes. Of 

these reviews, 1,118 will have 

undergone convened initial review and 

502 will have undergone expedited 

initial review based on the distribution 

of reviews presented in Table 3. We 

estimate that investigators spend an 

average of 15 minutes requesting a 

waiver of consent for recruitment 

activities when they submit a protocol 

for initial review. We further estimate 

that IRBs typically use two primary 

reviewers for convened review and one 

primary reviewer for expedited review, 

and that primary reviewers spend an 

average of 15 minutes determining 

whether informed consent can be 

waived. Based on the estimates in Table 

3, the dollar value of their time is 

calculated by multiplying hours by their 

estimated 2017–2026 wages and 

adjusting for overhead and benefits. 

Present value benefits of $1.25 million 

and annualized benefits of $0.15 million 

are estimated using a 3 percent discount 

rate, and present value benefits of $0.88 

million and annualized benefits of $0.13 

million are estimated using a 7 percent 

discount rate. Table 17 summarizes the 

quantified and nonquantified benefits 

and costs of eliminating the requirement 

to waive consent in certain subject 

recruitment activities. 

TABLE 17—SUMMARY OF ESTIMATED BENEFITS AND COSTS OF ELIMINATION OF REQUIREMENT TO WAIVE CONSENT IN

CERTAIN SUBJECT RECRUITMENT ACTIVITIES (§ ll.116(g)) 

Present value of 10 years 

by discount rate 

(millions of 2015 dollars) 

Annualized value over 10 

years 

by discount rate 

(millions of 2015 dollars) 

3 percent 7 percent 3 percent 7 percent 

Quantified Benefits: 

Decreased time associated with review ................................................... 1.25 0.88 0.15 0.13 

BENEFITS: 

Nonquantified Benefits: 

None. 

3 Percent 7 Percent 3 Percent 7 Percent 

COSTS: 

Quantified Costs: ........................ ........................ ........................ ........................

None.

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7250 Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 

TABLE 17—SUMMARY OF ESTIMATED BENEFITS AND COSTS OF ELIMINATION OF REQUIREMENT TO WAIVE CONSENT IN

CERTAIN SUBJECT RECRUITMENT ACTIVITIES (§ ll.116(g))—Continued 

Present value of 10 years 

by discount rate 

(millions of 2015 dollars) 

Annualized value over 10 

years 

by discount rate 

(millions of 2015 dollars) 

3 percent 7 percent 3 percent 7 percent 

Nonquantified Costs: 

None. 

o. Requirement for Posting of Consent 

Forms for Common Rule Department or 

Agency-Supported Clinical Trials 

(§ ll.116(h)) 

The final rule requires that for each 

clinical trial conducted or supported by 

a Federal department or agency, one 

IRB-approved form used to recruit 

subjects must be posted by the awardee 

or the federal department or agency 

component conducting the trial on a 

publicly available federal Web site that 

will be established as a repository for 

such informed consent forms. The 

consent form must be posted after the 

clinical trial is closed to recruitment 

and no later than 60 days after the last 

study visit by any subject, as required 

by the protocol. This provision permits 

federal departments or agencies to 

require or permit redactions to these 

consent forms. As described in Section 

XIV.H, federal departments or agencies 

have great latitude in what they may 

permit or require be redacted. 

We believe that public posting of 

consent forms will increase 

transparency, enhance confidence in the 

research enterprise, increase 

accountability, and inform the 

development of future consent forms, 

possibly resulting in future savings in 

time for investigators developing 

consent forms. Costs to the Federal 

Government in creating and maintaining 

such a repository are described in 

Section XIX.D.2.a of this RIA. 

According to queries of 

ClinicalTrials.gov, estimated 5,270 

clinical trials are conducted or 

supported by Common Rule agencies, of 

which an estimated 575 are regulated by 

provisions in the Federal Food, Drug, 

and Cosmetic (FD&C) Act and Trade 

Secrets Act based on the information 

presented in Table 3. For the purpose of 

this analysis, it is assumed that each 

clinical trial is associated with one 

consent form that must be submitted to 

the federal system by an investigator. 

It is unknown at this time in what 

other circumstances federal departments 

or agencies might permit or require 

redaction, thus the RIA calculates 

redaction time only in those studies for 

which the FD&C Act and Trade Secrets 

Act applies. For the 575 clinical trials 

regulated by provisions in the FD&C Act 

and Trade Secrets Act, it is estimated 

that investigators will spend an average 

of 30 minutes redacting information 

before submission. We estimate that 

investigators will spend an average of 15 

minutes submitting each consent form. 

Based on the estimates presented in 

Table 3, the dollar value of investigator 

time is calculated by multiplying hours 

by their estimated 2017–2026 wages and 

adjusting for overhead and benefits. 

In addition, submitted consent forms 

must be reviewed and made accessible 

to persons with disabilities in 

compliance with Section 508 

Amendment to the Rehabilitation Act of 

1973. We estimate that each consent 

form contains an average of 10 pages 

and that making each page 508- 

compliant costs an average of $30 per 

page. 

Present value costs of $15.4 million 

and annualized costs of $1.80 million 

are estimated using a 3 percent discount 

rate; present value costs of $11.0 million 

and annualized costs of $1.56 million 

are estimated using a 7 percent discount 

rate. Table 18 summarizes the 

quantified and nonquantified benefits 

and the requirement for posting of 

consent forms for Common Rule 

department or agency-supported clinical 

trials. 

TABLE 18—SUMMARY OF ESTIMATED BENEFITS AND COSTS OF REQUIREMENT FOR POSTING OF CONSENT FORMS FOR

COMMON RULE DEPARTMENT OR AGENCY-SUPPORTED CLINICAL TRIALS (§ ll.116(h)) 

Present value of 10 years 

by discount rate 

(millions of 2015 dollars) 

Annualized value over 10 

years 

by discount rate 

(millions of 2015 dollars) 

3 percent 7 percent 3 percent 7 percent 

Quantified Benefits: 

None ......................................................................................................... ........................ ........................ ........................ ........................

BENEFITS: 

Nonquantified Benefits: 

Increase transparency of Common Rule department or agency-supported clinical trials; improvement of clinical trial informed consent forms. 

3 Percent 7 Percent 3 Percent 7 Percent 

COSTS: 

Quantified Costs: 

Preparation and submission of consent forms for posting, and redaction 

of information ........................................................................................ 15.4 11.0 1.80 1.56 

Nonquantified Costs: 

None. 

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Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 7251 

p. Alteration in Waiver for 

Documentation of Informed Consent in 

Certain Circumstances 

(§ ll.117(c)(1)(iii)) 

The final rule adds a provision 

allowing a waiver of the requirement to 

obtain a signed informed consent form 

if the subjects are members of a distinct 

cultural group or community in which 

signing documents is not the norm. This 

will be allowed only if the research 

presents no more than minimal risk of 

harm to subjects and provided an 

appropriate alternative method is 

available to document that informed 

consent was obtained. 

Under the pre-2018 rule, IRBs could 

waive the requirement for the 

investigator to obtain a signed consent 

form for some or all subjects. The pre2018 criteria for such a waiver may not 

have been flexible enough for dealing 

with a variety of circumstances, such as 

when federally sponsored research is 

conducted in an international setting 

where, for example, cultural or 

historical reasons suggest that signing 

documents may be viewed as offensive 

and problematic. 

This should not involve cost as its 

intent is to improve the informed 

consent process by providing more 

flexibility regarding the documentation 

of consent (an ethical gain) while 

reducing administrative requirements 

for investigators and research subjects in 

specific circumstances. Thus, benefits 

and costs of this new provision are not 

quantified. Table 19 summarizes the 

nonquantified benefits and costs of 

alteration in waiver for documentation 

of informed consent in certain 

circumstances. 

TABLE 19—SUMMARY OF ESTIMATED BENEFITS AND COSTS OF ALTERATION IN WAIVER FOR DOCUMENTATION OF

INFORMED CONSENT IN CERTAIN CIRCUMSTANCES (§ ll.117(c)(1)(iii)) 

Present value of 10 

years by discount rate 

(millions of 2015 dollars) 

Annualized value over 10 

years by discount rate 

(millions of 2015 dollars) 

3 percent 7 percent 3 percent 7 percent 

BENEFITS: 

Quantified Benefits: 

None ......................................................................................................... ........................ ........................ ........................ ........................

Nonquantified Benefits: 

Improved informed consent process for distinct cultural groups and communities. 

COSTS: 

Quantified Costs: 

None ......................................................................................................... ........................ ........................ ........................ ........................

Nonquantified Costs: 

None. 

E. Alternative Approaches to the 

Definition of Human Subject (NPRM at 

§ ll.102(e)) and Related Provisions 

1. Overview 

We carefully considered the option of 

not pursuing regulatory action. 

However, because of shifts in science, 

technology, public engagement, and 

public expectations in the past 2 

decades, a wide range of stakeholders 

have raised concerns about the 

limitations of the existing ethical 

framework in research, arguing for a reevaluation of how the fundamental 

principles that underlie the Common 

Rule—respect for persons, beneficence, 

and justice—are applied in practice to 

the myriad new contexts in which U.S. 

research is conducted in the 21st 

century. 

The final rule addresses these 

concerns through three aims. The first 

aim is to increase human subjects’ 

ability and opportunity to make 

informed decisions. The second aim is 

to reduce potential for harm and 

promote justice by increasing the 

uniformity of human subject 

protections. The third aim is to facilitate 

current and evolving types of research 

that offer promising approaches to 

treating and preventing medical and 

societal problems by reducing ambiguity 

in interpretation of the regulations, 

increasing efficiencies in the review 

system, and reducing requirements on 

investigators when said requirements do 

not appear to provide meaningful 

protections to human subjects. We hope 

that these changes will also build public 

trust in the research system. We 

estimate that the benefits of this 

regulatory action exceed its costs, and as 

a result we have chosen to pursue this 

regulatory action. 

The NPRM proposed to expand the 

definition of human subjects to include 

research in which an investigator 

obtains, uses, studies or analyzes a 

biospecimen. This would have applied 

regardless of the identifiability of the 

biospecimen. Generally, investigators 

would not have been allowed to remove 

identifiers from biospecimens without 

obtaining informed consent or a waiver 

of consent. The NPRM also proposed to 

modify the criteria for waiver of consent 

in research involving biospecimens 

such that a waiver would be very rare. 

Written consent would generally have 

been required for such activities. Thus, 

this change would have significantly 

expanded the amount of research 

subject to the Common Rule. This 

requirement would not have applied to 

biospecimens and information already 

collected at the time the final rule is 

published. The NPRM proposed to 

exclude from its scope research 

activities involving nonidentified 

biospecimens where no new 

information about an individual is 

generated. Although activities such as 

developing new testing assays could 

have been excluded under this 

provision, it is anticipated that under 

the NPRM proposals, most research 

with biospecimens would have come 

under the rule. 

In addition to promoting respect for 

persons in the research enterprise, the 

alternative regulatory structure for 

research with biospecimens (whereby 

consent is sought for almost all research 

activities involving biospecimens) 

would have encouraged investigators to 

retain identifiers, which can enhance 

research by preserving the ability to link 

biospecimens to important additional 

information about the subject. 

Additionally, members of the regulated 

community have reported situations 

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7252 Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 

57Pentz RD, et al. Research on Stored Biological 

Samples: Views of African American and White 

American Cancer Patients. American Journal of 

Medical Genetics, Part A. 2006 Apr; 140(7):733– 

739. 

58Chen, DT et al. Research With Stored Biological 

Samples; What Do Research Participants Want? 

Archives of Internal Medicine 2005 Mar; 

165(6):652–655. 

59Scott EA, et al. Biospecimen Repositories: Are 

Blood Donors Willing to Participate? Transfusion. 

2010 September; 50(9):1943–1950. 

60Eiseman E., Haga S. Handbook of Human 

Tissue Sources: A National Resource of Human 

Tissue Samples. Washington, DC: RAND 

Corporation; 1999. 

where, even though not currently 

required by regulation, investigators 

were told by an IRB that they needed to 

obtain study-specific consent for 

research activities involving 

nonidentified biospecimens. Under the 

NPRM proposals, such a situation 

would not occur because consent—be it 

broad or study-specific—would always 

be obtained for research involving 

biospecimens. 

Though this proposal would promote 

the ethical principle of respect for 

persons, it also would have significantly 

increased the volume of studies for 

which investigators must seek and 

document informed consent (unless 

more stringent waiver criteria were 

met). Additionally, the NPRM 

acknowledged, and the regulated 

community reiterated, during the public 

comment period, that the majority of the 

studies that the NPRM proposal would 

have newly regulated were studies 

involving no more than minimal risk to 

human subjects. 

As an example of the tradeoffs 

between the NPRM proposal and the 

ultimate position taken in the final rule, 

some commenters noted that the 

proposal to cover all biospecimens 

under the Common Rule regardless of 

identifiability might privilege the 

Belmont Report’s principle of autonomy 

over the principle of justice. Because the 

NPRM would have required 

investigators to obtain informed consent 

in all but rare circumstances for 

research involving biospecimens, 

concern was expressed that this could 

result in lower representation rates in 

research of minority groups, 

marginalized members of society, and 

citizens receiving care in community 

health clinics (which would be less able 

to cover the costs of tracking consent 

status over time). We note that although 

the available literature suggests that 

minority consent rates are generally 

high, minority consent rates in some 

cases may be lower than for 

nonminorities.57 58 59 This discrepancy 

in turn could create issues in the 

applicability of research discoveries on 

the population as a whole. Respecting 

persons is a worthy goal, but the need 

to achieve representative samples (and 

thus helping to ensure the applicability 

of research findings across a population) 

also must be taken into consideration. In 

addition, the principle of beneficence 

requires that all reasonable efforts be 

made to improve the public good. To 

balance these sometimes competing 

interests, the final rule incentivizes 

asking potential subjects for permission 

in minimal risk activities (even if a 

waiver of informed consent could be 

sought from an IRB), while still allowing 

other avenues for this research to occur 

should compelling reasons exist or not 

obtaining informed consent. 

2. Estimated Impact of Alternative 

Approaches to the Final Rule 

The benefit and cost estimations 

presented below are based upon the 

proposals and structure presented in the 

NPRM, not the provisions included in 

the final rule. 

a. Estimating How Many Studies 

Involving Nonidentified Biospecimens 

Occur Each Year 

We estimate that each year 250,000 

studies are not currently subject to 

oversight by either the Common Rule or 

FDA regulations because they use 

biospecimens that have been stripped of 

identifiers. Extrapolations from 1999 

data 60 suggest that biospecimens are 

collected from as many as 30 million 

individuals each year and are stored for 

both clinical and research purposes. 

Based on conversations with experts in 

this area, this 1999 report represents the 

most recent, comprehensive analysis of 

the volume of nonidentified 

biospecimens used in research 

activities. 

Approximately 9 million individuals’ 

biospecimens (30 percent of those 

collected) are collected for research 

purposes. Approximately 6.3 million 

individuals’ biospecimens (30 percent) 

could potentially be used in future 

research studies. Thus, it is possible that 

investigators would have had to seek 

consent to secondary use of 

biospecimens or a waiver of consent for 

an additional 15 million individuals 

annually for secondary use of 

biospecimens. 

In the absence of comprehensive data, 

to calculate the number of protocols that 

would have been covered, we proposed 

two approaches. Under method one, we 

estimated that approximately 50 

biospecimens would have been used on 

average per research protocol involving 

biospecimens. This gave a potential 

300,000 new research protocols using 

nonidentified biospecimens. This 

estimate of 300,000 new research 

protocols was rounded down to 250,000 

new studies based on ANPRM 

comments and industry data, because it 

seemed reasonable to assume that the 

number of new biospecimen studies 

covered by the alternative proposal 

would equal the total number of new 

protocols conducted each year (i.e., the 

number of new biospecimen studies was 

likely close to the estimate of 246,382 

new annual studies each year). 

Under method two, biospecimen 

repository representatives reported that 

roughly 90 percent of their collections 

were used in nonidentified form in 

research activities that did not fall 

under the pre-2018 rule. Thus, only 10 

percent of biospecimen studies were 

covered under the pre-2018 rule, 

representing a 9:1 ratio of studies 

involving nonidentified biospecimens to 

studies involving identifiable 

biospecimens. Of the 246,382 new 

protocols each year that were 

nonexempt (Table 3), we assumed that 

10 to15 percent used identifiable 

biospecimens. This equated to between 

24,638 and 36,957 new studies each 

year using identifiable biospecimens. 

We estimated that the number of 

biospecimen studies that occurred on 

nonidentified biospecimens each year 

was approximately 9 times the number 

of studies using identifiable 

biospecimens, or between 221,742 and 

332,613 studies each year. Thus, under 

method two, an estimate of 250,000 new 

studies on nonidentified biospecimens 

each year was also reasonable. 

To facilitate research with 

biospecimens, the NPRM proposed to 

create separate elements of broad 

consent such that investigators and 

institutions could seek, and individuals 

could grant, consent for future 

unspecified research activities. The 

NPRM also proposed an exemption that 

relied on obtaining broad consent for 

future, unspecified research studies. To 

be eligible for the proposed exemption 

for specific secondary studies, broad 

consent must have been sought and 

obtained using the proposed Secretary’s 

template for broad consent, and the 

investigator must not have anticipated 

returning individual research results to 

subjects. 

b. Facilitating Research With 

Nonidentified Biospecimens Under the 

NPRM: Exemption for Specific, 

Secondary Studies When Broad Consent 

Had Been Sought and Obtained 

The NPRM proposed to allow broad 

consent to secondary research use of 

biospecimens or identifiable private 

information for unspecified research 

purposes. Such broad consent would 

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have specified elements and limitations, 

and could have been obtained in both 

the research and nonresearch setting. 

The proposed exemption was 

specifically for secondary research 

studies involving biospecimens and 

identifiable private information that had 

been or would have been acquired for 

purposes other than the currently 

proposed research study. If a secondary 

research study did not meet the 

requirements of this exemption, the 

investigator would have needed to seek 

IRB review of the study, and would 

have needed to obtain either studyspecific consent or a waiver of informed 

consent. Note that for biospecimens, an 

IRB would have applied the more 

stringent waiver criteria under which 

waiver of informed consent in research 

involving biospecimens would have 

been rare. For identifiable private 

information, an IRB would have applied 

the waiver criteria almost identical to 

the criteria in the pre-2018 rule. 

We anticipated that a majority of 

studies that would have used this 

exemption would have been 

biospecimen studies. The extent to 

which individuals conducting 

secondary research studies involving 

identifiable private information would 

have used this exemption is unknown, 

given the proposed rule provided 

additional pathways to facilitate such 

studies. To that end, the benefits and 

costs associated take into consideration 

only secondary research involving 

biospecimens. We further anticipated 

that the NPRM proposals would have 

resulted in higher value research with 

biospecimens being conducted with 

subjects’ consent and without the need 

for full IRB review, or the need to go 

back to subjects to obtain consent for 

every secondary research study, as long 

as certain conditions were met. 

Because the estimated 250,000 

biospecimen studies each year that 

would have been newly covered under 

the rule as a result of the proposed 

modification to the definition of human 

subject would likely have been minimal 

risk, we assume that all of these would 

have been eligible for the exemption for 

secondary use as long as broad consent 

had been sought and obtained. 

Benefits and costs associated with 

obtaining and tracking broad consent 

under this alternative proposal are 

discussed below. 

Because the compliance date for the 

expansion to the definition of human 

subject would have been 3 years after 

the date of publication of a final rule, 

the benefits and costs described below 

assume a start date of 2020. In the 

absence of the proposed exemption for 

secondary research studies, but taking 

into consideration the expansion to the 

definition of human subject, we 

estimate that each year, all 250,000 of 

these studies would undergo convened 

initial review. In subsequent years, we 

estimate that 120,000 protocols would 

undergo convened initial review, 89,700 

would undergo convened continuing 

review, and 40,300 would undergo 

expedited continuing review based on 

the distribution of reviews presented in 

Table 3. The estimated costs to 

institution officials, IRB administrators, 

IRB administrative staff, IRB chairs, IRB 

voting members, and investigators 

conducting these reviews are based on 

the estimates presented in Table 3. The 

dollar value of their time is calculated 

by multiplying hours by their estimated 

2017–2026 wages and adjusting for 

overhead and benefits. 

c. Facilitating Research With 

Nonidentified Biospecimens Under the 

NPRM: Seeking and Obtaining Broad 

Consent 

To facilitate secondary research using 

biospecimens and identifiable private 

information, the NPRM also proposed 

an exemption for storing and 

maintaining biospecimens and 

identifiable private information for 

future, unspecified, secondary research 

activities. Given the creation of this 

exemption, the NPRM envisioned that 

institutions would need to develop 

tracking systems to monitor which 

biospecimens or information could be 

used in secondary research by 

investigators. Because both the 

exemption for secondary research use 

described above, and the exemption 

required using the proposed Secretary’s 

broad consent, the NPRM assumed that 

a majority of investigators and 

institutions would employ the 

Secretary’s consent template. Thus, the 

NPRM anticipated that minimal time 

would have been spent updating 

consent forms or drafting new broad 

consent forms. 

We estimate that 6,428 FWA-holding 

institutions (80 percent) would have 

stored and maintained clinical and 

nonclinical biospecimens and 

identifiable private information for 

unspecified future research studies in 

the manner prescribed under the NPRM. 

As also discussed previously, 

extrapolations from 1999 data suggest 

that biospecimens are collected from as 

many as 30 million individuals each 

year and stored for both clinical and 

research purposes. Approximately 9 

million individuals’ biospecimens (30 

percent) are collected for research 

purposes, and thus consent would be 

sought in the research context for the 

secondary use of these biospecimens. 

For these 9 million individuals per year, 

an investigator would spend an 

estimated 20 minutes per person 

conducting the consent process specific 

to seeking broad consent, and the 

subjects would spend an estimated 20 

minutes engaging in the process of 

having their broad consent for future 

research uses of their biospecimens or 

information sought. This estimate of the 

investigator’s time also includes the 

time for the investigator to log the 

information into the appropriate 

database. We note that the NPRM RIA 

estimated that it would take 5 minutes 

for an investigator to seek broad consent 

in the research setting, and that 

prospective subjects would spend 5 

minutes having their broad consent 

sought. Based on public comments, we 

have revised this estimate to better 

reflect experience in the regulated 

community about how long it takes to 

seek and obtain consent. We further 

estimate that investigators would spend 

10 minutes of time per protocol 

updating their study specific consent 

form to include the language from the 

Secretary’s consent template. 

In the clinical setting, approximately 

21 million individuals’ biospecimens 

(70 percent of the estimated 30 million 

individuals’ biospecimens collected 

each year) are collected for clinical 

purposes. In the first year that the 

proposed changes would have been 

implemented, as many as 21 million 

broad, secondary use consent forms 

could have been collected from 

individuals. We anticipate 30 minutes 

of a subject’s time to engage in the 

consent process. We further anticipate 

30 minutes of an institutional 

employee’s time at the IRB 

Administrative Staff level to seek 

consent and put the information in the 

appropriate tracking system. As with the 

estimate for seeking and obtaining broad 

consent in the clinical setting, we have 

increased the estimate of how long it 

would take institutional employees to 

seek broad consent and how long 

prospective subjects would spend 

participating in the broad consent 

process based on public comments. 

The NPRM proposed that once an 

individual gave broad consent to use his 

or her biospecimens in future, 

unspecified research studies, that 

consent could cover any biospecimen 

collected from that individual over the 

course of a 10-year period. Note that an 

institution could retain and use the 

biospecimens collected indefinitely. 

This provision merely stated that every 

10 years an institution must ask people 

whether or not they may use newly 

collected biospecimens in research. 

Given that an institution needed to seek 

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broad consent from an individual only 

once over the course of a 10-year period, 

we assumed that after the first year the 

NPRM was implemented, the number of 

individuals from whom an institution 

would seek broad consent would 

decrease. 

To account for this, the RIA 

alternative approach assumes that after 

the first year, a fraction of the clinical 

subjects from whom broad consent was 

sought in year one would be sought in 

subsequent years. We anticipate that in 

year two, secondary use consent would 

be sought in the clinical context from 

10.5 million subjects (50 percent of the 

number of individuals involved in the 

year one estimates). We anticipate that 

in year three and after, secondary use 

consent would be sought in the clinical 

context from approximately 6.3 million 

subjects each year (30 percent of the 

number of individuals involved in the 

year one estimates). As in year one, we 

assume that a prospective subject would 

spend 30 minutes of time undergoing 

the consent process and that an 

institutional employee at the IRB 

Administrative Staff level would spend 

30 minutes of time conducting the 

consent process with an individual and 

updating the appropriate tracking 

system. 

d. Estimating the Cost of the Broad 

Consent Tracking System 

To appropriately track biospecimens 

or identifiable private information for 

which broad consent had been sought 

and obtained on an institutional level, 

an institution would need to develop an 

institution-wide repository-like schema. 

The costs include the design, 

implementation, and operation of the 

informatics system that would be 

required to document and keep current 

thousands of consent documents per 

year. In addition, the institution would 

have to come up with a system to mark 

or otherwise flag which biospecimens 

and pieces of identifiable private 

information could be used in future 

unspecified secondary research studies. 

Under the NPRM proposal, we 

estimate that 80 percent of the 8,035 

institutions with FWAs would develop 

these informatics systems (or modify 

existing systems) to facilitate research 

with nonidentified biospecimens. We 

estimate that under this proposal, 

institutions on average would require 

1.0 database administrator FTE to 

develop and maintain these systems. We 

note that as this estimate is a 

nationwide average, and we expect 

some institutions would require more 

database administrators, and others 

would require fewer. 

For all of the estimates described 

above, the estimated costs to institution 

officials, IRB administrators, IRB 

administrative staff, IRB chairs, IRB 

voting members, database 

administrators, and investigators of are 

based on the estimates presented in 

Table 3. The dollar value of their time 

is calculated by multiplying hours by 

their estimated 2017–2026 wages and 

adjusting for overhead and benefits. 

For the alternative proposal (i.e., the 

NPRM proposal to treat all 

biospecimens regardless of 

identifiability as covered under the 

Common Rule), present value costs of 

$19.7 billion and annualized costs of 

$2.31 billion are estimated using a 3 

percent discount rate; and present value 

costs of $14.2 billion and annualized 

costs of $2.02 billion are estimated 

using a 7 percent discount rate. Table 20 

summarizes the quantified and 

nonquantified benefits and costs of 

amending the definition of human 

subject and obtaining consent to 

secondary use of biospecimens and 

identifiable private information. 

TABLE 20—ALTERNATIVE PROPOSAL TO TREAT ALL BIOSPECIMENS AS COVERED UNDER THE COMMON RULE

Present value of 10 

years by discount rate 

(millions of 2015 dollars) 

Annualized value over 10 

years by discount rate 

(millions of 2015 dollars) 

3 percent 7 percent 3 percent 7 percent 

BENEFITS: 

Quantified Benefits: 

None ......................................................................................................... ........................ ........................ ........................ ........................

Nonquantified Benefits: 

Increased protections for human subjects. 

COSTS: 

Quantified Costs: 

Increase in number of reviews; time to update consent forms; document and track permissible and impermissible secondary uses of information and biospecimens; and cost to develop and maintain tracking system ............................................................................................. 19,670 14,214 2,306 2,024 

Nonquantified Costs: 

None. 

F. Regulatory Flexibility Analysis 

As discussed above, the RFA requires 

agencies that issue a regulation to 

analyze options for regulatory relief of 

small entities if a rule has a significant 

impact on a substantial number of small 

entities. HHS considers a rule to have a 

significant economic impact on a 

substantial number of small entities if at 

least 5 percent of small entities 

experience an impact of more than 3 

percent of revenue. 

We calculate the costs of the proposed 

changes to the Common Rule over 

2017–2026 to institutions with an FWA. 

The estimated annualized cost to 

institutions with an FWA, on average, is 

$2,516 using a 3 percent discount rate. 

The U.S. Small Business Administration 

establishes size standards that define a 

small entity. According to these 

standards, colleges, universities, and 

professional schools with revenues 

below $27.5 million and hospitals with 

revenues below $38.5 million are 

considered small entities. It is not 

anticipated that a majority of 

institutions with an FWA are in any of 

these categories. 

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Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 7255 

XX. Environmental Impact 

We have determined under 21 CFR 

25.30(k) that this action is of a type that 

does not individually or cumulatively 

have a significant effect on the human 

environment. Therefore, neither an 

environmental assessment nor an 

environmental impact statement is 

required. 

XXI. Paperwork Reduction Analysis 

This final rule contains collections of 

information that are subject to review 

and approval by the Office of 

Management and Budget (OMB) under 

the Paperwork Reduction Act (PRA), as 

amended (44 U.S.C. 3501–3520). A 

description of these provisions is given 

in this document with an estimate of the 

annual reporting and recordkeeping 

burden. 

Title: Federal Policy for the Protection 

of Human Subjects. 

Description: In this document is a 

discussion of the regulatory provisions 

we believe are subject to the PRA and 

the probable information collection 

burden associated with these 

provisions. In general, the following 

actions trigger the PRA: (i) Reporting; 

(ii) Recordkeeping. 

Description of Respondents: The 

reporting and recordkeeping 

requirements in this document are 

imposed on institutions, institutional 

review boards, and investigators 

involved in human subjects research 

conducted or supported or otherwise 

subject to regulation by any federal 

department or agency that takes 

administrative action that makes the 

policy applicable to such research. 

§ ll.101(a)(1) Extending Oversight to 

IRBs-Not Operated by an Institution 

Holding an FWA (OMB Control No 

0990–0260) 

Section ll.101 is amended, as 

described in § ll.101(a), to give 

Common Rule departments and 

agencies the authority to enforce 

compliance directly against IRBs that, 

are not operated by an assured 

institution. It is anticipated that 

institutions using an IRB that it does not 

operate will be reassured because 

compliance actions can be taken 

directly against the IRB responsible for 

the regulatory noncompliance, rather 

than the institutions that relied on that 

review. As a result of this change, we 

anticipate that FWA-holding 

institutions will increase their reliance 

on IRBs not operated by an FWAholding institution when appropriate. 

The OHRP database of assured 

institutions and registered IRBs shows 

that approximately 449 IRBs not 

operated by an institution holding an 

FWA will now be subject to oversight. 

These IRBs will develop an estimated 

average of 10 written agreements with 

other institutions each year as a result 

of this rule. We further estimate that 

each agreement will require an average 

of 10 hours of institution legal staff time 

and 5 hours of IRB administrator time 

to complete. We note that elsewhere in 

the final rule (specifically §§ll.103(e) 

and ll.115(a)(9)) requires that IRBs 

document the specific responsibilities 

that an institution and an organization 

operating an IRB each will undertake, 

when an institution relies on an IRB that 

it does not operate. The impact of these 

provisions on FWA-holding institutions 

is described below. 

§ ll.103(e) Documentation of IRB 

Oversight Reliance Requirement for 

Institution and Organization Operating 

the IRB (OMB Control No 0990–0260) 

To further strengthen the compliance 

enforcement authority provision in 

§ ll.101(a) and provide a record for 

oversight and compliance purposes, the 

final rule contains a requirement at 

§ ll.103(e), that for nonexempt 

research involving human subjects 

covered by this policy (or exempt 

research for which limited IRB takes 

place pursuant to §ll.104(d)(2)(iii), 

§ ll.104(d)(3)(i)(C), §ll.104(d)(7), 

or §ll.104(d)(8)) that take place at an 

institution in which IRB oversight is 

conducted by an IRB that is not 

operated by the institution, the 

institution and the organization 

operating the IRB shall document the 

institution’s reliance on the IRB for 

oversight of the research and the 

responsibilities that each entity will 

undertake to ensure compliance with 

the requirements of this policy. This 

might be accomplished through a 

written agreement between the 

institution and the IRB, or by 

implementing an institution-wide 

policy directive providing the allocation 

of responsibilities between the 

institution and an IRB that is not 

affiliated with the institution, or as set 

forth in a research protocol). In 

addition, a requirement is included at 

§ ll.115(a)(9) that an institution 

include documentation of such 

arrangements in the IRB records. 

Table 3 of the RIA section of the 

preamble shows that 5,164 FWAholding institutions do not have an IRB 

and 2,871 FWA-holding institutions 

have an IRB. We assume that the 5,164 

FWA-holding institutions without an 

IRB have an average of 1 IRB 

authorization agreement that will need 

to be modified as a result of the new 

requirements for agreements between 

institutions and IRBs not operated by 

the institutions in 2017. In addition, we 

assume that the 2,871 FWA-holding 

institutions with an IRB have an average 

of 0.20 IRB authorization agreements 

that will need to be modified in 2017. 

We estimate that each agreement will 

require an average of 10 hours of 

institution legal staff time and 5 hours 

of IRB administrator time to complete. 

The dollar value of their time is 

calculated by multiplying hours by their 

estimated 2017 wages and adjusting for 

overhead and benefits. 

§ ll.104(d)(5)(i) Posting of 

Information About Federally Funded or 

Supported Demonstration Projects 

Section 104(d)(5)(i) requires each 

federal department or agency 

conducting or supporting the research 

or demonstration projects covered under 

this exemption to establish, on a 

publicly accessible federal Web site or 

in such other manner as the department 

or agency head may determine, a list of 

the research and demonstration projects 

that the federal department or agency 

conducts or supports under this 

provision. We estimate that under the 

pre-2018 rule, approximately 1,000 

demonstration projects occurred each 

year. Under the modifications to this 

exemption in the final rule, we estimate 

that an additional 3,376 studies will fall 

under this exemption. Thus, 

approximately 4,376 studies will be 

subject to this posting requirement each 

year. We anticipate that investigators 

will spend approximately 15 minutes 

per study submitting information about 

these studies to the federal Web site. 

§ ll.114 Cooperative Research (OMB 

Control No 0990–0260) 

The final rule requires any institution 

located in the United States that is 

engaged in cooperative research to rely 

upon approval by a single IRB for that 

portion of the research that is conducted 

in the United States, as detailed in 

§ ll.114 (b)(1). The following research 

is not subject to the requirements of this 

provision, as described in §ll.114 

(b)(2): (1) Cooperative research for 

which more than single IRB review is 

required by law (including tribal law 

passed by the official governing body of 

a Native American or Alaska Native 

tribe); or (2) research for which any 

federal department or agency supporting 

or conducting the research determines 

and documents that the use of a single 

IRB is not appropriate for the particular 

study. 

The OHRP database of assurances 

shows that 8,035 institutions in the 

United States have an FWA. We 

estimate that these institutions will 

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7256 Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 

develop an average of 10 written joint 

IRB review agreements with other 

institutions or organizations in 2019 

before the first year of compliance. We 

further estimate that each agreement 

will require an average of 10 hours of 

institution legal staff time and 5 hours 

of IRB administrator time to complete. 

We estimate that 202,617 annual 

reviews of multi-institutional protocols 

take place, and an average of 5 reviews 

per multi-institutional protocol, 

implying that 40,523 multi-institutional 

protocols are reviewed each year. We 

further estimate that 16,209 (40 percent) 

of these multi-institutional studies are 

funded by NIH and thus will already be 

subject to NIH’s single IRB review 

policy. Accordingly, we estimate that 

approximately 97,256 annual reviews of 

protocols will no longer be conducted as 

a result of these proposed changes. Of 

these reviews, 32,211 would have 

undergone convened initial review, 

14,472 would have undergone 

expedited initial review, 34,896 would 

have undergone convened continuing 

review, and 15,678 would have 

undergone expedited continuing review 

based on the distribution of reviews 

presented in Table 3 in the RIA section 

of the preamble. 

§ ll.115(a)(3) Documenting the 

Rationale for Conducting Continuing 

Review of Research That Otherwise 

Would Not Require Continuing 

Review(OMB Control No 0990–0260) 

The final rule eliminates continuing 

review for many minimal risk studies, 

as detailed at §ll.109(f). Unless an 

IRB determines otherwise, continuing 

review of research is not required if: (1) 

The research is eligible for expedited 

review in accordance with §ll.110; 

(2) the research is reviewed by the IRB 

in accordance with the limited IRB 

review procedure described in several of 

the exemption categories (specifically, 

§ ll.104(d)(2)(iii), 

§ ll.104(d)(3)(i)(C), §ll.104(d)(7), 

or §ll.104(d)(8)); or (3) the research 

has progressed to the point that it 

involves data analysis (including 

analysis of identifiable information or 

identifiable biospecimens) or access to 

follow-up clinical data from procedures 

that subjects would undergo as part of 

clinical care. If an IRB chooses to 

conduct continuing review even when 

these conditions are met, the rationale 

for doing so must be documented 

according to a new provision at 

§ ll.115(a)(3). 

We estimate that 40,773 reviews will 

require documentation of the rationale 

for doing so (as required under 

§ ll.115(a)(3)). We also estimate that 

IRB voting members will spend 1 hour 

per review providing the necessary 

documentation. 

§§ ll.116(a)(5), (b)(9), (c)(7)–(9) and 

ll.117(b) Changes in the Elements of 

Consent, Including Documentation 

(OMB Control No 0990–0260) 

The final rule imposes a new 

requirement at § ll.116(a)(5)(i) 

informed consent must begin with a 

concise and focused presentation of the 

key information that is most likely to 

assist a prospective subject or legally 

authorized representative in 

understanding the reasons why one 

might or might not want to participate 

in the research. This part of informed 

consent must be organized and 

presented in a way that facilitates 

comprehension. This requirement 

applies to all informed consent process, 

except for broad consent obtained 

pursuant to § ll.116(d), which may 

warrant a different presentation. 

The final rule includes a new element 

of consent at §ll.116(b)(9) that 

requires one of the following statements 

be included for any research that 

involves the collection of identifiable 

private information or identifiable 

biospecimens: (1) A statement that 

identifiers might be removed from the 

identifiable private information or 

identifiable biospecimens and that after 

such removal, the information or 

biospecimens could be used for future 

research studies or distributed to 

another investigator for future research 

studies without additional informed 

consent from the subject or the legally 

authorized representative, if this might 

be a possibility; or (2) a statement that 

the subject’s information or 

biospecimens collected as part of the 

research, even if identifiers are 

removed, will not be used or distributed 

for future research studies. 

The final rule’s three additional 

elements of consent are in 

§ ll.116(c)(7), (8), and (9). These 

require that a subject be informed of the 

following, when appropriate: 

• That the subject’s biospecimens 

(even if identifiers are removed) may be 

used for commercial profit and whether 

the subject will or will not share in this 

commercial profit; 

• Whether clinically relevant research 

results, including individual research 

results, will be disclosed to subjects, 

and if so, under what conditions; 

• For research involving 

biospecimens, whether the research will 

(if known) or might include whole 

genome sequencing (i.e., sequencing of 

a human germline or somatic specimen 

with the intent to generate the genome 

or exome sequence of that specimen. 

These additional elements of consent 

will promote respect for persons and 

greater transparency in the research 

enterprise. Additionally, including the 

information referenced in these 

provisions in a consent form will help 

ensure that prospective subjects are 

given information necessary for 

understanding why one might choose 

whether to participate in a research 

study. 

The language at §ll.117(b)(1) in the 

final rule was modified to reference 

§ ll.116(a)(5)(i) and state that if a 

short form consent process is used, the 

key information required by 

§ ll.116(a)(5)(i) must be presented 

first to the prospective subject, before 

other information, if any, is provided. 

We estimate that 246,382 new 

protocols annually will use identifiable 

private information. For each protocol, 

we estimate that investigators will 

spend an average of 15 minutes in 2017 

updating consent forms to comply with 

the new requirements found in the final 

rule at § ll.116(a)(5), (b)(9), (c)(7), 

(c)(8), or (c)(9) (in Table 3 in the RIA 

section). 

We assume that few additional 

investigators will elect to offer the 

second option at §ll.116(b)(9), and 

that the investigators who currently 

offer equivalent options already track 

the permissible and impermissible uses 

of information in line with the 

requirements discussed above. As a 

result, we estimate that tracking will 

have no additional associated impacts. 

§ ll.116(h) Requirement for Posting 

of Consent Forms for Common Rule 

Department or Agency-Supported or 

Conducted Clinical Trials (OMB Control 

No 0990–0260) 

A new provision in the final rule, 

§ ll.116(h), requires that, for each 

clinical trial conducted or supported by 

a federal department or agency, one IRBapproved informed consent form used 

to enroll subjects must be posted by the 

awardee or federal department or 

agency component conducting the trial 

on a publicly available federal Web site 

that is established as a repository for 

such informed consent forms. The 

informed consent form must be 

published on the federal Web site after 

the trial is closed to recruitment, and no 

later than 60 days after the last study 

visit by any subject, as required by the 

protocol. 

If the federal department or agency 

supporting or conducting the clinical 

trial determines that certain information 

should not be made publicly available 

on a federal Web site (e.g., confidential 

commercial information), such Federal 

department or agency may permit or 

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61U.S. Department of Health and Human Services 

Tribal Consultation Policy. Retrieved from https:// 

www.hhs.gov/sites/default/files/iea/tribal/ 

tribalconsultation/hhs-consultation-policy.pdf. 

require redactions to the information 

posted. 

We believe that public posting of 

consent forms will increase 

transparency, enhance confidence in the 

research enterprise, increase 

accountability, and inform the 

development of future consent forms, 

possibly resulting in future savings in 

time for investigators developing 

consent forms. 

According to queries of 

ClinicalTrials.gov, an estimated 5,270 

clinical trials are conducted or 

supported by Common Rule agencies, of 

which an estimated 575 are regulated by 

provisions in the FD&C Act and Trade 

Secrets Act based on the information 

presented in Table 3 in the RIA section 

of the preamble. We assume that each 

clinical trial is associated with one 

consent form that must be submitted to 

the HHS system by an investigator. We 

estimate that investigators will spend an 

average of 15 minutes submitting each 

consent form. In addition, for the 575 

clinical trials regulated by provisions in 

the FD&C Act and Trade Secrets Act, we 

estimate that investigators will spend an 

average of 30 minutes redacting 

information before submission. 

TABLE 21—ESTIMATED ANNUAL REPORTING BURDEN

Sec. description Description of burden Number of 

respondents 

Number of 

responses per 

respondent 

Total annual 

responses 

Average hours 

per response Total hours 

101(a)—Extending Oversight Authority to IRBs 

not operated by an FWAholding institution.

Develop agreements .......... 449 10 4,490 15 67,350 

103(e)—IRB Reliance Documentation (institutions 

without an internal IRB).

Modify agreements ............. 5,164 1 5,164 15 77,460 

103(e)—IRB Reliance Documentation (institutions 

with an internal IRB).

Develop agreements .......... 2,871 0.20 574.20 15 8,613 

104(d)(5)(i)—Posting information about demonstration projects.Posting information ............ 4,376 1 4,376 0.25 1,094 

114—Cooperative Review .. Time to create agreements 

for all institutions involved 

in a study will rely on one 

IRB of record.

8,035 10 80,350 15 1,205,250 

115(a)(3)—Continuing Review Rationale Documentation.Provide rationale ................ 40,773 1 40,773 1 40,773 

116(a)(5), (b)(9), (c)(7)–(8) 

& 117(b)—Changes in 

elements of informed consent, including documentation.

Updating IC forms with new 

elements.

246,382 1 246,382 0.25 61,596 

116(h)—Requirement for 

posting consent forms for 

Common Rule department or agency-supported clinical trials.

Posting consent forms for 

new clinical trials.

5,270 1 5,270 0.25 1,318 

116(h)—Requirement for 

posting consent forms for 

Common Rule department or agency-supported clinical trials.

Redact information from 

consent forms.

575 1 575 0.50 288 

Total ............................. ............................................. ........................ ........................ ........................ ........................ 1,422,968 

The total estimated burden imposed 

by these information collection 

requirements is 1,422,968 burden hours. 

It should be noted that the burden 

estimates for the Common Rule include 

approved information requirements in 

OMB No. 0990–0260, Protection of 

Human Subjects: Compliance with 

Federal Policy/IRB Recordkeeping/

Informed Consent/Consent 

Documentation, approved through May 

31, 2018. As such, it will be amended 

and submitted to OMB as revisions to 

currently approved collections once the 

rule is finalized and the collections are 

due for renewal. 

In compliance with the Paperwork 

Reduction Act of 1995 (44 U.S.C. 

3507(d)), the information collection 

provisions of this rule will be submitted 

to OMB for review. These requirements 

will not be effective until OMB 

approves them. 

XXII. Tribal Consultation Statement 

We are committed to consulting with 

AI/AN tribes and tribal leadership to the 

extent practicable and permitted by law 

before promulgating any regulation that 

has tribal implications. As we 

developed this rule, we engaged with 

tribes through tribal consultation and 

the public comment process. The 

requirements in this final rule were 

informed by consultations with and 

comments from tribal representatives. 

On January 5, 2016, HHS conducted 

a tribal consultation through conference 

call in accordance with the HHS Tribal 

Consultation Policy 61 with tribal 

representatives to obtain comments on 

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7258 Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 

the proposed changes to the Common 

Rule. This conference call was 

moderated by Elizabeth Carr, a Tribal 

Affairs Specialist within HHS and a 

federal representative of HHS’s 

American Indian and Alaska Native 

Health Research Advisory Council. 

Tribal leaders and other interested 

parties were informed of this 

consultation through written 

communication. The written invitation 

included a solicitation for formal 

comments and information on how to 

submit a formal comment to the public 

docket. Public comments were also 

solicited during the consultation 

conference call. A transcript of this call 

was posted to the Regulations.gov 

public docket for the Common Rule on 

January 13, 2016. 

During the tribal consultation 

conference call, participants discussed: 

• Concern about the NPRM not 

acknowledging the role of tribal 

governments in research oversight of 

research occurring on tribal land or with 

tribal citizens; 

• Concern about the pre-2018 rule 

and the NPRM not explicitly 

acknowledging tribal sovereignty. HHS 

representatives acknowledged an 

outstanding legal question about 

whether rules created by tribal 

governments were encompassed by the 

provision in the pre-2018 rule and the 

NPRM’s statement that the policy does 

not affect any state or local laws or 

regulations that may otherwise be 

applicable and that provide additional 

protections for human subjects; 

• Concern about the NPRM not 

acknowledging the unique and 

significant impact that the proposed 

changes would have on American 

Indian and Alaska Native populations; 

• Concern that the NPRM does not 

address risks of research to communities 

and only addresses individual risks; 

• Concern that the NPRM proposals 

seem to reduce institutional 

responsibility but increase investigator 

responsibility. This presents a unique 

challenge when institutions have 

entered into agreements with tribal 

governments or tribal representatives, as 

opposed to individual investigators 

entering into these arrangements. The 

exemption decision tool was cited as an 

example of the proposals placing more 

responsibility on the investigators while 

perhaps reducing responsibility on the 

institutions; and 

• Concern about the single IRB 

review mandate for multi-institutional 

studies affecting the ability of tribal 

communities to conduct local reviews of 

research involving tribal citizens or 

research that takes place on tribal land. 

One commenter noted that a one size 

fits all approach to addressing American 

Indian and Alaska Native concerns in 

human subjects protections might not be 

appropriate as needs and concerns 

might vary from tribe to tribe. 

HHS reiterated its commitment to 

engaging in an ongoing dialogue with 

tribal communities and tribal 

representatives, and welcomed ongoing 

discussion and comment on how the 

Common Rule affects these groups. 

In addition to the January 2016 tribal 

consultation, we reviewed public 

comments from tribal representatives, 

and individuals and groups representing 

tribal interests to the ANPRM and 

NPRM. We received one comment on 

the ANPRM from a group representing 

tribal interests. This group noted ‘‘the 

long and challenging history’’ of 

research involving AI/AN populations, 

and how this history informs current 

research activities involving these 

groups. This comment argued that, for 

research involving AI/AN populations: 

• Continuing review should be 

required; 

• IRBs, not investigators or other 

parties, should determine whether a 

prospective study is exempt or excluded 

from the Common Rule; 

• IRBs should be required to consider 

potential harms to populations or 

groups, not just individuals, when 

reviewing research activities; 

• Incorporating tribal IRBs into the 

process for multi-institutional studies is 

a crucial aspect of respecting these 

populations and ensuring human 

subjects protections; 

• Study-specific informed consent 

forms should be required, and general, 

multi-purpose consent forms should be 

avoided; 

• Mandated information and 

biospecimen privacy safeguards would 

be a welcome improvement to the 

current research landscape and would 

help prevent harm to human subjects; 

and 

• Consultation with tribal 

representatives would be crucial should 

a proposed rule or final rule mandate 

single IRB review for multi-institutional 

studies. 

We received approximately 15 

comments on the NPRM from groups 

representing tribal interests. As 

described in Section II.E of this 

preamble, overarching concerns raised 

by these groups in comments to the 

NPRM included: 

• Lack of group consent requirements 

proposed in the NPRM; 

• Concern about the allowance for 

broad consent for future unspecified 

research uses; 

• Lack of consideration for research 

activities involving research with 

biospecimens or information from 

individuals who are no longer alive; 

• Mandating the use of single IRB 

review in multi-institutional research 

activities undermining the ability of 

tribal groups to conduct local review of 

studies; and 

• Concern about the breadth and 

depth of exclusions and exemptions 

proposed in the NPRM exempting or 

excluding activities that tribal 

populations might find sensitive and 

requiring IRB review. 

Commenters also raised concerns 

about the timing of the tribal 

consultation call and noted that the 

tribal consultation call occurred one day 

before the closing of the extended 

comment period for the NPRM. When 

HHS received notice that tribal 

representatives desired to consult on 

this proposed rule, a consultation was 

immediately scheduled in accordance 

with HHS policy. 

The final rule includes a modification 

to the provision requiring single IRB 

review, and several clarifications 

specifying that regulatory references to 

state and local law are intended to 

include tribal law, in response to 

concerns raised during the tribal 

consultation and in the NPRM public 

comments. As described in this 

preamble, the final rule clarifies in 

§ ll.101(f) that tribal governments can 

develop laws related to the protection of 

human subjects that are more protective 

than the Common Rule, and that these 

laws must be followed by federally 

funded researches in activities involving 

these populations. Section ll.114 now 

provides that if a tribal government 

requires review by more than one IRB 

by law in multi-institutional research, 

the single IRB review requirement in 

§ ll.114 does not apply. Additional 

clarification has also been made to 

§ ll.116(i) that tribal governments can 

develop their own informed consent 

standards that provide additional 

protections to subjects and that 

investigators conducting research 

involving populations under the 

jurisdiction of the tribal governments 

would have to follow these rules. 

Finally, additional language has been 

added to § ll.116(j) noting that 

nothing in § ll.116 is intended to 

limit the authority of a treating 

physician to the extent the authority is 

granted by tribal law. 

Additional details of public 

comments from individuals 

representing tribal interests are included 

above in the relevant public comment 

summaries for the various final rule 

provisions discussed in Sections II 

through XVIII of this preamble. 

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Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 7259 

62The National Commission for the Protection of 

Human Subjects of Biomedical and Behavioral 

Research.– Belmont Report. Washington, DC: U.S. 

Department of Health and Human Services. 1979. 63 Id. 

For the reasons set forth in this 

preamble, the Federal Policy for the 

Protection of Human Subjects is 

amended. 

Text of the Final Common Rule 

The text of the final common rule 

appears below: 

1. Part/subpart llis amended/

revised/added to read as follows: 

PART ll—PROTECTION OF HUMAN 

SUBJECTS 

ll.101 To what does this policy apply? 

ll.102 Definitions for purposes of this 

policy. 

ll.103 Assuring compliance with this 

policy—research conducted or supported 

by any Federal department or agency. 

ll.104 Exempt research. 

ll.105 [Reserved] 

ll.106 [Reserved] 

ll.107 IRB membership. 

ll.108 IRB functions and operations. 

ll.109 IRB review of research. 

ll.110 Expedited review procedures for 

certain kinds of research involving no 

more than minimal risk, and for minor 

changes in approved research. 

ll.111 Criteria for IRB approval of 

research. 

ll.112 Review by institution. 

ll.113 Suspension or termination of IRB 

approval of research. 

ll.114 Cooperative research. 

ll.115 IRB records. 

ll.116 General requirements for informed 

consent. 

ll.117 Documentation of informed 

consent. 

ll.118 Applications and proposals 

lacking definite plans for involvement of 

human subjects. 

ll.119 Research undertaken without the 

intention of involving human subjects. 

ll.120 Evaluation and disposition of 

applications and proposals for research 

to be conducted or supported by a 

Federal department or agency. 

ll.121 [Reserved] 

ll.122 Use of Federal funds. 

ll.123 Early termination of research 

support: Evaluation of applications and 

proposals. 

ll.124 Conditions. 

§ ll.101 To what does this policy 

apply? 

(a) Except as detailed in § ll.104, 

this policy applies to all research 

involving human subjects conducted, 

supported, or otherwise subject to 

regulation by any Federal department or 

agency that takes appropriate 

administrative action to make the policy 

applicable to such research. This 

includes research conducted by Federal 

civilian employees or military 

personnel, except that each department 

or agency head may adopt such 

procedural modifications as may be 

appropriate from an administrative 

standpoint. It also includes research 

conducted, supported, or otherwise 

subject to regulation by the Federal 

Government outside the United States. 

Institutions that are engaged in research 

described in this paragraph and 

institutional review boards (IRBs) 

reviewing research that is subject to this 

policy must comply with this policy. 

(b) [Reserved] 

(c) Department or agency heads retain 

final judgment as to whether a 

particular activity is covered by this 

policy and this judgment shall be 

exercised consistent with the ethical 

principles of the Belmont Report.62

(d) Department or agency heads may 

require that specific research activities 

or classes of research activities 

conducted, supported, or otherwise 

subject to regulation by the Federal 

department or agency but not otherwise 

covered by this policy comply with 

some or all of the requirements of this 

policy. 

(e) Compliance with this policy 

requires compliance with pertinent 

federal laws or regulations that provide 

additional protections for human 

subjects. 

(f) This policy does not affect any 

state or local laws or regulations 

(including tribal law passed by the 

official governing body of an American 

Indian or Alaska Native tribe) that may 

otherwise be applicable and that 

provide additional protections for 

human subjects. 

(g) This policy does not affect any 

foreign laws or regulations that may 

otherwise be applicable and that 

provide additional protections to human 

subjects of research. 

(h) When research covered by this 

policy takes place in foreign countries, 

procedures normally followed in the 

foreign countries to protect human 

subjects may differ from those set forth 

in this policy. In these circumstances, if 

a department or agency head determines 

that the procedures prescribed by the 

institution afford protections that are at 

least equivalent to those provided in 

this policy, the department or agency 

head may approve the substitution of 

the foreign procedures in lieu of the 

procedural requirements provided in 

this policy. Except when otherwise 

required by statute, Executive Order, or 

the department or agency head, notices 

of these actions as they occur will be 

published in the Federal Register or 

will be otherwise published as provided 

in department or agency procedures. 

(i) Unless otherwise required by law, 

department or agency heads may waive 

the applicability of some or all of the 

provisions of this policy to specific 

research activities or classes of research 

activities otherwise covered by this 

policy, provided the alternative 

procedures to be followed are consistent 

with the principles of the Belmont 

Report.63 Except when otherwise 

required by statute or Executive Order, 

the department or agency head shall 

forward advance notices of these actions 

to the Office for Human Research 

Protections, Department of Health and 

Human Services (HHS), or any 

successor office, or to the equivalent 

office within the appropriate Federal 

department or agency, and shall also 

publish them in the Federal Register or 

in such other manner as provided in 

department or agency procedures. The 

waiver notice must include a statement 

that identifies the conditions under 

which the waiver will be applied and a 

justification as to why the waiver is 

appropriate for the research, including 

how the decision is consistent with the 

principles of the Belmont Report. 

(j) Federal guidance on the 

requirements of this policy shall be 

issued only after consultation, for the 

purpose of harmonization (to the extent 

appropriate), with other Federal 

departments and agencies that have 

adopted this policy, unless such 

consultation is not feasible. 

(k) [Reserved] 

(l) Compliance dates and transition 

provisions: 

(1) For purposes of this section, the 

pre-2018 Requirements means this 

subpart as published in the 2016 edition 

of the Code of Federal Regulations. 

(2) For purposes of this section, the 

2018 Requirements means the Federal 

Policy for the Protection of Human 

Subjects requirements contained in this 

subpart. The compliance date for 

§ ll.114(b) (cooperative research) of 

the 2018 Requirements is January 20, 

2020. 

(3) Research initially approved by an 

IRB, for which such review was waived 

pursuant to § ll.101(i), or for which a 

determination was made that the 

research was exempt before January 19, 

2018, shall comply with the pre-2018 

Requirements, except that an institution 

engaged in such research on or after 

January 19, 2018, may instead comply 

with the 2018 Requirements if the 

institution determines that such ongoing 

research will comply with the 2018 

Requirements and an IRB documents 

such determination. 

(4) Research initially approved by an 

IRB, for which such review was waived 

pursuant to § ll.101(i), or for which a 

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7260 Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 

determination was made that the 

research was exempt on or after January 

19, 2018, shall comply with the 2018 

Requirements. 

(m) Severability: Any provision of this 

part held to be invalid or unenforceable 

by its terms, or as applied to any person 

or circumstance, shall be construed so 

as to continue to give maximum effect 

to the provision permitted by law, 

unless such holding shall be one of utter 

invalidity or unenforceability, in which 

event the provision shall be severable 

from this part and shall not affect the 

remainder thereof or the application of 

the provision to other persons not 

similarly situated or to other dissimilar 

circumstances. 

§ ll.102 Definitions for purposes of 

this policy. 

(a) Certification means the official 

notification by the institution to the 

supporting Federal department or 

agency component, in accordance with 

the requirements of this policy, that a 

research project or activity involving 

human subjects has been reviewed and 

approved by an IRB in accordance with 

an approved assurance. 

(b) Clinical trial means a research 

study in which one or more human 

subjects are prospectively assigned to 

one or more interventions (which may 

include placebo or other control) to 

evaluate the effects of the interventions 

on biomedical or behavioral healthrelated outcomes. 

(c) Department or agency head means 

the head of any Federal department or 

agency, for example, the Secretary of 

HHS, and any other officer or employee 

of any Federal department or agency to 

whom the authority provided by these 

regulations to the department or agency 

head has been delegated. 

(d) Federal department or agency 

refers to a federal department or agency 

(the department or agency itself rather 

than its bureaus, offices or divisions) 

that takes appropriate administrative 

action to make this policy applicable to 

the research involving human subjects it 

conducts, supports, or otherwise 

regulates (e.g., the U.S. Department of 

Health and Human Services, the U.S. 

Department of Defense, or the Central 

Intelligence Agency). 

(e)(1) Human subject means a living 

individual about whom an investigator 

(whether professional or student) 

conducting research: 

(i) Obtains information or 

biospecimens through intervention or 

interaction with the individual, and 

uses, studies, or analyzes the 

information or biospecimens; or (ii) 

Obtains, uses, studies, analyzes, or 

generates identifiable private 

information or identifiable 

biospecimens. 

(2) Intervention includes both 

physical procedures by which 

information or biospecimens are 

gathered (e.g., venipuncture) and 

manipulations of the subject or the 

subject’s environment that are 

performed for research purposes. 

(3) Interaction includes 

communication or interpersonal contact 

between investigator and subject. 

(4) Private information includes 

information about behavior that occurs 

in a context in which an individual can 

reasonably expect that no observation or 

recording is taking place, and 

information that has been provided for 

specific purposes by an individual and 

that the individual can reasonably 

expect will not be made public (e.g., a 

medical record). 

(5) Identifiable private information is 

private information for which the 

identity of the subject is or may readily 

be ascertained by the investigator or 

associated with the information. 

(6) An identifiable biospecimen is a 

biospecimen for which the identity of 

the subject is or may readily be 

ascertained by the investigator or 

associated with the biospecimen. 

(7) Federal departments or agencies 

implementing this policy shall: 

(i) Upon consultation with 

appropriate experts (including experts 

in data matching and re-identification), 

reexamine the meaning of ‘‘identifiable 

private information,’’ as defined in 

paragraph (e)(5) of this section, and 

‘‘identifiable biospecimen,’’ as defined 

in paragraph (e)(6) of this section. This 

reexamination shall take place within 1 

year and regularly thereafter (at least 

every 4 years). This process will be 

conducted by collaboration among the 

Federal departments and agencies 

implementing this policy. If appropriate 

and permitted by law, such Federal 

departments and agencies may alter the 

interpretation of these terms, including 

through the use of guidance. 

(ii) Upon consultation with 

appropriate experts, assess whether 

there are analytic technologies or 

techniques that should be considered by 

investigators to generate ‘‘identifiable 

private information,’’ as defined in 

paragraph (e)(5) of this section, or an 

‘‘identifiable biospecimen,’’ as defined 

in paragraph (e)(6) of this section. This 

assessment shall take place within 1 

year and regularly thereafter (at least 

every 4 years). This process will be 

conducted by collaboration among the 

Federal departments and agencies 

implementing this policy. Any such 

technologies or techniques will be 

included on a list of technologies or 

techniques that produce identifiable 

private information or identifiable 

biospecimens. This list will be 

published in the Federal Register after 

notice and an opportunity for public 

comment. The Secretary, HHS, shall 

maintain the list on a publicly 

accessible Web site. 

(f) Institution means any public or 

private entity, or department or agency 

(including federal, state, and other 

agencies). 

(g) IRB means an institutional review 

board established in accord with and for 

the purposes expressed in this policy. 

(h) IRB approval means the 

determination of the IRB that the 

research has been reviewed and may be 

conducted at an institution within the 

constraints set forth by the IRB and by 

other institutional and federal 

requirements. 

(i) Legally authorized representative 

means an individual or judicial or other 

body authorized under applicable law to 

consent on behalf of a prospective 

subject to the subject’s participation in 

the procedure(s) involved in the 

research. If there is no applicable law 

addressing this issue, legally authorized 

representative means an individual 

recognized by institutional policy as 

acceptable for providing consent in the 

nonresearch context on behalf of the 

prospective subject to the subject’s 

participation in the procedure(s) 

involved in the research. 

(j) Minimal risk means that the 

probability and magnitude of harm or 

discomfort anticipated in the research 

are not greater in and of themselves than 

those ordinarily encountered in daily 

life or during the performance of routine 

physical or psychological examinations 

or tests. 

(k) Public health authority means an 

agency or authority of the United States, 

a state, a territory, a political 

subdivision of a state or territory, an 

Indian tribe, or a foreign government, or 

a person or entity acting under a grant 

of authority from or contract with such 

public agency, including the employees 

or agents of such public agency or its 

contractors or persons or entities to 

whom it has granted authority, that is 

responsible for public health matters as 

part of its official mandate. 

(l) Research means a systematic 

investigation, including research 

development, testing, and evaluation, 

designed to develop or contribute to 

generalizable knowledge. Activities that 

meet this definition constitute research 

for purposes of this policy, whether or 

not they are conducted or supported 

under a program that is considered 

research for other purposes. For 

example, some demonstration and 

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Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 7261 

service programs may include research 

activities. For purposes of this part, the 

following activities are deemed not to be 

research: 

(1) Scholarly and journalistic 

activities (e.g., oral history, journalism, 

biography, literary criticism, legal 

research, and historical scholarship), 

including the collection and use of 

information, that focus directly on the 

specific individuals about whom the 

information is collected. 

(2) Public health surveillance 

activities, including the collection and 

testing of information or biospecimens, 

conducted, supported, requested, 

ordered, required, or authorized by a 

public health authority. Such activities 

are limited to those necessary to allow 

a public health authority to identify, 

monitor, assess, or investigate potential 

public health signals, onsets of disease 

outbreaks, or conditions of public health 

importance (including trends, signals, 

risk factors, patterns in diseases, or 

increases in injuries from using 

consumer products). Such activities 

include those associated with providing 

timely situational awareness and 

priority setting during the course of an 

event or crisis that threatens public 

health (including natural or man-made 

disasters). 

(3) Collection and analysis of 

information, biospecimens, or records 

by or for a criminal justice agency for 

activities authorized by law or court 

order solely for criminal justice or 

criminal investigative purposes. 

(4) Authorized operational activities 

(as determined by each agency) in 

support of intelligence, homeland 

security, defense, or other national 

security missions. 

(m) Written, or in writing, for 

purposes of this part, refers to writing 

on a tangible medium (e.g., paper) or in 

an electronic format. 

§ ll.103 Assuring compliance with 

this policy—research conducted or 

supported by any Federal department 

or agency. 

(a) Each institution engaged in 

research that is covered by this policy, 

with the exception of research eligible 

for exemption under §ll.104, and 

that is conducted or supported by a 

Federal department or agency, shall 

provide written assurance satisfactory to 

the department or agency head that it 

will comply with the requirements of 

this policy. In lieu of requiring 

submission of an assurance, individual 

department or agency heads shall accept 

the existence of a current assurance, 

appropriate for the research in question, 

on file with the Office for Human 

Research Protections, HHS, or any 

successor office, and approved for 

Federal-wide use by that office. When 

the existence of an HHS-approved 

assurance is accepted in lieu of 

requiring submission of an assurance, 

reports (except certification) required by 

this policy to be made to department 

and agency heads shall also be made to 

the Office for Human Research 

Protections, HHS, or any successor 

office. Federal departments and 

agencies will conduct or support 

research covered by this policy only if 

the institution has provided an 

assurance that it will comply with the 

requirements of this policy, as provided 

in this section, and only if the 

institution has certified to the 

department or agency head that the 

research has been reviewed and 

approved by an IRB (if such certification 

is required by §ll.103(d)). 

(b) The assurance shall be executed by 

an individual authorized to act for the 

institution and to assume on behalf of 

the institution the obligations imposed 

by this policy and shall be filed in such 

form and manner as the department or 

agency head prescribes. 

(c) The department or agency head 

may limit the period during which any 

assurance shall remain effective or 

otherwise condition or restrict the 

assurance. 

(d) Certification is required when the 

research is supported by a Federal 

department or agency and not otherwise 

waived under § ll.101(i) or exempted 

under §ll.104. For such research, 

institutions shall certify that each 

proposed research study covered by the 

assurance and this section has been 

reviewed and approved by the IRB. 

Such certification must be submitted as 

prescribed by the Federal department or 

agency component supporting the 

research. Under no condition shall 

research covered by this section be 

initiated prior to receipt of the 

certification that the research has been 

reviewed and approved by the IRB. 

(e) For nonexempt research involving 

human subjects covered by this policy 

(or exempt research for which limited 

IRB review takes place pursuant to 

§ ll.104(d)(2)(iii), (d)(3)(i)(C), or (d)(7) 

or (8)) that takes place at an institution 

in which IRB oversight is conducted by 

an IRB that is not operated by the 

institution, the institution and the 

organization operating the IRB shall 

document the institution’s reliance on 

the IRB for oversight of the research and 

the responsibilities that each entity will 

undertake to ensure compliance with 

the requirements of this policy (e.g., in 

a written agreement between the 

institution and the IRB, by 

implementation of an institution-wide 

policy directive providing the allocation 

of responsibilities between the 

institution and an IRB that is not 

affiliated with the institution, or as set 

forth in a research protocol). 

(Approved by the Office of Management and 

Budget under Control Number 0990–0260) 

§ ll.104 Exempt research. 

(a) Unless otherwise required by law 

or by department or agency heads, 

research activities in which the only 

involvement of human subjects will be 

in one or more of the categories in 

paragraph (d) of this section are exempt 

from the requirements of this policy, 

except that such activities must comply 

with the requirements of this section 

and as specified in each category. 

(b) Use of the exemption categories for 

research subject to the requirements of 

subparts B, C, and D: Application of the 

exemption categories to research subject 

to the requirements of 45 CFR part 46, 

subparts B, C, and D, is as follows: 

(1) Subpart B. Each of the exemptions 

at this section may be applied to 

research subject to subpart B if the 

conditions of the exemption are met. 

(2) Subpart C. The exemptions at this 

section do not apply to research subject 

to subpart C, except for research aimed 

at involving a broader subject 

population that only incidentally 

includes prisoners. 

(3) Subpart D. The exemptions at 

paragraphs (d)(1), (4), (5), (6), (7), and 

(8) of this section may be applied to 

research subject to subpart D if the 

conditions of the exemption are met. 

Paragraphs (d)(2)(i) and (ii) of this 

section only may apply to research 

subject to subpart D involving 

educational tests or the observation of 

public behavior when the investigator(s) 

do not participate in the activities being 

observed. Paragraph (d)(2)(iii) of this 

section may not be applied to research 

subject to subpart D. 

(c) [Reserved.] 

(d) Except as described in paragraph 

(a) of this section, the following 

categories of human subjects research 

are exempt from this policy: 

(1) Research, conducted in established 

or commonly accepted educational 

settings, that specifically involves 

normal educational practices that are 

not likely to adversely impact students’ 

opportunity to learn required 

educational content or the assessment of 

educators who provide instruction. This 

includes most research on regular and 

special education instructional 

strategies, and research on the 

effectiveness of or the comparison 

among instructional techniques, 

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7262 Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 

curricula, or classroom management 

methods. 

(2) Research that only includes 

interactions involving educational tests 

(cognitive, diagnostic, aptitude, 

achievement), survey procedures, 

interview procedures, or observation of 

public behavior (including visual or 

auditory recording) if at least one of the 

following criteria is met: 

(i) The information obtained is 

recorded by the investigator in such a 

manner that the identity of the human 

subjects cannot readily be ascertained, 

directly or through identifiers linked to 

the subjects; 

(ii) Any disclosure of the human 

subjects’ responses outside the research 

would not reasonably place the subjects 

at risk of criminal or civil liability or be 

damaging to the subjects’ financial 

standing, employability, educational 

advancement, or reputation; or 

(iii) The information obtained is 

recorded by the investigator in such a 

manner that the identity of the human 

subjects can readily be ascertained, 

directly or through identifiers linked to 

the subjects, and an IRB conducts a 

limited IRB review to make the 

determination required by 

§ ll.111(a)(7). 

(3)(i) Research involving benign 

behavioral interventions in conjunction 

with the collection of information from 

an adult subject through verbal or 

written responses (including data entry) 

or audiovisual recording if the subject 

prospectively agrees to the intervention 

and information collection and at least 

one of the following criteria is met: 

(A) The information obtained is 

recorded by the investigator in such a 

manner that the identity of the human 

subjects cannot readily be ascertained, 

directly or through identifiers linked to 

the subjects; 

(B) Any disclosure of the human 

subjects’ responses outside the research 

would not reasonably place the subjects 

at risk of criminal or civil liability or be 

damaging to the subjects’ financial 

standing, employability, educational 

advancement, or reputation; or 

(C) The information obtained is 

recorded by the investigator in such a 

manner that the identity of the human 

subjects can readily be ascertained, 

directly or through identifiers linked to 

the subjects, and an IRB conducts a 

limited IRB review to make the 

determination required by 

§ ll.111(a)(7). 

(ii) For the purpose of this provision, 

benign behavioral interventions are brief 

in duration, harmless, painless, not 

physically invasive, not likely to have a 

significant adverse lasting impact on the 

subjects, and the investigator has no 

reason to think the subjects will find the 

interventions offensive or embarrassing. 

Provided all such criteria are met, 

examples of such benign behavioral 

interventions would include having the 

subjects play an online game, having 

them solve puzzles under various noise 

conditions, or having them decide how 

to allocate a nominal amount of 

received cash between themselves and 

someone else. 

(iii) If the research involves deceiving 

the subjects regarding the nature or 

purposes of the research, this exemption 

is not applicable unless the subject 

authorizes the deception through a 

prospective agreement to participate in 

research in circumstances in which the 

subject is informed that he or she will 

be unaware of or misled regarding the 

nature or purposes of the research. 

(4) Secondary research for which 

consent is not required: Secondary 

research uses of identifiable private 

information or identifiable 

biospecimens, if at least one of the 

following criteria is met: 

(i) The identifiable private 

information or identifiable 

biospecimens are publicly available; 

(ii) Information, which may include 

information about biospecimens, is 

recorded by the investigator in such a 

manner that the identity of the human 

subjects cannot readily be ascertained 

directly or through identifiers linked to 

the subjects, the investigator does not 

contact the subjects, and the investigator 

will not re-identify subjects; 

(iii) The research involves only 

information collection and analysis 

involving the investigator’s use of 

identifiable health information when 

that use is regulated under 45 CFR parts 

160 and 164, subparts A and E, for the 

purposes of ‘‘health care operations’’ or 

‘‘research’’ as those terms are defined at 

45 CFR 164.501 or for ‘‘public health 

activities and purposes’’ as described 

under 45 CFR 164.512(b); or 

(iv) The research is conducted by, or 

on behalf of, a Federal department or 

agency using government-generated or 

government-collected information 

obtained for nonresearch activities, if 

the research generates identifiable 

private information that is or will be 

maintained on information technology 

that is subject to and in compliance 

with section 208(b) of the E-Government 

Act of 2002, 44 U.S.C. 3501 note, if all 

of the identifiable private information 

collected, used, or generated as part of 

the activity will be maintained in 

systems of records subject to the Privacy 

Act of 1974, 5 U.S.C. 552a, and, if 

applicable, the information used in the 

research was collected subject to the 

Paperwork Reduction Act of 1995, 44 

U.S.C. 3501 et seq. 

(5) Research and demonstration 

projects that are conducted or supported 

by a Federal department or agency, or 

otherwise subject to the approval of 

department or agency heads (or the 

approval of the heads of bureaus or 

other subordinate agencies that have 

been delegated authority to conduct the 

research and demonstration projects), 

and that are designed to study, evaluate, 

improve, or otherwise examine public 

benefit or service programs, including 

procedures for obtaining benefits or 

services under those programs, possible 

changes in or alternatives to those 

programs or procedures, or possible 

changes in methods or levels of 

payment for benefits or services under 

those programs. Such projects include, 

but are not limited to, internal studies 

by Federal employees, and studies 

under contracts or consulting 

arrangements, cooperative agreements, 

or grants. Exempt projects also include 

waivers of otherwise mandatory 

requirements using authorities such as 

sections 1115 and 1115A of the Social 

Security Act, as amended. 

(i) Each Federal department or agency 

conducting or supporting the research 

and demonstration projects must 

establish, on a publicly accessible 

Federal Web site or in such other 

manner as the department or agency 

head may determine, a list of the 

research and demonstration projects 

that the Federal department or agency 

conducts or supports under this 

provision. The research or 

demonstration project must be 

published on this list prior to 

commencing the research involving 

human subjects. 

(ii) [Reserved] 

(6) Taste and food quality evaluation 

and consumer acceptance studies: 

(i) If wholesome foods without 

additives are consumed, or 

(ii) If a food is consumed that contains 

a food ingredient at or below the level 

and for a use found to be safe, or 

agricultural chemical or environmental 

contaminant at or below the level found 

to be safe, by the Food and Drug 

Administration or approved by the 

Environmental Protection Agency or the 

Food Safety and Inspection Service of 

the U.S. Department of Agriculture. 

(7) Storage or maintenance for 

secondary research for which broad 

consent is required: Storage or 

maintenance of identifiable private 

information or identifiable 

biospecimens for potential secondary 

research use if an IRB conducts a 

limited IRB review and makes the 

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determinations required by 

§ ll.111(a)(8). 

(8) Secondary research for which 

broad consent is required: Research 

involving the use of identifiable private 

information or identifiable 

biospecimens for secondary research 

use, if the following criteria are met: 

(i) Broad consent for the storage, 

maintenance, and secondary research 

use of the identifiable private 

information or identifiable 

biospecimens was obtained in 

accordance with § ll.116(a)(1) 

through (4), (a)(6), and (d); 

(ii) Documentation of informed 

consent or waiver of documentation of 

consent was obtained in accordance 

with §ll.117; 

(iii) An IRB conducts a limited IRB 

review and makes the determination 

required by § ll.111(a)(7) and makes 

the determination that the research to be 

conducted is within the scope of the 

broad consent referenced in paragraph 

(d)(8)(i) of this section; and (iv) The 

investigator does not include returning 

individual research results to subjects as 

part of the study plan. This provision 

does not prevent an investigator from 

abiding by any legal requirements to 

return individual research results. 

(Approved by the Office of Management and 

Budget under Control Number 0990–0260) 

§ ll.105 [Reserved.] 

§ ll.106 [Reserved] 

§ ll.107 IRB membership. 

(a) Each IRB shall have at least five 

members, with varying backgrounds to 

promote complete and adequate review 

of research activities commonly 

conducted by the institution. The IRB 

shall be sufficiently qualified through 

the experience and expertise of its 

members (professional competence), 

and the diversity of its members, 

including race, gender, and cultural 

backgrounds and sensitivity to such 

issues as community attitudes, to 

promote respect for its advice and 

counsel in safeguarding the rights and 

welfare of human subjects. The IRB 

shall be able to ascertain the 

acceptability of proposed research in 

terms of institutional commitments 

(including policies and resources) and 

regulations, applicable law, and 

standards of professional conduct and 

practice. The IRB shall therefore include 

persons knowledgeable in these areas. If 

an IRB regularly reviews research that 

involves a category of subjects that is 

vulnerable to coercion or undue 

influence, such as children, prisoners, 

individuals with impaired decisionmaking capacity, or economically or 

educationally disadvantaged persons, 

consideration shall be given to the 

inclusion of one or more individuals 

who are knowledgeable about and 

experienced in working with these 

categories of subjects. 

(b) Each IRB shall include at least one 

member whose primary concerns are in 

scientific areas and at least one member 

whose primary concerns are in 

nonscientific areas. 

(c) Each IRB shall include at least one 

member who is not otherwise affiliated 

with the institution and who is not part 

of the immediate family of a person who 

is affiliated with the institution. 

(d) No IRB may have a member 

participate in the IRB’s initial or 

continuing review of any project in 

which the member has a conflicting 

interest, except to provide information 

requested by the IRB. 

(e) An IRB may, in its discretion, 

invite individuals with competence in 

special areas to assist in the review of 

issues that require expertise beyond or 

in addition to that available on the IRB. 

These individuals may not vote with the 

IRB. 

§ ll.108 IRB functions and 

operations. 

(a) In order to fulfill the requirements 

of this policy each IRB shall: 

(1) Have access to meeting space and 

sufficient staff to support the IRB’s 

review and recordkeeping duties; 

(2) Prepare and maintain a current list 

of the IRB members identified by name; 

earned degrees; representative capacity; 

indications of experience such as board 

certifications or licenses sufficient to 

describe each member’s chief 

anticipated contributions to IRB 

deliberations; and any employment or 

other relationship between each 

member and the institution, for 

example, full-time employee, part-time 

employee, member of governing panel 

or board, stockholder, paid or unpaid 

consultant; 

(3) Establish and follow written 

procedures for: 

(i) Conducting its initial and 

continuing review of research and for 

reporting its findings and actions to the 

investigator and the institution; 

(ii) Determining which projects 

require review more often than annually 

and which projects need verification 

from sources other than the 

investigators that no material changes 

have occurred since previous IRB 

review; and 

(iii) Ensuring prompt reporting to the 

IRB of proposed changes in a research 

activity, and for ensuring that 

investigators will conduct the research 

activity in accordance with the terms of 

the IRB approval until any proposed 

changes have been reviewed and 

approved by the IRB, except when 

necessary to eliminate apparent 

immediate hazards to the subject. 

(4) Establish and follow written 

procedures for ensuring prompt 

reporting to the IRB; appropriate 

institutional officials; the department or 

agency head; and the Office for Human 

Research Protections, HHS, or any 

successor office, or the equivalent office 

within the appropriate Federal 

department or agency of 

(i) Any unanticipated problems 

involving risks to subjects or others or 

any serious or continuing 

noncompliance with this policy or the 

requirements or determinations of the 

IRB; and 

(ii) Any suspension or termination of 

IRB approval. 

(b) Except when an expedited review 

procedure is used (as described in 

§ ll.110), an IRB must review 

proposed research at convened meetings 

at which a majority of the members of 

the IRB are present, including at least 

one member whose primary concerns 

are in nonscientific areas. In order for 

the research to be approved, it shall 

receive the approval of a majority of 

those members present at the meeting. 

(Approved by the Office of Management and 

Budget under Control Number 0990–0260) 

§ ll.109 IRB review of research. 

(a) An IRB shall review and have 

authority to approve, require 

modifications in (to secure approval), or 

disapprove all research activities 

covered by this policy, including 

exempt research activities under 

§ ll.104 for which limited IRB review 

is a condition of exemption (under 

§ ll.104(d)(2)(iii), (d)(3)(i)(C), and 

(d)(7), and (8)). 

(b) An IRB shall require that 

information given to subjects (or legally 

authorized representatives, when 

appropriate) as part of informed consent 

is in accordance with §ll.116. The 

IRB may require that information, in 

addition to that specifically mentioned 

in §ll.116, be given to the subjects 

when in the IRB’s judgment the 

information would meaningfully add to 

the protection of the rights and welfare 

of subjects. 

(c) An IRB shall require 

documentation of informed consent or 

may waive documentation in 

accordance with § ll.117. 

(d) An IRB shall notify investigators 

and the institution in writing of its 

decision to approve or disapprove the 

proposed research activity, or of 

modifications required to secure IRB 

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approval of the research activity. If the 

IRB decides to disapprove a research 

activity, it shall include in its written 

notification a statement of the reasons 

for its decision and give the investigator 

an opportunity to respond in person or 

in writing. 

(e) An IRB shall conduct continuing 

review of research requiring review by 

the convened IRB at intervals 

appropriate to the degree of risk, not 

less than once per year, except as 

described in § ll.109(f). 

(f)(1) Unless an IRB determines 

otherwise, continuing review of 

research is not required in the following 

circumstances: 

(i) Research eligible for expedited 

review in accordance with §ll.110; 

(ii) Research reviewed by the IRB in 

accordance with the limited IRB review 

described in § ll.104(d)(2)(iii), 

(d)(3)(i)(C), or (d)(7) or (8); 

(iii) Research that has progressed to 

the point that it involves only one or 

both of the following, which are part of 

the IRB-approved study: 

(A) Data analysis, including analysis 

of identifiable private information or 

identifiable biospecimens, or 

(B) Accessing follow-up clinical data 

from procedures that subjects would 

undergo as part of clinical care. 

(2) [Reserved.] 

(g) An IRB shall have authority to 

observe or have a third party observe the 

consent process and the research. 

(Approved by the Office of Management and 

Budget under Control Number 0990–0260) 

§ ll.110 Expedited review 

procedures for certain kinds of 

research involving no more than 

minimal risk, and for minor changes in 

approved research. 

(a) The Secretary of HHS has 

established, and published as a Notice 

in the Federal Register, a list of 

categories of research that may be 

reviewed by the IRB through an 

expedited review procedure. The 

Secretary will evaluate the list at least 

every 8 years and amend it, as 

appropriate, after consultation with 

other federal departments and agencies 

and after publication in the Federal 

Register for public comment. A copy of 

the list is available from the Office for 

Human Research Protections, HHS, or 

any successor office. 

(b)(1) An IRB may use the expedited 

review procedure to review the 

following: 

(i) Some or all of the research 

appearing on the list described in 

paragraph (a) of this section, unless the 

reviewer determines that the study 

involves more than minimal risk; 

(ii) Minor changes in previously 

approved research during the period for 

which approval is authorized; or 

(iii) Research for which limited IRB 

review is a condition of exemption 

under §ll.104(d)(2)(iii), (d)(3)(i)(C), 

and (d)(7) and (8). 

(2) Under an expedited review 

procedure, the review may be carried 

out by the IRB chairperson or by one or 

more experienced reviewers designated 

by the chairperson from among 

members of the IRB. In reviewing the 

research, the reviewers may exercise all 

of the authorities of the IRB except that 

the reviewers may not disapprove the 

research. A research activity may be 

disapproved only after review in 

accordance with the nonexpedited 

procedure set forth in §ll.108(b). 

(c) Each IRB that uses an expedited 

review procedure shall adopt a method 

for keeping all members advised of 

research proposals that have been 

approved under the procedure. 

(d) The department or agency head 

may restrict, suspend, terminate, or 

choose not to authorize an institution’s 

or IRB’s use of the expedited review 

procedure. 

§ ll.111 Criteria for IRB approval of 

research. 

(a) In order to approve research 

covered by this policy the IRB shall 

determine that all of the following 

requirements are satisfied: 

(1) Risks to subjects are minimized: 

(i) By using procedures that are 

consistent with sound research design 

and that do not unnecessarily expose 

subjects to risk, and 

(ii) Whenever appropriate, by using 

procedures already being performed on 

the subjects for diagnostic or treatment 

purposes. 

(2) Risks to subjects are reasonable in 

relation to anticipated benefits, if any, to 

subjects, and the importance of the 

knowledge that may reasonably be 

expected to result. In evaluating risks 

and benefits, the IRB should consider 

only those risks and benefits that may 

result from the research (as 

distinguished from risks and benefits of 

therapies subjects would receive even if 

not participating in the research). The 

IRB should not consider possible longrange effects of applying knowledge 

gained in the research (e.g., the possible 

effects of the research on public policy) 

as among those research risks that fall 

within the purview of its responsibility. 

(3) Selection of subjects is equitable. 

In making this assessment the IRB 

should take into account the purposes of 

the research and the setting in which 

the research will be conducted. The IRB 

should be particularly cognizant of the 

special problems of research that 

involves a category of subjects who are 

vulnerable to coercion or undue 

influence, such as children, prisoners, 

individuals with impaired decisionmaking capacity, or economically or 

educationally disadvantaged persons. 

(4) Informed consent will be sought 

from each prospective subject or the 

subject’s legally authorized 

representative, in accordance with, and 

to the extent required by, § ll.116. 

(5) Informed consent will be 

appropriately documented or 

appropriately waived in accordance 

with §ll.117. 

(6) When appropriate, the research 

plan makes adequate provision for 

monitoring the data collected to ensure 

the safety of subjects. 

(7) When appropriate, there are 

adequate provisions to protect the 

privacy of subjects and to maintain the 

confidentiality of data. 

(i) The Secretary of HHS will, after 

consultation with the Office of 

Management and Budget’s privacy office 

and other Federal departments and 

agencies that have adopted this policy, 

issue guidance to assist IRBs in 

assessing what provisions are adequate 

to protect the privacy of subjects and to 

maintain the confidentiality of data. 

(ii) [Reserved.] 

(8) For purposes of conducting the 

limited IRB review required by 

§ ll.104(d)(7)), the IRB need not make 

the determinations at paragraphs (a)(1) 

through (7) of this section, and shall 

make the following determinations: 

(i) Broad consent for storage, 

maintenance, and secondary research 

use of identifiable private information 

or identifiable biospecimens is obtained 

in accordance with the requirements of 

§ ll.116(a)(1)–(4), (a)(6), and (d); 

(ii) Broad consent is appropriately 

documented or waiver of 

documentation is appropriate, in 

accordance with § ll.117; and 

(iii) If there is a change made for 

research purposes in the way the 

identifiable private information or 

identifiable biospecimens are stored or 

maintained, there are adequate 

provisions to protect the privacy of 

subjects and to maintain the 

confidentiality of data. 

(b) When some or all of the subjects 

are likely to be vulnerable to coercion or 

undue influence, such as children, 

prisoners, individuals with impaired 

decision-making capacity, or 

economically or educationally 

disadvantaged persons, additional 

safeguards have been included in the 

study to protect the rights and welfare 

of these subjects. 

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§ ll.112 Review by Institution 

Research covered by this policy that 

has been approved by an IRB may be 

subject to further appropriate review 

and approval or disapproval by officials 

of the institution. However, those 

officials may not approve the research if 

it has not been approved by an IRB. 

§ ll.113 Suspension or Termination 

of IRB Approval of Research 

An IRB shall have authority to 

suspend or terminate approval of 

research that is not being conducted in 

accordance with the IRB’s requirements 

or that has been associated with 

unexpected serious harm to subjects. 

Any suspension or termination of 

approval shall include a statement of 

the reasons for the IRB’s action and 

shall be reported promptly to the 

investigator, appropriate institutional 

officials, and the department or agency 

head. 

(Approved by the Office of Management and 

Budget under Control Number 0990–0260) 

§ ll.114 Cooperative Research 

(a) Cooperative research projects are 

those projects covered by this policy 

that involve more than one institution. 

In the conduct of cooperative research 

projects, each institution is responsible 

for safeguarding the rights and welfare 

of human subjects and for complying 

with this policy. 

(b)(1) Any institution located in the 

United States that is engaged in 

cooperative research must rely upon 

approval by a single IRB for that portion 

of the research that is conducted in the 

United States. The reviewing IRB will 

be identified by the Federal department 

or agency supporting or conducting the 

research or proposed by the lead 

institution subject to the acceptance of 

the Federal department or agency 

supporting the research. 

(2) The following research is not 

subject to this provision: 

(i) Cooperative research for which 

more than single IRB review is required 

by law (including tribal law passed by 

the official governing body of an 

American Indian or Alaska Native tribe); 

or 

(ii) Research for which any Federal 

department or agency supporting or 

conducting the research determines and 

documents that the use of a single IRB 

is not appropriate for the particular 

context. 

(c) For research not subject to 

paragraph (b) of this section, an 

institution participating in a cooperative 

project may enter into a joint review 

arrangement, rely on the review of 

another IRB, or make similar 

arrangements for avoiding duplication 

of effort. 

§ ll.115 IRB Records 

(a) An institution, or when 

appropriate an IRB, shall prepare and 

maintain adequate documentation of 

IRB activities, including the following: 

(1) Copies of all research proposals 

reviewed, scientific evaluations, if any, 

that accompany the proposals, approved 

sample consent forms, progress reports 

submitted by investigators, and reports 

of injuries to subjects. 

(2) Minutes of IRB meetings, which 

shall be in sufficient detail to show 

attendance at the meetings; actions 

taken by the IRB; the vote on these 

actions including the number of 

members voting for, against, and 

abstaining; the basis for requiring 

changes in or disapproving research; 

and a written summary of the 

discussion of controverted issues and 

their resolution. 

(3) Records of continuing review 

activities, including the rationale for 

conducting continuing review of 

research that otherwise would not 

require continuing review as described 

in §ll.109(f)(1). 

(4) Copies of all correspondence 

between the IRB and the investigators. 

(5) A list of IRB members in the same 

detail as described in §ll.108(a)(2). 

(6) Written procedures for the IRB in 

the same detail as described in 

§ ll.108(a)(3) and (4). 

(7) Statements of significant new 

findings provided to subjects, as 

required by § ll.116(c)(5). 

(8) The rationale for an expedited 

reviewer’s determination under 

§ ll.110(b)(1)(i) that research 

appearing on the expedited review list 

described in § ll.110(a) is more than 

minimal risk. 

(9) Documentation specifying the 

responsibilities that an institution and 

an organization operating an IRB each 

will undertake to ensure compliance 

with the requirements of this policy, as 

described in § ll.103(e). 

(b) The records required by this policy 

shall be retained for at least 3 years, and 

records relating to research that is 

conducted shall be retained for at least 

3 years after completion of the research. 

The institution or IRB may maintain the 

records in printed form, or 

electronically. All records shall be 

accessible for inspection and copying by 

authorized representatives of the 

Federal department or agency at 

reasonable times and in a reasonable 

manner. 

(Approved by the Office of Management and 

Budget under Control Number 0990–0260) 

§ ll.116 General Requirements for 

Informed Consent 

(a) General. General requirements for 

informed consent, whether written or 

oral, are set forth in this paragraph and 

apply to consent obtained in accordance 

with the requirements set forth in 

paragraphs (b) through (d) of this 

section. Broad consent may be obtained 

in lieu of informed consent obtained in 

accordance with paragraphs (b) and (c) 

of this section only with respect to the 

storage, maintenance, and secondary 

research uses of identifiable private 

information and identifiable 

biospecimens. Waiver or alteration of 

consent in research involving public 

benefit and service programs conducted 

by or subject to the approval of state or 

local officials is described in paragraph 

(e) of this section. General waiver or 

alteration of informed consent is 

described in paragraph (f) of this 

section. Except as provided elsewhere 

in this policy: 

(1) Before involving a human subject 

in research covered by this policy, an 

investigator shall obtain the legally 

effective informed consent of the subject 

or the subject’s legally authorized 

representative. 

(2) An investigator shall seek 

informed consent only under 

circumstances that provide the 

prospective subject or the legally 

authorized representative sufficient 

opportunity to discuss and consider 

whether or not to participate and that 

minimize the possibility of coercion or 

undue influence. 

(3) The information that is given to 

the subject or the legally authorized 

representative shall be in language 

understandable to the subject or the 

legally authorized representative. 

(4) The prospective subject or the 

legally authorized representative must 

be provided with the information that a 

reasonable person would want to have 

in order to make an informed decision 

about whether to participate, and an 

opportunity to discuss that information. 

(5) Except for broad consent obtained 

in accordance with paragraph (d) of this 

section: 

(i) Informed consent must begin with 

a concise and focused presentation of 

the key information that is most likely 

to assist a prospective subject or legally 

authorized representative in 

understanding the reasons why one 

might or might not want to participate 

in the research. This part of the 

informed consent must be organized 

and presented in a way that facilitates 

comprehension. 

(ii) Informed consent as a whole must 

present information in sufficient detail 

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relating to the research, and must be 

organized and presented in a way that 

does not merely provide lists of isolated 

facts, but rather facilitates the 

prospective subject’s or legally 

authorized representative’s 

understanding of the reasons why one 

might or might not want to participate. 

(6) No informed consent may include 

any exculpatory language through 

which the subject or the legally 

authorized representative is made to 

waive or appear to waive any of the 

subject’s legal rights, or releases or 

appears to release the investigator, the 

sponsor, the institution, or its agents 

from liability for negligence. 

(b) Basic elements of informed 

consent. Except as provided in 

paragraph (d), (e), or (f) of this section, 

in seeking informed consent the 

following information shall be provided 

to each subject or the legally authorized 

representative: 

(1) A statement that the study 

involves research, an explanation of the 

purposes of the research and the 

expected duration of the subject’s 

participation, a description of the 

procedures to be followed, and 

identification of any procedures that are 

experimental; 

(2) A description of any reasonably 

foreseeable risks or discomforts to the 

subject; 

(3) A description of any benefits to the 

subject or to others that may reasonably 

be expected from the research; 

(4) A disclosure of appropriate 

alternative procedures or courses of 

treatment, if any, that might be 

advantageous to the subject; 

(5) A statement describing the extent, 

if any, to which confidentiality of 

records identifying the subject will be 

maintained; 

(6) For research involving more than 

minimal risk, an explanation as to 

whether any compensation and an 

explanation as to whether any medical 

treatments are available if injury occurs 

and, if so, what they consist of, or where 

further information may be obtained; 

(7) An explanation of whom to 

contact for answers to pertinent 

questions about the research and 

research subjects’ rights, and whom to 

contact in the event of a research-related 

injury to the subject; 

(8) A statement that participation is 

voluntary, refusal to participate will 

involve no penalty or loss of benefits to 

which the subject is otherwise entitled, 

and the subject may discontinue 

participation at any time without 

penalty or loss of benefits to which the 

subject is otherwise entitled; and 

(9) One of the following statements 

about any research that involves the 

collection of identifiable private 

information or identifiable 

biospecimens: 

(i) A statement that identifiers might 

be removed from the identifiable private 

information or identifiable 

biospecimens and that, after such 

removal, the information or 

biospecimens could be used for future 

research studies or distributed to 

another investigator for future research 

studies without additional informed 

consent from the subject or the legally 

authorized representative, if this might 

be a possibility; or 

(ii) A statement that the subject’s 

information or biospecimens collected 

as part of the research, even if 

identifiers are removed, will not be used 

or distributed for future research 

studies. 

(c) Additional elements of informed 

consent. Except as provided in 

paragraph (d), (e), or (f) of this section, 

one or more of the following elements 

of information, when appropriate, shall 

also be provided to each subject or the 

legally authorized representative: 

(1) A statement that the particular 

treatment or procedure may involve 

risks to the subject (or to the embryo or 

fetus, if the subject is or may become 

pregnant) that are currently 

unforeseeable; 

(2) Anticipated circumstances under 

which the subject’s participation may be 

terminated by the investigator without 

regard to the subject’s or the legally 

authorized representative’s consent; 

(3) Any additional costs to the subject 

that may result from participation in the 

research; 

(4) The consequences of a subject’s 

decision to withdraw from the research 

and procedures for orderly termination 

of participation by the subject; 

(5) A statement that significant new 

findings developed during the course of 

the research that may relate to the 

subject’s willingness to continue 

participation will be provided to the 

subject; 

(6) The approximate number of 

subjects involved in the study; 

(7) A statement that the subject’s 

biospecimens (even if identifiers are 

removed) may be used for commercial 

profit and whether the subject will or 

will not share in this commercial profit; 

(8) A statement regarding whether 

clinically relevant research results, 

including individual research results, 

will be disclosed to subjects, and if so, 

under what conditions; and 

(9) For research involving 

biospecimens, whether the research will 

(if known) or might include whole 

genome sequencing (i.e., sequencing of 

a human germline or somatic specimen 

with the intent to generate the genome 

or exome sequence of that specimen). 

(d) Elements of broad consent for the 

storage, maintenance, and secondary 

research use of identifiable private 

information or identifiable 

biospecimens. Broad consent for the 

storage, maintenance, and secondary 

research use of identifiable private 

information or identifiable 

biospecimens (collected for either 

research studies other than the proposed 

research or nonresearch purposes) is 

permitted as an alternative to the 

informed consent requirements in 

paragraphs (b) and (c) of this section. If 

the subject or the legally authorized 

representative is asked to provide broad 

consent, the following shall be provided 

to each subject or the subject’s legally 

authorized representative: 

(1) The information required in 

paragraphs (b)(2), (b)(3), (b)(5), and 

(b)(8) and, when appropriate, (c)(7) and 

(9) of this section; 

(2) A general description of the types 

of research that may be conducted with 

the identifiable private information or 

identifiable biospecimens. This 

description must include sufficient 

information such that a reasonable 

person would expect that the broad 

consent would permit the types of 

research conducted; 

(3) A description of the identifiable 

private information or identifiable 

biospecimens that might be used in 

research, whether sharing of identifiable 

private information or identifiable 

biospecimens might occur, and the 

types of institutions or researchers that 

might conduct research with the 

identifiable private information or 

identifiable biospecimens; 

(4) A description of the period of time 

that the identifiable private information 

or identifiable biospecimens may be 

stored and maintained (which period of 

time could be indefinite), and a 

description of the period of time that the 

identifiable private information or 

identifiable biospecimens may be used 

for research purposes (which period of 

time could be indefinite); 

(5) Unless the subject or legally 

authorized representative will be 

provided details about specific research 

studies, a statement that they will not be 

informed of the details of any specific 

research studies that might be 

conducted using the subject’s 

identifiable private information or 

identifiable biospecimens, including the 

purposes of the research, and that they 

might have chosen not to consent to 

some of those specific research studies; 

(6) Unless it is known that clinically 

relevant research results, including 

individual research results, will be 

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Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 7267 

disclosed to the subject in all 

circumstances, a statement that such 

results may not be disclosed to the 

subject; and 

(7) An explanation of whom to 

contact for answers to questions about 

the subject’s rights and about storage 

and use of the subject’s identifiable 

private information or identifiable 

biospecimens, and whom to contact in 

the event of a research-related harm. 

(e) Waiver or alteration of consent in 

research involving public benefit and 

service programs conducted by or 

subject to the approval of state or local 

officials—(1) Waiver. An IRB may waive 

the requirement to obtain informed 

consent for research under paragraphs 

(a) through (c) of this section, provided 

the IRB satisfies the requirements of 

paragraph (e)(3) of this section. If an 

individual was asked to provide broad 

consent for the storage, maintenance, 

and secondary research use of 

identifiable private information or 

identifiable biospecimens in accordance 

with the requirements at paragraph (d) 

of this section, and refused to consent, 

an IRB cannot waive consent for the 

storage, maintenance, or secondary 

research use of the identifiable private 

information or identifiable 

biospecimens. 

(2) Alteration. An IRB may approve a 

consent procedure that omits some, or 

alters some or all, of the elements of 

informed consent set forth in paragraphs 

(b) and (c) of this section provided the 

IRB satisfies the requirements of 

paragraph (e)(3) of this section. An IRB 

may not omit or alter any of the 

requirements described in paragraph (a) 

of this section. If a broad consent 

procedure is used, an IRB may not omit 

or alter any of the elements required 

under paragraph (d) of this section. 

(3) Requirements for waiver and 

alteration. In order for an IRB to waive 

or alter consent as described in this 

subsection, the IRB must find and 

document that: 

(i) The research or demonstration 

project is to be conducted by or subject 

to the approval of state or local 

government officials and is designed to 

study, evaluate, or otherwise examine: 

(A) Public benefit or service programs; 

(B) Procedures for obtaining benefits 

or services under those programs; 

(C) Possible changes in or alternatives 

to those programs or procedures; or 

(D) Possible changes in methods or 

levels of payment for benefits or 

services under those programs; and 

(ii) The research could not practicably 

be carried out without the waiver or 

alteration. 

(f) General waiver or alteration of 

consent—(1) Waiver. An IRB may waive 

the requirement to obtain informed 

consent for research under paragraphs 

(a) through (c) of this section, provided 

the IRB satisfies the requirements of 

paragraph (f)(3) of this section. If an 

individual was asked to provide broad 

consent for the storage, maintenance, 

and secondary research use of 

identifiable private information or 

identifiable biospecimens in accordance 

with the requirements at paragraph (d) 

of this section, and refused to consent, 

an IRB cannot waive consent for the 

storage, maintenance, or secondary 

research use of the identifiable private 

information or identifiable 

biospecimens. 

(2) Alteration. An IRB may approve a 

consent procedure that omits some, or 

alters some or all, of the elements of 

informed consent set forth in paragraphs 

(b) and (c) of this section provided the 

IRB satisfies the requirements of 

paragraph (f)(3) of this section. An IRB 

may not omit or alter any of the 

requirements described in paragraph (a) 

of this section. If a broad consent 

procedure is used, an IRB may not omit 

or alter any of the elements required 

under paragraph (d) of this section. 

(3) Requirements for waiver and 

alteration. In order for an IRB to waive 

or alter consent as described in this 

subsection, the IRB must find and 

document that: 

(i) The research involves no more 

than minimal risk to the subjects; 

(ii) The research could not practicably 

be carried out without the requested 

waiver or alteration; 

(iii) If the research involves using 

identifiable private information or 

identifiable biospecimens, the research 

could not practicably be carried out 

without using such information or 

biospecimens in an identifiable format; 

(iv) The waiver or alteration will not 

adversely affect the rights and welfare of 

the subjects; and 

(v) Whenever appropriate, the 

subjects or legally authorized 

representatives will be provided with 

additional pertinent information after 

participation. 

(g) Screening, recruiting, or 

determining eligibility. An IRB may 

approve a research proposal in which an 

investigator will obtain information or 

biospecimens for the purpose of 

screening, recruiting, or determining the 

eligibility of prospective subjects 

without the informed consent of the 

prospective subject or the subject’s 

legally authorized representative, if 

either of the following conditions are 

met: 

(1) The investigator will obtain 

information through oral or written 

communication with the prospective 

subject or legally authorized 

representative, or 

(2) The investigator will obtain 

identifiable private information or 

identifiable biospecimens by accessing 

records or stored identifiable 

biospecimens. 

(h) Posting of clinical trial consent 

form. (1) For each clinical trial 

conducted or supported by a Federal 

department or agency, one IRBapproved informed consent form used 

to enroll subjects must be posted by the 

awardee or the Federal department or 

agency component conducting the trial 

on a publicly available Federal Web site 

that will be established as a repository 

for such informed consent forms. 

(2) If the Federal department or 

agency supporting or conducting the 

clinical trial determines that certain 

information should not be made 

publicly available on a Federal Web site 

(e.g. confidential commercial 

information), such Federal department 

or agency may permit or require 

redactions to the information posted. 

(3) The informed consent form must 

be posted on the Federal Web site after 

the clinical trial is closed to 

recruitment, and no later than 60 days 

after the last study visit by any subject, 

as required by the protocol. 

(i) Preemption. The informed consent 

requirements in this policy are not 

intended to preempt any applicable 

Federal, state, or local laws (including 

tribal laws passed by the official 

governing body of an American Indian 

or Alaska Native tribe) that require 

additional information to be disclosed 

in order for informed consent to be 

legally effective. 

(j) Emergency medical care. Nothing 

in this policy is intended to limit the 

authority of a physician to provide 

emergency medical care, to the extent 

the physician is permitted to do so 

under applicable Federal, state, or local 

law (including tribal law passed by the 

official governing body of an American 

Indian or Alaska Native tribe). 

(Approved by the Office of Management and 

Budget under Control Number 0990–0260) 

§ ll.117 Documentation of informed 

consent. 

(a) Except as provided in paragraph 

(c) of this section, informed consent 

shall be documented by the use of a 

written informed consent form 

approved by the IRB and signed 

(including in an electronic format) by 

the subject or the subject’s legally 

authorized representative. A written 

copy shall be given to the person 

signing the informed consent form. 

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7268 Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 

(b) Except as provided in paragraph 

(c) of this section, the informed consent 

form may be either of the following: 

(1) A written informed consent form 

that meets the requirements of 

§ ll.116. The investigator shall give 

either the subject or the subject’s legally 

authorized representative adequate 

opportunity to read the informed 

consent form before it is signed; 

alternatively, this form may be read to 

the subject or the subject’s legally 

authorized representative. 

(2) A short form written informed 

consent form stating that the elements of 

informed consent required by §ll.116 

have been presented orally to the 

subject or the subject’s legally 

authorized representative, and that the 

key information required by 

§ ll.116(a)(5)(i) was presented first to 

the subject, before other information, if 

any, was provided. The IRB shall 

approve a written summary of what is 

to be said to the subject or the legally 

authorized representative. When this 

method is used, there shall be a witness 

to the oral presentation. Only the short 

form itself is to be signed by the subject 

or the subject’s legally authorized 

representative. However, the witness 

shall sign both the short form and a 

copy of the summary, and the person 

actually obtaining consent shall sign a 

copy of the summary. A copy of the 

summary shall be given to the subject or 

the subject’s legally authorized 

representative, in addition to a copy of 

the short form. 

(c)(1) An IRB may waive the 

requirement for the investigator to 

obtain a signed informed consent form 

for some or all subjects if it finds any 

of the following: 

(i) That the only record linking the 

subject and the research would be the 

informed consent form and the 

principal risk would be potential harm 

resulting from a breach of 

confidentiality. Each subject (or legally 

authorized representative) will be asked 

whether the subject wants 

documentation linking the subject with 

the research, and the subject’s wishes 

will govern; 

(ii) That the research presents no 

more than minimal risk of harm to 

subjects and involves no procedures for 

which written consent is normally 

required outside of the research context; 

or 

(iii) If the subjects or legally 

authorized representatives are members 

of a distinct cultural group or 

community in which signing forms is 

not the norm, that the research presents 

no more than minimal risk of harm to 

subjects and provided there is an 

appropriate alternative mechanism for 

documenting that informed consent was 

obtained. 

(2) In cases in which the 

documentation requirement is waived, 

the IRB may require the investigator to 

provide subjects or legally authorized 

representatives with a written statement 

regarding the research. 

(Approved by the Office of Management and 

Budget under Control Number 0990–0260) 

§ ll.118 Applications and proposals 

lacking definite plans for involvement 

of human subjects. 

Certain types of applications for 

grants, cooperative agreements, or 

contracts are submitted to Federal 

departments or agencies with the 

knowledge that subjects may be 

involved within the period of support, 

but definite plans would not normally 

be set forth in the application or 

proposal. These include activities such 

as institutional type grants when 

selection of specific projects is the 

institution’s responsibility; research 

training grants in which the activities 

involving subjects remain to be selected; 

and projects in which human subjects’ 

involvement will depend upon 

completion of instruments, prior animal 

studies, or purification of compounds. 

Except for research waived under 

§ ll.101(i) or exempted under 

§ ll.104, no human subjects may be 

involved in any project supported by 

these awards until the project has been 

reviewed and approved by the IRB, as 

provided in this policy, and certification 

submitted, by the institution, to the 

Federal department or agency 

component supporting the research. 

§ ll.119 Research undertaken 

without the intention of involving 

human subjects. 

Except for research waived under 

§ ll.101(i) or exempted under 

§ ll.104, in the event research is 

undertaken without the intention of 

involving human subjects, but it is later 

proposed to involve human subjects in 

the research, the research shall first be 

reviewed and approved by an IRB, as 

provided in this policy, a certification 

submitted by the institution to the 

Federal department or agency 

component supporting the research, and 

final approval given to the proposed 

change by the Federal department or 

agency component. 

§ ll.120 Evaluation and disposition 

of applications and proposals for 

research to be conducted or supported 

by a Federal department or agency. 

(a) The department or agency head 

will evaluate all applications and 

proposals involving human subjects 

submitted to the Federal department or 

agency through such officers and 

employees of the Federal department or 

agency and such experts and 

consultants as the department or agency 

head determines to be appropriate. This 

evaluation will take into consideration 

the risks to the subjects, the adequacy of 

protection against these risks, the 

potential benefits of the research to the 

subjects and others, and the importance 

of the knowledge gained or to be gained. 

(b) On the basis of this evaluation, the 

department or agency head may approve 

or disapprove the application or 

proposal, or enter into negotiations to 

develop an approvable one. 

§ ll.121 [Reserved] 

§ ll.122 Use of Federal funds. 

Federal funds administered by a 

Federal department or agency may not 

be expended for research involving 

human subjects unless the requirements 

of this policy have been satisfied. 

§ ll.123 Early termination of 

research support: Evaluation of 

applications and proposals. 

(a) The department or agency head 

may require that Federal department or 

agency support for any project be 

terminated or suspended in the manner 

prescribed in applicable program 

requirements, when the department or 

agency head finds an institution has 

materially failed to comply with the 

terms of this policy. 

(b) In making decisions about 

supporting or approving applications or 

proposals covered by this policy the 

department or agency head may take 

into account, in addition to all other 

eligibility requirements and program 

criteria, factors such as whether the 

applicant has been subject to a 

termination or suspension under 

paragraph (a) of this section and 

whether the applicant or the person or 

persons who would direct or has/have 

directed the scientific and technical 

aspects of an activity has/have, in the 

judgment of the department or agency 

head, materially failed to discharge 

responsibility for the protection of the 

rights and welfare of human subjects 

(whether or not the research was subject 

to federal regulation). 

§ ll.124 Conditions. 

With respect to any research project 

or any class of research projects the 

department or agency head of either the 

conducting or the supporting Federal 

department or agency may impose 

additional conditions prior to or at the 

time of approval when in the judgment 

of the department or agency head 

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Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 7269 

additional conditions are necessary for 

the protection of human subjects. 

Adoption of the Common Rules 

The adoption of the common rules by 

the participating agencies, as modified 

by agency-specific text, is set forth 

below. 

DEPARTMENT OF HOMELAND 

SECURITY 

List of Subjects in 6 CFR Part 46 

Human research subjects, Reporting 

and record-keeping requirements, 

Research. 

■ For the reasons stated in the preamble, 

the Department of Homeland Security 

adds 6 CFR part 46 as set forth at the 

end of the common preamble of this 

document. 

PART 46—PROTECTION OF HUMAN 

SUBJECTS 

Sec. 

46.101 To what does this policy apply? 

46.102 Definitions for purposes of this 

policy. 

46.103 Assuring compliance with this 

policy—research conducted or supported 

by any Federal department or agency. 

46.104 Exempt research. 

46.105 [Reserved] 

46.106 [Reserved] 

46.107 IRB membership. 

46.108 IRB functions and operations. 

46.109 IRB review of research. 

46.110 Expedited review procedures for 

certain kinds of research involving no 

more than minimal risk, and for minor 

changes in approved research. 

46.111 Criteria for IRB approval of research. 

46.112 Review by institution. 

46.113 Suspension or termination of IRB 

approval of research. 

46.114 Cooperative research. 

46.115 IRB records. 

46.116 General requirements for informed 

consent. 

46.117 Documentation of informed consent. 

46.118 Applications and proposals lacking 

definite plans for involvement of human 

subjects. 

46.119 Research undertaken without the 

intention of involving human subjects. 

46.120 Evaluation and disposition of 

applications and proposals for research 

to be conducted or supported by a 

Federal department or agency. 

46.121 [Reserved] 

46.122 Use of Federal funds. 

46.123 Early termination of research 

support: Evaluation of applications and 

proposals. 

46.124 Conditions. 

Authority: 5 U.S.C. 301; Pub. L. 107–296, 

sec. 102, 306(c); Pub. L. 108–458, sec. 8306. 

Reginald Brothers, 

Under Secretary for Science and Technology, 

DHS. 

DEPARTMENT OF AGRICULTURE 

List of Subjects in 7 CFR Part 1c 

Human research subjects, Reporting 

and record-keeping requirements, 

Research. 

■ For the reasons stated in the preamble, 

the Department of Agriculture revises 7 

CFR part 1c as set forth at the end of the 

common preamble of this document. 

PART 1c—PROTECTION OF HUMAN 

SUBJECTS 

Sec. 

1c.101 To what does this policy apply? 

1c.102 Definitions for purposes of this 

policy. 

1c.103 Assuring compliance with this 

policy—research conducted or supported 

by any Federal department or agency. 

1c.104 Exempt research. 

1c.105 [Reserved] 

1c.106 [Reserved] 

1c.107 IRB membership. 

1c.108 IRB functions and operations. 

1c.109 IRB review of research. 

1c.110 Expedited review procedures for 

certain kinds of research involving no 

more than minimal risk, and for minor 

changes in approved research. 

1c.111 Criteria for IRB approval of research. 

1c.112 Review by institution. 

1c.113 Suspension or termination of IRB 

approval of research. 

1c.114 Cooperative research. 

1c.115 IRB records. 

1c.116 General requirements for informed 

consent. 

1c.117 Documentation of informed consent. 

1c.118 Applications and proposals lacking 

definite plans for involvement of human 

subjects. 

1c.119 Research undertaken without the 

intention of involving human subjects. 

1c.120 Evaluation and disposition of 

applications and proposals for research 

to be conducted or supported by a 

Federal department or agency. 

1c.121 [Reserved] 

1c.122 Use of Federal funds. 

1c.123 Early termination of research 

support: Evaluation of applications and 

proposals. 

1c.124 Conditions. 

Authority: 5 U.S.C. 301; 42 U.S.C. 300v– 

1(b). 

Ann M. Bartuska, 

Acting Under Secretary for Research, 

Education, and Economics, USDA. 

DEPARTMENT OF ENERGY 

List of Subjects in 10 CFR Part 745 

10 CFR Part 745 

Human research subjects, Reporting 

and record-keeping requirements, 

Research. 

■ For the reasons stated in the preamble, 

the Department of Energy revises 10 

CFR part 745 as set forth at the end of 

the common preamble of this document. 

PART 745—PROTECTION OF HUMAN 

SUBJECTS 

Sec. 

745.101 To what does this policy apply? 

745.102 Definitions for purposes of this 

policy. 

745.103 Assuring compliance with this 

policy—research conducted or supported 

by any Federal department or agency. 

745.104 Exempt research. 

745.105 [Reserved] 

745.106 [Reserved] 

745.107 IRB membership. 

745.108 IRB functions and operations. 

745.109 IRB review of research. 

745.110 Expedited review procedures for 

certain kinds of research involving no 

more than minimal risk, and for minor 

changes in approved research. 

745.111 Criteria for IRB approval of 

research. 

745.112 Review by institution. 

745.113 Suspension or termination of IRB 

approval of research. 

745.114 Cooperative research. 

745.115 IRB records. 

745.116 General requirements for informed 

consent. 

745.117 Documentation of informed 

consent. 

745.118 Applications and proposals lacking 

definite plans for involvement of human 

subjects. 

745.119 Research undertaken without the 

intention of involving human subjects. 

745.120 Evaluation and disposition of 

applications and proposals for research 

to be conducted or supported by a 

Federal department or agency. 

745.121 [Reserved] 

745.122 Use of Federal funds. 

745.123 Early termination of research 

support: Evaluation of applications and 

proposals. 

745.124 Conditions. 

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7270 Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 

Authority: 5 U.S.C. 301; 42 U.S.C. 7254; 42 

U.S.C. 300v–1(b). 

Elizabeth Sherwood-Randall, 

Deputy Secretary of Energy. 

NATIONAL AERONAUTICS AND 

SPACE ADMINISTRATION 

List of Subjects in 14 CFR Part 1230 

14 CFR Part 1230 

Human research subjects, Reporting 

and record-keeping requirements, 

Research. 

■ For the reasons stated in the preamble, 

the National Aeronautics and Space 

Administration revises 14 CFR part 

1230 as set forth at the end of the 

common preamble of this document. 

PART 1230—PROTECTION OF HUMAN 

SUBJECTS 

Sec. 

1230.101 To what does this policy apply? 

1230.102 Definitions for purposes of this 

policy. 

1230.103 Assuring compliance with this 

policy—research conducted or supported 

by any Federal department or agency. 

1230.104 Exempt research. 

1230.105 [Reserved] 

1230.106 [Reserved] 

1230.107 IRB membership. 

1230.108 IRB functions and operations. 

1230.109 IRB review of research. 

1230.110 Expedited review procedures for 

certain kinds of research involving no 

more than minimal risk, and for minor 

changes in approved research. 

1230.111 Criteria for IRB approval of 

research. 

1230.112 Review by institution. 

1230.113 Suspension or termination of IRB 

approval of research. 

1230.114 Cooperative research. 

1230.115 IRB records. 

1230.116 General requirements for 

informed consent. 

1230.117 Documentation of informed 

consent. 

1230.118 Applications and proposals 

lacking definite plans for involvement of 

human subjects. 

1230.119 Research undertaken without the 

intention of involving human subjects. 

1230.120 Evaluation and disposition of 

applications and proposals for research 

to be conducted or supported by a 

Federal department or agency. 

1230.121 [Reserved] 

1230.122 Use of Federal funds. 

1230.123 Early termination of research 

support: Evaluation of applications and 

proposals. 

1230.124 Conditions. 

Authority: 5 U.S.C. 301;42 U.S.C. 300v– 

1(b). 

James D. Polk, 

Chief Health and Medical Officer, NASA. 

DEPARTMENT OF COMMERCE 

List of Subjects in 15 CFR Part 27 

15 CFR Part 27 

Human research subjects, Reporting 

and record-keeping requirements, 

Research. 

■ For the reasons stated in the preamble, 

the Department of Commerce revises 15 

CFR part 27 as set forth at the end of the 

common preamble of this document. 

PART 27—PROTECTION OF HUMAN 

SUBJECTS 

Sec. 

27.101 To what does this policy apply? 

27.102 Definitions for purposes of this 

policy. 

27.103 Assuring compliance with this 

policy—research conducted or supported 

by any Federal department or agency. 

27.104 Exempt research. 

27.105 [Reserved] 

27.106 [Reserved] 

27.107 IRB membership. 

27.108 IRB functions and operations. 

27.109 IRB review of research. 

27.110 Expedited review procedures for 

certain kinds of research involving no 

more than minimal risk, and for minor 

changes in approved research. 

27.111 Criteria for IRB approval of research. 

27.112 Review by institution. 

27.113 Suspension or termination of IRB 

approval of research. 

27.114 Cooperative research. 

27.115 IRB records. 

27.116 General requirements for informed 

consent. 

27.117 Documentation of informed consent. 

27.118 Applications and proposals lacking 

definite plans for involvement of human 

subjects. 

27.119 Research undertaken without the 

intention of involving human subjects. 

27.120 Evaluation and disposition of 

applications and proposals for research 

to be conducted or supported by a 

Federal department or agency. 

27.121 [Reserved] 

27.122 Use of Federal funds. 

27.123 Early termination of research 

support: Evaluation of applications and 

proposals. 

27.124 Conditions. 

Authority: 5 U.S.C. 301; 42 U.S.C. 300v– 

1(b). 

James Hock, 

Chief of Staff, Department of Commerce. 

SOCIAL SECURITY 

ADMINISTRATION 

List of Subjects in 20 CFR Part 431 

20 CFR Part 431 

Human research subjects, Reporting 

and record-keeping requirements, 

Research. 

■ For the reasons stated in the preamble, 

the Social Security Administration adds 

20 CFR part 431 as set forth at the end 

of the common preamble of this 

document. 

PART 431—PROTECTION OF HUMAN 

SUBJECTS 

Sec. 

431.101 To what does this policy apply? 

431.102 Definitions for purposes of this 

policy. 

431.103 Assuring compliance with this 

policy—research conducted or supported 

by any Federal department or agency. 

431.104 Exempt research. 

431.105 [Reserved] 

431.106 [Reserved] 

431.107 IRB membership. 

431.108 IRB functions and operations. 

431.109 IRB review of research. 

431.110 Expedited review procedures for 

certain kinds of research involving no 

more than minimal risk, and for minor 

changes in approved research. 

431.111 Criteria for IRB approval of 

research. 

431.112 Review by institution. 

431.113 Suspension or termination of IRB 

approval of research. 

431.114 Cooperative research. 

431.115 IRB records. 

431.116 General requirements for informed 

consent. 

431.117 Documentation of informed 

consent. 

431.118 Applications and proposals lacking 

definite plans for involvement of human 

subjects. 

431.119 Research undertaken without the 

intention of involving human subjects. 

431.120 Evaluation and disposition of 

applications and proposals for research 

to be conducted or supported by a 

Federal department or agency. 

431.121 [Reserved] 

431.122 Use of Federal funds. 

431.123 Early termination of research 

support: Evaluation of applications and 

proposals. 

431.124 Conditions. 

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Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 7271 

Authority: 5 U.S.C. 301; 42 U.S.C. 289(a). 

Carolyn W. Colvin, 

Acting Commissioner of Social Security. 

AGENCY FOR INTERNATIONAL 

DEVELOPMENT 

List of Subjects in 22 CFR Part 225 

22 CFR Part 225 

Human research subjects, Reporting 

and record-keeping requirements, 

Research. 

■ For the reasons stated in the preamble, 

the Agency for International 

Development revises 22 CFR part 225 as 

set forth at the end of the common 

preamble of this document. 

PART 225—PROTECTION OF HUMAN 

SUBJECTS 

Sec. 

225.101 To what does this policy apply? 

225.102 Definitions for purposes of this 

policy. 

225.103 Assuring compliance with this 

policy—research conducted or supported 

by any Federal department or agency. 

225.104 Exempt research. 

225.105 [Reserved] 

225.106 [Reserved] 

225.107 IRB membership. 

225.108 IRB functions and operations. 

225.109 IRB review of research. 

225.110 Expedited review procedures for 

certain kinds of research involving no 

more than minimal risk, and for minor 

changes in approved research. 

225.111 Criteria for IRB approval of 

research. 

225.112 Review by institution. 

225.113 Suspension or termination of IRB 

approval of research. 

225.114 Cooperative research. 

225.115 IRB records. 

225.116 General requirements for informed 

consent. 

225.117 Documentation of informed 

consent. 

225.118 Applications and proposals lacking 

definite plans for involvement of human 

subjects. 

225.119 Research undertaken without the 

intention of involving human subjects. 

225.120 Evaluation and disposition of 

applications and proposals for research 

to be conducted or supported by a 

Federal department or agency. 

225.121 [Reserved] 

225.122 Use of Federal funds. 

225.123 Early termination of research 

support: Evaluation of applications and 

proposals. 

225.124 Conditions. 

Authority: 5 U.S.C. 301; 42 U.S.C. 300v– 

1(b), unless otherwise noted. 

Irene Koek, 

Acting Deputy Assistant Administrator for 

Global Health, U.S. Agency for International 

Development. 

DEPARTMENT OF HOUSING AND 

URBAN DEVELOPMENT 

List of Subjects in 24 CFR Part 60 

24 CFR Part 60 

Human research subjects, Reporting 

and record-keeping requirements, 

Research. 

■ For the reasons stated in the preamble, 

the Department of Housing and Urban 

Development revises 24 CFR part 60 as 

set forth at the end of the common 

preamble of this document. 

PART 60—PROTECTION OF HUMAN 

SUBJECTS 

Sec. 

60.101 To what does this policy apply? 

60.102 Definitions for purposes of this 

policy. 

60.103 Assuring compliance with this 

policy—research conducted or supported 

by any Federal department or agency. 

60.104 Exempt research. 

60.105 [Reserved] 

60.106 [Reserved] 

60.107 IRB membership. 

60.108 IRB functions and operations. 

60.109 IRB review of research. 

60.110 Expedited review procedures for 

certain kinds of research involving no 

more than minimal risk, and for minor 

changes in approved research. 

60.111 Criteria for IRB approval of research. 

60.112 Review by institution. 

60.113 Suspension or termination of IRB 

approval of research. 

60.114 Cooperative research. 

60.115 IRB records. 

60.116 General requirements for informed 

consent. 

60.117 Documentation of informed consent. 

60.118 Applications and proposals lacking 

definite plans for involvement of human 

subjects. 

60.119 Research undertaken without the 

intention of involving human subjects. 

60.120 Evaluation and disposition of 

applications and proposals for research 

to be conducted or supported by a 

Federal department or agency. 

60.121 [Reserved] 

60.122 Use of Federal funds. 

60.123 Early termination of research 

support: Evaluation of applications and 

proposals. 

60.124 Conditions. 

Authority: 5 U.S.C. 301; 42 U.S.C. 300v– 

1(b) and 3535(d). 

Katherine M. O’Regan, 

Assistant Secretary for Policy Development 

and Research, Department of Housing and 

Urban Development. 

DEPARTMENT OF LABOR 

List of Subjects in 29 CFR Part 21 

29 CFR Part 21 

Human research subjects, Reporting 

and record-keeping requirements, 

Research. 

■ For the reasons stated in the preamble, 

the Department of Labor adds 29 CFR 

part 21 as set forth at the end of the 

common preamble of this document. 

PART 21—PROTECTION OF HUMAN 

SUBJECTS 

Sec. 

21.101 To what does this policy apply? 

21.102 Definitions for purposes of this 

policy. 

21.103 Assuring compliance with this 

policy—research conducted or supported 

by any Federal department or agency. 

21.104 Exempt research. 

21.105 [Reserved] 

21.106 [Reserved] 

21.107 IRB membership. 

21.108 IRB functions and operations. 

21.109 IRB review of research. 

21.110 Expedited review procedures for 

certain kinds of research involving no 

more than minimal risk, and for minor 

changes in approved research. 

21.111 Criteria for IRB approval of research. 

21.112 Review by institution. 

21.113 Suspension or termination of IRB 

approval of research. 

21.114 Cooperative research. 

21.115 IRB records. 

21.116 General requirements for informed 

consent. 

21.117 Documentation of informed consent. 

21.118 Applications and proposals lacking 

definite plans for involvement of human 

subjects. 

21.119 Research undertaken without the 

intention of involving human subjects. 

21.120 Evaluation and disposition of 

applications and proposals for research 

to be conducted or supported by a 

Federal department or agency. 

21.121 [Reserved] 

21.122 Use of Federal funds. 

21.123 Early termination of research 

support: Evaluation of applications and 

proposals. 

21.124 Conditions. 

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7272 Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 

Authority: 5 U.S.C. 301; 29 U.S.C. 551. 

Christopher P. Lu, 

Deputy Secretary of Labor. 

DEPARTMENT OF DEFENSE 

List of Subjects in 32 CFR Part 219 

32 CFR Part 219 

Human research subjects, Reporting 

and record-keeping requirements, 

Research. 

■ For the reasons stated in the preamble, 

the Department of Defense revises 32 

CFR part 219 as set forth at the end of 

the common preamble of this document. 

PART 219—PROTECTION OF HUMAN 

SUBJECTS 

Sec. 

219.101 To what does this policy apply? 

219.102 Definitions for purposes of this 

policy. 

219.103 Assuring compliance with this 

policy—research conducted or supported 

by any Federal department or agency. 

219.104 Exempt research. 

219.105 [Reserved] 

219.106 [Reserved] 

219.107 IRB membership. 

219.108 IRB functions and operations. 

219.109 IRB review of research. 

219.110 Expedited review procedures for 

certain kinds of research involving no 

more than minimal risk, and for minor 

changes in approved research. 

219.111 Criteria for IRB approval of 

research. 

219.112 Review by institution. 

219.113 Suspension or termination of IRB 

approval of research. 

219.114 Cooperative research. 

219.115 IRB records. 

219.116 General requirements for informed 

consent. 

219.117 Documentation of informed 

consent. 

219.118 Applications and proposals lacking 

definite plans for involvement of human 

subjects. 

219.119 Research undertaken without the 

intention of involving human subjects. 

219.120 Evaluation and disposition of 

applications and proposals for research 

to be conducted or supported by a 

Federal department or agency. 

219.121 [Reserved] 

219.122 Use of Federal funds. 

219.123 Early termination of research 

support: Evaluation of applications and 

proposals. 

219.124 Conditions. 

Authority: 5 U.S.C. 301; 42 U.S.C. 300v– 

1(b). 

Stephen P. Welby, 

Assistant Secretary of Defense (Research and 

Engineering). 

DEPARTMENT OF EDUCATION 

List of Subjects in 34 CFR Part 97 

Human research subjects, Reporting 

and record-keeping requirements, 

Research. 

■ For the reasons stated in the preamble, 

the Department of Education amends 34 

CFR part 97 as follows: 

PART 97—PROTECTION OF HUMAN 

SUBJECTS 

■ 1. The authority citation for part 97 

continues to read as follows: 

Authority: 5 U.S.C. 301; 20 U.S.C. 1221e– 

3, 3474; 42 U.S.C. 300v–1(b). 

■ 2. Subpart A is revised as set forth at 

the end of the common preamble of this 

document. 

Subpart A—Federal Policy for the 

Protection of Human Subjects (Basic 

ED Policy for Protection of Human 

Research Subjects) 

Sec. 

97.101 To what does this policy apply? 

97.102 Definitions for purposes of this 

policy. 

97.103 Assuring compliance with this 

policy—research conducted or supported 

by any Federal department or agency. 

97.104 Exempt research. 

97.105 [Reserved] 

97.106 [Reserved] 

97.107 IRB membership. 

97.108 IRB functions and operations. 

97.109 IRB review of research. 

97.110 Expedited review procedures for 

certain kinds of research involving no 

more than minimal risk, and for minor 

changes in approved research. 

97.111 Criteria for IRB approval of research. 

97.112 Review by institution. 

97.113 Suspension or termination of IRB 

approval of research. 

97.114 Cooperative research. 

97.115 IRB records. 

97.116 General requirements for informed 

consent. 

97.117 Documentation of informed consent. 

97.118 Applications and proposals lacking 

definite plans for involvement of human 

subjects. 

97.119 Research undertaken without the 

intention of involving human subjects. 

97.120 Evaluation and disposition of 

applications and proposals for research 

to be conducted or supported by a 

Federal department or agency. 

97.121 [Reserved] 

97.122 Use of Federal funds. 

97.123 Early termination of research 

support: Evaluation of applications and 

proposals. 

97.124 Conditions. 

John B. King Jr., 

Secretary of Education. 

DEPARTMENT OF VETERANS 

AFFAIRS 

List of Subjects in 38 CFR Part 16 

38 CFR Part 16 

Human research subjects, Reporting 

and record-keeping requirements, 

Research. 

■ For the reasons stated in the preamble, 

the Department of Veterans Affairs 

revises 38 CFR part 16 as set forth at the 

end of the common preamble of this 

document. 

PART 16—PROTECTION OF HUMAN 

SUBJECTS 

Sec. 

16.101 To what does this policy apply? 

16.102 Definitions for purposes of this 

policy. 

16.103 Assuring compliance with this 

policy—research conducted or supported 

by any Federal department or agency. 

16.104 Exempt research. 

16.105 [Reserved] 

16.106 [Reserved] 

16.107 IRB membership. 

16.108 IRB functions and operations. 

16.109 IRB review of research. 

16.110 Expedited review procedures for 

certain kinds of research involving no 

more than minimal risk, and for minor 

changes in approved research. 

16.111 Criteria for IRB approval of research. 

16.112 Review by institution. 

16.113 Suspension or termination of IRB 

approval of research. 

16.114 Cooperative research. 

16.115 IRB records. 

16.116 General requirements for informed 

consent. 

16.117 Documentation of informed consent. 

16.118 Applications and proposals lacking 

definite plans for involvement of human 

subjects. 

16.119 Research undertaken without the 

intention of involving human subjects. 

16.120 Evaluation and disposition of 

applications and proposals for research 

to be conducted or supported by a 

Federal department or agency. 

16.121 [Reserved] 

16.122 Use of Federal funds. 

16.123 Early termination of research 

support: Evaluation of applications and 

proposals. 

16.124 Conditions. 

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Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 7273 

Authority: 5 U.S.C. 301; 38 U.S.C. 501, 

7331, 7334; 42 U.S.C. 300v–1(b). 

Gina S. Farrisee, 

Deputy Chief of Staff, U.S. Department of 

Veterans Affairs. 

ENVIRONMENTAL PROTECTION 

AGENCY 

List of Subjects in 40 CFR Part 26 

40 CFR Part 26 

Human research subjects, Reporting 

and record-keeping requirements, 

Research. 

■ For the reasons stated in the preamble, 

the Environmental Protection Agency 

amends 40 CFR part 26 as follows: 

PART 26—PROTECTION OF HUMAN 

SUBJECTS 

■ 1. The authority citation for part 26 

continues to read as follows: 

Authority: 5 U.S.C. 301; 7 U.S.C. 136a(a) 

and 136w(a)(1); 21 U.S.C. 346a(e)(1)(C); sec. 

201, Pub. L. 109–54, 119 Stat. 531; and 42 

U.S.C. 300v–1(b). 

■ 2. Subpart A is revised as set forth at 

the end of the common preamble of this 

document. 

Subpart A—Basic EPA Policy for 

Protection of Subjects in Human 

Research Conducted or Supported by 

EPA 

Sec. 

26.101 To what does this policy apply? 

26.102 Definitions for purposes of this 

policy. 

26.103 Assuring compliance with this 

policy—research conducted or supported 

by any Federal department or agency. 

26.104 Exempt research. 

26.105 [Reserved] 

26.106 [Reserved] 

26.107 IRB membership. 

26.108 IRB functions and operations. 

26.109 IRB review of research. 

26.110 Expedited review procedures for 

certain kinds of research involving no 

more than minimal risk, and for minor 

changes in approved research. 

26.111 Criteria for IRB approval of research. 

26.112 Review by institution. 

26.113 Suspension or termination of IRB 

approval of research. 

26.114 Cooperative research. 

26.115 IRB records. 

26.116 General requirements for informed 

consent. 

26.117 Documentation of informed consent. 

26.118 Applications and proposals lacking 

definite plans for involvement of human 

subjects. 

26.119 Research undertaken without the 

intention of involving human subjects. 

26.120 Evaluation and disposition of 

applications and proposals for research 

to be conducted or supported by a 

Federal department or agency. 

26.121 [Reserved] 

26.122 Use of Federal funds. 

26.123 Early termination of research 

support: Evaluation of applications and 

proposals. 

26.124 Conditions. 

A. Stanley Meiburg, 

Acting Deputy Administrator, Environmental 

Protection Agency. 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

List of Subjects in 45 CFR Part 46 

45 CFR Part 46 

Human research subjects, Reporting 

and record-keeping requirements, 

Research. 

■ For the reasons stated in the preamble, 

the Department of Health and Human 

Services amends 45 CFR part 46 as 

follows: 

PART 46—PROTECTION OF HUMAN 

SUBJECTS 

■ 1. The authority citation for part 46 is 

revised to read as follows: 

Authority: 5 U.S.C. 301; 42 U.S.C. 289(a); 

42 U.S.C. 300v–1(b). 

■ 2. Subpart A is revised as set forth at 

the end of the common preamble of this 

document. 

Subpart A—Basic HHS Policy for 

Protection of Human Research 

Subjects 

Sec. 

46.101 To what does this policy apply? 

46.102 Definitions for purposes of this 

policy. 

46.103 Assuring compliance with this 

policy—research conducted or supported 

by any Federal department or agency. 

46.104 Exempt research. 

46.105 [Reserved] 

46.106 [Reserved] 

46.107 IRB membership. 

46.108 IRB functions and operations. 

46.109 IRB review of research. 

46.110 Expedited review procedures for 

certain kinds of research involving no 

more than minimal risk, and for minor 

changes in approved research. 

46.111 Criteria for IRB approval of research. 

46.112 Review by institution. 

46.113 Suspension or termination of IRB 

approval of research. 

46.114 Cooperative research. 

46.115 IRB records. 

46.116 General requirements for informed 

consent. 

46.117 Documentation of informed consent. 

46.118 Applications and proposals lacking 

definite plans for involvement of human 

subjects. 

46.119 Research undertaken without the 

intention of involving human subjects. 

46.120 Evaluation and disposition of 

applications and proposals for research 

to be conducted or supported by a 

Federal department or agency. 

46.121 [Reserved] 

46.122 Use of Federal funds. 

46.123 Early termination of research 

support: Evaluation of applications and 

proposals. 

46.124 Conditions. 

Sylvia M. Burwell, 

Secretary, HHS. 

NATIONAL SCIENCE FOUNDATION 

List of Subjects in 45 CFR Part 690 

45 CFR Part 690 

Human research subjects, Reporting 

and record-keeping requirements, 

Research. 

■ For the reasons stated in the preamble, 

the National Science Foundation revises 

45 CFR part 690 as set forth at the end 

of the common preamble of this 

document. 

PART 690—PROTECTION OF HUMAN 

SUBJECTS 

Sec. 

690.101 To what does this policy apply? 

690.102 Definitions for purposes of this 

policy. 

690.103 Assuring compliance with this 

policy—research conducted or supported 

by any Federal department or agency. 

690.104 Exempt research. 

690.105 [Reserved] 

690.106 [Reserved] 

690.107 IRB membership. 

690.108 IRB functions and operations. 

690.109 IRB review of research. 

690.110 Expedited review procedures for 

certain kinds of research involving no 

more than minimal risk, and for minor 

changes in approved research. 

690.111 Criteria for IRB approval of 

research. 

690.112 Review by institution. 

690.113 Suspension or termination of IRB 

approval of research. 

690.114 Cooperative research. 

690.115 IRB records. 

690.116 General requirements for informed 

consent. 

690.117 Documentation of informed 

consent. 

690.118 Applications and proposals lacking 

definite plans for involvement of human 

subjects. 

690.119 Research undertaken without the 

intention of involving human subjects. 

690.120 Evaluation and disposition of 

applications and proposals for research 

to be conducted or supported by a 

Federal department or agency. 

690.121 [Reserved] 

690.122 Use of Federal funds. 

690.123 Early termination of research 

support: Evaluation of applications and 

proposals. 

690.124 Conditions. 

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7274 Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations 

Authority: 5 U.S.C. 301; 42 U.S.C. 300v– 

1(b). 

Lawrence Rudolph, 

General Counsel, National Science 

Foundation. 

DEPARTMENT OF 

TRANSPORTATION 

List of Subjects in 49 CFR Part 11 

49 CFR Part 11 

Human research subjects, Reporting 

and record-keeping requirements, 

Research. 

■ For the reasons stated in the preamble, 

the Department of Transportation 

revises 49 CFR part 11 as set forth at the 

end of the common preamble of this 

document. 

PART 11—PROTECTION OF HUMAN 

SUBJECTS 

Sec. 

11.101 To what does this policy apply? 

11.102 Definitions for purposes of this 

policy. 

11.103 Assuring compliance with this 

policy—research conducted or supported 

by any Federal department or agency. 

11.104 Exempt research. 

11.105 [Reserved] 

11.106 [Reserved] 

11.107 IRB membership. 

11.108 IRB functions and operations. 

11.109 IRB review of research. 

11.110 Expedited review procedures for 

certain kinds of research involving no 

more than minimal risk, and for minor 

changes in approved research. 

11.111 Criteria for IRB approval of research. 

11.112 Review by institution. 

11.113 Suspension or termination of IRB 

approval of research. 

11.114 Cooperative research. 

11.115 IRB records. 

11.116 General requirements for informed 

consent. 

11.117 Documentation of informed consent. 

11.118 Applications and proposals lacking 

definite plans for involvement of human 

subjects. 

11.119 Research undertaken without the 

intention of involving human subjects. 

11.120 Evaluation and disposition of 

applications and proposals for research 

to be conducted or supported by a 

Federal department or agency. 

11.121 [Reserved] 

11.122 Use of Federal funds. 

11.123 Early termination of research 

support: Evaluation of applications and 

proposals. 

11.124 Conditions. 

Authority: 5 U.S.C. 301; 42 U.S.C. 300v– 

1(b). 

Anthony R. Foxx, 

Secretary of Transportation. 

[FR Doc. 2017–01058 Filed 1–18–17; 8:45 am] 

BILLING CODE 4150–36–P 

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