Vol. 80 Tuesday, 

No. 173 September 8, 2015 

Part II 

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 Justice 

28 CFR Part 46 


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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 

National Science Foundation 

45 CFR Part 690 

Department of Transportation 

49 CFR Part 11 

Federal Policy for the Protection of Human Subjects; Proposed Rules 


asabaliauskas on DSK5VPTVN1PROD with PROPOSALS
Federal Register / Vol. 80, No. 173 / Tuesday, September 8, 2015 / Proposed Rules 53933 

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 JUSTICE 

28 CFR Part 46 

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 Justice; 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: Notice of proposed rulemaking. 

SUMMARY: The departments and agencies 

listed in this document propose 

revisions to modernize, strengthen, and 

make more effective the Federal Policy 

for the Protection of Human Subjects 

that was promulgated as a Common 

Rule in 1991. This NPRM seeks 

comment on proposals to better protect 

human subjects involved in research, 

while facilitating valuable research and 

reducing burden, delay, and ambiguity 

for investigators. This proposed rule is 

an effort to modernize, simplify, and 

enhance the current system of oversight. 

The participating departments and 

agencies propose these revisions to the 

human subjects regulations because 

they believe these changes would 

strengthen protections for research 

subjects while facilitating important 

research. 

DATES: To be assured consideration, 

comments must be received at one of 

the addresses provided below, no later 

than 5 p.m. on December 7, 2015. 

ADDRESSES: You may submit comments, 

identified by docket ID number HHS– 

OPHS–2015–0008, by one of the 

following methods: 

• Federal eRulemaking Portal:http://

www.regulations.gov. Enter the above 

docket ID number in the ‘‘Enter 

Keyword or ID’’ field and click on 

‘‘Search.’’ On the next Web page, click 

on ‘‘Submit a Comment’’ action and 

follow the instructions. 

• Mail/Hand delivery/Courier [For 

paper, disk, or CD–ROM submissions] 

to: Jerry Menikoff, M.D., J.D., OHRP, 

1101 Wootton Parkway, Suite 200, 

Rockville, MD 20852. 

Comments received, including any 

personal information, will be posted 

without change to http://

www.regulations.gov. 

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: 

Executive Summary 

Purpose of the Regulatory Action 

Summary of the Major Provisions of the 

Proposed Regulatory Actions 

Estimated Costs and Benefits 

I. The Rationale for Modernizing the 

Common Rule 

A. The Changing Nature of Research 

B. Public Comments, Expert Advice, 

Stakeholder Dialogue 

C. Guiding Principles for Proposed 

Changes 

1. Question for Public Comment 

D. Organization of the NPRM 

II. Major Proposals To Modernize the 

Common Rule 

A. Proposed Changes to the Scope and 

Applicability of the Regulations 

1. Expanding the Definition of Human 

Subject to Cover Research With Nonidentified Biospecimens (NPRM at 

§§ll.102(e) and ll.101(b)(3)(i)) 

a. NPRM Goals 

b. Current Rule 

c. ANPRM Discussion 

d. NPRM Proposal 

i. Alternative Proposals 

e. What would change in the definition of 

‘‘human subject’’ under the primary 

proposal? 

f. Questions for Public Comment 

2. Explicit Exclusion of Activities From the 

Common Rule 

a. Exclusion of Activities That Are Deemed 

Not Research (NPRM at §ll.101(b)(1)) 

i. Program Improvement Activities (NPRM 

at §ll.101(b)(1)(i)) 

(1) NPRM Proposal 

(2) Questions for Public Comment 

ii. Oral History, Journalism, Biography, and 

Historical Scholarship Activities (NPRM 

at §ll.101(b)(1)(ii)) 

(1) ANPRM Discussion 

(2) NPRM Proposal 

iii. Criminal Justice Activities (NPRM at 

§ll.101(b)(1)(iii)) 

(1) NPRM Proposal 

iv. Quality Assurance and Quality 

Improvement Activities (NPRM at 

§ll.101(b)(1)(iv)) 

(1) NPRM Proposal 

v. Public Health Surveillance (NPRM at 

§ll.101(b)(1)(v)) 

(1) NPRM Proposal 

(2) Question for Public Comment 

vi. Intelligence Surveillance Activities 

(NPRM at §ll.101(b)(1)(vi)) 

(1) NPRM Proposal 

b. Exclusion of Activities That Are LowRisk and Already Subject to Independent 

Controls (NPRM at §ll.101(b)(2)) 

i. NPRM Goals 

ii. ANPRM Discussion 

iii. Educational Tests, Survey Procedures, 

Interview Procedures, or Observation of 

Public Behaviors (NPRM at 

§ll.101(b)(2)(i)) 

(1) NPRM Proposal 

(2) Questions for Public Comment 

iv. Research Involving the Collection or 

Study of Information That Has Been or 


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53934 Federal Register / Vol. 80, No. 173 / Tuesday, September 8, 2015 / Proposed Rules 

Will Be Collected (NPRM at 

§ll.101(b)(2)(ii)) 

(1) Current Rule 

(2) ANPRM Discussion 

(3) NPRM Proposal 

(4) Questions for Public Comment 

v. Research Conducted by a Government 

Agency Using Government-Generated or 

Government-Collected Data (NPRM at 

§ll.101(b)(2)(iii)) 

(1) NPRM Proposal 

(2) Questions for Public Comment 

vi. Certain Activities Covered by HIPAA 

(NPRM at §ll.101(b)(2)(iv)) 

(1) ANPRM Discussion 

(2) NPRM Proposal 

(3) Questions for Public Comment 

c. Applicability of Exclusions to the 

Subparts 

i. Current Rule 

ii. NPRM Proposals 

iii. Questions for Public Comment 

3. Proposed Exemptions (NPRM at 

§ll.104) 

a. Making Exempt Research Determinations 

(NPRM at §ll.104(c)) 

i. NPRM Goal 

ii. Current Rule 

iii. ANPRM Discussion 

iv. NPRM Proposal 

v. Questions for Public Comment 

b. Exemptions Subject to the 

Documentation Requirements of 

§ll.104(c) and No Other Section of the 

Proposed Rule 

i. Research Conducted in Established or 

Commonly Accepted Educational 

Settings (NPRM at §ll.104(d)(1); 

current Rule at §ll.101(b)(1)) 

(1) NPRM Goal 

(2) Current Rule 

(3) NPRM Proposal 

(4) Questions for Public Comment 

ii. Research and Demonstration Projects 

Conducted or Supported by a Federal 

Department or Agency (NPRM at 

§ll.104(d)(2); Current Rule at 

§ll.101(b)(5)) 

(1) NPRM Goal 

(2) Current Rule 

(3) ANPRM Discussion 

(4) NPRM Proposal 

(5) Questions for Public Comment 

iii. Research Involving Benign 

Interventions in Conjunction With the 

Collection of Data fFrom an Adult 

Subject (NPRM at §ll.104(d)(3)) 

(1) NPRM Goal 

(2) Current Rule 

(3) ANPRM Discussion 

(4) NPRM Proposal 

(5) Questions for Public Comment 

iv. Taste and Food Quality Evaluation and 

Consumer Acceptance Studies (NPRM at 

§ll.104(d)(4); Current Rule at 

§ll.101(b)(6)) 

(1) Question for Public Comment 

c. Exemptions Subject to the 

Documentation Requirements of 

§ll.104(c) and the Privacy Safeguards 

Described in §ll.105 

i. Questions for Public Comment 

ii. 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 (NPRM at 

§ll.104(e)(1)) 

(1) NPRM Goals 

(2) Current Rule 

(3) ANPRM Discussion 

(4) NPRM Proposal 

(5). Questions for Public Comment 

iii. Secondary Research Use of Identifiable 

Private Information (NPRM at 

§ll.104(e)(2)) 

(1) NPRM Goal 

(2) Current Rule 

(3) ANPRM Discussion 

(4) NPRM Proposal 

(5) Questions for Public Comment 

d. Exemptions Subject to the 

Documentation Requirements of 

§ll.104(c), the Privacy Safeguards 

Described in §ll.105, Limited IRB 

Review as Described in §ll.111(a)(9), 

and Broad Consent in Accordance With 

§ll.116(c) 

i. NPRM Goals 

ii. Current Rule 

iii. ANPRM Discussion 

iv. NPRM Proposals 

(1) Exemption for the Storage or 

Maintenance of Biospecimens or 

Identifiable Private Information for 

Secondary Research Use (NPRM at 

§ll.104(f)(1)) 

(2) Exemption for Secondary Research Use 

of Biospecimens or Identifiable Private 

Information Where Broad Consent Has 

Been Sought and Obtained (NPRM at 

§ll.104(f)(2)) 

v. Questions for Public Comment 

e. Applicability of Exemptions to the 

Subparts (NPRM at §ll.104(b); Current 

Rule at Footnote 1) 

i. Current Rule 

ii. NPRM Proposals 

ii. Questions for Public Comment 

f. What would change in the exemptions? 

B. Proposed Changes To Obtaining, 

Waiving, and Documenting Informed 

Consent (§§ll.116 andll.117) 

1. Required Elements of Informed Consent 

(NPRM at §ll.116(a), (b)) 

a. NPRM Goal 

b. Current Rule 

c. ANPRM Discussion 

d. NPRM Proposals 

e. What would change? 

f. Question for Public Comment 

2. Broad Consent to the Storage, 

Maintenance and Secondary Research 

Use of Biospecimens and Identifiable 

Private Information (NPRM at 

§ll.116(c), (d)) 

a. NPRM Goal 

b. Current Rule 

c. ANPRM Discussion 

d. NPRM Proposal 

e. What would change? 

f. Questions for Public Comment 

3. Waiver of Informed Consent or 

Documentation of Informed Consent 

(NPRM at §§ll.116(e), (f) and 

ll.117) 

a. NPRM Goals 

b. Current Rule 

c. ANPRM Discussion 

d. NPRM Proposals 

e. What would change? 

f. Questions for Public Comment 

4. Posting of Consent Forms 

a. NPRM Goals 

b. NPRM Proposal 

c. What would change? 

C. Proposed Changes To Protect 

Information and Biospecimens (NPRM at 

§ll.105) 

1. NPRM Goal 

2. Current Rule and Other Regulatory or 

Statutory Requirements 

3. ANPRM Discussion 

4. NPRM Proposals 

5. What would change? 

6. Questions for Public Comment 

D. Harmonization of Agency Guidance 

(NPRM at §ll.101(j)) 

1. NPRM Goal 

2. Current Rule 

3. ANPRM Discussion 

4. NPRM Proposal 

5. What would change? 

6. Question for Public Comment 

E. Cooperative Research (NPRM and 

Current Rule at §ll.114) and Proposal 

To Cover Unaffiliated IRBs Not Operated 

by an Institution Holding a Federalwide 

Assurance (NPRM at §ll.101(a)) 

1. NPRM Goal 

2. Current Rule 

3. Relevant Prior Proposals and 

Discussions 

4. NPRM Proposals 

5. What would change? 

6. Questions for Public Comment 

F. Changes To Promote Effectiveness and 

Efficiency in IRB Operations 

1. Continuing Review of Research (NPRM 

at §ll.109(f); Current Rule at 

§ll.109(e)) 

a. NPRM Goal 

b. Current Rule 

c. ANPRM Discussion 

d. NPRM Proposals 

e. What would change? 

2. Expedited Review Procedures and the 

Definition of ‘‘Minimal Risk’’ (NPRM at 

§§ll.110 and ll.102(j)) 

a. NPRM Goal 

b. Current Rule 

c. ANPRM Discussion 

d. NPRM Proposal 

e. What would change? 

f. Questions for Public Comment 

G. Proposed Changes to IRB Operational 

Requirements 

1. Proposed Criteria for IRB Approval of 

Research (NPRM at §ll.111) 

a. NPRM Goals 

b. Current Rule 

c. ANPRM Discussion 

d. NPRM Proposals 

e. What would change? 

f. Questions for Public Comment 

2. Proposed Revisions To IRB Operations, 

Functions, and Membership 

Requirements 

a. NPRM Goal 

b. Current Rule 

c. NPRM Proposal 

d. What would change? 

e. Question for Public Comment 

H. Other Proposed Changes 

1. Proposal To Extend the Common Rule to 

All Clinical Trials (With Exceptions) 

(NPRM at §ll.101(a)(1)) 

a. NPRM Goals 


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Federal Register / Vol. 80, No. 173 / Tuesday, September 8, 2015 / Proposed Rules 53935 

1 76 FR 44512 (Jul. 26, 2011). 

b. Current Rule 

c. ANPRM Discussion 

d. NPRM Proposal 

e. What Would Change? 

f. Questions for Public Comment 

2. Changes to the Assurance Process 

(NPRM at §§ll.103 and ll.108; 

Current Rule at §ll.103) 

a. NPRM Goal 

b. Current Rule 

c. NPRM Proposals 

d. What would change? 

e. Question for Public Comment 

3. Department or Agency Discretion About 

Applicability of the Policy (NPRM at 

§ll.101(c), (d), (i)) and Discretion 

Regarding Additional Requirements 

Imposed by the Conducting or 

Supporting Department or Agency 

(NPRM and Current Rule at §ll.124) 

a. NPRM Goals 

b. Current Rule 

c. NPRM Proposals 

4. Research Covered by This Policy 

Conducted in Foreign Countries (NPRM 

at §ll.101(h)) 

I. Effective and Compliance Dates of New 

Rule (NPRM at §ll.101(k)) 

1. Effective Dates 

2. Transition Provisions 

a. Research Initiated Prior to the Effective 

Date of This Subpart (NPRM at 

§ll.101(k)(1)) 

b. Use of Prior Collections of Biospecimens 

(NPRM at §ll.101(k)(2)) 

III. Regulatory Impact Analyses 

IV. Environmental Impact 

V. Paperwork Reduction Act 

VI. Summary of Comments Received on the 

2011 Common Rule ANPRM 

VII. 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 (HEW) 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 CFR part 46), often 

referred to as the ‘‘Common Rule’’ for 

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 type 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 for use with human 

biospecimens; and the growing use of 

electronic health data and other digital 

records to enable very large data sets to 

be 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 

unchanged over the last two decades. 

The regulations are codified in each 

department or agency’s title or chapter 

of the Code of Federal Regulations 

(CFR). The Common Rule was based on 

HHS’ regulations, 45 CFR part 46, 

subpart A, and includes identical 

language in the separate regulations of 

each department and agency. 

Although they have not issued the 

Common Rule in regulations, three 

departments and agencies currently 

comply with all subparts of the HHS 

protection of human subjects 

regulations at 45 CFR part 46. These are 

the Central Intelligence Agency (CIA), 

the Department of Homeland Security 

(DHS), and the Social Security 

Administration (SSA). DHS, and SSA 

are joining this proposed rulemaking 

with the intent of codifying the final 

rule in their own agency regulations. 

Pursuant to Executive Order 12333 of 

December 4, 1981, as amended, 

elements of the Intelligence Community 

must comply with the guidelines issued 

by the Department of Health and Human 

Services regarding research on human 

subjects found in 45 CFR part 46. This 

proposed rulemaking does not 

supersede the Executive Order. The 

Office of the Director of National 

Intelligence and the CIA will continue 

to adhere to the HHS guidelines, 

pursuant to the Executive Order, when 

the final rule is implemented. 

DHS, created after issuance of the 

Common Rule, is 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. This 

proposed rulemaking initiates the 

process of promulgating equivalent 

regulations, consistent with statute. 

Once DHS executes a final rule, DHS 

will comply with the DHS regulations as 

the requirements will be equivalent to 

compliance with HHS regulations at 45 

CFR part 46, subpart A. 

SSA was separated from HHS in 1995 

and, pursuant to the transition rules 

provided in Section 106 of title 1 of 

Public Law 103–296, must apply all 

regulations that applied to SSA before 

the separation, absent action by the 

Commissioner. Once the final rule is 

codified in SSA regulations, SSA will 

follow the SSA regulations instead of 

HHS regulations at 45 CFR part 46, 

subpart A. See Public Law 103–296 

§ 106(b), 108 Stat. 1464, 1476. 

Another department is joining this 

proposed rulemaking. The Department 

of Labor (DOL) is not a signatory to the 

current Common Rule, and is joining 

this proposed rulemaking in order to 

promulgate the Common Rule in DOL 

regulations and to apply the regulations 

to human subjects research that DOL 

may conduct or support, pending the 

scope of the final rule. 

Finally, note that there are two 

current Common Rule agencies that are 

not listed as part of this proposed 

rulemaking. The Department of Housing 

and Urban Development (HUD) 

supports this proposal, but due to 

certain statutory prepublication 

requirements governing HUD rules, 

HUD will adopt this proposal through a 

separate rulemaking. The Consumer 

Product Safety Commission (CPSC), 

subject to Commission vote, also 

intends to adopt this proposed rule 

through a separate rulemaking. 

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 advanced notice 

of public rulemaking (ANPRM) to 

request comment on how current 

regulations for protecting human 

subjects who participate in research 

might be modernized and revised to be 

more effective.1 The ANPRM sought 

comment on how to better protect 

human subjects who are involved in 

research while facilitating valuable 

research and reducing burden, delay, 

and ambiguity for investigators. 

Since the publication of the ANPRM, 

science has continued to advance, as 

has the dialogue regarding the changing 

nature of research and the preferred 

balance of protections for research 

participants among the principles of 

respect for persons, beneficence, and 

justice. Important elements of that 

debate have centered on the appropriate 

level of transparency in government and 

medicine and how patient and research 

participant expectations should be 

incorporated into government policies. 


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53936 Federal Register / Vol. 80, No. 173 / Tuesday, September 8, 2015 / Proposed Rules 

2 79 FR 63630 (Oct. 24, 2014). 

3National Institutes of Health. (2014, December 

14). Request for Comments on the Draft NIH Policy 

on the Use of a Single Institutional Review Board 

for Multi-Site Research. See more at: http://

grants.nih.gov/grants/guide/notice-files/NOT-OD15-026.html#sthash.fmjlNRi6.dpuf. Retrieved from 

National Institutes of Health, Office of Extramural 

Research: http://grants.nih.gov/grants/guide/noticefiles/NOT-OD-15-026.html. 

These factors have helped shape the 

development of the regulatory actions 

proposed in this NPRM. 

The proposal also benefits from 

public comments submitted in response 

to more recent policy proposals 

regarding specific topics such as 

informed consent through the Office for 

Human Research Protection (OHRP)’s 

Draft Guidance on Disclosing 

Reasonably Foreseeable Risks in 

Research Evaluating Standards of Care 2

and the use of a single institutional 

review board (IRB) for multi-site 

research studies through the National 

Institutes of Health (NIH)’s Draft Policy 

on the Use of a Single Institutional 

Review Board for Multi-Site Research.3

Finally, the NPRM more thoroughly 

addresses behavioral and social science 

research perspectives and the broader 

types of research conducted or 

otherwise supported by the other 

Common Rule agencies. Similarly, the 

proposal benefits from continuing 

efforts at HHS to harmonize human 

subjects policies, particularly between 

OHRP and the U.S. Food and Drug 

Administration (FDA). 

Summary of the Major Provisions of the 

Proposed Regulatory Action 

The goals of the NPRM are to increase 

human subjects’ ability and opportunity 

to make informed decisions; reduce 

potential for harm and increase justice 

by increasing the uniformity of human 

subject protections in areas such as 

information disclosure risk, coverage of 

clinical trials, and coverage of IRBs; and 

facilitate current and evolving types of 

research that offer promising 

approaches to treating and preventing 

medical and societal problems through 

reduced ambiguity in interpretation of 

the regulations, increased efficiencies in 

the performance of the review system, 

and reduced burdens on researchers that 

do not appear to provide commensurate 

protections to human subjects. It is 

hoped that these changes will also build 

public trust in the research system. 

An example of some major changes 

being proposed that will better protect 

research subjects and help build public 

trust are the rules relating to informed 

consent. With regard to informed 

consent in general (such as consent to 

participating in clinical trials), the rules 

would be significantly tightened to 

make sure that the process becomes 

more meaningful. Consent forms would 

no longer be able to be unduly long 

documents, with the most important 

information often buried and hard to 

find. They would need to give 

appropriate details about the research 

that is most relevant to a person’s 

decision to participate in the study, 

such as information a reasonable person 

would want to know, and present that 

information in a way that highlights the 

key information. In addition, to assure 

that these rules do indeed change 

current practices, there will be a onetime posting requirement for the 

consent forms for clinical trials, so that 

anyone drafting a consent form will do 

so knowing that it will eventually be 

subject to public scrutiny. 

In addition, informed consent would 

generally be required for secondary 

research with a biospecimen (for 

example, part of a blood sample that is 

left over after being drawn for clinical 

purposes), even if the investigator is not 

being given information that would 

enable him or her to identify whose 

biospecimen it is. Such consent would 

not need to be obtained for each specific 

research use of the biospecimen, but 

rather could be obtained using a 

‘‘broad’’ consent form in which a person 

would give consent to future 

unspecified research uses. 

The NPRM also attempts to strengthen 

the effectiveness and efficiency of the 

oversight system by making the level of 

review more proportional to the 

seriousness of the harm or danger to be 

avoided. Research that poses greater risk 

to subjects should receive more 

oversight and deliberation than less 

risky research. The NPRM seeks to 

avoid requirements that do not enhance 

protection and impose burden, which 

can decrease efficiency, waste resources, 

erode trust, and obscure the true ethical 

challenges that require careful 

deliberation and stakeholder input. 

Cumbersome and outdated regulatory 

standards overwhelm and distract 

institutions, IRBs, and investigators in 

ways that stymie efforts to appropriately 

address the real risks and benefits of 

research. 

The result of these types of changes, 

as the NPRM proposes to implement 

them, is that some studies that currently 

require IRB review would now become 

exempt. Some that are currently exempt 

would specifically be declared as 

outside the scope of the regulations 

(‘‘excluded’’), and thus would not 

require any administrative or IRB 

review. Further, in terms of determining 

when a study is exempt, a web-based 

‘‘decision tool’’ will be created. That 

decision tool will provide a 

determination of whether or not a study 

is exempt. That result, so long as the 

tool was provided with accurate 

information, will be presumed by the 

Common Rule agencies to be an 

appropriate determination of exempt 

status. Thus, it is expected that in many 

instances the tool would be used by the 

investigators themselves, thus obviating 

both the need for further review and the 

concern that the institution might be 

subjecting itself to future liability by 

allowing investigators to use the tool. 

For all of the excluded and exempt 

research activities, this NPRM also 

affirms the importance of applying the 

ethical principle of respect for persons, 

in addition to the importance of abiding 

by this principle in fully regulated nonexempt research involving human 

subjects. 

The following list encompasses the 

most significant changes to the Common 

Rule proposed in the NPRM: 

(1) Improve informed consent by 

increasing transparency and by 

imposing stricter new requirements 

regarding the information that must be 

given to prospective subjects, and the 

manner in which it is given to them, to 

better assure that subjects are 

appropriately informed before they 

decide to enroll in a research study. 

(2) Generally require informed 

consent for the use of stored 

biospecimens in secondary research (for 

example, part of a blood sample that is 

left over after being drawn for clinical 

purposes), even if the investigator is not 

being given information that would 

enable him or her to identify whose 

biospecimen it is. That consent would 

generally be obtained by means of broad 

consent (i.e., consent for future, 

unspecified research studies) to the 

storage and eventual research use of 

biospecimens. 

(3) Exclude from coverage under the 

Common Rule certain categories of 

activities that should be deemed not to 

be research, are inherently low risk, or 

where protections similar to those 

usually provided by IRB review are 

separately mandated. 

(4) Add additional categories of 

exempt research to accommodate 

changes in the scientific landscape and 

to better calibrate the level of review to 

the level of risk involved in the 

research. A new process would allow 

studies to be determined to be exempt 

without requiring any administrative or 

IRB review. Certain exempt and all nonexempt research would be required to 

provide privacy safeguards for 

biospecimens and identifiable private 

information. New categories include: 

a. certain research involving benign 

interventions with adult subjects; 


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b. research involving educational 

tests, surveys, interviews or 

observations of public behavior when 

sensitive information may be collected, 

provided that data security and 

information privacy protections policies 

are followed; 

c. secondary research use of 

identifiable private information 

originally collected as part of a nonresearch activity, where notice of such 

possible use was given; 

d. storing or maintaining 

biospecimens and identifiable private 

information for future, unspecified 

secondary research studies, or 

conducting such studies, when a broad 

consent template to be promulgated by 

the Secretary of HHS is used, 

information and biospecimen privacy 

safeguards are followed, and limited IRB 

approval of the consent process used is 

obtained. 

(5) Change the conditions and 

requirements for waiver or alteration of 

consent such that waiver of consent for 

research involving biospecimens 

(regardless of identifiability) will occur 

only in very rare circumstances. 

(6) Mandate that U.S. institutions 

engaged in cooperative research rely on 

a single IRB for that portion of the 

research that takes place within the 

United States, with certain exceptions. 

To encourage the use of IRBs that are 

otherwise not affiliated with or operated 

by an assurance-holding institution 

(‘‘unaffiliated IRBs’’), this NPRM also 

includes a proposal that would hold 

such IRBs directly responsible for 

compliance with the Common Rule. 

(7) Eliminate the continuing review 

requirement for studies that undergo 

expedited review and for studies that 

have completed study interventions and 

are merely analyzing data or involve 

only observational follow-up in 

conjunction with standard clinical care. 

(8) Extend the scope of the policy to 

cover all clinical trials, regardless of 

funding source, conducted at a U.S. 

institution that receives federal funding 

for non-exempt human subjects 

research. 

In sum, the proposed modifications 

described above are designed to 

continue to uphold the ethical 

principles upon which the Common 

Rule is based, as applied to the current 

social, cultural, and technological 

environment. 

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; Public Law 107–296, sec. 

102, 306(c); Public Law 108–458, sec. 

8306. Department of Agriculture, 5 

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

U.S.C. 301; 42 U.S.C. 7254. National 

Aeronautics and Space Administration, 

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

5 U.S.C. 301. Social Security 

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

289(a). Agency for International 

Development, 5 U.S.C. 301. Department 

of Justice, 5 U.S.C. 301; 28 U.S.C. 509– 

510. 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. 

Department of Veterans Affairs, 5 U.S.C. 

301; 38 U.S.C. 501, 7331, 7334. 

Environmental Protection Agency, 5 

U.S.C. 301. Department of Health and 

Human Services, 5 U.S.C. 301; 42 U.S.C. 

289. National Science Foundation, 5 

U.S.C. 301. Department of 

Transportation, 5 U.S.C. 301. 

Estimated Costs and Benefits 

Table 1 summarizes the quantified 

and non-quantified benefits and costs of 

all proposed changes to the Common 

Rule. Over the 2016–2025 period, 

present value benefits of $2,629 million 

and annualized benefits of $308 million 

are estimated using a 3 percent discount 

rate; present value benefits of $2,047 

million and annualized benefits of $291 

million are estimated using a 7 percent 

discount rate. Present value costs of 

$13,342 million and annualized costs of 

$1,564 million are estimated using a 3 

percent discount rate; present value 

costs of $9,605 million and annualized 

costs of $1,367 million are estimated 

using a 7 percent discount rate. Nonquantified benefits include improved 

human subjects protections in clinical 

trials and biospecimen research not 

currently subject to oversight; enhanced 

oversight of research reviewed by 

unaffiliated IRBs; increased uniformity 

in regulatory requirements among 

Common Rule agencies; standardization 

of human subjects protections when 

variation among review IRBs is not 

warranted; revised informed consent 

forms and processes; improved 

protection of biospecimens and 

individually identifiable private 

information; and increased transparency 

of Common Rule agency-supported 

clinical trials to inform the development 

of new consent forms. Non-quantified 

costs include the time needed for 

consultation among Common Rule 

agencies before federal guidance is 

issued; and the time needed by 

investigators to obtain, document, and 

track the permissible uses of 

biospecimens and identifiable private 

information for secondary research use. 

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

Benefits 

Present value of 10 years 

by discount rate 

(millions of 2013 dollars) 

Annualized value over 10 years 

by discount rate 

(millions of 2013 dollars) 

3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Benefits ................................................................................ 2,629 2,047 308 291 

Non-quantified Benefits 

Improved human subjects protections in clinical trials and biospecimen research not currently subject to oversight; enhanced oversight in 

research reviewed by unaffiliated IRBs; increased uniformity in regulatory requirements among Common Rule agencies; ethical benefit of 

respecting an individual’s wishes in how his or her biospecimens are used in future research; standardization of human subjects protections when variation among review IRBs is not warranted; improved informed consent forms and processes; improved protection of biospecimens and individually identifiable private information; better ensuring availability of biospecimens for future research activities; and 

increased transparency of Common Rule-supported clinical trials to inform the development of new consent forms. 

Costs 3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Costs 13,342 9,605 1,564 1,367 

Non-quantified Costs 

Time for consultation among Common Rule agencies before federal guidance is issued; time for investigators to obtain consent for secondary use of biospecimens or identifiable private information. 


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4 Gymrek M et al. ‘‘Identifying personal genomes 

by surname inference’’. Science 339.6117(2013) 0: 

321–324. 

5 Kaufman DJ et al. Public opinion about the 

importance of privacy in biobank research. 

American Journal of Human Genetics 2009 

Nov;85(5):643–654. 

6 Vermeulen E et al. A trial of consent procedures 

for future research with clinically derived biological 

samples. British Journal of Cancer 2009 Nov 

3;101(9):1505–1512. 

7Trinidad SB et al. Research practice and 

participant preferences: The growing gulf. Science 

2011 Jan 21; 331(6015):287–288. 

8Simon CM et al. Active choice but not too 

active: Public perspectives on biobank consent 

models. Genetics in Medicine. 2011 Sep;13(9):821– 

831. 

9Emanuel EJ, Wood A, Fleischman A, et al. 

Oversight of human participants research: 

Identifying problems to evaluate reform proposals. 

Annals of Internal Medicine 2004;141(4):282–291. 

10Maschke K. Human research protections: Time 

for regulatory reform? Hastings Center Report. 2008 

Mar-Apr; 38(2):19–22. 

11 Kim S, Ubel P, De Vries R. Pruning the 

regulatory tree. Nature 2009 Jan 29;457(7229):534– 

535. 

I. The Rationale for Modernizing the 

Common Rule 

A. The Changing Nature of Research 

In the last two decades there has been 

a paradigm shift in how research is 

conducted. Evolving technologies, 

including imaging, mobile technologies, 

and the growth in computing power 

have changed the scale 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. Research has also increased, 

evolved, and diversified in other areas, 

such as national security, crime and 

crime prevention, economics, 

education, and the environment, using a 

wide array of methodologies in the 

social sciences and multidisciplinary 

fields. 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. 

While 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 biospecimens and 

data. Clinical research networks 

connected through electronic health 

records (EHRs) have developed methods 

for extracting clinical data for research 

purposes and are working toward 

integration of research data into EHRs in 

a meaningful way. The overall volume 

of research has increased across the 

board, with growing reliance on 

research networks and multi-site 

studies. Large cohort studies number 

well into the hundreds in the United 

States alone and many collect 

biospecimens and data on the same 

people over many years. Recent trends 

clearly show that 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, and they have 

different expectations than when the 

Common Rule was first established. A 

more participatory research model is 

emerging in social, behavioral, and 

biomedical research, one in which 

potential research subjects and 

communities express their views about 

the value and acceptability of research 

studies. This participatory model has 

emerged alongside a broader trend in 

American society, facilitated by the 

widespread use of social media, in 

which Americans are increasingly 

sharing identifiable personal 

information and expect to be involved 

in decisions about how to further share 

the personal information, including 

health-related information that they 

have voluntarily chosen to provide. In 

many ways, these changes are 

extensions of the fact that over the past 

half-century, rather than being passive 

recipients of health advice and 

treatment, patients have gradually 

become more active in decisions about 

their health and health care. The shift 

from a paternalistic research 

environment to one where participants 

are active partners in biomedical and 

behavioral research is a critical 

development in human subjects 

research. 

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, for example, analyzing 

information obtained from medical 

records, administrative claims data, 

education records, criminal justice 

records, research data shared through 

data repositories, and existing 

biospecimens stored in repositories. 

Risks related to these types of research 

studies are largely informational, not 

physical; that is, harms could result 

primarily from the inappropriate release 

of information and not from the research 

interventions themselves. Nonetheless, 

those harms can be significant. 

New methods, more powerful 

computers, and easy access to large 

administrative datasets produced by 

local, state, and federal governments 

have meant that some types of data that 

formerly were treated as non-identified 

can now be re-identified through 

combining large amounts of information 

from multiple sources. In 2013, 

scientists demonstrated that the identity 

of individual research subjects could be 

ascertained by collating and analyzing 

certain types of genomic data, including 

genomic data from publicly available 

information sources.4 Thus, the 

possibility of fully identifying 

biospecimens and some types of data 

from which direct identifiers had been 

stripped or did not originally include 

direct identifiers has grown, requiring 

vigilance to ensure that such research be 

subject to appropriate oversight. Most 

importantly, people want to be asked for 

their permission. A growing body of 

survey data show that many prospective 

participants want to be asked for their 

consent before their biospecimens are 

used in research.5678

Because of these shifts in science, 

technology, and public engagement 

expectations, a wide range of 

stakeholders have raised concerns about 

the limitations of the existing 

framework, arguing for a re-evaluation 

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.9 10

Dialogue focuses around whether the 

current system: 

• Is sufficiently supportive of a 

participant-centered research model that 

adequately respects participants as 

partners; 

• is not sufficiently risk-based, 

resulting in both over- and underregulation of research activities; 11 12 13


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12Wendler D, Varma S. Minimal risk in pediatric 

research. Journal of Pediatrics. 2006 

Dec;149(6):855–861. 

13 Infectious Disease Society of America. Grinding 

to a halt: The effects of the increasing regulatory 

burden on research and quality improvement 

efforts. Clinical Infectious Diseases 2009 Aug 

1;49(3):328–335. 

14National Research Council. Protecting 

Participants and Facilitating Social and Behavioral 

Sciences Research. Washington, DC: National 

Academies Press, 2003. 

15Anderlik M. Commercial biobanks and genetic 

research: Ethical and legal issues. American Journal 

of Pharmacogenomics 2003;3(3):203–215. 

16Schrag ZM. How talking became human 

subjects research: The Federal regulation of the 

social sciences, 1965–1991. Journal of Policy 

History 2009 January; 21(01):3–37. 

17Hansson MG et al. Should donors be allowed 

to give broad consent to future biobank research? 

Lancet Oncology 2006 Mar; 7(3):266–269. 

18Murphy J et al. Public perspectives on 

informed consent for biobanking. American Journal 

of Public Health 2009 December; 99(12):2128–2134. 

19 Kaufman DJ et al. Public opinion about the 

importance of privacy in biobank research. 

American Journal of Human Genetics 2009 Nov; 

85(5):643–654. 

20Paasche-Orlow MK, Taylor HA, Brancati F. 

Readability standards for informed-consent forms as 

compared with actual readability. New England 

Journal of Medicine 2003 Feb 20; 348(8):721–726. 

21Schneider CE. The Hydra. Hastings Center 

Report 2010 Jul–Aug; 40(4):9–11. 

22Albala I, Doyle M, Appelbaum PS. The 

evolution of consent forms for research: A quarter 

century of changes. IRB Ethics & Human Research 

2010 May–June; 32(3):7–11. 

23Faden RR, Beauchamp TL, Kass NE. Informed 

consent, comparative effectiveness, and learning 

health care. New England Journal of Medicine 2014 

Feb 20;370(8):766–768. 

24 Dziak K et al. Variations among institutional 

review board reviews in a multisite health services 

research study. Health Services Research 2005 Feb; 

40(1):279–290. 

25Lynn J et al. The ethics of using quality 

improvement methods in health care. Annals of 

Internal Medicine 2007 May 1;146(9):666–673. 

26Heimer CA et al. Regulating creativity: 

Research and survival in the IRB iron cage. 

Northwestern University Law Review 2007; 

101:593–641. 

27 Green LA et al. Impact of institutional review 

board practice variation on observational health 

services research. Health Services Research 2006 

Feb; 41(1):214–230. 

28 Jansen LA. Local IRBs, multicenter trials, and 

the ethics of internal amendments. IRB 2005 Jul– 

Aug;27(4):7–11. 

29Schrag Z. Ethical Imperialism. Baltimore, MD: 

Johns Hopkins University Press, 2010. 

30National Research Council of the National 

Academies. (2014). Proposes Revisions to the 

Common Rule for the Protections of Human 

Subjects in the Behavioral and Social Science. The 

National Academies Press, 13–168. Retrieved from 

http://www.nap.edu/catalog/18614/proposedrevisions-to-the-common-rule-for-the-protection-ofhuman-subjects-in-the-behavioral-and-socialsciences. 

31National Institutes of Health. (2014, December 

14). Request for Comments on the Draft NIH Policy 

on the Use of a Single Institutional Review Board 

for Multi-Site Research. See more at: http://

grants.nih.gov/grants/guide/notice-files/NOT-OD15-026.html#sthash.fmjlNRi6.dpuf. Retrieved from 

National Institutes of Health, Office of Extramural 

Research: http://grants.nih.gov/grants/guide/noticefiles/NOT-OD-15-026.html. 

32 79 FR 63630 (Oct. 24, 2014). 

33 78 FR 48163 (Aug 7, 2013). 

34 79 FR 51345 (Aug. 28, 2014). 

• is sufficiently tailored to new and 

emerging areas of research, including 

social and behavioral research and 

research involving the collection and 

use of genetic information; 14 15 16 17 18 19

• effectively informs subjects of 

psychological, informational, or privacy 

risks; 20 21 22

• adequately accounts for the needs 

of a ‘‘learning’’ healthcare system for 

continual quality improvement; 23 24 25

• provides sufficient mechanisms to 

ensure the consistency, quality, and 

accountability of IRB decisionmaking.26 27 28 29

B. Public Comments, Expert Advice, 

Stakeholder Dialogue 

The revisions to the Common Rule 

proposed here are based upon a variety 

of sources of public, stakeholder, and 

expert comments and advice. First, the 

NPRM more thoroughly addresses social 

science and behavioral research 

perspectives, benefiting from guidance 

provided by a National Research 

Council’s consensus report entitled 

‘‘Proposed Revisions to the Common 

Rule for the Protection of Human 

Subjects in the Behavioral and Social 

Sciences.’’ 30 The Report was 

commissioned to ensure that the issues 

related to research involving human 

subjects in social and behavioral 

research would be addressed 

appropriately, in view of what had been 

said in the ANPRM. The Panel made 

numerous recommendations, including 

recommendations about what research 

studies should not undergo review, 

about calibrating the level of IRB review 

to the level of risk, about the desirability 

of privacy and confidentiality 

protections in social and behavioral 

research other than those of the Health 

Insurance Portability and 

Accountability Act of 1996 (HIPAA), 

and about improving informed consent 

by placing greater emphasis on the 

process of consent. The NPRM revises 

some of the ANPRM proposals in light 

of those recommendations. 

Second, since the publication of the 

ANPRM, HHS has continued to solicit 

public comment on a variety of human 

subjects related issues, including 

consent, the use of a single IRB for 

multi-site 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 interest: 

• NIH’s proposal that it expects the 

use of a single IRB for all multi-site 

research studies funded or conducted by 

the NIH.31 Under that proposal, all 

domestic sites of a multi-site study 

would be expected, as a condition of 

NIH funding, to use a single IRB of 

record. In response to this proposal, NIH 

received 165 comments from a range of 

stakeholders, including investigators, 

IRB members, and members of the 

public. The majority of respondents 

were supportive; however concerns 

were raised that it would be expensive 

and time-consuming to identify a single 

IRB for each new multi-site study. 

• OHRP’s draft guidance discussing 

the required content of consent language 

for research done within the standard of 

care.32 In August of 2013, prior to the 

publication of the draft guidance 

document, HHS held a public meeting 

to hear from the community on issues 

raised during the debate surrounding 

the SUPPORT study.33 The public 

meeting and the draft guidance 

document spurred a significant public 

discussion about the nature of the 

information included in informed 

consent forms, specifically how 

investigators should communicate the 

risks of research studies done within the 

standard of care. A total of 93 comments 

were received from bioethicists, 

investigators and research institutions, 

hospitals and physicians, IRB members, 

patient advocates, and industry. 

• To enhance human subject 

protections and reduce regulatory 

burden, OHRP and FDA have been 

actively working to harmonize the 

agencies’ regulatory requirements and 

guidance for human subject research, 

and the FDA’s draft guidance, ‘‘Use of 

Electronic Informed Consent in Clinical 

Investigations’’ was developed as part of 

these efforts. The draft guidance was 

issued in conjunction with an OHRP 

Federal Register notice soliciting 

comment on the whether joint final 

guidance would be useful for the 

regulated community, and whether 

FDA’s draft guidance would be 

appropriate for all research regulated 

under 45 CFR part 46, such as social 

and behavioral research studies. 

Comments were received largely 

favoring joint guidance, but with 

separate sections addressing research 

regulated solely by 45 CFR part 46. 

• NIH’s proposal to promote sharing 

of large-scale human genomic data 

generated from studies funded or 

conducted by NIH.34 The policy lays out 

an expectation that investigators 

generating genomic data get consent for 

future research use of those data. The 

NIH received 107 comments on the 

policy, including many that addressed 


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35The White House, Office of the Press Secretary. 

(2015, January 30). Fact Sheets: President Obama’s 

Precision Medicine Initiative. Retrieved from The 

White House: https://www.whitehouse.gov/thepress-office/2015/01/30/fact-sheet-presidentobama-s-precision-medicine-initiative. 

36Collins FS, Varmus H. A New Initiative on 

Precision Medicine. N Engl J Med 2015 Feb; 

372:793–795. 

37See also http://www.scientificamerican.com/

article/big-precision-medicine-plan-raises-patientprivacy-concerns/, http://www.nih.gov/

precisionmedicine/, and http://www.nih.gov/

precisionmedicine/. 

38National Commission for the Protection of 

Human Subjects of Biomedical and Behavioral 

Research. (1979). Belmont Report. Washington, DC: 

U.S. Department of Health & Human Services. 

Available at: http://www.hhs.gov/ohrp/

humansubjects/guidance/belmont.html. 

39Rothstein MA. Is deidentification sufficient to 

protect health privacy in research? American 

Journal of Bioethics Sep 2010; 10(9): 3–11. 40El Emam K et al. A systematic review of reidentification attacks on health data. PLoS One 

2011; 6(12):e28071. 

the concept of broad consent for 

unspecified future research use. 

There have also been developments 

on the legislative front that have 

informed the discussions leading up to 

this NPRM. In December of 2014, the 

Newborn Screening Saves Lives 

Reauthorization Act of 2014 (Pub. L. 

113–240), was signed into law. The new 

law makes a number of changes relevant 

to the HHS regulations for protecting 

research subjects, including declaring 

that research with newborn dried blood 

spots that is federally funded pursuant 

to the Public Health Service Act is to be 

considered research with human 

subjects, and the provisions allowing 

IRBs to waive consent will not apply. 

These changes will be effective until 

updates to the Common Rule are 

promulgated. In addition, in April of 

2015, the Medicare Access and CHIP 

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 they apply to activities 

involving clinical data registries. 

Most recently, with the launch of the 

President’s Precision Medicine Initiative 

(PMI),35 36 the Federal Government is 

proposing a new research cohort based 

on a model that puts participants at the 

center.37 To understand participant 

preferences the White House and PMI 

agencies have been hosting a series of 

roundtables and public workshops 

about public expectations for how 

participants want to engage in research 

today. These discussions have included 

individuals from many sectors, 

including prospective research 

participants, patients and patient 

advocates, privacy experts, bioethicists, 

academic and industry investigators, 

data scientists, technology innovators, 

healthcare institutions and providers. 

The government has heard many 

perspectives, with much alignment 

around the central tenet that 

participants should be active partners in 

research, and not merely passive 

subjects of research studies. Many are 

seeking a research environment where 

they can contribute to the greater good 

and have transparency into the research 

being conducted using their specimens 

and data. The conversations have 

focused on promoting the ethical 

principles of respect for persons, 

beneficence, and justice, as well as 

promoting other protections, such as 

data security and privacy. 

C. Guiding Principles for Proposed 

Changes 

In 1979, the Belmont Report 38 was 

predicated on three principles that were 

felt to be central to shaping an ethical 

framework for the conduct of research 

with human subjects. The three ethical 

principles are respect for persons, 

beneficence, and justice. Interpretation 

of, and balancing among, these three 

principles played a major role in 

shaping what became the development 

the federal regulations that have become 

known as the Common Rule. The 

preamble to the proposal considers 

whether and how the interpretation of 

these fundamental principles might be 

updated within the context of the 

current technological, social, cultural, 

and ethical environment. That 

consideration involves explicitly 

identifying the interplay among the 

principles. The Common Rule provides 

a framework for how researchers and 

IRBs weigh the often conflicting 

implications of these three principles. 

Beneficence: Individuals who 

participate in research contribute their 

time and may assume significant risks to 

advance the research enterprise. Their 

valuable contributions produce 

knowledge that benefits society at large. 

The Belmont Report describes the 

principle of beneficence as the goal of 

maximizing possible benefits of research 

and minimizing possible harms. This 

principle has been interpreted to, in 

part, emphasize the benefit associated 

with the knowledge that might be 

generated by a research study. 

Evaluating beneficence requires 

examining the likelihood that 

knowledge would be generated, and 

how important or useful that knowledge 

might be to the population. When more 

weight is given to research that has the 

potential to generate a great deal of 

knowledge, particularly knowledge that 

could be very useful to society (such as 

how to treat serious diseases that are 

currently untreatable), policies would 

lean in favor of encouraging and 

facilitating more of that type of research. 

A distinct aspect of the principle of 

beneficence concerns the benefits and 

risks to the specific persons who would 

be participating in a particular research 

study. In the example of a randomized 

clinical trial comparing two treatments 

for a disease, the benefits and risks to 

the subjects in the trial are distinct from 

the possible benefits to society as a 

whole from learning which of the two 

treatments is better. This aspect of 

beneficence assumes that there are 

limits on the risks to which people 

should be subject, even if they are 

willing to undergo those risks. 

Society is in an information age. In all 

facets of one’s life information about 

that person is generated, stored, shared, 

analyzed, and often provides 

tremendous societal value. People share 

information about themselves with large 

numbers of people with the click of a 

button, and this trend of rapid and 

widespread sharing is only likely to 

grow. The increase in concern about 

unauthorized and inadvertent 

information disclosure, in combination 

with newer research techniques that 

increase the volume and nature of 

identifiable data suggest the need for the 

Common Rule to more explicitly 

address data security and privacy 

protection. 

Of particular interest for this proposal 

is addressing risks from inappropriate 

disclosure of information generated 

from biospecimens. One way to protect 

subjects from such risks is to bring 

under oversight research for which risks 

are greater of subjects being identified 

and information being inappropriately 

disclosed. Although it may be difficult 

to identify individuals from their nonidentified biospecimens at present, and 

most investigators would have no need 

to do so unless they were seeking 

additional associated phenotypic 

information, certain technologies and 

methods can be used to generate data 

that are unique to the individual who 

provides the biospecimen, and those 

data can sometimes be combined with 

other data sources to identify the 

individual. In the future, technologies 

will facilitate the use and analysis of 

greater variety and volumes of 

information, and there is a possibility 

that it will be increasingly difficult, if 

not impossible, to make biospecimens 

fully non-identified. In fact, a number of 

reports have already demonstrated the 

ability to re-identify individuals from 

biospecimens or data that lack direct 

identifiers.39 40 As analytic techniques 

become more sophisticated and large 


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datasets become more accessible, it will 

not be possible to guarantee that an 

individual could never be identified 

from a biospecimen or combination or 

data sources, particularly if whole 

genome sequencing is conducted. 

Respect for Persons: The Belmont 

Report describes this concept as the 

notion of treating people as autonomous 

agents, and allowing them to make 

choices based on their own judgments 

and opinions. Inherent in the principle 

of autonomy is the concept of 

transparency—clearly providing the 

information necessary for the research 

participant to make such judgments. 

Transparency requires a clear 

articulation of risks, potential benefits, 

and alternatives to participating in a 

research study, as well as the purpose 

of the research. The principle of 

autonomy encompasses the value 

ascribed to an individual’s right to know 

how one’s data is being used and who 

will have access to it. As such autonomy 

also covers the paired concept of 

protecting those persons who lack the 

capability to make such decisions. 

There are a variety of different ways of 

demonstrating respect for persons. 

Obtaining informed consent from 

human subjects for the collection and 

analysis of information about them is 

one means of implementation of respect 

for persons in the research context. 

Informed consent is designed to ensure 

that each individual approached to 

participate in a research study fully 

understands the risks and potential 

benefits of the study so that they have 

sufficient information to make an 

individualized calculation as to whether 

or not the tradeoffs inherent in 

participation are worth it for them to 

agree to participate. Both the potential 

harms and benefits tend to be greater in 

the context of a clinical trial where 

subjects are randomized to one or 

another of two possible treatments with 

significantly different suspected risks 

than in situations where subjects are 

simply asked to provide, for instance, a 

urine sample. 

Notice, in which individuals are 

informed about how data will be used, 

but explicit consent is not obtained, is 

another means of facilitating 

transparency. Notice is sometimes used 

in the context of informing people about 

how data collected for non-research 

purposes (e.g., when providing 

information in the context of applying 

for public benefits) might be used for 

either general or specific research 

purposes. Another method for showing 

respect for persons with regard to using 

data about them for research could be 

providing them with a right to opt out 

of such research, by, for example, filing 

a form stating such a wish with the 

holder of the data. 

Related, implicit consent might be 

obtained when a research subject 

completes a questionnaire. If they did 

not wish to provide the information, 

presumably they would not be 

answering the questions. The NPRM 

contains a number of provisions that are 

designed to further promote respect for 

participants through increases in both 

transparency and opportunities for 

consent. 

Justice: The Belmont Report describes 

this principle as being about fairness in 

terms of who receives the benefits from 

research and who bears its burdens. One 

of the most direct applications of the 

principle of justice to the Common Rule 

relates to determining who is studied 

and how subjects are selected. This 

principle also is relevant to protection 

of vulnerable populations. In addition, 

the idea of justice is relevant to one of 

core goals of this NPRM: Clarifying 

important aspects of the Common Rule 

where there has been ambiguity in 

interpretation. To the extent that IRBs 

and others interpret the regulations in 

significantly different ways, the result is 

that participants in research can end up 

being treated in very different ways, 

even when they are participating in the 

same study. Thus this idea is embedded 

in all of the NPRM’s attempts to make 

sure that these rules are applied in a 

more uniform and consistent manner. 

The three ethical principles of the 

Belmont Report often cannot all be 

fulfilled at the same time. In many 

cases, it will be necessary to choose 

which of those principles will deserve 

the greatest adherence. This NPRM, at 

its heart, represents an attempt to 

evaluate the weights to be applied to 

each of these three core principles in a 

variety of specific contexts. Giving 

greater weight to one of the principles 

will frequently mean a decreased ability 

to fulfill one of the other principles. By 

necessity, value judgments, influenced 

by the social norms of the time, drive 

the implementation of the broad 

principles underlying the Belmont 

Report. The efficacy of the oversight 

system also requires proportionality in 

weighing the application of these three 

principles. This is reflected in the 

analysis that follows, in terms of 

evaluating the specific aspects of 

beneficence, respect for persons, and 

justice that relate to a particular issue, 

and weighing those aspects against one 

another. Research that poses greater risk 

should receive more attention and 

deliberation than less risky research, 

and the degree and type of oversight 

should be commensurate with the level 

of risk. In addition, requirements that do 

not enhance protection but that impose 

burden can increase inefficiency, waste 

resources, erode trust, and obscure the 

ethical challenges that require careful 

deliberation and stakeholder input. 

Cumbersome and outdated regulatory 

standards overwhelm and distract 

oversight bodies and other stakeholders 

from appropriately addressing the real 

risks and benefits of research. 

There is tremendous support for 

research in this country. American 

society values advances in knowledge 

and has reaped the reward of many key 

insights that have led to increases in 

quality of life and a doubling of our life 

expectancy in the last century. There 

would not have been such strides in 

medical and behavioral research 

without the willingness of individuals 

to join research studies. Participants are 

told that they are not likely to benefit 

directly from any given study, yet they 

choose to participate for the greater 

good. Beneficence is a powerful driver. 

On the other hand, members of the 

public deserve, and indeed now expect, 

to know how publicly-funded research 

is being conducted and overseen, and 

need to have confidence that the 

interests of research participants are 

adequately protected. Transparency is 

key for developing trust, especially 

between investigators, funders, 

regulators, and the public. 

Our reassessment of these ethical 

principles in the context of current 

technology and social norms suggests 

the need for changes to the Common 

Rule that: (1) Increase subject autonomy 

by increasing human subjects’ ability 

and opportunity to make informed 

decisions; (2) reduce potential for harm 

and increase justice by increasing the 

uniformity of human subject protections 

in areas such as information disclosure 

risk, coverage of clinical trials, and 

coverage of IRBs; and (3) increase 

beneficence by facilitating current and 

evolving types of research that offer 

promising approaches to treating and 

preventing medical and societal 

problems though reduced ambiguity in 

interpretation of the regulations, 

increased efficiencies in the 

performance of the review system, and 

reduced burdens on researchers that do 

not appear to provide commensurate 

protections to human subjects. If a 

reasonable balance is struck between 

protecting human research subjects, 

minimizing the administrative burden 

of the system, and engendering public 

trust, this should maximize beneficence 

and raise all ships. 

Public comment is sought not only on 

the provisions outlined below, but on 

whether the proposals strike a 

reasonable balance among the core 


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41See supra notes 5–8. 

42Presidential Commission for the Study of 

Bioethical Issues. (2012). Privacy and Progress in 

Whole Genome Sequencing. Washington, DC: 

Presidential Commission for the Study of Bioethical 

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

default/files/PrivacyProgress508_1.pdf. 

ethical principles. A better balance 

among the core principles should 

increase the strength of the partnership 

between the research enterprise and the 

public, and even greater scientific 

understanding and innovation will be 

fostered. 

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. 

1. Question for Public Comment 

1. Public comment is sought on 

whether the proposed changes will 

achieve the objectives of (i) decreasing 

administrative burden, delay and 

ambiguity for investigators, institutions, 

and IRBs, and (ii) strengthening, 

modernizing, and making the 

regulations more effective in protecting 

research subjects. 

D. Organization of the NPRM 

Section II of the NPRM, which 

immediately follows, describes in detail 

the major proposals for revisions to the 

Common Rule. In general, the changes 

that are likely to be of greatest 

significance are discussed in the earlier 

parts of section II of this preamble. 

Section II.A is devoted to changes that 

affect which activities are subject to the 

Common Rule. Following that section 

are discussions devoted to changes 

relating to informed consent (section 

II.B), changes relating to privacy 

safeguards for the research use of 

information and biospecimens (section 

II.C), and a proposal to encourage 

greater harmonization of guidance 

across the agencies that adhere to the 

Common Rule (section II.D). 

Discussions of changes relating to how 

IRBs operate, including a proposal to 

reduce the number of reviews by 

different IRBs that take place for multisite studies, are in the several sections 

that follow (sections II.E, F and G). The 

final section (section II.H) collects a 

variety of other changes, including 

expanding the scope of the rule to cover 

clinical trials that are not federally 

funded but are conducted at institutions 

that received some federal funding for 

research with human subjects. 

The three sections that follow then 

discuss various administrative review 

requirements: Regulatory Impact 

Analyses (section III), Environmental 

Impact (section IV), and Paperwork 

Reduction Act (section V). The final 

section of the document (section VII) 

provides the full regulatory text of the 

proposed changes to the Common Rule. 

Section VI provides a comprehensive 

summary of responses received to the 

2011 Common Rule ANPRM. 

II. Major Proposals To Modernize the 

Common Rule 

A. Proposed Changes to the Scope and 

Applicability of the Regulations 

1. Expanding the Definition of Human 

Subject to Cover Research with Nonidentified Biospecimens (NPRM at 

§§ ll.102(e) and ll.101(b)(3)(i)) 

This section focuses on the ethical 

principles associated with the 

secondary research use of biospecimens. 

These biospecimens may have been 

originally collected from either research 

or non-research settings (e.g., leftover 

portion of tissue from a clinical biopsy). 

a. NPRM Goals 

One of the goals of this NPRM is 

facilitating cutting edge research in 

genomics and other ‘omics’ such as the 

transcriptome and the microbiome, 

which generate a wealth of data from 

biospecimens designed to inform the 

development of treatments and 

preventative measures for chronic 

diseases such as cancer. Facilitating 

such research, however, requires 

navigating complex ethical issues. The 

key question is, under what 

circumstances should the Common Rule 

govern what research investigators are 

able to do with biospecimens that have 

been collected for some other (e.g., 

clinical) purpose? (Note that if a 

researcher interacted with an individual 

to actually collect a biospecimen for 

research purposes—for example, 

obtaining a saliva sample—that 

‘‘primary’’ research activity is already 

covered under the current regulations, 

and is not the focus of the change 

discussed in this section.) In this case, 

maximizing the societal value of 

research would mean reducing barriers 

to the secondary use of biospecimens to 

the extent possible. 

However, there is a growing 

recognition that many people want to 

have some degree of control over the 

circumstances in which an investigator 

can derive information about them, 

above and apart from their interest in 

whether or not that information might 

be inappropriately disclosed. More 

specifically, a growing body of literature 

shows that in general people prefer to 

have the opportunity to consent (or 

refuse to consent) to research involving 

their own biological materials.41

Furthermore, in 2012, the Presidential 

Commission for the Study of Bioethical 

Issues highlighted the ethical 

importance of obtaining consent for 

genomics research and recommended 

that ‘‘unauthorized whole genome 

sequencing without the consent of the 

individual from whom the sample 

came’’ be prohibited.42 Their rationale 

for reaching this conclusion was based 

on concerns relating to privacy as well 

as autonomy. 

In assigning weights to the principles 

of beneficence and respect for persons 

in the context of research with 

biospecimens, strong consideration was 

given to the fact that failure to 

acknowledge and give appropriate 

weight to this distinct autonomy interest 

in research using biospecimens could, 

in the end, diminish public support for 

such research, and ultimately jeopardize 

our ability to be able to conduct the 

appropriate amount of future research 

with biospecimens. To that end, the 

proposals given below are designed to 

meet the goals of increasing 

transparency in when and how 

biospecimens collected in a variety of 

circumstances will be used for research 

purposes and increasing opportunities 

for consent. Various ways in which 

these goals might be achieved are the 

subject of alternative proposals 

discussed below. 

b. Current Rule 

The application of the current 

regulations to secondary research use of 

a biospecimen is tied to the 

identifiability of the biospecimen in the 

hands of the researcher. In particular, 

the definition of human subject in the 

current Common Rule at §ll.102(f) 

states that a human subject is a living 

individual about whom an investigator 

(whether professional or student) 

conducting research obtains data 

through intervention or interaction with 

the individual, or identifiable private 

information. Private information is 

described as information that is 

individually identifiable (i.e., the 

identity of the subject is or may readily 

be ascertained by the investigator or 

associated with the information) in 

order for obtaining the information to 

constitute research involving human 

subjects. 

Consistent with historical 

interpretation of identifiable private 

information under the Common Rule, 

the terms ‘‘non-identified’’ or ‘‘nonidentifiable’’ are used throughout this 


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Federal Register / Vol. 80, No. 173 / Tuesday, September 8, 2015 / Proposed Rules 53943 

43National Congress of American Indians. 

Havasupai Tribe and the lawsuit settlement 

aftermath. Retrieved on November 17, 2014, from 

http://genetics.ncai.org/case-study/havasupaiTribe.cfm. 

NPRM to signify biospecimens or data 

that have been stripped of identifiers 

such that an investigator cannot readily 

ascertain a human subject’s identity. Reidentification of non-identified or nonidentifiable biospecimens or 

information may be possible, depending 

on the circumstances. The term ‘‘deidentified’’ is distinct; it is only used in 

this proposal to refer specifically to the 

HIPAA standard of non-identifiability. 

Thus, where there is no intervention 

or interaction with an individual, 

central to determining whether human 

subjects are involved in a research 

activity covered by the current Common 

Rule is determining the meaning of 

‘‘identifiable.’’ Under the current Rule, 

provided the biospecimens and data 

were collected for purposes other than 

the currently proposed research, it is 

permissible for investigators to conduct 

research on biospecimens and data that 

have been stripped of all identifiers 

without obtaining consent because the 

non-identified biospecimens and data 

do not meet the regulatory definition of 

human subject. 

It is, however, worth noting that 

although informed consent is not 

strictly required by the current 

regulations when research takes place 

using non-identified biospecimens, 

some IRBs have indicated that they are 

requiring that investigators explicitly 

obtain consent for future analysis of 

biospecimens collected in the research 

setting, and some are refusing to waive 

consent for use of biospecimens 

collected in non-research contexts. 

c. ANPRM Discussion 

The ANPRM asked whether consent 

should be required before an 

investigator could conduct research on 

a non-identified biospecimen. It further 

asked, if consent were to be required, 

could such consent be obtained by 

having a person provide consent for 

unspecified future research with the 

biospecimen, instead of requiring that 

specific consent be obtained each time 

that the biospecimen would actually be 

used in a research study. 

Although HHS does not consider 

whole genome analysis to produce 

identifiable private information unless 

additional information is available to 

the investigator that would enable the 

investigator to ‘‘readily ascertain’’ the 

identity of the individual, it is 

acknowledged that a time when 

investigators will be able readily 

ascertain the identity of individuals 

from their genetic information may not 

be far away. The ANPRM suggested that, 

regardless of what information is 

removed, it is theoretically possible to 

extract DNA from a biospecimen itself 

and potentially link it to otherwise 

available data to identify individuals. In 

addition, irrespective of whether 

biospecimens are considered 

individually identifiable, the ANPRM 

sought comment on whether the 

regulations should be changed to allow 

human subjects to decide whether their 

biospecimens would be available for 

research. 

The ANPRM asked whether some 

types of genomic data should be 

considered identifiable and, if so, which 

types (e.g., genome-wide single 

nucleotide polymorphism [SNP] 

analyses or whole genome sequences). It 

also asked whether a human 

biospecimen should be considered 

inherently identifiable. 

The ANPRM also suggested that the 

definition of identifiability in the 

Common Rule be modified to better 

harmonize it with other regulatory 

definitions of identifiability within 

HHS. The ANPRM considered adopting 

the HIPAA Privacy Rule’s standards of 

what constitutes individually 

identifiable information, a limited data 

set, and de-identified information (as 

defined under HIPAA), in order to 

address inconsistencies regarding these 

definitions and concepts between the 

HIPAA Privacy Rule and the Common 

Rule. 

More specifically, as described above, 

private information is not considered to 

be identifiable under the current 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. In 

contrast, 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)). 

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), 

and thus not all investigators are part of 

a covered entity and required to comply 

with those rules. Moreover, the HIPAA 

Rules do not apply specifically to 

biospecimens in and of themselves. 

Public comments in response to the 

2011 ANPRM regarding covering all 

biospecimens raised a series of 

important concerns. A majority of the 

commenters opposed the ANPRM’s 

suggested requirement of consent for 

research use of all biospecimens, 

regardless of identifiability, particularly 

if applied to samples collected before 

the effective date of the regulation. 

Some commenters cited lack of 

convincing evidence of harm caused by 

research use of non-identified clinical 

biospecimens without consent; they 

noted that they were not convinced that 

the principle of autonomy outweighs or 

trumps the principle of beneficence. 

They expressed concern that doing so 

would significantly slow advances in 

research and human health. 

Others acknowledged the erosion of 

public trust that can result from highprofile disputes involving the use of 

non-identified biospecimens collected 

during research.43 Commenters cited the 

costs to collect, log, and track consent 

status of data and biospecimens 

collected in a clinical setting to ensure 

that any restrictions on the research use 

of such resources were honored. 

However, it is important to note that it 

appears that many commenters were 

reacting to concerns that any change in 

the Common Rule with respect to 

consent for use of biospecimens would 

be applied retroactively—that is, to 

samples already collected. 

Some patient advocacy organizations 

also expressed concerns about the 

consequences of requiring consent for 

the use of non-identified biospecimens. 

Other commenters noted that the 

recommendation to require consent 

might inappropriately give greater 

weight to the Belmont Report’s 

principle of autonomy over the 

principle of justice, because requiring 

consent could result in lower 

participation rates in research by 


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53944 Federal Register / Vol. 80, No. 173 / Tuesday, September 8, 2015 / Proposed Rules 

44 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. http://

www.amstat.org/meetings/jsm/2011/

onlineprogram/

AbstractDetails.cfm?abstractid=302255. 

minority groups and marginalized 

members of society. Yet, most of the 

comments from individual members of 

the public strongly supported consent 

requirements for use of their 

biospecimens, regardless of 

identifiability. 

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 does not 

involve risk to the research participant. 

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 reidentification from a system intrusion of 

databases was only 0.22%.44 In contrast, 

some commenters supported the idea of 

requiring consent for research use of all 

biospecimens, with one commenter 

noting simply that ‘‘research use of data 

initially collected for non-research 

purposes should always require 

informed consent.’’ 

Several commenters stated that if the 

Common Rule were modified such that 

all biospecimens were covered under 

the rule regardless of identifiability 

there still might be some activities 

involving biospecimens that should be 

considered exempt or excluded from 

coverage. Suggestions included: 

• Identifying markers for cancer 

prognosis or prediction of response to 

cancer therapy, or identifying cancer 

molecular targets (molecular research) 

• Basic science research (including 

analysis of biological processes) 

• Research on rare conditions and 

diseases 

• Pediatric research 

• Research with samples that lack 

potentially identifying information, 

such as serum or plasma not 

containing DNA 

• Biospecimens lacking nucleic acids 

(such as certain red blood cells, 

expiratory gases) 

• Blood culture bacteria 

• Bacterial and viral specimens (this 

was listed in a comment as a public 

health issue) 

• Protein analysis 

• Statistical method development (to 

the extent that this development is 

related to biospecimens) 

• New molecular methods to detect 

infectious agents 

• Use of specimens to develop and 

validate new assays for infectious 

agents 

• Archival paraffin blocks 

With respect to the 2011 proposal to 

adopt the HIPAA Privacy Rule’s 

definition of identifiability, a majority of 

the public commenters strongly 

opposed the idea. They indicated that 

the HIPAA Privacy Rule’s standard of 

identifiability would expand what is 

considered identifiable for purposes of 

the Common Rule and thus greatly 

impede relatively low-risk research 

without adding meaningful protections 

for human subjects. In particular, they 

asserted that the HIPAA standards were 

created to protect against disclosure of 

health information contained in medical 

records. As such, commenters argued, 

they are not appropriate for many types 

of research that would be covered by the 

Common Rule (e.g., behavioral and 

social science research). Others said this 

would be an extreme change in response 

to an as yet unidentified or clear 

problem. Commenters said that the 

information most at risk for 

inappropriate disclosure is the type of 

private health information that is 

already protected under the HIPAA 

Rules. Commenters feared that such a 

change in policy, while ‘‘harmonizing’’ 

the Common Rule to certain HIPAA 

standards, would create inordinate 

burdens in terms of new documentation 

requirements and result in a 

requirement to apply the HIPAA 

standards to all types of research, 

regardless of the level of risk. 

d. NPRM Proposal 

Regardless of the scale on which 

harms may have occurred in the past, 

continuing to allow secondary research 

with biospecimens collected without 

consent for research places the publiclyfunded 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. As such, 

one of the most fundamental changes 

proposed in this NPRM is to the 

definition of human subject (proposed 

§ ll.102(e)). The proposal is for the 

obtaining, use, study, or analysis of 

biospecimens to be covered under the 

Common Rule, regardless of 

identifiability. Covering biospecimens 

regardless of identifiability avoids 

codifying any given interpretation of the 

quickly evolving debates regarding 

whether certain analytic results (e.g., 

decoding the whole genome) should be 

considered to yield identifiable data. 

(Accompanying this proposal are some 

minor wording changes to other 

portions of that definition that are 

merely intended to clarify how the word 

‘‘obtains’’ is currently interpreted by 

OHRP.) 

Thus, the focus of this proposal is to 

require informed consent for research 

involving biospecimens in all but a 

limited number of circumstances. The 

consent would not need to be obtained 

for each specific study using the 

biospecimen, but could instead be 

obtained through broad consent for 

future unspecified research (described 

in more detail in sections II.A.3.d and 

II.B of this preamble). 

An increase in trust and partnership 

is likely to increase participation rates 

in research; using individuals’ samples 

and data without permission will hinder 

true partnership. Better communication 

and community engagement with 

patients, particularly in geographic 

areas and for population subgroups 

where consent rates are lower than 

average, should be a priority for the 

research community. 

In response to comments received 

about the 2011 ANPRM, the NPRM 

proposes to have the new definition of 

human subject apply prospectively, that 

is, it will only apply to research 

involving biospecimens that will be 

collected in the future. Additionally, in 

recognizing that this proposal will have 

major implications for the operational 

functioning of the research enterprise, 

compliance with this provision would 

be delayed until three years after 

publication of a final rule. 

Also consistent with comments 

received on the ANPRM, it is proposed 

that a subset of secondary research on 

stored biospecimens would be allowed 

without consent. Specifically, research 

designed to only generate information 

about the person that is already known 

would be considered outside of the 

scope of the Common Rule. This 

exclusion would include but not be 

limited to the development and 

validation of certain tests and assays 

(such as research to develop a 

diagnostic test for a condition using 

specimens from individuals known to 

have the condition and those known not 

to have the condition), quality assurance 

and control activities, and proficiency 

testing. This provision would be 

implemented through a new exclusion 

from the regulations at 

§ ll.101(b)(3)(i), which has 

specifically been designed to reflect the 

underlying ethical principles. 

If the research is designed not to 

generate any new information about the 


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Federal Register / Vol. 80, No. 173 / Tuesday, September 8, 2015 / Proposed Rules 53945 

person, but only confirm something 

about them that is already known, then 

the interest in respecting the person’s 

autonomy would appear to be relatively 

weak. As an example, imagine that a 

person is known to have a particular 

genetic disease, and the research 

involves evaluating a new product that 

might in a few minutes, at low cost, 

produce a result showing whether a 

person has that disease. The person’s 

autonomy interest in whether or not 

such a study could take place would 

seem little different from that of anyone 

in a study that involved secondary use 

of identifiable information about them. 

In addition, the proposal permits IRBs 

to waive the requirement for informed 

consent, but the requirements for 

approval of such waivers would be very 

strict, and such waivers will only occur 

in rare circumstances. Note also that the 

exclusions proposed in 

§ ;llll.101(b)(1)(i), (iii)–(vi) would 

also allow for the use of biospecimens 

without consent in certain limited 

circumstances; these additional 

exclusions are discussed in section 

II.A.2 of this preamble, below. 

This proposal would not modify the 

Common Rule standard of identifiability 

(in contrast to what was discussed in 

the 2011 ANPRM). That is, the standard 

for determining when an investigator 

has sufficient information to readily 

ascertain the identity of an individual is 

not being changed under this proposal. 

Thus, coverage of information derived 

from biospecimens (whether or not the 

biospecimen was initially collected in 

the research or non-research context), or 

indeed any other type of information, 

would be the same under this proposal 

as is the case under the current 

Common Rule. 

i. Alternative Proposals 

In this section, we discuss two 

alternative proposals, both of which 

maintain ‘‘identifiability’’ as the 

lynchpin for determining applicability 

of the Common Rule to biospecimens. 

These models increase transparency and 

opportunities for consent over and 

above what is provided for in the 

current Common Rule, but in a smaller 

set of circumstances than provided for 

under the primary proposal discussed 

above. 

Alternative Proposal A: Expand the 

Definition of ‘‘Human Subject’’ To 

Include Whole Genome Sequencing 

(WGS) 

Rather than consider all research 

using biospecimens as constituting 

human subjects research, this 

alternative proposal would expand the 

definition of human subjects to include 

only specifically whole genome 

sequencing data, or any part of the data 

generated as a consequence of whole 

genome sequencing, regardless of the 

individual identifiability of 

biospecimens used to generate such 

data. Under this alternative, whole 

genome sequencing would be 

considered the sequencing of a human 

germline or somatic biospecimen with 

the intent to generate the genome or 

exome sequence of that biospecimen. 

Thus, under this alternative, the 

regulations would then apply both to 

research that would generate whole 

genome sequencing data, the use of any 

part of the generated data, and to 

research involving secondary use of any 

part of whole genome sequencing data 

that was originally generated for other 

purposes than the proposed research. 

Investigators conducting whole genome 

sequencing research could not avoid the 

need to comply with the Common Rule 

by removing identifiers from 

biospecimens or data, because whole 

genome sequence data in and of itself 

would meet the definition of human 

subject. Under this alternative, a new 

exemption would also be created that 

would allow such research to be 

considered exempt if consent to 

secondary future research use were 

obtained in accordance with proposed 

new requirements at §ll.116(c) and 

standards were met for protecting 

information and biospecimens as 

proposed at § ll.105. A waiver of 

consent would be permitted, but would 

be modeled on the more stringent 

waiver criteria proposed for research 

involving biospecimens at 

§ ll.116(f)(2). 

Explicit consent to conduct research 

using whole genome sequencing data 

can be considered ethically important 

because such data can provide 

important insights into the health of 

individuals as well as their relatives. 

Moreover, whole genome sequence data 

gathered for one purpose may reveal 

important information, perhaps 

unanticipated and unplanned for, years 

later. Finally, whole genome sequence 

data are unique for each individual, or 

at the very least, highly unlikely to be 

the same as any other individual. Thus, 

the current allowable practice of 

removing identifiers from biospecimens 

and data to conduct whole genome 

sequencing research without consent 

might not sufficiently protect both the 

privacy and autonomy interests of the 

subject. 

As is currently the case, under this 

alternative, investigators’ use of 

individually identifiable biospecimens, 

collected for purposes other than the 

currently proposed research study, 

would continue to be considered human 

subjects research. However, the 

secondary research use of non-identified 

information or non-identified 

biospecimens would continue to fall 

outside of the scope of the Common 

Rule, with the exception of whole 

genome sequence data as described 

above. 

One of the less obvious differences in 

scope between the primary proposal and 

this Alternative A relates to what 

research could be done with the data 

generated from whole genome 

sequencing that had taken place for 

clinical purposes. Under the primary 

proposal, the data produced by such 

sequencing could continue to be used 

for research, without additional consent, 

so long as it did not meet the definition 

of being identifiable private 

information. (HHS does not currently 

consider whole genome sequencing data 

to meet that definition for purposes of 

the Common Rule.) Under this 

Alternative A, consent would be 

required before using that data for 

research purposes. 

In contrast with the primary proposal 

in this NPRM, this Alternative Proposal 

A could be viewed as giving greater 

weight to the principle of beneficence, 

while giving less weight to the principle 

of respecting the autonomy of persons. 

It would require consent only for the 

type of studies that many people seem 

most concerned about (genomic 

research, including secondary use of 

genomic information that was produced 

for clinical purposes). And given that at 

the moment there is relatively little 

whole genome sequencing research 

taking place (in comparison to other 

types of biospecimen research; see 

section III.F of this preamble for more 

information), it would appear to 

currently impose a somewhat lesser 

burden in terms of obtaining and 

tracking consent than the main NPRM 

proposal. 

The major concern with this 

alternative proposal is that it would 

codify only a single technology as 

producing information that would be 

subject to the Common Rule, 

necessitating a re-evaluation of the 

scope of the Rule when technologies 

now in development to study, for 

instance, other ‘‘omics,’’ become more 

widespread. 

Alternative Proposal B: Classifying 

Certain Biospecimens Used in 

Particular Technologies as Meeting the 

Criteria for ‘‘Human Subject’’ 

This Alternative Proposal B would 

expand the definition of human subjects 

to include the research use of 

information that was produced using a 


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45Executive Office of the President, Office of 

Management and Budget. (2007). Memorandum for 

the Heads of Executive Departments and Agencies. 

Retrieved from The White House: https://

www.whitehouse.gov/sites/default/files/omb/

memoranda/fy2007/m07-16.pdf. 

technology applied to a biospecimen 

that generates information unique to an 

individual such that it is foreseeable 

that, when used in combination with 

publicly available information, the 

individual could be identified. 

Information that met this standard 

would be referred to as bio-unique 

information. This proposal is 

conceptually very similar to Alternative 

Proposal A. The main difference is that 

the scope is somewhat broader: Whereas 

Alternative A requires consent for 

whole genome sequencing, Alternative 

B would require consent for genomic 

sequencing of even small portions of a 

person’s genome, and also require 

consent for the use of other technologies 

that might be developed that similarly 

can generate information unique to a 

person. 

There are three separate conditions 

that would all need to be met before 

information would constitute biounique information: (1) It would have to 

have been produced by applying to a 

biospecimen a technology that is 

capable of producing information that is 

unique to an individual; (2) The 

technology would have to be used to 

produce enough information such that 

the information produced is likely to be 

unique to an individual; and (3) There 

would need to be publicly available 

information that, when combined with 

the information produced by the use of 

the technology, would create the 

possibility that some of the individuals 

whose biospecimens were analyzed 

using the technologies could be 

identified. 

The major concern with this 

alternative proposal is that, in order to 

make such a requirement responsive to 

scientific and technological 

developments, HHS would have to 

continually evaluate new technologies 

and the nature and amount of 

information produced using such 

technologies. Not only would this 

involve resources and expertise that 

may not be available to Federal 

departments and agencies, it would 

introduce ongoing uncertainty that may 

actually increase delays in important 

research. 

e. What would change in the definition 

of ‘‘human subject’’ under the primary 

proposal? 

• It is anticipated that the compliance 

date for the proposed expansion of the 

definition would be three years after the 

publication date. The main consequence 

of this change would be that informed 

consent (which could be broad, as 

described in sections II.A.3.d and II.B of 

this preamble) would generally be 

required before research use of 

biospecimens not covered by an 

exclusion. 

• All biospecimens used for research 

purposes that do not fall under an 

exclusion (see proposed 

§ ll.101(b)(3)(i), and also 

§ ll.101(b)(1)(i), (iii)–(vi)) and are 

collected after the compliance date 

would be subject to the requirements of 

this rule, regardless of identifiability. 

f. Questions for Public Comment 

2. Would providing a definition of 

biospecimen be helpful in 

implementing this provision? If so, how 

might the definition draw a line 

between when a biospecimen is covered 

by the Common Rule, and when 

processing of biological materials (e.g., 

to create a commercial product used for 

treatment purposes) has sufficiently 

altered the materials so that they should 

not be subject to the regulations? Would 

only covering biospecimens that include 

nucleic acids draw an appropriate line? 

3. To what extent do the issues raised 

in this discussion suggest the need to be 

clearer and more direct about the 

definition of identifiable private 

information? How useful and 

appropriate is the current modifier 

‘‘may be readily ascertained’’ in the 

context of modern genomic technology, 

widespread data sharing, and high 

speed computing? One alternative is to 

replace the term ‘‘identifiable private 

information’’ with the term used across 

the Federal Government: Personally 

identifiable information (PII). The Office 

of Management and Budget’s 45 concept 

of PII refers to information that can be 

used to distinguish or trace an 

individual’s identity (such as their 

name, social security number, biometric 

records, etc.) alone, or when combined 

with other personal or identifying 

information which is linked or linkable 

to a specific individual, such as date 

and place of birth, mother’s maiden 

name, etc. It is acknowledged that 

replacing ‘‘identifiable private 

information’’ with ‘‘PII’’ would increase 

the scope of what is subject to the 

Common Rule. However, the practical 

implications of such an expansion, 

other than the need to ensure that the 

data are security stored and otherwise 

protected against disclosure, may be 

minimal. Public comment is requested 

on the advantages and disadvantages of 

such a change. 

4. Which of the three proposals 

regarding the definition of human 

subject achieves the most reasonable 

tradeoff between the principles of 

autonomy (including transparency and 

level of trust) versus beneficence (as 

measured by facilitating valuable 

research)? 

5. Public comment is sought regarding 

any concerns that you have about each 

of the three proposals, including 

concerns about implementation or 

burden to investigators and institutions. 

2. Explicit Exclusion of Activities From 

the Common Rule 

The NPRM creates a new section in 

the regulations referred to as 

‘‘exclusions.’’ This section outlines 

eleven specific types of activities that 

will be outside the scope of the 

regulations. These activities will 

therefore not have to satisfy any 

regulatory requirements, nor is it 

expected (unlike exempt research) that 

they will undergo any type of review 

process to determine this status. The 

exclusions will eliminate uncertainty 

regarding some activities that are not 

research, and identify some activities 

that arguably might be judged to be 

research, but whose contribution to 

public welfare is so imperative that they 

should proceed without having to 

satisfy the regulatory requirements. The 

exclusions also identify certain research 

activities that are sufficiently low-risk 

and nonintrusive that the protections 

provided by the regulations are an 

unnecessary use of time and resources, 

whereas the potential benefits of the 

research are substantial. 

The Common Rule has been criticized 

for not being clear about how to 

interpret what activities are covered by 

the policy and for inappropriately being 

applied to and inhibiting certain 

activities. The first six exclusion 

categories are for activities that are 

deemed not to be research for the 

purposes of this policy, without needing 

to consider whether the regulatory 

definition applies. The definition of 

research does not provide such a clear 

and precise way of distinguishing 

among similar activities that it is 

immediately obvious which activities 

fall under the definition and which do 

not. By creating exclusion categories 

that are deemed not research, these 

activities are more clearly distinguished 

as not having to satisfy the regulatory 

requirements. 

Three of the exclusions seek to 

eliminate any uncertainty about 

whether certain internal program 

improvement activities, historical or 

journalistic inquiries, or quality 

assurance or improvement activities 

satisfy the definition of research. The 

other three exclusions include some 


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activities that fall into to a gray area that 

encompasses some activities that 

arguably might be judged to be research, 

but that are part of inherently 

governmental functions that have 

purposes other than research, such as 

responsibilities to protect public health 

and welfare (see exclusions for criminal 

investigations, public healthy 

surveillance, and intelligence 

surveillance). These activities promote 

recognized specific goods that are 

crucial to the public welfare, and should 

be carried out without any hindrances 

that satisfying regulatory requirements 

might impose. For these activities, the 

principles of beneficence and justice 

outweigh any intrusions on individual 

autonomy that the regulations might 

have prevented. 

The next four categories of proposed 

exclusions are for activities that are 

considered low-risk either in themselves 

or because there are appropriate 

safeguards already in place independent 

of the Common Rule. Here the level of 

risk, the potential benefits, and the 

nature of human participation in this 

research are such that the principle of 

beneficence determines that the 

research activities may go forward 

without the need to impose the 

protections of the Common Rule. 

The last exclusion applies to research 

involving the secondary use of nonidentified biospecimens when the 

research is limited to generating 

information about the subject that is 

already known. As such, this research 

does not need any additional 

protections provided by these 

regulations and the potential benefits of 

this research justify it under the 

principle of beneficence. Because this 

exclusion directly relates to the 

proposed changes in the definition of 

‘‘human subject’’ to include all 

biospecimens, it is discussed above in 

section II.A.1 of this preamble. 

It should be noted that the fact that 

the NPRM now specifically includes a 

list of certain excluded activities should 

not be seen as altering the fact that 

many other activities that do not meet 

the criteria for being subject to the 

Common Rule remain outside the scope 

of the rule. For example, an activity that 

does not meet the regulatory definition 

of research, or does not involve human 

subjects, would still not be subject to 

these regulations. 

Currently, the Common Rule excludes 

from coverage (1) activities that do not 

meet the definition of research 

(§ ll.102(d) of the current Rule); (2) 

activities that are not described as 

research subject to regulation 

(§ ll.102(e) of the current Rule); and 

(3) activities that do not involve a 

human subject (§ ll.102(f) of the 

current Rule). 

The ANPRM asked questions about 

the definition of research and whether 

various activities should be excluded 

from the Common Rule, either by 

changing the definition of research or by 

adding exemptions, or both. The 

ANPRM sought comment on whether 

and, if so, how, the Common Rule 

should be changed to clarify whether 

quality improvement activities, program 

evaluation studies, or public health 

activities are covered. It also asked 

whether there are specific types of 

studies for which the existing rules are 

inappropriate. If so, comments were 

sought on whether this problem should 

be addressed through modifications to 

the exemption categories, or by 

changing the definition of ‘‘research’’ 

used in the Common Rule to exclude 

some of these studies, or a combination 

of both. 

If the definition of research were to be 

changed, public comment was sought 

on how excluded activities should be 

defined (e.g., ‘‘quality improvement’’ or 

‘‘program evaluation’’). With regard to 

quality improvement activities, the 

public was asked to comment on 

whether it might be useful to adopt the 

distinction made by the HIPAA Privacy 

Rule, which distinguishes between 

‘‘health care operations’’ and ‘‘research’’ 

activities, defining ‘‘health care 

operations’’ to include, among other 

activities, ‘‘conducting quality 

assessment and improvement activities, 

including outcomes evaluation and 

development of clinical guidelines, 

provided that the obtaining of 

generalizable knowledge is not the 

primary purpose of any studies resulting 

from such activities.’’ 

a. Exclusion of Activities that are 

Deemed Not Research (NPRM 

at §ll.101(b)(1)) 

The first set of six exclusions involve 

activities that will be excluded from the 

regulations because they will be deemed 

to not involve research. Three of the 

first six exclusions (discussed in 

sections II.A.1.a.i, ii, and iv, below) 

provide clarity regarding the 

applicability of the Common Rule to 

activities about which institutions have 

raised questions in the past as to 

whether these activities meet the 

regulatory definition of research. These 

exclusions aim to reduce the time and 

effort involved trying to determine 

whether the regulations apply, and in 

unnecessary reviews of these activities. 

The other three of these exclusions 

(discussed in sections II.A.1.iii, v, and 

vi below) apply to activities that are 

largely inherently government functions 

that have purposes other than research, 

and, when conducted by a government 

employee or contractor, are subject to a 

variety of other statutes, regulations, 

and polices that are designed to protect 

individual privacy and data security, as 

well as provide notice to those 

providing the information as to the uses 

to which the information will be put 

(see, for example, the Privacy Act of 

1974). These activities promote 

recognized specific goods that are 

crucial to the public welfare, and 

because of this they should be carried 

out without any hindrances that 

satisfying the Common Rule regulatory 

requirements might impose. For these 

activities, the principle of beneficence 

outweighs any intrusions on individual 

autonomy that the regulations might 

have prevented, and this allows these 

important activities to proceed without 

delay. 

The ANPRM asked whether various 

activities such as quality improvement, 

public health activities, or program 

evaluations studies should be excluded 

from the rule. 

i. Program Improvement Activities 

(NPRM at § ll.101(b)(1)(i)) 

(1) NPRM Proposal 

The first exclusion, proposed in the 

NPRM at § ll.101(b)(1)(i), is for data 

collection and analysis, including the 

use of biospecimens, for an institution’s 

own internal operational monitoring 

and program improvement purposes, if 

the data collection and analysis is 

limited to the use of data or 

biospecimens originally collected for 

any purpose other than the currently 

proposed activity, or is obtained 

through oral or written communications 

with individuals (e.g., surveys or 

interviews). This category is excluded 

because these activities are designed for 

various administrative purposes related 

to using information to improve the 

quality of services provided by a 

specific institution, and are not 

designed to produce generalizable 

knowledge. A majority of commenters to 

the 2011 ANPRM supported excluding 

program evaluation activities from the 

scope of the Common Rule. Many of 

these commenters argued that the public 

benefits resulting from this type of 

activity justified its practice, 

particularly given the generally low-risk 

involved. 

An example of an activity that would 

satisfy this exclusion is a survey of 

hospital patients to evaluate and 

improve the quality of meals delivered 

to hospital patients. An example of an 

activity that would not satisfy this 

exclusion is a prospective observational 


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study of patient treatments to analyze 

the comparative effectiveness of two 

different standard of care treatments 

frequently used to treat the same 

medical condition. 

(2) Questions for Public Comment 

6. Public comment is sought for 

whether this excluded activity should 

simply be discussed in the text of the 

final rule’s preamble, and guidance 

produced to assist investigators in 

making such a determination, or 

whether any other similar exclusions 

should be addressed. 

7. Public comment is sought for 

whether biospecimens should not be 

included in any of these exclusion 

categories, and if so, which ones. 

ii. Oral History, Journalism, Biography, 

and Historical Scholarship Activities 

(NPRM at § ll.101(b)(1)(ii)) 

(1) ANPRM Discussion 

The ANPRM asked whether there 

were any fields of study (such as 

classics, history, languages, literature, 

and journalism) whose usual methods of 

inquiry were not intended to or should 

not be covered by the Common Rule. 

(2) NPRM Proposal 

The second proposed exclusion, in 

the NPRM at §ll.101(b)(1)(ii) is for 

oral history, journalism, biography and 

historical scholarship activities that 

focus directly on the specific 

individuals about whom the 

information is collected. 

The overwhelming majority of public 

comments to the 2011 ANPRM 

responding to the question about 

excluding specific fields of study from 

the regulatory requirements of the 

Common Rule supported explicitly 

excluding certain activities from the 

definition of research versus modifying 

the exemption categories. The 

overwhelming majority of these 

comments focused on oral history. Some 

of the comments were virtually identical 

and appear to have been coordinated. 

Many of the comments reflected the 

view that the Common Rule was not 

designed or intended to include oral 

history activities, and that the ethical 

codes pertaining to oral history 

procedures are not consistent with the 

application of the ethical principles 

reflected in the Common Rule. 

A smaller number of similar 

comments were submitted with respect 

to various humanities disciplines and 

journalism. A significant minority of 

commenters opposed the exclusion of 

any fields of study, arguing that the 

activity itself rather than the academic 

discipline or training of the investigator 

should be the basis for the assessment 

of whether the activity should be 

excluded. Some of the commenters 

recommended that the definition of 

research be focused more explicitly by 

being limited to ‘‘biomedical and 

behavioral research,’’ in accordance 

with the statutory provision underlying 

the Common Rule. A significant number 

of commenters recommended that 

guidance should be issued to clarify 

how the definition of research should be 

applied, with cases and explanations. 

While the NPRM does not propose to 

modify the definition of ‘‘research’’, it 

does propose to explicitly exclude oral 

history, journalism, biography, and 

historical scholarship activities that 

focus directly on the specific 

individuals about whom the 

information or biospecimens is 

collected. In the kinds of activities 

referred to here, the ethical requirement 

is to provide an accurate and evidencebased portrayal of the individuals 

involved, and not to protect them from 

public scrutiny. Therefore, the 

protections afforded to individuals by 

the Common Rule seem unhelpful in 

furthering the aforementioned ethical 

goal in this context. Additionally, these 

fields of research have their own codes 

of ethics, according to which, for 

example, consent is obtained for oral 

histories. It is believed that because of 

these reasons, explicit exclusion of 

these activities from the scope of the 

Common Rule is appropriate. 

iii. Criminal Justice Activities (NPRM at 

§ ll.101(b)(1)(iii)) 

(1) NPRM Proposal 

The third category of activities that 

the NPRM excludes from the proposed 

rule encompasses data collection and 

analysis that enables the uniform 

delivery of criminal justice. The scope 

of this exclusion is collection and 

analysis of data, 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 excluded are necessary for the 

operation and implementation of the 

criminal justice system. 

The provision would essentially 

codify current Federal interpretation 

that such activities are not deemed to be 

research under the Common Rule. The 

addition of this provision is designed to 

avoid the imposition of disparate 

requirements by IRBs with overlapping 

jurisdiction when a data collection or 

analysis activity 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 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 offenders and certain sensitive 

civil employment applicants. At the 

same time, through its Laboratory 

Division and other components the FBI 

routinely collects human biospecimens 

at crime scenes from or relating to 

victims 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 information of criminal 

offenders for the Federal Government 

and for the overwhelming majority of 

state governments who elect to 

participate and share information 

through those FBI systems. 

iv. Quality Assurance and Quality 

Improvement Activities (NPRM 

at §ll.101(b)(1)(iv)) 

(1) NPRM Proposal 

The fourth category of excluded 

activities covers quality assurance or 

improvement activities involving the 

implementation of an accepted practice 

to improve the delivery or quality of 

care or services (including, but not 

limited to, education, training, and 

changing procedures related to care or 

services) if the purposes are limited to 

altering the utilization of the accepted 

practice and collecting data or 

biospecimens to evaluate the effects on 

the utilization of the practice. This 

exclusion does not cover the evaluation 

of an accepted practice itself. 

As an example of an activity that 

would satisfy this exclusion, assume 

that there is an accepted practice that is 

known to reduce the likelihood of an 

infection after the insertion of a central 

line. A randomized study in which half 

the participating institutions would be 

assigned to have the staff undergo an 

educational intervention about the need 

to use that accepted practice, and the 

other half would not undergo that 

intervention, would satisfy this 

exclusion, since it would only be 

intended to see if the intervention 

resulted in greater use of the accepted 

practice. In contrast, imagine a different 

study that was designed to determine 


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how well that accepted practice, when 

it is used, reduces infections. That study 

would not satisfy this exclusion, since 

it would be studying the effectiveness of 

the practice itself, in contrast to 

studying an effort to increase use of the 

practice. 

Over the past several years, including 

in response to the 2011 ANPRM, OHRP 

has received comments from many 

individuals and organizations 

expressing concern that some readings 

of the definition of ‘‘research’’ would 

imply that the regulations apply to 

quality improvement activities, thereby 

potentially interfering with the ability of 

health care and other professionals to 

enhance the delivery or quality of care 

or services involving the use of accepted 

practices. Indeed, a majority of 

commenters to the 2011 ANPRM 

supported excluding quality 

improvement activities from the scope 

of the Common Rule. These quality 

improvement activities are in many 

instances conducted by health care and 

other organizations under clear legal 

authority to change internal operating 

procedures to increase safety or 

otherwise improve performance, often 

without the consent of staff or clients, 

followed by monitoring or evaluation of 

the effects. These activities are generally 

conducted in circumstances where 

independent privacy, confidentiality, 

and security safeguards are in place, 

minimizing the chances of harm. These 

efforts, some of which could be judged 

to be research, should be carried out 

because of the recognized public good 

they achieve. This exclusion is intended 

to avoid impeding such efforts where 

the Common Rule’s requirements might 

have a chilling effect on the ability to 

learn from, and conduct, important 

types of innovation. 

Recognizing that some quality 

improvement efforts should not be 

considered to involve research as it is 

defined in the Common Rule can allay 

many of these concerns. Thus, this 

exclusion is being proposed to deal with 

quality improvement activities that are 

aimed at implementing practices that 

are already accepted, with the goal of 

improving the delivery or quality of 

treatments or services. This exclusion 

would permit measuring and reporting 

provider performance data for practice 

management, clinical, or administrative 

uses. As proposed, this exclusion does 

not include evaluations of different 

accepted practices themselves, however, 

such as activities designed to determine 

whether a particular accepted medical 

treatment is or is not more effective than 

another. 

This provision also covers quality 

improvement activities that are not 

related to delivery of patient care, but 

rather involve the delivery or quality of 

other public benefit or social services. 

For example, institutions and other 

entities may provide social services, 

educational offerings, or other beneficial 

activities where there is empirical 

evidence of the value of those efforts, 

and they may wish to evaluate different 

ways of enhancing the delivery or 

quality of those existing services. This 

exclusion has been written broadly to 

include such activities. 

The rationale for this excluded 

category is that these activities are 

designed only to improve the 

implementation of a practice that is 

already accepted, not to evaluate the 

effectiveness and value of the accepted 

practice itself, and thus would generally 

be expected to pose little if any risks to 

the recipients of those practices, and are 

directly aimed at improving the 

practical use of those practices. This 

does not include quality improvement 

activities designed with a research 

purpose relating to the safety and 

efficacy of the accepted practice. It is 

accordingly important to note that 

activities that do involve such 

research—for example, assigning 

patients to different versions of 

treatments that are within the standard 

of care in order to evaluate the 

differences between those treatments in 

terms of effectiveness or risks—would 

not come within this exclusion. In the 

educational context, for example, 

activities where students are assigned to 

experimental and control groups to 

determine the effectiveness of 

experimental teaching methodologies 

would also not come within this 

exclusion. Furthermore, that type of 

activity would also not meet a separate 

requirement of this exclusion—that the 

activity be related to the delivery of (i.e., 

implementing) an accepted form of care, 

and not an attempt to evaluate the 

efficacy or risks of that form of care. 

v. Public Health Surveillance (NPRM at 

§ ll.101(b)(1)(v)) 

(1) NPRM Proposal 

The fifth category of excluded 

activities involves public health 

surveillance activities, including the 

collection and testing of biospecimens, 

conducted, supported, requested, 

ordered, required, or authorized by a 

public health authority and limited to 

those necessary to allow the public 

health authority to identify, monitor, 

assess, or investigate potential public 

health signals or the onset of a disease 

outbreak, including trends, or signals, 

and patterns in diseases, or sudden 

increase in injuries from using a 

consumer product, or conditions of 

public health importance, from data, 

and including 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. A majority of commenters to 

the 2011 ANPRM supported excluding 

public health activities from the scope 

of the Common Rule. 

The rationale for excluding some 

public health surveillance activities is 

that 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 its 

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 privacy, 

confidentiality and security safeguards 

for the information collected. 

Public health surveillance refers to 

the collection, analysis, and use of data 

to target public health 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 in response to reports of 

potential outbreaks. The line between 

public health surveillance and 

epidemiological research can be 

difficult to draw, as the same 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 

activities that meet the public health 

surveillance exclusion: 

• 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 (AERS), the Vaccine 

Adverse Event Reporting System 

(VAERS), Manufacturer and User 

Facility Device Experience (MAUDE) 

database, the Medical Product Safety 

Network (MedSun), and the Sentinel 

Initiative); 

• Surveillance activities designed to 

enable a public health authority to 

identify unexpected changes in the 


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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 

influenza viruses 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. 

On the other hand, subsequent 

research using information collected 

during a public health surveillance 

activity, for instance genetic analysis of 

biospecimens, would not fall under this 

exclusion, but would likely be covered 

under one or more of the other 

exclusions for low-risk research or 

exemptions. 

Additional examples of activities that 

would not fall under the exclusion 

include: Exploratory studies designed to 

better understand risk factors, including 

genetic predisposition, for chronic 

diseases; exploratory studies designed 

elucidate the relationships between 

biomarkers of exposure and biomarkers 

of disease; exploratory studies of 

potential relationships between 

behavioral factors (e.g., diet) and 

indicators of environmental exposures. 

These types of activities would be 

considered research, and thus subject to 

the Common Rule, even if conducted by 

a Federal agency with a public health 

mandate. To clarify this proposed 

exclusion the NPRM also proposes a 

new regulatory definition of public 

health authority proposed in 

§ ll.102(k). 

(2) Question for Public Comment 

8. Public comment is requested on 

whether the parameters of the 

exclusions are sufficiently clear to 

provide the necessary operational 

guidance, or whether any additional 

criteria or parameters should be applied 

to clarify or narrow any of these 

exclusions. 

vi. Intelligence Surveillance Activities 

(NPRM at § ll.101(b)(1)(vi)) 

(1) NPRM Proposal 

The sixth category of excluded 

activities that will not be considered 

research involves surveys, interviews, 

surveillance activities and related 

analyses, or the collection and use of 

biospecimens where these activities are 

conducted by a defense, national 

security, or homeland security authority 

solely for authorized intelligence, 

homeland security, defense, or other 

national security purposes. 

The rationale for excluding the 

defense or national security-related 

activities is similar to that described 

above regarding public health 

surveillance activities. The lawful 

conduct of the departments’ and 

agencies’ mandated missions for 

actively protecting national security, 

homeland security, and homeland 

defense are fundamentally not research. 

These activities may incorporate the 

collection and analysis of identifiable 

information, but they are not designed 

to develop or contribute to generalizable 

knowledge; rather, they are solely 

conducted to fulfill a department or 

agency’s legal mandate to ensure the 

safety and protection of the United 

States, its people, and its national 

security interests. This exclusion 

codifies the current interpretation of the 

Common Rule. Research conducted or 

sponsored by Federal departments and 

agencies using this exclusion will 

continue to be subject to this regulation. 

b. Exclusion of Activities That Are LowRisk and Already Subject to 

Independent Controls (NPRM 

at §ll.101(b)(2)) 

i. NPRM Goals 

The NPRM proposes to exclude four 

categories of research activities that do 

not entail physical risk and are nonintrusive, either in themselves or 

because they are subject to policies that 

provide oversight independent of the 

Common Rule. Although the activities 

are research, they will not be required 

to receive any form of determination or 

IRB approval—including expedited 

review. Additionally, statements of 

purpose, benefit, and voluntariness as 

well as consent are not required unless 

the entity conducting the research, 

collecting data, or providing data is also 

subject to separate statutes and 

regulations requiring such statements. 

Some of the activities proposed for 

exclusion are categories that appear as 

exemptions in the current Rule. It is 

proposed that the marginal protections 

provided by the Common Rule are not 

consistent with the amount of 

researcher time and institutional 

resources that they currently draw. 

By reclassifying certain research 

activities from being exempt to being 

excluded, the proposed rule would 

eliminate the need for any 

administrative or IRB review. All 

investigators performing excluded 

studies are expected to act in a way that 

is consistent with the principles 

outlined in the Belmont Report, even if 

the Common Rule does not impose 

requirements on excluded work. For 

instance, consistent with the spirit of 

respect for persons, investigators should 

tell prospective subjects the purpose of 

the information collection and, where 

appropriate, that they can choose to 

participate or not in these activities, 

although investigators are not explicitly 

required to do so. 

Designating certain research fully 

outside of the bounds of the Common 

Rule means that investigators are selfdetermining whether their own research 

is covered by the law. As such, the 

proposal to add these categories is based 

on the assumption that all investigators 

will be accurately determining whether 

their proposed activity is outside the 

scope of the Common Rule. There is no 

current proposal outlining how 

decisions will be made for determining 

whether a research activity is eligible for 

exclusion and by whom or how 

differences among collaborators would 

be handled. As readers review each of 

the exclusion categories below, please 

consider whether the benefits associated 

with reducing the delay for researchers 

are countervailed by potential increases 

in risk of harm. 

Throughout this NPRM, the term 

‘‘low-risk’’ is used to denote research 

activities that do not entail physical 

risk, and where both the probability and 

magnitude of other risks, once required 

protections are applied, are 

hypothesized to be low. Public 

comment is sought on whether there are 

instances in the regulatory text where 

the term ‘‘low-risk’’ is used, but these 

conditions do not apply, and whether 

there is a better way to characterize this 

category of risk. 

ii. ANPRM Discussion 

The ANPRM discussed criticisms of 

the current rule that it does not 

adequately calibrate the review process 

to the level of risk of the research, 

particularly in social and behavioral 

research. It also discussed whether 

answering questions should be 

sufficient indication of willingness to 

participate in survey or interview 


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46Executive Office of the President, OMB. (Sept. 

2006). Standards and Guidelines for Statistical 

Surveys. Retrieved from The White House: 

https://www.whitehouse.gov/sites/default/files/

omb/inforeg/statpolicy/standards_stat_surveys.pdf. 

research. It distinguished between 

informational or psychological risks and 

physical risks, and raised questions 

about how effectively IRB review 

provides protections from informational 

or psychological risks. 

iii. Educational Tests, Survey 

Procedures, Interview Procedures, or 

Observation of Public Behaviors (NPRM 

at §ll.101(b)(2)(i)) 

(1) NPRM Proposal 

The exclusion at §ll.101(b)(2)(i) is 

for research, not including 

interventions, that involves the use of 

educational tests (cognitive, diagnostic, 

aptitude, achievement), survey 

procedures, interview procedures, or 

observation of public behavior 

(including visual or auditory recording) 

uninfluenced by the investigators, if at 

least one of the following is met: 

• The information is recorded by the 

investigator in such a manner that 

human subjects cannot be identified, 

directly or through identifiers linked to 

the subjects; or 

• 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 research will involve a 

collection of information subject to the 

Paperwork Reduction Act of 1995, 44 

U.S.C. 3501 et seq., research information 

will be maintained on information 

technology that is subject to and in 

compliance with section 208(b) of the EGovernment Act of 2002, 44 U.S.C. 3501 

note, and all of the information 

collected, used, or generated as part of 

the research will be maintained in a 

system or systems of records subject to 

the Privacy Act of 1974, 5 U.S.C. 552a. 

The exclusion does not include 

research activities in which any sort of 

intervention is used, in addition to the 

specified methods of information 

collection. Also, the term ‘‘survey’’ as 

used here refers to information collected 

about individuals via questionnaire or 

similar procedures (e.g., the Current 

Population Survey conducted by the 

Census). ‘‘Human subjects’’ do not 

include organizations or businesses. 

‘‘Survey,’’ as used here, does not 

include the collection of biospecimens 

or other types of information collection 

that might involve invasive procedures. 

Thus, a survey that included 

information collections in addition to 

verbal or written responses, including 

the collection of a biospecimen or the 

use of some other physically invasive 

procedures (e.g., a diagnostic test and 

blood spot or buccal swab) could not 

use this exclusion. 

This exclusion includes the research 

activities in current exemption category 

2 in the (current Common Rule at 

§ ll.101(b)(2)), and some additional 

government information collection 

research activities using the same 

methods. As in the current exemption 

category 2, this proposed exclusion 

includes research studies whose 

methods consist of the use of 

educational tests, survey procedures or 

interview procedures, or observation of 

public behavior uninfluenced by the 

investigators, 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 

exclusion provides a list of the specific 

harms that must be considered, which is 

the same as in the current exemption 

category, with the addition of the 

specific harm of being damaging 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 proposed exclusion does not 

include the first element in the current 

exemption category at 

§ ll.101(b)(3)(i), which is the element 

pertaining 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. The 

rationale for this change in the proposed 

NPRM is that it does not seem 

appropriate to single out this category of 

subjects for different treatment in this 

way. 

The third element of this proposed 

exclusion covers research activities 

using the same methods identified 

above even when the data are recorded 

with identifiers and the information 

recorded may be personally sensitive or 

private but not explicitly damaging to 

an individual, if the research is subject 

to specified federal statutes and 

regulations that require data security 

and subject privacy protections. Under 

this proposal, the preponderance of 

research conducted by Federal 

employees and contractors that collects 

information exclusively through 

educational tests, questionnaires, or 

observations of behavior would no 

longer be subject to the Common Rule 

because most such collections would be 

subject to the Paperwork Reduction Act 

of 1995, would be maintained on 

information technology that is subject to 

and in compliance with section 208(b) 

of the E-Government Act of 2002, and 

all of the information collected, used, or 

generated as part of the research would 

be maintained in a system or systems of 

records subject to the Privacy Act of 

1974. Furthermore, consistent with 

these laws, OMB’s Standard 2.2 in its 

‘‘Standards and Guidelines for 

Statistical Surveys’’ 46 identifies the 

required notifications to potential 

survey respondents. 

Specifically, Standard 2.2 states that 

Federal agencies must ensure that each 

information collection instrument 

clearly states the reasons the 

information is planned to be collected; 

the way such information is planned to 

be used to further the proper 

performance of the functions of the 

agency; whether responses to the 

collection of information are voluntary 

or mandatory (citing authority); the 

nature and extent of confidentiality to 

be provided, if any (citing authority); an 

estimate of the average respondent 

burden together with a request that the 

public direct to the agency any 

comments concerning the accuracy of 

this burden estimate and any 

suggestions for reducing this burden; 

the OMB control number; and a 

statement that an agency may not 

conduct and a person is not required to 

respond to an information collection 

request unless it displays a currently 

valid OMB control number. These 

policies are rooted in the Fair 

Information Practice Principles that 

cover the following concepts: Individual 

participation, transparency, authority, 

purpose specification and use 

limitation, minimization, access and 

amendment, redress, quality and 

integrity, security, training, integration, 

and accountability. It is proposed that 

the information risk protections 

afforded by these laws and their 

implementing regulations are generally 

stronger than the privacy protections 

that result from IRB review, and would 

result in affording more uniform 

protections to participants. 

The rationale for excluding these 

research activities from the Common 

Rule, even when the research is not 

otherwise subject to additional federal 

controls, is that consent is inherent to 

participation and that the risks most 

likely to be experienced by subjects are 

related to disclosure of anonymous, 

non-sensitive information and are thus 

categorized as ‘‘low.’’ Said another way, 

all individuals, including vulnerable 

populations, would understand that 

actively providing response to 


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educational tests, surveys, or interview 

procedures constitutes consent to 

participate and that the risk associated 

with such participation would be 

related to disclosure of the information 

they provided. The exclusion 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, survey and interview 

procedures which 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. 

This exclusion is based on the 

assumption that the activities covered 

by this category are largely 

informational, and thus the most 

important role that an IRB might play 

with respect to reducing potential harms 

is to ensure data security and privacy 

protections. Under this assumption, the 

proposed exclusion 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. However, 

there are situations in which this 

assumption would not always hold. For 

instance, administration of a 

questionnaire or participation in a focus 

group on a sensitive topic may induce 

significant stress in some individuals, or 

individuals approached about taking a 

survey may feel compelled to 

participate. Whether and how the 

exclusion should be bounded so that the 

final rule achieves a balance among the 

principles of beneficence, autonomy, 

and justice is the subject of the request 

for comment on this proposed 

exclusion. 

In addition, this exclusion is in 

keeping with one of the goals of this 

NPRM, namely to reduce burden on 

research that includes sufficient 

protections to research subjects. By 

proposing that this exclusion could be 

satisfied if the information to be 

collected is subject to the Paperwork 

Reduction Act of 1995, would be 

maintained on information technology 

that is subject to and in compliance 

with section 208(b) of the E-Government 

Act of 2002, and all of the information 

collected, used, or generated as part of 

the research would be maintained in a 

system or systems of records subject to 

the Privacy Act of 1974, the NPRM 

notes that the privacy protections 

afforded by these laws are generally 

comparable, if not stronger, than the 

privacy protections that result from IRB 

review. 

(2) Questions for Public Comment 

9. Public comment is requested on the 

extent to which covering any of these 

activities under the Common Rule 

would substantially add to the 

protections provided to human research 

subjects. 

10. Public comment is sought on 

whether this exclusion should only 

apply to research activities in which 

notice is given to prospective subjects or 

their legally authorized representatives 

as a regulatory requirement. If so, please 

comment on what kind of information 

should be included in the notice such 

as the research purpose, privacy 

safeguards, contact information, ability 

to opt-out, etc. Would requiring notice 

as a condition of this exempt research 

strike a good balance between autonomy 

and beneficence? 

11. Public comment is sought 

regarding whether it is reasonable to 

rely on investigators to make selfdeterminations for the types of research 

activities covered in this particular 

exclusion category. If so, should 

documentation of any kind be generated 

and retained? 

12. Public comment is sought 

regarding whether some or all of these 

activities should be exemptions rather 

than exclusions. 

13. Public comment is sought 

regarding whether these exclusions 

should be narrowed such that studies 

with the potential for psychological risk 

are not included. Are there certain topic 

areas of sensitive information that 

should not be covered by this 

exclusion? If so, please provide 

exemplary language to characterize such 

topic areas in a manner that would 

provide clarity for implementing the 

Rule. 

14. For activities captured under the 

third element of this exclusion, do 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, 

should the exclusion be broadened to 

also cover secondary analysis of 

information collected pursuant to such 

activities? 

15. Public comment is requested on 

the extent to which excluding any of 

these research activities from the 

Common Rule could result an actual or 

perceived reduction or alteration of 

existing rights or protections provided 

to human research subjects. Are there 

any risks to scientific integrity or public 

trust that may result from excluding 

these research activities from the 

Common Rule? 

iv. Research Involving the Collection or 

Study of Information that has been or 

will be Collected (NPRM 

at §ll.101(b)(2)(ii)) 

(1) Current Rule 

This exclusion appears in the current 

Common Rule as exemption category 4 

(current Rule at §ll.101(b)(4)). This 

exemption currently applies to research 

involving the use of existing data, 

documents, records, and pathological or 

diagnostic specimens, but only if the 

sources are publicly available or if the 

information is recorded by investigators 

in such a manner that subjects cannot be 

identified, directly or through 

identifiers linked to them. 

(2) ANPRM Discussion 

The ANPRM proposed retaining this 

exemption as an exemption (not an 

exclusion). The ANPRM asked 

questions about whether the current 

limitations specified in exempt category 

4 (research involving the use of existing 

information or biospecimens, 

§ ll.101(b)(4) in the current Rule) 

should be eliminated. Specifically, the 

ANPRM suggested that the category 

would be revised to eliminate the word 

‘‘existing.’’ With this elimination, the 

exemption would be broadened to cover 

the use of information or biospecimens 

that were or will be collected for 

purposes other than the suggested 

research, rather than requiring that all of 

the information or biospecimens already 

exist at the time the study is suggested 

for exemption. 

(3) NPRM Proposal 

The second category of low-risk 

research activities excluded from the 

proposed rule is a revised version of the 

current Rule’s exemption category 4 

(current Rule at §ll.101(b)(4)). The 

NPRM proposal is that the excluded 

category at § ll.101(b)(2)(ii) includes 

research involving the collection or 

study of information that has been or 

will be acquired solely for non-research 

activities or was acquired for research 

studies other than the proposed research 

study when the sources are publicly 

available, or the information is recorded 

by the investigator in such a manner 

that human subjects cannot be 

identified, directly or through 

identifiers linked to the subjects, the 

investigator does not contact the 

subjects, and the investigator will not 

re-identify subjects or otherwise 

conduct an analysis that could lead to 


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47United States Office of Management and 

Budget, February 14, 2014, Memorandum to Heads 

of Executive Departments and Agencies; Guidance 

for Providing and Using Administrative Data for 

Statistical Purposes https://www.whitehouse.gov/

sites/default/files/omb/memoranda/2014/m-14- 

06.pdf. This guidance builds on three previously 

issued OMB memoranda designed to increase the 

value of existing data: Sharing Data While 

Protecting Privacy (M–11–02 of November 3, 2010), 

Open Data Policy-Managing Information as an 

Asset (M–13–13 of May 9, 2013), and Next Steps in 

the Evidence and Innovation Agenda (M–13–17 of 

July 26, 2013). 

creating individually identifiable 

private information. 

In light of the proposed expansion of 

the rule to cover certain biospecimens 

regardless of identifiability, this 

category has been modified such that it 

does not include secondary research use 

of biospecimens. Many of the comments 

supported the discussion in the ANPRM 

of eliminating the requirement that the 

information be ‘‘existing’’ at the time the 

study was suggested for exemption. 

Thus, in addition to changing this 

category of activities from being 

exempted to being excluded, the 

proposed exclusion does not require 

that the data exist as of the time that the 

study commences, but rather is 

expanded to include the secondary 

research use of data collected in the 

future for research or non-research 

purposes. The underlying logic behind 

the exclusion in proposed 

§ ll.101(b)(2)(ii) is that such research 

involves no direct interaction or 

intervention with human subjects, and 

any research use of the information does 

not impose any additional personal or 

informational risk to the subjects, 

because (1) the information is already 

available to the public, and so any risk 

it may include exists already, or (2) the 

information recorded by the investigator 

cannot be identified, and no connection 

to or involvement of the subjects is 

contemplated. Any requirements of the 

Common Rule would not provide 

additional protections to subjects, and 

could add substantial administrative 

burden on IRBs, institutions, and 

investigators. Creating this excluded 

category avoids that problem. 

(4) Questions for Public Comment 

16. Public comment is sought 

regarding whether it is reasonable to 

rely on investigators to make selfdeterminations for the types of research 

activities covered in this particular 

exclusion category. If so, should 

documentation of any kind be generated 

and retained? 

17. Public comment is requested on 

the extent to which covering any of 

these activities under the Common Rule 

would substantially add to the 

protections provided to human research 

subjects. Is there a way in which this 

exclusion should be narrowed? Public 

comment is also sought regarding 

whether activities described here should 

appear as an exclusion or as an 

exemption. 

v. Research Conducted by a Government 

Agency using Government-Generated or 

Government-Collected Data (NPRM at 

§ ll.101(b)(2)(iii)) 

(1) NPRM Proposal 

The third category of low-risk 

research activities excluded from the 

proposed rule at §ll.101(b)(2)(iii) is 

research conducted by a federal 

department or agency using 

government-generated or governmentcollected information obtained for nonresearch purposes (including criminal 

history data), if the information 

originally involved a collection of 

information subject to the Paperwork 

Reduction Act of 1995, 44 U.S.C. 3501 

et seq., the information is 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, and all of the 

information collected, used, or 

generated as part of the research is 

maintained in a system or systems of 

records subject to the Privacy Act of 

1974, 5 U.S.C. 552a. This proposed 

exclusion is consistent with the Federal 

Government’s emphasis on minimizing 

the burden on the public and 

maximizing the value of the information 

collected by the Federal Government, 

while protecting participant privacy and 

data security.47 This exclusion is 

proposed for situations in which both 

the original data collection and the 

subsequent (secondary) analysis are 

subject to data security, participant 

privacy, and notice requirements 

associated with the named federal 

statutes and regulations. As such, it 

does not seem that the delay imposed by 

obtaining a determination as ‘‘exempt’’ 

or ‘‘expedited’’ is likely to increase the 

protections provided to those who have 

already provided the government with 

information for other purposes. Public 

comment is requested on the extent to 

which covering any these activities 

under the Common Rule would 

substantially add to the protections 

provided to human research subjects. 

(2) Questions for Public Comment 

18. Public comment is sought on 

whether this or a separate exclusion 

should also include research involving 

information collected for non-research 

purposes by non-federal entities where 

there are comparable privacy safeguards 

established by state laws and 

regulations, or whether such nonfederally conducted research would be 

covered by the proposed exemption at 

§ ll.104(e)(2). 

19. Public comment is requested on 

the extent to which covering any of 

these activities under the Common Rule 

would substantially add to the 

protections provided to human research 

subjects. 

20. Public comment is sought 

regarding whether it is reasonable to 

rely on investigators to make selfdeterminations for the types of research 

activities covered in this particular 

exclusion category. If so, should 

documentation of any kind be generated 

and retained? 

21. Public comment is sought 

regarding whether some or all of these 

activities should be exemptions rather 

than exclusions. 

vi. Certain Activities Covered by HIPAA 

(NPRM at § ll.101(b)(2)(iv)) 

(1) ANPRM Discussion 

The public was asked to comment on 

whether it might be useful to adopt the 

distinction made by the HIPAA Privacy 

Rule, which distinguishes between 

‘‘health care operations’’ and ‘‘research’’ 

activities, defining ‘‘health care 

operations’’ to include, among other 

activities, ‘‘conducting quality 

assessment and improvement activities, 

including outcomes evaluation and 

development of clinical guidelines, 

provided that the obtaining of 

generalizable knowledge is not the 

primary purpose of any studies resulting 

from such activities.’’ The public was 

asked to comment about this 

specifically in the context of quality 

improvement activities. 

(2) NPRM Proposal 

The fourth category of low-risk 

research activities excluded from the 

proposed rule, found at 

§ ll.101(b)(2)(iv), covers activities that 

are regulated under the HIPAA Privacy 

Rule (i.e., covered entities). These are 

activities whose risks relate only to 

privacy and confidentiality, and are 

already subject to independent controls 

provided by HIPAA. Specifically, it is 

proposed that research, as it is defined 

in this proposed rule, that involves the 

use of protected health information by 

a HIPAA covered entity for ‘‘health care 

operations,’’ ‘‘public health activities,’’ 

or ‘‘research,’’ as those three terms are 

defined under the HIPAA Rules, would 


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be excluded from the Common Rule. 

This proposed exclusion would not 

apply if the investigator that receives 

and uses individually identifiable 

health information for a research study 

was not covered by the HIPAA Rules, 

even if the entity disclosing the 

individually identifiable health 

information to the investigator was 

covered by the HIPAA Rules. The 

exclusion is limited in this way to 

ensure that it only applies to research 

studies and information that are already 

subject to independent privacy, 

confidentiality, and security 

protections. 

A majority of comments on the 2011 

ANPRM favored distinguishing between 

research and health care operations, as 

such terms are defined in the HIPAA 

Privacy Rule and the Health Information 

Technology for Economic and Clinical 

Health (HITECH) Act, and excluding the 

latter from the policy. Some 

commenters noted that people involved 

in these various activities are protected 

in other ways, and alluded to the sorts 

of measures that provide protection. 

Others suggested that any exclusions 

should be limited to data collection and 

analysis activities, or to activities below 

a certain threshold of risk (i.e., minimal 

risk). A minority of comments objected 

to these exclusions, arguing that these 

activities represent encroachments on 

their individual rights and privacy, and 

that oversight in accordance with the 

Common Rule requirements would be 

more protective. The proposed 

exclusion excludes only certain 

activities that involve data collection 

and analysis, where privacy safeguards 

are in place. 

(3) Questions for Public Comment 

22. Public comment is requested 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 

human subjects involved in such 

research studies. 

23. Public comment is sought 

regarding to what extent the HIPAA 

Rules and HITECH adequately address 

the beneficence, autonomy, and justice 

aspects for the collection of new 

information (versus information 

collected or generated in the course of 

clinical practice, e.g., examination, 

treatment, and prevention). Should this 

exclusion be limited to data collected or 

generated in the course of clinical 

practice? If additional data collection is 

allowable, should it be limited to what 

is on the proposed Secretary’s list of 

minimal risk activities (discussed in 

more detail below in II.F.2 of this 

preamble)? 

24. Public comment is requested on 

whether additional or fewer activities 

regulated under the HIPAA Privacy Rule 

should be included in this exclusion. 

c. Applicability of Exclusions to the 

Subparts 

i. Current Rule 

The current Common Rule does not 

contain exclusion categories, though as 

discussed above, some of the proposed 

exclusions are similar to activities that 

are exempt under the current 

regulations, which therefore might 

provide a basis for comparison. 

All of the current exemption 

categories can be applied to research 

that is subject to subpart B. None of the 

current exemption categories can be 

applied to research that is subject to 

subpart C. 

The exemptions in the current Rule 

generally apply to subpart D. However, 

the exemption at §ll.101(b)(2), for 

research involving educational tests, 

survey or interview procedures, or 

observation of public behavior does not 

apply to subpart D except for research 

involving educational tests or 

observations of public behavior when 

the investigators do not participate in 

the activities being observed. 

ii. NPRM Proposals 

Language specifying the application 

of the exclusions to the subparts can be 

found in the NPRM at § ll.101(b)(2) 

and (3). 

It is proposed that all of the exclusion 

categories in § ll.101(b)(2) and (3) 

apply to research that is subject to 

subpart B, and therefore the 

requirements imposed by subpart B 

would not need to be met. 

It is similarly proposed that all of the 

exclusion categories in §ll.101(b)(2) 

and (3) apply to research involving 

prisoners, therefore the requirements of 

subpart C would not need to be met. 

This would narrow the scope of 

research currently requiring subpart C 

review and certification to OHRP. 

Considerations in favor of this 

conclusion include the preponderance 

of low-risk socio-behavioral research 

designed to improve prisoner welfare, 

including studies that focus on 

substance abuse treatment, community 

reintegration, and services utilization; 

the occurrence of prisoner-subjects in 

research not targeting prisoner 

populations; the occurrence of prisonersubjects in databases or registries; and 

the broad regulatory interpretation of 

the subpart C ‘‘prisoner’’ definition. 

Public comment is requested on 

whether the application of these 

exclusions to research involving 

prisoners is appropriate and acceptable. 

It is proposed that all of the exclusion 

categories in § ll.101(b)(2) apply to 

research subject to subpart D, with the 

exception that the exclusion proposed 

under §ll.101(b)(2)(i) would only 

apply to research involving educational 

tests or observations of public behavior 

when the investigator does not 

participate in the activities being 

observed. This limitation would 

maintain the protection currently 

provided by the similar application of 

the current exemption §ll.101(b)(2) 

to research involving children, and 

would continue to require IRB review 

under the Common Rule and additional 

IRB review under subpart D of 45 CFR 

part 46 when the research involves 

surveys or interview procedures with 

children or observation of public 

behavior when the investigator 

participates in the activities being 

observed. 

iii. Questions for Public Comment 

25. Should research involving 

prisoners be allowed to use any or all 

of the exclusions found at 

§ ll.101(b)(2) and (3), as currently 

proposed? 

26. Are there certain provisions 

within the broader categories proposed 

at §ll.101(b)(2) and (3) to which the 

subparts should or should not apply? 

3. Proposed Exemptions (NPRM at 

§ ll.104) 

The Common Rule has been criticized 

for inadequately calibrating the review 

process to the risk of research. Some 

have argued that, particularly given the 

paucity of information suggesting 

significant risks to subjects in certain 

types of survey and interview-based 

research, the current system 

overregulates such research. Further, 

many critics see little evidence that 

most IRB review of social and 

behavioral research effectively protects 

subjects from psychological or 

informational risks. Overregulating 

social and behavioral research in 

general may serve to distract attention 

from identification of social and 

behavioral research studies that do pose 

ethical challenges and thus merit 

significant oversight. 

The proposed exemption categories 

and attendant policies and procedures 

related to exemptions appear in the 

NPRM at § ll.104, and are guided by 

the following policy goals: 


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48Office for Human Research Protections. (2011, 

January 20). Exempt Research Determination FAQs. 

Retrieved from Frequently Asked Questions About 

Human Research: http://www.hhs.gov/ohrp/policy/

faq/index.html. 

• To create procedural efficiencies for 

IRBs, administrators and investigators in 

making and receiving exemption 

determinations, thereby reducing the 

overall IRB workload and the wait time 

for investigators to begin their work. 

• To ensure that reasonable 

safeguards are in place for certain lower 

risk research activities not fully 

excluded under the current Common 

Rule by requiring that research in 

certain exemption categories follow 

elements of the proposed rule, but not 

be required to undergo full IRB review 

according to the full set of criteria at 

§ ll.111(a)(1)–(8) and other regulatory 

requirements of the Common Rule . 

Note that all of the exemption 

categories in the current Rule have been 

carried over to the proposed Rule in one 

or another form. In particular, some of 

the current Rule’s exemptions have now 

become exclusions under the NPRM 

(and thus subject to no administrative or 

IRB review), while some remain in the 

NPRM’s exempt categories section. 

Under the current Common Rule, 

research may qualify for exemption 

from the regulatory policy if it falls into 

one of the six current categories at 

§ ll.101(b)(1)–(6). Such studies are 

fully exempt from the regulations. The 

current regulations do not specify who 

at an institution may determine that 

research is exempt under §ll.101(b). 

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 human subjects research is exempt. 

OHRP has recommended that 

institutions should 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 are acceptable assuming 

compliance with applicable regulations. 

The NPRM proposes to retain the term 

‘‘exempt,’’ (rather than ‘‘excused,’’ as 

suggested in the ANPRM) but require 

that exempt research comply with 

certain provisions of the proposed rule 

such as proposed privacy safeguards at 

§ ll.105 (discussed below). This 

policy retains and, in important respects 

(through a new safe harbor provision), 

expands the current flexibility of 

institutions to develop a system in 

which someone at the institution— 

including the investigator, unless 

prohibited by law—uses an exemption 

decision tool to make the exemption 

determination. 

It is important to recognize that while 

in some cases there are new 

requirements that have been imposed on 

the exemption categories that do not 

exist in the current version of the 

exemption categories, this usually does 

not actually represent a tightening of the 

rules for those exemptions. To the 

contrary, these changes are generally 

being made to allow the exemption in 

question to be expanded to cover 

activities that are not currently exempt. 

For example, adherence to new privacy 

standards is a new requirement in order 

for certain surveys to be exempt, but 

these are surveys that under the current 

Common Rule would require IRB 

review. 

The proposed eight exemptions are 

divided into three groupings according 

to the kind of risk characteristically 

involved and what protections are 

called for: (1) Low-risk interventions 

that do not require application of 

standards for information and 

biospecimen protection; (2) research 

that may involve sensitive information 

that requires application of standards 

for information and biospecimen 

protection described in proposed 

§ ll.105; and (3) secondary research 

involving biospecimens and identifiable 

private information that requires 

application of privacy safeguards 

discussed at proposed §ll.105, broad 

consent as discussed in proposed 

§ ll.116(c), and limited IRB review as 

discussed in proposed §ll.111(a)(9). 

a. Making Exempt Research 

Determinations (NPRM at § ll.104(c)) 

i. NPRM Goal 

The goal of this NPRM proposal is to 

create procedures for appropriate 

exemption determinations in a manner 

that does not waste time and effort. 

ii. Current Rule 

In developing policies and procedures 

addressing the exemptions, OHRP 

currently recommends that when an 

exemption determination is made, the 

specific exemption category or 

categories should be included in the 

record of the material supplied to the 

IRB and this information should be 

available for oversight purposes. In 

addition, OHRP guidance has said that 

institutional policies and procedures 

should identify clearly who is 

responsible for making exemption 

decisions. OHRP notes that under 

current policy 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 (§ll.101(c)) and 

that authority continues under the 

proposed regulations. 

iii. ANPRM Discussion 

The ANPRM discussed a mechanism 

to (1) register exempt research, and (2) 

audit a small but appropriate portion of 

such research, which would still be 

subject to other regulatory protections 

such as the suggested data security and 

information protection standards and 

certain consent requirements. 

The ANPRM discussed a tracking 

mechanism to enable institutions to 

assure that such research meets the 

criteria for inclusion in the suggested 

‘‘excused’’ categories. The original 

recommendations would require 

investigators to register their study with 

an institutional office by completing a 

brief form, thus eliminating the current 

practice of not allowing investigators to 

begin conducting such studies until a 

reviewer had determined it meets the 

criteria for excused research. This 

would make the institution aware of key 

information about the research (such as 

the purpose of the research and the 

name of the study’s principal 

investigator), without also requiring that 

the activity undergo a review that, if not 

done in a timely manner, could slow the 

research without adding any significant 

protection to subjects. In addition, the 

institution could choose to review some 

of the submissions at the time they are 

filed and, if deemed appropriate, require 

that the study be sent for expedited 

review or, in rare cases, convened IRB 

review. It would be made clear that the 

regulations would not require, and in 

fact, would discourage, having each of 

these registration forms undergo a 

comprehensive administrative or IRB 

review prior to commencing the study 

or even afterward. 

The auditing requirement was 

intended to encourage institutions to 

use the regulatory flexibility suggested 

for the exempt categories of research. 

The auditing requirement would have 

provided institutions with information 

needed to assess their compliance with 

the new ‘‘excused’’ categories without 

unnecessarily subjecting all such 

research to either prospective review, or 

even routine review sometime after the 

study is begun. Note that currently, 

OHRP recommends that there be some 

type of review by someone other than 

the investigator to confirm that a study 

qualifies as exempt, and many 

institutions do impose such a 

requirement even though such a 

requirement is extra-regulatory.48


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The ANPRM also asked whether it 

was acceptable for investigators to 

independently determine whether their 

research was exempt, whether review of 

all registrations should be required, and 

whether there should be a time 

limitation or waiting period before 

excused research could begin. 

The ANPRM also asked whether it 

was appropriate to require institutions 

holding a Federalwide assurance (FWA) 

to conduct retrospective audits of a 

percentage of the excused studies to 

make sure they qualify for inclusion in 

an excused category, and if so, how 

such audits should be conducted. 

iv. NPRM Proposal 

The NPRM proposes to adopt an 

exemption determination 

documentation requirement which is 

somewhat different from the registration 

system suggested in the 2011 ANPRM. 

To assist investigators and institutions 

in making a timely and accurate 

determination of exemption status the 

NPRM at § ll.104(c) states that federal 

departments or agencies will develop 

one or more exemption determination 

tools. Federal departments or agencies 

may create their own tool, or rely on a 

tool created by another department or 

agency (including the web-based tool 

created by HHS). The tool, which has 

not yet been developed, will be 

designed in such a way that if the 

person using the tool inputs accurate 

information about the study, the tool 

will produce an outcome which is the 

determination as to whether the study is 

exempt or not. Institutions may rely on 

use of the federally developed tool by 

investigators as a ‘‘safe harbor’’ for this 

determination: So long as the 

information that was provided to the 

tool was accurate, result of the 

application of the tool will be presumed 

by the federal departments or agencies 

to be an appropriate determination of 

exempt status. Use of the tool will be 

voluntary; each institution and agency 

would determine whether to rely on the 

decision tool for their determinations, 

and if so, who would be allowed to 

operate it. Institutions, if they so choose, 

could continue 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, it is 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. It should also be 

noted that for FDA-regulated device 

studies IRB review is required by 

statute. 

The NPRM also proposes 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. 

Maintenance of the output of the 

completed decision tool would fulfill 

this recordkeeping requirement. 

In general, commenters to the 2011 

ANPRM were not necessarily opposed 

to the concept of registration but sought 

further information on what this process 

would entail. Public commenters also 

expressed concerns about allowing an 

investigator to independently make the 

determination that his or her research is 

exempt. Other commenters suggested 

that this practice would be acceptable 

for some investigators, whose research 

is well known to IRB members, and is 

clearly within an exempt category. The 

ANPRM noted concerns that some 

exempt research was unnecessarily 

delayed by requirements of some 

institutions to review the research to 

make an exemption decision. 

Several institutions reported that they 

already as a matter of policy require 

investigators to submit exempt studies 

to the IRB, not necessarily for full board 

review, but to ensure that the exempt 

determination is valid. These decisions 

typically are made by the IRB 

administrator and never involve full 

review unless there is concern about the 

exemption status. Thus, they felt the 

registration requirement was 

unnecessary and would add new 

administrative burdens for research 

already considered low-risk. 

Other commenters, such as 

investigators conducting research 

currently considered exempt, were 

strongly opposed to a registration 

requirement because it would add a new 

burden to conducting less than minimal 

risk and exempt research. In addition, 

commenters raised concerns about the 

administrative burden and need for a 

retrospective audit system of registered 

research. 

This NPRM proposal is anticipated to 

provide more flexibility than the 

registration requirement originally 

proposed, while helping to ensure that 

correct determinations of exempt status 

are made. The existence of a ‘‘safe 

harbor’’ mechanism will hopefully 

encourage institutions to create policies 

that allow investigators to use the tool, 

and thus to be able to more quickly 

commence their research without 

needing additional administrative or 

IRB reviews for these types of studies. 

Other people at the institution who have 

access to accurate information about a 

proposed study may also utilize the 

tool, which will also allow research to 

go forward unimpeded. 

In addition, it is proposed that a 

change to § ll.109(a) be made to 

clarify that the Common Rule does not 

give IRBs the authority to review or 

approve, require modification in or 

disapprove research that qualifies for 

exemption under § ll.104(d), (e), or 

(f)(2). 

There is no auditing requirement in 

this NPRM proposal. Consequently, it 

does not address concerns raised at the 

ANPRM stage regarding potential 

conflict of interest if the investigator is 

providing the information to operate the 

decision tool. Public comment is sought 

on this idea regarding the operational 

details for further development of this 

proposal. Depending upon the 

comments received on this proposal, 

additional operational details regarding 

the proposed federally sponsored 

decision tool would be developed and 

subject to public comment. It should 

also be noted that the lack of an auditing 

requirement would not prohibit an 

institution from performing postapproval monitoring of exemption 

determinations according to the 

institution’s standard operating 

procedure. 

v. Questions for Public Comment 

27. Public comment is sought 

regarding how likely it would be that 

institutions would allow an investigator 

to independently make an exempt 

determination for his or her own 

research without additional review by 

an individual who is not involved in the 

research and immersed in human 

research protection e.g., a member of the 

IRB Staff. 

28. Public comment is sought 

regarding whether an investigator would 

be able to contrive his or her responses 

to the automated exemption decision 

tool in order to receive a desired result 

i.e., an exempt determination, even if it 

does not accurately reflect the research 

activities. 

29. Public comment is sought on 

whether it would be more appropriate 

for some of the exempt categories than 

others to rely on the exemption 

determination produced by the decision 

tool where investigators themselves 

input the data into the tool, or whether 

there should be further administrative 

review in such circumstances. 

30. Public comment is sought 

regarding whether relying on the 

exemption determination produced by 

the decision tool where investigators 

themselves input the data into the tool 


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as proposed would reduce public trust 

in research. 

31. Public comment is sought 

regarding how likely it would be that 

institutions would rely on such a 

decision tool to provide a safe harbor for 

an investigator making a determination 

that the proposed research qualifies for 

an exemption, or whether developing 

such a tool would not be worthwhile, 

and whether institutions would be able 

to adequately manage exemption 

determinations without the use of the 

decision tool. 

32. Public comment is sought 

regarding what additional information 

should be required to be kept as a record 

other than the information submitted 

into the decision tool, for example, a 

study abstract, the privacy safeguards to 

be employed, or any notice or consent 

document that will be provided. 

33. Public comment is sought 

regarding the value of adding an 

auditing requirement. 

b. Exemptions Subject to the 

Documentation Requirements of 

§ ll.104(c) and No Other Section of 

the Proposed Rule 

Four exemptions are proposed that 

will not be subject to any additional 

requirements apart from the need to 

keep a record of the determination that 

the study was exempt. Three of these 

four exemptions in proposed 

§ ll.104(d) are versions of exemptions 

found in the current rule. A revised 

version of exemption category 1 in the 

current Common Rule (research 

conducted in established or commonly 

accepted educational settings) is found 

at proposed § ll.104(d)(1) in the 

NPRM. A revised version of the current 

exemption category 5 (research and 

demonstration projects) is found at 

proposed 

§ ll.104(d)(2). Exemption category 6 

in the current Common Rule (taste and 

food quality evaluations) is found in the 

NPRM at § ll.104(d)(4), and is 

unchanged. 

i. Research Conducted in Established or 

Commonly Accepted Educational 

Settings (NPRM at §ll.104(d)(1); 

Current Rule at §ll.101(b)(1)) 

(1) NPRM Goal 

The goal is to retain an exemption for 

a considerable portion of education 

research, but to provide for review if the 

research might adversely affect students’ 

opportunity to learn required 

educational content, or the assessment 

of educators. 

(2) Current Rule 

The current exemption category 1 

(§ ll.101(b)(1) in the current Rule) is 

for research conducted in established or 

commonly accepted educational 

settings, involving normal educational 

practices, such as (i) research on regular 

and special education instructional 

strategies, or (ii) research on the 

effectiveness of or the comparison 

among instructional techniques, 

curricula, or classroom management 

methods. 

(3) NPRM Proposal 

The first exemption category is for 

research conducted in established or 

commonly accepted educational settings 

when it specifically involves normal 

educational practices. 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, so long as the 

research is not likely to adversely 

impact students’ opportunity to learn 

required educational content in that 

educational setting or the assessment of 

educators who provide instruction. 

This exemption category is a revised 

version of the first exemption category 

in the current Common Rule. The 

rationale for the revision is that there 

are concerns about whether the conduct 

of some research projects of this type 

might draw sufficient time and attention 

away from the delivery of the regular 

educational curriculum, and thereby 

have a detrimental effect on student 

achievement. The current education 

system places a strong emphasis on 

student performance on tests in core 

curriculum areas such as reading, 

science, and mathematics, which have a 

significant effect on such things as grade 

promotion and student assignment to 

different courses, and cumulatively 

influence student attainment and 

achievement. It could also have a 

negative effect on teachers being 

evaluated on the basis of student 

performance. The exemption category is 

designed to not include such research 

projects. Otherwise, the exemption is 

retained in order 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. 

(4) Questions for Public Comment 

34. Public comment is sought on 

whether this exemption category should 

only apply to research activities in 

which notice that the information 

collected will be used for research 

purposes 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 is sought on what kind of 

information should be included in the 

notice, such as the research purpose, 

privacy safeguards, contact information, 

etc. Comment is also sought on how 

such a notice should be delivered, e.g., 

publication in a newspaper or posting in 

a public place such as the school where 

the research is taking place, or by 

individual email or postal delivery. 

Note that other requirements, such as 

those of the Family Educational Rights 

and Privacy Act (FERPA) or the 

Protection of Pupil Rights Amendment, 

may also apply. Would requiring notice 

as a condition of this exempt research 

strike a good balance between autonomy 

and beneficence? 

35. Public comment is sought on 

whether the privacy safeguards of 

§ ll.105 should apply to the research 

included in § ll.104(d)(1), given that 

such research may involve risk of 

disclosure of identifiable private 

information. 

ii. Research and Demonstration Projects 

Conducted or Supported by a Federal 

Department or Agency (NPRM at 

§ ll.104(d)(2); Current Rule at 

§ ll.101(b)(5)) 

(1) NPRM Goal 

The NPRM exemption proposed at 

§ ll.104(d)(2) is for research and 

demonstration projects involving public 

benefit or service programs, and is a 

slightly revised version of exemption 5 

in the current Common Rule. 

The proposed regulatory revision and 

change in interpretation of the 

exemption is designed to clarify the 

scope of the exemption so that more 

research studies would be exempt. It is 

believed that these changes would make 

the exemptions 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 deliver 

social goods, consistent with the 

principle of beneficence. 

(2) Current Rule 

The current version of this exemption 

category was originally created based on 

the recognition that alternative 

processes are in place in which ethical 

issues raised by research in public 

benefit or service programs are be 

addressed by the officials who are 

familiar with the programs and 

responsible for their successful 

operation under state and federal laws. 

These alternative processes implicitly 

consider risk, but there is not a 

predefined scope for the likelihood or 


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49 48 FR 9266 (Mar. 4, 1983). 

50See 48 FR 9266–9270 (Mar 4, 1983). (OPRR 

Guidance on 45 CFR 46.101(b)(5), Exemption for 

Research and Demonstration Projects on Public 

Benefit and Service Programs, http://www.hhs.gov/ 

ohrp/policy/exmpt-pb.html). 

magnitude of risk in these research 

activities. In fact, the Secretary of HHS 

noted in 1983 that these demonstration 

and service projects are already subject 

to procedures which provide for 

extensive review by high level officials 

in various program administration 

offices. The Secretary further noted that 

review by an IRB would be duplicative 

and burdensome to state and local 

agencies and to other entities 

participating in demonstration projects. 

It was thought that removal of this 

unnecessary layer of review would not 

only reduce the cost of the projects but 

also help avoid unnecessary delays in 

project implementation.49

OHRP has interpreted the current 

exemption category 5 (§ll.101(b)(5) 

in the current Common Rule) to apply 

only to those research and 

demonstration projects designed to 

study a ‘‘public benefit or service 

program’’ that a Common Rule 

department or agency itself administers, 

and for which the public benefit or 

service program exists independent of 

any research initiative. As an example, 

OHRP has in the past said that a 

research study to evaluate a Centers for 

Medicare & Medicaid Services (CMS)- 

administered demonstration project 

comparing two different mechanisms for 

reimbursing providers under Medicare 

or Medicaid would meet this 

exemption. However, this exemption 

would not apply to some types of 

research, for example, the evaluation of 

clinical trials (e.g., a National of 

Institutes of Health-funded clinical trial 

comparing two treatment regimens for 

heart disease), even if such studies 

would inform Medicare reimbursement 

policies. 

(3) ANPRM Discussion 

The ANPRM asked several questions 

about the interpretation and 

applicability of current exemption 

category 5 (current Common Rule at 

§ ll.101(b)(5)), including the scope of 

the current interpretation of the category 

5 exemption. The ANPRM also asked if 

the current category 5 guidance entitled, 

‘‘OPRR Guidance on 45 CFR 

46.101(b)(5),’’ 50 should be revised, or if 

additional guidance on the 

interpretation of exemption category 5 is 

needed. 

More specifically, the ANPRM asked 

whether this exemption should be 

revised to assure that it is not 

misinterpreted or misapplied, whether 

broadening it would result in 

inappropriately increasing risks to 

subjects, how such risks might be 

mitigated, and whether OHRP guidance 

should be revised. 

(4) NPRM Proposal 

The second proposed exemption 

category (NPRM at 

§ ll.104(d)(2)) 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, and that are designed to 

study, evaluate, 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. 

It is proposed that each federal 

department or agency conducting or 

supporting the research and 

demonstration projects would be 

required to establish, on a publicly 

accessible federal Web site or in such 

other manner as the department or 

agency head may prescribe, 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 would be 

required to be published on this list 

prior to or upon commencement of the 

research. Agencies and departments 

would be able to create or use their own 

Web sites for this purpose, or use a Web 

site created by OHRP. Note that for 

studies exempted pursuant to 

§ ll.104(d)(2), the recordkeeping 

requirement at proposed § ll.104(c) 

would be deemed to be satisfied by the 

published list required under proposed 

§ ll.104(d)(2)(i). 

There were few responses to the 

questions posed on this exemption in 

the 2011 ANPRM. However, those that 

did comment noted that this category is 

often misunderstood by IRBs and, at 

best, would benefit from clearer 

guidance. Commenters said that 

examples would help investigators and 

IRBs understand when research 

activities included in demonstration 

projects constitute human subjects 

research subject to the Common Rule. 

Commenters noted that many activities 

in demonstration projects do not 

contribute to generalizable knowledge 

as they produce results that are relevant 

only to the program being assessed; as 

such, many of these activities do not 

meet the Common Rule’s regulatory 

definition of ‘‘research’’ and thus fall 

outside of the rule. Other commenters 

said that some activities in this category 

are mandated or required by law or 

regulation and should not be considered 

to be under the purview of the Common 

Rule. It was noted that the critical issue 

in these studies should be protecting 

privacy and as long as measures are in 

place to do so, additional protections 

are not required. 

The revision of the language in this 

exemption clarifies the original 

language to say that a federally 

conducted project examining any aspect 

of a public benefit or service program 

would qualify for the exemption. The 

clauses concerning procedures for 

obtaining benefits, other changes in 

programs and procedures, and changes 

in methods or levels of payment are 

merely examples of such projects, and 

are not considered to be all-inclusive. 

In addition, OHRP proposes to clarify 

its interpretation of public benefit and 

service programs which are being 

evaluated as part of the research to 

include public benefit or service 

programs that a Common Rule 

department or agency does not itself 

administer through its own employees 

or agents, but rather funds (i.e., 

supports) through a grant or contract 

program. Therefore, the exemption 

would be clarified to apply to research 

and demonstration projects supported 

through federal grants or cooperative 

agreements, for example. These 

activities include appropriate privacy, 

confidentiality and security safeguards 

for any biospecimen and information 

used in this research. For example, 

information collected in some 

demonstration projects are subject to the 

protections of the HIPAA rules, and 

Federal agencies include conditions in 

grants or cooperative agreements which 

require the recipient to protect the 

confidentiality of all project-related 

information that includes personally 

identifying information. 

It is believed that these changes 

would make the exemptions 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 deliver social goods. The proposed 

changes to this exemption would 

require OHRP to revise its existing 

guidance document on this exemption 

accordingly. 

These changes would bring the 

language into conformance with other 

provisions of the rule that refer to 

research ‘‘conducted or supported’’ by 

Federal agencies. Both current practice 

and the edited language cover such 


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research, whether it is conducted 

directly by federal staff or through a 

contract, cooperative agreement, or 

grant. These methods of administration 

are, of course, always subject to 

department or agency head approval, 

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 the 

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. 

Although research such as that 

described above is exempt, an 

additional requirement is proposed. In 

the interest of transparency, 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 Secretary may prescribe, 

a list of the research and demonstration 

projects which the federal department 

or agency conducts or supports under 

this provision. The research or 

demonstration project must be 

published on this list prior to or upon 

commencement of the research. The 

agency determines what will be 

included on this list and maintains its 

oversight. Agencies that already publish 

research and demonstration projects on 

a publicly accessible Web site could 

satisfy this proposed requirement if the 

existing Web site were to include 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 create any 

delay to the research. HHS will develop 

a resource that all Common Rule 

agencies may use to satisfy the 

requirement at proposed 

§ ll.104(d)(2)(i). Alternatively, an 

agency can make its own Web site. 

Currently, there is no such 

comprehensive listing of studies that 

have been determined to have met this 

exemption, so this requirement would 

also enable Common Rule departments 

and agencies to better assess the types 

of projects that use this exemption, and 

consider whether any changes to its 

scope would be appropriate. 

(5) Questions for Public Comment 

36. Public comment is sought on 

whether this exemption category should 

only apply to research activities in 

which notice is given to prospective 

subjects or their legally authorized 

representatives as a regulatory 

requirement. If so, comment is sought 

on what kind of information should be 

included in the notice, e.g., the research 

purpose, privacy safeguards, or contact 

information. Also comment on how 

such a notice should be delivered; e.g., 

publication in a newspaper or posting in 

a public place, or by individual email or 

postal delivery. Would requiring notice 

as a condition of this exempt research 

strike a good balance between autonomy 

and beneficence? In many cases, it may 

be that individual notice or consent to 

all potentially affected persons before 

the research or demonstration 

commences is ordinarily impossible in 

the conduct of such studies. For 

example, if a research or demonstration 

project will affect all inhabitants of a 

large geographic area (e.g., a housing, a 

police patrol, a traffic control, or 

emergency response experiment), or all 

clients or employees of a particular 

program or organization or setting will 

be subject to a new procedure being 

tested (e.g. a new approach to improving 

student performance, a new antismoking or anti-obesity program, a new 

method for evaluating employee 

performance), would it be possible to 

make participation voluntary for all 

affected individuals, or even to identify 

and inform all affected individuals in 

advance? 

37. Public comment is sought on 

whether this exemption category is 

appropriate based on the recognition 

that alternative processes are in place in 

which ethical issues raised by research 

in public benefit or service programs 

would be addressed by the officials who 

are familiar with the programs and 

responsible for their successful 

operation under state and federal laws, 

rather than meeting specific risk-based 

criteria, or whether risk limitations 

should be included, and if so, what 

those limitations should be. Though 

long-standing, this exemption has never 

identified specific risk-based criteria, or 

risk limitations to bound the type of 

projects that may be covered. When 

originally promulgated, the exemption 

did stipulate that following the review 

of such projects, if the Secretary 

determines that the research or 

demonstration project presents a danger 

to the physical, mental, or emotional 

well-being of a participant or subject, 

then written informed consent would be 

required. Public comment is sought on 

whether to limit the risk that can be 

imposed on subjects while using this 

exemption, and if so, how to 

characterize those limits in a clear 

fashion. If more than minimal risk 

interventions are included, public 

comment is sought on whether, for 

transparency, this should be made clear 

in the regulatory text. 

With regard to the issue of risks 

encountered by participants in such 

research or demonstration projects, 

comments are also sought regarding the 

argument that any and every 

demonstration project involving 

changes in public benefit or service 

programs (e.g., water or sewage 

treatment programs or pollution control 

programs, programs involving 

educational procedures, or programs 

involving emergency procedures related 

to extreme weather events, etc.) exposes 

those affected to possible risks of some 

kind. In this regard, those risks are 

ordinarily and perhaps always no 

different in kind or magnitude than 

those involved in simply making the 

change in procedures without using 

research tools to evaluate them. For 

example, health care providers could be 

required to perform certain sanitation 

reforms to prevent patient infections 

whether or not such reforms were first 

tested in practice through a research or 

demonstration project. It is common for 

all Federal departments and agencies 

that regulate private or public 

organizations to impose conditions of 

participation in public programs 

providing for safety, program integrity, 

financial reporting, etc. Public comment 

is sought regarding whether there 

should be conditions (e.g., an individual 

notice or consent requirement) imposed 

on such research or demonstration 

projects involving public benefit or 

service programs which might lead to 

significant impediments or limitations 

on testing and evaluation before or after 

being imposed program-wide. Would 

the effect of imposing expensive or 

impracticable conditions on public 

benefits or services evaluations be to 

reduce the number of such evaluations 

and consequently to expose program 

participants to increased risk through 

exposure to untested reforms? 

38. Public comment is sought on 

whether the existing privacy safeguards 

for such activities, including the Privacy 

Act, HIPAA rules, and other federal or 

state privacy safeguards provide 

sufficient independent controls, or 

whether other safeguards such as the 

privacy safeguards of §ll.105 should 

be applied. 


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iii. Research involving benign 

interventions in conjunction with the 

collection of data from an adult subject 

(NPRM at § ll.104(d)(3)) 

(1) NPRM Goal 

The goal of this proposed new 

exemption for studies that involve 

benign interventions is to eliminate IRB 

review of these low-risk studies to 

reduce time and effort, allow IRBs to 

focus more attention on research with 

higher risks or presenting other ethical 

challenges, and to enable this research 

to go forward. 

(2) Current Rule 

Currently, research studies in the 

social and behavioral sciences that do 

not qualify for exemption category 2 

(current Common Rule at 

§ ll.101(b)(2)), but that involve 

certain types of well-understood 

interactions with subjects (e.g., asking 

someone to watch a video and then 

conducting word association tests), 

require either convened board or 

expedited IRB review. 

(3) ANPRM Discussion 

The ANPRM considered whether to 

include on the list of exempt studies 

certain types of social and behavioral 

research conducted with competent 

adults that would involve specified 

types of benign interventions commonly 

used in social and behavioral research, 

that are known to involve virtually no 

risk to subjects, and for which prior 

review does little to increase protections 

to subjects. These would be 

methodologies that are familiar to 

people in everyday life and in which 

verbal or similar responses would 

constitute the research data being 

collected. The ANPRM asked whether 

this category should include research in 

which there is deception. 

(4) NPRM Proposal 

The proposed exemption at 

§ ll.104(d)(3) is new and includes 

research involving benign interventions 

in conjunction with the collection of 

data from an adult subject through 

verbal or written responses (including 

data entry) or video recording if the 

subject prospectively agrees to the 

intervention and data collection and at 

least one of the following is met: 

• The information obtained is 

recorded in such a manner that human 

subjects cannot be identified directly or 

through identifiers linked to the 

subjects; or 

• 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. 

For the purpose of this proposed 

provision, benign interventions would 

be brief in duration, harmless, painless, 

not physically invasive, not likely to 

have a significant adverse lasting impact 

on the subjects, and it would be 

required that the investigator has no 

reason to think the subjects will find the 

interventions offensive or embarrassing. 

If these criteria were met, such benign 

interventions might include research 

activities in which a subject is asked to 

read materials, review pictures or 

videos, play online games, solve 

puzzles, or perform cognitive tasks. If 

the research involves deceiving the 

subjects regarding the nature or 

purposes of the research, this exemption 

would not be applicable unless the 

subject authorizes the deception. For the 

purpose of this proposed 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. 

Many commenters to the 2011 

ANPRM supported adding another 

exemption category of research for 

certain types of social and behavioral 

activities, conducted with competent 

adults, that would involve specified 

types of benign interventions beyond 

educational tests, surveys, focus groups, 

interviews, and similar procedures that 

are commonly used in social and 

behavioral research, that are known to 

involve virtually no risk to subjects, and 

for which IRB review does little to 

increase protections for subjects. 

However, many commenters were 

opposed to the requirement that subjects 

be ‘‘competent adults’’ in order for the 

expanded exemption to apply, asking 

whether tests of competency would be 

required for such research to proceed. 

This new exemption category 

addresses research involving benign 

interventions, in which information is 

collected through verbal or written 

responses and recorded in a manner 

such that human subjects cannot be 

identified, or where the disclosure of 

responses would not place the subjects 

at risk of criminal or civil liability or be 

damaging to the subjects’ financial 

standing, employability, educational 

advancement, or reputation. Here, a 

‘‘benign intervention’’ is categorized as 

one that is temporary and painless, 

producing no lasting negative impacts. 

Examples of benign interventions might 

include research activities in which a 

subject is asked to read materials, 

review pictures or videos, play online 

games, solve puzzles, or perform 

cognitive tasks, so long as the 

interventions meet the requirements for 

this category. 

The NPRM proposes to allow this 

type of research to occur without the 

requirements of informed consent or 

data security protections because 

neither the intervention nor the 

identifiability of the information is 

likely to result in harm to the subject, 

and the subject must prospectively agree 

to the intervention and the data 

collection. This exemption would 

include some research using authorized 

deception, where there is a prospective 

agreement by the research subject to 

participate in the activity after being 

informed that he or she will be unaware 

or misled regarding the nature of the 

research (§ll.104(d)(3)(iii)–(iv)). 

Subjects must be adults, but the 

provision does not specify that they 

must be competent, and so tests of 

competency are not necessary; however, 

the presumption is that in keeping with 

the principle of respect for persons, 

these subjects will not be taken 

advantage of. This new exemption 

category is being added because respect 

for persons is accomplished through the 

prospective subject’s prospective 

agreement or authorization, 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. 

(5) Questions for Public Comment 

39. Public comment is sought on 

whether this exemption category should 

only apply to research activities in 

which notice is given to prospective 

subjects or their legally authorized 

representatives as a regulatory 

requirement. If so, comment is sought 

on what kind of information should be 

included in the notice, such as the 

research purpose (if authorized 

deception is not utilized), privacy 

safeguards, contact information, etc. 

Would requiring notice as a condition of 

this exempt research strike a good 

balance between autonomy and 

beneficence? 

40. Public comment is sought 

regarding what improvements could be 

made to the language describing the 

type of interventions in this exemption 

category so as to make clear what 

interventions would or would not 

satisfy this exemption category. 

41. Public comment is sought on 

whether it is reasonable, for purposes of 

this exemption, to rely on the 

exemption determination produced by 

the decision tool where investigators 


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themselves input the data into the tool, 

or whether there should be further 

administrative review in such 

circumstances. 

iv. Taste and Food Quality Evaluation 

and Consumer Acceptance Studies 

(NPRM at § ll.104(d)(4); current Rule 

at §ll.101(b)(6)) 

The exemption proposed in 

§ ll.104(d)(4) is found in the current 

Common Rule at §ll.101(b)(6). This 

exemption is for taste and food quality 

evaluation and consumer acceptance 

studies 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 EPA or the 

Food Safety and Inspection Service of 

the U.S. Department of Agriculture. 

This exemption is retained unchanged 

from the current Common Rule. The 

research activities included under this 

intervention are relatively benign, no 

sensitive information is collected, and 

presumably subjects are made aware of 

the nature of the activity before they 

participate, and may exercise their 

autonomy in choosing whether or not to 

participate. However, since the research 

activities involve physical interventions 

with the subject, the rules relating to 

exemption determinations and the 

record-keeping requirement for exempt 

activities are appropriate. 

(1) Question for Public Comment 

42. Public comment is sought on 

whether this exemption category should 

be narrowed to apply only to research 

activities in which notice is given to 

prospective subjects or their legally 

authorized representatives as a 

regulatory requirement. If so, comment 

is sought on what kind of information 

should be included in the notice such 

as the research purpose, privacy 

safeguards, contact information, etc. 

Would requiring notice as a condition of 

this exempt research strike a good 

balance between autonomy and 

beneficence? Should prospective 

subjects be given the explicit 

opportunity to opt out of such research? 

c. Exemptions Subject to the 

Documentation Requirements of 

§ ll.104(c) and the Privacy Safeguards 

Described in § ll.105 

Two exemption categories are 

proposed which will be subject to the 

documentation requirement and the 

new privacy safeguards. The first 

exemption category is for certain 

research involving educational tests, 

surveys, interviews, or observation of 

public behavior. The second category is 

for secondary research use of 

identifiable private information 

originally collected for non-research 

purposes where notice was given. 

One of the functions of IRB review 

when a study presents only 

informational risks is to ensure the 

sufficiency of the investigator’s plan for 

protecting any identifiable private 

information that will be collected, 

created, or used as part of the study. In 

keeping with one of the goals of this 

NPRM and as discussed in section II.A.3 

of this preamble, to reduce burden 

associated with research that includes 

sufficient protections to research 

subjects, this NPRM proposes to 

eliminate the need for IRB review for 

studies involving the collection of 

identifiable private information when 

collected through educational tests 

(cognitive, diagnostic, aptitude, 

achievement), survey procedures, 

interview procedures, or observation of 

public behavior (including visual or 

auditory recording), or in studies 

involving only the secondary analysis of 

identifiable private information 

originally collected for non-research 

purposes when the proposed privacy 

safeguards at § ll.105 are met. The 

newly proposed § ll.105 offers three 

avenues to meeting the data security 

and privacy protection requirements, all 

three of which are posited to be at least 

as protective as those usually that result 

from IRB review. 

• The investigator is required by law 

to comply with, or voluntarily complies 

with, the HIPAA Rules; 

• The activity is conducted by federal 

departments and agencies, and the 

activity 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 

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.; or 

• The investigator complies with the 

privacy safeguards promulgated by the 

Secretary of HHS (which standards will 

be designed so that they could be 

readily implemented by an individual 

investigator, and would involve 

minimal cost and effort to implement). 

It is believed that the protections 

afforded by the Paperwork Reduction 

Act, section 208 of the E-Government 

Act, and the Privacy Act in combination 

with each other are generally equivalent 

to the privacy protections that result 

from IRB review. It is similarly believed 

that the privacy protections afforded by 

HIPAA in the context of the studies 

exempted under § ll.104(e) justify 

eliminating IRB review. 

The proposed section 105 also 

includes limitations on the use, release, 

and disclosure of the identifiable private 

information collected or maintained for 

research subject to this Rule. 

Although most if not all of these 

requirements are already in effect for 

federal entities and HIPAA covered 

entities, they will likely be new to some 

institutions and their investigators. The 

intent is that Secretary would develop a 

list of ‘‘reasonable and appropriate 

safeguards’’ that would be easily 

implemented by investigators. As such, 

it is envisioned that the Secretary’s 

privacy safeguards described in 

proposed §ll.105 would be designed 

as a checklist that could be easily 

monitored by investigators and IRB 

members alike. In the case where IRB 

members have additional expertise, they 

may choose to deviate from the 

Secretary’s list. Acknowledging that it is 

difficult for the public to fully comment 

on the implications of such a checklist 

before it has been developed; the Rule 

includes a requirement that the 

Secretary solicit public comment on the 

proposed minimum safeguards. 

i. Questions for Public Comment 

43. Public comment is sought on the 

concept of requiring such minimum 

safeguards and limitations on 

disclosure, as well as whether the 

requirements of the proposed §ll.105 

would constitute a broadening of IRB 

responsibilities rather than a 

streamlining of the implementation of 

responsibilities that many IRBs already 

adopted. If an institution does view this 

as an inordinate broadening of 

responsibilities, does the institution 

currently have in place alternative 

mechanisms for ensuring data security 

and participant privacy in a research 

context? Suggestions for alternative 

approaches to meeting public 

expectation that federally sponsored 

research safeguard their data and protect 

privacy are sought during this public 

comment period. 

44. Public comment is sought 

regarding whether the proposed Rule’s 

information security requirements for 

biological specimens and identifiable 

private information are highly technical 

and require a level of expertise not 

currently available to most IRBs. Do 

these security requirements 

unrealistically expand IRB 

responsibilities beyond current 

competencies? 


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ii. 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 

(NPRM at § ll.104(e)(1)) 

(1) NPRM Goals 

The goal of the proposed exemption at 

§ ll.104(e)(1) is to eliminate the need 

for IRB review of certain low-risk 

studies that involve collecting 

information by means of educational 

tests, surveys, interviews, or observation 

of public behavior. The intent is that 

this change would reduce IRB and 

investigator time and effort in reviewing 

and submitting protocols, and would 

allow IRBs to focus more attention on 

research with higher risks or presenting 

other ethical challenges, would respect 

autonomy, and would enable this 

research to go forward. 

(2) Current Rule 

The current Common Rule only 

allows these activities, involving the 

recording of identifiable information 

about research subjects, to be exempt if 

the disclosure of the identifiable 

information outside the research could 

not reasonably place the subjects at risk 

of criminal or civil liability or be 

damaging to the subjects’ financial 

standing, employability, or reputation. 

(3) ANPRM Discussion 

The ANPRM discussed criticisms of 

the current Common Rule that it does 

not adequately calibrate the review 

process to the level of risk of the 

research, particularly in social and 

behavioral research. It also discussed 

whether answering questions should be 

sufficient indication of willingness to 

participate in survey or interview 

research. It distinguished between 

informational or psychological risks and 

physical risks, and raised questions 

about how effectively IRB review 

provides protections from informational 

or psychological risks. 

Specifically, the ANPRM discussed 

expanding the current exemption 

category 2 (current Rule at 

§ ll.101(b)(2)) to include all studies 

involving educational tests, surveys, 

interviews, and similar procedures, so 

long as the subjects are competent 

adults, without any further 

qualifications (but subject to the data 

security and information protection 

standards). 

(4) NPRM Proposal 

The exemption proposed in 

§ ll.104(e)(1) covers research, not 

including interventions, involving the 

use of educational tests (cognitive, 

diagnostic, aptitude, achievement), 

survey procedures, interview 

procedures or observation of public 

behavior (including visual or auditory 

recording), if the information obtained 

is recorded in such a manner that 

human subjects can be identified 

directly or through identifiers linked to 

the subjects. The research in this 

category is exempt from most 

requirements of the NPRM, but 

investigators must adhere to the privacy 

safeguards outlined in proposed 

§ ll.105. Note that the language used 

in this exemption is very similar to that 

used in the current exemption 2, 

proposed exclusion § ll.101(b)(2)(i), 

and the proposed exemption at 

§ ll.104(d)(3); unlike the language in 

those three places, however, the 

proposed exemption at § ll.104(e)(1) 

would allow for research to be exempt 

where sensitive identifiable private 

information is collected the release of 

which could pose some measure of risk. 

However, the exemption is subject to 

adherence to the proposed §ll.105 

privacy safeguards, which are designed 

to limit the chances that the release of 

that information would lead to harm. 

This exemption category includes 

research involving test development, 

and use of tests that have not already 

been shown to be valid or reliable, 

inasmuch as such research activity is 

desirable in order to determine the their 

validity and reliability, and the 

exemption category provides safeguards 

to ensure that results will not be used 

to evaluate student achievement. Note 

that the activities that are currently 

exempted under exemption category 2 

(involving similar ways to collect 

information, but only where either the 

identity of the subject is not recorded or 

disclosure of the information would not 

have any adverse consequences to the 

subject) would be moved under the 

NPRM to the proposed exclusion at 

§ ll.101(b)(2)(i), rather than being 

under an exemption. That proposed 

exclusion is discussed in section II.A.2 

of this preamble. Note also that this 

proposed exemption would cover the 

research activities under the exemption 

in the current Rule at 

§ ll.101(b)(3)(ii), such as the research 

activities funded subject to the 

Department of Justice statute related to 

certificates of confidentiality (42 U.S.C. 

3789g) and the information collections 

subject to the confidentiality provisions 

of the Education Sciences Reform Act 

(20 U.S.C. 9573) of the Department of 

Education. Presumably the safeguards 

provided by these statutes satisfy the 

privacy safeguards of the proposed 

§ ll.105. 

Consistent with the spirit of the 

principle of respect for persons, 

investigators should provide 

prospective subjects with sufficient 

information to make an informed 

decision about participation. Public 

comment is sought regarding whether 

some kind of notice must be given as a 

regulatory requirement for this 

exemption, and if so, what kind of 

information must be included in that 

notice. 

The rationale for characterizing these 

activities as low-risk is that prospective 

subjects can decline to participate or 

answer specific questions in procedures 

they are already familiar with from the 

experiences of daily life, and, 

importantly, that the information will be 

protected through the new privacy 

safeguards of § ll.105. The 

availability of this exemption is 

designed to reduce the volume of 

information collection that IRBs 

process, thereby enabling them to 

devote more time and attention to 

research studies which pose greater 

risks or involve ethical challenges. 

The underlying assumptions and 

rationale for this exemption mirror the 

rationale for the exclusion proposed in 

§ ll.101(b)(2)(i)(C). Here again it is 

presumed that the subjects are 

sufficiently familiar with survey and 

interview procedures and educational 

tests to be able to knowingly and 

willingly provide the information, or 

decline to participate. The rationale for 

this exemption category is that 

prospective subjects can decline to 

participate or answer specific questions 

in procedures they are already familiar 

with from the experiences of daily life, 

and that the information collected will 

be protected through the privacy 

safeguards of § ll.105. 

However, there are situations in 

which these assumptions would not 

always hold. For instance, 

administration of a questionnaire or 

participation in a focus group on a 

sensitive topic may induce significant 

stress in some individuals, or 

individuals approached about taking a 

survey may feel compelled to 

participate. Whether and how this 

exemption should be bounded so that 

the final rule archives a balance among 

the principles of beneficence, 

autonomy, and justice is the subject of 

a request for public comment on this 

proposed exemption. The use of this 

exemption is designed to enable IRBs to 

devote more time and attention to 

research studies which pose greater 

risks or involve more challenging 

ethical concerns. 


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(5) Questions for Public Comment 

45. Public comment is sought on 

whether the proposed exemption 

regarding the use of educational tests, 

survey procedures, interview 

procedures, or observation of public 

behavior (§ll.104(e)(1)) should be 

applied to research involving the use of 

educational tests with children and 

whether it should also be applied to 

research involving the use of survey or 

interview procedures with children. If 

so, for research involving children, 

should the permissible survey or 

interview topics be limited in some 

way? 

46. Public comment is sought on 

whether this exemption category should 

only apply to research activities in 

which notice is given to prospective 

subjects or their legally authorized 

representatives as a regulatory 

requirement. If so, comment is sought 

on what kind of information should be 

included in the notice such as the 

research purpose, privacy safeguards, 

contact information, etc. Would 

requiring notice as a condition of this 

exempt research strike a good balance 

between autonomy and beneficence? 

Should prospective subjects be given 

the explicit opportunity to opt out of 

such research? 

47. Public comment is sought on 

whether it is reasonable, for purposes of 

this exemption, to rely on the 

exemption determinations produced by 

the decision tool where investigators 

themselves input the data into the tool, 

or whether there should be further 

administrative review in such 

circumstances? 

48. Public comment is sought on 

whether this exemption category should 

be narrowed such that studies with the 

potential for psychological risk are not 

included. Are there certain topic areas 

of sensitive information that should not 

be covered by this exemption? If so, 

please provide exemplary language to 

characterize such topic areas in a 

manner that would provide clarity for 

implementing the Rule. 

iii. Secondary Research Use of 

Identifiable Private Information (NPRM 

at §ll.104(e)(2)) 

(1) NPRM Goal 

The goal of the proposed new 

exemption category at §ll.104(e)(2) is 

to facilitate secondary research using 

identifiable private information that has 

been or will be collected or generated 

for non-research purposes, when prior 

notice has been given and privacy 

safeguards and prohibitions on re-use of 

the information are in place. 

Technological developments and the 

creation of large databases have 

significantly increased the potential 

benefits of secondary research analyses. 

The proposed exemption category 

would eliminate the need for IRB review 

of certain low-risk studies that only 

involve secondary use of identifiable 

private information that was collected 

for non-research purposes. The 

information would be protected under 

the privacy safeguards of §ll.105, and 

respect for persons would be 

demonstrated through a requirement for 

notice. The proposed exemption is 

limited to the research use of the 

identifiable private information for the 

purposes of the specific research for 

which the investigator or recipient 

entity requested access to the 

information, not for any further 

secondary research use. This proposed 

exemption is intended to reduce IRB 

and investigator time and effort, and 

allow IRBs to focus more attention on 

research with higher risks or presenting 

other ethical challenges. The exemption 

would enable beneficial secondary 

research to occur without being 

impeded by administrative or IRB 

review, but with privacy safeguards to 

avoid harm and a notice requirement to 

show respect for persons. Public 

comment is sought regarding this 

proposal, including what limits in scope 

it should have, what controls and 

protections should be attached above 

and beyond the privacy safeguards of 

§ ll.105, and how best to respect the 

autonomy or other interests of the 

individuals who are the subjects of the 

information. 

(2) Current Rule 

Under the current Common Rule, 

secondary research studies using 

identifiable private information undergo 

IRB review and approval, often using 

the expedited review procedure. If the 

activity satisfies the relevant criteria, the 

IRB may waive the requirement for 

informed consent, which IRBs typically 

do. 

(3) ANPRM Discussion 

The ANPRM proposed that with 

regard to an investigator’s use of preexisting data (i.e., data that were 

previously collected for purposes other 

than the currently proposed research 

study) originally collected for nonresearch purposes, then, as is currently 

the rule, written consent or waiver of 

consent would only be required if the 

investigator obtains information that 

identifies the subjects. Under the 

ANPRM, there would accordingly have 

been no change in the current ability of 

investigators to conduct such research 

using de-identified data or a limited 

data set, as such terms are used in the 

HIPAA Rules, without obtaining 

consent. 

Second, the ANPRM proposed that if 

the data were originally collected for 

research purposes, then consent would 

be required regardless of whether the 

investigator obtains identifiers. This 

would have been a change with regard 

to the current interpretation of the 

Common Rule in the case where the 

investigator does not obtain any 

identifiers. That is, the allowable 

current practice of telling the subjects, 

during the initial research consent, that 

the information they are providing will 

be used for one purpose, and then after 

stripping identifiers, allowing it to be 

used for a new purpose to which the 

subjects never consented, would not 

have been allowed. 

(4) NPRM Proposal 

The NPRM proposal here is for a new 

exemption covering the secondary 

research use of identifiable private 

information that has been or will be 

acquired for non-research purposes, if 

the following are met: 

• Prior notice has been given to the 

individuals to whom the identifiable 

private information pertains that such 

information may be used in research; 

• The privacy safeguards of 

§ ll.105 are required; and 

• The identifiable private information 

is used only for purposes of the specific 

research for which the investigator or 

recipient entity requested access to the 

information. 

Under the current system, IRBs 

frequently waive consent for research 

involving the secondary use of 

identifiable private information, 

particularly when the data sets are large 

or drawn from multiple institutions. In 

such circumstances, IRBs often impose 

privacy and data security protection 

requirements. However, since this 

proposed exemption category requires 

that the privacy safeguards at § ll.105 

are in place, requiring these studies to 

undergo IRB review will provide little 

or no additional protections to subjects, 

while continuing to generate potentially 

substantial burdens on investigators and 

IRBs and diverting IRB resources away 

from research that may involve more 

serious ethical challenges. 

Under this proposed exemption there 

will be greater protections for these 

research subjects than is currently the 

case. The new privacy safeguards of 

§ ll.105 would be applied to this 

research, and would be the same 

safeguards that would be used for many 

other types of research under the NPRM. 

In addition, the scope of the exemption 

is limited to the specific research for 


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which the investigator or recipient 

entity requested access to the 

information, so the otherwise 

permissible uses, releases and 

disclosures under § ll.105(c) would 

not apply to research covered by this 

exemption. Respect for persons would 

be given more weight insofar as the 

subjects would now receive notice that 

research might take place, which is 

currently not required. 

Further, in many cases, other laws 

such as HIPAA also provide protections 

in the research context for the 

information that would be subject to 

this proposed exemption (e.g., clinical 

records), such that additional Common 

Rule requirements for consent may not 

be necessary 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 proposal 

does not disturb those laws. 

The NPRM proposal limits the use of 

this exemption to cases in which 

individuals have been informed that the 

information may be used in research 

with the goal of ensuring that research 

under this exemption exhibits respect 

for persons. In particular, by ensuring 

that subjects are notified that their 

information may be used for research, 

this notice requirement may enhance 

subject autonomy. 

Alternative scopes for this provision 

are also proposed for consideration. A 

narrower scope could be envisioned that 

would limit the exemption to data 

generated by the Federal Government 

for which a privacy impact assessment 

has been conducted pursuant to section 

208(b) of the E-Government Act of 2002, 

44 U.S.C. 3601 et seq., that fully 

describes the ways that the information 

will be accessed, used, maintained, 

disseminated, and protected, and there 

is a formal written agreement between 

the investigator and the federal agency 

that requires the investigator to apply 

the same practices and safeguards as 

those addressed in the privacy impact 

assessment. Such a narrower 

interpretation might be easier to 

implement, and the line between 

§ ll.104(e)(2) and (f)(2) would be 

clearer. 

Alternatively, it could be broadened 

to allow additional research uses of the 

information beyond the specific 

research for which the investigator or 

recipient entity obtained the 

information. 

The proposed exemption category 

could also be revised to change the 

manner in which respect for persons 

would be demonstrated by requiring 

that individuals have been given the 

opportunity to opt out of any secondary 

research with their identifiable private 

information. This would mean that 

subjects could exercise their autonomy 

to choose not to allow their information 

to be used, although this would not 

meet the even higher standard of fully 

informed active consent. Under this 

alternative, which would give 

prospective subjects the opportunity to 

opt out, it could be argued that the 

balance would be struck even more in 

favor of respect for persons by limiting 

the exemption to research where more 

than prior notice was required. This 

would restrict the exemption to research 

where an even greater measure of 

respect for persons had occurred, that is, 

that the individuals had been given the 

right to decline to participate in 

research, rather than simply being 

notified that such research was going to 

take place. Public comment is sought 

regarding this alternative approach as 

well. 

Finally, it also should be noted that 

section 511 of the Medicare Access and 

CHIP Reauthorization Act of 2015 

requires the Secretary to issue a 

clarification or modification with 

respect to the application of these 

regulations to certain activities 

involving clinical data registries. This 

exemption category might allow certain 

research activities of these clinical data 

registries not otherwise covered by the 

proposed HIPAA-related exclusion at 

§ ll.101(b)(2)(iv) (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. 

(5) Questions for Public Comment 

49. Public comment is sought on the 

types of research that should fall under 

the proposed exemption. Should the 

proposed exemption be available to all 

types of research using identifiable data 

collected for non-research purposes or 

should the exemption be available only 

to a more limited subset of research? For 

example, should the proposed 

exemption apply only for research using 

records and information already subject 

to comprehensive privacy and other 

protections in other Federal laws (e.g., 

records held by the Federal Government 

subject to the Federal Privacy Act, or 

records governed by HIPAA or FERPA)? 

Depending upon the scope of the 

exemption, the relationship between 

this exemption and the exemption 

proposed at § ll.104(f)(2) would need 

to be clarified. Since a major 

justification for including this 

exemption is to reduce burden on IRBs, 

should the proposed exemption apply 

only to research for which IRBs 

typically waive informed consent, that 

is, where the research could not 

practicably be carried out without a 

waiver of informed consent, and the 

rights and welfare of subjects will not be 

adversely affected by the waiver? 

Finally, is there a sufficient need for this 

exemption at all given the other 

proposed exclusions and exemptions? 

50. Public comment is sought 

regarding whether the proposed 

exemption should be limited to research 

in which individuals had been informed 

of the potential future research use of 

their information, and given the 

opportunity to opt out of having their 

identifiable private information used for 

research. If the proposed exemption 

should be limited in this way, what 

information should be included in the 

opportunity to opt out? If the 

opportunity to opt out is made a 

condition of the exemption category 

how should it be structured (e.g., how 

long and under what circumstances 

should it remain in effect) and what, if 

any, impact should the opt out have on 

other provisions of the rule, such as the 

ability of an IRB to waive informed 

consent for a subsequent research study 

using the individual’s information? Are 

there other or alternative mechanisms 

that should be required to respect 

individuals’ autonomy and other 

interests? 

51. Public comment is sought 

regarding what should constitute notice 

for purposes of this exemption category. 

Given the many different types of data 

that would be covered by this provision 

(e.g., data from private entities used for 

social or behavioral science research, 

government records for which laws 

already establish standards for notice, 

and data publicly available for 

harvesting from the internet), would it 

be possible to develop a uniform 

‘‘notice’’ requirement? What type of 

notice, in terms of its dissemination and 

scope, should be considered to meet this 

requirement of the proposed exemption? 

With regard to the dissemination of the 

notice, should the notice requirement be 

permitted to be fulfilled through a 

general public notice, not specifically 

directed to individuals who are 

potential research subjects, such as the 

notice allowable under the Privacy Act? 

Would a prominent notice posted in all 

clinics or other relevant public places 

where information will be collected be 

acceptable? Should each individual 

whose data could be used receive their 

own notice, such as is required of direct 

treatment providers covered by the 


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HIPAA Privacy Rule? With regard to the 

content of the notice required by this 

proposed exemption, what kind of 

information should be included in the 

notice, such as the types of research that 

might be conducted, privacy safeguards, 

contact information, etc.? 

52. Public comment is sought on 

whether, on the other hand, prior notice 

is necessary. Is the notice requirement 

proposed for this exemption a 

meaningful and important measure to 

respect individual autonomy, 

particularly if the notice requirement 

could be fulfilled through a general 

public posting? Current practices 

suggest that IRBs will frequently waive 

informed consent for studies involving 

the secondary use of identifiable private 

information collected for non-research 

purposes. If the exemption were to 

exclude the notice requirement, but 

continue to require application of the 

data security and privacy safeguards of 

§ ll.105 and restrict the use of 

identifiable private information to only 

purposes of the specific research for 

which the investigator obtained the 

information, would the exemption 

better strike a reasonable balance 

between respect for persons and 

beneficence, while eliminating the 

current requirement for IRB review? 

53. Public comment is sought as to 

whether this exemption would provide 

appropriate protections for research 

conducted by clinical data registries, 

while enabling these research activities 

to proceed without delay, and what 

should be included in guidance 

regarding such activities. Public 

comment is sought regarding the extent 

to which other exclusions or exemption 

categories would apply to research 

conducted by clinical data registries, 

such that the conditions of this 

exemption category would not apply. 

d. Exemptions Subject to the 

Documentation Requirements of 

§ ll.104(c), the Privacy Safeguards 

Described in § ll.105, Limited IRB 

Review as Described in §ll.111(a)(9), 

and Broad Consent in Accordance With 

§ ll.116(c) 

i. NPRM Goals 

The goal of this proposed rule is to 

enable the conduct of research in the 

rapidly growing area of research 

involving biospecimens, especially 

genetic analyses, while recognizing the 

autonomy interests of people to decide 

whether or not to participate in this area 

of research. Some people have a 

particular interest in whether research 

will be carried out with their 

biospecimens, and want to exercise 

some control over their biospecimens. 

At the same time, biospecimen 

repositories are being created to enable 

innumerable research studies in the 

future, and the pace of technology 

development is such that the specific 

research studies to be carried out with 

those biospecimens is unknown at the 

time the biospecimens are collected. 

ii. Current Rule 

The current Rule requires IRB review 

and approval of research involving 

identifiable private information, 

including individually identifiable 

biospecimens. IRB waiver of informed 

consent is allowable under the Common 

Rule, if the research study satisfies the 

criteria for waiver of informed consent. 

The current Rule also allows for 

research without consent when a 

biospecimen is used for research under 

conditions where the investigator does 

not possess information that would 

allow him or her to identify the person 

whose biospecimen is being studied. 

iii. ANPRM Discussion 

The ANPRM considered requiring 

written general consent for secondary 

research use of biospecimens originally 

collected in research or non-research 

settings regardless of whether they 

include identifiers. The ANPRM 

proposed an excused or exempt category 

for research involving the secondary use 

of biospecimens originally collected for 

either research or non-research purposes 

if there was written broad consent for 

the research use of the biospecimens, 

typically obtained at the time of the 

original collection. The ANPRM also 

considered whether the broad consent 

should include check-off boxes allowing 

subjects to consent or decline consent 

for types of research raising unique 

concerns. 

iv. NPRM Proposals 

The NPRM includes two exemptions 

proposed in § ll.104(f) to facilitate 

storage, maintenance, and secondary 

research use of biospecimens and 

identifiable private information. 

Generally the exemption at 

§ ll.104(f)(1) will first be employed to 

allow the storage or maintenance for 

secondary research use of biospecimens 

or identifiable private information, by 

means of broad consent being obtained. 

Following that, the secondary research 

that will be conducted using such 

biospecimens or identifiable private 

information could often be exempted 

under §ll.104(f)(2). 

A majority of commenters opposed 

the suggestion that there be consent 

requirements for the research use of 

non-identifiable biospecimens collected 

for purposes other than the current 

research study. Some commenters also 

favored requiring IRB review and 

approval for specific studies involving 

the use of identifiable private 

information and identifiable 

biospecimens, rather than permitting 

the use of a broad consent for future use 

to satisfy the regulatory requirement for 

consent. These commenters indicated 

that IRB review of specific research 

studies, and the IRB’s consideration of 

whether a study-specific informed 

consent should be required or whether 

informed consent could be waived, was 

more protective of human subjects than 

the ANPRM recommendation permitting 

use of a broad consent for future use. 

Commenters to the 2011 ANPRM 

were mostly concerned with the cost 

and burden that would be imposed by 

the requirement to obtain consent for 

future research use of all biospecimens, 

regardless of identifiability. 

Commenters anticipated these costs to 

include obtaining consent from 

participants and the administrative 

efforts required to keep track of the 

consent status of biospecimens. Most 

commenters did not provide detailed 

cost estimates with their comments; 

data are specifically requested in 

response to this NPRM. In addition, 

estimates of the type and number of 

studies that could not be pursued using 

existing samples and data because of the 

absence of sufficient consent are 

requested. Comment is also sought on 

the value to the public and research 

participants of being asked their 

permission for research use of their data 

and biospecimens. 

While consideration was given to the 

opposition expressed by ANPRM 

commenters of a consent requirement 

for secondary research use of nonidentified biospecimens, the NPRM 

proposes to require that consent be 

obtained for the research use of nonidentified biospecimens, but to allow for 

that consent to be broad. Thus, while 

consent would be required for the 

research use of non-identified 

biospecimens, one would not have to 

obtain study-specific consent for the 

research use of those biospecimens, 

drastically reducing the burden imposed 

by this new requirement. 

The NPRM proposal includes several 

protections for secondary research use 

of biospecimens in addition to the broad 

consent. Research activities falling 

under the exemption at §ll.104(f) are 

subject to the requirements under 

proposed §ll.104(c). This would 

require that exemption determinations 

be made by someone knowledgeable of 

the regulations, or by the to-be-created 

exemption determination tool (when 

utilized by an investigator or other 


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individual). Additionally, the 

documentation requirement would 

allow institutions to better know the 

scope and volume of secondary research 

studies conducted at an institution. Also 

note that § ll.104(f)(1) requires that an 

IRB review the consent process through 

which broad consent would be obtained 

in the non-research context, to further 

allay ethical concerns about obtaining 

broad consent in clinical and other nonresearch contexts. 

(1) Exemption for the Storage or 

Maintenance of Biospecimens or 

Identifiable Private Information for 

Secondary Research Use (NPRM at 

§ ll.104(f)(1)) 

The first exemption in this group, at 

proposed §ll.104(f)(1), is for storage 

or maintenance for secondary research 

use of biospecimens or identifiable 

private information that have been or 

will be acquired for research studies 

other than for the proposed research 

study, or for non-research purposes, if 

the following criteria are met: 

• Written consent for the storage, 

maintenance, and secondary research 

use of the information or biospecimens 

is obtained using the broad consent 

template that the Secretary of HHS will 

develop. Oral consent, if obtained 

during the original data collection and 

in accordance with the elements of 

broad consent outlined in §ll.116(c) 

and (d)(3), would be satisfactory for the 

research use of identifiable private 

information initially acquired in 

accordance with activities excluded 

under §ll.101(b)(2)(i) or exempt in 

accordance with § ll.104(d)(3) or (4), 

or §ll.104(e)(1); and 

• The reviewing IRB conducts a 

limited IRB review of the process 

through which broad consent will be 

sought, and, in some cases, of the 

adequacy of the privacy safeguards 

described in § ll.105. 

This exemption category only allows 

for the storage or maintenance for 

secondary research use of biospecimens 

or identifiable private information. Note 

that this exemption does not exempt the 

creation of any data or the actual new 

collection of any biospecimens from a 

person through a research interaction or 

intervention. (For example, if the 

proposed research activities involved 

creating a research repository of DNA 

samples that would be obtained from 

people through cheek swabs, the 

collection of the cheek swabs would 

mean that the creation of the research 

repository would require IRB review, 

and would not be exempt.) This exempt 

category is for secondary research use of 

biospecimens and identifiable private 

information and applies to 

biospecimens and identifiable private 

information that were initially collected 

for purposes other than the proposed 

research activity. The term ‘other than 

the proposed activity’ here means that 

the information or biospecimens were or 

will be collected for a different research 

study or for a non-research purpose. 

In the case of a research study 

involving the actual new collection of 

biospecimens such as a clinical trial, the 

informed consent process could include 

obtaining informed consent for the 

original study (which study would not 

be exempt and would require IRB 

review and the usual type of consent 

document as required under 

§ ll.116(a) and (b)), and for secondary 

research use of the biospecimens. The 

informed consent form for the latter step 

(the secondary research use) could make 

use of the Secretary’s template, in which 

case the biospecimen would be eligible 

for maintenance or storage under 

§ ll.104(f)(1) with limited IRB review 

or for a secondary research study under 

§ ll.104(f)(2). If the Secretary’s 

template for broad consent is not used, 

the storage or maintenance for 

secondary research use would not meet 

this exemption and the consent form 

would need to be reviewed and 

approved by an IRB, either along with 

the IRB review of the original study, if 

the maintenance and storage for 

secondary research is known and 

described, or later, if it is not. Note also 

that if the Secretary’s template is not 

used, the § ll.104(f)(2) exemption, as 

discussed below, would not apply to 

exempt any actual secondary research 

studies conducted using the stored 

biospecimens. IRB review would be 

needed for each of those studies, unless 

the research met one of the proposed 

exclusions at § ll.101(b)(1) or (b)(3), 

or the exemption found in proposed 

§ ll.104(d)(2). 

This exemption requires written 

informed consent using the Secretary’s 

template for broad consent for 

secondary research, or oral consent, in 

specified circumstances. This broad 

consent requirement will enable 

subjects the choice to include their 

biospecimens and information in this 

research. The consent form using the 

Secretary’s template would include the 

information required in §ll.116(c). 

Oral broad consent would also need to 

include all of the elements of consent at 

§ ll.116(c), and would only be 

permissible for the research use of 

identifiable private information, not 

biospecimens, when the identifiable 

private information was initially 

acquired as part of any of the following 

four excluded or exempt categories of 

research: (1) The exclusion related to 

research, not involving interventions, 

that involves the use of educational 

tests, survey procedures, interview 

procedures, or observation of public 

behavior (§ll.101(b)(2)(i)); (2) the 

exemption related to research involving 

benign interventions (§ ll.104(d)(3)); 

(3) the exemption related to taste and 

food quality evaluation and consumer 

acceptance studies (§ ll.104(d)(4)); or 

(4) the exemption related to research 

involving the use of educational tests, 

survey procedures, interview 

procedures, or observation of public 

behavior (§ll.104(e)(1)). 

It is proposed that oral broad consent 

only be permitted to satisfy these 

exemptions regarding the secondary use 

of identifiable private information 

(§ ll.104(f)(1) and (f)(2)) if the 

identifiable private information was 

initially acquired as part of any of the 

four above-mentioned exclusion and 

exemption categories because these four 

categories are the only ones that are 

expected to typically involve some 

interaction with human subjects, and 

thus give investigators the opportunity 

to obtain oral consent from subjects for 

the secondary use of research data 

obtained as part of the initial research 

study. 

This exemption also requires adhering 

to the privacy safeguards described in 

the proposed section §ll.105. 

The exemption also includes a 

requirement for limited IRB review 

(§ ll.111(a)(9)). The purpose of this 

limited IRB review is to ensure that the 

process of obtaining consent will occur 

in an appropriate way, because there 

may be some circumstances (for 

example, when someone is admitted for 

emergency care), when the individual is 

not able to make an informed 

considered decision. This IRB review 

will, for many institutions, be 

essentially a ‘‘one-time’’ event (as 

opposed to being needed for specific 

research studies); the IRB would review 

an overall general institutional protocol 

for the manner in which people can 

provide broad consent for the 

maintenance or storage of their 

biospecimens for future secondary 

research. Such a general institutional 

protocol would need to identify the 

circumstances in which broad consent 

would be sought for secondary research 

use of biospecimens so that the IRB 

could determine that these 

circumstances are consistent with the 

requirements for voluntary informed 

consent as described in the introductory 

language to proposed §ll.116. 

In addition, if there will be a change 

in the way the biospecimens and 

information will be maintained for the 

secondary research purposes, rather 


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than simply changing the eligibility for 

secondary research status of 

biospecimens or information already 

being maintained for other purposes, 

then limited IRB review must also 

ensure that the biospecimen and 

information protection standards are 

still met. For example, if it is envisioned 

that the identifiable private information 

collected will be stored both at the 

institution obtaining the information, 

and also stored at a second institution, 

an IRB would also need to determine if 

the §ll.105 privacy safeguards are 

adequate. 

(2) Exemption for Secondary Research 

Use of Biospecimens or Identifiable 

Private Information where Broad 

Consent has been Sought and Obtained 

(NPRM at § ll.104(f)(2)) 

The second exemption in this 

exemption group, at §ll.104(f)(2), is 

for research involving the use of 

biospecimens or identifiable private 

information that have been stored or 

maintained for secondary research use, 

if consent for the storage and 

maintenance of the information and 

biospecimens was obtained as detailed 

using the broad consent template that 

the Secretary of HHS will develop. Note 

that oral broad consent would be 

allowed to the extent permitted under 

proposed §ll.104(f)(1)(i)(A). If the 

investigator anticipates that individual 

research results will be provided to a 

research subject, the research may not 

be exempted under this provision and 

must be reviewed by the IRB and 

informed consent for the research must 

be obtained to the extent required by 

proposed §ll.116(a) and (b). 

This exemption category at 

§ ll.104(f)(2) is for the actual 

secondary research studies that will be 

conducted using biospecimens or 

identifiable private information that 

have been stored for unspecified 

secondary research studies. This 

exemption does not include additional 

analyses being conducted to support or 

augment the original research study for 

which the information or biospecimens 

were originally collected. 

The proposed exemption category at 

§ ll.104(f)(2) requires that the privacy 

safeguards at § ll.105 are met, and 

that broad consent to the earlier storage 

or maintenance of the biospecimens and 

information had already been obtained 

consistent with the requirements of 

§ ll.104(f)(1). This means that for 

secondary research using biospecimens 

informed consent must have been 

obtained using a consent form using the 

Secretary’s template. It is presumed that 

research involving newborn blood spots 

would frequently take place using this 

provision. 

The rationale for these two 

exemptions is that they provide for 

obtaining broad consent from subjects 

for the research use of specimens, 

honoring the principle of respect for 

persons, they provide protections for the 

information involved through the 

privacy safeguards of §ll.105, and the 

limited IRB review proposed at 

§ ll.111(a)(9) ensures that the privacy 

safeguards and informed consent 

process are indeed adequate. 

The exemption at §ll.104(f)(2) 

would not apply to research in which 

the investigator anticipates that research 

results will be provided to a subject. If 

it is anticipated that individual research 

results will be returned to subjects, then 

the research would not meet this 

exemption and IRB review and approval 

would be required, and informed 

consent would need to be obtained to 

the extent required by §ll.116(a) and 

(b). If the investigator does not 

anticipate that individual research 

results will be provided to a research 

subject as part of the research plan, but 

later decides to return research results 

to subjects, an IRB must review and 

approve the plan for returning these 

results to the subjects. It is understood 

that the prospective IRB review 

provision set forth here does not 

override existing law, such as the 

HIPAA Privacy Rule or the Federal 

Privacy Act, which give individuals the 

right to access certain information about 

themselves in specified circumstances. 

In addition, it is recognized that clinical 

care needs may demand prompt 

reporting of findings to patients who are 

also human subjects, in which case it is 

expected that investigators would 

anticipate that such research results will 

be provided to a subject, and this 

exemption would not apply. 

It is generally recognized that where, 

for example, a series of genetic analyses 

are performed, in a significant 

percentage of instances investigators 

will be learning information, not 

necessarily related to the specific 

purpose of their studies, that would 

nonetheless be significant to 

participants in terms of making 

decisions about their health care. For 

example, it might be learned that a 

woman has a gene mutation that 

significantly increases her risk of breast 

or ovarian cancer. The proposed rule 

does not specifically impose any 

obligations on investigators to provide 

such information to participants, so long 

as the consent form is clear that no such 

information will be given to the 

participants. This could have a negative 

impact on the current efforts to increase 

the willingness of people to allow their 

biospecimens to be used in research, if 

they are less inclined to provide broad 

consent to such research when 

investigators are not making any 

commitment to return important 

information that is unexpectedly 

learned about a participant. This could 

lead some investigators to decide to 

include in their protocols provisions for 

returning such results to subjects. The 

consequence is that such protocols will 

not be eligible for the proposed 

exemption at § ll.104(f)(2), and thus 

would undergo full IRB review 

primarily for the purpose of determining 

what information participants should be 

provided regarding such ‘‘unexpected’’ 

(i.e., not related to the purpose of the 

research) genetic findings. In contrast, if 

a study only involved use of 

biospecimens, and no results were to be 

returned to subjects, no IRB review 

would be required under the NPRM 

proposals unless IRB review is required 

by law (e.g., FDA-regulated devices). 

At the same time, it is likely that 

many IRBs do not have any particular 

unique expertise in making these 

determinations about returning results, 

which again could lead to inappropriate 

variability in disclosure from study to 

study, and would seem to be in conflict 

with the ethical goal of justice. 

One option that has been considered 

would be to create a federal panel of 

experts to make determinations about 

which unexpected findings should be 

disclosed to human subjects in research, 

and what information should be given 

to subjects about themselves. If this 

alternative proposal were adopted, then 

it would not be necessary to have full 

IRB review of these protocols. A 

consequence of this option would be 

that these types of studies could be 

exempt even if they proposed to return 

research results to subjects, so long as 

disclosures were made consistent with 

the rules announced by the federal 

panel. However, it is not clear that such 

a panel’s guidance would be superior to 

that of IRBs. 

v. Questions for Public Comment 

54. Public comment is sought on 

whether the NPRM’s proposal of 

exemption §ll.104(f)(2) is the best 

option, or whether there is a better way 

to balance respect for persons with 

facilitating research. 

55. Public comment is sought on 

whether and how the provision 

regarding the return of research results 

in the proposed exemption 

§ ll.104(f)(2) should be revised. 

56. Public comment is sought on 

whether there should be an additional 

exemption that would permit the 


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51 67 FR 62432 (Oct. 7, 2002). 

collection of biospecimens through 

minimally invasive procedures (e.g., 

cheek swab, saliva). 

e. Applicability of Exemptions to the 

Subparts (NPRM at §ll.104(b); 

Current Rule at Footnote 1) 

i. Current Rule 

In the current Common Rule, the 

application of the exemptions 

articulated in the current Common Rule 

in §ll.101(b) to the subparts is 

specified through footnote 1 of the 

current Rule. It states that the 

exemptions do not apply to research 

involving prisoners, and are also limited 

in their application to research 

involving children. The current 

exemption at § ll.101(b)(2) for 

research involving educational tests, 

survey or interview procedures or 

observations of public behavior does not 

apply to subpart D, except for research 

involving educational tests or 

observations of public behavior when 

the investigator does not participate in 

the activities being observed. The 

current exemptions do apply to subpart 

B. 

ii. NPRM Proposals 

While the exemptions in the NPRM 

are based largely on exemptions in the 

current Common Rule, not all of the 

exemptions proposed in the NPRM will 

apply to subparts B–D. Language at 

§ ll.104(b) explains how the proposed 

exemptions may be applied to the 

subparts. The language at 

§ ll.104(b)(1) states that all of the 

exemptions at § ll.104 may be 

applied to research conducted under 

subpart B. 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 a broader 

population that consists mostly of nonprisoners but that incidentally includes 

some number of prisoners. Finally, 

§ ll.104(b)(3) states that the 

exemptions at § ll.104(d)(1), (2), (4), 

§ ll.104(e)(2) and (f)(1) and (2) may be 

applied to research conducted under 

subpart D. The exemption at 

§ ll.104(e)(1) cannot be applied to 

research involving children under 

subpart D, 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 this NPRM does not 

propose changes to the HHS regulations 

at 45 CFR part 46, subparts B, C and D, 

consideration is being given to whether 

the proposed exemption categories 

articulated in § ll.104 should apply in 

research involving prisoners under 

subpart C, either if the research consists 

mostly of non-prisoners and only 

incidentally includes some number of 

prisoners, as proposed in the NPRM, or 

if the research intends to involve 

prisoners as research subjects. 

Originally developed in 1976 by the 

National Commission, subpart C has at 

times come under scrutiny for its 

restrictive construction. The subpart 

was written in the wake of harsh 

criticism regarding research abuses 

involving prisoners that occurred or 

became public in the 1960s and 1970s. 

As a result, subpart C was written to 

permit research involving incarcerated 

persons only if the study fits one of four 

categories at 45 CFR 46.306(a)(2) (an 

‘‘epidemiological waiver’’ category was 

added in 2002 51), and requires an 

institution to ‘‘certify’’ to the Secretary, 

HHS, before research can proceed. An 

additional original restriction conveyed 

through footnote 1 of the current 

Common Rule specifies that research 

involving prisoners may not be 

considered exempt under any of the 

current exemption categories. 

Public comment is requested on 

whether the revised exemption 

categories should be permitted to apply 

to research involving prisoners. 

Considerations include the 

preponderance of low-risk, sociobehavioral research focused on prisoner 

welfare, substance abuse treatment, 

community reintegration, and services 

utilization; the occurrence of prisonersubjects 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. 

ii. Questions for Public Comment 

57. Public comment is sought on 

whether research involving prisoners 

should be permitted to apply any or all 

of the exemption categories found at 

proposed §ll.104, either if the 

research consists mostly of nonprisoners and only incidentally includes 

some number of prisoners, as proposed 

in the NPRM, or if the research intends 

to involve prisoners as research 

subjects. 

58. Would it be preferable for 

language at § ll.104(b)(2) to resemble 

the 2002 epidemiologic waiver criteria 

and state that the exemptions apply 

except for research where prisoners are 

a particular focus of the research? 

59. Is the proposed application of the 

exemptions to subparts B and D 

appropriate? 

f. What would change in the 

exemptions? 

• All exemption language would be 

found at § ll.104. 

• The eight proposed exemptions in 

§ ll.104 would be divided into three 

groupings: (1) Low-risk interventions 

where no other requirement of the 

proposed rule (including informed 

consent and data protection) are 

necessary other than the determination 

and recording requirements 

(§ ll.104(d)); (2) research activities 

where the information protection 

measures at § ll.105 must be applied 

(§ ll.104(e)); (3) secondary research 

involving biospecimens and identifiable 

private information that requires 

application of privacy safeguards at 

proposed §ll.105, broad consent as 

discussed at proposed §ll.116(c), and 

limited IRB review as discussed at 

proposed §ll.111(a)(9). 

• Existing exemption categories 1, 5, 

and 6 (current §ll.101(b)(1), (5), and 

(6)) would be retained at 

§ ll.104(d)(1), (2), and (4). 

Specifically the current exemption for 

research on public benefit programs or 

demonstration projects 

(§ ll.101(b)(5) in the current Rule; 

§ ll.104(d)(2) in the NPRM) would be 

clarified and 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. A 

requirement for publishing a list of 

studies under this exemption would 

apply for Federal agencies or 

departments conducting or supporting 

such studies. 

• A new exemption would be created 

for certain research involving benign 

interventions. 

• A new exemption would be created 

for 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. 

• A new exemption would be created 

for secondary research use of 

identifiable private information 

originally collected for non-research 

purposes. 

• A new exemption would be created 

for activities relating to the storage and 

maintenance, for secondary research 

use, of biospecimens and identifiable 

private information. 

• A new exemption would be created 

to exempt secondary research studies 


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52Secretary’s Advisory Committee on Human 

Research Protections. (2009, March 4). 

Recommendations from the Subcommittee for the 

Inclusion of Individuals with Impaired Decision 

Making in Research (SIIIDR). Retrieved from Office 

for Human Research Protections: http://

www.hhs.gov/ohrp/sachrp/

20090715letterattach.html. 

53Presidential Commission for the Study of 

Bioethical Issues. (2015). Gray Matters: Topics at 

Intersection of Neuroscience, Ethics and Society. 

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

default/files/GrayMatter_V2_508.pdf. 

that would use the biospecimens and 

identifiable private information stored 

or maintained under the above new 

exemption. 

B. Proposed Changes To Obtaining, 

Waiving, and Documenting Informed 

Consent (§§ll.116 and ll.117) 

The NPRM proposals address: (1) The 

organization and presentation of 

information included in the consent 

document and the process to facilitate a 

prospective subject’s decision about 

whether to participate in research; (2) 

the elements of consent, basic and 

additional; (3) broad consent to the 

storage or maintenance for secondary 

research use of biospecimens and 

identifiable private information, and the 

use of such stored biospecimens and 

information for specific research 

studies; and (4) attendant changes in the 

waiver or alteration criteria for consent. 

The NPRM proposes several changes 

to the Common Rule with regard to the 

elements of informed consent and when 

it must be obtained (see further 

discussion below regarding proposed 

changes to the conditions for waiver of 

consent). In addition, it makes several 

new proposals that were not included in 

the ANPRM questions, but are offered in 

response to public comments received 

as well as internal discussions within 

HHS and with the other Common Rule 

agencies. 

These include the development of a 

Secretary’s template, which will be 

issued in draft for public comment at a 

later date (the NPRM at § ll.116(d)) 

for broad consent to the storage or 

maintenance for secondary research use 

of biospecimens, and identifiable 

private information and the use of such 

stored biospecimens and information for 

specific research studies. Broad consent 

would be permissible for the storage or 

maintenance for secondary research use 

of such information and biospecimens 

that were originally collected for either 

research studies other than the proposed 

research or non-research purposes. This 

broad consent document would meet 

the consent requirements for the storage 

or maintenance of biospecimens and 

identifiable private information for 

secondary research, as well as the use of 

such stored material for individual 

research studies. 

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 seems prudent 

to consider changes to current 

regulations relating to those issues. 

Some critics, including potential and 

former research subjects, object to 

research performed on a person’s 

biospecimens or information without 

consent. Conversely, investigators and 

patient advocacy groups are concerned 

that the need for informed consent for 

every use of a biospecimen or data 

element will greatly inhibit research. 

They worry that obtaining individual 

consent for each separate research study 

will create unmanageable logistical 

demands, making valuable research 

impossible. 

As an additional means of increasing 

transparency and facilitating the 

development of more informative 

informed consent forms, it is proposed 

that a copy of the final version of the 

consent form for clinical trials 

conducted or supported by a Common 

Rule department or agency would need 

to be posted on a publicly available 

Federal Web site. Within 60 days after 

the trial was closed to recruitment, the 

awardee or the federal department or 

agency conducting the clinical trial 

would be required to post the consent 

document, the name of the clinical trial 

and information about whom to contact 

for additional details about the trial. 

In addition to the specific changes 

proposed to § ll.116, comment is 

sought on whether Common Rule 

agencies should modify the definition of 

‘‘legally authorized representative’’ 

(LAR). The current Rule defines LAR at 

§ ll.102(c) 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. While the 

NPRM proposes to retain this language, 

OHRP is aware that this definition has 

been problematic for states in which 

there is no applicable law permitting an 

LAR to consent in either a clinical or a 

research context. In the absence of such 

a law, it is almost always the case that 

community or other standards (such as 

institutional policies) define hierarchies 

or identify individuals who may 

provide legally acceptable consent, for 

clinical (non-research) purposes, on 

behalf of others who cannot consent for 

themselves. However, the current 

regulations are interpreted to not allow 

such standards to constitute applicable 

law for purposes of the regulations, and 

thus such individuals are not 

considered legally authorized 

representatives for purposes of the 

Common Rule. Concerns that the 

Common Rule’s current definition of 

LAR may be inappropriately hindering 

the conduct of research with subjects 

who lack capacity to consent have been 

raised by the Secretary’s Advisory 

Committee on Human Research 

Protections (SACHRP),52 the 

Presidential Commission for the Study 

of Bioethical Issues,53 and others in the 

research community. 

Comment is therefore sought on 

whether a revision that would expand 

the current definition to also permit an 

LAR to be defined by an accepted 

common practice standard that is used 

in a state for determining who can 

legally consent to clinical care would be 

consistent with the ethical principles 

underlying the Common Rule. Such a 

revision would broaden the definition of 

LAR and permit investigators to use 

accepted common practice, such as an 

established state or local hierarchy, to 

allow another person to provide consent 

to research participation. In the absence 

of such a revision, it would remain the 

case that in certain states, there would 

appear to be no way (short of taking the 

often difficult legal step of obtaining the 

appointment of a legal guardian) to 

enroll subjects lacking decision-making 

capacity in research studies. Given that 

the current interpretation of current 

§ ll.102(c) generally is based on the 

proposition that the person who can 

legally consent on behalf of someone 

else for a particular clinical procedure 

to take place should have the authority 

to consent for research purposes, it 

could be viewed as inappropriate to 

maintain the current Rule, which 

produces different results in terms of 

when research can take place in those 

states that have specific laws governing 

such clinical consent and those that 

accomplish the same legal outcome 

through less formal regimes. 

1. Required Elements of Informed 

Consent (NPRM at §ll.116(a), (b)) 

a. NPRM Goal 

Many claim that consent forms have 

evolved to protect institutions rather 

than to provide potential research 

subjects with some of the most 

important pieces of information that a 

person would need in order to make an 

informed decision about whether to 


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54Levine RJ. Informed consent: Some challenges 

to the universal validity of the western model. J Law 

Med Ethics 1991;19(3–4):207–213. 

55Menikoff J, Richards E. What the Doctor Didn’t 

Say: The Hidden Truth about Medical Research. 

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

123. 

56Beardsley 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. 

57For general requirements for informed consent 

see §ll.116 in the current Rule, and 21 CFR 

50.20, .25 for 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(c) and (d)). 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)) Thus, FDA regulations contain only two 

exceptions from informed consent under 21 CFR 

50.23–24. 

enroll in a research study.54 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—the forms 

often function as sales documents or as 

a means to protect against institutional 

liability rather than as genuine aids to 

good decision-making.55 There is also a 

growing body of literature that suggests 

informed consent forms have grown too 

lengthy and complex, adversely 

affecting their ability to convey the 

information needed for prospective 

participants to make an informed 

decision about participating in 

research.56

The goal of the proposed changes to 

the informed consent form and process 

is to facilitate prospective subjects’ 

decision about whether or not to 

participate in a research study, thereby 

enhancing autonomy. 

b. Current Rule 

Currently, under the Common Rule, 

investigators generally must ensure that 

the subjects’ informed consent to 

participate in research is obtained.57

The regulations currently require that 

the consent forms include at least eight 

specific items of information. Various 

aspects of the consent forms have been 

heavily criticized, as have the amount of 

time IRBs devote to editing and revising 

them. 

c. ANPRM Discussion 

The ANPRM discussed revising the 

regulations to provide greater specificity 

about how consent forms should be 

written and what information they 

should contain. The goal would be 

consent documents that are shorter, 

when appropriate, more readily 

understood, less confusing, that contain 

all of the key information in sufficient 

detail, and that can serve as an aid to 

help someone make an informed 

decision about whether to participate in 

a study. 

d. NPRM Proposals 

Public comments were largely in favor 

of finding ways to improve consent 

forms. However, commenters cited 

several systemic concerns that could be 

obstacles to shortening and simplifying 

forms, such as regulatory, legal, and 

institutional requirements, and the 

complexity of some studies. Of those 

responding to questions about the 

causative factors, blame for making 

forms long and complex was shared by 

sponsors of clinical trials, IRBs, 

regulatory agencies, and institutional 

legal counsel. The types of information 

cited as contributing to the excessive 

lengths of forms included the 

requirement to describe all reasonably 

foreseeable research risks and the 

complexity of study procedures. There 

was no consensus on how to better 

explain alternatives to research 

participation and few comments were 

submitted on this topic. 

Commenters offered a few suggestions 

for modifying or deleting the required 

elements of consent, such as removing 

boilerplate language that only protects 

institutions and research sponsors, as 

well as removing some of the required 

elements for minimal risk research. 

However, many felt that guidance, 

rather than regulatory change, would 

better improve the development of 

consent forms. Although many 

commenters noted the need for shorter 

and more comprehensible consent 

forms, most felt that the required 

elements of consent articulated in the 

Common Rule are sufficient. 

Commenters overwhelmingly supported 

the goals articulated in the ANPRM, but 

cautioned against an overly prescriptive 

or rigid approach to consent forms. 

However, several commenters requested 

guidance on what might be included in 

a consent form for future research use of 

identifiable information and identifiable 

biospecimens to ensure that such forms 

satisfied the consent requirements of the 

Common Rule. 

A majority of commenters supported 

the development of regulations or 

guidance designed to encourage 

assessment of the extent to which 

human subjects comprehend consent 

forms, at least for certain types of higher 

risk studies or certain types of subject 

populations. Others argued that the 

regulations at § ll.116 already contain 

language implying the need to ensure 

comprehension through the use of the 

terms ‘‘legally effective informed 

consent’’ and ‘‘language understandable 

to the subject.’’ 

Finally, many commenters supported 

making changes to HIPAA authorization 

requirements, as necessary, to conform 

to provisions of the Common Rule. In 

addition, most commenters were 

supportive of requiring investigators to 

disclose in consent forms certain 

information about the financial 

relationships they have with study 

sponsors. 

To that end, the NPRM proposes 

adding new language to the introductory 

text of § ll.116 to address the 

questions asked in the ANPRM about 

strengthening the informed consent 

requirements. It reorients the language 

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, and to provide 

an opportunity to discuss that 

information. It requires that the 

information be presented in sufficient 

detail relating to the specific research. 

Furthermore, in recognition of the 

complaints that current consent forms 

are too commonly complicated 

documents that primarily are used to 

protect sponsors from legal liability, the 

NPRM would require (as described in 

the in the revised introductory language 

to §ll.116) that the information in 

these forms be organized and presented 

in a way that did 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. For example, for 

some research studies, it could be 

important for the discussion of the 

purpose of the research and the 

reasonably foreseeable risks of the 

research to be discussed together so that 

prospective subjects would better 

understand how participation in the 

study might alter their clinical care and 

ultimately, their health. 

It is also proposed that in obtaining 

informed consent, the investigator 

would be required to present first the 

information required by this section, 

before providing other information, if 

any, to the subject. This would mean 

that the consent document could only 

include the elements of consent that 

were required by the rule, with any 

other information included in an 

appendix. This is intended to lead to 

substantially shorter 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 

a long and overly complex document. 

Public comments did not provide 

consensus on desirable changes to the 

elements of informed consent. Thus, 


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this language aims to emphasize the 

necessity of addressing the basic 

elements of informed consent, as 

described in § ll.116(a), in a userfriendly but sufficiently detailed 

manner that facilitates comprehension 

of the risks and potential benefits of the 

research. Because commenters agree 

that informed consent forms should be 

written in appropriate language, this 

proposal reinforces the need to include 

information using language 

understandable to the subject. This goal 

is consistent with Federal Plain 

Language guidelines and the Federal 

Plain Writing Act of 2010. The Secretary 

will publish guidance at a later time to 

explain how consent forms can be 

written in order to comply with the 

requirements of this policy. It is not 

envisioned that the regulations would 

require a formal assessment to evaluate 

an individual’s competency, but that 

such a practice may be appropriate for 

certain populations. That this ambiguity 

already exists in the current regulations 

with regard to what constitutes ‘‘legally 

effective informed consent’’ is 

acknowledged. 

In addition, the NPRM proposes 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 must be included in the 

consent document and not the 

appendices. In other words, when 

consent is combined with authorization, 

the authorization elements should be 

considered to constitute one of the 

required elements of consent. 

Since research with non-identified 

data does not involve ‘‘human subjects’’ 

under proposed § ll.102(e), it is 

proposed that a new element of 

informed consent be required 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 used 

for secondary research studies without 

the protections provided by this policy. 

The new basic element of consent 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) 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 would 

not be used or distributed for future 

research studies, even in a nonidentified form. This proposed 

additional element of informed consent 

is intended to create greater 

transparency and enable prospective 

research subjects to make a more 

informed decision about whether to 

participate in research. Prospective 

subjects can always decline to 

participate in the initial research if they 

object to the statement provided. These 

changes would not apply to ongoing 

human subjects research in which 

human subjects were involved prior to 

the effective date of this rule. 

It is anticipated that very few 

investigators will elect to offer the 

option to restrict the future research use 

of non-identified data, in part because of 

the challenges of marking and tracking 

such decisions. However, should they 

offer this option, then institutions and 

investigators will have to develop a 

system for tracking impermissible uses 

of non-identified information. Since 

most investigators will likely elect to 

inform subjects that identifiers might be 

removed from the data and distributed 

for future research without additional 

informed consent, it would be 

reasonable for investigators and 

institutions to generally assume that the 

secondary research use of non-identified 

information would be permissible 

unless marked otherwise. 

It is possible that investigators could 

choose to include additional statements 

about their plans to use non-identified 

data for future research studies. For 

example, investigators could agree to 

give subjects an option about whether 

subjects’ non-identified research data 

could be used for future research 

studies, or could agree to seek 

additional informed consent from 

subjects before using or sharing nonidentified data for future research 

studies. However, it is anticipated that 

such commitments by investigators 

would be uncommon, and so the NPRM 

does not propose including such 

statements in the informed consent form 

or process. If such commitments about 

the future use of non-identified 

information were made by investigators 

in the informed consent form or process, 

investigators would need to satisfy these 

commitments, which would also require 

the development of a tracking system. 

The NPRM also proposes adding three 

additional elements of consent at 

§ ll.116(b)(7)–(9) that, when 

appropriate, would be required to be 

included in the informed consent form 

and process. These three additional 

elements of consent all pertain to issues 

that have become more relevant in 

recent years as science has advanced 

and the nature of research has changed. 

The proposed new element at 

§ ll.116(b)(7) 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. The proposed new 

element at § ll.116(b)(8) 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. The proposed new element 

at §ll.116(b)(9) would provide 

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. Since the 

information that would be required to 

be disclosed under these three proposed 

additional elements of consent is often 

relevant to an individual’s decision of 

whether to participate in a research 

study, currently such information is 

sometimes included in informed 

consent forms under the current 

Common Rule. The NPRM proposes to 

require inclusion of these additional 

elements, when appropriate, to better 

ensure that prospective subjects are 

more consistently provided with this 

information when it is information that 

a reasonable person would want to 

know in order to make an informed 

decision about whether to participate in 

a research study. These three proposed 

additional elements of consent are also 

relevant to seeking an individual’s 

broad consent to the storage, 

maintenance, and secondary research 

use of biospecimens or identifiable 

private information, so it is proposed 

that broad consent obtained under 

§ ll.116(c) also include these 

additional elements, when applicable. 

These clarifications and additions 

would have to meet the documentation 

requirements at § ll.117(b)(1)–(2). 

e. What would change? 

• New language would strengthen the 

informed consent requirements to make 

sure that the most appropriate 

information is presented to prospective 

subjects in sufficient detail and in a 

format that is tied to understandability. 

• New language would clarify that, 

when a HIPAA authorization is 

combined with consent, the HIPAA 

authorization elements must be part of 

the core elements of the consent. 

• When identifiable private 

information is collected for research 

purposes, consent would be required to 

notify subjects if their non-identified 


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58 78 FR 5611–5613 (Jan 25, 2013). 

information could be utilized for future 

research studies without additional 

consent. 

• The Secretary will publish guidance 

in the future to explain how consent 

forms can be written to comply with the 

regulatory requirements. 

• Three additional elements of 

consent would be required, when 

appropriate. 

f. Question for Public Comment 

60. What topics should be addressed 

in future guidance on improving the 

understandability of informed consent? 

2. Broad Consent to the Storage, 

Maintenance and Secondary Research 

Use of Biospecimens and Identifiable 

Private Information (NPRM at 

§ ll.116(c), (d)). 

a. NPRM Goal 

One of the primary objectives of the 

NPRM is to make the strength of 

protections commensurate with the 

level of risks of the research, and by so 

doing, reduce unnecessary 

administrative burdens on research. 

That objective has been viewed as being 

particularly relevant to research 

involving only secondary use of 

biospecimens and identified data, 

which is relatively low-risk if 

appropriate protections of privacy and 

confidentiality are in place, including 

protections against the misuse of 

biospecimens or data that could cause 

harm to research subjects. 

b. Current Rule 

The increasing use of information and 

biospecimens in research, often into the 

future and beyond the point at which an 

individual is directly involved in the 

information or biospecimen collection, 

requires rethinking the elements of 

consent in those circumstances to 

ensure that potential research subjects 

understand how their information or 

biospecimens might be used as well as 

the risks and potential benefits of such 

use. Critics of the existing rules have 

observed that the current requirements 

for informed consent for future research 

with pre-existing information and 

biospecimens are confusing and 

consume substantial amounts of 

investigators’ and IRBs’ time and 

resources. 

Under the current requirements of the 

Common Rule, if identifiers are 

removed, biospecimens and data that 

have been collected for purposes other 

than the proposed research can 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 Common 

Rule investigators may be allowed in 

certain situations to obtain a consent 

that is broader than for a specific 

research study, such as for a research 

repository that involves obtaining 

biospecimens from living individuals to 

create a repository for future research 

studies. In these cases, an IRB may 

determine that the original consent for 

the creation of the research repository 

satisfies the requirements of the 

Common Rule for the conduct of the 

future research, provided that the 

elements of consent under §ll.116 

continue to be satisfied for the future 

research. Despite this existing flexibility 

in the Common Rule, it is believed that 

the current elements of consent required 

under §ll.116 often do not continue 

to be satisfied for the future research. 

With respect to HIPAA, HHS’s prior 

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.58 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. 

c. ANPRM Discussion 

The ANPRM suggested generally 

requiring written consent for research 

use of any biospecimens collected for 

clinical purposes after the effective date 

of the new rules (such as research with 

excess pathological specimens). Such 

consent could be obtained by use of a 

brief standard consent form agreeing to 

generally permit future research. This 

brief consent could be broad enough to 

cover all biospecimens to be collected 

related to a particular set of encounters 

with an institution (e.g., hospitalization) 

or even to any biospecimens to be 

collected at any time by that institution. 

These studies using biospecimens 

collected for clinical purposes would 

also fall under the expanded and 

revised exempt categories, and thus 

would not require IRB review or any 

routine administrative or IRB review but 

would be subject to the data security 

and information protection standards. 

This discussed modification would 

conform the rules for research use of 

clinically collected biospecimens to the 

rules for biospecimens collected for 

research purposes. The general rule 

would be that a person needs to give 

consent, in writing, for research use of 

their biospecimens, though that consent 

need not be study-specific, and could 

cover open-ended future research. The 

ANPRM envisioned that consent could 

be waived in certain limited 

circumstances and sought comment on 

appropriate criteria for waiving consent. 

The ANPRM suggested that this 

standardized broad consent form would 

permit the subject to say no to all future 

research. In addition, the ANPRM 

acknowledged that there are likely to be 

a handful of special categories of 

research with biospecimens that, given 

the unique concerns they might raise for 

a significant segment of the public, 

could be dealt with by check-off boxes 

allowing subjects to separately agree (or 

not) to that particular type of research. 

More specifically, the ANPRM asked 

whether certain flexible consent 

requirements could be imposed on some 

of these studies that would permit the 

use of a broad consent for future use, 

with a requirement that a subject’s 

specific consent would be required 

before their biospecimens could be used 

for special categories of research. 

Further, the ANPRM suggested 

maintaining the current prohibition that 

participation in a research study (such 

as a clinical trial) could not be 

conditioned on agreeing to allow future 

open-ended research using a 

biospecimen. With regard to the 

secondary research use of pre-existing 

data, on those occasions when oral 

consent was acceptable under the 

regulations for the initial data 

collection, the ANPRM envisioned that 

subjects would have typically provided 

their oral consent for future research at 

the time of the initial data collection; a 

written consent form would not have to 

be signed in that circumstance. 

The ANPRM also noted that there 

would be rules that would allow for 

waiver of consent under specified 

circumstances, though those conditions 

would not necessarily be the same as 

those for other types of research. 

d. NPRM Proposal 

Similar to what was discussed in the 

2011 ANPRM, the NPRM proposes to 

allow broad consent to cover the storage 

or maintenance for secondary research 

use of biospecimens and identifiable 

private information. Broad consent 

would be permissible for the storage or 

maintenance for secondary research of 

such information and biospecimens that 


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were originally collected for either 

research studies other than the proposed 

research or non-research purposes. The 

broad consent document would also 

meet the consent requirement for the 

use of such stored biospecimens and 

information for individual research 

studies. As is currently the case, consent 

would not be required for the secondary 

research use of non-identified private 

information, such as the research use of 

medical records that have had all 

identifiers removed. The NPRM also 

proposes to facilitate research that uses 

information or biospecimens collected 

for purposes other than the currently 

proposed research by adding a new 

consent provision for such research at 

§ ll.116(c), which would permit 

individuals to provide broad consent for 

the storage or maintenance for 

secondary research use of their 

information and biospecimens that 

would not be study-specific, and would 

be sufficient to satisfy the consent 

requirement for two proposed 

exemptions at § ll.104(f)(1) and (f)(2). 

Since it is proposed that the 

definition of human subject be 

expanded to include all biospecimens, 

the NPRM proposes to facilitate research 

using biospecimens by permitting broad 

consent to be obtained for their storage 

or maintenance for secondary research. 

In addition, a new exemption at 

§ ll.104(f)(2) would permit the 

secondary research use of biospecimens 

without a subject being given 

information about the specific research 

study if broad consent under 

§ ll.116(c) and (d) was obtained and 

the privacy safeguards at §ll.105 

were met. 

Public comments on the 2011 ANPRM 

revealed variable opinions on the issue 

of broad consent. Several commenters 

indicated that there is no need for 

additional regulations, with one 

university stating that it ‘‘strongly 

opposes more restrictive regulations 

about the use of these biospecimens and 

sees no need to change the current 

regulations, even or perhaps especially 

in the case of secondary data analysis.’’ 

Other commenters opposed broad 

consent, stating that investigators and 

clinicians should obtain specific 

consent from individuals for each 

research project. This opposition was 

made on the ethical grounds that 

because individuals are not fully 

informed of specific research purposes 

for broad consent, they can never be 

truly informed about the use of their 

data. In contrast, other commenters 

expressed clear support for general 

consent for secondary research use of 

biospecimens and data collected during 

research to exempt the research from 

IRB review, noting that ‘‘we support the 

suggestion in the ANPRM to encourage 

general consent for the secondary 

research use of biospecimens and data 

and where this is not obtained IRB 

review is required.’’ Other commenters 

favored requiring IRB review over 

permitting the use of a broad consent to 

approve secondary research use of 

identifiable data or biospecimens. These 

commenters believed that IRB 

consideration of consent requirements 

for individual research studies was 

more protective of human subjects than 

the ANPRM suggestions to permit broad 

consent for future use. 

It is 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 under §ll.116(c) and 

(d) as part of a research protocol to 

create a research repository of 

biospecimens or information. However, 

in other cases it is expected that 

institutions, particularly institutions 

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. 

Since broad consent is a different 

form of informed consent than informed 

consent for a specific research study, in 

which individuals must be given 

information about a particular research 

study to be conducted with their 

biospecimens and information, the 

proposed requirements for broad 

consent under § ll.116(c) and (d) 

would include several of the basic and 

additional elements of informed consent 

under §ll.116(a) and (b), but not all, 

and would include several additional 

required elements. The proposed 

elements of broad consent are intended 

to ensure that the individual would be 

provided with sufficient information to 

make an informed decision about 

whether to agree to provide broad 

consent for a wide variety of research 

that may be unforeseen at the time in 

which consent is being sought. 

The NPRM proposes to require that 

the 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. 

Broad consent for the research use of 

biospecimens or identifiable private 

information that were originally 

collected for a research study would 

generally be described in the consent 

document for the study that would be 

generating the research biospecimens or 

information. Therefore, it is proposed 

that broad consent to the secondary 

research use of biospecimens and 

identifiable private information 

collected as part of a research study 

could cover all such research material. 

However, in the non-research context, 

it is recognized that the biospecimens 

and information that the subject would 

be asked to permit to be stored or 

maintained and used for a wide range of 

secondary research studies would not be 

as readily understood as in the research 

context, since such non-research 

collections are usually less predictable 

or defined. Therefore, the NPRM 

proposes that broad consent for the 

research use of biospecimens or 

identifiable private information 

obtained for non-research 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 rationale for these limitations is 

that individuals will not know what 

biospecimens and information about 

them will be collected by an institution 

in the future. The 10-year time limit 

may make it more likely that an 

individual will have a better 

understanding of the biospecimens and 

information that would be covered by 

the broad consent, and may be a 

sufficiently long enough time period to 

appropriately facilitate secondary 

research using biospecimens and 

information. The NPRM proposes to 

include the standard for who is a child 

based upon the definition of ‘‘children’’ 

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

time the child became 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 


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biospecimens or identifiable private 

information for research, unless one of 

the exclusions or exemptions were 

applicable. 

The Common Rule departments and 

agencies contemplated proposing that 

the scope of broad consent to secondary 

research use of individually identifiable 

clinical information or biospecimens 

that were originally collected for nonresearch purposes would be limited to 

(1) clinical information and 

biospecimens already existing at the 

institution at the time broad consent 

was sought, and (2) clinical information 

and biospecimens collected as part of an 

identified clinical encounter. Although 

it was recognized that this limitation 

related to an identified clinical 

encounter would give individuals more 

meaningful information about the scope 

of future clinical information and 

biospecimens that would be covered by 

their broad consent, it was determined 

that limiting the scope of the broad 

consent in this manner would be very 

difficult to implement and would 

require rigorous tracking on an 

individual-subject basis. Therefore, this 

proposal was not included in the 

NPRM, and was instead replaced with 

the above proposal that uses a limitation 

based on a period of years. 

In addition, the Common Rule 

departments and agencies contemplated 

proposing that for nonclinical 

information collected for non-research 

purposes (e.g., education and court 

records, financial records, military 

records, employee records, or motor 

vehicle records), broad consent would 

only be required to include a clear 

description of the types of records or 

information that were or will be 

collected and the period of time or event 

during which information collection 

may occur. However, it was decided 

that all biospecimens and identifiable 

private information originally collected 

for non-research purposes should be 

bound by the same limitations, 

regardless of whether the materials were 

originally collected for clinical or 

nonclinical purposes. 

The proposed element of broad 

consent, at (§ ll.116(c)(1)(iv)), 

includes 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. 

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 is expected that the investigator 

would honor this commitment by not 

stripping identifiers. The regulations 

would not require investigators to make 

such a commitment. 

Another of the proposed elements of 

broad consent, at (§ll.116(c)(1)(viii)), 

relates to the public posting of nonidentifiable 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 is being 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 

description of the risks associated with 

public access to the data. 

To facilitate the use of broad consent, 

the NPRM proposes that the Secretary of 

HHS will publish in the Federal 

Register templates for broad consent 

that would contain all of the required 

elements of consent in these situations. 

It is envisioned that there would be at 

least two broad consent templates 

developed: One for information and 

biospecimens originally collected in the 

research context, and another for 

information and biospecimens 

originally collected in the non-research 

context. 

In addition, two exemptions are 

proposed related to facilitating 

secondary research use of biospecimens 

and identifiable private information 

when the Secretary’s broad consent 

template is used. These exemptions are 

described in section II.A.3 of this 

preamble. 

The NPRM also proposes that the 

template for consent established by the 

Secretary may serve as the written 

consent form in circumstances when the 

proposed exemption categories at 

§ ll.104(f) require written consent. In 

circumstances where § ll.104(f)(1) 

allows for oral consent, a subject’s oral 

consent for secondary research use of 

identifiable private information must be 

documented such that the consent is 

associated with the subject’s identifiable 

information. If this requirement is met 

through the use of written 

documentation, the subject would not 

be required to sign anything. 

e. What would change? 

• No change would be made in the 

current regulatory framework allowing 

research use of non-identified private 

information without consent, except 

that, when relevant, individuals would 

be given an option to consent or refuse 

to consent to the inclusion of their data, 

with the removal of certain identifiers, 

in a publicly available database. 

• Broad consent would be 

permissible for the storage or 

maintenance for secondary research use 

of biospecimens and identifiable private 

information, and for the use of such 

stored material for individual research 

studies. 

• No change would be made to the 

definition of ‘‘legally authorized 

representative.’’ 

f. Questions for Public Comment 

61. Public comment is sought on 

whether broad consent to secondary 

research use of information and 

biospecimens collected for non-research 

purposes should be permissible without 

a boundary, or whether there should be 

a time limitation or some other type of 

limitation 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, is the 

NPRM proposal of up to 10 years a 

reasonable limitation? Would a 

limitation related to an identified 

clinical encounter better inform 

individuals of the clinical information 

and biospecimens that would be 

covered by a broad consent document? 

62. Public comment is sought on 

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. 

63. Public comment is sought on 

whether oral consent should be 

permissible in limited circumstances as 

proposed under exemption 

§ ll.104(f)(1). 

64. Would research subjects continue 

to be appropriately protected if the 


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59 Green LA, Lowery JC, Kowalski CP, 

Wyszewianski L. Impact of institutional review 

board practice variation on observational health 

services research. Health Serv Res 2006;41:214–230. 

60Sanders AB, Hiller K, Duldner J. Researchers’ 

understanding of the federal guidelines for waiver 

of and exception from informed consent. Acad 

Emerg Med 2005;12:1045–1049. 

61Secretary’s Advisory Committee on Human 

Research Protections (2008, January 31). SACHRP 

Letter to HHS Secretary. Retrieved from Advisory 

Committee (SACHRP): http://www.hhs.gov/ohrp/

sachrp/sachrpletter013108.html. 

62See supra note 59. 

definition of ‘‘legally authorized 

representative’’ were broadened to 

include individuals authorized by 

accepted common practice to consent 

on behalf of another individual to 

participation in clinical procedures? If 

the definition of ‘‘legally authorized 

representative’’ was broadened in this 

way, public comment is sought on the 

interpretation of ‘‘accepted’’ and 

‘‘common’’ as these terms would be 

used in the revised definition. 

3. Waiver of Informed Consent or 

Documentation of Informed Consent 

(NPRM at §§ ll.116(e), (f) and 

ll.117) 

a. NPRM Goals 

The goals of the proposals related to 

the waiver of informed consent and the 

documentation of informed consent are 

to uphold individuals’ autonomy 

interests in determining whether their 

biospecimens and identifiable private 

information may be used for secondary 

research, to facilitate the recruitment of 

prospective research subjects, and to 

create more flexible rules for 

documenting informed consent for 

certain subject populations. 

b. Current Rule 

Currently the Common Rule permits 

an IRB to waive the requirements for 

obtaining informed consent under two 

sets of circumstances described at 

§ ll.116(c) or (d)). The most common 

set of circumstances requires that four 

specific criteria be satisfied 

(§ ll.116(d)). 

Under the current Common Rule at 

§ ll.117(c), IRBs may waive the 

requirement for the investigator to 

obtain a signed consent form for some 

or all subjects. The current criteria for 

such a waiver may not be flexible 

enough for dealing with a variety of 

circumstances, such as when federally 

sponsored research is conducted in an 

international setting where for cultural 

or historical reasons signing documents 

may be viewed as offensive and 

problematic. 

c. ANPRM Discussion 

The ANPRM asked whether changes 

to the regulations would clarify the 

current four criteria for waiver of 

informed consent and facilitate their 

consistent application. The ANPRM also 

asked for comments on the information 

investigators should be required to 

provide to prospective subjects in 

circumstances where the regulations 

would permit oral consent. Additional 

questions focused on whether there are 

additional circumstances under which it 

should be permissible to waive the 

usual requirements for obtaining or 

documenting informed consent, and 

whether there are types of research in 

which oral consent without 

documentation should not be permitted. 

d. NPRM Proposals 

Many commentators have argued that 

these conditions for waiver of consent 

are vague and applied haphazardly at 

different institutions.59 60 In response to 

these concerns, SACHRP, through its 

Subcommittee on Subpart A, developed 

several recommendations regarding the 

interpretation of these waiver criteria.61

In particular, commenters have 

questioned the meaning of the criterion 

at §ll.116(d)(2) that the waiver or 

alteration will not adversely affect the 

rights and welfare of the subjects. 

Questions have also been raised about 

the meaning of the term ‘‘practicably’’ as 

used in § ll.116(d)(3), which states 

that the research could not practicably 

be carried out without the waiver or 

alteration. 

Further, some have argued that the 

requirements for obtaining waivers of 

informed consent or waivers of 

documentation of informed consent are 

confusing and inflexible, which leads to 

inconsistent application.62 These 

problems may not be inherent in the 

language of the Common Rule, but there 

may be some changes to the regulations 

or clarifications as to how to interpret 

and implement such regulations that 

could improve informed consent forms 

and the informed consent process. 

The NPRM offers several proposals 

related to the waiver or alteration of 

informed consent provisions 

(§ ll.116(c) and (d) in the current rule, 

§ ll.116(e) and (f) in the NPRM). The 

NPRM proposes at §ll.116(f)(1)(iv) to 

retain the language found in 

§ ll.116(d)(2) of the current Rule 

regarding the necessity to evaluate the 

rights and welfare of subjects before 

issuing a waiver of consent or altering 

consent procedures. Despite the 

vagueness of the term, IRBs should 

consider whether there are 

considerations distinct from the risk of 

harm and discomfort that the IRB 

should be able to take into account in 

deciding whether to approve a waiver or 

alteration of informed consent. Note that 

SACHRP’s recommendations included a 

comment that the IRB should determine 

‘‘. . . that the waiver or alteration does 

not adversely impact the ethical nature 

or scientific rigor of the research. . . ,’’ 

which implies that there could be 

ethical considerations other than the 

degree of risk that could legitimately 

affect the IRB’s decision. 

This criterion can be interpreted to 

include rights conferred by pertinent 

federal law or regulation, relevant state 

or local law, the stipulations at 

§ ll.101(e) and (f) (in both the NPRM 

and the current Rule), or laws in other 

countries where research is to be 

conducted. It could also include 

considerations of privacy or the right to 

decide how someone is going to be 

treated, where the IRB determines that 

subjects have such a right that the 

waiver would adversely impact, or 

where the waiver would preclude them 

from obtaining a benefit they would 

otherwise receive. We recognize that 

further guidance regarding this criterion 

would be helpful. 

HHS has also evaluated the utility of 

the term ‘‘practicably’’ contained in the 

elements of waiver or alteration of 

consent (§ll.116(d)(3) in the current 

Rule). The NPRM proposes to keep this 

terminology at § ll.116(f)(1)(ii) in the 

NPRM. SACHRP has noted that the 

commonly accepted definitions of the 

term ‘‘practicably’’ are (1) feasible; (2) 

capable of being effected, done or put 

into practice; and (3) that may be 

practiced or performed; capable of being 

done or accomplished with available 

means or resources. SACHRP 

emphasized this criterion states that the 

research could not practicably be 

carried out without the waiver or 

alteration. In other words, it would not 

be practicable to perform the research 

(as it has been defined in the protocol 

by its specific aims and objectives) if 

consent was required. Thus it is 

impracticable to perform the research, 

and not just impracticable to obtain 

consent. SACHRP also offered the 

following concepts to help an IRB 

determine whether the research could 

not be practicably carried out without 

the waiver of consent: (1) Scientific 

validity would be compromised if 

consent was required; (2) ethical 

concerns would be raised if consent 

were required; (3) there is a 

scientifically and ethically justifiable 

rationale why the research could not be 

conducted with a population from 

whom consent can be obtained; (4) 

practicability should not be determined 


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63See Secretary’s Advisory Committee on Human 

Research Protections (2008, January 31). SACHRP 

Letter to HHS Secretary. Retrieved from Advisory 

Committee (SACHRP): http://www.hhs.gov/ohrp/

sachrp/sachrpletter013108.html. 

solely by considerations of convenience, 

cost, or speed.63

SACHRP’s recommendations are 

consistent with OHRP’s interpretation of 

this waiver criterion. Consideration was 

given to replacing the term practicably 

with another term such as feasibly, but 

HHS is uncertain whether such a change 

would improve the understanding of 

this criterion. Thus the NPRM proposes 

to retain this phrase. 

Few comments to the 2011 ANPRM 

were received on this topic although 

many commenters expressed support for 

clarifying the key terms through 

guidance or altering the criteria. In 

particular, most comments on this topic 

noted the confusion that IRBs face when 

trying to understand the meaning of the 

terms ‘‘practicably’’ and ‘‘adversely 

affect the rights and welfare of 

subjects.’’ Some commenters expressed 

the opinion that the waiver criterion 

concerning rights and welfare should be 

interpreted to include reference to rights 

conferred by other federal laws or 

regulations, state or local laws, or laws 

in other countries where research is to 

be conducted. Some comments reflected 

concerns about privacy or security. 

Several commenters also pointed to the 

need to consider community norms 

throughout the consent process, 

including its documentation. 

The NPRM proposes to add a new 

waiver criterion at §ll.116(f)(1)(iii), 

which would require that, for research 

involving access to or use of identifiable 

biospecimens or identifiable 

information, 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 that the 

research could not practicably be 

conducted without access to and use of 

the protected health information. The 

principle embodied in this additional 

criterion is that non-identified 

information should be used whenever 

possible in order to respect subjects’ 

interests in protecting the 

confidentiality of their data and 

biospecimens. 

Additional more stringent waiver 

conditions apply to research involving 

biospecimens, specifically that (1) there 

are 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. Under this new, more 

stringent waiver standard, the 

circumstances in which a waiver could 

be granted by an IRB should be 

extremely rare. 

The Common Rule departments and 

agencies considered whether to require 

institutions or IRBs to report to OHRP 

when this waiver of consent for research 

involving the use of biospecimens was 

approved by an IRB. If such a reporting 

were required, it is envisioned that 

OHRP could use the information to 

consider whether the waiver provision 

was being implemented appropriately or 

whether regulatory changes might be 

needed (e.g., because such waivers were 

too frequently being granted). It is 

estimated that such a reporting 

requirement would constitute almost no 

burden to institutions, since the very 

premise behind the waiver provision is 

that such waivers should be extremely 

rare. It is also recognized that such a 

reporting requirement might deter IRBs 

from utilizing the waiver provision. The 

NPRM does not include a reporting 

requirement to OHRP when this waiver 

of consent is approved by an IRB, but 

public comments are requested on 

whether such a reporting requirement 

should be included in the final rule. 

The Common Rule departments and 

agencies also considered whether the 

NPRM should propose that a waiver of 

consent not be permissible for 

secondary research involving the use of 

biospecimens. The purpose of such a 

requirement would be to encourage 

investigators to seek broad consent for 

such research. This proposal was not 

included in the NPRM, but public 

comments are requested on whether 

such a prohibition to waive informed 

consent should be included in the final 

rule. 

In addition, the NPRM proposes 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 is proposed 

that this refusal would need to be 

recorded by the investigator to better 

ensure that the subject’s wishes would 

be honored. 

The proposal to not allow any waivers 

of consent by an IRB with regard to the 

secondary research use of identifiable 

private information if an individual was 

asked to consent to such use, and 

refused to consent, was thoroughly 

considered during the drafting of this 

document. On the one hand, a core 

initial motivation for this NPRM has 

been the recognition that we should not 

be imposing unnecessary burdens on 

low-risk research that is capable of 

producing important knowledge. Reusing data that has been generated for 

other purposes, when appropriate 

protections for privacy and 

confidentiality are in place, seems to fit 

within that category. 

Moreover, with society’s growing 

abilities to rapidly generate massive 

data sets, and manipulate such data 

using cutting-edge algorithms, research 

using ‘‘big data’’ seems more important 

than ever. At the same time, however, 

it is recognized that if an individual is 

asked to provide consent and declines 

or refuses to do so, the individual’s 

choice should be honored, except 

perhaps under only very rare 

circumstances that justify overriding an 

individual’s autonomy interest. 

Most of the provisions in this NPRM 

regarding the research use of 

identifiable private information have led 

to the conclusion that, when there are 

appropriate privacy protections in 

place, the balance between respect for 

persons and beneficence should come 

out in favor of facilitating the research, 

including not requiring informed 

consent in many instances. In 

recognition of this circumstance, while 

the NPRM proposes new consent 

requirements related to biospecimens 

(justified primarily by the special 

autonomy interest of a person in 

controlling the research use of such 

biospecimens), it does not impose such 

consent requirements with regard to 

research use of a person’s identifiable 

private information. Accordingly, in 

most respects, the current Rules—which 

do allow such use without consent, 

provided that an IRB has reviewed the 

study and found that it meets the 

criteria for the waiver of consent—are 

retained with regard to the secondary 

research use of such information. For 

research involving the secondary use of 

identifiable private information, waivers 

of consent appear to currently be quite 

frequently given by IRBs, and represent 

a significant (and likely growing) 

portion of the research universe. 

Accordingly, even after the 

implementation of this NPRM, an 

individual will still generally not have 

the right to prevent secondary research 

taking place using their identifiable 

private information, in the event that an 

IRB approves a waiver of consent for 

such a study. (Indeed, this is only one 

of the circumstances in which the 

NPRM allows such research to take 

place without consent; the NPRM has 

actually expanded such circumstances 

through some of the exclusions and 

exemptions, based on the ethical 

analysis mentioned above.) The main 

alteration of this rule by the NPRM 


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would be in the circumstance described 

above: Where the individual happened 

to be asked to sign a broad consent 

regarding the use of that information, 

and they refused to do so. If that 

happened, an IRB would no longer be 

able to waive consent. 

This is a complicated issue, and as 

discussed below, comments are sought 

on various aspects of the proposal to 

allow for broad consent for secondary 

use of identifiable private information, 

including whether it is appropriate to 

include the limitation on an IRB’s 

ability to waive consent where a person 

has been asked to sign a broad consent 

form, but refused. 

The NPRM also clarifies that waivers 

of informed consent and the waivers 

related to documenting informed 

consent might not be permitted for 

research subject to FDA regulation. For 

example, research conducted with a 

waiver of informed consent, or its 

documentation, may, if submitted in 

support of a marketing application to 

FDA, become subject to certain 

applicable informed consent 

requirements under 21 CFR part 50. 

A provision has also been added at 

§ ll.116(g) in the NPRM to address 

concerns that the current regulations 

require an IRB to determine that 

informed consent can be waived under 

the current § ll.116(d) (§ll.116 (e) 

and (f) in the NPRM) before 

investigators may record identifiable 

private information for the purpose of 

identifying and contacting prospective 

subjects for a research study. This 

requirement to waive informed consent 

is viewed as burdensome and 

unnecessary to protect subjects, and is 

not consistent with FDA’s regulations, 

which do not require informed consent 

or a waiver of informed consent for such 

activities. This proposal in the NPRM is 

intended to address these concerns and 

to make the Common Rule consistent 

with the FDA’s regulations by 

eliminating the requirement for the IRB 

to waive informed consent for these 

activities while explicitly assuring that 

the information will be protected. 

With regard to documentation 

requirements, the NPRM proposes 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. The goal here is to reduce 

the length and complexity of the 

document and to ensure that the 

elements of information essential to 

decision-making receive priority by 

appearing in the main document. 

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. 

Finally, as discussed above, to 

facilitate 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, 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 

regulatory language proposed at 

§ ll.117(c)(4) would also clarify that 

waivers of documentation may not be 

permitted for research subject to 

regulation by FDA. 

e. What would change? 

• A new waiver criterion would be 

added at § ll.116(f)(1)(iii) requiring 

that, for research involving access to or 

use of biospecimens or identifiable 

information, the research could not 

practicably be carried out without 

accessing or using identifiers. 

• Additional waiver criteria would 

apply to research involving the use of 

biospecimens. 

• If a person was asked to provide 

broad consent to store or maintain for 

secondary research use biospecimens or 

identifiable private information and 

refused to do so, a waiver of consent 

would not be allowed with respect to 

the research use of such person’s 

biospecimens or private identifiable 

information. 

• A new provision would be added at 

§ ll.116(g) stating that an IRB may 

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, through oral or written 

communication or by accessing records, 

in order to obtain informed consent, if 

the research proposal includes an 

assurance that the investigator will 

implement standards for protecting the 

information obtained in accordance 

with and to the extent required by 

§ ll.105. 

• The language at §ll.117(b)(1) 

would be altered to specify that the 

consent document should include only 

the language required by §ll.116, 

with appendices included to cover any 

additional information. The goal here is 

to reduce the length and complexity of 

the document and to ensure that the 

elements of information essential to 

decision-making receive priority by 

appearing in the consent document. 

• A new provision would be added at 

§ ll.117(c)(1)(iii) 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. This would be allowed only if the 

research presents no more than minimal 

risk of harm to subjects and provided 

there is an appropriate alternative 

method for documenting that informed 

consent was obtained. 

f. Questions for Public Comment 

65. Public comment is sought on how 

the waiver criterion regarding 

‘‘practicably’’ at § ll.116(d)(3) could 

be explicitly defined or otherwise 

clarified (e.g., what term should replace 

‘‘practicably’’?). 

66. Public comment is sought on the 

proposed differences between the 

criteria for waiving informed consent for 

the research use of biospecimens versus 

identifiable information. 

67. Public comment is sought on 

whether the proposal to permit an IRB 

to waive consent for research involving 

the use of biospecimens should be 

included in the regulations. 

68. Public comment is sought on the 

proposal to permit an IRB to waive 

consent for the secondary use of 

biospecimens or information originally 

collected for research purposes, even if 

the original research study required 

subjects’ informed consent. 

69. Public comment is sought 

regarding how likely investigators are to 

seek broad consent for the use of 

identifiable private information (as 

contrasted with biospecimens), given 

that there are provisions within the 

NPRM that would make it easier to do 

such research without consent (such as 

the new exemption at §ll.104(e)(2)). 

In this regard, note that 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 

might 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 


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information and tracking when people 

provide consent or refuse to do so, are 

the benefits to the system likely to 

outweigh the costs, and if so, should the 

broad consent provisions be limited to 

obtaining broad consent for research use 

of biospecimens? 

70. Public comment is sought on the 

proposed prohibition on waiving 

consent when an individual has been 

asked to provide broad consent under 

§ ll.116(c) and refused. 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 secondary use 

consent 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? 

4. Posting of Consent Forms 

a. NPRM Goals 

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. 

b. NPRM Proposal 

Thus, the NPRM proposes a new 

provision at § ll.116(h)(1) 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. 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. It is anticipated that 

the Web site will be searchable. 

Under proposed § ll.116(h)(2), the 

consent form must be published on the 

Web site within 60 days after the trial 

is closed for recruitment. By final 

consent form, it is anticipated that 

investigators generally will post the 

version of the consent form that had 

been most recently approved by an IRB. 

Note that even though a newer consent 

form could be developed after the 

timeframe specified here, investigators 

would only be required to post one 

consent form. Thus, even if a 

modification to a consent form occurs 

after it has been posted, investigators 

would not be required to re-post an 

updated document. Moreover, only one 

posting would be required for each 

multi-site study. There is no expectation 

that a version would need to be posted 

for each study site. 

A Web site would 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. 

c. What would change? 

• A new provision at §ll.116(h) 

would require that, for clinical trials 

conducted or supported by a Common 

Rule department or agency, a copy of 

the final version of a consent form 

would have to be posted on a publicly 

available federal Web site within 60 

days after the trial is closed for 

recruitment. 

C. Proposed Changes To Protect 

Information and Biospecimens (NPRM 

at §ll.105) 

1. NPRM Goal 

IRBs were not designed to evaluate 

risks to privacy and confidentiality, and 

often have little expertise in these 

matters. Setting uniform specific 

standards will help to assure 

appropriate privacy and confidentiality 

protections to all subjects, without the 

administrative burden of needing a 

specific committee review of the privacy 

and confidentiality protections of each 

study. 

Increasing research use of genetic 

information, information obtained from 

biospecimens, and the ability to more 

easily merge multiple sources of 

administrative and survey datasets (e.g., 

medical records, claims data, vital 

records, and information about lifestyle 

behaviors from surveys) have increased 

the stakes associated with data breaches. 

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. The risks of 

a large portion of social and behavioral 

research are also generally informational 

risks. 

The goal of the NPRM here is to create 

information privacy protections that 

would apply to research, calibrated to 

the level of identifiability and 

sensitivity of the information being 

collected. 

2. Current Rule and Other Regulatory or 

Statutory Requirements 

Currently, the Common Rule at 

§ ll.111(a)(7) requires that IRBs 

evaluate each study with regard to all 

levels of risk and are expected to 

determine whether the privacy of 

subjects and the confidentiality of their 

information are protected. Under the 

Common Rule, IRBs must review each 

individual study’s protection plan to 

determine whether it is adequate with 

respect to the informational risks of that 

study. 

In addition, the HIPAA Privacy Rule 

addresses some of these 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 164, Subparts A and C) 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 

respects to their business associates), 

and not all investigators are part of a 

covered entity. Moreover, the Privacy 

Rule does not apply specifically to 

biospecimens in and of themselves. 

Separate from the HIPAA Rules, the 

Privacy Act of 1974, as amended (5 

U.S.C. 552a) requires Federal agencies 

to protect certain information in their 

possession and control. However, it 

does not apply to non-Federal 

investigators. 

3. ANPRM Discussion 

The ANPRM suggested establishment 

of 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 contained in a 

biospecimen. It put forward the idea 

that these standards might be modeled 

after certain standards of the HIPAA 

Rules and asked a series of questions 

about how best to protect private 

information. 


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4. NPRM Proposals 

Some public comments reflected 

confusion about the focus of the 

suggested standards and whether they 

would apply to information or 

biospecimens that were not individually 

identifiable. Although most commenters 

confirmed the need to protect the 

privacy and confidentiality of 

information of human subjects in 

research, a majority expressed serious 

concerns about the merits of requiring 

all investigators to meet standards 

modeled on certain HIPAA standards, 

such as those in the HIPAA Security 

Rule. Most commenters expressed the 

opinion that certain HIPAA standards 

are not well suited to some research of 

various kinds carried out by 

investigators not subject to the HIPAA 

Rules. Some commenters claimed that 

the HIPAA privacy safeguards do not 

adequately protect individuals’ 

information. Many commenters claimed 

that standards modeled after certain 

HIPAA standards would be 

unnecessarily burdensome for studies in 

the behavioral and social sciences 

where the data are often less sensitive 

than health information. 

Some comments maintained that 

HIPAA-like standards would not always 

be suitable for the variety of research 

methods and procedures for the 

collection and storage of information in 

research activities not subject to the 

HIPAA Rules. Some commented that 

certain HIPAA standards would not be 

suitable because of the location of the 

research activity, or because the kind of 

institution supporting the research was 

significantly different from a covered 

entity. Others thought the HIPAA 

standards create confusion and 

complications for investigators and 

institutions that would increase if 

standards modeled on certain HIPAA 

standards were applied across the 

board. At the same time, regardless of 

the specific standards to be employed 

under this approach, several 

commenters noted that the additional 

administrative burden that might be 

created by establishing a data security 

and information protection system 

could be offset by the decreased time 

and attention IRBs would have to invest 

in reviewing every study that required 

data or biospecimen protections. They 

also noted that many institutions 

already have required data and 

biospecimen protection systems in 

place. 

Some commenters noted that 

expansion of some of the exemption 

categories could only be ethically 

acceptable if those research activities 

were subject to a requirement for data 

security and information protection, 

because information collected for some 

research studies would no longer be 

collected under a research plan 

approved by an IRB. With regard to an 

absolute prohibition against reidentifying de-identified data, many 

commenters expressed concern, and 

provided reasons why re-identification 

might be valid or even desirable, 

including the need to return clinically 

relevant research results to an 

individual. For example, if the research 

uncovers information that might have 

important clinical significance for an 

individual, re-identification could be 

used so that the individual could get 

care. In addition, they pointed out that 

the current Common Rule requires 

investigators who re-identify nonidentified private information as part of 

a research study to comply with the 

current Common Rule regulatory 

requirements. 

The NPRM proposes 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 the idea discussed in 

the ANPRM of adopting the standards 

solely modeled on certain standards of 

the HIPAA Rules, the NPRM proposes 

several sets of standards, and allows a 

choice about which to use. First, the 

NPRM proposes to have the Secretary of 

HHS publish a list of specific measures 

that an institution or investigator can 

use to meet the requirements. The list 

would be evaluated and amended, as 

appropriate, after consultation with 

other Common Rule departments and 

agencies. The proposed list will be 

published in the Federal Register, and 

public comment on the proposed list 

will be sought before the list is 

finalized. 

The list of specific safeguards that 

would be identified by the Secretary 

will be designed such that they could be 

readily implemented by the individual 

investigator, could build on existing 

safeguards already in place to protect 

research data, and would involve 

minimal cost and effort to implement. 

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. These standards 

would also assure that access to 

electronic information is only 

authorized for appropriate use. Finally, 

these safeguards would assure that 

information and biospecimens posing 

informational risks to subjects would be 

protected according to appropriate 

standards. 

Second, 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 are proposed to protect 

information that is subject to the HIPAA 

Rules. The NPRM also proposes to 

clarify at § ll.105(d) that the 

provisions at § ll.105 do 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 to satisfy the 

§ ll.105 privacy protections 

requirements. 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 of 

§ ll.105 will be deemed satisfied. 

For the purposes of informing the 

development of the §ll.105 privacy 

safeguards, comment is sought on what 

types of safeguards would be 

appropriate. 

There are additional statutes or acts 

that mandate the protection of privacy 

and confidentiality of identifiable 

private information that may be 

reasonable to include in §ll.105(b) as 

additional standards which, if research 

is already subject to those standards or 

a voluntarily election to comply with 

them is made, should perhaps be 

viewed as meeting the new requirement. 

These include: 

• The Confidential Information 

Protection and Statistical Efficiency Act, 

44 U.S.C. 3501 note; 

• The Family Educational Rights and 

Privacy Act of 1974, 20 U.S.C. 1232g; 

• The Census Act, 13 U.S.C. 1 et seq.; 

• Agency for Healthcare Research & 

Quality (AHRQ) statutory provision 

protecting the confidentiality of 

identifiable data obtained for research 

purposes by AHRQ or its contractors 

and grantees, 42 U.S.C. 299c–3(c); 

• The CDC National Center for Health 

Statistics (NCHS) statutory 

confidentiality provision at Section 

308(d) of the Public Health Service Act, 


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42 U.S.C. 242m(d) (using nearly 

identical language to the AHRQ 

statutory provision referenced above); 

• The Substance Abuse and Mental 

Health Services Administration 

authorizing statute regarding 

confidentiality of alcohol and drug 

abuse patient records at 42 U.S.C. 

290dd–2; 

• The Department of Justice statute 

related to confidentiality of information 

used by the Office of Justice Programs 

at 42 U.S.C. 3789g; 

• The Department of Education 

statute related to Education Sciences 

Reform at 20 U.S.C. 9573. 

Public comment is sought on whether 

any of the above referenced statutes or 

acts would serve the goals of §ll.105. 

Note that the statutes and acts 

referenced in § ll.105(b) are currently 

referenced in the proposed exclusions at 

§ ll.101(b)(2)(i) (exclusion for 

surveys, educational tests, and public 

observation) and § ll.101(b)(2)(iii) 

(exclusion for federal departments or 

agencies to use pre-existing federally 

generated non-research data). To that 

end, public comment is also sought as 

to whether the goals of the NPRM are 

served by referencing any of the 

aforementioned statutes, acts, or 

standards in the exclusions proposed in 

§ ll.101(b)(2)(i) and (iii). 

In order to reduce burden on IRBs that 

may under the current regulation be 

tasked with ensuring that safeguards are 

commensurate with informational risk, 

IRB review of required safeguards 

generally would not be required. Note 

that while the proposed language at 

§ ll.111(a)(7) requires that IRBs 

consider if the privacy safeguards at 

§ ll.105 are sufficient to protect the 

privacy of subjects and the 

confidentiality of data, the presumption 

would be that these privacy safeguards 

are sufficient in most circumstances. 

The new section includes conditions 

for use and disclosure of research 

information to other entities, consistent 

with those protections to participants in 

research conducted by Federal 

employees and their contractors. It 

requires that protections be in place 

when biospecimens or identifiable 

private information are shared for 

appropriate research or other purposes 

as specified in the rule. Unless required 

by law, the NPRM would limit the redisclosure of biospecimens and 

identifiable private information that 

were obtained for research purposes to 

the following four purposes: (1) For 

human subjects research regulated 

under the Common Rule; (2) for public 

health purposes; (3) for any lawful 

purpose with the consent of the subject; 

or (4) for other research purposes if the 

institution or investigator has obtained 

adequate assurances that: The recipient 

investigator will implement and 

maintain the level of safeguards 

required by this provision, and the 

research has been approved by an IRB 

under §ll.111 (except for human 

subjects research that qualifies for 

exclusion under proposed § ll.101(b) 

or exemption under proposed §ll.104 

and the recipient will not further 

disclose the biospecimens or 

identifiable private information except 

as permitted by this provision (NPRM at 

§ ll.105(c)). 

These four purposes are additional 

uses or disclosures of biospecimens or 

identifiable private information 

collected in research, because the 

subjects themselves consented, or 

because the information and 

biospecimens will continue to be 

safeguarded, or because the public 

health will be served. For the purposes 

of this requirement, an institution or 

investigator must obtain adequate 

assurances through the use of a written 

agreement with the recipient of the 

biospecimens or identifiable private 

information that the recipient will abide 

by these conditions. In developing this 

provision, Common Rule departments 

and agencies discussed whether it was 

appropriate to limit the re-disclosure of 

biospecimens and identifiable private 

information ‘‘unless [such a disclosure 

was] required by law’’ or if some other 

standard (such as ‘‘unless [such a 

disclosure was] authorized by law’’) 

would be appropriate. Public comment 

is sought on whether limiting redisclosure to four specific 

circumstances unless such a disclosure 

was ‘‘required by law’’ is too restrictive, 

or whether more permissive standards 

would better facilitate the NPRM goal of 

fostering the secondary research use of 

information. 

Also, research involving the 

collection and use of biospecimens or 

identifiable private information that 

would qualify for an exemption under 

section §ll.104(e) and (f) must 

conform to the privacy safeguards 

proposed in § ll.105. A proposed 

change also appears at §ll.115(c), 

requiring that IRB records that contain 

identifiable private information also be 

safeguarded through compliance with 

the safeguards proposed at §ll.105. 

In addition to ensuring that 

biospecimens and identifiable private 

information are protected, a benefit of 

this new provision is that IRBs would 

not be required to review the individual 

plans for safeguarding information and 

biospecimens for each research study, 

so long as investigators will adhere to 

them. While there is a presumption that 

the proposed § ll.105 privacy 

safeguards are sufficient, an IRB may 

determine that a particular activity 

requires more than what is discussed in 

§ ll.105. Once IRBs are familiar with 

standard institutional and investigator 

adopted protections, it is anticipated 

that they will become more comfortable 

with the fact that they need not review 

every protocol for privacy safeguards. In 

addition, there will be an overall 

reduction in regulatory burden because 

IRBs will not have to review security 

provisions on a case-by-case basis. 

Finally, the proposed exemptions 

found at § ll.104(e) and (f), which 

will permit a larger number of protocols 

to proceed without IRB review if 

specific conditions are met, are 

conditioned on investigators and 

institutions meeting these privacy and 

security requirements. Note that there is 

currently no requirement for an IRB to 

determine whether investigators are 

adhering to the §ll.105 privacy 

safeguards for research exempted under 

§ ll.104(e) or (f). 

5. What would change? 

• The NPRM would create a set of 

standards for the protection of 

information for research to create an 

effective and efficient means of 

implementing appropriate protections 

for information and biospecimens. 

• The NPRM also proposes to include 

limitations for the use and disclosure of 

information and biospecimens. 

• IRBs would be required to safeguard 

their records in compliance with the 

provisions at § ll.105 if the records 

contain identifiable private information. 

6. Questions for Public Comment 

71. Public comment is sought 

regarding whether particular 

information security measures should 

be required for certain types of 

information or research activities and, if 

so, what measures and for what types of 

information or research. Specifically, 

should the safeguards be calibrated to 

the sensitivity of the information to be 

collected? 

72. Are the proposed limitations on 

re-disclosure more or less restrictive 

than necessary? Are there additional 

purposes for which re-disclosure of 

biospecimens or identifiable private 

information should be permitted? 

D. Harmonization of Agency Guidance 

(NPRM at § ll.101(j)) 

1. NPRM Goal 

From the outset of the development of 

the Common Rule, the importance of 

consistency across the Federal 

Government has been recognized. Each 


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Common Rule department or agency 

may issue its own guidance regarding 

the protection of human subjects. 

Consequently, there may be variations 

in the guidance issued. 

As the label of the Common Rule 

suggests, there seems to be a compelling 

case for consistency across Federal 

departments and agencies regarding 

guidance on the protections of human 

subjects. Nevertheless, there are 

arguments in favor of some departments 

or agencies imposing specific 

requirements, apart from the Common 

Rule, that are tailored to certain types of 

research. The various agencies that 

oversee the protection of human 

subjects range from regulatory agencies, 

to those agencies and departments that 

conduct research, and to those that 

support and sponsor research. In 

addition, in some cases, statutory 

differences among the agencies have 

resulted in different regulatory 

requirements and agency guidance. Not 

only do the agencies have different 

relationships to the research, but they 

also oversee very different types and 

phases of research and thus there may 

be reasonable justifications for 

differences in guidance. Moreover, 

achieving consensus across the entire 

Federal Government may be arduous, 

preventing timely issuance of guidance. 

2. Current Rule 

Each Common Rule agency, and the 

FDA, is authorized to issue its own 

guidance with regard to interpreting and 

implementing the regulations protecting 

human subjects. That guidance may 

substantially differ from agency to 

agency. 

Currently, there are multiple efforts to 

address variation in guidance across the 

Federal Government, but there is no 

regulatory requirement for agencies to 

consult other departments prior to 

issuance of a policy, to the extent 

appropriate. As a result, interdepartmental communication is 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 been working closely to 

ensure harmonization of guidance and 

regulation to the extent possible, given 

the differing statutory authorities and 

regulatory missions. 

3. ANPRM Discussion 

The ANPRM did not suggest any 

specific approaches to harmonization 

but asked for public comment on a set 

of questions focused on: (1) The extent 

to which differences in guidance on 

research protections from different 

agencies strengthen or weaken 

protections for human subjects; (2) the 

extent to which differences in guidance 

on research protections from different 

agencies facilitate or inhibit the conduct 

of research domestically and 

internationally; and (3) the desirability 

of all Common Rule agencies issuing 

one set of guidance. 

4. NPRM Proposal 

Responses to questions in the 2011 

ANPRM about the need for 

harmonization across Common Rule 

agencies reflected widespread support 

for such efforts. Several commenters 

acknowledged the difficulty of getting 

all Common Rule 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 proposes that the 

regulations contain language at 

§ ll.101(j) requiring consultation 

among the Common Rule 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. 

The Department believes this 

proposal appropriately recognizes the 

importance of harmonized guidance by 

creating an expectation that guidance 

should only be issued after consultation 

among the Common Rule agencies, 

while also permitting guidance to be 

issued without such consultation when 

it is not feasible. The proposal also 

recognizes that harmonization will not 

always be possible or desirable given 

the varied missions of the agencies that 

oversee the protection of human 

subjects and differences in statutory 

authorities. Although the NPRM 

proposal is limited to requiring 

consultation for the purpose of 

harmonization, the Common Rule 

agencies may wish to consult with one 

another before issuing guidance for 

reasons other than the purpose of 

harmonization, and the proposal would 

not preclude this. Some concerns have 

been expressed that the proposed 

language in § ll.101(j) does not go far 

enough to mandate harmonization in 

guidance between Common Rule 

agencies. Others are concerned that this 

provision would, in effect, mean that 

Common Rule agencies issue fewer 

guidance documents because of lengthy 

internal government review and 

approval processes. Public comment is 

sought about the effectiveness of the 

consultation language proposed in 

§ ll.101(j), and whether this language 

should require more (or less) than 

consultation amongst Common Rule 

agencies before guidance is issued. 

For example, FDA intends to modify 

its regulations in light of this NPRM, to 

the extent appropriate, considering its 

unique statutory framework and 

regulatory mission. In developing 

guidance that interprets its human 

subject protection regulations that 

mirror the requirements found in the 

Common Rule, FDA may seek 

consultation with the Common Rule 

agencies, to the extent feasible. Further, 

FDA and OHRP will continue to work 

together in developing guidance on their 

respective regulatory requirements that 

are found both in FDA regulations and 

in the Common Rule, to the extent 

feasible. 

5. What would change? 

• The regulations would contain 

language at § ll.101(j) requiring 

consultation among the Common Rule 

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. 

6. Question for Public Comment 

73. Will the proposed language at 

§ ll.101(j) be effective in achieving 

greater harmonization of agency 

guidance, and if not, how should it be 

modified? 

E. Cooperative Research (NPRM and 

Current Rule at §ll.114) and Proposal 

To Cover Unaffiliated IRBs Not 

Operated by an Institution Holding a 

Federalwide Assurance (NPRM at 

§ ll.101(a)) 

1. NPRM Goal 

The goal is to enhance and streamline 

the review process, reduce 

inefficiencies, and hold unaffiliated 

IRBs directly accountable for regulatory 

compliance, without compromising 

ethical principles and protections. 

2. Current Rule 

Currently, an institution engaged in 

non-exempt human subjects research 

conducted or supported by any Federal 

department or agency that has adopted 

the Common Rule is required to hold an 

OHRP-approved FWA or another 

assurance of compliance approved by 

the Federal department or agency 

conducting or supporting the research. 

The FWA mandates the application of 

the Common Rule only to certain 

federally funded research projects. Most 

institutions voluntarily extend the 

applicability of the Common Rule to all 

the research conducted at their 


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64According to the OHRP’s FWA Database, 

twenty-five percent of institutions with an active 

FWA have formally extended the Common Rule to 

all research conducted at those institutions, 

regardless of funding source (by ‘‘checking the box’’ 

on their assurance). Comments from the regulated 

community suggest that most institutions, however, 

voluntarily follow the requirements of the Common 

Rule in all research activities conducted at these 

institutions. 

65See FDA Guidance at: Guidance for Industry: 

Using a Centralized IRB Review Process in 

Multicenter Clinical Trials. (2006, March). 

Retrieved from U.S. Food and Drug Administration: 

http://www.fda.gov/downloads/

RegulatoryInformation/Guidances/UCM127013.pdf. 

66 In general, an institution is considered engaged 

in a particular non-exempt human subjects research 

project when its employees or agents for the 

purposes of the research project obtain: (1) Data 

about the subjects of the research through 

intervention or interaction with them; (2) 

identifiable private information about the subjects 

of the research; or (3) the informed consent of 

human subjects for the research. Office for Human 

Research Protections. (2008, October 16). Guidance 

on Engagement of Institutions in Human Subjects 

Research. Retrieved from Policy & Guidance: 

http://www.hhs.gov/ohrp/policy/engage08.htmll. 

67 74 FR 9568 (Mar. 5, 2009). 

68 74 FR 9578 (Mar. 5, 2009). 

69 74 FR 9578 (Mar. 5, 2009). Also available at 

http://www.hhs.gov/ohrp/newsroom/rfc/

com030509.html. 

institutions, even research not 

conducted or supported by one of the 

federal departments or agencies that 

have adopted the Common Rule.64

However, such extensions are not 

required. Many observers have called 

for legislation that would extend the 

Common Rule protections to all 

research with human subjects 

conducted in the United States, 

regardless of funding source. 

In addition, IRBs not affiliated with 

an institution holding an FWA are not 

directly subject to oversight for 

compliance through the vehicle of the 

FWA. OHRP’s current practice of 

enforcing compliance with the Common 

Rule in situations where an institution 

relies on an external IRB is through the 

institutions that are engaged in human 

subjects research, even in circumstances 

when the regulatory violation is directly 

related to the responsibilities of an 

external IRB. Thus, certain aspects of 

the regulations are not directly applied 

to external IRBs. 

External IRB review of cooperative 

research may be problematic given the 

current lack of direct regulatory 

accountability and the large volume of 

cooperative reviews. The inefficiencies 

of multiple IRB reviews for cooperative 

studies adds bureaucratic complexity to 

the review process, and delays initiation 

of research projects without evidence 

that multiple reviews provide additional 

protections to subjects. 

The Common Rule currently requires 

that each institution engaged in a 

cooperative research study obtain IRB 

approval of the study, although it does 

not require that a separate local IRB at 

each institution conduct such review. In 

many cases, however, a local IRB for 

each institution does independently 

review the research protocol, informed 

consent forms and other materials, 

sometimes resulting in hundreds of 

reviews for one study. When any one of 

these IRBs requires changes to the 

research protocol that are adopted for 

the entire study, investigators must resubmit the revised protocol to all of the 

reviewing IRBs. This process can take 

many months and can significantly 

delay the initiation of research projects 

and recruitment of subjects into studies. 

In 2006, the FDA issued guidance 

intended to assist sponsors, institutions, 

IRBs, and clinical investigators by 

facilitating the use of a centralized IRB 

review process in cooperative clinical 

trials of investigational new drugs.65

Currently, the choice to have 

cooperative research reviewed by a 

central IRB, or by an IRB at another 

institution, is voluntary under the 

Common Rule. In practice, most 

institutions have been reluctant to 

replace review by their local IRBs with 

review by a central IRB. 

3. Relevant Prior Proposals and 

Discussions 

The choice to have cooperative 

research reviewed by a single 

unaffiliated IRB (or by an external IRB 

operated by or affiliated with another 

FWA-holding institution) currently is 

voluntary. In practice, most institutions 

have been reluctant to replace review by 

their local IRBs with review by a single 

IRB. Participants in two meetings on 

alternative IRB models co-sponsored by 

OHRP in November 2005 and November 

2006 indicated that one of the key 

factors influencing institutions’ 

decisions about this issue is OHRP’s 

current practice of enforcing compliance 

with the Common Rule through the 

institutions that were engaged in human 

subjects research,66 even in 

circumstances when the regulatory 

violation is directly related to the 

responsibilities of an external IRB. 

In 2009, OHRP issued an ANPRM in 

the Federal Register requesting 

information and comments from the 

public about whether the office should 

pursue a notice of proposed rulemaking 

to enable OHRP to hold IRBs and the 

institutions or organizations operating 

the IRBs directly accountable for 

meeting certain regulatory requirements 

of the Common Rule.67 OHRP 

contemplated this regulatory change to 

encourage institutions to rely on IRBs 

that are operated by another institution 

or organization, when appropriate. In 

this ANPRM, OHRP stated that it 

believed that such a regulatory change 

in its enforcement authority might 

address one of the main disincentives 

institutions have cited as inhibiting 

them from exercising the regulatory 

flexibility that currently permits 

institutions to implement a variety of 

cooperative review arrangements and to 

rely on the review of an IRB operated by 

another institution or organization. If 

institutions become more willing to rely 

on cooperative review arrangements and 

on review of IRBs operated by other 

institutions or organizations, this could 

reduce administrative burdens 

associated with implementing the 

Common Rule without diminishing 

human subject protections. 

The ANPRM sought public comment 

on the feasibility, advantages, and 

disadvantages of mandating that all 

domestic (United States) sites in a study 

involving more than one institution rely 

on a single IRB for that study. This 

would apply regardless of whether the 

study underwent convened review or 

expedited review. Further, it would 

only affect which IRB would be 

designated as the reviewing IRB for 

institutional compliance with the IRB 

review requirements of the Common 

Rule. It 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 internal ethics reviews, 

though such reviews would no longer 

have any regulatory status in terms of 

compliance with the Common Rule. 

Based on public comments received 

to the 2009 ANPRM 68 on the issue of 

IRB accountability and to address 

institutions’ concerns about OHRP’s 

practice of enforcing compliance with 

the Common Rule through the 

institutions that are engaged in human 

subjects research, the 2011 ANRPM also 

suggested that appropriate 

accompanying changes could be made 

in enforcement procedures to hold 

external IRBs directly accountable for 

compliance with certain regulatory 

requirements.69 This change was 

discussed only for United States sites in 

multi-institutional studies. The ANPRM 

suggested that, in most cases, 

independent local IRB reviews of 

international sites are appropriate 

because it might be difficult for an IRB 

in the U.S. to adequately evaluate local 

conditions in a foreign country that 

could play an important role in the 

ethical evaluation of the study. 


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70Secretary’s Advisory Committee on Human 

Research Protections. (2015). Recommendations 

Regarding the Draft NIH Policy on the Use of a 

Single Institutional Review Board for Multi-site 

Research. Retrieved from Office for Human 

Research Protections: http://www.hhs.gov/ohrp/

sachrp/commsec/useofasingle_irb.html. 

In late 2014, NIH issued a Request for 

Comments on the Draft NIH Policy on 

the Use of a Single Institutional Review 

Board for Multisite Research. The 

response to NIH’s proposed policy was 

robust and largely supportive, with 

many institutions citing both reduced 

duplication of effort and faster initiation 

of research as important factors. A 

minority, however, pointed to the 

importance of maintaining independent 

local IRB review, and expressed doubt 

over the anticipated efficiencies and 

cost savings that would be incurred 

through a centralized model. SACHRP 

commented on this draft policy, and 

was generally supportive of voluntary 

increased use of a single IRB for multisite studies, as such use may decrease 

differences among site implementation 

of protocols. SACHRP concluded that a 

uniform mandate of single IRB review 

for all domestic multi-site studies was 

premature, and recommended a more 

incentivized approach at this time.70

4. NPRM Proposals 

These issues attracted a large number 

of comments to the 2011 ANPRM, and 

revealed nearly evenly divided 

perspectives. Investigators and disease 

advocacy groups tended to favor the 

single IRB review requirement. IRB and 

institutional representatives tended to 

be opposed to the possible requirement, 

though many indicated single IRB 

review should be encouraged. Support 

was especially strong for single IRB 

review for cooperative clinical trials for 

which the evaluation of a study’s social 

value, scientific validity, and risks and 

benefits, and the adequacy of the 

informed consent form and process 

generally do not require the unique 

perspective of a local IRB. Moreover, 

depending on the nature of the study, 

FDA may not permit differences in 

protocols across sites, which further 

bolstered commenters’ views that the 

requirements be harmonized across the 

Common Rule and FDA requirements. 

Commenters reported incidences of 

IRBs continuously second-guessing each 

other, which delayed studies to the 

point that subject recruitment 

opportunities were foregone or lost. 

This problem seemed especially critical 

in studies of rare diseases and cancers, 

which nearly always involve multiple 

research sites. 

Support for the use of a single IRB, 

however, was not restricted to clinical 

trials. Several commenters cited long 

delays and burdensome requirements 

resulting from multiple reviews of 

studies in the behavioral and social 

sciences. In addition to the view that 

these administrative requirements do 

not enhance protections, supporters of a 

single IRB review of cooperative studies 

cited the frequent need for maintaining 

consistency across sites, which can be 

degraded by multiple reviews. 

Despite support for the ANPRM 

suggestion, several commenters 

expressed concern about making such a 

provision mandatory, stating that the 

current regulations at §ll.114 permit 

the use of joint review arrangements for 

cooperative research. They noted that 

although this option exists, institutions 

might be hesitant to use it because of 

liability concerns and the unwillingness 

of institutions or IRBs to rely on the 

judgment of other institutions or IRBs. 

However, several commenters expressed 

concern about signaling the 

acceptability of a single IRB for review 

while allowing institutions to continue 

to conduct their own ethics review, 

fearing that such a policy would not 

correct the current situation, which 

tends to favor multiple reviews. Thus, 

they commented that mandating a single 

IRB might be the only way to achieve 

the goals of streamlining review while 

ensuring protections. 

Another issue raised was the need to 

set clearer expectations of the 

responsibilities of local IRBs that are not 

designated as the central IRB. A number 

of commenters supporting the 

requirement for a central IRB also 

requested that OHRP issue guidance on 

how to select the IRB, responsibilities of 

all parties, and compliance and 

enforcement policies. Several 

commenters also requested that OHRP 

develop a template for reliance 

agreements to replace inter-institutional 

agreements currently in use. 

Those who expressed concern about 

the use of a single IRB said some 

studies, especially in the behavioral and 

social sciences, might involve 

significant contextual issues reflecting 

community norms, standards, and 

practices, or local culture and customs. 

Use of a distant IRB might not consider 

and best protect subjects based on 

community norms. Others noted that 

such concerns can be addressed by 

investigators or IRBs submitting ‘‘points 

to consider’’ regarding significant 

contextual or cultural considerations of 

relevance to their site. 

A primary issue posed by those 

opposed to mandating use of a single 

IRB in cooperative studies focused on 

potential loss of accountability and 

increased liability for the institutions 

where the research is conducted but 

where the reviewing IRB is not located. 

Taking into consideration this public 

debate and various sources of public 

comments, the NPRM proposes a 

requirement at § ll.114(b)(1) 

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 proposed § ll.114(b)(2), this 

requirement would not apply to: (1) 

Cooperative research for which more 

than single IRB review is required by 

law (e.g., FDA-regulated devices); 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. 

Based on comments to OHRP’s 2011 

ANPRM, the NPRM also proposes to 

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

would explicitly give Common Rule 

departments and agencies the authority 

to enforce compliance directly against 

unaffiliated IRBs that are not operated 

by an assured institution. This change is 

proposed to address concerns about 

OHRP’s current practice of enforcing 

compliance with the Common Rule 

through the institutions that are engaged 

in human subjects research, even in 

circumstances when the regulatory 

violation is directly related to the 

responsibilities of an external IRB. In 

large part, this change was made to 

facilitate the use of a single IRB in 

cooperative research, allowing OHRP to 

enforce compliance with the Common 

Rule through non-compliant external 

IRBs rather than the institutions that 

were engaged in human subjects 

research. This proposal should 

encourage institutions to be more 

willing to rely on a single IRB for 

cooperative research as required under 

the NPRM proposal at §ll.114. It 

would reassure institutions using an 

external IRB because compliance 

actions could be taken directly against 

the IRB responsible for the flawed 

review, rather than the institutions that 

relied on that review. 

Some public commenters responding 

to the 2011 ANPRM cautioned that 

extending compliance oversight to 

external IRBs might serve as a 

disincentive for some IRBs to be the IRB 

of record for cooperative research. A 

majority of commenters expressed an 

opposing view; that is, holding external 

IRBs directly accountable for 

compliance with the regulations would 

increase the comfort level of institutions 

in accepting the regulatory review of an 

external IRB. 


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71See Office for Human Research Protections 

(OHRP)—Categories of Research That May Be 

Reviewed by the Institutional Review Board (IRB) 

through an Expedited Review Procedure. November 

9, 1998, http://www.hhs.gov/ohrp/policy/

expedited98.html. 

Related to this issue is a new 

provision proposed at §ll.103(e) 

regarding policies for documenting an 

institution’s reliance on an external IRB. 

That provision states that for nonexempt research involving human 

subjects covered by this policy that 

takes place at an institution in which 

IRB oversight is conducted by an IRB 

that is not affiliated with the institution, 

the institution and the IRB should 

establish and follow written procedures 

identifying the compliance 

responsibilities of each entity. These 

procedures should be set forth in an 

agreement between the institution and 

the IRB specifying the responsibilities of 

each entity in ensuring compliance with 

the requirements of this policy. 

This would only apply to U.S.- 

conducted portions of studies because 

the flexibility to make use of external 

local IRB reviews of 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. This 

proposal only affects the decision 

regarding how an IRB would be 

designated as the reviewing IRB for 

institutional compliance with the IRB 

review requirements of the Common 

Rule. The reviewing IRB is 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 solicit input regarding 

which IRB would be most appropriate to 

designate as the IRB of record. Public 

comment is sought on how this will 

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 internal IRB reviews, 

though such reviews would no longer 

have any regulatory status in terms of 

compliance with the Common Rule. 

Although a local IRB may conduct its 

own additional internal review, such a 

review would not be binding on the 

local site if not adopted by the single 

IRB, and the terms of it would not be 

enforced by OHRP. 

Relevant local contextual issues (e.g., 

investigator competence, site suitability) 

pertinent to most studies can be 

addressed through mechanisms other 

than local IRB review. For research 

where local perspectives might be 

distinctly important (e.g., in relation to 

certain kinds of vulnerable populations 

targeted for recruitment), local IRB 

review could be limited to such 

consideration(s); but again, IRB review 

is not the only mechanism for 

addressing such issues. The evaluation 

of a study’s social value, scientific 

validity, and risks and benefits, and the 

adequacy of the informed consent form 

and process generally do not require the 

unique perspective of a local IRB. 

The proposal also modifies the 

current regulations by removing the 

requirement that only with the approval 

of the department or agency head may 

an institution participating in a 

cooperative project enter into a joint 

review arrangement, rely upon the 

review of another IRB, or make similar 

arrangements for avoiding duplication 

of effort. Such approval is no longer 

required. 

Some detractors of mandated single 

IRB review for cooperative research 

point to concerns regarding 

implementation logistics, and the time 

necessary to establish new policies, 

procedures, and agreements; 

recognizing this concern, the proposed 

compliance date is three years from the 

publication of the final rule. 

5. What would change? 

• IRBs not affiliated with an assured 

institution that review research covered 

by the Common Rule would be subject 

to direct compliance oversight regarding 

IRB regulatory requirements. 

• All U.S. institutions engaged in a 

cooperative study would rely upon a 

single IRB for that study, with some 

exceptions. 

6. Questions for Public Comment 

74. Is mandated single IRB review for 

all cooperative research a realistic 

option at this time? Please provide 

information about the likely costs and 

benefits to institutions. Will additional 

resources be necessary to meet this 

requirement in the short term? Should 

savings be anticipated in the long run? 

75. What areas of guidance would be 

needed for institutions to comply with 

this requirement? Is there something 

that OHRP could do to address concerns 

about institutional liability, such as the 

development of model written 

agreements? 

76. Would it 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? If so, what should 

these criteria be? 

77. Are the exceptions proposed 

appropriate and sufficient, or should 

there be additional exceptions to this 

mandate for single IRB review than 

those proposed in the NPRM? If 

additional exceptions should be 

included, please provide a justification 

for each additional exception 

recommended. 

78. Is three years appropriate timing 

to establish compliance with this 

provision? 

F. Changes To Promote Effectiveness 

and Efficiency in IRB Operations 

1. Continuing Review of Research 

(NPRM at § ll.109(f); Current Rule at 

§ ll.109(e)) 

a. NPRM Goal 

The goal is to reduce or eliminate the 

need for continuing review in specific 

circumstances, thereby reducing 

regulatory burden that does not 

meaningfully enhance protection of 

subjects. 

b. Current Rule 

The current regulations at 

§ ll.109(e) require 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 is used, continuing 

review of research must 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. In order for research undergoing 

continuing review to be approved, it 

must receive the approval of a majority 

of those members present at the meeting 

(§ ll.108(b)). 

An IRB may 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 71

and found by the reviewer(s) to involve 

no more than minimal risk. OHRP may 

restrict, suspend, terminate, or choose 

not to authorize an IRB’s use of the 

expedited review procedure 

(§ ll.110(d)). 

c. ANPRM Discussion 

The ANPRM requested comments on 

eliminating continuing review for all 

minimal risk studies that undergo 

expedited review, unless the reviewer 

explicitly justifies why continuing 

review would enhance protection of 

research subjects. For studies initially 

reviewed by a convened IRB, continuing 

review would not be required, unless 


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72See Office for Human Research Protections 

(OHRP)—Categories of Research That May Be 

Reviewed by the Institutional Review Board (IRB) 

through an Expedited Review Procedure. November 

9, 1998, http://www.hhs.gov/ohrp/policy/

expedited98.html. 

specifically mandated by the IRB, after 

the study reaches the stage where 

procedures are limited to either (1) 

analyzing data (even if it is identifiable), 

or (2) accessing follow-up clinical data 

from procedures that subjects would 

undergo as part of standard care for 

their medical condition or disease. 

d. NPRM Proposals 

The NPRM proposes at §ll.109(f) 

eliminating continuing review for many 

minimal risk studies (namely those that 

qualify for expedited review), unless the 

reviewer documents why continuing 

review should take place (as would be 

required by § ll.115(a)(8)). 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 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, 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 exemption under 

§ ll.104(f)(1). 

Further, the NPRM proposes at 

§ ll.109(f)(2) that an IRB must receive 

annual confirmation that such 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). This confirmation 

allows the IRB to administratively 

account for research that is occurring 

without continuing review. Investigators 

would continue to be required to submit 

changes to the protocol to the IRB. This 

requirement aims to address concerns 

some might have about institutional 

liability relating to the status of ongoing 

research, the possibility for increased 

noncompliance among investigators no 

longer required to ‘‘check in,’’ and 

possible breakdowns in lines of 

communications between investigators 

and IRBs. Institutions will have 

significant flexibility in how they 

implement this requirement. For 

example, some might rely on an 

automated electronic communication 

with the investigator at one-year 

intervals after the study was initiated 

that might merely require the 

investigator to type ‘‘yes’’ indicating 

that the study is ongoing and that no 

changes have been made. It is therefore 

anticipated that this requirement can be 

met with minimal time and effort on the 

part of investigators and IRBs. 

Investigators would still have the 

current obligations to report various 

developments (such as unanticipated 

problems or proposed changes to the 

study) to the IRB. 

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)(8). 

The NPRM, at §ll.115(a)(3), 

proposes a new requirement for IRBs to 

maintain records of continuing reviews. 

Because the NPRM proposes a new 

provision that eliminates the need for 

continuing review under specific 

circumstances 

(§ ll.109(f)(1)), the NPRM at 

§ ll.115(a)(8) also proposes that IRBs 

need to justify the need for continuing 

review in cases where they will not 

follow the provision in §ll.109(f)(1). 

e. What would change? 

• Continuing review would be 

eliminated for all studies that undergo 

expedited review, unless the reviewer 

explicitly justifies why continuing 

review would enhance protection of 

research subjects. 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. 

However, investigators would be 

required 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. 

• 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 

exemption under § ll.104(f)(1). 

2. Expedited Review Procedures and the 

Definition of ‘‘Minimal Risk’’ (NPRM at 

§§ ll.110 and ll.102(j)) 

a. NPRM Goal 

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 current definition of minimal risk 

within the Common Rule, particularly 

because the terms ‘‘ordinarily 

encountered in daily life’’ and ‘‘routine 

physical or psychological 

examinations’’ are not clarified. The 

goal is to help eliminate this ambiguity 

as it pertains to expedited review, and 

improve the efficiency and consistency 

of minimal risk determinations for some 

activities. 

b. Current Rule 

The concept of ‘‘minimal risk’’ is 

central to numerous aspects of the 

Common Rule, the determination of 

which affects the type of review 

required, 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. 

The current definition of minimal risk 

at §ll.102(i) encompasses 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.’’ 

Under the Common Rule at 

§ ll.110, a research study can 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,72 and is found by the 

reviewer(s) to involve no more than 

minimal risk. 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 the members of the IRB. 

Research that is eligible for expedited 

review requires continuing review at 

least annually. 

c. ANPRM Discussion 

The ANPRM suggested updating the 

current list of research activities eligible 

for expedited review; this list was last 

updated in 1998. It also considered 

mandating that a federal panel 

periodically (such as every year or every 

two years) review and update the list, 

based on a systematic, empirical 

assessment of the levels of risk. This 

would provide greater clarity about 

what would be considered to constitute 

minimal risk, and create a process that 

allows for routinely reassessing and 

updating the list of research activities 

that would qualify as minimal risk. The 

ANPRM asked for public comments on 

categories of research that should be 

considered for addition to the current 

list. 


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The ANPRM asked for public 

comment on whether the current 

regulatory definition of minimal risk is 

appropriate. The ANPRM further 

suggested that the ‘‘default’’ assumption 

would be that a study otherwise eligible 

for expedited review will be considered 

minimal risk unless a reviewer 

documents the rationale for classifying 

the study as involving more than 

minimal risk. 

Finally, the ANPRM discussed the 

idea that continuing review would not 

be required of studies that are eligible 

for expedited review unless the 

reviewer, at the time of initial review, 

determines that continuing review is 

required, and documents why. In 

follow-up to this discussion, the 

ANPRM asked for comments on 

whether IRBs should be required to 

report instances when they overrode the 

default presumption that research 

appearing on the posted list did not 

warrant review by a convened IRB. 

d. NPRM Proposal 

Based on public comments on the 

ANPRM, the NPRM proposes changes to 

the current regulatory language at 

§ ll.110(b)(1) regarding expedited 

review, and will 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 is in contrast to the 

current regulations, which require that 

an IRB use the expedited review 

procedure only if the reviewer 

determines 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. Therefore, 

this proposed change represents a 

change to the default position, and now 

says that research included on the list 

only involves minimal risk, unless the 

IRB makes a determination that the 

research is actually greater than 

minimal risk. Thus, it is anticipated that 

more studies that involve no more than 

minimal risk would undergo expedited 

review, rather than full review, which 

would relieve burden on IRBs. 

This proposal is in line with public 

comment to the 2011 ANPRM. 

Commenters overwhelmingly welcomed 

the clarification that categories of 

research found on the published list 

should be presumed to be minimal risk. 

However, commenters were largely 

opposed to requiring IRBs to report 

instances when they conducted a review 

by the convened membership (versus an 

expedited review) for studies appearing 

on the list. They were opposed because 

of the additional administrative burden 

and also because they felt such a 

requirement would undermine the 

purview of local review and open IRBs 

up to second-guessing by OHRP. 

Public comments to the 2011 ANPRM 

expressed both a desire to retain the 

current definition (slightly less than 

half) and a desire for changing it 

(slightly more than half). There were 

few common themes in the suggested 

changes to the language other than 

seeking clarification on what baselines 

an IRB should consider in determining 

the meaning of ‘‘daily life’’ and ‘‘routine 

physical or psychological 

examinations.’’ Several commenters 

acknowledged the difficulty of arriving 

at a concise definition for all 

circumstances. Those opposed to 

changing the definition said that IRBs 

generally understand how to interpret 

the language and that difficult or 

challenging application of the definition 

will persist regardless of the definition 

for those areas of research where risks 

are difficult to assess. Commenters 

recognized that the risks encountered in 

daily life can vary greatly depending on 

many factors, for example, where people 

live, what kind of work they are 

involved in, what their social and 

economic environment is, and their 

baseline health status. Thus, IRBs need 

to consider all of these issues in making 

a determination about the level of risk. 

Thus, the NPRM does not propose to 

modify the definition of minimal risk 

(NPRM at § ll.102(j)), but rather 

proposes 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 will be re-evaluated 

periodically, but at least every 8 years, 

based on recommendations from federal 

departments and agencies and the 

public. Note that this will not be an 

exhaustive list of all activities that 

should be considered minimal risk 

under the Common Rule, but will allow 

IRBs to rely on the determination of 

minimal risk for activities appearing on 

the list. IRBs will still need to make 

minimal risk determinations about 

activities that do not appear on this list. 

In addition, the NPRM proposes to 

eliminate the parenthetical phrase ‘‘of 

one year or less’’ at § ll.110(b)(2) 

since annual continuing review of 

research eligible for expedited review 

and research that progresses to the point 

of only involving specified limited 

activities will no longer be required for 

all ongoing human subjects research. 

The NPRM also proposes that the 

regulations be revised at §ll.110(a) 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 will be 

prepared for public comment outside 

the scope of the NPRM. 

For several reasons, the NPRM 

proposes no changes in the requirement 

that expedited review be conducted by 

an IRB member. First, public comments 

on the 2011 ANPRM were divided on 

the value of allowing a non-IRB member 

to conduct such reviews. Those with 

concerns questioned whether permitting 

someone other than an IRB member to 

conduct expedited review would have 

unintended consequences, such as 

either increasing or decreasing the 

number of studies deemed acceptable 

for expedited review, or by increasing 

liabilities for the institution. Second, 

IRB staff members would likely 

constitute the pool of non-IRB members 

qualified to conduct expedited review, 

and the current regulations permit IRB 

staff members to be IRB members. HHS 

does not believe a regulatory change is 

warranted to facilitate expedited review. 

Finally, the NPRM contains a 

requirement at § ll.115(a)(9) 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). 

Such documentation could provide a 

basis for the Secretary’s future 

determinations about the 

appropriateness of the list, and allow for 

greater internal consistency at 

institutions. In response to public 

comment on the 2011 ANPRM, the 

NPRM does not propose to require that 

institutions report such determinations 

directly to OHRP. Commenters were 

largely opposed to requiring IRBs to 

report instances when they conducted a 

review by the convened membership 

(versus an expedited review) for studies 

appearing on the list. They were 

opposed because of the additional 

administrative burden and also because 

they felt such a requirement would 

undermine the purview of local review 

and open IRBs up to second-guessing by 

OHRP. 

e. What would change? 

• Expedited review can occur for 

studies on the Secretary’s list unless the 

reviewer(s) determine(s) that the study 

involves more than minimal risk. 

• Evaluation of the list of expedited 

review categories would occur every 8 

years, followed by publication in the 

Federal Register and solicitation of 

public comment. 

• IRBs will be required to document 

their rationale when they override the 

presumption that studies on the 


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Secretary’s expedited review list involve 

greater than minimal risk. 

• The Secretary of HHS will create 

and publish and maintain a list of 

activities that should be considered 

minimal risk. 

f. Questions for Public Comment 

79. How often should the Secretary’s 

list of minimal risk activities be 

updated? Should advice be solicited 

from outside parties when updating the 

list? 

80. Is this Secretarial list of minimal 

research activities a useful tool for the 

research community, or does it 

represent a loss of IRB flexibility in risk 

determination? 

G. Proposed Changes to IRB Operational 

Requirements 

1. Proposed Criteria for IRB Approval of 

Research (NPRM at §ll.111) 

a. NPRM Goals 

These revisions modernize the rule by 

(1) creating new forms of IRB review for 

activities relating to storing or 

maintaining data and biospecimens for 

later secondary use, and for the review 

of studies involving certain types of 

such secondary use; (2) revising two of 

the existing criteria for approval of 

research, where there are special 

considerations related to the 

involvement of vulnerable populations 

and for privacy and confidentiality of 

data provisions; and (3) adding a 

provision regarding plans to review the 

return of individual results to 

participants. 

b. Current Rule 

There are several determinations that 

an IRB must generally make before it 

can approve a study, which are spelled 

out in current Common Rule at 

§ ll.111. These relate, among other 

things, to minimizing risks to subjects, 

determining that there is an appropriate 

relationship between risks and benefits, 

and assuring the equitable selection of 

subjects. The regulations generally 

require all of these determinations to be 

made with regard to any study that must 

undergo IRB review. 

c. ANPRM Discussion 

The ANPRM asked whether all of the 

§ ll.111 criteria should still be 

required for approval of studies that 

qualify for expedited review, and if not, 

which ones should not be required. 

Currently, before an IRB may approve a 

research study, including research that 

is being reviewed under an expedited 

procedure, the IRB must find that the 

criteria at 

§ ll.111 have been met. 

d. NPRM Proposals 

Based on comment to the 2011 

ANPRM, the NPRM does not propose to 

modify the § ll.111 criteria that apply 

to research reviewed under the 

expedited procedure versus research 

reviewed under full board review. The 

NPRM does however propose 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 

research, where there are special 

considerations related to the 

involvement of vulnerable populations 

and for privacy and confidentiality of 

data provisions; and (3) adding a 

provision regarding plans to review the 

return of individual results to 

participants. 

The first set of changes relates to 

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 apply to storage or 

maintenance for secondary research use 

of biospecimens or identifiable private 

information. This provision would 

eliminate the need for an IRB to make 

the usual determinations with regard to 

such an activity. Instead, the IRB would 

be required to determine that the 

procedures for obtaining broad consent 

to the storage or maintenance of 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 to 

determine that the biospecimen and 

privacy safeguards at §ll.105 are 

satisfied for the creation of any related 

storage database or repository. Note that 

in many instances there will be no such 

change. For example, an individual 

could sign a consent form allowing 

broad unspecified future research use of 

information contained in their medical 

records, and that information would 

remain where it is, but be tagged in 

some manner to indicate that the 

individual has provided such consent. 

This in effect means that the default 

for such secondary research studies 

using either biospecimens or 

identifiable information will be that the 

initial broad consent would be 

sufficient, and that there will be no need 

to obtain a new consent from 

individuals for each specific research 

study that is conducted with the 

biospecimens and information. 

The second proposal, relating to 

vulnerable subjects, is intended to 

address an inconsistency in the current 

regulations among three provisions in 

the current Common Rule that address 

requirements related to the 

consideration of vulnerable populations: 

§§ ll.107(a), ll.111(a)(3), and 

ll.111(b). Under the current Rule, 

only §ll.111(b) of these three 

provisions provides that vulnerability to 

coercion or undue influence is the type 

of vulnerability that should be 

considered. It is 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 is intended to 

provide greater consistency and clarity 

in IRB consideration of vulnerability of 

subject populations in research 

activities and appropriate protections. A 

comparable change is also proposed at 

§ ll.107(a), pertaining to IRB 

membership. In addition, of these same 

three provisions in the current Rule, 

only §ll.107(a) identifies 

‘‘handicapped’’ individuals (which the 

NPRM proposes be changed to 

‘‘physically disabled’’ individuals as 

discussed below in section II.G.2.c. of 

the preamble) as a vulnerable category 

of subjects. Therefore, to enhance 

consistency and clarity among these 

three provisions, it is 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 is being sought on these 

proposed changes to the provisions 

related to vulnerable populations. Since 

it is proposed that the only vulnerability 

that needs to be considered is 

vulnerability to coercion or undue 

influence, and not other types of 

vulnerability, it is appropriate to review 

the subject populations to determine 

whether all of these subject populations 

identified in these three provisions 

should be considered vulnerable to 

coercion or undue influence. In 

particular, public comment is sought 


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53988 Federal Register / Vol. 80, No. 173 / Tuesday, September 8, 2015 / Proposed Rules 

73Presidential Commission for the Study of 

Bioethical Issues. (2013, December). Anticipate and 

communicate: Ethical management of incidental 

and secondary findings in the clinical, research, 

and direct-to-consumer contexts. Retrieved from 

Presidential Commission for the Study of Bioethical 

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

FINALAnticipateCommunicate_PCSBI_0.pdf. 

74Wolf SM et al. Managing incidental findings in 

human subjects research: Analysis and 

recommendations. J Law Med Ethics 2008 Summer; 

36(2):219–248, 211. 

75Ofri D. 2013. Medicine’s problem of ‘incidental 

findings.’ Atlantic Monthly. 

about 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. 

The third proposed change would be 

an addition of paragraph (a)(8) to 

§ ll.111 clarifying that if an 

investigator submits as part of the 

protocol a plan for returning individual 

research results, the IRB will evaluate 

the appropriateness of the plan. IRBs 

need not determine whether there 

should be a plan for returning 

individual research results. Although 

many IRBs probably already review 

plans for return of results, many studies 

do not include this feature. Challenges 

can arise regarding return of individual 

research results when it is not clear if 

the findings have clinical validity or 

utility, or when the knowledge imparted 

may cause psychological distress or 

social harm. These issues have been the 

subject of frequent discussion, 

particularly regarding the Clinical 

Laboratory Improvement Amendments 

of 1988, 42 U.S.C. 263a.73 74 75

An additional change is related to the 

proposed changes at §ll.105, and 

would clarify that it is not 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). It is 

assumed that once institutions and 

investigators have established policies 

and procedures for compliance with the 

new privacy safeguards at §ll.105 

(and it is expected that many already 

have already such procedures in place), 

that IRBs will be confident in omitting 

that aspect of their review of research, 

as it does not pose unusual privacy or 

security risks to subjects. It is proposed 

that this requirement will be modified 

to recognize that the requirements at 

§ ll.105 will apply to all nonexcluded research (unless the criteria 

for exemptions are met). The default 

position should be that if the privacy 

safeguards at § ll.105 are being met, 

there is no need for additional IRB 

review of a research study’s privacy and 

security protections. However, there 

might be extraordinary cases in which 

an IRB determines that privacy 

safeguards above and beyond those 

called for in §ll.105 are necessary. 

Therefore, it is proposed that IRBs will 

be responsible for ensuring there are 

adequate provisions to protect the 

privacy of subjects and to maintain the 

security of data only if the IRB 

determines that the protections required 

in §ll.105 are insufficient. 

e. What would change? 

• A new version of more limited IRB 

approval criteria would be created for 

activities relating to the storage or 

maintenance of biospecimens and 

identifiable private information for the 

purposes of later doing secondary 

research with them. 

• IRBs considering the 

§ ll.111(a)(3) approval criterion 

regarding equitable selection of subjects 

would need to focus on issues related to 

coercion or undue influence in research 

with vulnerable populations and not 

other considerations related to 

vulnerability. 

• 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)). 

• IRBs would need to consider the 

requirements for investigators to protect 

information, and biospecimens as a 

criterion for approval of research only if 

they find the protections under 

§ ll.105 are not sufficiently 

protective. 

• If a plan for returning research 

results is included as part of a protocol, 

IRBs would be required to determine 

whether the plan is appropriate. IRBs 

would not be required to determine 

whether such a plan is needed. 

f. Questions for Public Comment 

81. What should IRBs consider when 

reviewing the plans for returning 

research results, for example, what 

ethical, scientific, or clinical concerns? 

82. Is the §ll.111(a)(3) and (b) 

focus on issues related to coercion or 

undue influence in research with 

vulnerable populations, and not other 

considerations related to vulnerability, 

appropriate? Note that this focus also 

appears in proposed §ll.107(a). 

83. Should pregnant women and 

those with physical disabilities be 

included in the category of 

subpopulations that may be vulnerable 

to coercion or undue influence? 

2. Proposed Revisions to IRB 

Operations, Functions, and Membership 

Requirements 

a. NPRM Goal 

The goal is to improve IRB operations 

and make relevant sections consistent 

with other areas of the NPRM. 

b. Current Rule 

The current Rule outlines IRB 

functions and operations at §§ll.108 

and ll.103, and membership 

requirements at § ll.107. 

c. NPRM Proposals 

The NPRM contains several proposals 

for changes in IRB operations, functions, 

and membership requirements. First, 

the requirements for recordkeeping by 

IRBs no longer appear in § ll.103 of 

the rule. They are now described in 

§ ll.108(a)(2), (3), and (4). 

Also as previously discussed, IRBs 

would be required to safeguard their 

records in compliance with the privacy 

protections described in proposed 

§ ll.105 if the records contain 

individually identifiable information. 

Finally, there are four changes to the 

IRB membership requirements at 

§ ll.107(a). The first change is the 

elimination of the requirement that IRBs 

not consist entirely of individuals of one 

gender or profession. This provision is 

unnecessary, because the requirement 

that IRB membership reflect members of 

varying backgrounds and diversity, 

including gender, will accomplish the 

same effect. The deletion of this 

provision in the NPRM is not intended 

to alter the composition of IRBs from 

what had been established in the 

current Rule. 

For the reasons discussed above in 

section II.G.1.d, three additional 

changes are proposed to §ll.107(a). It 

is proposed that §ll.107(a) be 

modified so that consideration of 

vulnerability of a subject population 

would be limited to vulnerability to 

coercion or undue influence. This 

proposed change is consistent with the 

proposal at § ll.111(a)(3). The 

proposed change is intended to result in 

greater consistency and clarity in IRB 

consideration of vulnerability of subject 

populations in research activities and 

appropriate protections. 

The third change in §ll.107(a) is 

the insertion of ‘‘economically or 

educationally disadvantaged persons’’ 

as an example of a vulnerable 

population, requiring an IRB to give 

consideration to membership expertise 

in this area. This language is already 

included in the current Rule at 

§ ll.111(a)(3) and § ll.111(b). 

Adding this category of individuals to 


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76The FWA covers all non-exempt human 

subjects research at the submitting institution that 

is conducted or supported by HHS, or funded by 

any other federal department or agency that has 

adopted the Common Rule and relies upon the 

FWA. It is not project specific. Domestic 

institutions may voluntarily extend their FWA (and 

thus a Common Rule department or agency’s 

regulatory authority) to cover all human subjects 

research at the submitting institution regardless of 

the source of support for the particular research 

activity. See Office for Human Research Protections. 

(2011, June 17). What research does the 

Federalwide Assurance (FWA) cover? Retrieved 

from Frequently Asked Questions: http://

www.hhs.gov/ohrp/policy/faq/assurance-process/

what-research-does-fwa-cover.html. 

those who may be considered 

vulnerable to coercion or undue 

influence at § ll.107(a) is intended to 

create greater consistency among these 

three provisions. 

In order to modernize the regulatory 

language, the fourth change in proposed 

§ ll.107(a) is the replacement of the 

term ‘‘handicapped’’ persons with 

‘‘physically disabled persons’’ as an 

example of a vulnerable population, 

requiring an IRB to give consideration to 

membership expertise in this area. 

d. What would change? 

• The provision regarding IRBs 

avoiding membership that consists 

entirely of individuals of one gender or 

profession would be eliminated because 

the requirement that IRB membership 

reflect members of varying backgrounds 

and diversity, including gender, would 

accomplish the same goal. 

• The provision regarding the IRB’s 

expertise in the review of research 

involving a vulnerable category of 

subjects would be limited to the 

subjects’ vulnerability to coercion or 

undue influence 

• The phrase economically or 

educationally disadvantaged persons is 

included as an example of a vulnerable 

category of subjects, requiring an IRB to 

give consideration to membership 

expertise in this area. 

• The term ‘‘handicapped’’ persons is 

replaced with ‘‘physically disabled 

persons’’ as an example of a vulnerable 

category of subjects, requiring an IRB to 

give consideration to membership 

expertise in this area. 

e. Question for Public Comment 

84. Should populations be considered 

vulnerable for reasons other than 

vulnerability to coercion or undue 

influence? Are the proposed categories 

appropriate? 

H. Other Proposed Changes 

1. Proposal To Extend the Common Rule 

to All Clinical Trials (With Exceptions) 

(NPRM at § ll.101(a)(1)) 

a. NPRM Goals 

The goal of this proposal is to ensure 

that studies that generally pose the most 

risk to potential subjects (such as 

surgical clinical trials), are encapsulated 

by the Common Rule. The proposal 

attempts to balance the goals of ensuring 

that studies where the Common Rule 

provides meaningful protections to 

subjects are covered under the rule, 

while studies where the administrative 

burdens of the Common Rule outweigh 

any potential benefits to subjects are not 

covered. 

b. Current Rule 

The Common Rule applies to all 

research involving human subjects that 

is conducted or supported by a Federal 

department or agency that has adopted 

the policy (§ ll.101(a)). 

c. ANPRM Discussion 

The ANPRM discussed the possibility 

of the Common Rule applying to all 

studies, regardless of funding source, 

that are conducted by a U.S. institution 

that receives some federal funding for 

human subjects research from a 

Common Rule agency. 

The ANPRM also asked the public to 

consider a regulatory option to partially 

fulfill the goal of extending Common 

Rule protections to all human subjects 

research in the United States. The 

discussed policy would require 

domestic institutions that receive some 

federal funding from a Common Rule 

agency for non-exempt research with 

human subjects to extend the Common 

Rule protections to all human subjects 

research studies conducted at their 

institution. 

d. NPRM Proposal 

In response to ANPRM feedback, the 

Common Rule NPRM proposes an 

extension that would ensure that 

clinical trials are covered by the 

Common Rule if conducted at an 

institution in the United States that 

receives federal support for non-exempt 

and non-excluded human subjects 

research, regardless of the funding 

source of the specific clinical trial. 

Note that the purpose of the clinical 

trials extension is to ensure that clinical 

trials that would otherwise not be 

covered by some body of federal 

research ethics regulations are covered. 

To that end, if a clinical trial is already 

subject to FDA oversight but not 

Common Rule oversight, since that 

clinical trial is subject to human 

subjects protection regulations, this 

change would not affect it. Also note 

that this proposed extension is based on 

whether an institution receives funding 

specifically for non-exempt and nonexcluded research. This is because the 

Common Rule departments and 

agencies have a more substantial 

relationship with institutions that 

receive support from a Common Rule 

department or agency to conduct nonexempt and non-excluded human 

subjects research than those institutions 

that receive such support for only 

exempt and excluded human subjects 

research. 

Although supporting the principle 

that all human subjects research 

regardless of funding source should be 

conducted ethically, public commenters 

generally expressed concern and 

caution about the ANPRM consideration 

for a variety of reasons. Behavioral and 

social science investigators thought that 

this approach would unnecessarily 

bring less-than-minimal-risk research 

funded by non-federal sources (e.g., 

surveys or observational studies 

supported by the nonprofit sector) 

under burdensome regulatory 

requirements while not enhancing 

protections. Some commenters argued 

that the increased regulatory burden 

that would ensue was not warranted 

and would shift scarce oversight 

resources to review of research studies 

that are generally non-problematic and 

frequently supported by non-federal 

funds, such as some student or 

institutional research. 

Others argued that such a change was 

an overreach of federal oversight and 

constituted an unfunded mandate. 

Commenters from large academic 

research institutions felt that this 

change inappropriately focused heavily 

on academic institutions, which 

generally extend protections to all 

human subjects research at their 

institution, even if they have not 

‘‘checked the box’’ 76 on their FWA 

indicating that they do so. They argued 

that such a change would not reach 

those institutions already operating 

outside the federal research system and 

would limit flexibility in making riskbased determinations about the levels of 

review required. 

Industry also expressed concern about 

having to comply with two sets of 

regulations, that is, FDA regulations as 

well as the Common Rule. The ANPRM 

did not clarify that the changes under 

consideration would not require 

compliance with the Common Rule of 

non-federally funded research subject to 

regulation by FDA. However, there 

might continue to be research that 

would be subject to both sets of 

regulations involving federal funding of 

research concerning an FDA-regulated 

product. 


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Those commenters who supported a 

formal extension of the regulations cited 

the need to have one set of standards for 

all research, regardless of funding 

source; however, many noted that 

absent legislation covering all human 

subjects research conducted in the 

United States, it would be difficult to 

cover all research through a regulatory 

approach alone—gaps would still 

remain. 

Thus, the NPRM proposes changes in 

the regulatory language at 

§ ll.101(a)(2) to state that the policy 

extends to all clinical trials as defined 

by this policy, irrespective of funding 

source, that meet all of 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 is not 

excluded from this policy under 

§ ll.101(b)(2), and the research does 

not qualify for exemption in accordance 

with §ll.104; (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. 

For purposes of this policy, the NPRM 

proposes at § ll.102(b) that a clinical 

trial be 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 

outcomes,’’ the NPRM contemplates the 

reality that clinical trials may occur 

outside of the biomedical context. The 

studies addressed in the proposed 

definition of clinical trial at 

§ ll.102(b) are more likely to involve 

greater-than-minimal risk, and, 

therefore, require the highest level of 

oversight. Limiting the extension of the 

regulations to only the highest risk 

research is consistent with the goal of a 

more risk-based approach to review. For 

example, surgical clinical trials that do 

not receive support from a Common 

Rule department or agency often are 

outside of the scope of FDA’s human 

subjects protection regulations. Thus, 

many of these unfunded activities are 

currently not subject to the protections 

afforded by the human subjects 

protection system. This NPRM proposal 

would cause many of these trials to 

come under the purview of the Common 

Rule. 

e. What would change? 

• Clinical trials as defined by 

proposed §ll.102(b), irrespective of 

funding source, would be subject to 

oversight, given specified conditions. 

f. Questions for Public Comment 

85. Public comment is sought on 

whether there might be unintended 

consequences from the clinical trials 

expansion proposed in the NPRM in 

§ ll.101(a)(2)(i)). Unintended 

consequences may include an increase 

in burden or costs, or an inappropriate 

redistribution of costs. 

86. Public comment is sought as to 

whether the criterion that the policy 

extends to all clinical trials conducted 

at an institution that receives federal 

support (see the NPRM at 

§ ll.101(a)(2)(i)) should be further 

clarified in some way. For example, 

should it specify a timeframe for 

support (e.g., within the past number of 

years), or a minimum monetary 

threshold value? 

87. Public comment is sought on 

whether the definition of clinical trial 

(NPRM at § ll.102(b)) should include 

additional explanation of what is 

encompassed by the term behavioral 

health-related outcomes. 

2. Changes to the Assurance Process 

(NPRM at §§ ll.103 and ll.108; 

Current Rule at §ll.103) 

a. NPRM Goal 

There has been concern expressed by 

some, such as SACHRP, that the current 

assurance process may be unduly 

burdensome for institutions and does 

not provide meaningful protections for 

human subjects. The changes proposed 

to the assurance process are intended to 

reduce unnecessary administrative 

burdens. 

b. Current Rule 

Requirements at § ll.103 delineate 

procedural requirements for institutions 

and IRBs to follow to comply with the 

Common Rule. 

c. NPRM Proposals 

A number of substantive and 

procedural modifications are proposed 

to §ll.103 of the Common Rule. The 

NPRM proposes to move the IRB 

recordkeeping requirements from 

§ ll.103(b)(4) and (5) of the Common 

Rule. They are now described in the 

NPRM in § ll.108(a)(3) and (4), which 

pertains to IRB functions and operations 

Additionally, the NPRM proposes to 

eliminate the current Common Rule 

requirement at § ll.103(b)(1) that an 

institution provide a statement of 

ethical principles with which an 

institution will abide as part of the 

assurance process. This change was 

made because this provision is generally 

not enforced. Further, for international 

institutions that may receive U.S. 

government 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 U.S. government funding. 

OHRP specifically has received many 

questions about the extent to which 

international institutions must adhere to 

the ethical principles designated as part 

of the assurance process in research 

activities conducted by the institution 

that receive no Common Rule 

department or agency funding. In order 

to provide clarity to these international 

institutions that such measures are not 

required, the NPRM proposes to delete 

the requirement at §ll.103(b)(1). 

The NPRM also proposes 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 current Common 

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

sufficient meeting space and staff to 

support IRB reviews and recordkeeping 

requirements is found in the NPRM at 

§ ll.108(a)(1). Note that 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. 

Additionally, the NPRM proposes to 

eliminate the current requirement in 

§ ll.103(b)(3) that an up-to-date list of 

the IRB members and their 

qualifications be included in an 

institution’s assurance. Instead, 

proposed §§ll.108(a)(2) and 

ll.115(a)(5) require that an IRB or the 

institution prepare and maintain a 

current list of IRB members. This 

modification also eliminates the current 

requirement in § 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 

assurance approved by HHS for 

federalwide use is accepted. SACHRP 

recommended on March 28, 2008, that 

OHRP pursue harmonizing the Common 

Rule with FDA’s human subjects 

protection regulations by eliminating 

the requirement to submit IRB 

membership lists. SACHRP members 

felt that submitting IRB membership 

lists and reporting all changes in IRB 

membership to OHRP added little to the 

protection of human subjects and that 

eliminating these requirements therefore 

would reduce unnecessary 


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77Secretary’s Advisory Committee on Human 

Research Protections. (2008, September 18). 

SACHRP Letter to HHS Secretary. Retrieved from 

Office for Human Research Protections: http://

www.hhs.gov/ohrp/sachrp/

sachrpletter091808.html. 

78See Secretary’s Advisory Committee on Human 

Research Protections (SACHRP). (2014, March 13). 

Final Recommendations on Assurances and 

Engagement. Retrieved from SACHRP’s Meetings: 

http://www.hhs.gov/ohrp/sachrp/mtgings/mtg03- 

14/assurancesandengagement

recommendations.html. 

administrative burdens on institutions 

and OHRP.77

Note that in implementing the NPRM 

an additional, non-regulatory change is 

planned to the assurance mechanism. 

The current option of ‘‘checking the 

box’’ on an FWA to extend HHS’s (or 

other Common Rule supporting 

agencies’) regulatory authority to studies 

conducted by an institution that do not 

receive federal support would be 

eliminated. Importantly, for research 

other than clinical trials, institutions 

could, if they so desired, continue for 

purposes of their own internal rules to 

voluntarily extend the regulations to all 

research conducted by the institution, 

but this voluntary extension would no 

longer be part of the assurance process 

and the research would not be subject 

to OHRP oversight. This change would 

be expected to have the beneficial effect 

of encouraging some institutions to 

explore a variety of new flexible 

approaches to overseeing low-risk 

research that is not funded by a 

Common Rule agency, thus furthering 

the goal of this NPRM to decrease 

inappropriate administrative burdens on 

such research. 

In addition, the NPRM proposes to 

remove the provision found in the 

current Common Rule at §ll.103(d) 

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. 

To further strengthen the new 

provision at § ll.101(a) giving 

Common Rule departments and 

agencies explicit authority to enforce 

compliance directly against IRBs that 

are not affiliated with an assured 

institution, language is proposed at 

§ ll.103(e) requiring each IRB, 

institution, or organization that has 

oversight responsibility for non-exempt 

research involving human subjects 

covered by this policy and conducted by 

another institution to have and follow 

procedures for documenting the 

institution’s reliance on the unaffiliated 

IRB and the respective responsibilities 

of each entity for meeting the regulatory 

requirements of this policy. This is 

already a requirement under the terms 

of a FWA. Such agreements would have 

to be included as part of the IRB 

records, per a proposed requirement at 

§ ll.115(a)(10). This change is 

proposed to address concerns about 

OHRP’s current practice of enforcing 

compliance with the Common Rule 

through the institutions that were 

engaged in human subjects research, 

even in circumstances when the 

regulatory violation is directly related to 

the responsibilities of an external IRB. 

Finally, the NPRM would eliminate 

the requirement in the current Common 

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. 

Note that each assured institution 

continues to have responsibility for 

ensuring that the IRBs upon which it 

relies are registered with OHRP and are 

appropriately constituted to review and 

approve the human subjects research, as 

required under §§ ll.107 and 

ll.108. 

In developing the NPRM proposals 

related to the assurance process, 

consideration was given to the 2014 

SACHRP recommendation that the 

assurance of compliance required under 

§ ll.103 be provided through the 

grant-making or contract process, as one 

of multiple ‘‘Representations and 

Certifications’’ already made by 

institutions when they apply for federal 

grants, contracts or cooperative 

agreements.78 SACHRP suggested that 

such a proposal may reduce 

administrative burden on IRB offices 

responsible for the FWA process 

without significantly diminishing the 

protection that these offices provide 

human subjects. 

Ultimately, SACHRP’s 

recommendation was not adopted as an 

NPRM proposal because of concerns 

regarding the impact that removal of the 

FWA process would have on the ability 

for Common Rule departments and 

agencies to determine their compliance 

authority in certain circumstances. As 

part of SACHRP’s recommended change 

to the assurance process, it was 

envisioned that only the primary 

awardee of a grant or contract would be 

required to obtain an assurance, and 

that this assurance would be provided 

through the grant-making or contract 

process. Subawardees or subcontractors 

may also be engaged in human subjects 

research, which extends the funding 

Common Rule department’s or agency’s 

authority to such institutions. However, 

Common Rule departments or agencies 

may not be able to ascertain that such 

institutions are required to follow the 

Common Rule for such human subjects 

research at their institution in the 

absence of an assurance filed with a 

Common Rule department or agency 

(including OHRP). In addition, some 

institutions have over a thousand grants 

or contracts with Common Rule 

departments and agencies and therefore 

would have over a thousand assurances. 

Certain institutional changes (for 

example, changes in the signatory 

official or human protections 

administrator) will require assurances to 

be updated. Ensuring that assurances 

are appropriately updated and keeping 

track of these updates are likely to pose 

challenges to Common Rule 

departments or agencies. 

d. What would change? 

• The regulatory requirement that an 

institution identify a set of ethical 

principles on which an institution will 

rely in all research conducted at that 

institution, regardless of funding source 

for the activity, would be deleted. 

• The regulatory requirement that a 

written assurance include a list of IRB 

members for each IRB designated under 

the assurance would be replaced by the 

requirement that a written assurance 

include a statement that, for each 

designated IRB, the institution, or when 

appropriate the IRB, prepares and 

maintains 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 regulatory requirement 

specifying 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. 

• The requirement would be deleted 

that a department or agency head’s 

evaluation of an assurance take into 

consideration the adequacy of the 

proposed IRB in light of the anticipated 

scope of the institution’s activities and 


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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. 

• For non-exempt human subjects 

research that takes place at an 

institution in which IRB oversight is 

conducted by an IRB not affiliated with 

that institution, the institution and nonaffiliated IRB must establish and follow 

written procedures that identify 

compliance responsibilities of each 

entity that are set forth in a written 

agreement between the institution and 

the IRB. 

e. Question for Public Comment 

88. Would protection to human 

subjects in research be enhanced if 

OHRP conducted routine periodic 

inspections to ensure that the 

membership of IRBs designated under 

FWAs satisfy the requirements of 

§ ll.107? 

3. Department or Agency Discretion 

about Applicability of the Policy (NPRM 

at §ll.101(c), (d), (i)) and Discretion 

Regarding Additional Requirements 

Imposed by the Conducting or 

Supporting Department or Agency 

(NPRM and current Rule at § ll.124) 

a. NPRM Goals 

The goals of the NPRM revisions in 

these sections are to: (1) Formally codify 

the general practice that the ethical 

standards articulated in the Belmont 

Report is the ethical standard that 

Common Rule departments or agencies 

will use in determining whether an 

activity is covered under this policy; 

and (2) ensure that when relevant, either 

the department or agency conducting or 

supporting an activity may require 

additional protections for human 

subjects. 

b. Current Rule 

The current Common Rule allows in 

§ ll.101(c), (d), (i) for Federal 

department or agency heads to 

determine which specific activities or 

classes of activities are covered by the 

rule. 

c. NPRM Proposals 

As described in section II.A.2 above, 

the NPRM proposes to exclude specific 

categories of low-risk research and nonresearch activities from the scope of the 

Common Rule in order to reduce 

regulatory burden. Of course, there will 

be cases that call for the exercise of 

careful judgment in determining 

whether activities are in an exclusion 

category, or whether they are within the 

scope of the Common Rule. The NPRM 

proposes to retain the Common Rule’s 

current 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 

proposes an additional clause that 

Federal department or agency heads 

must exercise their authority consistent 

with the principles of the Belmont 

Report, in order to require these Federal 

department and agency heads to make 

these judgments in consideration of the 

ethical protection of human research 

subjects. 

The NPRM also proposes at 

§ ll.101(d) that the agency may 

require additional protections for 

specific types of research supported or 

conducted by the agency or department; 

however advance public notice will be 

required when those additional 

requirements apply to entities outside of 

the Federal agency itself. This 

requirement is intended to promote 

harmonization between 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 

proposes 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 waiver must be supported by an 

argument that the alternative procedures 

to be followed are consistent with the 

principles of the Belmont Report. Here 

again, the addition of this provision is 

to make explicit the ethical basis 

underpinning how waiver decisions 

have and must be considered. 

New definitions of ‘‘Department or 

agency head’’ and ‘‘Federal department 

or agency’’ are provided at § ll.102(c) 

and (d) in the NPRM to help clarify 

these requirements. The NPRM 

proposes in § ll.102(d) adding a 

definition of ‘‘Federal department or 

agency’’ in order to avoid confusion as 

to whether this phrase encompasses 

Federal departments or agencies that do 

not follow the Common Rule, and to 

clarify that this phrase refers to the 

department or agency itself, not its 

bureaus, offices or divisions. This is 

consistent with HHS’s historical 

interpretation of the current Rule. To 

distinguish this from the definition of 

Department or agency head found in the 

current regulations at §ll.102(a) (and 

found in the NPRM at § ll.102(c)), the 

example of the Secretary of HHS has 

been inserted to provide clarity. In 

addition, the definition of ‘‘institution’’ 

has been changed at §ll.102(f) in the 

NPRM to clarify that departments can be 

considered institutions for the purposes 

of this policy. 

4. Research Covered by This Policy 

Conducted in Foreign Countries (NPRM 

at §ll.101(h)) 

The current Common Rule at 

§ ll.101(h) articulates that 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. 

The current provision provides 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 

base. In this situation, the current 

Common Rule provides that 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. 

The NPRM proposes to remove the 

specific example provided in this 

provision. A concern with providing a 

specific example of internationally 

recognized ethical document is that 

such a document is subject to change 

independent of HHS or other Common 

Rule agencies, and therefore could be 

modified to contain provisions that are 

inconsistent with U.S. laws and 

regulations. 

I. Effective and Compliance Dates of 

New Rule (NPRM at §ll.101(k)) 

1. Effective Dates 

It is anticipated that the effective date 

of the final rule will be one year after 

publication in the Federal Register. The 

compliance date of the new rules would 

also be one year from the publication of 

the Final Rule, with two exceptions 

discussed below. However, a provision 

that is anticipated to provide additional 

regulatory flexibility to institutions or 

investigators could voluntarily be 

implemented 90 days from the 

publication of the Final Rule. This 90- 

day delay would give the Common Rule 

departments and agencies time to 

develop the documents and tools 

needed to assist institutions in 

implementing some of these provisions 

(e.g., the Secretary’s broad consent 

template, and privacy safeguards under 

§ ll.105). The provisions that would 

provide additional regulatory flexibility 

include: 

• the proposed exclusions in 

§ ll.101(b); 


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• the proposed exemptions in 

§ ll.104(d), (e) and (f); 

• the proposal to no longer require 

IRB review of grant applications 

(§ ll.103(f) in the current Common 

Rule); 

• the proposal to eliminate the 

regulatory requirement in § ll.103 

specifying that changes in IRB 

membership be reported to the 

department or agency head, or to OHRP 

when an HHS-approved assurance is 

approved; 

• the proposed provision in 

§ ll.109(f) to eliminate the continuing 

review requirement for studies that 

undergo expedited review and for 

studies that have completed study 

interventions and are merely analyzing 

data or involve only observational 

follow up in conjunction with standard 

clinical care; 

• the proposed provision in 

§ ll.116(g) stating that an IRB may 

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, through oral or written 

communication or by accessing records, 

in order to obtain informed consent, if 

the research proposal includes an 

assurance that the investigator will 

implement standards for protecting the 

information obtained in accordance 

with and to the extent required by the 

§ ll.105 privacy safeguards; and 

• the new provision in 

§ ll.117(c)(1)(iii) 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, 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. 

In two cases, institutions would have 

longer than one year to comply: (1) The 

proposal for the Common Rule to cover 

all biospecimens (§ ll.102(e) in the 

NPRM); and (2) the proposal in 

§ ll.114(b)(1) regarding identifying a 

single IRB that would be responsible for 

the review of certain multi-institutional 

clinical trials. The compliance date for 

these requirements would be three years 

after the publication of the final rule to 

allow institutions the necessary time to 

develop institutional policies and 

procedures necessary to implement 

these provisions. Comment is sought 

about whether a different approach to 

phasing in these provisions would allow 

the regulated community to better 

implement the changes proposed in this 

NPRM. Additional possibilities 

discussed amongst the Common Rule 

agencies included providing smaller 

institutions more time to implement 

these two changes, and somehow 

incentivizing early compliance with 

these provisions. 

Further, the extension of the 

regulations 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 received 

federal funding for non-exempt research 

in an award made after the effective date 

of the final rule. 

2. Transition Provisions 

The ANPRM suggested that any 

change related to the extent to which 

biospecimens are covered under the 

Common Rule would only apply to 

biospecimens collected after the 

effective date of the revised Common 

Rule. Commenters noted concerns about 

imposing consent requirements on the 

use of biospecimens already collected— 

that is, not grandfathering in such 

resources—especially if these 

biospecimens are non-identified. 

Requiring that consent be obtained for 

the use of these materials could result 

in their being rendered useless for 

research, which would represent a cost 

of its own in terms of lost opportunity. 

This concern was based on the practical 

limitations involved in obtaining 

consent for biospecimens that were deidentified in the past, given that it may 

not be possible to re-contact the original 

source. 

a. Research Initiated Prior to the 

Effective Date of This Subpart (NPRM at 

§ ll.101(k)(1)) 

The NPRM addresses the transition 

provisions for human subjects research 

(as defined in the NPRM) initiated 

before the effective date of the policy. 

Ongoing human subjects research 

initiated prior to the effective date of the 

final rule may choose to comply with 

the provisions that provide additional 

regulatory flexibility discussed above, 

but would not need to comply with 

additional requirements related to: 

• Coverage of clinical trials 

(§ ll.101(a)(2)); 

• Written procedures for 

documenting an institution’s reliance on 

an unaffiliated IRB (§ll.103(e)); 

• New exempt research categories 

and determination requirements 

(§ ll.104(c)–(f)); 

• Information and biospecimen 

protection requirements (§ ll.105); 

• New IRB roster and written 

procedural requirements 

(§ ll.108(a)(2)); 

• Continuing review requirements 

(§ ll.109(f)(2)); 

• Additional IRB approval criteria for 

information safeguards and return of 

results plans (§ ll.111(a)(7) and (8)); 

• Requirements for cooperative 

research (§ll.114); 

• IRB recordkeeping requirements for 

documenting an institution’s reliance on 

an unaffiliated IRB and exemption 

determinations (§ll.115(a)(10) and 

(11)); and 

• Requirements for obtaining and 

documenting informed consent 

(§§ ll.116 and ll.117) that become 

effective on the date of the final rule. 

b. Use of Prior Collections of 

Biospecimens (NPRM at 

§ ll.101(k)(2)) 

Research involving the use of prior 

collections of biospecimens is permitted 

if the biospecimens were collected for 

either research or non-research purposes 

before the effective date of this subpart, 

and research use of the biospecimens 

occurs only after removal of any 

individually identifiable information 

associated with the biospecimens. 

If prior collections of biospecimens 

are not individually identifiable, 

research using such non-identified 

biospecimens would continue to be not 

covered by the regulations even after the 

effective date of this policy. 

Similarly, if prior collections of 

biospecimens are being stored or 

maintained in an individually 

identifiable form, but identifiers are 

removed from the biospecimens before 

being obtained by an investigator, the 

investigator’s use of such 

nonidentifiable biospecimens would 

continue to be not covered by the 

regulations even after the effective date 

of this policy. 

III. Regulatory Impact Analyses 

A. Introduction 

HHS has examined the impacts of this 

proposed 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, Public Law 96–354 (September 

19, 1980); the Unfunded Mandates 

Reform Act of 1995, Public Law 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 


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79 5 U.S.C. 603 

80 5 U.S.C. 601 

81 2 U.S.C. 1532 

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 proposed rule 

would 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 

of small businesses if a rule has a 

significant impact on a substantial 

number of small entities.79 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’’).80 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 proposed rule would not have a 

significant economic impact on a 

substantial number of small entities. 

Supporting analysis is provided in 

section III.G below. 

Section 202(a) of the Unfunded 

Mandates Reform Act of 1995 81 requires 

that agencies prepare a written 

statement, which includes 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 $141 

million, using the most current (2013) 

implicit price deflator for the gross 

domestic product. HHS expects this 

proposed rule to result in expenditures 

that would exceed this amount. 

Executive Order 13132 establishes 

certain requirements that an agency 

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 proposed rule, if finalized, would 

not contain policies that would have 

substantial direct effects on the States, 

on the relationship between the 

National Government and the States, or 

on the distribution of power and 

responsibilities among the various 

levels of government. The proposed 

changes in the rule represent the 

Federal Government regulating its own 

program. Accordingly, HHS concludes 

that the proposed 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. Summary of the Proposed Rule 

This NPRM is being issued to propose 

revisions to modernize, strengthen, and 

make more effective the current 

regulations for protecting human 

subjects. This proposed rule enhances 

clarity and transparency of the consent 

process by imposing stricter new 

requirements regarding the information 

that must be given to prospective 

subjects including the elements of 

consent in a variety of circumstances. It 

will also allow consent to the secondary 

research use of biospecimens and 

identifiable private information, given 

specific conditions are met. Enhanced 

protections to subjects are also achieved 

through greater transparency by posting 

of informed consent forms used in 

clinical trials. Several proposed changes 

(such as explicitly excluding certain 

activities from the rule, expanding the 

categories of research exempt from some 

of the requirements of the proposed 

rule, and eliminating continuing review 

by an IRB in some situations) would 

relieve the burden of unnecessary or 

unwarranted stringent review of some 

low-risk studies that do not pose threats 

to the welfare of subjects. Other 

proposed changes expand the reach of 

the regulations by covering all clinical 

trials, regardless of funding source, and 

by changing the definition of human 

subject to include research in which an 

investigator uses, studies, or analyzes a 

biospecimen. Single IRB review for 

multi-institutional studies would also 

be generally required, except where 

local IRB review is required by law, to 

reduce duplicative IRB reviews. Still 

other revisions clarify or revise 

requirements for and responsibilities of 

IRB review and documentation. New 

exempt categories are proposed, 

requiring that investigators and 

institutions comply with minimum 

standards for protecting privacy. A new 

process is also proposed through which 

investigators may input information 

about a prospective study into a tool in 

order for that tool to generate exemption 

determinations. 

1. Accounting Table 

Table 1 summarizes the quantified 

and non-quantified benefits and costs of 

all proposed changes to the Common 

Rule. Over the 2016–2025 period, 

present value benefits of $2,629 million 

and annualized benefits of $308 million 

are estimated using a 3 percent discount 

rate; present value benefits of $2,047 

million and annualized benefits of $291 

million are estimated using a 7 percent 

discount rate. Present value costs of 

$13,342 million and annualized costs of 

$1,564 million are estimated using a 3 

percent discount rate; present value 

costs of $9,605 million and annualized 

costs of $1,367 million are estimated 

using a 7 percent discount rate. Nonquantified benefits include improved 

human subjects protections in clinical 

trials and biospecimen research not 

currently subject to oversight; enhanced 

oversight of research reviewed by 

unaffiliated IRBs; increased uniformity 

in regulatory requirements among 

Common Rule agencies; standardization 

of human subjects protections when 

variation among review IRBs is not 

warranted; revised informed consent 

forms and processes; improved 

protection of biospecimens and 

identifiable private information; and 

increased transparency of Common Rule 

agency-supported clinical trials to 

inform the development of new consent 

forms. Non-quantified costs include the 

time needed for consultation among 

Common Rule agencies before federal 

guidance is issued; and the time needed 

by investigators to obtain, document, 

and track the permissible uses of 

biospecimens and identifiable private 

information for secondary research use. 


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82The current 15 Common Rule signatory 

agencies are: Department of Agriculture; 

Department of Energy; National Aeronautics and 

Space Administration; Department of Commerce; 

Consumer Product Safety Commission; Agency for 

International Development; Department of Housing 

and Urban Development; Department of Justice; 

Department of Defense; Department of Education; 

Continued 

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

Benefits 

Present value of 10 years 

by discount rate 

(millions of 2013 dollars) 

Annualized value over 10 years 

by discount rate 

(millions of 2013 dollars) 

3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Benefits .................................................................................. 2,629 2,047 308 291 

Non-quantified Benefits 

Improved human subjects protections in clinical trials and biospecimen research not currently subject to oversight; enhanced oversight in 

research reviewed by unaffiliated IRBs; increased uniformity in regulatory requirements among Common Rule agencies; ethical benefit of 

respecting an individual’s wishes in how his or her biospecimens are used in future research; standardization of human subjects protections when variation among review IRBs is not warranted; improved informed consent forms and processes; improved protection of biospecimens and identifiable private information; better ensuring availability of biospecimens for future research activities; and increased 

transparency of Common Rule-supported clinical trials to inform the development of new consent forms. 

Costs 3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Costs 13,342 9,605 1,564 1,367 

Non-quantified Costs 

Time for consultation among Common Rule agencies before federal guidance is issued; time for investigators to obtain consent for secondary use of biospecimens or identifiable private information. 

Table 2 summarizes the quantified 

present value benefits and costs of each 

proposed change to the Common Rule 

using a 3 percent discount rate. 

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

Proposed change 

Present value of 10 years at a 

3 percent discount rate 

(millions of 2013 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 ............................................................................. .............................. 208 

Extending Oversight to IRBs Unaffiliated With an Institution Holding an FWA .......................................... .............................. 84.6 

Extending Common Rule Compliance Oversight to Clinical Trials Regardless of Funding Source .......... .............................. 18.3 

Excluding Activities from the Requirements of the Common Rule because They are not Research ........ 74.0 ..............................

Excluding Low-Risk Research from the Requirements of the Common Rule ............................................ 740 ..............................

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

Expanding the Definition of Human Subject to Include Research involving Non-Identified Biospecimens 

and Creating an Exemption for Secondary Research Using Biospecimens or Identifiable Private Information .................................................................................................................................................. .............................. 101 

Modifying the Assurance Requirements ...................................................................................................... 5.81 ..............................

Requirement for Written Procedures and Agreements for Reliance on External IRBs .............................. .............................. 11.3 

Eliminating the Requirement that the Grant Application Undergo IRB Review and Approval ................... 310 ..............................

Tracking and Documenting Exemption Determinations .............................................................................. .............................. ..............................

Amending the Research and Demonstration Project Exemption ................................................................ 37.0 0.36 

Expansion of Research Activities Exempt from IRB Review ...................................................................... 70.0 ..............................

Exemption for the Storage and Maintenance of Biospecimens and Identifiable Private Information for 

Future, Unspecified Secondary Research Activities after Consent has been Sought and Obtained ..... .............................. 1.58 

Protection of Information and Biospecimens ............................................................................................... .............................. 457 

Elimination of Continuing Review of Research Under Specific Conditions ................................................ 145 38.8 

Amending the Expedited Review Procedures ............................................................................................. 16.8 2.71 

Revised Criteria for IRB Approval of Research .......................................................................................... 126 0.07 

Cooperative Research ................................................................................................................................. 1,103 155 

Changes in the Basic Elements of Consent, Including Documentation ..................................................... .............................. 4.55 

Obtaining Consent to Secondary Use of Biospecimens and Identifiable Private Information .................... .............................. 12,245 

Elimination of Requirement to Waive Consent in Certain Subject Recruitment Activities ......................... 1.21 ..............................

Requirement for Posting of Consent Forms for Clinical Trials supported by Common Rule Department 

or Agencies .............................................................................................................................................. .............................. 14.6 

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

C. Need for the Proposed Rule 

Federal regulations governing the 

protection of human subjects in research 

have been in place for more than three 

decades, and 20 years have passed since 

the Common Rule was adopted by 15 

Federal departments and agencies 82 in 


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Department of Veterans Affairs; Environmental 

Protection Agency; Department of Health and 

Human Services; National Science Foundation; and 

Department of Transportation. 83 In addition to the signatory Common Rule 

departments and agencies, three departments and 

agencies have not issued the Common Rule but 

currently apply 45 CFR Part 46: The Central 

Intelligence Agency, the Social Security 

Administration, and the Department of Homeland 

Security. 

84See, e.g.,, L Abbott and C. Grady, A Systematic 

Review of the Empirical Literature Evaluating IRBs: 

What We Know and What We Still Need to Learn. 

http://www.ncbi.nlm.nih.gov/pmc/articles/

PMC3235475/. 

an effort to promote uniformity, 

understanding, and compliance with 

human subject protections. Today 18 

departments and agencies have adopted 

the rule.83 As such, compliance with the 

Common Rule is a condition for 

receiving federal funding from one of 

these agencies. Note that an additional 

agency (Department of Labor) is joining 

this proposed rulemaking in order to 

promulgate the Common Rule in DOL 

regulations and to apply the regulations 

to human subjects research that DOL 

may conduct or support, pending the 

scope of the final rule. 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. Although the 

regulations have been amended over the 

years, the enterprise has changed to the 

point that the current regulations might 

be outdated in some important ways. 

Under the current system, the 

regulated community notes that limited 

IRB resources are often diverted away 

from focusing on higher-risk studies 

because of the considerable time spent 

reviewing low-risk and minimal-risk 

research. Theoretically, this can result 

in inadequate attention devoted to 

research that could seriously harm 

subjects and unnecessary delay of very 

low-risk research. From the perspective 

of human subjects participating in 

research, the length and complexity of 

consent forms has been increasing even 

for relatively low-risk studies, hindering 

subject understanding of the research 

activities in which they participate. 

Current and prospective research 

subjects have increasingly indicated that 

they would like to be asked about the 

future research use of their 

biospecimens. This desire is not 

necessarily based on concern of 

inappropriate disclosure or use of 

personally identifiable private 

information generated from the 

biospecimen, but rather is rooted in the 

sense that subjects should, whenever 

possible, be asked about such future 

research use. Finally, the current system 

contains some oversight gaps that 

should be addressed to ensure that the 

system is covering the riskiest studies 

and that should compliance-related 

issues occur, the IRBs responsible for 

these issues may be held responsible. 

Provisions are needed to ensure the 

Rule’s consistency with the principles 

of Belmont Report and to protect 

privacy in the context of increasing 

cybercrime and the introduction of 

modern research methods that may 

jeopardize subject privacy while not 

unnecessarily slowing research. 

Thus, this NPRM proposes 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) requiring that 

the informed consent form present the 

required information before providing 

any other information to a prospective 

subject; (3) revising and adding to the 

required elements of consent; (4) 

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 (5) changing 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 identifiable 

private information without individuals’ 

informed consent for the purpose of 

screening, recruiting, or determining 

eligibility of prospective human subjects 

of research. 

Provisions that strengthen humans 

subjects protections include: (1) A 

provision that would hold IRBs not 

affiliated with engaged institutions 

directly responsible for compliance; (2) 

extending the scope of the policy to 

research most likely to involve greaterthan-minimal risk, that is, clinical trials; 

and (3) creating standard privacy 

safeguards for biospecimens and 

information. 

Provisions that strengthen the extent 

to which the ethics system promotes the 

principle of respect for persons: (1) 

Requiring informed consent for most 

research activities involving 

biospecimens, regardless of 

identifiability; (2) allowing for waiver of 

informed consent in research activities 

involving biospecimens only in rare 

circumstances; and (3) adding a 

provision that would prohibit waiver of 

consent if someone has been asked to 

provide their broad consent for future 

research use of their biospecimens or 

identified private information, and that 

person refuses to give such consent. 

New provisions that would allow 

IRBs greater flexibility to focus 

resources on higher-risk research 

include: (1) Distinguishing categories of 

activities that would be excluded from 

the rule; 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; (2) 

eliminating an administrative 

requirement for reporting IRB rosters; 

(3) removing the requirement that IRBs 

must review and approve grant 

applications; (4) eliminating under 

certain specific circumstances, 

continuing review for minimal risk 

studies that undergo expedited review; 

(5) clarifying when expedited review 

can occur; and (6) mandating use of a 

single IRB for multi-institutional 

studies. 

D. Analysis of Benefits and Costs 

In this section, the analysis of the 

quantified and non-quantified benefits 

and costs of the proposed changes to the 

Common Rule are presented. First, the 

common assumptions of the analysis are 

discussed. Then, this section presents 

the estimated quantified and nonquantified benefits and costs of the 

specific changes. Because of the lack of 

available data about IRB effectiveness 

and how IRBs function operationally,84

many of the estimations in this analysis 

are based on anecdotal evidence. On all 

assumptions and estimates presented 

below, public comment is requested on 

the accuracy of these assumptions and 

on whether better data sources are 

available to support the analysis. 

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 proposed 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 


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85Bell 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. 

86To derive this estimate, the number of new 

protocols, estimated above, is divided by the 

average number of new protocols 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. 

characteristics of the reviews 

themselves. As previously stated, public 

comment is requested on these and 

other estimates used throughout the 

analysis. 

According to the OHRP database of 

registered institutions and IRBs, there 

are approximately 8,035 institutions 

with a 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, for a 

total of 3,499 IRBs. 

The OHRP database of registered 

institutions and IRBs shows that there 

are 675,390 annual reviews of nonexempt protocols involving human 

subjects. It is estimated that there are 

324,187 initial protocol reviews (48 

percent) and 351,203 continuing 

protocol reviews (52 percent) based on 

estimates reported in Bell et al.85 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 there are 472,773 reviews 

of single-site protocols (70 percent) and 

202,617 reviews of multi-site protocols 

(30 percent) based on estimates reported 

in Bell et al. This analysis also assumes 

that there are on average 5 IRB reviews 

per multiple-site protocol. This implies 

that there are 472,773 single-site 

protocols and 40,523 multi-site 

protocols, for a total of 513,296 

protocols. The above implies that there 

are approximately 246,382 new 

protocols each year. 

Based on queries of ClinicalTrials.gov, 

it is estimated that HHS supports 909 

new clinical trials annually, of which 

575 are regulated by FDA. In addition, 

it is estimated that there are 1,399 

clinical trials currently not subject to 

oversight by either the Common Rule or 

FDA regulations. Finally, based on 

queries of ClinicalTrials.gov, Common 

Rule agencies support approximately 

5,270 studies total. 

Many individuals in various 

occupations would be affected by the 

proposed changes to the Common Rule. 

It is 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 institutions and IRBs shows 

that there are 10,197 full-time 

equivalents (FTEs) staff persons at IRBs 

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 

administrative staff. The OHRP database 

of IRB 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 there are 439,968 

investigators who conduct human 

subjects research in the United States.86

The hourly wages of individuals 

affected by the proposed changes to the 

Common Rule is estimated 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 

proposed changes to the Common Rule 

are assumed to be Step 5 within their 

GS-level 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 2016– 

2025, 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. 

The RIA calculates 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. The RIA assumes 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. It is further assumed 

that convened review requires twice as 

many person-hours as expedited review. 

Table 3 shows the number of entities 

affected by the proposed 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 a Federalwide Assurance .......................................................................................................................................... 8,035 

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

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

IRBs ..................................................................................................................................................................................................... 3,499 

Occupations 

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


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

Description Estimate 

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 (2013) ..................................................................................................................................................................... $48.20 

Institution legal staff (2013) ................................................................................................................................................................. $63.24 

IRB administrators (2013) .................................................................................................................................................................... $63.24 

IRB administrative staff (2013) ............................................................................................................................................................ $16.72 

IRB chairs (2013) ................................................................................................................................................................................. $46.36 

IRB voting members (2013) ................................................................................................................................................................ $46.36 

Investigators (2013) ............................................................................................................................................................................. $35.75 

Database administrators (2013) .......................................................................................................................................................... $38.69 

Prospective Human Subjects (2013) ................................................................................................................................................... $22.25 

Federal employees in the District of Columbia, Baltimore, and Northern Virginia (2013): 

GS–9 Step 5 ............................................................................................................................................................................. $28.04 

GS–13 Step 5 ........................................................................................................................................................................... $48.35 

GS–14 Step 5 ........................................................................................................................................................................... $57.13 

GS–15 Step 5 ........................................................................................................................................................................... $67.21 

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 non-exempt 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%) .................................................................................................................................................. 242,330 

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

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

Annual reviews of multi-site 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-site protocol ........................................................................................................... 5 

Clinical Trials 

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

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

Active clinical trials currently not regulated by the Common Rule or FDA regulations ...................................................................... 1,399 

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 


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

Description Estimate 

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 Proposed Changes 

Presented below is an analysis of the 

quantified and non-quantified benefits 

and costs of the proposed changes to the 

Common Rule. For each proposed 

change, we describe and explain the 

need for 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 proposed 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. 

Finally, OHRP would need to develop 

guidance, templates, lists, and a number 

of electronic resources (as stated in the 

NPRM). 

The RIA estimates that institution 

officials, IRB administrators, IRB 

administrative staff, IRB chairs, IRB 

voting members, and investigators 

would each spend 5 hours to learn the 

proposed changes to the Common Rule. 

It is also estimated that institution 

officials would spend two 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 proposed changes to the 

Common Rule in 2016, 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 

($48.20), and by the adjustment factor 

for benefits and overhead (2). 

In order to develop the resources 

required by the NPRM, it is anticipated 

that OHRP would need: 

• Three staff people at the GS–14 

level to: (1) Promote harmonization 

efforts to issue guidance across Common 

Rule agencies and departments; (2) 

develop a number of ‘‘Secretary’s Lists’’ 

(akin to guidance documents) 

referenced in the rule that would be 

periodically reviewed and revised; (3) 

develop template agreements/contracts 

for use by the regulated community; (4) 

manage the administrative transition to 

the new processes proposed in the 

NPRM; and, (5) develop the language 

and technical requirements for a webbased tool that would allow 

investigators (and others) to determine if 

a project fits into a category of research 

exempt from certain regulatory 

requirements. 

• One staff person at the GS–13 level 

to manage process changes proposed in 

the NPRM, and assist with 

implementation for the web-based tools 

and portals proposed. 

• One staff person at the GS–9 level 

to provide technical support for the 

web-based portals proposed in the 

NPRM. 

In addition, the first year after a 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 non-personnel costs: 

• Technical development of a webbased tool that investigators (and others) 

may use to determine if a project fits 

into a category of research that is 

exempt from certain regulatory 

requirements ($350,000) 

• Technical development of two webbased portals for investigators to post 

final consent forms for HHS-funded 

clinical trials, and for investigators that 

conduct certain types of demonstration 

projects to post information about said 

projects ($200,000) 

• Developing five educational 

seminars (including travel) to educate 

the public about the requirements of the 

new rule ($200,000) 

• Upgrading equipment for education 

activities ($50,000) 

Present value costs of $208 million 

and annualized costs of $24.3 million 

are estimated using a 3 percent discount 

rate; present value costs of $199 million 

and annualized costs of $28.3 million 

are estimated using a 7 percent discount 

rate. Table 4 summarizes the quantified 


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and non-quantified 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

Benefits 

Present value of 10 years 

by discount rate 

(millions of 2013 dollars) 

Annualized value over 10 years 

by discount rate 

(millions of 2013 dollars) 

3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Benefits 

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

Non-quantified Benefits 

None (although benefits discussed in association with other provisions would be impossible without this activity).

Costs 3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Costs 

Time and money to learn new requirements, update training materials, and develop tools ................................................................. 208 199 24.3 28.3 

Non-quantified Costs 

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

b. Extending Oversight to IRBs 

Unaffiliated With an Institution Holding 

a Federalwide Assurance (NPRM at 

§ ll.101(a)) 

The NPRM proposes a change to place 

unaffiliated IRBs within the realm of 

entities to which the policy applies. 

This new provision gives Common Rule 

departments and agencies explicit 

authority to enforce compliance directly 

against IRBs that are not affiliated with 

an assured institution. This change 

addresses concerns about OHRP’s 

current practice of enforcing compliance 

with the Common Rule through the 

institutions that were engaged in human 

subjects research, even in circumstances 

when the regulatory violation is directly 

related to the responsibilities of an 

external IRB. This change should 

encourage institutions to more willingly 

rely on qualified unaffiliated IRBs for 

cooperative research, as is required 

under the proposed changes at 

§ ll.114 (see section III.D.2.s of this 

RIA below). 

The OHRP database of assured 

institutions and registered IRBs shows 

that there are approximately 449 IRBs 

not affiliated with an institution holding 

an FWA that would now be subject to 

oversight. These IRBs would develop an 

estimated average of 10 written 

agreements with other institutions each 

year as a result of this proposal. It is 

further estimated that each agreement 

would 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 

2016–2025 wages and adjusting for 

overhead and benefits. 

Present value costs of $84.6 million 

and annualized costs of $9.93 million 

are estimated using a 3 percent discount 

rate; present value costs of $69.2 million 

and annualized costs of $9.86 million 

are estimated using a 7 percent discount 

rate. Table 5 summarizes the quantified 

and non-quantified 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 FEDERALWIDE ASSURANCE (NPRM AT § ll.101(a)) 

Benefits 

Present value of 10 years 

by discount rate 

(millions of 2013 dollars) 

Annualized value over 10 years 

by discount rate 

(millions of 2013 dollars) 

3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Benefits 

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

Non-quantified Benefits 

Encouragement to institutions to rely on unaffiliated IRBs when appropriate. 

Costs 3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Costs 

Developing IRB authorization agreements ....................................... 84.6 69.2 9.93 9.86 

Non-quantified Costs 

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


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c. Extending Common Rule Compliance 

Oversight to Clinical Trials Regardless 

of Funding Source (NPRM at 

§ ll.101(a)(2)) 

The proposed rule would extend the 

regulations to cover clinical trials 

conducted at an institution in the 

United States that receives federal 

support from a Common Rule 

department or agency for non-exempt, 

non-excluded human subjects research, 

regardless of the funding source of the 

specific clinical trial. Extension of the 

rules would not apply to clinical trials 

already regulated by FDA. 

A small percentage of clinical trials 

currently are not subject to oversight by 

either the Common Rule or FDA 

regulations. This change in policy gives 

OHRP the authority to conduct 

oversight compliance of clinical trials 

not otherwise subject to human subjects 

protection regulations. The benefits to 

be gained in terms of equitable and just 

distribution of protections to all subjects 

of clinical trials warrant closing this gap 

in the current system. Moreover, while 

it is expected that this extension would 

apply to only a small percentage of 

clinical trials, they are the type of 

studies that often pose the greatest risks 

to subjects. Since this extension is 

expected to bring research that poses the 

most risk to research subjects under the 

rules, it is presumed that the current 

option in the FWA that allows 

institutions to voluntarily extend the 

funding Common Rule department or 

agency’s compliance oversight authority 

to all research conducted at an 

institution regardless of funding source 

(i.e., ‘‘checking the box’’) would be 

unnecessary. 

Although more research would be 

covered by the policy, the extension is 

contingent on an entity receiving federal 

support for non-exempt human subjects 

research; thus, the entity already should 

have an established IRB in place and 

would not incur costs establishing one 

or contracting with an unaffiliated IRB. 

The RIA estimates that there are 1,399 

clinical trials currently not subject to 

oversight by either the Common Rule or 

FDA regulations. It is estimated that in 

2016 all 1,399 of these clinical trials 

would undergo convened initial review. 

In subsequent years, an estimated 672 

protocols would undergo convened 

initial review, 502 would undergo 

convened continuing review, and 225 

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 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 

2016–2025 wages and adjusting for 

overhead and benefits. 

Present value costs of $18.3 million 

and annualized costs of $2.15 million 

are estimated using a 3 percent discount 

rate; present value costs of $15.1 million 

and annualized costs of $2.15 million 

are estimated using a 7 percent discount 

rate. Table 6 summarizes the quantified 

and non-quantified benefits and costs of 

oversight for clinical trials currently not 

subject to oversight. 

TABLE 6—SUMMARY OF ESTIMATED BENEFITS AND COSTS OF EXTENDING COMMON RULE COMPLIANCE OVERSIGHT FOR

CLINICAL TRIALS REGARDLESS OF FUNDING SOURCE (NPRM AT § ll.101(a)(2)) 

Benefits 

Present value of 10 years 

by discount rate 

(millions of 2013 dollars) 

Annualized value over 10 years 

by discount rate 

(millions of 2013 dollars) 

3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Benefits 

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

Non-quantified Benefits 

Improving institutional willingness to use unaffiliated IRBS, thereby facilitating the implementation of the proposed changes to §ll.114 

(Cooperative Research). 

Costs 3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Costs 

Increase in number of reviews ......................................................... 18.3 15.1 2.15 2.15 

Non-quantified Costs 

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

d. Activities Excluded From the 

Requirements of the Common Rule 

Because They Are Not Research (NPRM 

at §ll.101(b)(1)) 

Six categories of activities would be 

excluded from the regulatory 

requirements of the Common Rule 

because they are not considered 

research as defined in §ll.102(l) in 

the NPRM: (1) Certain data collection 

and analysis activities conducted for an 

institution’s own internal operation and 

program improvement purposes; (2) 

certain activities that focus directly on 

the specific individuals about whom the 

information is collected (i.e., oral 

history, journalism, biography, and 

historical scholarship); (3) certain 

collection and analysis activities 

conducted by a criminal justice agency 

solely for criminal justice investigative 

purposes; (4) certain quality assurance 

or improvement activities; (5) certain 

public health surveillance activities; 

and (6) certain activities conducted by 

a defense, national security, or 

homeland security authority. The 

proposal in the NPRM to explicitly list 

certain activities that are not considered 

‘‘research’’ for the purposes of this 

policy is not intended to suggest that 

these are the only six categories that 

may be considered not to meet the 

definition of ‘‘research.’’ 

Federal agencies (and some 

institutions in the regulated community) 

engaged in activities considered in these 

exclusions already interpret such 

activities as excluded from the 

regulations. Thus, in general, the 

exclusions found in proposed 

§ ll.101(b)(1) represent a proposed 

codification of current practice. 

However, comments to the ANPRM 

suggested that at many institutions, 

activities that would now be explicitly 

excluded from the policy are being 

routinely reviewed by IRBs. While many 


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87See e.g., Schrag, ZM ‘‘Smithsonian Frees Oral 

History, Journalism, and Folklore,’’ Institutional 

Review Blog, 30 July 2010, http:// 

www.institutionalreviewblog.com/2010/07/ 

smithsonian-frees-oral-history.html. See also ‘‘More 

Universities Deregulate Oral History’’, 7 April 2010, 

http://www.institutionalreviewblog.com/2010/04/ 

more-universities-deregulate-oral.html. 

88See e.g., Baily, MA ‘‘Quality Improvement 

Methods in Health Care,’’ in From Birth to Death 

and Bench to Clinic: The Hastings Center Bioethics 

Briefing Book for Journalists, Policymakers, and 

Campaigns, ed. Mary Crowley (Garrison, NY: The 

Hastings Center, 2008), 147–152 http:// 

www.thehastingscenter.org/Publications/ 

BriefingBook/Detail.aspx?id=2204. 

institutions are specifically creating 

policies to state that oral history or 

journalism activities do not require IRB 

review,87 institutions vary and some 

continue to require IRB review for other 

activities (such as quality improvement 

activities 88) that may not meet the 

Common Rule’s definition of research. 

Thus, explicitly excluding these six 

categories because they are to be 

considered not research would provide 

clarity to the regulatory community 

about what constitutes research per this 

policy, and also likely result in a modest 

decrease in the number of IRB reviews 

that occur each year in institutions. 

Institutions, investigators, and IRBs 

involved in supporting, conducting, or 

reviewing these activities would no 

longer incur the costs of IRB review and 

approval and continuing review. 

Activities that were not intended to be 

subject to the regulations would clearly 

be excluded, allowing such activities to 

proceed without delays caused by the 

need for IRB submission, review, and 

approval. 

It is estimated that 6,754 annual 

reviews of protocols (1.0 percent) would 

no longer be conducted as a result of the 

exclusions proposed in §ll.101(b)(1). 

Of these reviews, 2,237 would have 

undergone convened initial review, 

1,005 would have undergone expedited 

initial review, 2,423 would have 

undergone convened continuing review, 

and 1,089 would 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 

2016–2025 wages and adjusting for 

overhead and benefits. 

Present value benefits of $74.0 million 

and annualized benefits of $8.67 million 

are estimated using a 3 percent discount 

rate, and present value benefits of $60.5 

million and annualized benefits of $8.61 

million are estimated using a 7 percent 

discount rate. Table 7 summarizes the 

quantified and non-quantified benefits 

and costs of excluding these activities 

from the requirements of the Common 

Rule. 

TABLE 7—SUMMARY OF ESTIMATED BENEFITS AND COSTS OF EXCLUDING ACTIVITIES FROM THE REQUIREMENTS OF THE

COMMON RULE BECAUSE THEY ARE NOT RESEARCH (NPRM AT § ll.101(b)(1)) 

Benefits 

Present value of 10 years 

by discount rate 

(millions of 2013 dollars) 

Annualized value over 10 years 

by discount rate 

(millions of 2013 dollars) 

3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Benefits 

Reduction in number of reviews ....................................................... 74.0 60.5 8.67 8.31 

Non-quantified Benefits 

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

Costs 3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Costs 

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

Non-quantified Costs 

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

e. Low-Risk Research Activities 

Excluded From the Requirements of the 

Common Rule Because They Are 

Already Subject to Independent 

Controls (NPRM at §ll.101(b)(2)) 

The NPRM proposes that four 

additional categories of research 

activities be explicitly excluded from 

the regulatory requirements of the 

Common Rule because they are low-risk 

and already subject to independent 

controls in the absence of the 

protections of the Common Rule. These 

are: (1) Certain research activities that 

involve the use of certain educational 

tests, survey procedures, interview 

procedures, or observation of public 

behavior (a revised version of current 

exemption category 2); (2) certain 

research activities involving the 

collection or study of information (a 

revised version of current exemption 

category 4); (3) certain research 

activities conducted by a government 

agency using government-generated, 

non-research data; and (4) certain data 

collection and analysis activities using 

identifiable health information subject 

to the HIPAA Privacy Rule. 

The current Common Rule articulates 

two exemptions (current Rule at 

§ ll.101(b)(2) and (4)) that appear in 

a similar format in the proposed NPRM 

exclusions. Current Common Rule 

exemption category 2 is found in the 

NPRM in § ll.101(b)(2)(i); current 

exemption category 4 is found in NPRM 

§ ll.101(b)(2)(ii). In addition to being 

considered excluded from the rule 

(rather than exempt from certain 

requirements of the rule), current 

exemption category 2 (NPRM 

§ ll.101(b)(2)(i)) has been clarified to 

state that interventions in conjunction 

with collection of data through the use 

of educational tests, survey procedures, 

interview procedures or observation of 

public behavior uninfluenced by the 

investigator (including visual or 

auditory recording) may not be used in 

research activities that qualify for this 

exclusion. For the research activities at 

issue in the NPRM at § ll.101(b)(2)(i), 

it is presumed that the activities poses 

little to no risk to subjects, and that the 

subjects knowingly and willingly 


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provide the information, or decline to 

participate. Thus, IRB review of the 

research and consent related documents 

are not believed to be necessary for such 

activities. 

Four changes are proposed to current 

exemption category 4 (NPRM at 

§ ll.101(b)(2)(ii)). First, the provision 

would now be considered excluded 

from the rule, not just exempt from 

certain requirements of the rule. 

Second, the provision no longer 

includes pathological specimens or 

diagnostic specimens. Third, NPRM 

§ ll.101(b)(2)(ii) removes the word 

‘‘existing’’ from the provisions. This is 

intended to clarify the scope of the 

exclusion to allow for information that 

will be collected in the future. Finally, 

a condition is added requiring that the 

exclusion may only be used when the 

investigator has no plans to contact 

subjects, re-identify subject, or 

otherwise conduct an analysis that 

could lead to creating identifiable 

private information. 

Neither the exclusion at NPRM 

§ ll.101(b)(2)(iii) (certain research 

activities conducted by a government 

agency using government-generated, 

non-research data) nor the exclusion at 

NPRM §ll.101(b)(2)(iv) (certain data 

collection and analysis activities using 

identifiable health information subject 

to the HIPAA Privacy Rule) appear in 

the current Rule. These research 

activities are excluded because human 

subjects are independently protected 

through other mechanisms or laws. It is 

anticipated that the exclusion of 

activities regulated by HIPAA as health 

care operation activities, public health 

activities, or research (NPRM at 

§ ll.101(b)(2)(iv)) would represent a 

significant reduction in the volume of 

activities an IRB reviews. For example, 

the proposed exclusion at 

§ ll.101(b)(2)(iv) would mean that at 

institutions subject to the HIPAA 

regulations, projects where one is 

simply analyzing protected health 

information from medical charts would 

not be required to undergo IRB review. 

Institutions, investigators, and IRBs 

involved in supporting, conducting, or 

reviewing these activities would no 

longer incur the costs of IRB review, 

approval, and continuing review. 

Activities that were not intended to be 

subject to the regulations would clearly 

be excluded, allowing such activities to 

proceed without delays caused by the 

need for IRB submission, review, and 

approval. 

The RIA estimates that 67,539 annual 

reviews of protocols (10.0 percent) 

would no longer be conducted as a 

result of the proposed exclusions in 

§ ll.101(b)(2). It is anticipated that the 

exclusion of certain activities covered 

by the HIPAA Privacy Rule would drive 

the estimated reduction in annual IRB 

reviews of protocols. Of these reviews, 

22,369 would have undergone convened 

initial review, 10,050 would have 

undergone expedited initial review, 

24,233 would have undergone convened 

continuing review, and 10,887 would 

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 

2016–2025 wages and adjusting for 

overhead and benefits. 

Present value benefits of $740 million 

and annualized benefits of $86.7 million 

are estimated using a 3 percent discount 

rate, and present value benefits of $605 

million and annualized benefits of $86.1 

million are estimated using a 7 percent 

discount rate. Table 8 summarizes the 

quantified and non-quantified benefits 

and costs of excluding these activities 

from the requirements of the Common 

Rule. 

TABLE 8—SUMMARY OF ESTIMATED BENEFITS AND COSTS OF EXCLUDING LOW-RISK RESEARCH FROM THE

REQUIREMENTS OF THE COMMON RULE (NPRM AT § ll.101(b)(2)) 

Benefits 

Present value of 10 years 

by discount rate 

(millions of 2013 dollars) 

Annualized value over 10 years 

by discount rate 

(millions of 2013 dollars) 

3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Benefits 

Reduction in number of reviews ....................................................... 740 605 86.7 86.1 

Non-quantified Benefits 

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

Costs 3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Costs 

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

Non-quantified Costs 

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

f. Clarifying and Harmonizing 

Regulatory Requirements and Agency 

Guidance (NPRM at §ll.101(j) 

The proposed rule would require 

consultation among the Common Rule 

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. The 

proposal also recognizes that 

harmonization would not always be 

possible or desirable given the varied 

missions of the agencies that oversee the 

protection of human subjects and 

differences in statutory authorities. Note 

that this is a codification of 

harmonization efforts currently 

occurring across Common Rule 

agencies. 

This proposal appropriately 

recognizes the importance of 

harmonized guidance for the regulated 

community by creating, as much as 

possible, consistent interpretations of 

the regulations. 

There is no compliance requirement 

for the regulated community associated 

with this provision. It is anticipated that 

harmonization would create greater 


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89Eiseman, E., Haga, S. (1999). Handbook of 

Human Tissue Sources: A National Resource of 

Human Tissue Samples. Washington, DC: RAND 

Corporation. 

uniformity in the regulatory 

requirements for investigators, 

institutions, and IRBs, which could 

reduce confusion and time spent 

complying with multiple sets of 

regulations. Costs for achieving 

harmonization would be borne by the 

Common Rule agencies. 

As this change likely would not 

impact staffing requirements at 

Common Rule agencies, no costs are 

quantified here. It is possible however, 

that the harmonization requirement 

could result in it taking longer for 

Common Rule agency guidance to be 

approved and issued to the public. 

Similarly, as it is unclear the extent to 

which this change would reduce the 

time IRBs spend on reviewing protocols, 

benefits are also not quantified. Table 9 

summarizes the non-quantified benefits 

and costs of clarifying and harmonizing 

regulatory requirements and agency 

guidance. 

TABLE 9—SUMMARY OF ESTIMATED BENEFITS AND COSTS OF CLARIFYING AND HARMONIZING REGULATORY

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

Benefits 

Present value of 10 years 

by discount rate 

(millions of 2013 dollars) 

Annualized value over 10 years 

by discount rate 

(millions of 2013 dollars) 

3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Benefits 

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

Non-quantified Benefits 

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

regulations should be interpreted. 

Costs 3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Costs 

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

Non-quantified Costs 

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

g. Expanding the Definition of Human 

Subject To Include Research Involving 

Non-Identified Biospecimens and 

Creating an Exemption for Secondary 

Research Using Biospecimens or 

Identifiable Private Information (NPRM 

at §§ll.102(e), ll.101(b)(3)(i), and 

ll.104(f)(2)) 

The NPRM proposes to expand the 

definition of human subjects to include 

research in which an investigator 

obtains, uses, studies or analyzes a 

biospecimen. This would apply 

regardless of the identifiability of the 

biospecimen. Generally, investigators 

would not be allowed to remove 

identifiers from biospecimens without 

obtaining informed consent or a waiver 

of consent. Written consent would 

generally be required for such activities. 

Thus, this change will significantly 

expand the amount of research that is 

subject to the Common Rule. This 

requirement would not apply to 

biospecimens and information already 

collected at the time the final rule is 

published. Proposed § ll.101(b)(3)(i) 

would exclude research activities 

involving non-identified biospecimens 

where no new information about an 

individual is generated. While activities 

such as developing new testing assays 

could be excluded under this provision, 

it is anticipated that under the NPRM 

proposals, most research with 

biospecimens would now fall under the 

Rule. 

At its core, this proposal is intended 

to promote the ethical principle of 

respect for persons. In addition to 

promoting respect for persons in the 

research enterprise, the proposed 

regulatory structure for research with 

biospecimens (whereby consent is 

sought for almost all research activities 

involving biospecimens) will encourage 

investigators to retain identifiers, which 

can enhance research by preserving the 

ability to link to important additional 

information about the subject. 

Additionally, members of the regulated 

community have reported situations 

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 

current NPRM proposals, such a 

situation would not occur because 

consent—be it broad or study specific— 

would always be obtained for research 

involving biospecimens. 

While this proposal will promote the 

ethical principle of respect for persons, 

it also will significantly increase the 

volume of studies for which 

investigators must seek and document 

informed consent (unless more stringent 

waiver criteria are met). The RIA 

estimates that there are 250,000 studies 

using biospecimens each year that are 

not currently subject to oversight by 

either the Common Rule or FDA 

regulations because they have been 

stripped of identifiers. Extrapolations 

from 1999 data 89 suggest that 

biospecimens are collected from as 

many as 30 million individuals and are 

stored each year for both clinical and 

research purposes. Approximately 9 

million individuals’ biospecimens (30 

percent) are collected for research 

purposes. As a conservative estimate, 

approximately 6.3 million individuals’ 

biospecimens (30 percent) could 

potentially be used in future research 

studies. Thus, it is possible that 

investigators would 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 

will now be covered, two approaches 

are proposed; public comment is 

requested on these estimates and 

approaches. Under method one, it is 

estimated that approximately 50 

biospecimens will be used on average 

per research protocol involving 

biospecimens. This gives a potential 

300,000 new research protocols using 


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non-identified biospecimens. This 

estimate of 300,000 new research 

protocols is rounded down to 250,000 

new studies because based on ANPRM 

comments and industry data, it seems 

reasonable to assume that, as a 

conservative estimate, the number of 

new biospecimen studies encapsulated 

by the proposed rule would equal the 

total number of new protocols 

conducted each year (i.e., the number of 

new biospecimen studies is likely close 

to the estimate of 246,382 new annual 

studies). 

Under method two, biospecimen 

repository representatives report that 

roughly 90 percent of their collections 

are used in non-identified form in 

research activities that do not fall under 

the current Common Rule. Thus, only 

10 percent of biospecimen studies are 

currently covered by the Common Rule, 

representing a 9:1 ratio of studies 

involving non-identified biospecimens 

to studies involving identifiable 

biospecimens. Of the 246,382 new 

protocols each year that are non-exempt 

(Table 3), we assume conservatively that 

10–15 percent are using identifiable 

biospecimens. This equates to between 

24,638 and 36,957 new studies each 

year using identifiable biospecimens. As 

previously discussed, it is estimated 

that the number of biospecimen studies 

that occur on non-identified 

biospecimens each year is 

approximately 9 times the number of 

studies using identifiable biospecimens, 

or between 221,741 and 332,613 studies 

each year. Thus, under method two, an 

estimate of 250,000 new studies on nonidentified biospecimens each year is 

also reasonable. 

In order to facilitate research with 

biospecimens, the NPRM proposes to 

create separate elements of broad 

consent (NPRM at §ll.116(c), 

discussed in III.D.2.u below) such that 

investigators and institutions may seek, 

and individuals may grant, consent for 

future unspecified research activities. 

The NPRM also proposes an exemption 

that relies on obtaining broad consent 

for future, unspecified research studies 

(NPRM at § ll.104(f)(2)). In order to be 

eligible for the exemption proposed in 

§ ll.104(f)(2), broad consent must 

have been sought and obtained using 

the Secretary’s template for broad 

consent (described in proposed 

§ ll.116(d)(3)), and the investigator 

must not anticipate returning individual 

research results to subjects. To facilitate 

secondary research using biospecimens 

and identifiable private information, the 

NPRM also proposes an exemption for 

the storage and maintenance of 

biospecimens and identifiable private 

information for future, unspecified, 

secondary research activities (NPRM at 

§ ll.104(f)(1)), which is described in 

more detail in Section III.D.2.n below). 

The exemption proposed at 

§ ll.104(f)(2) is specifically for 

secondary research studies involving 

biospecimens and identifiable private 

information that have been or will be 

acquired for purposes other than the 

currently proposed research study. If a 

secondary research study does not meet 

the requirements of this exemption 

category, the investigator would need to 

seek IRB review of the study, and would 

need to obtain either study-specific 

consent or a waiver of informed consent 

under the Common Rule. Note that for 

biospecimens an IRB would apply the 

more stringent waiver criteria at 

proposed §ll.116(e)(2) or (f)(2). For 

identifiable private information, an IRB 

would apply the waiver criteria at 

proposed §ll.116(e)(1) or (f)(1), 

which are almost identical to the waiver 

criteria in the current Common Rule. 

The proposed exemption at 

§ ll.104(f)(2), also ensures that in 

secondary research conducted with 

biospecimens or identifiable private 

information, appropriate privacy 

safeguards are in place (through 

requiring adherence to the privacy 

safeguards described in § ll.105). 

Thus, although this provision is an 

expansion in the nature of research that 

is exempt, it is accompanied by certain 

requirements and safeguards. 

It is anticipated that a majority of 

studies that utilize this exemption will 

be biospecimen studies. The extent to 

which individuals conducting 

secondary research studies involving 

identifiable private information will 

utilize this exemption is unknown given 

that there are additional pathways 

under this proposed rule to facilitate 

secondary research activities involving 

identifiable private information is 

unknown. To that end, the benefits and 

costs associated with this provision only 

take into consideration secondary 

research involving biospecimens. It is 

further anticipated that these revisions 

will result 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 are met. 

Because the estimated 250,000 

biospecimen studies each year that will 

be newly covered under the rule as a 

result of the proposed modification to 

the definition of human subject will 

likely be low or minimal risk, the RIA 

assumes that all of these will be eligible 

for the § ll.104(f)(2) exemption (so 

long as consent—broad or study 

specific—was sought and obtained). 

Benefits and costs associated with 

obtaining and tracking broad consent 

are discussed below in section III.D.2.u 

of this RIA. Because the compliance 

date for the expansion to the definition 

of human subject will be three years 

after the date of publication of a final 

rule, the benefits and costs described 

below assume a start date of 2019. 

As required under §ll.104(c), an 

exemption determination must be made 

and documented for each of the 250,000 

newly covered biospecimen studies. It is 

anticipated that in 50 percent of these 

studies (125,000 studies), investigators 

will spend 30 minutes entering 

information into the HHS-created 

decision tool in order for that tool to 

generate an exemption determination. In 

the remaining 125,000 studies, it is 

anticipated that investigators will spend 

30 minutes preparing and submitting 

information about the study to an 

individual able to make exemption 

determinations (per § ll.104(c)). An 

individual at the IRB voting member 

level will spend an estimated 30 

minutes per study to make an 

exemption determination. 

In the absence of the proposed exempt 

category of research at §ll.104(f)(2) 

but taking into consideration the 

expansion to the definition of human 

subject, it is estimated that each year, all 

250,000 of these studies will undergo 

convened initial review. In subsequent 

years, it is estimated 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 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 

2016–2025 wages and adjusting for 

overhead and benefits. 

Present value costs of $101 million 

and annualized costs of $11.9 million 

are estimated using a 3 percent discount 

rate; present value costs of $77.8 million 

and annualized costs of $11.1 million 

are estimated using a 7 percent discount 

rate. Table 10 summarizes the 

quantified and non-quantified benefits 

and costs of amending the definition of 

human subject. 


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TABLE 10—SUMMARY OF EXPANDING THE DEFINITION OF HUMAN SUBJECT TO INCLUDE RESEARCH INVOLVING NON-IDENTIFIED BIOSPECIMENS AND CREATING AN EXEMPTION FOR SECONDARY RESEARCH USING BIOSPECIMENS OR IDENTIFIABLE PRIVATE INFORMATION (NPRM AT §§ ll.102(e), ll.101(b)(3)(i), AND ll.104(f)(2)) 

Benefits 

Present value of 10 years 

by discount rate 

(millions of 2013 dollars) 

Annualized value over 10 years 

by discount rate 

(millions of 2013 dollars) 

3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Benefits 

Reduction in number of IRB reviews that would have otherwise 

occurred as a result of the expansion of the definition of human 

subject ........................................................................................... .......................... .......................... .......................... ..........................

Non-quantified Benefits 

Ethical benefit of respecting an individual’s wishes in how his or her biospecimens are used in future; ensuring protection of human subjects in research activities involving non-identifiable biospecimens. 

Costs 3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Costs 

Determining that these studies are exempt in accordance with 

§ll.104(c) ................................................................................. 101 77.8 11.9 11.1 

Non-quantified Costs 

Potential reduction in number of biospecimens available for research. 

h. Modifying the Assurance 

Requirements (current Rule at 

§ ll.103(b)(1), (b)(3), (d)) 

The NPRM proposes to modify the 

requirements of the assurance process in 

the following ways. First, the NPRM 

proposes to delete the requirement in 

the current Common Rule at 

§ ll.103(b)(1) of identifying a 

statement of principles governing all 

research at an institution. As discussed 

in section II.H.2 of this preamble, the 

requirement for institutions to designate 

a set of ethical principles to which that 

institution will abide in all research 

activities is generally not enforced. 

Further, for international institutions 

that may receive U.S. government 

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 U.S. government 

funding. In order to provide clarity to 

these international institutions that such 

measures are not required for activities 

that receive no Common Rule 

department or agency support, this 

provisions has been deleted. 

The requirement that a written 

assurance include a list of IRB members 

for each IRB designated under the 

assurance would be replaced by the 

requirement that the assurance include 

a statement that for each designated IRB 

the institution, or when appropriate the 

IRB, prepares and maintains 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 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 proposed changes to the IRB 

roster requirement are expected to 

reduce administrative burden and have 

the following additional beneficial 

effects, without having any significant 

impact on the protection of human 

subjects: 

• Reduction in the administrative 

burdens on institutions related to the 

submission of IRB membership lists to 

OHRP and, in some cases, to the 

departments and agencies that process 

their own assurances; 

• Reduction in the administrative 

burdens on OHRP with respect to 

reviewing and processing new and 

updated IRB membership lists as part of 

the IRB registration process, as well as 

reductions, in some cases, in the 

administrative burdens on other 

departments and agencies that receive 

and review IRB membership lists and 

changes in IRB membership as part of 

their own assurance processes; 

• In some cases, reduction in the 

volume of records that need to be 

created and retained by the departments 

and agencies regarding the review and 

processing of IRB membership lists; and 

• Simplification of the process for the 

electronic submission and acceptance of 

IRB registrations via the OHRP Web site. 

In addition, HHS anticipates 

modifying the FWA so that institutions 

would no longer have the option to 

‘‘check the box’’ on an assurance and 

voluntarily extend the funding Common 

Rule department or agency’s regulatory 

authority to all research conducted at an 

institution regardless of funding source. 

For research other than clinical trials, 

institutions could continue to 

voluntarily apply the regulations to all 

research conducted by the institution, 

but this voluntary extension would no 

longer be part of the FWA. Members of 

the regulated community report that 

whether or not they ‘‘check the box’’ on 

an assurance form, they tend to 

voluntarily apply the regulations to all 

research activities taking place at an 

institution regardless of funding. Thus, 

the removal of this option on an 

assurance form likely would not impact 

community practice. To that end, no 

costs have been associated with this 

provision. 

Finally, the current requirement at 

§ ll.103(d) that a department or 

agency head’s evaluation of an 

assurance take into consideration 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 


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and continuing review procedures in 

light of the probable risks, and the size 

and complexity of the institution, would 

be deleted. 

The deletion of this provision would 

eliminate an administrative process that 

is 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. 

The RIA estimates 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 2016–2025 

wages and adjusting for overhead and 

benefits. 

Present value benefits of $5.81 million 

and annualized benefits of $0.68 million 

are estimated using a 3 percent discount 

rate; present value benefits of $4.10 

million and annualized benefits of $0.58 

million are estimated using a 7 percent 

discount rate. Table 11 summarizes the 

quantified and non-quantified benefits 

and costs of the proposed change to the 

IRB roster requirement. 

TABLE 11—SUMMARY OF ESTIMATED BENEFITS AND COSTS OF PROPOSED CHANGE TO MODIFYING THE ASSURANCE

REQUIREMENTS (CURRENT RULE AT § ll.103(b)(1), (b)(3), (d)) 

Benefits 

Present value of 10 years 

by discount rate 

(millions of 2013 dollars) 

Annualized value over 10 years 

by discount rate 

(millions of 2013 dollars) 

3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Benefits 

Reduction in time for IRB administrative staff and OHRP staff to 

submit, review, and process IRB membership lists ...................... 5.81 4.10 0.68 0.58 

Non-quantified Benefits 

Reduction in volume of records created by an institution 

Costs 3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Costs 

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

Non-quantified Costs 

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

i. Requirement for Written Procedures 

and Agreements for Reliance on 

External IRBs (NPRM at §§ll.103(e) 

and ll.115(a)(10)) 

Language is proposed at §ll.103(e) 

requiring each IRB, institution, or 

organization that has oversight 

responsibility for non-exempt research 

involving human subjects covered by 

this policy and conducted by another 

institution to have a written agreement 

identifying the respective 

responsibilities of the IRB organization 

and the engaged institution for meeting 

the regulatory requirements of this 

policy. This is already a requirement 

under the terms of an FWA but this 

requirement increases the level of detail 

that has to be included in such 

agreements, specifically the roles and 

responsibilities of each party. In 

addition, a requirement is added at 

§ ll.115(a)(10) that institutions or 

IRBs retain the agreement between the 

institution and IRB specifying the 

responsibilities that each entity would 

undertake to ensure compliance with 

the requirements of proposed 

§ ll.103(e). 

The new requirements for agreements 

between institutions and external IRBs 

would not apply to research initiated 

before the effective date of the rule. 

However, the new requirements would 

affect existing agreements between 

institutions and external IRBs in cases 

where the existing agreements are not 

study-specific, but rather pertain to all 

research conducted by the institution or 

to a category or categories of human 

subjects research. 

Initially, costs would be involved in 

drafting, revising, and conducting 

managerial review of agreements to 

ensure they satisfy these new 

requirements. Anticipated benefits 

include enhanced protection of human 

subjects in research reviewed by 

nonaffiliated IRBs, and greater reliance 

on external IRBs as the IRB of record for 

cooperative research, as stipulated in 

proposed §ll.114. 

Table 3 shows that there are 5,164 

FWA-holding institutions without an 

IRB and 2,871 FWA-holding institutions 

with an IRB. We assume that the 5,164 

FWA-holding institutions without an 

IRB have an average of 1 IRB 

authorization agreement that would 

need to be modified as a result of the 

new requirements for agreements 

between institutions and external IRBs 

in 2016. 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 2016. We 

estimate that each agreement would 

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 2016 wages and adjusting for 

overhead and benefits. 

Present value costs of $11.3 million 

and annualized costs of $1.32 million 

are estimated using a 3 percent discount 

rate; present value costs of $10.8 million 

and annualized costs of $1.54 million 

are estimated using a 7 percent discount 

rate. Table 12 summarizes the 

quantified and non-quantified benefits 

and costs of the requirement for written 

procedures and agreements for reliance 

on external IRBs (§§ll.103(e) and 

ll.115(a)(10) in the NPRM). 


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TABLE 12—SUMMARY OF REQUIREMENT FOR WRITTEN PROCEDURES AND AGREEMENTS FOR RELIANCE ON EXTERNAL

IRBS (NPRM AT §§ ll.103(e) AND ll.115(a)(10)) 

Benefits 

Present value of 10 years 

by discount rate 

(millions of 2013 dollars) 

Annualized value over 10 years 

by discount rate 

(millions of 2013 dollars) 

3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Benefits 

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

Non-quantified Benefits 

Enhanced human subjects protections in research reviewed by nonaffiliated IRBs and encouragement to institutions to rely on external 

IRBs when appropriate 

Costs 3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Costs 

Time to modify written agreements between IRBs and institutions 11.3 10.8 1.32 1.54 

Non-quantified Costs 

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

j. Eliminating the Requirement That the 

Grant Application Undergo IRB Review 

and Approval (Current Rule at 

§ ll.103(f)) 

The proposed rule would eliminate 

the requirement in the current Rule at 

§ ll.103(f) that grant applications 

undergo IRB review and approval for 

the purposes of certification. As 

described in section II.h.2 of this 

preamble, 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. 

Eliminating the requirement that the 

grant application undergo IRB review 

and approval would reduce 

administrative costs to investigators and 

IRB voting members. The proposed 

change likely would not reduce 

protections for human subjects or 

impose other costs. 

The RIA estimates that there are 

324,187 initial reviews of protocols 

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, 

it is assumed that each protocol 

reviewed by an IRB is associated with 

one grant application or other funding 

proposal. The RIA estimates that 

investigators spend an average of 15 

minutes compiling their grant 

applications when they submit a 

protocol for initial review. Further, it is 

estimated 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 

2016–2025 wages and adjusting for 

overhead and benefits. 

Present value benefits of $310 million 

and annualized benefits of $36.3 million 

are estimated using a 3 percent discount 

rate, and present value benefits of $219 

million and annualized benefits of $31.1 

million are estimated using a 7 percent 

discount rate. Table 13 summarizes the 

quantified and non-quantified benefits 

and costs of eliminating the requirement 

that the grant application undergo IRB 

review and approval. 

TABLE 13—SUMMARY OF ESTIMATED BENEFITS AND COSTS OF ELIMINATING THE REQUIREMENT THAT THE GRANT

APPLICATION UNDERGO IRB REVIEW AND APPROVAL (CURRENT RULE AT § ll.103(f)) 

Benefits 

Present value of 10 years 

by discount rate 

(millions of 2013 dollars) 

Annualized value over 10 years 

by discount rate 

(millions of 2013 dollars) 

3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Benefits 

Decreased time associated with review ........................................... 310 219 36.3 31.1 

Non-quantified Benefits 

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

Costs 3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Costs 

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

Non-quantified Costs 

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


asabaliauskas on DSK5VPTVN1PROD with PROPOSALS
Federal Register / Vol. 80, No. 173 / Tuesday, September 8, 2015 / Proposed Rules 54009 

k. Tracking and Documenting 

Exemption Determinations (NPRM at 

§§ ll.104(c) and ll.115(a)(11)) 

New in the NPRM is a proposal at 

§ ll.104(c) that Federal departments 

and agencies would develop an 

exemption determination tool for use by 

investigators and institutions. Under the 

proposed rule, unless otherwise 

required by law, exemption 

determinations may be made by (1) an 

individual who is knowledgeable about 

the exemption categories and who has 

access to sufficient information to make 

an informed and reasonable 

determination, or (2) the investigator 

who accurately inputs information into 

the federally created web-based decision 

tool (NPRM at §ll.104(c)). Also new 

in the NPRM is a requirement at 

proposed §ll.115(a)(11) that an IRB 

maintain records of exemption 

determinations. Additionally, proposed 

§ ll.104(c) specifies that the use of the 

exemption determination tool would 

satisfy the documentation requirement 

in proposed § ll.115(a)(11). 

While the documentation requirement 

for exemption determinations is new, 

comments from members of the 

regulated community suggest that most 

institutions have systems in place 

already to make and document 

exemption determinations. Thus, the 

requirement of proposed 

§ ll.115(a)(11) would likely have a 

negligible impact on institutions. 

Additionally, it is anticipated that use of 

the exemption determination tool 

described in proposed §ll.104(c) 

would likely represent a reduction in 

burden for institutions and 

investigators. First, institutions are not 

responsible for creating the decision 

tool; the Federal Government is. The 

costs associated with the development 

and maintenance of this tool are 

discussed above in section III.D.2.a of 

this RIA. Second, except for protocols 

for which IRB review is required by law 

and those for which the exemption tool 

is unable to issue determinations (and 

therefore still have to be submitted to an 

IRB for review), IRB offices would no 

longer need to devote significant 

resources to processing and reviewing 

studies for exemption because the use of 

the tool by the investigator would 

suffice. Third, the investigator would no 

longer need to engage in the timeintensive task of developing and 

submitting a formal application to an 

IRB for an exemption determination, 

which is standard practice at many 

institutions. Instead, the investigator 

would be able to answer questions in 

the to-be-created tool, and then be able 

to commence work if determination 

generated by the tool indicates that the 

proposed research activity meets one of 

the exemption categories. 

The quantifiable benefits and costs 

associated with the use of the §l.104(c) 

decision tool are documented in each 

RIA discussion of exemption categories 

(sections II.D.2.f, l, m, n of this RIA). 

Note that while §l104(c) requires that 

an exemption determination be made 

before an exempt study may begin, the 

use of the proposed exemption 

determination tool is not mandated. 

Rather, the tool to be created by HHS is 

an option proposed in order to reduce 

burden on the investigators and 

institutions. Additionally, note that at 

present it is unknown how many 

studies are exempted under the current 

Rule each year. Thus, this RIA is only 

able to provide quantifiable benefits and 

costs for studies that are estimated to be 

newly exempted. 

Table 14 summarizes the nonquantified benefits and costs of the 

tracking requirements for exemption 

determinations and the criteria for those 

eligible to make exemption decisions in 

NPRM §l.104(c). 

TABLE 14—SUMMARY OF ESTIMATED BENEFITS AND COSTS OF TRACKING AND DOCUMENTING EXEMPTION

DETERMINATIONS (NPRM AT §§ ll.104(c) AND ll.115(a)(11)) 

Benefits 

Present value of 10 years 

by discount rate 

(millions of 2013 dollars) 

Annualized value over 10 years 

by discount rate 

(millions of 2013 dollars) 

3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Benefits 

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

Non-quantified Benefits 

Reduced administrative burden for IRBs in reviewing exemption determinations, reduced time for investigators to receive an exemption determination. 

Costs 3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Costs 

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

Non-quantified Costs 

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

l. Exemption for Research and 

Demonstration Projects (NPRM at 

§ l.104(d)(2)) 

The current exemption related to 

research and demonstration projects 

(current Rule at §l.101(b)(5)) would be 

revised to clarify that certain Common 

Rule agency or department supported 

activities currently fall within that 

scope. OHRP also proposes to broaden 

its interpretation of public benefit and 

service programs which are being 

evaluated as part of the research to 

include public benefit or service 

programs that an agency does not itself 

administer through its own employees 

or agents, but rather funds (i.e., 

supports) through a grant or contract 

program. It has been OHRP’s 

interpretation that the current 

exemption category 5 only applies to 

those research and demonstration 

projects designed to study a ‘‘public 

benefit or service program’’ that a 

Common Rule agency or department 

itself administers, and for which the 

public benefit or service program exists 

independent of any research initiative. 

The proposed regulatory revision and 

change in OHRP’s interpretation of the 

exemption is designed to clarify and 

broaden the scope of the exemption so 

that more research studies would be 

exempt. It is believed that these changes 

would make the exemption easier to 

apply appropriately and is expected to 


asabaliauskas on DSK5VPTVN1PROD with PROPOSALS
54010 Federal Register / Vol. 80, No. 173 / Tuesday, September 8, 2015 / Proposed Rules 

90Estimates 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/ResearchStatistics-Data-and-Systems/Statistics-Trends-andReports/ActiveProjectReports/APR_2011_

Edition.html. 

reduce the number of studies that would 

be required to undergo IRB review. 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 deliver 

social goods without requiring IRB 

review and approval. The proposed 

changes to this exemption would 

require OHRP to revise its existing 

guidance document on this exemption 

accordingly. Costs associated with this 

revision are accounted for in section 

III.D.2.a above. 

In addition, a requirement has been 

added 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 Secretary of HHS may 

prescribe, a list of the research and 

demonstration projects which the 

Federal department or agency conducts 

or supports under this provision. The 

research or demonstration project must 

be published on this list prior to or 

upon commencement of the research. 

This exemption is needed for 

government entities to carry out 

activities related to their important 

public health mission and functions; in 

acknowledgement of the fact that morethan-minimal-risk studies could be 

conducted under this exemption, the 

posting requirement promotes increased 

transparency in these activities. 

Note that a study’s exemption 

documentation requirement at 

§ l.104(c) is satisfied by a Federal 

department or agency posting minimal 

information about the research or 

demonstration project on a federal, 

publicly accessible Web site. Thus, in 

general, an institutional official would 

not have to post any information to this 

Web site. 

It is estimated that approximately 

1,000 exempt research and 

demonstration studies are currently 

conducted each year.90 It is further 

estimated that due to the change in 

OHRP’s interpretation of the research 

and demonstration project exemption, 

an additional 3,377 annual reviews of 

protocols (0.5 percent) would no longer 

be conducted. Of these 3,377 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. Comment is 

requested on the accuracy of the 

estimates of the number of research and 

demonstration projects conducted each 

year. 

The 4,377 estimated annual studies 

conducted under this exemption would 

need to be posted to a federal Web site 

as required by §l.104(d)(2)(i). It is 

anticipated that it would take 

individuals at the IRB administrative 

staff level 15 minutes per study to post 

the study to the Web site. Note that 

costs related to developing the Web site 

to which information about 

demonstration projects would be posted 

are calculated in section III.D.2.a of this 

RIA. 

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 

2016–2025 wages and adjusting for 

overhead and benefits. 

Present value benefits of $37.0 million 

and annualized benefits of $4.34 million 

are estimated using a 3 percent discount 

rate, and present value benefits of $30.3 

million and annualized benefits of $4.31 

million are estimated using a 7 percent 

discount rate. Present value costs of 

$0.36 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 15 

summarizes the quantified and nonquantified benefits and costs of 

amending an exempt category. 

TABLE 15—SUMMARY OF ESTIMATED BENEFITS AND COSTS OF AMENDING THE RESEARCH AND DEMONSTRATION

PROJECT EXEMPTION (NPRM AT § ll.104(d)(2)) 

Benefits 

Present value of 10 years 

by discount rate 

(millions of 2013 dollars) 

Annualized value over 10 years 

by discount rate 

(millions of 2013 dollars) 

3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Benefits 

Reduction in the number of studies requiring IRB review ............... 37.0 30.3 4.34 4.31 

Non-quantified Benefits 

Reduction in time to determine whether the exemption applies to research and demonstration studies; increased transparency to the public 

in the types of research activities conducted under this exemption 

Costs 3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Costs 

Communication of the exempt research and demonstration studies 0.36 0.30 0.04 0.04 

Non-quantified Costs 

Possible delays in commencement of exempt research and demonstration studies until posting has occurred; revising federal guidance 

documents 


asabaliauskas on DSK5VPTVN1PROD with PROPOSALS
Federal Register / Vol. 80, No. 173 / Tuesday, September 8, 2015 / Proposed Rules 54011 

m. Expansion of Research Activities 

Exempt From IRB Review (NPRM at 

§ ll.104(d)(3), (e)(1), (e)(2)) 

Three proposed exemptions in the 

NPRM would expand the types of 

activities that could occur without any 

IRB review (expedited or full-board). A 

new exemption at proposed 

§ ll.104(d)(3) covers research 

involving benign interventions in 

conjunction with the collection of data 

from an adult subject through verbal or 

written responses (including data entry) 

or video recording if the subject 

prospectively agrees to the intervention 

and data collection and at least one of 

two criteria is met. 

A second exemption at proposed 

§ ll.104(e)(1) covers research 

involving the use of educational tests 

(cognitive, diagnostic, aptitude, 

achievement), survey procedures, 

interview procedures or observation of 

public behavior (including visual or 

auditory recording), if the information 

obtained is recorded in such a manner 

that human subjects can be identified 

directly or through identifiers linked to 

the subjects. A third exemption at 

proposed §ll.104(e)(2) would permit 

the secondary research use of 

identifiable private information 

originally collected for non-research 

purposes, so long as notice was 

provided to the prospective human 

subjects about the research activities 

and the identifiable private information 

is used only for purposes of the specific 

research for which the investigator or 

recipient entity obtained the 

information. 

Because the new exemptions at 

§ ll.104(e)(1) and (2) permits 

investigators to record potentially 

sensitive information about research 

subjects in an identifiable form, such 

activities must comply with the privacy 

safeguards found at §ll.105 in the 

proposed Rule. Some of this research 

may be eligible for expedited review 

under the current rule, and would now 

be exempt from even that level of IRB 

review under the proposed rule. This 

would result in costs savings associated 

with IRB submission, review, and 

approval. In addition, most institutions 

already have information protection 

systems and policies in place and are 

likely to already meet the privacy 

safeguards of proposed §ll.105. 

It is estimated that 6,754 annual 

reviews of protocols (0.5 percent) would 

no longer be conducted as a result of 

these proposed changes. Of these 

reviews, 2,236 would have undergone 

convened initial review, 1,004 would 

have undergone expedited initial 

review, 2,424 would have undergone 

convened continuing review, and 1,088 

would have undergone expedited 

continuing review based on the 

distribution of reviews presented in 

Table 3. 

As required under §ll.104(c), an 

exemption determination must be made 

and documented for each of these 6,754 

newly exempted studies. It is 

anticipated that in 50 percent of these 

studies (3,377 studies), investigators 

will spend 30 minutes entering 

information into the HHS-created 

decision tool in order for that tool to 

generate an exemption determination. In 

the remaining 3,377 studies, it is 

anticipated that investigators will spend 

30 minutes preparing and submitting 

information about the study to an 

individual able to make exemption 

determinations (per § ll.104(c)). An 

individual at the IRB voting member 

level will spend an estimated 30 

minutes per study to make an 

exemption determination. 

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 

2016–2025 wages and adjusting for 

overhead and benefits. 

The estimated costs associated with 

new privacy and security standards are 

presented section III.D.2.o of this RIA. 

Present value benefits of $70.0 million 

and annualized benefits of $8.20 million 

are estimated using a 3 percent discount 

rate, and present value benefits of $57.2 

million and annualized benefits of $8.16 

million are estimated using a 7 percent 

discount rate. Table 16 summarizes the 

quantified and non-quantified benefits 

and costs of modifying the exemption 

categories for research involving adults. 

TABLE 16—SUMMARY OF ESTIMATED BENEFITS AND COSTS OF CREATING NEW EXEMPTION CATEGORIES (NPRM AT

§ ll.104(d)(3), (e)(1), (e)(2))) 

Benefits 

Present value of 10 years 

by discount rate 

(millions of 2013 dollars) 

Annualized value over 10 years 

by discount rate 

(millions of 2013 dollars) 

3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Benefits 

Reduction in number of reviews ....................................................... 70.0 57.2 8.20 8.16 

Non-quantified Benefits 

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

Costs 3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Costs 

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

Non-quantified Costs 

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


asabaliauskas on DSK5VPTVN1PROD with PROPOSALS
54012 Federal Register / Vol. 80, No. 173 / Tuesday, September 8, 2015 / Proposed Rules 

n. Exemption for the Storage and 

Maintenance of Biospecimens and 

IdentPrivate Information for Future, 

Unspecified Secondary Research 

Activities After Consent Has Been 

Sought and Obtained (NPRM at 

§§ ll.104(f)(1) and ll.111(a)(9)) 

The NPRM proposes a specific 

exemption for storage and maintenance 

of biospecimens (regardless of 

identifiability) and identifiable private 

information for future, unspecified 

secondary research activities after 

consent has been sought and obtained. 

The idea behind this exemption is that 

an institution can store and maintain 

biospecimens and identifiable private 

information for future research studies 

without being required to have a 

specific repository creation protocol 

developed, reviewed, and approved by 

an IRB. To be eligible for the exemption, 

the institution or an investigator must 

seek broad consent for the future use of 

biospecimens and information using the 

Secretary’s broad consent template. 

Biospecimens and identifiable private 

information from both the research or 

non-research contexts may be 

designated under this exemption for 

future unspecified research studies. As 

part of the condition for this proposed 

exemption, an IRB would be required to 

do a one-time, limited review of the 

consent process using the expedited 

review procedure (as would be required 

in proposed § l l.111(a)(9)). The 

privacy safeguards outlined in proposed 

§ l l.105 would apply to these 

activities. Note that if moving the 

biospecimens or information collected 

for use in future unspecified research 

studies is envisioned, as part of the 

limited IRB review described in § l 

l.111(a)(9), an IRB would also need to 

review the adequacy of the privacy 

safeguards described in § l l.105. 

Non-quantified benefits of this 

provision include clearer instructions to 

the regulated community about the 

extent to which creating system for 

storing and maintaining 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, this provision also 

incentivizes the creation of institutionwide, comprehensive systems for the 

storage and maintenance of 

biospecimens and identifiable private 

information for future, unspecified 

secondary research activities, which 

would foster more research while 

remaining respectful of subject 

autonomy. Because of the benefits to 

investigators of being eligible for a new 

exemption if secondary research 

activities are conducted using 

biospecimens or identifiable private 

information maintained or stored 

according to § l l.104(f)(1), 

institutions would be further 

incentivized to implement and develop 

such a system. Also note that while FDA 

is unable to harmonize with the 

Common Rule on many of the 

exemptions due to specific requirements 

in FDA’s authorizing statutes, including 

the §l l.104(f)(2) exemption, research 

that is also subject to the FDA 

regulations would be eligible for this 

exemption. 

Because of the proposal for the rule to 

cover all biospecimens regardless of 

identifiability, it is anticipated that a 

majority of institutions would elect to 

develop a system for storing and 

maintaining biospecimens and 

identifiable private information for 

future, unspecified secondary research 

activities as allowed under the proposed 

exemption at § l l.104(f)(1). This RIA 

estimates that 6,428 FWA holding 

institutions (80 percent) would develop 

such a mechanism for storing and 

maintaining biospecimens and 

identifiable private information for 

future, unspecified secondary research 

activities. The RIA anticipates that 1,607 

FWA institutions (20 percent) would 

not develop this type of mechanism, 

either due to the lower volume of 

research overall conducted at that 

institution or because the institution 

conducts mostly social and behavioral 

research. At each of the 6,428 

institutions where a storage and 

maintenance schema exemptible under 

NPRM §l l.104(f)(1) is developed, it 

is assumed that an individual at the IRB 

administrator level would spend two 

hours at each institution reviewing the 

consent process through which a 

subject’s broad consent to future 

research uses of his or her biospecimens 

or information is sought. 

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 

2016–2025 wages and adjusting for 

overhead and benefits. 

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 

2016–2025 wages and adjusting for 

overhead and benefits. 

Present value costs of $1.58 million 

and annualized benefits of $0.19 million 

are estimated using a 3 percent discount 

rate, and present value benefits of $1.48 

million and annualized benefits of $0.21 

million are estimated using a 7 percent 

discount rate. Table 17 summarizes the 

quantified and non-quantified benefits 

and costs of modifying the exemption 

categories for research involving adults. 

TABLE 17—EXEMPTION FOR THE STORAGE AND MAINTENANCE OF BIOSPECIMENS AND IDENTIFIABLE PRIVATE INFORMATION FOR FUTURE, UNSPECIFIED SECONDARY RESEARCH ACTIVITIES AFTER CONSENT HAS BEEN SOUGHT AND OBTAINED (NPRM AT §§ ll.104(f)(1) AND ll.111(a)(9)) 

Benefits 

Present value of 10 years 

by discount rate 

(millions of 2013 dollars) 

Annualized value over 10 years 

by discount rate 

(millions of 2013 dollars) 

3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Benefits 

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

Non-quantified Benefits 

Fostering research with biospecimens and identifiable private information 

Costs 3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Costs 


asabaliauskas on DSK5VPTVN1PROD with PROPOSALS
Federal Register / Vol. 80, No. 173 / Tuesday, September 8, 2015 / Proposed Rules 54013 

TABLE 17—EXEMPTION FOR THE STORAGE AND MAINTENANCE OF BIOSPECIMENS AND IDENTIFIABLE PRIVATE INFORMATION FOR FUTURE, UNSPECIFIED SECONDARY RESEARCH ACTIVITIES AFTER CONSENT HAS BEEN SOUGHT AND OBTAINED (NPRM AT §§ ll.104(f)(1) AND ll.111(a)(9))—Continued 

Benefits 

Present value of 10 years 

by discount rate 

(millions of 2013 dollars) 

Annualized value over 10 years 

by discount rate 

(millions of 2013 dollars) 

3 Percent 7 Percent 3 Percent 7 Percent 

Obtaining limited IRB review of consent process ............................ 1.58 1.48 0.19 0.21 

Non-quantified Costs 

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

o. Privacy Safeguards for Biospecimens 

and Identifiable Private Information 

(NPRM at §§ ll.105 and ll.115(c)) 

Increasing research use of genetic 

information, information obtained from 

biospecimens, medical records, and 

administrative claims data has altered 

the nature of the risks to those whose 

information is being used in research. 

The risks related to these types of 

research are not physical but rather are 

informational through, for example, the 

unauthorized release or use of 

information about subjects. Currently, 

IRBs evaluate each study with regard to 

all levels of risk and are expected to 

determine whether the privacy of 

subjects and the confidentiality of their 

information is protected. Under the 

current Common Rule, IRBs must 

review each individual study’s 

protection plan to determine whether it 

is adequate with respect to the 

informational risks of that study. 

The proposed rule would impose a 

new requirement that institutions and 

investigators implement appropriate 

security safeguards for biospecimens 

and identifiable private information. 

The purpose of these safeguards is to 

assure that access to biospecimens and 

individually identifiable private 

information is only authorized in 

appropriate circumstances and that 

informational risks are managed by 

applying appropriate safeguards to 

information and biospecimens. To 

ensure that the requisite limitations on 

use and disclosure are met, an 

institution or investigator can obtain 

adequate assurances through the use of 

a written agreement with the recipient 

of the information or biospecimens. In 

addition, a new provision is proposed at 

§ ll.115(c) that requires that the 

institution or IRB retaining IRB records 

shall safeguard, if relevant, individually 

identifiable private information 

contained in those records in 

compliance with the privacy safeguards 

proposed at § ll.105. 

Under the proposal, the HHS 

Secretary would develop a set of 

minimum standards for the protection 

of information for research outside of 

the current scope of the HIPAA 

standards to create an effective and 

efficient means of implementing 

appropriate protections for 

biospecimens and information. This list 

would be developed in consultation 

with other Common Rule agencies and 

would be published in the Federal 

Register. 

Consequently, the IRBs would not be 

required to review the individual plans 

for safeguarding information and 

biospecimens for each research study, 

so long as investigators would adhere to 

one or the other set of standards. It is 

anticipated that once IRBs are familiar 

with standard institutional- and 

investigator-imposed protections they 

would become more comfortable with 

the fact that they need not review every 

protocol for security standards. In 

addition, IRBs would not have to review 

security provisions on a case-by-case 

basis, which would result in cost 

savings in terms of time. 

It is expected that most research 

institutions would already have most of 

these protections in place, especially 

those institutions that are subject in 

whole or part to the HIPAA rules. Other 

fiduciary, legal, and proprietary 

responsibilities related to obtaining and 

storing biospecimens are likely to 

encompass the protections proposed for 

securing biospecimens. Also note that 

the envisioned security measures that 

will appear on the Secretary’s List 

would be less stringent than what many 

institutions have already implemented. 

It should also be noted that the NPRM 

proposal would result in uniform 

baseline standards for security. Costs 

associated with developing the 

Secretary’s List in accordance with 

proposed §ll.105 are accounted for in 

section III.D.2.a of this RIA. 

It is estimated that 803 of the 8,035 

institutions with FWAs (10 percent) 

would need to update their privacy and 

security standards to comply with the 

new requirements. At these institutions, 

institutional officials and institutional 

legal staff would each spend an 

estimated 80 hours in 2016 and 20 

hours in subsequent years to update and 

monitor their privacy and security 

standards. In addition, the RIA 

estimates that 43,997 of 439,968 

investigators (10 percent) would be 

required to adopt the updated privacy 

and security standards. These 

investigators would each spend an 40 

hours in 2016 and 10 hours in 

subsequent years to comply. Based on 

the estimates presented in Table 3, the 

dollar value of their time is calculated 

by multiplying hours by their estimated 

2016–2025 wages and adjusting for 

overhead and benefits. Public comments 

are requested on these estimates. 

Present value costs of $457 million 

and annualized costs of $53.6 million 

are estimated using a 3 percent discount 

rate; present value costs of $347 million 

and annualized costs of $49.4 million 

are estimated using a 7 percent discount 

rate. Table 18 summarizes the 

quantified and non-quantified benefits 

and costs to protect information and 

biospecimens. 


asabaliauskas on DSK5VPTVN1PROD with PROPOSALS
54014 Federal Register / Vol. 80, No. 173 / Tuesday, September 8, 2015 / Proposed Rules 

TABLE 18—SUMMARY OF ESTIMATED BENEFITS AND COSTS OF PROTECTION OF INFORMATION AND BIOSPECIMENS

(NPRM AT §§ ll.105 AND ll.115(c)) 

Benefits 

Present value of 10 years 

by discount rate 

(millions of 2013 dollars) 

Annualized value over 10 years 

by discount rate 

(millions of 2013 dollars) 

3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Benefits 

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

Non-quantified Benefits 

Improved protection of individually identifiable private information and biospecimens. 

Costs 3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Costs 457 347 53.6 49.4 

Time for institutions to update and adopt new privacy and security standards. 

Non-quantified Costs 

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

p. Elimination of Continuing Review of 

Research under Specific Conditions 

(NPRM at §§ ll.109(e), (f) and 

ll.115(a)(3), (8)) 

The NPRM proposes eliminating 

continuing review for many minimal 

risk studies, unless the reviewer 

explicitly justifies why continuing 

review would enhance protection of 

research subjects. 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 one or both of the following: 

(1) Analyzing data (even if it is 

identifiable private), or (2) accessing 

follow-up clinical data from procedures 

that subjects would undergo as part of 

standard care for their medical 

condition or disease. 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). 

It is also proposed that continuing 

review of research eligible for expedited 

review in accordance with §ll.110 

not be required, although an IRB may 

determine that continuing review of 

research eligible for expedited review is 

necessary. When an IRB requires 

continuing review of such studies, this 

too must be documented in compliance 

with a proposed requirement at 

§ ll.115(a)(8). 

Requiring continuing review for 

studies that are minimal risk (and 

eligible for expedited review at the 

onset) or that no longer pose greater 

than minimal risk presents a regulatory 

burden that does not meaningfully 

enhance protection of subjects. Further, 

the requirement takes time from the 

IRB’s review of higher risk studies. 

This would result in less time spent 

by institutions, IRBs, and investigators 

in terms of time spent preparing for and 

conducting continuing review. This is a 

one-time compliance burden in Year 1 

for institutions to update their systems 

to no longer send continuing review 

reminders to certain investigators. There 

would be increased recordkeeping 

requirements, however, for institutions 

to comply with §ll115(a)(3) and 

(a)(8). Because we estimate that 90 

percent of protocols that previously had 

to undergo continuing view would no 

longer need to, there is an overall net 

benefit. However, 10 percent of studies 

would require a new recordkeeping 

component. The benefits in terms of 

cost savings would begin in year one 

and extend indefinitely. However, costs 

would be associated with the 

requirement that IRBs document cases 

in which they elect to conduct 

continuing review when it is not a 

regulatory requirement. 

The RIA estimates that there are 

108,873 expedited continuing reviews 

of protocols annually based on the 

distribution of reviews presented in 

Table 3. Of these reviews, the RIA 

further estimates that 81,546 reviews (75 

percent) would not be eliminated by 

other proposed changes to the Common 

Rule (such as the modifications 

proposed at §§ ll.101(b); 

ll.104(d)(1)–(3), (e)(1), and (f)). It is 

estimated that 40,773 of these 81,546 

reviews (50 percent) would be 

discontinued and the remaining 40,773 

reviews (50 percent) would continue 

and require documentation of the 

rationale for doing so. The RIA also 

estimates that IRB voting members 

would spend 1 hour per review 

providing documentation. In addition, 

administrative staff at each IRB would 

spend an estimated 10 hours in 2016 

updating their communication systems 

to no longer send continuing review 

reminders to certain 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 

2016–2025 wages and adjusting for 

overhead and benefits. 

Present value benefits of $145 million 

and annualized benefits of $17.0 million 

are estimated using a 3 percent discount 

rate, and present value benefits of $119 

million and annualized benefits of $16.9 

million are estimated using a 7 percent 

discount rate. Present value costs of 

$38.8 million and annualized costs of 

$4.55 million are estimated using a 3 

percent discount rate; present value 

costs of $31.9 million and annualized 

costs of $4.54 million are estimated 

using a 7 percent discount rate. Table 19 

summarizes the quantified and nonquantified benefits and costs of the 

elimination of continuing review of 

research under specific conditions. 


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TABLE 19—SUMMARY OF ESTIMATED BENEFITS AND COSTS OF THE ELIMINATION OF CONTINUING REVIEW OF RESEARCH

UNDER SPECIFIC CONDITIONS (NPRM AT §§ ll.109(e), (f) AND ll.115(a)(3), (8)) 

Benefits 

Present value of 10 years 

by discount rate 

(millions of 2013 dollars) 

Annualized value over 10 years 

by discount rate 

(millions of 2013 dollars) 

3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Benefits 145 119 17.0 16.9 

Reduction in number of continuing reviews.

Non-quantified Benefits 

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

Costs 3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Costs 

Time to document rationale for conducting continuing review and 

update IRB communication systems ............................................ 38.8 31.9 4.55 4.54 

Non-quantified Costs 

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

q. Expedited Review Procedures (NPRM 

at §§ll.110 and ll.115(a)(9)) 

The proposed rule would make minor 

changes regarding expedited review, to 

change the default position such that 

expedited review can occur for studies 

on the HHS Secretary’s list unless the 

reviewer(s) determine(s) that the study 

involves more than minimal risk. The 

NPRM also proposes that, in 

consultation with other Common Rule 

departments or agencies, the expedited 

review categories be reviewed every 

eight years and amended as appropriate, 

followed by publication in the Federal 

Register and solicitation of public 

comment. Finally, there would be a new 

requirement at proposed § ll.115(a)(9) 

concerning IRB records 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). 

Additionally, in order to assist 

institutions in determining whether an 

activity is minimal-risk, the NPRM 

proposes in § ll.102(j) that the 

Secretary of HHS will maintain 

guidance that includes a list of activities 

considered to be minimal risk. The costs 

associated with developing and 

maintaining this guidance document are 

accounted for above in III.D.2.a of this 

RIA. 

The proposed changes to the 

expedited review procedures are 

expected to reduce the IRB workload by 

increasing the number of studies that 

undergo expedited review rather than 

convened review. The documentation 

requirement does not produce 

additional requirements because IRBs 

must keep records of determinations 

regardless. This just stipulates that the 

reason for an override must be 

described. However, costs would be 

associated with the requirement that 

IRBs document cases in which they 

elect to conduct convened IRB review 

when it is not a regulatory requirement. 

It is estimated that there are 223,689 

convened initial reviews and 242,330 

convened continuing reviews of 

protocols annually based on the 

distribution of reviews presented in 

Table 3. Of these 223,689 convened 

initial reviews, it is estimated that 2,237 

reviews (1 percent) are eligible for 

expedited review because they are in a 

category of research that appears on the 

HHS Secretary’s list. Of these 2,237 

reviews, it is estimated that 1,118 

reviews (50 percent) would undergo 

expedited review and the remaining 

1,118 reviews (50 percent) would 

undergo convened review and require 

documentation of the rationale for doing 

so. 

Of the 242,330 convened continuing 

reviews, it is estimated that 2,423 

reviews (1 percent) are eligible for 

expedited review because they are in a 

category of research that would appear 

on the Secretary’s list. Of these 2,423 

reviews, the RIA estimates that 1,212 

reviews (50 percent) would undergo 

convened review and would require 

documentation of the rationale for doing 

so. Due to the proposed elimination of 

continuing review of research under 

specific conditions (§ ll.109(e) and 

(f); §ll.115(a)(3) and (a)(8)), the 

remaining 1,212 reviews (50 percent) 

would not require review. Of these 

1,212 reviews, the RIA estimates that 

606 reviews (50 percent) would not 

occur and the remaining 606 reviews 

(50 percent) would undergo expedited 

continuing review and require 

documentation of the rationale for doing 

so. The RIA estimates that IRB voting 

members would spend 1 hour per 

review providing documentation when 

required. The cost associated with 

reviewing and amending the list is 

accounted for in section III.D.2.a of this 

RIA. 

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 

2016–2025 wages and adjusting for 

overhead and benefits. 

Present value benefits of $16.8 million 

and annualized benefits of $1.97 million 

are estimated using a 3 percent discount 

rate, and present value benefits of $13.7 

million and annualized benefits of $1.95 

million are estimated using a 7 percent 

discount rate. Present value costs of 

$2.71 million and annualized costs of 

$0.32 million are estimated using a 3 

percent discount rate; present value 

costs of $2.21 million and annualized 

costs of $0.32 million are estimated 

using a 7 percent discount rate. Table 20 

summarizes the quantified and nonquantified benefits and costs of the 

elimination of expedited review 

procedures. 


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TABLE 20—SUMMARY OF ESTIMATED BENEFITS AND COSTS OF AMENDING THE EXPEDITED REVIEW PROCEDURES (NPRM 

AT §§ ll.110 AND ll.115(a)(9)) 

Benefits 

Present value of 10 years 

by discount rate 

(millions of 2013 dollars) 

Annualized value over 10 years 

by discount rate 

(millions of 2013 dollars) 

3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Benefits 16.8 13.7 1.97 1.95 

Reduction in number of reviews.

Non-quantified Benefits 

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

Costs 3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Costs 

Time to document rationale for conducting expedited review ......... 2.71 2.21 0.32 0.32 

Non-quantified Costs 

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

r. Revised Criteria for IRB Approval of 

Research (NPRM at §ll.111) 

Two changes are proposed in the 

criteria for IRB approval of research. 

One pertains to the new requirements 

proposed at § ll.105 to protect 

biospecimens and individually 

identifiable private information used in 

research. The regulations at 

§ ll.111(a)(7) currently require that in 

order to approve research covered by 

this policy, the IRB shall determine that 

when appropriate, there are adequate 

provisions to protect the privacy of 

subjects and to maintain the 

confidentiality of data. This requirement 

would be modified to recognize that the 

requirements at § ll.105 would apply 

to all non-exempt research (unless the 

criteria for exemptions are met). The 

default position should be that if the 

provisions at § ll.105 are being met, 

there is no need for additional IRB 

review of a research study’s privacy and 

confidentiality protections. However, 

there might be extraordinary cases in 

which an IRB determines that privacy 

safeguards above and beyond those 

called for in §ll.105 are necessary. 

Therefore, it is proposed that IRBs 

would be responsible for ensuring there 

are adequate provisions to protect the 

privacy of subjects and to maintain the 

confidentiality of data only if the IRB 

determines that the protections required 

in §ll.105 are insufficient. 

The second proposed change relates 

to the new exemption at § ll.104(f)(2) 

that includes a criterion at (f)(2)(ii) that 

the exemptions do not apply if the 

investigator intends to return individual 

research results to subjects. Thus, a new 

provision would be added at 

§ ll.111(a)(8) clarifying that IRBs need 

to review any plan in a research 

protocol for returning individual 

research results to subjects and to 

determine whether it is appropriate. 

Although many IRBs probably already 

review plans for return of results, and 

many studies do not include this 

feature, it would not be required that 

IRBs review all projects to determine if 

there should be a plan. 

The RIA estimates that there are 

324,187 initial reviews of protocols 

annually, of which 223,689 involve 

convened review and 100,498 involve 

expedited review based on the 

distribution of reviews presented in 

Table 3. The RIA estimates 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 reviewing the security plans 

for biospecimens or identifiable private 

information. Of the 324,187 initial 

reviews, we estimate that 108,062 

reviews (33 percent) would include a 

plan for returning results to subjects and 

that primary reviewers would spend an 

average of 15 minutes reviewing these 

plans. Based on the estimates in Table 

3, the dollar value of their time is 

calculated by multiplying hours by their 

estimated 2016–2025 wages and 

adjusting for overhead and benefits. 

Present value benefits of $126 million 

and annualized benefits of $14.8 million 

are estimated using a 3 percent discount 

rate, and present value benefits of $89.1 

million and annualized benefits of $12.7 

million are estimated using a 7 percent 

discount rate. Present value costs of 

$66.6 thousand and annualized costs of 

$7.8 thousand using a 3 percent 

discount rate; present value costs of 

$62.3 thousand and annualized costs of 

$8.9 thousand using a 7 percent 

discount rate. Table 21 summarizes the 

quantified and non-quantified benefits 

and costs of the revised criteria for IRB 

approval of research. 

TABLE 21—SUMMARY OF ESTIMATED BENEFITS AND COSTS OF REVISED CRITERIA FOR IRB APPROVAL OF RESEARCH

(NPRM AT § ll.111) 

Benefits 

Present value of 10 years 

by discount rate 

(millions of 2013 dollars) 

Annualized value over 10 years 

by discount rate 

(millions of 2013 dollars) 

3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Benefits 

Decreased time associated with each review .................................. 126 89.1 14.8 12.7 

Non-quantified Benefits 

Increased opportunities for research subjects to learn the results of studies in which they participated. 


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TABLE 21—SUMMARY OF ESTIMATED BENEFITS AND COSTS OF REVISED CRITERIA FOR IRB APPROVAL OF RESEARCH

(NPRM AT § ll.111)—Continued 

Benefits 

Present value of 10 years 

by discount rate 

(millions of 2013 dollars) 

Annualized value over 10 years 

by discount rate 

(millions of 2013 dollars) 

3 Percent 7 Percent 3 Percent 7 Percent 

Costs 3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Costs 

Time to review plans for returning results to subjects ..................... 0.07 0.06 0.008 0.009 

Non-quantified Costs 

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

s. Cooperative Research (NPRM at 

§§ ll.114, ll.103(e), and 

ll.101(a)) 

The proposed rule would mandate 

that all domestic sites in a cooperative 

study rely upon a single IRB for that 

study, regardless of the source of 

funding, unless otherwise required by 

law (e.g., FDA-regulated device studies). 

Common Rule funding departments or 

agencies would also have the authority 

to determine that use of a single 

reviewing IRB is not appropriate for a 

particular study (so long as that decision 

is documented). This policy would 

apply regardless of whether the study 

underwent convened IRB review or 

expedited review. This proposal only 

affects the decision about which IRB 

would be designated as the reviewing 

IRB for compliance purposes. Related to 

this is a new provision at §ll.103(e) 

requiring procedures that the institution 

and IRB would follow for documenting 

the institution’s reliance on the IRB for 

oversight and the responsibilities of 

each entity. Also related to this, a new 

provision at § ll.101(a) would give 

Common Rule departments and 

agencies the explicit authority to 

enforce compliance directly against 

IRBs that are not affiliated with an 

assured institution. In addition, the 

proposed rule would be modified to 

remove the current requirement at 

§ ll.103(d) that only with the 

approval of the department or agency 

head, an institution participating in a 

cooperative project may enter into a 

joint review arrangement, rely upon the 

review of another IRB, or make similar 

arrangements for avoiding duplication 

of effort. 

Currently, the choice to have 

cooperative research reviewed by a 

single IRB is voluntary under the 

Common Rule. In practice, most 

institutions have been reluctant to 

replace review by their local IRBs with 

review by a single IRB in part because 

of OHRP’s current practice of enforcing 

compliance with the Common Rule 

through the institutions that were 

engaged in human subjects research, 

even in circumstances when the 

regulatory violation is directly related to 

the responsibilities of an external IRB. 

Review by multiple IRBs for cooperative 

research can add bureaucratic 

complexity to the review process and 

delay initiation of research projects 

without evidence that multiple reviews 

provide additional protections to 

subjects. Thus, the proposed changes at 

§ ll.101(a) are included in this NPRM 

to address this concern in anticipation 

of greater reliance on external IRBs in 

cooperative research, and to promote 

less bureaucratic complexity in the 

review process in multi-site studies. 

Ultimately, these revisions are 

expected to lower costs associated with 

multiple reviews for investigators, 

institutions, and IRBs. There may be 

some cost shifting as certain IRBs take 

on the role of reviewing IRB; however, 

these will be offset by savings at other 

IRBs 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 

standardization in agreements will be 

achieved, and that reliance on single 

IRBs will be accepted because of their 

assured inclusion in oversight, which 

will result in reduced costs associated 

with multiple reviews and time savings 

for investigators who no longer must 

wait for multiple reviews to occur, with 

subsequent revisions and amendments. 

Likely, the hours spent here will replace 

hours spent reviewing and processing a 

submission that otherwise would be 

approved by the institution’s IRB. 

The OHRP database of registered 

institutions and IRBs shows that there 

are 8,035 institutions with an FWA. The 

RIA estimates that these institutions 

would develop an average of 10 written 

joint review agreements with other 

institutions in 2019 prior to the first 

year of compliance. The RIA further 

estimates that each agreement would 

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 2016 and 2019 wages and 

adjusting for overhead and benefits. 

It is estimated that there are 202,617 

annual reviews of multi-site protocols, 

and an average of 5 reviews per multisite protocol, implying that there are 

40,523 multi-site protocols reviewed 

each year. Of these protocols, an 

estimated 36,471 protocols (90 percent) 

do not involve medical devices; as a 

result, 4 of every 5 reviews would be 

eliminated. Accordingly, the RIA 

estimates that 145,884 annual reviews of 

protocols would no longer be conducted 

as a result of these proposed changes. Of 

these reviews, 48,317 would have 

undergone convened initial review, 

21,708 would have undergone 

expedited initial review, 52,343 would 

have undergone convened continuing 

review, and 23,517 would 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 and based on 

the estimates presented in Table 3. The 

dollar value of their time is calculated 

by multiplying hours by their estimated 

2019–2025 wages and adjusting for 

overhead and benefits. 

Present value benefits of $1,103 

million and annualized benefits of $129 

million are estimated using a 3 percent 

discount rate, and present value benefits 

of $849 million and annualized benefits 

of $121 million are estimated using a 7 

percent discount rate. Present value 

costs of $155 million and annualized 

costs of $18.1 million are estimated 

using a 3 percent discount rate; present 

value costs of $138 million and 


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54018 Federal Register / Vol. 80, No. 173 / Tuesday, September 8, 2015 / Proposed Rules 

annualized costs of $19.7 million are 

estimated using a 7 percent discount 

rate. Table 22 summarizes the 

quantified and non-quantified benefits 

and costs of cooperative research. 

TABLE 22—SUMMARY OF ESTIMATED BENEFITS AND COSTS OF COOPERATIVE RESEARCH (NPRM AT §§ ll.114, 

ll.103(e), AND ll.101(a)) 

Benefits 

Present value of 10 years 

by discount rate 

(millions of 2013 dollars) 

Annualized value over 10 years 

by discount rate 

(millions of 2013 dollars) 

3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Benefits 

Reduction in number of reviews ....................................................... 1,103 849 129 121 

Non-quantified Benefits 

Standardization of human subjects protections when variation among review IRBs is not warranted. 

Costs 3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Costs 

Time requirement to develop model reliance agreement and written joint review agreements .......................................................... 155 138 18.1 19.7 

Non-quantified Costs 

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

t. Changes in the Elements of Consent, 

Including Documentation (NPRM at 

§§ ll.116(a)(9), (b)(7)–(9), and 

ll.117(b) in the NPRM) 

A new element of consent at 

§ ll.116(a)(9) applies to identifiable 

private information collected as part of 

a research activity. When identifiable 

private information is collected for 

research purposes, subjects must be 

provided with a statement describing 

the extent to which a subject’s 

information will be made non-identified 

and used in future activities. An 

investigator must include in a consent 

form one of two statements: 

• A statement that all identifiable 

information might be removed from the 

data and the data that is not identifiable 

could be used for future research studies 

or distributed to another investigator for 

future research studies without 

additional informed consent from the 

subject, if this might be a possibility; or 

• A statement that the subject’s data 

collected as part of the research, from 

which identifiable information is 

removed, will not be used or distributed 

for future research studies. 

The addition of the requirement to 

notify subjects of how their nonidentified information might be used is 

viewed as a measure of respect for 

subjects, by informing them of possible 

uses of their information. Potential 

subjects can always decline to 

participate in the initial research if they 

are not willing to consent to the 

statement provided. This measure 

addresses concerns about people not 

being fully informed that their nonidentified information could be used for 

research without their consent. These 

changes are expected to improve 

informed consent forms and processes, 

and ideally result in more informed 

decisions by prospective research 

subjects about whether to participate in 

research. The intent is to create greater 

transparency and improve the informed 

consent process. This addition would 

have to meet the documentation 

requirements at § ll.117(b). 

While this new provision would 

require investigators to inform 

prospective subjects of how their nonidentified information originally 

collected for research purposes might be 

used in future research studies, it is not 

expected that this change to have a 

measurable effect on the administrative 

costs to the research system. Under the 

current regulations, a majority of 

investigators do not restrict the future 

research use of non-identifiable 

information. Therefore, it is expected 

that in implementing this new 

notification requirement, the vast 

majority of investigators would elect 

option (1). In addition, under the 

current regulations, investigators may 

voluntarily restrict the future research 

use of non-identifiable information, 

such as in certain research involving 

vulnerable populations or a rare disease. 

We do not expect the new notification 

requirement to result in an increase in 

the number of investigators who would 

include option (2) in their consent forms 

and processes. When investigators 

choose to restrict the future research use 

of non-identifiable information under 

the current Rules, statements about such 

restricted future use are generally 

already included in the consent forms 

and processes. Therefore, for such 

research, the notification requirement is 

not expected to result in any change in 

practice. 

Since this notification requirement is 

not expected to change investigators’ 

secondary use of non-identifiable 

information originally collected for 

research purposes, it is anticipated that 

investigators and institutions already 

have systems in place to track any 

restrictions investigators currently 

choose to implement. As likely is 

currently the case, it is anticipated that 

very few investigators would elect to 

offer the second option listed above 

because of the challenges of marking 

and tracking such decisions. 

Furthermore, since most investigators 

will likely elect the first option listed 

above, it would be reasonable for 

investigators and institutions to assume 

that the secondary research use of 

information would be permissible 

unless marked otherwise. Therefore, it 

would not be necessary to routinely 

track information obtained using the 

first option. 

Three additional elements of consent 

are proposed in §ll.116(b)(7)–(9). 

These three require that a subject be 

informed of the following, when 

relevant: 

• That the subject’s biospecimens 

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; and 


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• An option for the subject or the 

representative 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. 

These additional elements of consent 

are proposed to promote the goal of 

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 all 

information necessary for understanding 

why one might want to participate (or 

not) in a research study. 

The RIA estimates that there are 

246,382 new protocols annually using 

identifiable information. For each 

protocol, it is estimated that 

investigators would spend an average of 

15 minutes in 2016 updating consent 

forms to comply with the new 

requirements found in the NPRM at 

§ ll.116(a)(9) or (b)(7)–(9). Based on 

the estimates presented in Table 3, the 

dollar value of investigators’ time is 

calculated by multiplying hours by their 

estimated 2016 wages and adjusting for 

overhead and benefits. 

The RIA assumes that no additional 

investigators would elect to offer the 

second option at §ll.116(a)(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, the RIA estimates that there are 

no additional costs associated with 

tracking. Public comment is requested 

on these assumptions. 

Present value costs of $4.55 million 

and annualized costs of $0.53 million 

are estimated using a 3 percent discount 

rate; present value costs of $4.25 million 

and annualized costs of $0.60 million 

are estimated using a 7 percent discount 

rate. Table 23 summarizes the 

quantified and non-quantified benefits 

and costs of changes in the basic 

elements of consent, including 

documentation. 

TABLE 23—SUMMARY OF ESTIMATED BENEFITS AND COSTS OF CHANGES IN THE ELEMENTS OF CONSENT, INCLUDING

DOCUMENTATION (NPRM AT §§ ll.116(a)(9), (b)(7)–(9) AND ll.117(b)) 

Benefits 

Present value of 10 years 

by discount rate 

(millions of 2013 dollars) 

Annualized value over 10 years 

by discount rate 

(millions of 2013 dollars) 

3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Benefits 

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

Non-quantified Benefits 

Improved informed consent forms and processes. 

Costs 3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Costs 

Time to update consent forms ......................................................... 4.55 4.25 0.53 0.60 

Non-quantified Costs 

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

u. Obtaining Consent to Secondary Use 

of Biospecimens and Identifiable Private 

Information (NPRM at §§ll.116(c)(1), 

(d)(1), (d)(4) and ll.117(c)(3)) 

The NPRM proposes to allow the use 

of broad consent to secondary research 

use of biospecimens or identifiable 

private information for unspecified 

research purposes. Such broad consent 

would have specified elements and 

limitations, and could be collected in 

both the research and non-research 

setting. 

Given the creation of the exemption 

for the maintenance and storage of 

biospecimens and identifiable private 

information for future, unspecified 

secondary research activities found in 

the NPRM at §ll.104(f)(1), it is 

envisioned that institutions creating 

these research repositories would need 

to develop tracking systems to monitor 

which biospecimens or what 

information may be used in secondary 

research by investigators. The Secretary 

of HHS would publish in the Federal 

Register one or more templates for 

broad consent (NPRM at 

§ ll.116(d)(1)) that would contain all 

of the required elements of consent for 

broad, secondary use consent (NPRM at 

§ ll.116(c)). If investigators or 

institutions use the consent template 

without any changes and seek to use the 

exemption at § ll.104(f)(2), IRB 

review is not required for these 

secondary studies, unless IRB review is 

required by law (e.g., FDA-regulated 

device studies). 

Seeking and obtaining consent to 

secondary research use of biospecimens 

and identifiable information is an 

additional flexibility proposed in the 

NPRM. However, it is not required. If 

broad consent has not been sought for 

the future research use of biospecimens 

or identifiable private information, then 

an investigator would need to have his 

or her project reviewed by an IRB and 

seek either study-specific consent or a 

waiver of informed consent under the 

Common Rule. As discussed in section 

II.B of this preamble, the NPRM 

proposes stricter waiver criteria (NPRM 

at §ll.116(e)(2) and (f)(2)) for 

biospecimens than for identifiable 

private information; these strict waiver 

criteria would apply regardless of 

whether the biospecimens are readily 

identifiable to the investigator. These 

waiver criteria would in effect make 

secondary research using a biospecimen 

largely impossible in the absence of 

obtaining subjects’ broad consent for 

future use of their biospecimens. 

Because investigators would be required 

to use the Secretary’s template for 

obtaining broad consent in order to be 

eligible for the new exemptions 

proposed in § ll.104(f), it is expected 

that minimal time would be spent 

updating consent forms or drafting 

wholly new consent forms. OHRP 

would develop one or more Secretary’s 

templates for obtaining broad consent to 

secondary use of biospecimens or 

identifiable private information for 

subsequent use by investigators and 

institutions. OHRP staff time associated 

with developing this resource is 


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91Eiseman, E., Haga, S. (1999). Handbook of 

Human Tissue Sources: A National Resource of 

Human Tissue Samples. Washington, DC: RAND 

Corporation. 

accounted for in section III.D.2.a of this 

RIA. 

As discussed earlier in this RIA 

(section III.D.2.n) it is anticipated that 

6,428 FWA holding institutions (80 

percent) would store and maintain 

clinical and non-clinical biospecimens 

and identifiable private information for 

unspecified future research studies in 

the manner prescribed under the new 

proposed exemption at §ll.104(f)(1). 

As also discussed previously, 

extrapolations from 1999 data 91 suggest 

that biospecimens are collected from as 

many as 30 million individuals and are 

stored each year 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 five minutes per person 

conducting the consent process specific 

to seeking broad consent, and the 

subjects would spend an estimated five 

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. The RIA further estimates that 

investigators would spend 10 minutes of 

time per protocol updating their studyspecific 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 rule 

is implemented, as many as 21 million 

broad, secondary use consent forms 

could be collected from individuals. 

The RIA anticipates 10 minutes of a 

subject’s time to engage in the consent 

process. The RIA further anticipates 10 

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. 

The NPRM proposes in 

§ ll.116(c)(1)(ii)(B) that once an 

individual gives broad consent to use 

his or her biospecimens in future, 

unspecified research studies, that 

consent may cover any biospecimen 

collected over the course of a 10 year 

period. Note that an institution may 

retain and use the biospecimens 

collected indefinitely. This provision is 

merely stating that every 10 years an 

institution must ask people whether or 

not they may use newly collected 

biospecimens in research. Given that an 

institution must seek broad consent 

from an individual only once over the 

course of a 10 year period, it is assumed 

that after the first year the rule is 

implemented, the number of individuals 

from whom an institution seeks broad 

consent will decrease. 

To account for this, the RIA assumes 

that after the first year that the rule is 

implemented, a fraction of the clinical 

subjects from whom secondary use 

consent is sought in year one would be 

sought in subsequent years. It is 

anticipated 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). It is anticipated 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, the RIA 

assumes that a prospective subject 

would spend 10 minutes of time 

undergoing the consent process and that 

an institutional employee at the IRB 

Administrative Staff level would spend 

10 minutes of time conducting the 

consent process with an individual and 

updating the appropriate tracking 

system. 

Note that assumptions are not made 

about the extent to which institutions 

will use the tracked broad consent for 

the use of identifiable private 

information. While all institutions that 

conduct research with biospecimens 

will essentially need to create a research 

repository to continue that type of work 

under the NPRM proposals, such is not 

the case with identifiable private 

information. Identifiable private 

information is covered under the NPRM 

as it is under the current Rule. To that 

end, a research repository containing 

identifiable private information is not 

necessary to the research enterprise. 

Thus, the RIA notes that institutions 

likely will elect to store identifiable 

private information in these 

repositories, but it is unknown the 

extent to which institutions will elect to 

do this and the volume of identifiable 

private information that might be stored. 

Therefore, estimates are not provided 

specifically about the potential costs of 

obtaining broad consent and tracking 

the consent for future use of identifiable 

private information. 

The costs of the tracking system 

associated with an institution-wide 

secondary use research repository are 

the design, implementation, and 

operation of the informatics system that 

would be required to document and 

keep up with thousands of consent 

documents per year. In addition, the 

institution would have to come up with 

some system to ‘‘mark’’ or otherwise 

note which biospecimens and pieces of 

identifiable private information had 

been consented for use, and which ones 

had not, to make sure an individual’s 

wishes regarding future use of his or her 

biospecimens and identifiable private 

information are carried out. It is 

estimated that these requirements 

would impose additional costs to 

develop or modify existing tracking 

systems at 80 percent of 8,035 

institutions with FWAs. It is estimated 

that these requirements would require 

1.0 database administrator FTEs on 

average at these institutions. Based on 

the estimates presented in Table 3, we 

calculate the dollar value of their time 

by multiplying hours by their estimated 

2016–2025 wages and adjusting for 

overhead and benefits. Public comment 

is requested on these estimates. 

Present value costs of $12,245 million 

and annualized costs of $1,435 million 

are estimated using a 3 percent discount 

rate; present value costs of $8,697 

million and annualized costs of $1,238 

million are estimated using a 7 percent 

discount rate. Table 24 summarizes the 

quantified and non-quantified benefits 

and costs of obtaining consent to 

secondary use of biospecimens and 

identifiable private information. 


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Federal Register / Vol. 80, No. 173 / Tuesday, September 8, 2015 / Proposed Rules 54021 

TABLE 24—SUMMARY OF ESTIMATED BENEFITS AND COSTS OF OBTAINING CONSENT TO SECONDARY USE OF

BIOSPECIMENS AND IDENTIFIABLE PRIVATE INFORMATION (NPRM AT §§ ll.116(c)(1), (d)(1), (d)(4) AND ll.117(c)(3)) 

Benefits 

Present value of 10 years 

by discount rate 

(millions of 2013 dollars) 

Annualized value over 10 years 

by discount rate 

(millions of 2013 dollars) 

3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Benefits 

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

Non-quantified Benefits 

Improved informed consent forms and processes, and reduction in time that would have been spent seeking and obtaining consent for secondary research use; retaining identifiers in research; better ensuring of the availability of biospecimens for future research activities. 

Costs 3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Costs 

Time to update consent forms, document, and submit permissible 

and impermissible secondary uses of data; develop and maintain tracking system ...................................................................... 12,245 8,697 1,435 1,238 

Non-quantified Costs 

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

v. Elimination of Requirement To Waive 

Consent in Certain Subject Recruitment 

Activities (NPRM at §ll.116(g)) 

The proposed rule would allow 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, through oral or written 

communication or by accessing records, 

if the research proposal includes 

appropriate provisions to protect the 

privacy of those individuals and to 

maintain the confidentiality of the 

identifiable private information. 

This addresses concerns that the 

current regulations require an IRB to 

determine that informed consent can be 

waived under the current §ll.116(d) 

before investigators may record 

identifiable private information for the 

purpose of screening, recruiting, or 

determining the eligibility of 

prospective subjects for a research 

study, provided that the research 

proposal includes an assurance that the 

investigator would meet the 

requirements for protecting the 

information as described in proposed 

§ ll.105. The current requirement is 

viewed as burdensome and unnecessary 

to protect subjects, and is inconsistent 

with FDA’s regulations, which do not 

require a waiver of consent for such 

recruitment activities. 

This should result in some time and 

cost savings for both investigators and 

IRBs, but it would likely be small. The 

savings would come from IRBs no 

longer needing to consider whether 

informed consent can be waived for 

such preparatory-to-research activities. 

Savings would accrue for investigators 

who can proceed with such activities in 

less time. 

The RIA estimates that 1,621 annual 

initial reviews of protocols (0.5 percent) 

involve a waiver of consent for 

recruitment activities that would not be 

required as a result of these proposed 

changes. Of these reviews, 1,118 would 

have undergone convened initial review 

and 502 would have undergone 

expedited initial review based on the 

distribution of reviews presented in 

Table 3. It is estimated that investigators 

spend an average of 15 minutes 

requesting a waiver of consent for 

recruitment activities when they submit 

a protocol for initial review. It is further 

estimated 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 2016–2025 wages and 

adjusting for overhead and benefits. 

Present value benefits of $1.21 million 

and annualized benefits of $0.14 million 

are estimated using a 3 percent discount 

rate, and present value benefits of $0.85 

million and annualized benefits of $0.12 

million are estimated using a 7 percent 

discount rate. Table 25 summarizes the 

quantified and non-quantified benefits 

and costs of eliminating the requirement 

to waive consent in certain subject 

recruitment activities. 

TABLE 25—SUMMARY OF ESTIMATED BENEFITS AND COSTS OF ELIMINATION OF REQUIREMENT TO WAIVE CONSENT IN

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

Benefits 

Present value of 10 years 

by discount rate 

(millions of 2013 dollars) 

Annualized value over 10 years 

by discount rate 

(millions of 2013 dollars) 

3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Benefits 

Decreased time associated with review ........................................... 1.21 0.85 0.14 0.12 

Non-quantified Benefits 

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


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54022 Federal Register / Vol. 80, No. 173 / Tuesday, September 8, 2015 / Proposed Rules 

TABLE 25—SUMMARY OF ESTIMATED BENEFITS AND COSTS OF ELIMINATION OF REQUIREMENT TO WAIVE CONSENT IN

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

Benefits 

Present value of 10 years 

by discount rate 

(millions of 2013 dollars) 

Annualized value over 10 years 

by discount rate 

(millions of 2013 dollars) 

3 Percent 7 Percent 3 Percent 7 Percent 

Costs 3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Costs 

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

Non-quantified Costs 

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

w. Requirement for Posting of Consent 

Forms for Common Rule AgencySupported Clinical Trials (NPRM at 

§ ll.116(h)) 

A new provision would require that 

investigators or institutions post a copy 

of the final version of the consent form 

for each clinical trial conducted or 

supported by HHS on a publicly 

available federal Web site that would be 

established as an archive for such 

consent forms. The name of the clinical 

trial and information about whom to 

contact for additional information must 

be published with the consent form. The 

consent form must be published on the 

federal Web site within 60 days after the 

trial is closed to recruitment. 

It is recognized that certain 

information contained in an informed 

consent form is protected from 

disclosure under the Freedom of 

Information Act, the Trade Secrets Act, 

and/or FDA implementing regulations, 

and, therefore all informed consent 

forms for FDA-regulated trials covered 

by this requirement would be subject to 

redaction before being posted. 

It is believed that public posting of 

consent forms would 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. 

It is expected that the Federal Web 

site would enable consent documents to 

be easily uploaded. Additional costs to 

the government would involve 

managing and maintaining the archive. 

According to queries of 

clinicaltrials.gov, there are an estimated 

5,270 clinical trials 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 HHS system by an investigator. The 

RIA estimates that investigators would 

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, it is estimated 

that investigators would spend an 

average of 30 minutes redacting 

information before submission. 

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 508-compliance costs an 

average of $30 per page. Based on the 

estimates presented in Table 3, the 

dollar value of their time is calculated 

by multiplying hours by their estimated 

2016–2025 wages and adjusting for 

overhead and benefits. 

Present value costs of $14.6 million 

and annualized costs of $1.71 million 

are estimated using a 3 percent discount 

rate; present value costs of $10.4 million 

and annualized costs of $1.49 million 

are estimated using a 7 percent discount 

rate. Table 26 summarizes the 

quantified and non-quantified benefits 

and the requirement for posting of 

consent forms for HHS-supported 

clinical trials. 

TABLE 26—SUMMARY OF ESTIMATED BENEFITS AND COSTS OF REQUIREMENT FOR POSTING OF CONSENT FORMS FOR

COMMON RULE AGENCY-SUPPORTED CLINICAL TRIALS (NPRM AT § ll.116(h)) 

Benefits 

Present value of 10 years 

by discount rate 

(millions of 2013 dollars) 

Annualized value over 10 years 

by discount rate 

(millions of 2013 dollars) 

3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Benefits 

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

Non-quantified Benefits 

Increase transparency of HHS-supported clinical trials and inform the development of new consent forms. 

Costs 3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Costs 

Development and management of website, and preparation and 

submission of consent forms for posting ...................................... 14.6 10.4 1.71 1.49 

Non-quantified Costs 

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


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x. Alteration in Waiver for 

Documentation of Informed Consent in 

Certain Circumstances (NPRM at 

§ ll.117(c)(1)(iii)) 

A new provision would be added 

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 for whom 

signing documents is not the norm. This 

would be allowed only if the research 

presents no more than minimal risk of 

harm to subjects and provided there is 

an appropriate alternative method for 

documenting that informed consent was 

obtained. 

Under the current Rule IRBs may 

waive the requirement for the 

investigator to obtain a signed consent 

form for some or all subjects. The 

current criteria for such a waiver may 

not be flexible enough for dealing with 

a variety of circumstances, such as 

when federally sponsored research that 

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 costs 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. 

Benefits and costs of this new 

provision are not quantified. Table 27 

summarizes the non-quantified benefits 

and costs of alteration in waiver for 

documentation of informed consent in 

certain circumstances. 

TABLE 27—SUMMARY OF ESTIMATED BENEFITS AND COSTS OF ALTERATION IN WAIVER FOR DOCUMENTATION OF

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

Benefits 

Present value of 10 years 

by discount rate 

(millions of 2013 dollars) 

Annualized value over 10 years 

by discount rate 

(millions of 2013 dollars) 

3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Benefits 

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

Non-quantified Benefits 

Improved informed consent process for distinct cultural groups and communities. 

Costs 3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Costs 

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

Non-quantified Costs 

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

E. Sensitivity Analysis 

The total estimated costs of the 

proposed changes to the Common Rule 

are sensitive to assumptions regarding 

consent to secondary use of 

biospecimens and information. The RIA 

estimates that 60 percent of institutions 

with an assurance would implement a 

tracking system. Those institutions 

would require 1.0 FTEs on average to 

develop and maintain a tracking system. 

The sensitivity of estimated costs to 

these baseline assumptions is analyzed 

by calculating costs under alternative 

assumptions. That these institutions 

could instead require 0.75 FTEs or 1.25 

FTEs on average to develop and 

maintain a tracking system is 

considered. That 50 percent or 70 

percent of assurance holding 

institutions could implement such a 

tracking system (rather than 60 percent) 

is also considered. Table 28 reports 

present value costs using a 3 percent 

discount rate for these alternative and 

baseline assumptions. 

TABLE 28—ESTIMATED PRESENT VALUE COSTS USING A 3 PERCENT DISCOUNT RATE (MILLIONS OF 2013 DOLLARS) OF

COSTS OF OBTAINING CONSENT TO SECONDARY USE OF BIOSPECIMENS AND IDENTIFIABLE PRIVATE INFORMATION

USING BASELINE AND ALTERNATIVE ASSUMPTIONS

FTEs required at each institution 

Percentage of institutions that implement a 

tracking system 

70 percent 80 percent 90 percent 

0.75 FTEs .................................................................................................................................... 8,700 9,666 10,633 

1.00 FTEs .................................................................................................................................... 10,956 12,245 13,534 

1.25 FTEs .................................................................................................................................... 13,212 14,823 16,435 

F. Alternative Approaches to the 

Definition of Human Subject (NPRM at 

§ ll.102(e)) and Related Provisions 

Two alternative approaches for the 

treatment of biospecimens under the 

proposed rule were considered. These 

alternative proposals centered on 

concerns about potential identifiability 

of biospecimens and data derived from 

biospecimens. 

Alternative Proposal A: Expand the 

Definition of ‘‘Human Subject’’ to 

Include Whole Genome Sequencing 

(WGS) 

Under Alternative Proposal A, the 

regulations at proposed § ll.102(e) 

would be amended to expand the 


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54024 Federal Register / Vol. 80, No. 173 / Tuesday, September 8, 2015 / Proposed Rules 

definition of human subjects to include 

more specifically whole genome 

sequencing data, or any part of the data 

generated as a consequence of whole 

genome sequencing, regardless of the 

individual identifiability of specimens 

used to generate such data. Investigators 

would not be allowed to remove 

identifiers from specimens or data to 

conduct whole genome sequencing 

without obtaining informed consent or a 

waiver of consent, because obtaining 

whole genome sequencing data about an 

individual would in and of itself cause 

the individual to meet the definition of 

a human subject. Written consent would 

generally be required for such activities. 

This requirement would not apply to 

specimens and information already 

collected at the time the final rule is 

published. 

Recent developments have made it 

possible to use whole genome 

sequencing information to re-identify 

non-identified data. Thus, even if such 

information is not ‘‘individually 

identifiable’’ (per the current Rule’s 

standard of identifiability) it is 

appropriate to expand the definition of 

human subjects research in this way to 

afford individuals who are the subjects 

of such research the same protections as 

those given to the subjects of research 

using identifiable information or 

specimens. Therefore, it is anticipated 

that this change would increase 

protections for subjects of whole 

genome sequencing research. It would 

also increase the volume of studies for 

which investigators must seek and 

document informed consent, unless 

more stringent waiver criteria were met, 

and institutions will have to track the 

consent status of specimens and data. In 

addition, IRBs would have to review 

these studies unless the research meets 

the new proposed exemption in 

proposed §ll.104(f)(2). 

It is estimated that there are 300 

studies using whole genome sequencing 

data that are not subject to oversight by 

either the Common Rule or FDA 

regulations. This RIA estimates that 

under this alternative, 90 percent of 

these studies (270) would be eligible for 

the exemption proposed in 

§ ll.104(f)(2). For the remaining 30 

studies, it is anticipated that these 

would not be eligible for the exemption, 

and would require full IRB review. As 

required under § ll.104(c), an 

exemption determination would be 

made and documented for each of the 

270 exemptible whole genome 

sequencing studies. It is anticipated that 

in 50 percent of these studies (135 

studies), investigators will spend 30 

minutes entering information into the 

HHS-created decision tool in order for 

that tool to generate an exemption 

determination. In the remaining 135 

studies, it is anticipated that 

investigators will spend 30 minutes 

preparing and submitting information 

about the study to an individual able to 

make exemption determinations (per 

§ ll.104(c)). An individual at the IRB 

voting member level will spend an 

estimated 30 minutes per study to make 

an exemption determination. 

In the absence of the proposed exempt 

category at § ll.104(f)(2), we estimate 

that in 2016 all 300 of these studies 

would undergo convened initial review. 

In subsequent years, an estimated 144 

protocols would undergo convened 

initial review, 108 would undergo 

convened continuing review, and 48 

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 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 

2016–2025 wages and adjusting for 

overhead and benefits. 

For Alternative Proposal A, present 

value costs of $0.57 million and 

annualized costs of $0.07 million are 

estimated using a 3 percent discount 

rate; and present value costs of $0.47 

million and annualized costs of $0.07 

million are estimated using a 7 percent 

discount rate. Table 29 summarizes the 

quantified and non-quantified benefits 

and costs of amending the definition of 

human subject. 

TABLE 29—SUMMARY OF ESTIMATED BENEFITS AND COSTS OF THE ALTERNATIVE PROPOSAL A FOR MODIFYING THE

DEFINITION OF HUMAN SUBJECT (NPRM AT § ll.102(e)) 

Benefits 

Present value of 10 years 

by discount rate 

(millions of 2013 dollars) 

Annualized value over 10 years 

by discount rate 

(millions of 2013 dollars) 

3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Benefits 

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

Non-quantified Benefits 

Ensuring human subjects are protected in whole genome sequencing research not currently subject to oversight. 

Costs 3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Costs 

Increase in number of reviews ......................................................... 0.57 0.47 0.07 0.07 

Non-quantified Costs 

Time to obtain consent for activities involving whole genome sequencing 

Alternative Proposal B: Classifying 

Certain Biospecimens Used in Certain 

Technologies as Meeting the Criteria for 

‘‘human subject’’ 

Under Alternative Proposal B, the 

regulations at proposed § ll.102(e) 

would be expanded to include 

biospecimens used in a technology 

capable of producing biologically 

unique information about a subject as 

well as the biologically unique 

information derived from a 

biospecimen. Only those technologies 

specifically listed on a newly created 

Secretary’s List would be considered to 

have met this definition. For example, if 

whole genome sequencing was a 

technology included on the Secretary’s 

List, then activities where a 

biospecimen (regardless of the 

investigator’s ability to readily identify 

the person from whom the biospecimen 

was collected) was used in whole 


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genome sequencing research would be 

subject to the rules. Additionally, 

activities involving the information 

generated from a biospecimen used in a 

technology that appeared on this 

Secretary’s List (regardless of the 

investigator’s ability to readily identify 

a subject) would also fall under these 

regulations. Information derived from a 

technology appearing on the Secretary’s 

List described above would be referred 

to as ‘‘bio-unique’’ information. 

This expansion would modestly 

increase the studies encompassed under 

the rule. This estimate is based on what 

is known about whole genomic research 

technologies that results in genome 

sequencing data (including DNA and 

RNA sequence data) that is unique to a 

single individual. It is estimated that 

there are 898 genomic research studies 

not currently subject to oversight that 

result in genome sequencing data 

unique to a single individual. 

One of the primary objectives of the 

NPRM has been to make the strength of 

protections commensurate with the 

level of risks of the research, and by 

doing so reduce unnecessary 

administrative burdens on research. 

That objective has been viewed as being 

particularly relevant to research 

involving only secondary use of 

biospecimens and data, which is 

relatively low-risk if appropriate 

protections of privacy and 

confidentiality are in place. Alternative 

Proposal B targets activities involving 

biospecimens where concerns about 

information risks indicate that 

additional regulatory oversight for these 

studies is appropriate. 

When the proposed exemption 

category at § ll.104(f)(2) is 

considered, this RIA estimates that 

under Alternative Proposal B, 808 

studies (90 percent) would be eligible 

for exemption. For the remaining 89 

studies, it is anticipated that these 

would not satisfy the §ll.104(f)(2) 

requirements and would require full IRB 

review. 

As required under §ll.104(c), an 

exemption determination would be 

made and documented for each of the 

808 exemptible genomic research 

studies described above. It is anticipated 

that in 50 percent of these studies (404 

studies), investigators will spend 30 

minutes entering information into the 

HHS-created decision tool in order for 

that tool to generate an exemption 

determination. In the remaining 404 

studies, it is anticipated that 

investigators will spend 30 minutes 

preparing and submitting information 

about the study to an individual able to 

make exemption determinations (per 

§ ll.104(c)). An individual at the IRB 

voting member level will spend an 

estimated 30 minutes per study to make 

an exemption determination. 

In the absence of the proposed exempt 

category of research at §ll.104(f)(1), 

the RIA estimates that as a result of the 

proposed expansion to the definition of 

human subject, all 898 of these studies 

would undergo convened initial review. 

In subsequent years, an estimated 431 

protocols will undergo convened initial 

review, 322 will undergo convened 

continuing review, and 145 will 

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 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 

2016–2025 wages and adjusting for 

overhead and benefits. 

For Alternative B, present value costs 

of $1.69 million and annualized costs of 

$0.20 million are estimated using a 3 

percent discount rate; present value 

costs of $1.39 million and annualized 

costs of $0.20 million are estimated 

using a 7 percent discount rate. Table 30 

summarizes the quantified and nonquantified benefits and costs of 

amending the definition of human 

subject. 

TABLE 30—SUMMARY OF ESTIMATED BENEFITS AND COSTS OF THE ALTERNATIVE PROPOSAL B FOR MODIFYING THE

DEFINITION OF HUMAN SUBJECT (NPRM AT § ll.102(e)) 

Benefits 

Present value of 10 years 

by discount rate 

(millions of 2013 dollars) 

Annualized value over 10 years 

by discount rate 

(millions of 2013 dollars) 

3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Benefits 

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

Non-quantified Benefits 

Ensuring that informational risks are minimized in research activities involving technologies capable of producing bio-unique information. 

Costs 3 Percent 7 Percent 3 Percent 7 Percent 

Quantified Costs 

Increase in number of reviews ......................................................... 1.69 1.39 0.20 0.20 

Non-quantified Costs 

Time to obtain consent for activities involving the generation or use of bio-unique information. 

G. 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 to 

institutions with an FWA over 2016– 

2025 and then subtract the cost savings 

to these institutions over the same 

period. The estimated average 

annualized net cost to institutions with 

an FWA is $153,671 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 


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institutions with an FWA are in one of 

these categories. 

IV. 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. 

V. Paperwork Reduction Act 

This proposed 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. 

We invite comments on these topics: 

(1) The accuracy of the estimate of 

burden of the proposed collection of 

information; (2) ways to enhance the 

quality, utility, and clarity of the 

information to be collected; and, (3) 

ways to minimize the burden of the 

collection of information on 

respondents, including through the use 

of automated collection techniques, 

when appropriate, and other forms of 

information and technology. 

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) Disclosure; (iii) 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. To what does this policy 

apply (OMB Control No. 0990–0260) 

Section ll.101 is being amended to 

place unaffiliated Institutional Review 

Boards (IRBs) within the realm of 

entities to which the policy applies as 

described in § ll.101(a) . This new 

provision gives Common Rule 

departments and agencies explicit 

authority to enforce compliance directly 

against IRBs that are not affiliated with 

an assured institution. This change 

should encourage institutions to more 

willingly rely on qualified unaffiliated 

IRBs for cooperative research, as is 

required under the proposed changes at 

§ ll.114. Burden estimates are 

included below in 

§ ll.114 summary. 

Section ll.101 is also being 

amended to extend the regulations to 

cover clinical trials conducted at an 

institution in the United States that 

receives federal support from a Common 

Rule department or agency for nonexempt human subjects research, 

regardless of the funding source of the 

trial as described in §ll101(a)(2). 

Extension of the regulations would not 

apply to clinical trials already regulated 

by FDA. We estimate that there are 

1,399 clinical trials currently not subject 

to oversight by either the Common Rule 

or FDA regulations. We estimate that in 

2016 all 1,399 of these clinical trials 

will undergo convened initial review. In 

subsequent years, we estimate that 672 

protocols will undergo convened initial 

review, 502 will undergo convened 

continuing review, and 225 will 

undergo expedited continuing review. 

We estimate the burden to institution 

officials, IRB administrators, IRB 

administrative staff, IRB chairs, IRB 

voting members, and investigators of 

conducting these reviews (24 hours per 

protocol) based on the estimates 

presented in Table 3 of section III of the 

preamble. 

§ ll.103. Assuring Compliance With 

This Policy—Research Conducted or 

Supported by Any Federal Department 

or Agency (OMB Control No. 0990–0260) 

Section ll.103 is being amended, at 

§ ll.103(e), to require that for nonexempt research involving human 

subjects covered by this policy that 

takes place at an institution in which 

IRB oversight is conducted by an 

unaffiliated 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., in 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 

affiliated with the institution). Burden 

estimates are included below in 

§ ll.114. 

§ ll.104 Exempt Research (OMB 

Control No. 0990–0260) 

Section ll.104 is being proposed, as 

described in § ll.104(c), to require 

federal departments and agencies to 

develop a decision tool to assist in 

exemption determinations. Under the 

proposed rule, unless otherwise 

required by law, exemption 

determinations may be 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, or by the investigator or 

another individual at the institution 

who enters accurate information about 

the proposed research into the decision 

tool, which would provide a 

determination as to whether the study is 

exempt. If the tool is used, further 

assessment or evaluation of the 

exemption determination is not 

required. Burden estimates are included 

below in § ll.115(a)(11). 

Section ll.104 is being proposed, as 

described in § ll.104(d)(2), to require 

each federal department or agency 

conducting or supporting the research 

or demonstration projects exempted 

under §ll.104(d), to establish on a 

publicly accessible federal Web site or 

in such other manner as the department 

or agency head may prescribe, 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 or upon 

commencement of the research. We 

estimate that 4,377 exempt research and 

demonstration studies will be posted to 

the Web site annually, and that the 

information will be submitted to the 

Web site by individuals at the IRB 

administrative staff level, an estimate of 

1.82 person-hours per protocol (7966.14 

burden hours). 

§ ll.105 Protection of Biospecimens 

and Identifiable Private Information, 

(OMB Control No. 0990–0260) 

Section ll.105 is being proposed, as 

detailed in § ll.105(a), to require 

institutions and investigators 

conducting research subject to the 

Common Rule, or that is exempt under 

§§ ll.104(e) or (f) to implement and 

maintain reasonable and appropriate 

safeguards to protect biospecimens, or 

identifiable private information they 

collect, store or use for research. The 

Secretary of HHS will establish and 

publish a list of specific measures that 

the institution or investigator may 

implement that will be deemed to 

satisfy the requirement for reasonable 


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and appropriate safeguards. The list will 

be evaluated as needed, but at least 

every 8 years, and amended, as 

appropriate, after consultation with 

other federal departments and agencies. 

Institutions and investigators may 

choose either to apply the safeguards 

identified by the Secretary as necessary 

to protect the security or integrity of and 

limit disclosure of biospecimens and 

electronic and non-electronic 

identifiable private information or to 

apply safeguards that meet the 

standards in 45 CFR 164.308, 164.310, 

164.312, and 45 CFR 164.530(c). For 

federal departments and agencies that 

conduct research activities that is or 

will be maintained on information 

technology that is subject to and in 

compliance with section 208(b) of the EGovernment Act of 2002, 44 U.S.C. 3601 

et seq., 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., these research activities 

automatically will be considered in 

compliance with the Secretary’s 

reasonable and appropriate safeguards 

standards, unless or until any additional 

safeguards are identified by the 

Secretary of HHS. 

We estimate that 803 of the 8,035 

institutions with FWAs (10 percent) will 

be required to update their privacy and 

security standards to comply with the 

new requirements. At these institutions, 

we estimate that institutional officials 

and institutional legal staff will each 

spend 80 hours in 2016 and 20 hours in 

subsequent years to update and monitor 

their privacy and security standards. In 

addition, we estimate that 43,997 of 

439,968 investigators (10 percent) will 

be required to adopt the updated 

privacy and security standards. We 

estimate that these investigators will 

each spend 40 hours in 2016 and 10 

hours in subsequent years to do so. 

§ ll.111 Criteria for IRB Approval of 

Research, (OMB Control No. 0990–0260) 

Section ll.111 is being amended at 

§ ll.111(a)(8) to add a new 

requirement that if the investigator 

proposes a research plan for returning 

relevant results to subjects, then the IRB 

must determine that the plan is 

appropriate. We estimate that there are 

324,187 initial reviews of protocols 

annually. Of the 324,187 initial reviews, 

we estimate that 108,062 reviews (33 

percent) will include a plan for 

returning results to subjects and that 

primary reviewers will spend an average 

of 15 minutes reviewing these plans. 

§ ll.114 Cooperative Research (OMB 

Control No. 0990–0260) 

Section ll.114 is being amended, as 

described in § ll.114(b)(1) to require 

any institution located in the United 

States (U.S.) that is engaged in 

cooperative research to rely upon 

approval by a single IRB for that portion 

of the research conducted in the U.S. As 

described in § ll.114(b)(2), 

cooperative research for which more 

than single IRB review is required by 

law (e.g., FDA-regulated device studies); 

or 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 need not comply with this 

requirement. The OHRP database of 

registered institutions and IRBs shows 

that there are 8,035 institutions with an 

FWA. We estimate that these 

institutions will develop an average of 

10 written joint review agreements with 

other institutions in 2018 prior to the 

first year of compliance. 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. 

§ ll.115 IRB Records (OMB Control 

No. 0990–0260) 

Section ll.115 is being amended, in 

§ ll.115(a)(8), to require the rationale 

for requiring continuing review for 

research that otherwise would not 

require continuing review as described 

in §ll.109(f)(1). 

We estimate that there are 108,873 

expedited continuing reviews of 

protocols annually based on the 

distribution of reviews presented in 

Table 3 of the Regulatory Impact 

Analyses section of the preamble. Of 

these reviews, we estimate that 81,546 

reviews (75 percent) will not be 

eliminated by other proposed changes to 

the Common Rule at §§ll.101(b), 

ll.104(d)(1)–(3), ll.104(e)(1). We 

estimate that 40,773 of these 81,546 

reviews (50 percent) will be 

discontinued and the remaining 40,773 

reviews (50 percent) will continue and 

require documentation of the rationale 

for doing so. We estimate that IRB 

voting members will spend 1 hour per 

review providing documentation. In 

addition, we estimate that 

administrative staff at each IRB (total of 

3,499 IRBs) will spend 10 hours in 2016 

updating their communication systems 

to no longer send continuing review 

reminders to certain investigators. 

Section ll.115 is being amended at 

§ ll.115(a)(9) to require that the 

rationale for an expedited reviewer’s 

determination that research appearing 

on the expedited list described in 

§ ll.111(b)(1)(i) is more than minimal 

risk (i.e., an override of the presumption 

that studies on the Secretary’s list are 

minimal risk). 

We estimate that there are 223,689 

convened initial reviews and 242,330 

convened continuing reviews of 

protocols annually based on the 

distribution of reviews presented in 

Table 3 of the Regulatory Impact 

Analyses section of the preamble. Of 

these 223,689 convened initial reviews, 

we estimate that 2,237 reviews (1 

percent) are eligible for expedited 

review because they are in a category of 

research that appears on the Secretary’s 

list. Of these 2,237 reviews, we estimate 

that 1,118 reviews (50 percent) will 

undergo expedited review and the 

remaining 1,118 reviews (50 percent) 

will undergo convened review and 

require documentation of the rationale 

for doing so. 

Of the 242,330 convened continuing 

reviews, we estimate that 2,423 reviews 

(1 percent) are eligible for expedited 

review because they are in a category of 

research that appears on the HHS 

Secretary’s list. Of these 2,423 reviews, 

we estimate that 1,212 reviews (50 

percent) will undergo convened review 

and will require documentation of the 

rationale for doing so. Due to the 

proposed elimination of continuing 

review of research under specific 

conditions (§§ll.109(f); 

ll.115(a)(3), (8)), the remaining 1,212 

reviews (50 percent) will not require 

review. Of these 1,212 reviews, we 

estimate that 606 reviews (50 percent) 

will not occur and the remaining 606 

reviews (50 percent) will undergo 

expedited continuing review and 

require documentation of the rationale 

for doing so. We estimate that IRB 

voting members will spend 1 hour per 

review providing documentation when 

required. 

Sectionll.115 is being amended, at 

§ ll.115(a)(10) to require the written 

agreement between an institution and 

an external IRB specifying the 

responsibilities that each entity will 

undertake to ensure compliance with 

the requirements described in 

§ ll.103(e). 

Table 3 of section III of the preamble 

shows that there are 5,164 FWA-holding 

institutions without an IRB and 2,871 

FWA-holding institutions with an IRB. 

We assume that the 5,164 FWA-holding 

institutions without an IRB have an 

average of 1 IRB authorization 

agreement that would need to be 


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modified as a result of the new 

requirements for agreements between 

institutions and external IRBs in 2016. 

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 2016. 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. 

Section ll.115, is being amended, 

in §ll.115(a)(11), to require records 

relating to exemption determinations as 

described in § ll.104(c). As part of 

this new requirement, OHRP will create 

an interactive exemption determination 

tool. We estimate that 6,754 annual 

reviews of protocols would no longer be 

conducted as a result of proposed 

changes under § ll.104. As required 

under §ll.104(c), an exemption 

determination must be made and 

documented for each of these 6,754 

newly exempted studies. It is 

anticipated that in 50 percent of these 

studies (3,377 studies), investigators 

will spend 30 minutes entering 

information into the HHS-created 

decision tool in order for that tool to 

generate an exemption determination. In 

the remaining 3,377 studies, it is 

anticipated that investigators will spend 

30 minutes preparing and submitting 

information about the study to an 

individual able to make exemption 

determinations (per § ll.104(c)). An 

individual at the IRB voting member 

level will spend an estimated 30 

minutes per study to make an 

exemption determination. 

§§ ll.116 and ll.117 General 

Requirements for Informed Consent 

(OMB Control No. 0990–0260) 

Section ll.116 is being amended, as 

described in § ll.116(a)(9), to add a 

new basic element of consent that 

would apply to any research collection 

of identifiable private information. One 

of the following statements about such 

research collection much be provided to 

subjects: (i) A statement that identifiers 

might be removed from the data and the 

data that is not identifiable 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, (ii) a 

statement that the subject’s data 

collected as part of the research, from 

which identifiers are removed, will not 

be used or distributed for future 

research studies. We estimate that there 

are 246,382 new protocols annually 

using individually identifiable 

information. For each protocol, we 

estimate that investigators will spend an 

average of 15 minutes in 2016 updating 

consent forms to comply with the new 

requirements. 

Section ll.116 is being amended, as 

described in § ll.116(c) to allow broad 

consent to cover the storage, 

maintenance, and secondary research 

use of biospecimens 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 non-research purposes. The 

broad consent document would also 

meet the consent requirement for the 

use of such stored biospecimens and 

information for individual research 

studies. 

We anticipate 6,428 FWA holding 

institutions (80 percent) will develop an 

institution-wide research repository of 

biospecimens and identifiable private 

information available for future research 

in the manner prescribed under the new 

proposed exemption at § ll.104(f)(1). 

We estimate that 80 percent of 

institutions with an FWA (6,428 

institutions) will implement a tracking 

system. Those institutions will require 

1.0 FTEs on average to develop and 

maintain a tracking system. 

It is anticipated that many 

investigators will choose to seek such 

consent in order to save time and 

burden by avoiding the need to (1) seek 

and obtain consent to every specific 

future research use, (2) seek full IRB 

review for research that meets one of the 

exempt research categories, or (3) seek 

IRB review for a waiver of consent. 

Sectionll.116 is being amended, as 

described in § ll.116(h), to require 

that a copy of the final version of the 

consent form for each clinical trial 

conducted or supported by a Federal 

department or agency component 

conducting the trial on a publicly 

available federal Web site that will be 

established as a repository for such 

consent forms. The informed consent 

form must be posted in such form and 

manner as the department or agency 

head may prescribe, which will include 

at a minimum posting, in addition to the 

informed consent form, the name of the 

clinical trial and information about 

whom to contact for additional details 

about the clinical trial. The consent 

form must be published on the federal 

Web site within 60 days after the trial 

is closed to recruitment. 

We estimate that Common Rule 

departments and agencies supports 

5,270 new clinical trials annually, of 

which 575 are regulated by provisions 

in the FD&C Act and Trade Secrets Act 

based on the information presented in 

Table 3 of the Regulatory Impact 

Analyses section of the preamble. For 

the purpose of this analysis, we assume 

that each clinical trial is associated with 

one consent form that must be 

submitted 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. 

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Table 30- Estimated Annual Reporting Burden 

Sec. Description Description of Num.of Num.of Total annual Avg. Hrs Total Hrs 

burden Respondents responses responses per 

per response 

respondent 

10l(a)(2)--Expansion of Initial review 1,399.00 1.00 1,399.00 24.00 33,576.00 

rule to cover clinical trials 

not otherwise regulated by 

the FDA 

1 04( d)(2)(i)--Posting Posting 4,377.00 1.00 4,377.00 1.82 7,966.14 

requirement for research minimal 

and demonstration information 

projects about study to 

federal website 

lOS-Protection of lOs and legal 803.00 1.00 803.00 80.00 64,240.00 

Biospecimens and staff to develop 

Identifiable Private policies and 

information procedures to 

implement 

standards 

105--Biospecimen and time for 43,997.00 1.00 43,997.00 40.00 1,759,880.00 

information safe guards investigators to 

comply with 

new 

requirements 
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Sec. Description Description of Num.of Num.of Total annual Avg. Hrs Total Hrs 

burden Respondents responses responses per 

per response 

respondent 

111(a)(8)--IRB review of IRB reviewer 108,062.00 1.00 108,062.00 0.25 27,015.50 

plans to return research time to review 

result plans to return 

research results 

114--New requirement for Time to create 8,035.00 1.00 8,035.00 15.00 120,525.00 

one IRB of record for agreements for 

multi-site studies all institutions 

involved in a 

study will rely 

on one IRB of 

record 

115(a)(8)--Documenting Create 40,773.00 1.00 40,773.00 1.00 40,773.00 

IRB rationale for requiring documentation 

continuing IRB review for 

research that would 

otherwise not require it 

115(a)(8)--Documenting Update systems 3,499.00 1.00 3,499.00 10.00 34,990.00 

IRB rationale for requiring 

continuing IRB review for 

research that would 

otherwise not require it 
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Sec. Description Description of Num.of Num.of Total annual Avg. Hrs Total Hrs 

burden Respondents responses responses per 

per response 

respondent 

115(a)(9)--Documenting Initial review 1,118.00 1.00 1,118.00 1.00 1,118.00 

IRB rationale for 

determining that research 

on the expedited review 

list is more than minimal 

risk 

115(a)(9)--Documenting Continuing 606.00 1.00 606.00 1.00 606.00 

IRB rationale for review 

determining that research 

on the expedited review 

list is more than minimal 

risk 

115(a)(IO)--Written Institutions with 5,164.00 1.00 5,164.00 15.00 77,460.00 

agreement btwn noiRE 

institutions and agreement 

unaffiliated IRB s modifications 

documenting 

responsibilities 

115(a)(IO)--Written Institutions with 2,871.00 0.20 574.20 15.00 8,613.00 

agreement btwn IRB agreement 

institutions and modifications 

unaffiliated IRB s 

documenting 

responsibilities 
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Sec. Description Description of Num.of Num.of Total annual Avg. Hrs Total Hrs 

burden Respondents responses responses per 

per response 

respondent 

115(a)(l1)--Records IRB offices 40,773.00 1.00 40,773.00 11.00 448,503.00 

related to exemption processing 

determinations documentation 

116(a)(9) & 117(b )(2)-- Updating IC 246,382.00 1.00 246,382.00 0.25 61,595.50 

New required element of forms 

informed consent telling 

subjects how their nonidentifiable data or 

specimens might be used 

116(c) & 117(c)(3)-- Obtain consent 9,000,000.00 1.00 9,000,000.00 0.25 2,250,000.00 

Obtaining and research setting 

documenting broad 

secondary use consent 

116(c) & 117(c)(3)-- Obtain consent 21,000,000.00 1.00 21,000,000.00 0.17 3,570,000.00 

Obtaining and non-research 

documenting broad setting 

secondary use consent 

116(c) & 117(c)(3)-- Modify tracking 21,000,000.00 1.00 21,000,000.00 0.17 3,570,000.00 

Obtaining and system 

documenting broad 

secondary use consent 

116(h)--Requirement to Posting consent 5,270.00 1.00 5,270.00 0.25 1,317.50 

post consent forms for forms for new 

clinical trials clinical trials 
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The total estimated burden imposed 

by these information collection 

requirements is 12,155,926 burden 

hours. 

It should be noted that the burden 

estimates for the Common Rule include 

those approved information 

requirements in: (1) OMB No. 0990– 

0260, Protection of Human Subjects: 

Compliance with Federal Policy/IRB 

Recordkeeping/Informed Consent/

Consent Documentation, approved 

through May 31, 2018; (2) OMB No. 

0990–0263, Assurance Identification/

IRB Certification/Declarations of 

Exemption Form (Common Rule), 

approved through March 31, 2018; (3) 

OMB No. 0990–0278, Federalwide 

Assurance (FWA) for the Protection of 

Human Subjects, approved through 

August 31, 2017; and, (4) OMB No. 

0990–0279, HHS, Registration of an 

Institutional Review Board ((IRB), 

approved through August 31, 2015. As 

such, they 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. 

To ensure that comments on these 

new information collection 

requirements are received, OMB 

recommends that written comments be 

faxed to the Office of Information and 

Regulatory Affairs, OMB, Attn: [OS Desk 

Officer, FAX: 202–395–6974, or emailed 

to oira_submission@omb.gov. All 

comments should be identified with the 

title ‘‘Federal Policy for the Protection 

of Human Subjects.’’ 

In compliance with the Paperwork 

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

3507(d)), the information collection 

provisions of this proposed rule will be 

submitted to OMB for review. These 

requirements will not be effective until 

OMB approves them. 

VI. Summary of Comments Received on 

the 2011 Common Rule ANPRM 

A. Initial Step Toward Modernization of 

the Common Rule: The Advance Notice 

of Proposed Rulemaking (ANPRM) 

In considering changes in the 

Common Rule, the ANPRM requested 

comment on possible changes to seven 

aspects of the current regulatory 

framework. 

1. Ensuring Risk-Based Protections 

2. Streamlining IRB Review of 

Cooperative Studies 

3. Improving Informed Consent 

4. Strengthening Data Protections To 

Minimize Information Risks 

5. Data Collection To Enhance System 

Oversight 

6. Extension of Federal Regulations 

7. Clarifying and Harmonizing 

Regulatory Requirements and Agency 

Guidance 

Public comments on the ANPRM 

initially were requested by September 

26, 2011; however, in response to public 

requests for an extension, the comment 

period was extended until October 26, 

2011. A total of 1,051 comments were 

received, with many commenters 

responding to all 74 questions posed. 

Investigators comprised the largest 

group of commenters. Comments were 

also received from: Trade and 

professional associations; medical and 

social/behavioral research 

organizations; disease and patient 

advocacy groups; IRB members and 

staff; individual, private companies and 

the organizations representing them; 

and patients and research subjects. A 

large number of comments were lengthy 

and detailed, reflecting thoughtful 

consideration of the issues discussed. 

Many responses reflected the input of 

large research and health care 

organizations, including public 

university systems, research 

universities, academic medical centers, 

and medical schools, as well as 

networked health care providers. The 

greatest number of comments focused 

on the section addressing risk-based 

protections. 

In addition to reviewing the public 

responses to the ANPRM, in preparing 

the NPRM, the deliberations of the 

Presidential Commission for the Study 

of Bioethical Issues (the Commission) 

were taken into account. Consideration 

was also given to public comments 

received on the request for information 

issued by the Commission on March 2, 


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92 76 FR 11482 (Mar. 2, 2011). 

93Research not subject to the Common Rule may 

still be subject to FDA regulation or the HIPAA 

Privacy Rule. 

94See, e.g., the proposal on IRB accountability 

released by OHRP in 2009, at http://www.hhs.gov/ 

ohrp/newsroom/rfc/com030509.html. 

95 74 FR 9578 (Mar. 5, 2009). 

96The FWA covers all nonexempt human 

subjects research at the submitting institution that 

is HHS-conducted or –supported, or funded by any 

other federal department or agency that has adopted 

the Common Rule and relies upon the FWA. It is 

not project specific. Domestic institutions may 

voluntarily extend their FWA (and thus a Common 

Rule department or agency’s regulatory authority) to 

cover all human subjects research at the submitting 

institution regardless of the source of support for 

the particular research activity. See Office for 

Human Research Subject Protections. (2011, June 

17). What research does the Federalwide Assurance 

(FWA) cover? Retrieved from Frequently Asked 

Questions: http://www.hhs.gov/ohrp/policy/faq/

assurance-process/what-research-does-fwacover.html. 

2011, that sought public comment on 

the current federal and international 

standards for protecting the health and 

well-being of participants in scientific 

studies supported by the federal 

government.92

These suggested revisions to the 

Common Rule may affect other 

regulatory protections, such as the other 

subparts of the HHS human subjects 

protection regulations in 45 CFR part 46 

(Subparts B, C, and D, which deal with 

particular populations of vulnerable 

subjects, and Subpart E which addresses 

registration of IRBs), FDA regulations, 

and the HIPAA Privacy Rule (45 CFR 

parts 160 and 164, Subparts A and E). 

It is contemplated that other regulatory 

provisions implicated by the changes to 

the Common Rule may need to be 

harmonized, to the extent appropriate, 

with any final regulations modifying the 

Common Rule, through rule 

modification or guidance. Additionally, 

guidance and other information would 

also be revised and/or written to the 

extent necessary and appropriate.93

B. ANPRM Issues and Public Comments 

Related To Improving Protections 

1. Expanding the Scope of the Common 

Rule 

The ANPRM asked for public 

comments regarding two potential 

changes to the regulations at § ll.101. 

The first would subject unaffiliated IRBs 

(IRBs that are not operated by an FWAholding institution) that review research 

covered by the Common Rule to the 

requirements of the Common Rule. The 

second would extend the scope of 

research covered by the regulations. 

Holding Unaffiliated IRBs Directly 

Accountable for Compliance With 

Certain Regulatory Requirements: To 

address institutions’ concerns about 

OHRP’s practice of enforcing 

compliance with the Common Rule 

through the institutions that are engaged 

in human subjects research, the ANPRM 

asked for comments on making 

appropriate changes to the Common 

Rule enforcement procedures so 

external IRBs are held directly 

accountable for compliance with certain 

regulatory requirements.94

Based on public comments received 

to a 2009 ANPRM 95 on the issue of IRB 

accountability, the July 2011 Common 

Rule ANPRM considered adding a new 

provision that would give Common Rule 

departments and agencies the authority 

to enforce compliance directly against 

IRBs that are not affiliated with an 

institution that has an assurance 

registered with HHS. This provision 

would not extend the scope of research 

that is covered by the regulations; 

rather, it would expand the scope of 

those entities subject to compliance 

oversight. 

Some public commenters responding 

to the 2011 ANPRM cautioned that 

extending compliance oversight to 

unaffiliated IRBs might serve as a 

disincentive for some IRBs to be the IRB 

of record for cooperative research. A 

majority of commenters expressed an 

opposing view; that is, holding external 

IRBs directly accountable for 

compliance with the regulations would 

increase the comfort level of institutions 

in accepting the regulatory review of an 

external IRB. 

Extension of Common Rule to 

Domestic Sites Funded by Common 

Rule Agencies: The ANPRM asked the 

public to consider a regulatory option to 

partially fulfill the goal of extending 

Common Rule protections to all human 

subjects research in the United States. 

The discussed policy would require 

domestic institutions that receive some 

federal funding from a Common Rule 

agency for nonexempt research with 

human subjects to extend the Common 

Rule protections to all human subjects 

research studies conducted at their 

institution. 

Although supporting the principle 

that all human subjects research 

regardless of funding source should be 

conducted ethically, public commenters 

generally expressed concern and 

caution about the ANPRM consideration 

for a variety of reasons. Behavioral and 

social science researchers thought that 

this approach would unnecessarily 

bring less-than-minimal-risk research 

funded by non-federal sources (e.g., 

surveys or observational studies 

supported by the nonprofit sector) 

under burdensome regulatory 

requirements while not enhancing 

protections. Some commenters argued 

that the increased regulatory burden 

that would ensue was not warranted 

and would shift scarce oversight 

resources to review of research studies 

that are generally non-problematic and 

frequently supported by non-federal 

funds, such as some student or 

institutional research. 

Others argued that such a change was 

an overreach of federal oversight and 

constituted an unfunded mandate. 

Commenters from large academic 

research institutions felt that this 

change inappropriately focused heavily 

on academic institutions, which 

generally extend protections to all 

human subjects research at their 

institution, even if they have not 

‘‘checked the box’’ 96 on their FWA 

indicating that they do so. They argued 

that such a change would not reach 

those institutions already operating 

outside the federal research system and 

would limit flexibility in making riskbased determinations about the levels of 

review required. 

Industry also expressed concern about 

having to comply with two sets of 

regulations, that is, FDA regulations at 

21 CFR parts 50 and 56 as well as the 

Common Rule. The ANPRM did not 

clarify that the changes under 

consideration would not require 

compliance with the Common Rule of 

non-federally funded research subject to 

regulation by FDA. However, there 

might continue to be research that 

would be subject to both sets of 

regulations involving federal funding of 

research concerning an FDA-regulated 

product. 

Those commenters who supported a 

formal extension of the regulations cited 

the need to have one set of standards for 

all research, regardless of funding 

source; however, many noted that 

absent legislation covering all human 

subjects research conducted in the 

United States, it would be difficult to 

cover all research through a regulatory 

approach alone—gaps would still 

remain. 

2. Safeguards for Information 

Definition of Private Information and 

Applying the HIPAA Standards of 

‘‘Identifiability’’ to Research Governed 

by the Common Rule: The ANPRM 

suggested that the definition of 

‘‘identifiability’’ in the Common Rule be 

modified to better harmonize it with 

other regulatory definitions of 

‘‘identifiability’’ within HHS. The 

ANPRM considered adopting for 

purposes of the Common Rule the 

HIPAA Privacy Rule’s standards of what 

constitutes individually identifiable 

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identified information, in order to 

address inconsistencies regarding these 

definitions and concepts between the 

HIPAA Privacy Rule and the Common 

Rule. In addition, the ANPRM indicated 

that a prohibition on the reidentification of de-identified 

information (as defined in the HIPAA 

Privacy Rule) was being considered. 

Private information is not considered 

to be identifiable under the Common 

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. In 

contrast, under the HIPAA Privacy Rule, 

health information is de-identified and 

thus exempt from the 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)). 

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 

respects to their business associates), 

and not all investigators are part of a 

covered entity. Moreover, the HIPAA 

Rules do not apply specifically to 

biospecimens in and of themselves. 

A majority of the public commenters 

strongly opposed the ideas discussed in 

the ANPRM regarding the definition of 

‘‘identifiability’’. Many indicated that 

the HIPAA Privacy Rule’s more 

stringent standard of identifiability 

would expand what is considered 

identifiable for purposes of the Common 

Rule and thus greatly impede generally 

low-risk research without adding 

meaningful protections for human 

subjects. In particular, they asserted that 

the HIPAA standards were created to 

protect against disclosure of health 

information contained in medical 

records. As such, commenters argued, 

they are not appropriate for many types 

of research that would be covered by the 

Common Rule (e.g., behavioral and 

social science research). Others said this 

would be an extreme change in response 

to an as yet unidentified or clear 

problem. Commenters said that the 

information most at risk for 

inappropriate disclosure is the type of 

private health information that is 

already protected under the HIPAA 

Rules. Commenters feared that such a 

change in policy, while ‘‘harmonizing’’ 

the Common Rule certain HIPAA 

standards, would create inordinate 

burdens in terms of new documentation 

requirements and result in a 

requirement to apply the HIPAA 

standards to all types of research, 

regardless of the level of risk. 

Several commenters expressed 

concern about a prohibition against reidentifying de-identified private 

information (as defined by HIPAA), 

noting that sometimes it will be 

appropriate for investigators to reidentify such information, for example, 

to return research results that have 

clinical relevance to the subjects. Also, 

some commenters noted that some 

research is specifically designed to test 

strategies for re-identifying de-identified 

(as defined by HIPAA) information, so 

an absolute prohibition against reidentification would halt such research. 

Protecting Information: The ANPRM 

suggested establishment of 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 

contained in a biospecimen. It put 

forward the idea that these standards 

might be modeled after certain 

standards of HIPAA Rules and asked a 

series of questions about how best to 

protect private information. 

Some public comments reflected 

confusion about the focus of the 

suggested standards and whether they 

would apply to information or 

biospecimens that were not individually 

identifiable. Although most commenters 

confirmed the need to protect the 

privacy and confidentiality of 

information of human subjects in 

research, a majority expressed serious 

concerns about the merits of requiring 

all investigators to meet standards 

modeled on certain HIPAA standards, 

such as those in the HIPAA Security 

Rule. Most commenters expressed the 

opinion that certain HIPAA standards 

are not well suited to some research of 

various kinds carried out by 

investigators not subject to the HIPAA 

Rules. Some commenters claimed that 

the HIPAA privacy standards do not 

adequately protect individuals’ 

information. Many commenters claimed 

that standards modeled after certain 

HIPAA standards would be 

unnecessarily burdensome for studies in 

the behavioral and social sciences 

where the data are often less sensitive 

than health information. 

Some comments maintained that 

HIPAA like standards would not always 

be suitable for the variety of research 

methods and procedures for the 

collection and storage of information in 

research activities not subject to the 

HIPAA Rules. Some commented that 

certain HIPAA standards would not be 

suitable because of the location of the 

research activity, or because the kind of 

institution supporting the research was 

significantly different from a covered 

entity. Others thought the HIPAA 

standards create confusion and 

complications for investigators and 

institutions that would increase if 

standards modeled on certain HIPAA 

standards were applied across the 

board. At the same time, regardless of 

the specific standards to be employed 

under this approach, several 

commenters noted that the additional 

administrative burden that might be 

created by establishing a data security 

and information protection system 

could be offset by the decreased time 

and attention IRBs would have to invest 

in reviewing every study that required 

data or biospecimen protections. They 

also noted that many institutions 

already have required data and 

biospecimen protection systems in 

place. 

Some commenters noted that 

expansion of some of the exemption 

categories could only be ethically 

acceptable if those research activities 

were subject to a requirement for data 

security and information protection, 

because information collected for some 

research studies would no longer be 

collected under a research plan 

approved by an IRB. With regard to an 

absolute prohibition against reidentifying de-identified data, many 

commenters expressed concern, and 

provided reasons why re-identification 

might be valid or even desirable, 

including the need to return clinically 

relevant research results to an 

individual. For example, if the research 

uncovers information that might have 

important clinical significance for an 

individual, re-identification could be 

used so that the individual could get 

care. In addition, they pointed out that 


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the current Common Rule requires 

investigators that re-identify 

nonidentified private information as 

part of a research study to comply with 

the current Common Rule regulatory 

requirements. 

3. Improving Informed Consent, 

Including Requiring Informed Consent 

for Research Use of Biospecimens and 

the Use of Broad Consent for Secondary 

Research Use of Biospecimens and 

Information 

The public was asked to comment on: 

The length and complexity of informed 

consent forms; additional information, if 

any, that should be required by the 

regulations to assure that consent forms 

appropriately inform subjects about 

alternatives to participation, as well as 

whether or not there should be 

modifications or deletions to the 

required elements; whether subject 

comprehension should be assessed, and 

if so, under what circumstances; 

whether changes to the Common Rule 

would necessitate conforming changes 

to the authorization requirements of the 

HIPAA privacy requirements; and 

whether additional requirements in the 

consent process are warranted, such as 

financial disclosures by investigators. 

The ANPRM also requested comment on 

the need for regulation of consent for 

the following: Research use of 

biospecimens collected for clinical 

purposes, consent for research use of 

pre-existing data, and consent to 

secondary research use of data and 

biospecimens. 

Consent for Research Use of 

Biospecimens and Information 

Generally: The ANPRM also requested 

comment on the value of generally 

requiring written consent for research 

use of any biospecimens collected for 

clinical purposes after the effective date 

of the new rules (such as research with 

excess pathology biospecimens). Such 

consent could be obtained by use of a 

brief standard consent form agreeing to 

generally permit future research. This 

brief consent could be broad enough to 

cover all biospecimens to be collected 

related to a particular set of encounters 

with an institution (e.g., hospitalization) 

or even to any biospecimens to be 

collected at any time by that institution. 

The general rule as discussed in the 

ANPRM would be that a person needs 

to give consent, in writing, for research 

use of their biospecimens, though that 

consent need not be study-specific, and 

could cover open-ended future research. 

The ideas presented in the ANPRM 

would be a substantial change from the 

current Rules in several ways. First, the 

current Rules allow research without 

consent when a biospecimen is used for 

research under conditions where the 

researcher does not possess information 

that would allow them to identify the 

person whose biospecimen is being 

studied. Thus, biospecimens collected 

as part of a non-research protocol (e.g., 

clinical care) could be made 

nonidentified and used in research as 

long as the researcher cannot identify 

the source of the biospecimen. The 

ANPRM consideration would no longer 

allow that to occur, generally requiring 

researchers to obtain consent for 

research use of clinical biospecimens, 

even if nonidentified. A waiver of 

consent under limited circumstances 

was contemplated in the ANPRM, but 

no specific waiver criteria were 

discussed. 

A majority of the commenters 

opposed the ANPRM’s suggested 

requirement to have consent for 

research use of all biospecimens, 

regardless of identifiability, on both 

administrative and ethical grounds. 

Administrative reasons for opposition to 

the suggested consent requirements 

included the prohibitive costs to collect, 

log, and track consent status of data and 

biospecimens, and the considerable 

administrative efforts that would be 

required to keep track of the consent 

status. Commenters opposed to the 

suggested consent requirements on 

ethical grounds cited increased privacy 

risks to subjects arising from the need to 

maintain links between the consent 

documents and the biospecimens or 

data in order to ensure that any 

restrictions on the research use of such 

resources were honored. They also 

expressed their belief that convincing 

evidence of harm caused by research 

use of nonidentified clinical 

biospecimens without consent is 

lacking, especially when considering 

the public health benefit of such use, 

and noting that they were not convinced 

that the principle of autonomy 

outweighs or trumps the principle of 

beneficence. Some patient advocacy 

organizations also expressed concerns 

about the consequences of requiring 

consent for the use of nonidentified 

biospecimens. Yet, most of the 

comments from individual members of 

the public strongly supported consent 

requirements for use of their 

biospecimens, regardless of 

identifiability, or data. 

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 does 

not involve risk to the research 

participant. One commenter noted that 

‘‘In our extensive professional 

experience working with biospecimens 

on a daily basis, the current system has 

worked well and has greatly enriched 

the opportunity for discoveries that 

were unknown at the time of collection 

and when research does not require 

subject identification or involve patient 

risk.’’ In contrast, some commenters 

supported the idea of requiring consent 

for research use of all biospecimens, 

with one commenter noting simply that 

‘‘research use of data initially collected 

for non-research purposes should 

always require informed consent.’’ 

Commenters particularly noted 

concerns about imposing consent 

requirements on the use of 

biospecimens already collected—that is, 

not grandfathering in such resources— 

especially if these biospecimens are 

nonidentified. Requiring that consent be 

obtained for the use of these materials 

could result in their being rendered 

useless for research, which would 

represent a cost of its own in terms of 

lost opportunity. This concern was 

based on the practical limitations 

involved in obtaining consent for 

biospecimens that were de-identified in 

the past, given that it may not be 

possible to re-contact the original 

source. 

The objections raised by the 

commenters about the possible adverse 

consequences of requiring consent for 

the use of nonidentified biospecimens— 

including, in particular, the proposition 

that such a change might significantly 

compromise an important and relatively 

low-risk area of research—resulted in 

suggestions in the comments that this 

should be systematically assessed before 

suggesting any new rules. In fact, 

several commenters suggested that data 

be collected on the cost and feasibility 

of instituting such a requirement before 

revising the Common Rule. 

Consent Rules for Research Use of 

Pre-existing Data: The ANPRM asked 

for comments on revising the consent 

rules for research use of data previously 

collected for purposes other than the 

suggested research study. First, if the 

data were originally collected for nonresearch purposes, then, as is currently 

the rule, written consent would only be 

required if the researcher obtains 

information that identifies the subjects. 

There would accordingly be no change 

in the current ability of researchers to 

conduct such research using deidentified data or a limited data set, as 

such terms are used in the HIPAA 

Rules, without obtaining consent. 

Second, if the data were originally 

collected for research purposes, then 

consent would be required regardless of 

whether the investigator obtains 

identifiers. Note that this would be a 


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change with regard to the current 

interpretation of the Common Rule in 

the case where the researcher does not 

obtain any identifiers. That is, the 

allowable current practice of telling the 

subjects, during the initial research 

consent, that the information they are 

providing will be used for one purpose, 

and then after stripping identifiers, 

allowing it to be used for a new purpose 

to which the subjects never consented, 

would not be allowed. 

Consent to Secondary Research Use 

of Data and Biospecimens Through 

Broad Consent: The ANPRM suggested 

that consent for the use of biospecimens 

or data could be obtained using a 

standard, short form, in which the 

subject could be asked to provide broad 

consent, that is, consent for a variety of 

potential future uses of their 

biospecimens or data. The requirement 

for consent could be waived in certain 

circumstances. These changes would 

apply only to biospecimens and data 

collected after the effective date of a 

new final rule. 

Public comments revealed variable 

opinions on this issue. Several 

commenters indicated that there is no 

need for additional regulations, with 

one university stating that it ‘‘strongly 

opposes more restrictive regulations 

about the use of these biospecimens and 

sees no need to change the current 

regulations, even or perhaps especially 

in the case of secondary data analysis.’’ 

Other commenters opposed broad 

consent, stating that researchers and 

clinicians should obtain specific 

consent from individuals for each 

research project. This opposition was 

made on the ethical grounds that 

because individuals are not fully 

informed of specific research purposes 

for broad consent, they can never be 

truly informed about the use of their 

data. In contrast, other commenters 

expressed clear support for general 

consent for secondary research use of 

biospecimens and data collected during 

research to exempt the research from 

IRB review, noting that ‘‘we support the 

suggestion in the ANPRM to encourage 

general consent for the secondary 

research use of biospecimens and data 

and where this is not obtained IRB 

review is required.’’ Other commenters 

favored requiring IRB review over 

permitting the use of a broad consent to 

approve secondary research use of 

identifiable data or biospecimens. These 

commenters believed that IRB 

consideration of consent requirements 

for individual research studies was 

more protective of human subjects than 

the ANPRM suggestions to permit broad 

consent for future use. 

With regard to the burden of obtaining 

consent for the research use of deidentified biospecimens, this 

requirement could be less burdensome 

than anticipated due to the ANPRM’s 

suggested allowance of broad consent. 

While the ANPRM suggested requiring 

consent for the use of biospecimens, it 

suggested allowing a one-time, broad 

consent for future uses to be obtained 

with a template form which, if used 

without changes, would not require IRB 

review, and could be obtained at the 

same time as the initial research or 

clinical consent. Some commenters, 

particularly patients and patient 

advocacy groups, expressed concern 

about the burden of re-consenting 

patients for broad consent after 

biospecimens were collected. 

Several commenters suggested that 

data be collected on the cost and 

feasibility of instituting such a 

requirement before revising the 

Common Rule. 

In most instances, the consent 

requirements described above would 

have been met at the time that the 

biospecimens or data were initially 

collected, when, under the ANPRM the 

subject would have signed a standard, 

brief general consent form allowing for 

secondary research. This brief consent 

could be broad enough to cover all data 

and biospecimens to be collected related 

to a particular set of encounters with an 

institution (e.g., hospitalization) or to 

any data or biospecimens to be collected 

at any time by the institution, even as 

part of a research protocol. 

The ANPRM suggested that this 

standardized broad consent form would 

permit the subject to say no to all future 

research. In addition, the ANPRM 

acknowledged that there are likely to be 

a handful of special categories of 

research with biospecimens that, given 

the unique concerns they might raise for 

a significant segment of the public, 

could be dealt with by check-off boxes 

allowing subjects to separately say agree 

or disagree to that particular type of 

research. 

Further, the ANPRM suggested that 

the current prohibition that 

participation in a research study (such 

as a clinical trial) could not be 

conditioned on agreeing to allow future 

open-ended research using a 

biospecimen would be maintained. 

With regard to the secondary research 

use of pre-existing data, on those 

occasions when oral consent was 

acceptable under the regulations for the 

initial data collection, the ANPRM 

envisioned that subjects would have 

typically provided their oral consent for 

future research at the time of the initial 

data collection; a written consent form 

would not have to be signed in that 

circumstance. 

The ANPRM suggested that these 

changes would only be applied 

prospectively, not retrospectively. In 

other words, they would only apply to 

biospecimens and data that are collected 

after the effective date of the new rules. 

It also noted that there would be rules 

that would allow for waiver of consent 

under specified circumstances, though 

those conditions would not necessarily 

be the same as those for other types of 

research. 

Improving Consent Forms and 

Modifying the Required Elements of 

Consent: Public comments were largely 

in favor of finding ways to improve 

consent forms. However, commenters 

cited several systemic concerns that 

could be obstacles to shortening and 

simplifying forms, such as regulatory, 

legal, and institutional requirements, 

and the complexity of some studies. Of 

those responding to questions about the 

causative factors, blame for making 

forms long and complex was shared by 

sponsors of clinical trials, IRBs, 

regulatory agencies, and institutional 

legal counsel. The types of information 

cited as contributing to the excessive 

lengths of forms included the 

requirement to describe all reasonably 

foreseeable research risks and the 

complexity of study procedures. There 

was no consensus on how to better 

explain alternatives to research 

participation and few comments were 

submitted on this topic. 

Commenters offered a few suggestions 

for modifying or deleting the required 

elements of consent, such as removing 

boilerplate language that only protects 

institutions and research sponsors, as 

well as removing some of the required 

elements for minimal risk research. 

However, many felt that guidance, 

rather than regulatory change, would 

better improve the development of 

consent forms. Although many 

commenters noted the need for shorter 

and more comprehensible consent 

forms, most felt that the required 

elements of consent articulated in the 

Common Rule are sufficient. 

Commenters overwhelmingly supported 

the goals articulated in the ANPRM, but 

cautioned against an overly prescriptive 

or rigid approach to consent forms. 

However, several commenters requested 

guidance on what might be included in 

a consent form for future research use of 

identifiable information and identifiable 

biospecimens to ensure that such forms 

satisfied the consent requirements of the 

Common Rule. 

A majority of commenters supported 

the development of regulations or 

guidance designed to encourage 


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assessment of the extent to which 

human subjects comprehend consent 

forms, at least for certain types of higher 

risk studies or certain types of subject 

populations. Others argued that the 

regulations at § ll.116 already contain 

language implying the need to ensure 

comprehension through the use of the 

terms ‘‘legally effective informed 

consent’’ and ‘‘language understandable 

to the subject.’’ 

Finally, many commenters supported 

making changes to HIPAA authorization 

requirements, as necessary to conform 

to provisions of the Common Rule. In 

addition, most commenters were 

supportive of requiring investigators to 

disclose in consent forms certain 

information about the financial 

relationships they have with study 

sponsors. 

Criteria for Waiver of Consent: The 

ANPRM asked whether changes to the 

regulations would clarify the current 

four criteria for waiver of informed 

consent and facilitate their consistent 

application. Few comments were 

received on this topic although many 

commenters expressed support for 

clarifying the key terms through 

guidance or altering the criteria. In 

particular, most comments on this topic 

noted the confusion that IRBs face when 

trying to understand the meaning of the 

terms ‘‘practicable’’ and ‘‘adversely 

affect the rights and welfare of 

subjects.’’ Some commenters expressed 

the opinion that the waiver criterion 

concerning rights and welfare should be 

interpreted to include reference to rights 

conferred by other federal laws or 

regulations, state or local laws, or laws 

in other countries where research is to 

be conducted. Some comments reflected 

concerns about privacy or security. 

The ANPRM also asked for comments 

on the information investigators should 

be required to provide to prospective 

subjects in circumstances where the 

regulations would permit oral consent. 

Additional questions focused on 

whether there are additional 

circumstances under which it should be 

permissible to waive the usual 

requirements for obtaining or 

documenting informed consent, and 

whether there are types of research in 

which oral consent without 

documentation should not be permitted. 

There were few responses to these 

questions and no common themes or 

consensus among those submitted. 

However, several commenters pointed 

to the need to consider community 

norms throughout the consent process, 

including its documentation. 

4. Improving the Collection and 

Analysis of Adverse Event Reports 

The ANPRM asked the public to 

consider a number of changes to 

improve the current system for the realtime prompt collection of data regarding 

adverse events. The changes that the 

ANPRM stated were under 

consideration were intended to simplify 

and consolidate the reporting of 

information that is already required to 

be reported by an investigator, and not 

to expand the information that has to be 

reported. In addition to these changes, 

the ANPRM indicated that the Federal 

Government was also considering 

creating a central web-based repository 

to house a great deal of the information 

collected through the portal. 

Although a number of commenters 

applauded the goal of easing and 

harmonizing reporting requirements, 

most expressed concerns about 

collecting data on unanticipated 

problems and adverse events in a 

central database. Those who supported 

the concept of centralized reporting 

asked for more detail on what such a 

system would entail. More specifically, 

several commenters noted that IRBs 

sometimes struggle with what should be 

reported and with distinguishing 

between the Common Rule term 

‘‘unanticipated problems’’ and the FDA 

term ‘‘adverse events.’’ Commenters 

noted that under the Common Rule at 

§ ll.103(b)(5), each institution 

determines through its own policies the 

procedures for reporting unanticipated 

problems to department or agency 

heads. As a result, there is no 

standardized definition of 

‘‘unanticipated problems,’’ so each 

institution may be reporting different 

events. Commenters also sought better 

guidance on those terms and 

encouraged agencies to clarify meanings 

and reporting requirements. 

Commenters stated that a 

standardized, streamlined set of data 

elements, a single web-based reporting 

tool that facilitates delivery to agencies 

and oversight bodies, and harmonized 

Federal agency guidance would simplify 

the process. However, many expressed 

skepticism that harmonization across 

Federal agencies could occur. 

With regard to a centralized database, 

many commenters expressed concerns 

regarding the value in terms of cost and 

time with compiling such data, gleaned 

from diverse studies and sources, in 

order to conduct an integrated analysis. 

They commented that it is unclear how 

the data would be useful beyond a 

specific study and unclear who would 

have access to the data and how it 

would be managed and interpreted to 

better inform the regulatory process. 

Commenters asked, if the data reporting 

is real-time, who is expected to develop 

such a system and review incoming data 

to coordinate the appropriate response? 

Many commenters questioned the 

validity of data collected in such a 

generic manner and the ability to draw 

generalizable conclusions based on data 

collected from varied sources and 

contexts. Several commenters said that 

before implementing such a central 

repository, a thorough cost-benefit 

analysis should be conducted regarding 

strengths and limitations of similar data 

repositories. Until the utility of such a 

centralized system could be 

demonstrated, especially when 

compared to the current decentralized 

system, many felt the burden of creating 

such a system would not be 

counterbalanced by the benefit of added 

protections. Along these lines, 

commenters also questioned the utility 

of counting how many human subjects 

are enrolled in trials, stating that this 

would not be a meaningful way to 

develop risk estimates. 

Many commenters cited the adequacy 

of current reporting systems, despite the 

need for improvement. Centralized 

reporting of adverse events would 

represent a dramatic change from how 

events are collected and reported now. 

For example, sponsors of clinical trials 

are responsible for continuously 

monitoring their trials, adverse events 

must be reported to sponsors, and new 

reporting would not substitute for 

reports to sponsors. In addition, under 

FDA regulations, when applicable, 

safety information from non-U.S. 

clinical trials may need to be reported. 

Moreover, sponsors and funding 

agencies probably would not rely on 

extracting information from a federal 

database as the source of information to 

meet all of their safety oversight 

obligations and would likely still 

require investigators to complete 

adverse event case report forms as well 

as rely on the use of Data Safety 

Monitoring Boards. Commenters also 

raised concerns that the use of an 

electronic centralized reporting system 

could be a substantial burden on 

investigators, may potentially decrease 

investigators’ willingness to participate 

in trials, and may encourage the 

conduct of studies outside the 

regulations. If reporting systems were 

now required to also gather and store 

unanticipated problems in addition to 

adverse events, commenters said the 

system would become unwieldy, run 

the risk of creating long lag times in 

analysis, and draw low risk events into 

a system that should be focused on the 


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97 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. http://

www.amstat.org/meetings/jsm/2011/

onlineprogram/

AbstractDetails.cfm?abstractid=302255. 

98Pentz 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 1; 140(7):733– 

9. 

99Chen DT et al. Research With Stored Biological 

Samples; What Do Research Participants Want? 

Archives of Internal Medicine. 2005 Mar 28; 

165(6):652–5. 

100Scott et al. Biospecimen Repositories: Are 

Blood Donors Willing to Participate? Transfusion. 

2010 September; 50(9): 1943–1950. 

highest risk studies. Several 

commenters recommended that more 

efforts be made to improve current 

reporting systems, particularly 

ClinicalTrials.gov. 

Based on the public comments, the 

NPRM does not pursue a centralized 

reporting system and thus this issue is 

not addressed further. OHRP will 

continue to engage in discussions with 

FDA and Common Rule departments 

and agencies regarding clarifying 

reporting terms and requirements. 

5. Identifiability of Biospecimens 

The ANPRM suggested that, 

regardless of what information is 

removed, it is possible to extract DNA 

from a biospecimen itself and 

potentially link it to otherwise available 

data to identify individuals. In addition, 

irrespective of whether biospecimens 

are considered individually identifiable, 

the ANPRM sought comment on 

whether the regulations should be 

changed to respect individuals’ interest 

in being able to decide whether their 

biospecimens would be available for 

research, even if the biospecimen was 

not associated with any identifiable 

information. Consequently, it asked for 

public comment on the value of 

categorizing all research involving the 

primary collection of biospecimens as 

well as storage and secondary analysis 

of existing biospecimens as research 

involving identifiable information. 

The ANPRM asked whether some 

types of genomic data should be 

considered identifiable and, if so, which 

types (e.g., genome-wide single 

nucleotide polymorphism [SNP] 

analyses or whole genome sequences). It 

also asked whether human 

biospecimens should be considered 

inherently identifiable. A majority of 

commenters opposed changing the 

Common Rule to consider all 

biospecimens identifiable as defined by 

the existing regulations at 

§ ll.102(f)(2) (and thereby 

categorizing their use as research 

involving a human subject), and 

expressed concern that doing so would 

significantly slow advances in research 

and human health. Several commenters 

noted that, although it is theoretically 

plausible to identify a person based on 

his or her 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 reidentification from a system intrusion of 

databases was only 0.22%.97 Other 

commenters cited the administrative 

burden that would be exacted should 

such an interpretation be implemented, 

without sufficient evidence that such an 

interpretation would be reasonable or 

enhance protections. 

Commenters were mostly concerned 

with the cost and burden that would be 

imposed by the requirement to obtain 

consent. Commenters anticipated these 

costs to include obtaining consent from 

participants and the administrative 

efforts required to keep track of the 

consent status of biospecimens. Most 

commenters did not provide detailed 

cost estimates with their comments; 

data are specifically requested in 

response to this NPRM. In addition, 

estimates of the type and number of 

studies that could not be pursued using 

existing samples and data because of the 

absence of sufficient consent are 

requested. Comment is also sought on 

the value to the public and research 

participants of being asked their 

permission for research use of their data 

and specimens. 

Several commenters also stated that if 

the Common Rule were modified such 

that all biospecimens were covered 

under the rule regardless of their 

identifiability, there still might be some 

activities involving biospecimens or 

types of biospecimens that should be 

considered exempt or ‘‘excused.’’ 

Suggestions included: 

• Identifying markers for cancer 

prognosis or prediction of response to 

cancer therapy, or identifying cancer 

molecular targets (molecular research) 

• Basic science research (including 

analysis of biological processes) 

• Research of rare conditions and 

diseases 

• Pediatric research 

• Research with samples that lack 

potentially identifying information, 

such as serum or plasma not containing 

DNA 

• Biospecimens lacking nucleic acids 

(such as certain red blood cells, 

expiratory gases) 

• Blood culture bacteria 

• Bacterial and viral specimens (this 

was listed in a comment as a public 

health issue) 

• Protein analysis 

• Statistical method development (to 

the extent that this development is 

related to biospecimens) 

• New molecular methods to detect 

infectious agents 

• Use of specimens to develop and 

validate new assays for infectious agents 

• Archival paraffin blocks 

One commenter also suggested that 

the Rule could propose a definition for 

biospecimen such that the term does not 

include sample types that lack DNA. 

In addition, some commenters noted 

that the recommendation to require 

consent might privilege the Belmont 

Report’s principle of autonomy over the 

principle of justice, because requiring 

consent could result in lower 

participation rates in research by 

minority groups and marginalized 

members of society. The literature on 

consent rates in studies involving 

biospecimens suggests that while 

minority consent rates in some cases 

may be lower than non-minorities, 

when asked to consent, minority 

consent rates are still higher than 

projected.98 99 100 Furthermore, better 

communication and community 

engagement with members of specific 

minority groups is needed to 

understand and address concerns 

related to research, and these measures 

could substantially improve 

participation rates. An increase in trust 

and partnership is likely to increase 

participation rates; using their samples 

and data without permission will hinder 

true partnership. 

C. ANPRM Issues and Public Comments 

Related To Reducing Regulatory Burden 

1. Activities Excluded From the Policy 

The ANPRM asked questions about 

the definition of research and whether 

various activities should be excluded 

from the Common Rule, either by 

changing the definition of research or by 

adding exemptions, or both. The 

ANPRM sought comment on whether 

and, if so, how, the Common Rule 

should be changed to clarify whether 

quality improvement activities, program 

evaluation studies, or public health 

activities are covered. It also asked 

whether there are specific types of 

studies for which the existing rules are 

inappropriate. If so, comments were 

sought on whether this problem should 

be addressed through modifications to 

the exemption categories, or by 

changing the definition of ‘‘research’’ 

used in the Common Rule to exclude 


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101Office for Human Research Protections. (2011, 

January 20). Exempt Research Determination FAQs. 

Retrieved from Frequently Asked Questions About 

Human Research: http://www.hhs.gov/ohrp/policy/

faq/index.html. 

some of these studies, or a combination 

of both. 

If the definition of research were to be 

changed, public comment was sought 

on how excluded activities should be 

defined (e.g., ‘‘quality improvement’’ or 

‘‘program evaluation’’). With regard to 

quality improvement activities, the 

public was asked to comment on 

whether it might be useful to adopt the 

distinction made by the HIPAA Privacy 

Rule, which distinguishes between 

‘‘health care operations’’ and ‘‘research’’ 

activities, defining ‘‘health care 

operations’’ to include, among other 

activities, ‘‘conducting quality 

assessment and improvement activities, 

including outcomes evaluation and 

development of clinical guidelines, 

provided that the obtaining of 

generalizable knowledge is not the 

primary purpose of any studies resulting 

from such activities.’’ 

A majority of public comments 

supported excluding the following from 

the regulatory requirements: quality 

improvement activities, public health 

activities, and program evaluation. 

Many of these commenters argued that 

the public benefits resulting from these 

activities justified their practice, 

particularly given the generally low risk 

involved. Some argued that for some 

legally mandated activities designed to 

accomplish a public good, it would be 

inappropriate for IRBs or individuals to 

be able to impede or thwart the 

execution of those mandated activities. 

A majority of comments also favored 

distinguishing between research and 

health care operations, as such terms are 

defined in the HIPAA Privacy Rule, and 

excluding the latter from the policy. 

Some commenters noted that people 

involved in these various activities are 

protected in other ways, and alluded to 

the sorts of measures that provide a 

measure of protection. Others suggested 

that any exclusions should be limited to 

data collection and analysis activities, 

or to activities below a certain threshold 

of risk (i.e., minimal risk). A minority of 

comments objected to these exclusions, 

arguing that these activities represent 

encroachments on their individual 

rights and privacy, and that oversight in 

accordance with the Common Rule 

requirements would be more protective. 

The overwhelming majority of public 

comments responding to the question 

about excluding specific fields of study 

from the regulatory requirements of the 

Common Rule supported explicitly 

excluding certain activities from the 

definition of research versus modifying 

the exemption categories. The 

overwhelming majority of these 

comments focused on oral history. Some 

of the comments were virtually identical 

and appear to have been coordinated. 

Many of the comments reflected the 

view that the Common Rule was not 

designed or intended to include oral 

history activities, and that the ethical 

codes pertaining to oral history 

procedures are not consistent with the 

application of ethical principles 

reflected in the Common Rule. 

A smaller number of similar 

comments were submitted with respect 

to various humanities disciplines and 

journalism. A significant minority of 

commenters opposed the exclusion of 

any fields of study, arguing that the 

activity itself rather than the academic 

discipline or training of the investigator 

should be the basis for the assessment 

of whether the activity should be 

excluded. Some of the commenters 

recommended that the definition of 

research be focused more explicitly by 

being limited to ‘‘biomedical and 

behavioral research,’’ in accordance 

with the statutory provision underlying 

the Common Rule. A significant number 

of commenters recommended that 

guidance should be issued to clarify 

how the definition of research should be 

applied, with cases and explanations. 

2. Research Exempt From IRB Oversight 

Exemption Determination: The 

ANPRM discussed a mechanism to (1) 

register exempt research, and (2) audit 

a small but appropriate portion of such 

research, which would still be subject to 

other regulatory protections such as the 

suggested data security and information 

protection standards and certain 

consent requirements. The term 

‘‘excused’’ rather than ‘‘exempt’’ was 

recommended to describe these 

categories of research, because they are 

not entirely exempt from oversight. 

The ANPRM discussed a tracking 

mechanism to enable institutions to 

assure that such research meets the 

criteria for inclusion in the suggested 

‘‘excused’’ categories. The original 

recommendations would require 

investigators to register their study with 

an institutional office by completing a 

brief form, thus eliminating the current 

practice of not allowing investigators to 

begin conducting such studies until a 

reviewer had determined it met the 

criteria for excused research. This 

would make the institution aware of key 

information about the research (such as 

the purpose of the research and the 

name of the study’s principal 

investigator), without also requiring that 

the activity undergo a review that, if not 

done in a timely manner, could slow the 

research without adding any significant 

protection to subjects. In addition the 

institution could choose to review some 

of the submissions at the time they are 

filed and, if deemed appropriate, require 

that the study be sent for expedited 

review or, in rare cases, convened IRB 

review. It would be made clear that the 

regulations would not require, and in 

fact, would discourage, having each of 

these registration forms undergo a 

comprehensive administrative or IRB 

review prior to commencing the study 

or even afterward. 

The auditing requirement was 

intended to encourage institutions to 

use the regulatory flexibility suggested 

for the ‘‘excused’’ categories of research. 

The auditing requirement would have 

provided institutions with information 

needed to assess their compliance with 

the new ‘‘excused’’ categories without 

unnecessarily subjecting all such 

research to either prospective review, or 

even routine review sometime after the 

study is begun. Note that currently, 

OHRP recommends that there be some 

type of review by someone other than 

the investigator to confirm that a study 

qualifies as exempt, and many 

institutions do impose such a 

requirement even though such a 

requirement is extra-regulatory.101

The ANPRM also asked whether this 

research should be called ‘‘excused’’ or 

some other term, whether it was 

acceptable for investigators to 

independently determine whether their 

research was excused, whether review 

of all registrations should be required, 

and whether there should be a time 

limitation or waiting period before 

excused research could begin. The 

ANPRM also asked whether it was 

appropriate to require institutions 

holding an FWA to conduct 

retrospective audits of a percentage of 

the excused studies to make sure they 

qualify for inclusion in an excused 

category, and if so, how such audits 

should be conducted. 

Commenters overwhelmingly 

expressed concerns about adopting the 

term ‘‘excused’’ to describe this area of 

research and suggested the term 

‘‘registered’’ should such a system be 

adopted. Commenters recommended the 

term ‘‘registered’’ because such studies 

would not be exempt or excused from 

other requirements, such as compliance 

with data and security provisions as 

well as, in certain circumstances, 

informed consent requirements. In 

general, commenters were not 

necessarily opposed to the concept of 

registration but sought further 

information on what this process would 

entail. 


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102 Informed consent is legally effective if, in part, 

it is both obtained from the subject or the subject’s 

legally authorized representative and documented 

in a manner that is consistent with the HHS 

protection of human subjects regulations and with 

applicable laws of the jurisdiction in which the 

research is conducted. See Office for Human 

Research Protections. (2011, January 20). What is 

the meaning of ‘‘legally effective informed 

consent?’’. Retrieved from Frequently Asked 

Questions: http://www.hhs.gov/ohrp/policy/faq/

informed-consent/what-is-legally-effectiveinformed-consent.html. 

103 63 FR 60364 (Nov 9, 1998). Also available at, 

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

Public commenters also expressed 

concerns about allowing an investigator 

to independently make the 

determination that his or her research is 

exempt. Other commenters suggested 

that this practice would be acceptable 

for some investigators, whose research 

is well known to IRB members, and is 

clearly within an exempt category. The 

ANPRM noted concerns that some 

exempt research was unnecessarily 

delayed by requirements of some 

institutions to review the research to 

make an exemption decision. 

Several institutions reported that they 

already as a matter of policy require 

investigators to submit exempt studies 

to the IRB, not necessarily for full board 

review, but to ensure that the exempt 

determination is valid. These decisions 

typically are made by the IRB 

administrator and never involve full 

review unless there is concern about the 

exemption status. Thus, they felt the 

registration requirement was 

unnecessary and would add new 

administrative burdens for research 

already considered low risk. 

Other commenters, such as 

investigators conducting research 

currently considered exempt, were 

strongly opposed to a registration 

requirement because it would add a new 

burden to conducting less than minimal 

risk and exempt research. In addition, 

commenters raised concerns about the 

administrative burden and need for a 

retrospective audit system of registered 

research. 

Exemption Categories: The ANPRM 

considered revising the regulations 

regarding studies currently considered 

exempt by expanding the current 

exemption category 2 (research 

involving educational tests, surveys, 

focus groups, interviews, and similar 

procedures, found in the current Rule at 

§ ll.101(b)(2)) to include all studies 

involving educational tests, surveys, 

interviews, and similar procedures so 

long as the subjects are competent 

adults, without any further 

qualifications. It also considered adding 

a new category for certain types of 

behavioral and social science research 

that goes beyond using only survey 

methodology, but nonetheless involves 

only specified minimal risk procedures, 

so long as the subjects are competent 

adults (but subject to the data security 

and information protection standards). 

The term ‘‘competent’’ as used in the 

ANPRM referred to adults who would 

be able to provide ‘‘legally effective 

informed consent,’’ as currently 

required by § ll.116.102

The ANPRM also considered whether 

to include on the list of exempt studies 

certain types of social and behavioral 

research conducted with competent 

adults that would involve specified 

types of benign interventions commonly 

used in social and behavioral research, 

that are known to involve virtually no 

risk to subjects, and for which prior 

review does little to increase protections 

to subjects. These would be 

methodologies that are familiar to 

people in everyday life and in which 

verbal or similar responses would 

constitute the research data being 

collected. For example, an investigator 

might ask subjects to watch a video, 

read a paragraph, or solve puzzles, and 

then ask them some questions to elicit 

word associations or time performance 

of activities. The specific methodologies 

might be spelled out in regulations, or 

they might be promulgated via a 

periodic mechanism to announce and 

update lists similar to the list that is 

published for activities that may be 

reviewed by an IRB using the expedited 

review procedures.103

A majority of commenters supported 

the ANPRM discussion on expanding 

current exemption category 2 (current 

Rule at § ll.101(b)(2)) by eliminating 

the limitations related to the recording 

of identifiable information and the harm 

that could result if a subject’s responses 

were disclosed. However, many 

commenters were opposed to the 

requirement that subjects be ‘‘competent 

adults’’ in order for the expanded 

exemption to apply, asking whether 

tests of competency would be required 

for such research to proceed. 

Many commenters also supported 

adding another exemption category of 

research for certain types of social and 

behavioral activities, conducted with 

competent adults, that would involve 

specified types of benign interventions 

beyond educational tests, surveys, focus 

groups, interviews, and similar 

procedures that are commonly used in 

social and behavioral research, that are 

known to involve virtually no risk to 

subjects, and for which IRB review does 

little to increase protections for subjects. 

The ANPRM asked questions about 

whether the current limitations 

specified in exempt category 4 (research 

involving the use of existing 

information or biospecimens, 

§ ll.101(b)(4) in the current Rule) 

should be eliminated. Specifically, the 

ANPRM suggested that the category 

would be revised to eliminate the word 

‘‘existing.’’ With this elimination, the 

exemption would be broadened to cover 

the use of information or biospecimens 

that were or will be collected for 

purposes other than the suggested 

research, rather than requiring that all of 

the information or biospecimens already 

exist at the time the study is suggested 

for exemption. 

The ANPRM also discussed whether 

research involving only the use of data 

or biospecimens collected for other 

purposes, even if the investigator 

intends to retain identifiers, should 

come within a new exemption category; 

studies that include a plan to provide 

individual research results to subjects 

would not qualify for this proposed 

exemption. In addition, the ANPRM 

asked whether certain flexible consent 

requirements could be imposed on some 

of these studies that would permit the 

use of a broad consent for future use, 

with a requirement that a subject’s 

specific consent would be required 

before their biospecimens could be used 

for special categories of research. 

Many of the comments supported the 

discussion in the ANPRM of eliminating 

the requirement that the information or 

biospecimens be ‘‘existing’’ at the time 

the study was suggested for exemption. 

However, a majority strongly disagreed 

that biospecimens should be considered 

or treated as though they were 

inherently identifiable. A majority also 

opposed the suggestion that there be 

consent requirements for the research 

use of nonidentifiable biospecimens 

collected for purposes other than the 

current research study. 

Some commenters also favored 

requiring IRB review and approval for 

the use of identifiable private 

information and identifiable 

biospecimens, rather than permitting 

the use of a broad consent for future use 

to satisfy the regulatory requirement for 

consent. These commenters indicated 

that IRB review of specific research 

studies, and the IRB’s consideration of 

whether a study specific informed 

consent should be required or whether 

informed consent could be waived, was 

more protective of human subjects than 

the ANPRM recommendation of 

permitting use of a broad consent for 

future use. 

The ANPRM asked several questions 

about the interpretation and 

applicability of current exemption 

category 5 (current Rule at 


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104See 48 FR 9266–9270 (Mar 4, 1983). (OPRR 

Guidance on 45 CFR 46.101(b)(5), Exemption for 

Research and Demonstration Projects on Public 

Benefit and Service Programs, http://www.hhs.gov/ 

ohrp/policy/exmpt-pb.html). 

105The current rule states that 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. (45 CFR 46.102(i)). 

§ ll.101(b)(5)), including the scope of 

the current interpretation of the category 

5 exemption. The ANPRM also asked if 

the current category 5 guidance entitled, 

‘‘OPRR Guidance on 45 CFR 

46.101(b)(5)’’ 104 should be revised, or if 

additional guidance on the 

interpretation of exemption category 5 is 

needed. 

There were few responses to these 

questions. However, those that did 

comment noted that this category is 

often misunderstood by IRBs and, at 

best, would benefit from clearer 

guidance. Commenters said that 

examples would help investigators and 

IRBs understand when research 

activities included in demonstration 

projects constitute human subjects 

research subject to the Common Rule. 

Commenters noted that many activities 

in demonstration projects do not 

contribute to generalizable knowledge 

as they produce results that are relevant 

only to the program being assessed; as 

such, many of these activities do not 

meet the Common Rule’s regulatory 

definition of ‘‘research’’ and thus fall 

outside of the rule. Other commenters 

said that some activities in this category 

are mandated or required by law or 

regulation and should not be considered 

to be under the purview of the Common 

Rule. It was noted that the critical issue 

in these studies should be protecting 

privacy and as long as measures are in 

place to do so, additional protections 

are not required. 

3. Expedited Review 

The ANPRM discussed and sought 

comment on three possible changes to 

the review of research through 

expedited review: (1) Revising the 

definition of minimal risk, which is one 

of the criteria for determining whether 

a study is eligible for expedited review; 

(2) changing the default position so that 

research on the expedited review list 

could generally be presumed to involve 

minimal risk; (3) revising the criteria for 

approval of research studies under 

expedited review; and (4) allowing 

appropriately trained individuals who 

are not IRB members to conduct 

expedited reviews. 

Definition of Minimal Risk: The 

ANPRM asked for public comment on 

whether the current regulatory 

definition of minimal risk 105 was 

appropriate. The definition of minimal 

risk has relevance to determining 

whether a protocol is eligible for 

expedited review. Public comments 

expressed both a desire to retain the 

current definition (slightly less than 

half) and a desire for changing it 

(slightly more than half). There were 

few common themes in the suggested 

changes to the language other than 

seeking clarification on what baselines 

an IRB should consider in determining 

the meaning of ‘‘daily life’’ and ‘‘routine 

physical or psychological 

examinations.’’ Several commenters 

acknowledged the difficulty of arriving 

at a concise definition for all 

circumstances. Those opposed to 

changing the definition said that IRBs 

generally understand how to interpret 

the language and that difficult or 

challenging application of the definition 

will persist regardless of the definition 

for those areas of research where risks 

are difficult to assess. Commenters 

recognized that the risks encountered in 

daily life can vary greatly depending on 

many factors, for example, where people 

live, what kind of work they are 

involved in, what their social and 

economic environment is, and their 

baseline health status. Thus, IRBs need 

to consider all of these issues in making 

a determination about the level of risk. 

Eligibility for Expedited Review: The 

ANPRM suggested updating the current 

list of research activities eligible for 

expedited review; this list was last 

updated in 1998. It also considered 

mandating that a federal panel 

periodically (such as every year or every 

two years) review and update the list, 

based on a systematic, empirical 

assessment of the levels of risk. This 

would provide greater clarity about 

what would be considered to constitute 

minimal risk, and create a process that 

allows for routinely reassessing and 

updating the list of research activities 

that would qualify as minimal risk. The 

ANPRM asked for public comments on 

categories of research that should be 

considered for addition to the current 

list. 

Several commenters provided 

suggestions for additions to the list of 

research activities eligible for expedited 

review. Others encouraged OHRP to 

consider developing principles for 

expedited review, rather than creating a 

revised list of research activities. 

Commenters suggested a more timely 

and consistent review of the list because 

of the rapidly changing state of science 

and technology. 

The ANPRM also discussed the 

potential adoption of a default 

presumption in the rule that a study that 

includes only activities on the 

expedited review list is a minimal risk 

study and should receive expedited 

review. A reviewer would have the 

option of determining that the study 

should be reviewed by a convened IRB 

when that conclusion is supported by 

the specific circumstances of the study. 

The ANPRM also asked for comments 

on whether IRBs should be required to 

report instances when they overrode the 

default presumption that research 

appearing on the posted list did not 

warrant review by a convened IRB. 

Commenters overwhelmingly 

welcomed the clarification that 

categories of research found on the 

published list should be presumed to be 

minimal risk. However, commenters 

were largely opposed to requiring IRBs 

to report instances when they 

conducted a review by the convened 

membership (versus an expedited 

review) for studies appearing on the list. 

They were opposed because of the 

additional administrative burden and 

also because they felt such a 

requirement would undermine the 

purview of local review and open IRBs 

up to second-guessing by OHRP. 

Criteria for Approval under 

Expedited Review: The ANPRM asked 

whether all of the §ll.111 criteria 

should still be required for approval of 

studies that qualify for expedited 

review, and if not, which ones should 

not be required. Currently, before an IRB 

may approve a research study, including 

research that is being reviewed under an 

expedited procedure, the IRB must find 

that the criteria at §ll.111 have been 

met. 

With regard to revising the criteria 

used for expedited review, comments 

were mixed. Nearly half of those 

commenting expressed concerns about 

establishing two sets of ethical 

standards for IRB review—one for 

convened review and one for expedited 

review. They asserted ethical and 

administrative concerns about operating 

under two sets of conditions and 

principles—that is, expedited review 

should not be viewed as less stringent 

than review conducted by a convened 

IRB. 

Those commenters in favor of 

retaining the current criteria wrote that 

a double standard could result in 

arbitrary IRB decision making. In 

addition, many wrote that the current 

criteria are well understood by IRB 

members and the tendency to review a 

protocol through a convened IRB when 

expedited review would be permissible 

is more a function of institutional 


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106 74 FR 9578 (Mar. 5, 2009). Also available at 

http://www.hhs.gov/ohrp/newsroom/rfc/

com030509.html. 

concerns about liability than the 

regulatory requirements. They cited the 

regulatory language at §ll.111, which 

frequently contains the phrase ‘‘wgeb 

appropriate,’’ so that the reviewer(s) can 

exercise discretion in whether all of the 

criteria need to be applied. 

Those in favor of revising the 

elements most often cited the 

irrelevance of some of the criteria for 

minimal risk research, such as the need 

to ensure that risks to subjects are 

reasonable in relation to anticipated 

benefits (§ll.111)(a)(2)). They stated 

that in the case of minimal risk research, 

the need to balance risks with benefits 

is not pertinent. Some commenters 

asked OHRP to develop guidance for the 

expedited reviewer in interpreting the 

most relevant criteria during expedited 

review. 

Several commenters noted that if the 

revised regulations remove the 

requirement for continuing review of 

studies initially reviewed through 

expedited review it would alleviate 

administrative burden; thus more 

extreme measures such as revising the 

review criteria would be less 

compelling. 

Who May Conduct Expedited 

Reviews: The ANPRM asked for public 

comment on the advantages and 

disadvantages of requiring that 

expedited review be conducted by an 

IRB member versus an appropriately 

trained individual, such as the manager 

of the IRB office, who need not be a 

member of the IRB. 

With regard to allowing a non-IRB 

member to conduct expedited review, 

comments were divided nearly evenly 

between those who opposed such a 

change and those who supported it. 

Those who opposed it cited the need for 

continuity and consistency across IRBs, 

as well as expressing concerns about 

accountability and liability. Those in 

favor of such a revision cited the 

expertise of IRB staff members and their 

ability to review many expedited 

studies at the same level as a member 

of the IRB. 

4. Streamlining IRB Review 

Cooperative Research: The ANPRM 

sought public comment on the 

feasibility, advantages, and 

disadvantages of mandating that all 

domestic (U.S.) sites in a study 

involving more than one institution rely 

on a single IRB for that study. This 

would apply regardless of whether the 

study underwent convened review or 

expedited review. Further, it would 

only affect which IRB would be 

designated as the reviewing IRB for 

institutional compliance with the IRB 

review requirements of the Common 

Rule. It 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 internal ethics reviews, 

though such reviews would no longer 

have any regulatory status in terms of 

compliance with the Common Rule. 

To address institutions’ concerns 

about OHRP’s practice of enforcing 

compliance with the Common Rule 

through the institutions that are engaged 

in human subjects research, the ANRPM 

also suggested that appropriate 

accompanying changes could be made 

in enforcement procedures to hold 

external IRBs directly accountable for 

compliance with certain regulatory 

requirements.106 This change was 

discussed only for U.S. sites in multiinstitutional studies. The ANPRM 

suggested that, in most cases, 

independent local IRB reviews of 

international sites are appropriate 

because it might be difficult for an IRB 

in the U.S. to adequately evaluate local 

conditions in a foreign country that 

could play an important role in the 

ethical evaluation of the study. 

This issue attracted a large number of 

comments, and revealed nearly evenly 

divided perspectives. Researchers and 

disease advocacy groups tended to favor 

the single IRB review requirement. IRB 

and institutional representatives tended 

to be opposed to the possible 

requirement, though many indicated 

single IRB review should be encouraged. 

Support was especially strong for single 

IRB review for cooperative clinical trials 

for which the evaluation of a study’s 

social value, scientific validity, and 

risks and benefits, and the adequacy of 

the informed consent form and process 

generally do not require the unique 

perspective of a local IRB. Moreover, 

depending on the nature of the study, 

FDA may not permit differences in 

protocols across sites, which further 

bolstered commenters’ views that the 

requirements be harmonized across the 

Common Rule and FDA requirements. 

Commenters reported incidences of 

IRBs continuously second-guessing each 

other, which delayed studies to the 

point that subject recruitment 

opportunities were foregone or lost. 

This problem seemed especially critical 

in studies of rare diseases and cancers, 

which nearly always involve multiple 

research sites. 

Support for the use of a single IRB, 

however, was not restricted to clinical 

trials. Several commenters cited long 

delays and burdensome requirements 

resulting from multiple reviews of 

studies in the behavioral and social 

sciences. In addition to the view that 

these administrative requirements do 

not enhance protections, supporters of a 

single IRB review of cooperative studies 

cited the frequent need for maintaining 

consistency across sites, which can be 

degraded by multiple reviews. 

Despite support for the ANPRM 

suggestion, several commenters 

expressed concern about making such a 

provision mandatory, stating that the 

current regulations at §ll.114 

currently permit the use of joint review 

arrangements for cooperative research. 

They noted that although this option 

exists, institutions might be hesitant to 

use it because of liability concerns and 

the unwillingness of institutions or IRBs 

to rely on the judgment of other 

institutions or IRBs. However, several 

commenters expressed concern about 

signaling the acceptability of a single 

IRB for review while allowing 

institutions to continue to conduct their 

own ethics review, fearing that such a 

policy would not correct the current 

situation, which tends to favor multiple 

reviews. Thus, they commented that 

mandating a single IRB might be the 

only way to achieve the goals of 

streamlining review while ensuring 

protections. 

Another issue raised was the need to 

set clearer expectations of the 

responsibilities of local IRBs that are not 

designated as the central IRB. A number 

of commenters supporting the 

requirement for a central IRB also 

requested that OHRP issue guidance on 

how to select the IRB, responsibilities of 

all parties, and clarifying compliance 

and enforcement policies. Several 

commenters also requested that OHRP 

develop a template for reliance 

agreements to replace inter-institutional 

agreements currently in use. 

Those who expressed concern about 

the use of a single IRB said some 

studies, especially in the behavioral and 

social sciences, might involve 

significant contextual issues reflecting 

community norms, standards, and 

practices, or local culture and customs. 

Use of a distant IRB might not consider 

and best protect subjects based on 

community norms. Others noted that 

such concerns can be addressed by 

investigators or IRBs submitting ‘‘points 

to consider’’ regarding significant 

contextual or cultural considerations of 

relevance to their site. 

A primary issue posed by those 

opposed to mandating use of a single 

IRB in cooperative studies focused on 

potential loss of accountability and 

increased liability for the institutions 


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107Office for Human Research Protections. (2010, 

November 10). Identifying the Point When 

Continuing Review is no Longer Necessary. 

Retrieved from Guidance on IRB Continuing Review 

of Research: http://www.hhs.gov/ohrp/policy/

continuingreview2010.html#section-k. 

where the research is conducted but 

where the reviewing IRB is not located. 

Streamlining Documentation 

Requirements for Expedited Studies: 

Under the current Common Rule, 

investigators typically must submit the 

same documents including a detailed 

protocol, informed consent forms, and 

any other supporting documents, 

regardless of whether the study will be 

reviewed by a convened IRB or be 

approved by the expedited review 

process. The ANPRM suggested that 

although it is important to document 

why research qualifies for expedited 

review, it is unclear whether the time 

and effort expended in such preparation 

activities result in increased benefit in 

terms of protecting subjects. 

The ANPRM further suggested that 

standard templates for protocols and 

consent forms and sample versions of 

those documents that are specifically 

designed for use in the most common 

types of studies might facilitate 

expedited review. Such forms would 

need to be carefully designed to 

eliminate those elements that are of 

relevance only in studies that pose 

greater than minimal risks and to 

substantially reduce the current burden 

of researchers involved in producing 

these documents and of the IRB 

members who review them. The 

ANPRM asked whether there were 

specific changes that could be made to 

reduce the burden imposed on 

investigators and their staffs in terms of 

meeting the requirements to submit 

documents to an IRB, without 

decreasing protections to subjects. 

There were few comments on 

streamlining the document submission 

requirements for expedited review, and 

there was no consensus among those 

who did comment about how to achieve 

that goal. 

Continuing Review: The ANPRM 

asked for public comments on 

eliminating continuing review for all 

minimal risk studies that undergo 

expedited review, unless the reviewer 

explicitly justifies why continuing 

review would enhance protection of 

research subjects. 

Additionally, the ANPRM suggested 

that, for studies initially reviewed by a 

convened IRB, continuing review would 

not be required after the study reaches 

the stage where procedures are limited 

to either: (1) Analyzing data (even if it 

is identifiable), or (2) accessing followup clinical data from procedures that 

subjects would undergo as part of 

standard care for their medical 

condition or disease (such as periodic 

CT scans to monitor whether the 

subjects’ cancers have recurred or 

progressed) unless specifically 

mandated by the IRB,. This would be a 

change from the current Rules, which 

require at least expedited IRB review of 

the activities described in (1) and (2) 

above. The requirement that research 

involving greater than minimal risk be 

reviewed by a convened IRB would not 

be changed from the current system. 

By eliminating the requirement for 

continuing review of these activities, the 

ANPRM suggested that this change 

would allow for more effective use of 

IRBs’ time by enabling the IRB to focus 

on reviewing information that is 

necessary to ensure protection of 

research subjects. Requiring annual 

continuing review of research studies 

involving only activities that are already 

well-documented to generally involve 

no more than minimal risk may provide 

little if any added protection to subjects, 

and it may be preferable for IRB 

resources to be devoted to research that 

poses greater than minimal risk. 

The ANPRM asked for public 

comment on whether it would be 

appropriate to require IRBs to submit 

periodic reports to OHRP in the 

instances in which they choose to 

override the default policy of no 

continuing review required for the 

situations described above. The 

information, if collected by OHRP, 

might be useful in developing future 

guidance or revising the categories of 

research eligible for expedited review. 

A large majority of public comments 

were in favor of the suggested revisions. 

Many were comfortable with continuing 

to allow IRBs or reviewers the discretion 

to require continuing review in certain 

circumstances, citing the historical 

position of OHRP in considering the 

regulations as the floor, rather than the 

ceiling, for protecting the subjects of 

research. Those who were opposed to 

the revisions cited concerns about 

institutional liability, the possibility for 

increased noncompliance among 

investigators no longer required to 

‘‘check in,’’ and possible breakdowns in 

lines of communications between 

investigators and IRBs. Others expressed 

concerns about how an IRB will know 

that a study has ended and suggested 

that investigators be required to file a 

notice of closure of a study. 

Note that the November 10, 2010, 

document entitled, ‘‘Guidance on IRB 

Continuing Review of Research’’ states: 

OHRP is aware that many IRBs require 

investigators to submit final closeout reports 

when a research study is completed or no 

longer involves human subjects. Since the 

HHS regulations at 45 CFR part 46 do not 

require submission of such reports, 

institutions are free to decide whether and 

when such reports are required and what 

their content should include.107

Commenters overwhelmingly 

opposed requiring IRBs to periodically 

report on the instances when they (or a 

reviewer) elect to override the default 

position of no continuing review 

required. The reasons for opposition 

included: (1) Additional administrative 

burden that would negate the reduced 

burden gained; (2) the possibility that 

requiring such reporting would 

discourage IRBs/reviewers from making 

an override decision; and (3) concerns 

that such reports would lead to OHRP 

second-guessing IRB decisions and 

imposing compliance oversight in an 

extra-regulatory decision. Several 

commenters suggested that OHRP could 

use other means than this requirement 

for developing guidance and improving 

educational efforts regarding expedited 

and continuing review. 

5. Improving Harmonization 

The ANPRM did not suggest any 

specific approaches to harmonization 

but asked for public comment on a set 

of questions focused on: (1) The extent 

to which differences in guidance on 

research protections from different 

agencies strengthen or weaken 

protections for human subjects; (2) the 

extent to which differences in guidance 

on research protections from different 

agencies facilitate or inhibit the conduct 

of research domestically and 

internationally; and (3) the desirability 

of all Common Rule agencies issuing 

one set of guidance. 

Responses to questions about the need 

for harmonization across Common Rule 

agencies reflected widespread support 

for such efforts. Several commenters 

acknowledged the difficulty of getting 

all Common Rule agencies to agree on 

all issues, as each has a different 

mission and research portfolio. 

However, they encouraged seeking 

harmonized guidance whenever 

possible. 

Regulatory Text 

For the reasons set forth in the 

preamble, it is proposed that the Federal 

Policy for the Protection of Human 

Subjects be amended as follows: 

PART llPROTECTION OF HUMAN 

SUBJECTS 

ll.101 To what does this policy apply? 

ll.102 Definitions for purposes of this 

policy. 


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Federal Register / Vol. 80, No. 173 / Tuesday, September 8, 2015 / Proposed Rules 54045 

1Under this provision, only 45 CFR part 46, 

subpart A, applies to all clinical trials meeting the 

applicable conditions. This provision does not 

require clinical trials to comply with the 

requirements of 45 CFR part 46, subparts B, C, and 

D. 

ll.103 Assuring compliance with this 

policy—research conducted or supported 

by any Federal department or agency. 

ll.104 Exempt research. 

ll.105 Protection of biospecimens and 

identifiable private information. 

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 provided in paragraph 

(b) of this section, and as detailed in 

§ ll.104, this policy applies to the 

research described in paragraphs (a)(1) 

and (2) of this section. The entities that 

must comply with this policy are 

institutions that are engaged in research 

described in paragraphs (a)(1) or (2) of 

this section, and institutional review 

boards (IRBs) reviewing research that is 

subject to this policy. 

(1) 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. 

(2) All clinical trials as defined by this 

policy, irrespective of funding source, 

that meet all of the following 

conditions: 

(i) The clinical trials are conducted by 

an institution that receives support from 

a Federal department or agency for 

human subjects research that is not 

excluded from this policy under 

§ ll.101(b)(2) and does not qualify for 

exemption in accordance with 

§ ll.104; 

(ii) The clinical trials are not subject 

to regulation by the Food and Drug 

Administration; and 

(iii) The clinical trials are conducted 

at an institution located within the 

United States.1

(b) The following categories of 

activities are excluded from this policy, 

and no procedural, recordkeeping, or 

other requirements of this policy apply 

to the activities other than the 

conditions specified for the relevant 

category or categories: 

(1) The following activities are 

excluded because they are deemed not 

to be research, as defined in 

§ ll.102(l), for the purposes of this 

regulation: 

(i) Data collection and analysis, 

including the use of biospecimens, for 

an institution’s own internal operational 

monitoring and program improvement 

purposes, if the data collection and 

analysis is limited to the use of data or 

biospecimens originally collected for 

any purpose other than the currently 

proposed activity, or is obtained 

through oral or written communications 

with individuals (e.g., surveys or 

interviews). 

(ii) Oral history, journalism, 

biography, and historical scholarship 

activities that focus directly on the 

specific individuals about whom the 

information is collected. 

(iii) Collection and analysis of data, 

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. 

(iv) Quality assurance or 

improvement activities involving the 

implementation of an accepted practice 

to improve the delivery or quality of 

care or services (including, but not 

limited to, education, training, and 

changing procedures related to care or 

services) if the purposes are limited to 

altering the utilization of the accepted 

practice and collecting data or 

biospecimens to evaluate the effects on 

the utilization of the practice. This 

exclusion does not cover the evaluation 

of an accepted practice itself. 

(v) Public health surveillance 

activities, including the collection and 

testing of biospecimens, conducted, 

supported, requested, ordered, required, 

or authorized by a public health 

authority and limited to those necessary 

to allow the public health authority to 

identify, monitor, assess, or investigate 

potential public health signals or the 

onset of a disease outbreak, including 

trends, or signals, and patterns in 

diseases, or a sudden increase in 

injuries from using a consumer product, 

or conditions of public health 

importance, from data, and including 

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. 

(vi) Surveys, interviews, surveillance 

activities and related analyses, or the 

collection and use of biospecimens 

conducted by a defense, national 

security, or homeland security authority 

solely for authorized intelligence, 

homeland security, defense, or other 

national security purposes. 

(2) The following activities are 

excluded because they are considered to 

be low-risk human subjects research, 

when already subject to independent 

controls without application of these 

regulatory requirements. These 

exclusions do not apply when the 

research includes the collection or 

analysis of biospecimens. All of the 

following exclusion categories apply to 

research subject to this policy and to 

research subject to the additional 

requirements of 45 CFR part 46, 

subparts B, C, and D, however, the 

exclusion at paragraph (b)(2)(i) of this 

section applies only to research subject 

to subpart D for research involving 

educational tests, or observations of 

public behavior when the investigator 

does not participate in the activities 

being observed. 

(i) Research, not including 

interventions, that involves the use of 

educational tests (cognitive, diagnostic, 

aptitude, achievement), survey 

procedures, interview procedures, or 

observation of public behavior 

(including visual or auditory recording) 

uninfluenced by the investigators, if at 

least one of the following criteria is met: 

(A) The information is recorded by 

the investigator in such a manner that 

human subjects cannot be identified, 

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 


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2The National Commission for the Protection of 

Human Subjects of Biomedical and Behavioral 

Research, The Belmont Report: Ethical Principles 

and Guidelines for the Protection of Human 

Subjects of Research (Apr. 18, 1979). 3 Id. 

at risk of criminal or civil liability or be 

damaging to the subjects’ financial 

standing, employability, educational 

advancement, or reputation; or 

(C) The research will involve a 

collection of information subject to the 

Paperwork Reduction Act of 1995, 44 

U.S.C. 3501 et seq.; research information 

will be maintained on information 

technology that is subject to and in 

compliance with section 208(b) of the EGovernment Act of 2002, 44 U.S.C. 3501 

note; and all of the information 

collected, used, or generated as part of 

the research will be maintained in a 

system or systems of records subject to 

the Privacy Act of 1974, 5 U.S.C. 552a. 

(ii) 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, when either of the following two 

criteria is met: 

(A) These sources are publicly 

available, or 

(B) The information is recorded by the 

investigator in such a manner that 

human subjects cannot be identified, 

directly or through identifiers linked to 

the subjects, the investigator does not 

contact the subjects, and the investigator 

will not re-identify subjects or otherwise 

conduct an analysis that could lead to 

creating identifiable private 

information. 

(iii) Research conducted by a Federal 

department or agency using 

government-generated or governmentcollected information obtained for nonresearch purposes (including criminal 

history data), if the information 

originally involved a collection of 

information subject to the Paperwork 

Reduction Act of 1995, 44 U.S.C. 3501 

et seq.; the information is 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; and all of the 

information collected, used, or 

generated as part of the research is 

maintained in a system or systems of 

records subject to the Privacy Act of 

1974, 5 U.S.C. 552a. 

(iv) Research as defined by this policy 

that involves only data collection and 

analysis involving the recipient’s use of 

identifiable health information when 

such 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 the purpose of 

‘‘public health activities’’ as described 

under 45 CFR 164.512(b). 

(3) The following activities are 

excluded because they are considered to 

be low-risk human subjects research 

activities that do not meaningfully 

diminish subject autonomy. The 

following exclusion category applies to 

research subject to this policy and to 

research subject to the additional 

requirements of 45 CFR part 46, 

subparts B, C, or D. 

(i) The secondary research use of a 

non-identified biospecimen that is 

designed only to generate information 

about an individual that already is 

known, including but not limited to the 

development and validation of certain 

tests and assays (such as research to 

develop a diagnostic test for a condition 

using specimens from individuals 

known to have the condition and those 

known not to have the condition), 

quality assurance and control activities, 

and proficiency testing. 

(ii) [Reserved] 

(c) Department or agency heads retain 

final judgment as to whether a 

particular activity is covered by this 

policy, which judgment shall be 

exercised consistent with the ethical 

principles of the Belmont Report.2

(d) Department or agency heads may 

require additional protections for 

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. Advance public notice will 

be required when those additional 

requirements apply to entities outside of 

the Federal department or agency itself. 

(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 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.3 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 in Belmont Report. Each 

Federal department or agency 

conducting or supporting the research 

must establish, on a publicly accessible 

federal Web site, a list of the research 

for which a waiver has been issued. 

(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) Transition provisions—(1) 

Research initiated prior to the 

compliance dates. Ongoing human 

subjects research in which human 

subjects (as defined by this policy) were 

involved prior to the compliance dates 

for the cited provisions need not comply 

with the additional requirements of this 

subpart at §§ ll.101(a)(2), ll.103(e), 

ll.104(c) through (f), ll.105, 

ll.108(a)(2), ll.109(f)(2), 

ll.111(a)(7) and (8), ll.114, 

ll.115(a)(10) and (11), ll.116, and 

ll.117 that became effective on 

[effective date of the final rule]. 


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(2) Use of prior collections of 

biospecimens. Research involving the 

use of prior collections of biospecimens 

that meets both of the following criteria 

need not comply with the requirements 

of these regulations: 

(i) The biospecimens were collected 

for either research or non-research 

purposes before the compliance date for 

the additional requirements of this 

subpart at § ll.102(e)(1)(iii), and 

(ii) Research use of the biospecimens 

occurs only after removal of any 

individually identifiable information 

associated with the biospecimens. 

§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, 

HHS, and any other officer or employee 

of any Federal department or agency to 

whom the authority provided to the 

department or agency head by these 

regulations 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., HHS, the 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 data through intervention 

or interaction with the individual, and 

uses, studies, or analyzes the data; 

(ii) Obtains, uses, studies, analyzes, or 

generates identifiable private 

information; or 

(iii) Obtains, uses, studies, or analyzes 

biospecimens. 

(2) Intervention includes both 

physical procedures by which data 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 shared or made 

public (e.g., a medical record or 

clinically obtained biospecimen). 

(5) Identifiable private information is 

private information that is individually 

identifiable (i.e., the identity of the 

subject is or may readily be ascertained 

by the investigator or associated with 

the information). 

(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. 

(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. The Secretary of HHS will 

maintain guidance that includes a list of 

activities considered to involve no more 

than minimal risk. This list will be reevaluated no later than every 8 years 

based on recommendations from the 

Federal departments and agencies and 

the public. 

(k) Public health authority (consistent 

with 45 CFR 164.501) 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 

service programs may include research 

activities. 

§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 excluded 

from this policy under §ll.101(b) or 

eligible for exemption under 

§ ll.104(d), 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 

federalwide 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. 

(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 


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otherwise condition or restrict the 

assurance. 

(d) Certification is required when the 

research is supported by a Federal 

department or agency and not otherwise 

excluded under § ll.101(b), waived 

under §ll.101(i), or exempted under 

§ ll.104(d), (e), or (f)(2). Institutions 

shall certify that each proposal for 

research covered by this §ll.103 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 §ll.103 be 

initiated prior to receipt of the 

certification that the research has been 

reviewed and approved by the IRB. 

(e) For non-exempt research involving 

human subjects covered by 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 

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., in 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 

affiliated with the institution). 

(Approved by the Office of Management 

and Budget under Control Number.) 

§ll.104 Exempt research. 

(a) Unless otherwise required 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 paragraphs (d) 

through (f) of this section are not subject 

to the requirements of this policy, other 

than those specified in the 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 § ll.104 may be applied to 

research conducted under subpart B if 

the conditions of the exemption are met. 

(2) Subpart C. The exemptions at this 

§ ll.104 do not apply to research 

conducted under subpart C, except for 

research aimed at a broader population 

that consists mostly of non-prisoners 

but that incidentally includes some 

number of prisoners. 

(3) Subpart D. Only the exemptions at 

paragraphs (d)(1), (2), (4), (e)(2), and 

(f)(1) and (2) of this section may be 

applied to research conducted under 

subpart D if the conditions of the 

exemption are met. 

(c) Federal departments and agencies 

shall develop a decision tool to assist in 

exemption determinations. Unless 

otherwise required by law, exemption 

determinations shall be 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, or by the investigator or 

another individual at the institution 

who enters accurate information about 

the proposed research into the decision 

tool, which will provide a 

determination as to whether the study is 

exempt. If the decision tool is used, 

further assessment or evaluation of the 

exemption determination is not 

required. An institution or, when 

appropriate, the IRB, must maintain 

records of exemption determinations 

made for research subject to the 

requirements of this policy for which 

the institution or IRB exercises oversight 

responsibility. These 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. 

Maintenance of the completed decision 

tool shall be considered to fulfill this 

recordkeeping requirement. 

(1) For studies exempted pursuant to 

paragraph (d)(2) of this section, the 

recordkeeping requirement will be 

deemed satisfied by the published list 

required at paragraph (d)(2)(i) of this 

section. 

(2) [Reserved]. 

(d) The following categories of exempt 

human subjects research generally 

involve a low-risk intervention with 

human subjects, must be recorded as 

required in paragraph (c) of this section, 

and do not require application of 

standards for information and 

biospecimen protection provided in 

§ ll.105 or informed consent. Only 

paragraph (d)(2) of this section allows 

for the collection and use of 

biospecimens: 

(1) Research conducted in established 

or commonly accepted educational 

settings when it specifically involves 

normal educational practices. 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 that are not likely to adversely 

impact students’ opportunity to learn 

required educational content in that 

educational setting or the assessment of 

educators who provide instruction. 

(2) 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, and that 

are designed to study, evaluate, 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. 

(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 prescribe, 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 or upon 

commencement of the research. 

(ii) [Reserved] 

(3)(i) Research involving benign 

interventions in conjunction with the 

collection of data from an adult subject 

through verbal or written responses 

(including data entry) or video 

recording if the subject prospectively 

agrees to the intervention and data 

collection and at least one of the 

following criteria is met: 

(A) The information obtained is 

recorded in such a manner that human 

subjects cannot be identified directly or 

through identifiers linked to the 

subjects; or 

(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. 

(ii) For the purpose of this provision, 

benign 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. 

If these criteria are met, such benign 

interventions might include research 

activities in which a subject is asked to 

read materials, review pictures or 

videos, play online games, solve 

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(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 as described in 

paragraph (d)(3)(iv) of this section. 

(iv) For the purpose of this provision, 

authorized deception is 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. 

(4) 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. 

(e) The following categories of exempt 

human subjects research allow for the 

collection of sensitive information about 

human subjects, must not involve 

biospecimens, must be recorded as 

required in paragraph (c) of this section, 

and require application of standards for 

information and biospecimen protection 

provided in § ll.105: 

(1) Research, not including 

interventions, involving the use of 

educational tests (cognitive, diagnostic, 

aptitude, achievement), survey 

procedures, interview procedures, or 

observation of public behavior 

(including visual or auditory recording), 

if the information obtained is recorded 

in such a manner that human subjects 

can be identified directly or through 

identifiers linked to the subjects. 

(2) Secondary research use of 

identifiable private information that has 

been or will be acquired for nonresearch purposes, if the following 

criteria are met: 

(i) Prior notice has been given to the 

individuals to whom the identifiable 

private information pertains that such 

information may be used in research; 

and 

(ii) The identifiable private 

information is used only for purposes of 

the specific research for which the 

investigator or recipient entity requested 

access to the information. 

(f) The following categories of exempt 

human subjects research involve 

biospecimens or identifiable private 

information, must be recorded as 

required in paragraph (c) of this section, 

require application of standards for 

information and biospecimen protection 

as described in §ll.105, and require 

informed consent and limited IRB 

review to the extent described in each 

category or otherwise required by law: 

(1)(i) Storage or maintenance for 

secondary research use of biospecimens 

or identifiable private information that 

have been or will be acquired for 

research studies other than for the 

proposed research study, or for nonresearch purposes, if the following 

criteria are met: 

(A) Written consent for the storage, 

maintenance, and secondary research 

use of the information or biospecimens 

is obtained in accordance with 

§ ll.116(c) and (d)(2), and the 

template published by the Secretary of 

HHS in accordance with §ll.116(d)(1) 

must be used. Oral consent, if obtained 

during the original data collection and 

in accordance with §ll.116(c) and 

(d)(3), would be satisfactory for the 

research use of identifiable private 

information initially acquired in 

accordance with activities excluded 

from this policy under 

§ ll.101(b)(2)(i) or exempt from this 

policy in accordance with 

§ ll.104(d)(3) or (4), or 

§ ll.104(e)(1); 

(B) The reviewing IRB makes the 

determinations required by 

§ ll.111(a)(9). 

(ii) [Reserved.] 

(2)(i) Research involving the use of 

biospecimens or identifiable private 

information that have been stored or 

maintained for secondary research use, 

if consent for the storage, maintenance, 

and secondary research use of the 

information and biospecimens was 

obtained as detailed in paragraph 

(f)(1)(i)(A) of this section. 

(ii) If the investigator anticipates that 

individual research results will be 

provided to a research subject, the 

research may not be exempted under 

this provision and must be reviewed by 

the IRB and informed consent for the 

research must be obtained to the extent 

required by § ll.116(a) and (b). 

§ll.105 Protection of biospecimens and 

identifiable private information. 

(a) In General. Institutions and 

investigators conducting research that is 

subject to this policy, or that is exempt 

from this policy under §ll.104(e) or 

(f), involving the collection, storage, or 

use of biospecimens or identifiable 

private information, shall implement 

and maintain reasonable and 

appropriate safeguards as specified in 

paragraph (b) of this section to protect 

biospecimens or identifiable private 

information that they collect, obtain, 

receive, maintain, or transmit for 

research. The safeguards shall 

reasonably protect against anticipated 

threats or hazards to the security or 

integrity of the information or 

biospecimens, as well as reasonably 

protect the information and 

biospecimens from any intentional or 

unintentional use, release, or disclosure 

that is in violation of paragraph (c) of 

this section. IRB review of the 

safeguards required by this section is 

not required, except to the extent 

required by § ll.104(f)(1). 

(b) Safeguards requirements. The 

Secretary of HHS shall establish and 

publish for public comment a list of 

specific measures that the institution or 

investigator may implement that will be 

deemed to satisfy the requirement for 

reasonable and appropriate safeguards. 

The list will be evaluated as needed, but 

at least every 8 years, and amended, as 

appropriate, after consultation with 

other Federal departments and agencies. 

The institutions and investigators 

identified in paragraph (a) of this 

section shall implement paragraph (a) of 

this section by choosing either to apply 

the safeguards identified by the 

Secretary as necessary to protect the 

security or integrity of and limit 

disclosure of biospecimens and 

electronic and non-electronic 

identifiable private information, or to 

apply safeguards that meet the 

standards in 45 CFR 164.308, 164.310, 

164.312, and 45 CFR 164.530(c). For 

Federal departments and agencies that 

conduct research activities that is or 

will be maintained on information 

technology that is subject to and in 

compliance with section 208(b) of the EGovernment 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., these 

research activities automatically will be 

considered in compliance with the 

Secretary’s reasonable and appropriate 

safeguards standards, unless or until 

any additional safeguards are identified 

by the Secretary of HHS. 

(c) Limitations on use, release, and 

disclosure. Unless otherwise required by 

law, institutions and investigators shall 

use or release biospecimens or use or 

disclose identifiable private information 

collected or maintained for research 

only: 

(1) For human subjects research 

regulated by this policy; 

(2) For public health purposes; 

(3) For any lawful purpose with the 

consent of the subject; or 


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(4) For other research purposes if the 

institution or investigator has obtained 

adequate assurances from the recipient 

that 

(i) The recipient will implement and 

maintain the level of safeguards 

required by paragraph (b) of this section; 

(ii) Except for research that qualifies 

for exclusion under §ll.101(b) or 

exemption under § ll.104 the 

releasing or disclosing institution or 

investigator shall obtain documentation 

from the recipient that the research has 

been approved under §ll.111 to the 

extent required before releasing 

biospecimens or disclosing identifiable 

private information; and 

(iii) The recipient shall not further 

release the biospecimens or disclose 

identifiable private information except 

for human subjects research regulated 

by this policy, or for other purposes 

permitted by this paragraph. For the 

purposes of this requirement, an 

institution or investigator shall obtain 

adequate assurances through the use of 

a written agreement with the recipient 

that the recipient will abide by these 

conditions. 

(d) The provisions of this section do 

not amend or repeal, and shall not be 

construed to amend or repeal, the 

requirements of 45 CFR parts 160 and 

164 for the institutions or investigators, 

including Federal departments or 

agencies, to which these regulations are 

applicable pursuant to 45 CFR 160.102. 

§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, 

pregnant women, physically or mentally 

disabled persons, 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 such 

changes in approved research, during 

the period for which IRB approval has 

already been given, may not be initiated 

without IRB review and approval 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. 

§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 that do not 

qualify for exemption pursuant to 

§ ll.104(d), (e), or (f)(2). 

(b) 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 

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 

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 


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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 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 

(B) Accessing follow-up clinical data 

from procedures that subjects would 

undergo as part of standard care for 

their medical condition; or 

(iii) Research reviewed by the IRB in 

accordance with the limited IRB review 

procedure described in § ll.111(a)(9). 

(2) The IRB must receive confirmation 

on an annual basis that the research is 

still ongoing and that no changes have 

been made to the research that would 

require the IRB to conduct continuing 

review of the research. 

(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.) 

§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, 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 that is being reviewed to 

determine whether it qualifies for 

exemption in accordance with 

§ ll.104(f)(1) in order to determine 

that the requirements of §ll.111(a)(9) 

are satisfied. 

(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 non-expedited 

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 and 

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, 

pregnant women, physically or mentally 

disabled persons, 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, in 

accordance with, and to the extent 

required by, § 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, in addition to 

the requirements in §ll.105, if the 

IRB determines that the standards for 

information and biospecimen protection 

in §ll.105 are not sufficient to protect 

the privacy of subjects and the 

confidentiality of data. 

(8) If the investigator proposes a 

research plan for returning clinically 

relevant results to subjects, that the plan 

is appropriate. 

(9) For purposes of conducting the 

limited IRB review as required by 

§ ll.104(f)(1), the IRB need not make 

the determinations at paragraphs (a)(1) 

through (8) of this section, and shall 

determine that the following 

requirements are satisfied: 

(i) The procedures for obtaining broad 

consent for storage, maintenance, and 

secondary research use of biospecimens 

or identifiable private information will 

be conducted in accordance with the 

requirements of the first paragraph in 

§ ll.116. 

(ii) If there will be a change for 

research purposes in the way the 

biospecimens or information are stored 

or maintained, that the privacy and 

information protection standards at 

§ ll.105 are satisfied for the creation 

of any related storage database or 

repository. 

(b) When some or all of the subjects 

are likely to be vulnerable to coercion or 

undue influence, such as children, 

prisoners, pregnant women, physically 

or mentally disabled persons, or 

economically or educationally 

disadvantaged persons, additional 

safeguards have been included in the 

study to protect the rights and welfare 

of these subjects. 

§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 


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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.) 

§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 selected by the Federal department or 

agency supporting or conducting the 

research or, if there is no funding 

agency, by the lead institution 

conducting the research. 

(2) The following research is not 

subject to the requirements of this 

provision: 

(i) Cooperative research for which 

more than single IRB review is required 

by law; or 

(ii) 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. 

(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 has progressed to the point 

that it involves only one or both of the 

following: 

(i) Data analysis, including analysis of 

identifiable private information, or 

(ii) Accessing follow-up clinical data 

from procedures that subjects would 

undergo as part of standard care for 

their medical condition. 

(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(b)(5). 

(8) The rationale for requiring 

continuing review for research that 

otherwise would not require continuing 

review as described in §ll.109(f)(1). 

(9) The rationale for an expedited 

reviewer’s determination that research 

appearing on the expedited review list 

described in § ll.110(b)(1)(i) is more 

than minimal risk. 

(10) The written agreement between 

an institution and an organization 

operating an IRB specifying the 

responsibilities that each entity will 

undertake to ensure compliance with 

the requirements of this policy, as 

described in § ll.103(e). 

(11) Records relating to exemption 

determinations, as described in 

§ ll.104(c). 

(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. 

(c) The institution or IRB retaining the 

records shall safeguard identifiable 

private information contained within 

these records in compliance with 

§ ll.105. 

(Approved by the Office of Management 

and Budget under Control Number.) 

§ll.116 General requirements for 

informed consent. 

Except as provided elsewhere in this 

policy, no investigator may involve a 

human subject in research covered by 

this policy unless the investigator has 

obtained the legally effective informed 

consent of the subject or the subject’s 

legally authorized representative. An 

investigator shall seek such consent 

only under circumstances that provide 

the prospective subject or the 

representative sufficient opportunity to 

consider whether or not to participate 

and that minimize the possibility of 

coercion or undue influence. The 

information that is given to the subject 

or the representative shall be in 

language understandable to the subject 

or the representative. The prospective 

subject or the 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. 

The information must be presented in 

sufficient detail relating to the specific 

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 

representative’s understanding of the 

reasons why one might or might not 

want to participate. In obtaining 

informed consent, the investigator must 

present first the information required by 

this section, before providing other 

information, if any, to the subject or the 

representative. Any informed consent 

form must include only the 

requirements of informed consent under 

this section, and appendices that 

include any other information provided 

to the subject or the representative. If an 

authorization required by 45 CFR parts 

160 and 164 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. No informed consent, 

whether oral or written, may include 

any exculpatory language through 

which the subject or the 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. 


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(a) Basic elements of informed 

consent. Except as provided in 

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

in seeking informed consent the 

following information shall be provided 

to each subject or the 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: 

(i) A statement that identifiers might 

be removed from the data and the data 

that is not identifiable 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 

(ii) A statement that the subject’s data 

collected as part of the research, from 

which identifiers are removed, will not 

be used or distributed for future 

research studies. 

(b) Additional elements of informed 

consent. Except as provided in 

paragraphs (c), (e), or (f) of this section, 

when appropriate, one or more of the 

following elements of information shall 

also be provided to each subject or the 

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 

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 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) An option for the subject or the 

representative 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. 

(c)(1) Elements of informed consent 

for broad consent to the storage, 

maintenance, and secondary research 

use of biospecimens or identifiable 

private information. If the subject or the 

representative will be asked to provide 

broad consent to the storage or 

maintenance of biospecimens or 

identifiable private information, 

collected for either research studies 

other than the proposed research or 

non-research purposes, and the 

secondary research use of this stored 

material, the information required in 

paragraphs (a)(2), (3), (5), and (7) and, if 

applicable, (b)(7) through (9) of this 

section, shall be provided to each 

subject, with the following additional 

information: 

(i) A general description of the types 

of research that may be conducted with 

information and biospecimens and the 

information that is expected to be 

generated from the research, the types of 

information or biospecimens that might 

be used in research, and the types of 

institutions that might conduct research 

with the biospecimens or information; 

(ii) A description of the scope of the 

informed consent must be provided, 

including: 

(A) A clear description of the types of 

biospecimens or information that were 

or will be collected and the period of 

time during which biospecimen or 

information collection will occur. This 

may include all biospecimens and 

information from the subject’s medical 

record or other records existing at the 

institution at the time informed consent 

is sought; and 

(B) For purposes of paragraph 

(c)(1)(ii)(A) of this section, the period of 

time during which biospecimen or 

information collection will occur cannot 

exceed 10 years from the date of 

consent. For research involving children 

as subjects, that time period cannot 

exceed 10 years after parental 

permission is obtained or until the child 

reaches the legal age for consent to the 

treatments or procedures involved in 

the research, whichever time period is 

shorter. The time limitations described 

do not apply to biospecimens or 

information that initially will be 

collected for research purposes. 

(iii) A description of the period of 

time during which an investigator can 

continue to conduct research using the 

subject’s biospecimens and information 

described in paragraph (c)(1)(ii)(A) of 

this section (e.g., a certain number of 

years, or indefinitely); 

(iv) 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 that the subject 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, and 

information about whom to contact in 

order for the subject to withdraw 

consent. The statement must make clear 

that information or biospecimens that 

already have been distributed for 

research use may not be retrieved; 

(v) If applicable, a statement notifying 

the subject or the representative that the 

subject or the representative will not be 

informed of the details of any specific 

research studies that might be 

conducted, including the purposes of 

the research, that will use the subject’s 

information and biospecimens; 

(vi) If applicable, a statement 

notifying the subject or the 


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representative of the expectation that 

the subject’s information and 

biospecimens are likely to be used by 

multiple investigators and institutions 

and shared broadly for many types of 

research studies in the future, and this 

information and the biospecimens might 

be identifiable when shared; 

(vii)The names of the institution or set 

of institutions at which the subject’s 

biospecimens or information were or 

will be collected, to the extent possible 

(in recognition that institutions might 

change names or cease to exist); and 

(viii) If relevant, 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. This option must 

be prominently noted, and must include 

a description of risks of public access to 

the data. 

(2) [Reserved] 

(d)(1) The Secretary of HHS will 

establish, and publish in the Federal 

Register for public comment, templates 

for consent that will contain all of the 

required elements of informed consent 

under paragraph (c) of this section. IRB 

review of the broad secondary use 

informed consent form obtained in 

accordance with paragraph (c) of this 

section is required unless the consent is 

obtained using only this template, 

without any changes. 

(2) If § ll.104(f)(1) requires written 

consent, the consent for research use of 

biospecimens or identifiable private 

information must be documented by the 

use of a written consent form signed by 

the subject or the representative. The 

template for consent for research use 

established by the Secretary may serve 

as the written consent form. A copy 

shall be given to the person signing the 

form. 

(3) If § ll.104(f)(1) allows for oral 

consent, a subject’s or the 

representative’s oral consent for 

research use of identifiable private 

information must be documented such 

that the consent is associated with the 

subject’s identifiable private 

information. If this requirement is met 

through the use of written 

documentation, the subject or the 

representative is not required to sign the 

documentation. 

(4) If the subject or the representative 

declines to consent to the research use 

of biospecimens or identifiable private 

information, this must be documented 

appropriately. 

(e)(1) 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. An IRB may approve a consent 

procedure that does not include, or that 

alters, some or all of the elements of 

informed consent set forth above, or 

waive the above requirement to obtain 

informed consent, provided the IRB 

finds and documents 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. 

(2) Additional criteria for waiver or 

alteration of consent for biospecimens. 

For research involving the use of 

biospecimens, an IRB may approve a 

consent procedure that does not 

include, or that alters, some or all of the 

elements of informed consent set forth 

above, or waive the above requirements 

to obtain informed consent, provided 

the IRB finds and documents the criteria 

in paragraph (e)(1) of this section, and 

the following additional criteria: 

(i) There are compelling scientific 

reasons to conduct the research; and 

(ii) The research could not be 

conducted with other biospecimens for 

which informed consent was obtained 

or could be obtained. 

(3) 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 

requirements of this section at 

paragraph (c) of this section, and 

refused to consent, an IRB cannot waive 

consent for either the storage or 

maintenance for secondary research use, 

or for the secondary research use, of 

those biospecimens or information. 

(f)(1) Waiver or alteration of consent. 

An IRB may approve a consent 

procedure that does not include, or that 

alters, some or all of the elements of 

informed consent set forth above, or 

waive the above requirements to obtain 

informed consent, provided the IRB 

finds and documents 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 accessing 

or using identifiable biospecimens or 

identifiable information, the research 

could not practicably be carried out 

without accessing or using identifiers; 

(iv) The waiver or alteration will not 

adversely affect the rights and welfare of 

the subjects; and 

(v) Whenever appropriate, the 

subjects will be provided with 

additional pertinent information after 

participation. 

(2) Additional criteria for waiver or 

alteration of consent for research 

involving biospecimens. For research 

involving the use of biospecimens, an 

IRB may approve a consent procedure 

that does not include, or that alters, 

some or all of the elements of informed 

consent set forth above, or waive the 

above requirements to obtain informed 

consent, provided the IRB finds and 

documents the criteria in paragraph 

(f)(1) of this section, and the following 

additional criteria: 

(i) There are compelling scientific 

reasons for the research use of the 

biospecimens; and 

(ii) The research could not be 

conducted with other biospecimens for 

which informed consent was obtained 

or could be obtained. 

(3) 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 

requirements of paragraph (c) of this 

section, and refused to consent, an IRB 

cannot waive consent for either the 

storage or maintenance for secondary 

research use, or for the secondary 

research use, of those biospecimens or 

information. 

(g) An IRB may approve a research 

proposal in which investigators obtain, 

through oral or written communication 

or by accessing records, identifiable 

private information without individuals’ 

informed consent for the purpose of 

screening, recruiting, or determining the 

eligibility of prospective human subjects 

of research, provided that the research 

proposal includes an assurance that the 

investigator will implement standards 

for protecting the information obtained, 

in accordance with and to the extent 

required by § ll.105. 

(h)(1) A copy of the final version of 

the informed consent form for each 

clinical trial conducted or supported by 

a Federal department or agency 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 informed 

consent form must be posted in such 

form and manner as the department or 

agency head may prescribe, which will 


asabaliauskas on DSK5VPTVN1PROD with PROPOSALS
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include at a minimum posting, in 

addition to the informed consent form, 

the name of the clinical trial and 

information about whom to contact for 

additional details about the clinical 

trial. 

(2) The informed consent form must 

be posted on the federal Web site within 

60 days after the trial is closed to 

recruitment. 

(i) The informed consent 

requirements in this policy are not 

intended to preempt any applicable 

Federal, state, or local laws that require 

additional information to be disclosed 

in order for informed consent to be 

legally effective. 

(j) 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. 

(Approved by the Office of Management 

and Budget under Control Number.) 

§ll.117 Documentation of informed 

consent. 

(a) Except as provided in paragraph 

(c) of this section, and except for 

research for which consent is obtained 

in accordance with §ll.116(c), 

informed consent shall be documented 

by the use of a written informed consent 

form approved by the IRB and signed by 

the subject or the subject’s legally 

authorized representative. A copy shall 

be given to the person signing the 

informed consent form. 

(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 includes a form containing only the 

information required by § ll.116, and 

appendices that include any other 

information. 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 

information required by § ll.116 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 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 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 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 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 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. 

Documentation must include a 

description as to why signing forms is 

not the norm for the distinct cultural 

group or community. 

(2) In cases in which the 

documentation requirement is waived, 

the IRB may require the investigator to 

provide subjects with a written 

statement regarding the research. 

(3) This waiver does not apply to 

research for which consent is required 

to be documented in accordance with 

§ ll.116(d)(2), (3), or (4). 

(4) Documentation of informed 

consent may not be waived under 

paragraphs (c)(1)(i) or (iii) of this section 

for research subject to regulation by the 

Food and Drug Administration unless 

otherwise authorized by 21 CFR 

56.109(c)(1). 

(Approved by the Office of Management 

and Budget under Control Number.) 

§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 excluded under 

§ ll.101(b), waived under 

§ ll.101(i), or exempted under 

§ ll.104(d), (e), or (f)(2), 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 excluded under 

§ ll.101(b), waived under 

§ ll.101(i), or exempted under 

§ ll.104(d), (e), or (f)(2), 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. 


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54056 Federal Register / Vol. 80, No. 173 / Tuesday, September 8, 2015 / Proposed Rules 

§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 

additional conditions are necessary for 

the protection of human subjects. 

DEPARTMENT OF HOMELAND 

SECURITY 

6 CFR Part 46 

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 proposes to add 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 Protection of biospecimens and 

identifiable private information. 

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 

7 CFR Part 1c 

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 

proposes to revise 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 Protection of biospecimens and 

identifiable private information. 

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. 

Catherine Woteki 

Under Secretary for Research, Education, and 

Economics, USDA. 

DEPARTMENT OF ENERGY 

10 CFR Part 745 

List of Subjects in 10 CFR Part 745 

Human research subjects, Reporting 

and record-keeping requirements, 

Research. 

For the reasons stated in the 

preamble, the Department of Energy 

proposes to revise 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 Protection of biospecimens and 

identifiable private information. 

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. 


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745.111 Criteria for IRB approval of 

research. 

745.112 Review by institution. 

745.113 Suspension or termination of IRB 

approval of research. 

745114 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. 

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

Elizabeth Sherwood-Randall, 

Deputy Secretary of Energy. 

NATIONAL AERONAUTICS AND 

SPACE ADMINISTRATION 

14 CFR Part 1230 

List of Subjects in 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 proposes to revise 

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 Protection of biospecimens and 

identifiable private information. 

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. 

Richard S. Williams, 

Chief Health and Medical Officer. 

DEPARTMENT OF COMMERCE 

15 CFR Part 27 

List of Subjects in 15 CFR Part 27 

Human research subjects, Reporting 

and record-keeping requirements, 

Research. 

For the reasons stated in the 

preamble, the Department of Commerce 

proposes to revise 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 Protection of biospecimens and 

identifiable private information. 

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. 

James Hock, 

Chief of Staff, Department of Commerce. 

SOCIAL SECURITY 

ADMINISTRATION 

20 CFR Part 431 

List of Subjects in 20 CFR Part 431 

Human research subjects, Reporting 

and record-keeping requirements, 

Research. 

For the reasons stated in the 

preamble, the Social Security 

Administration proposes to add 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 Protection of biospecimens and 

identifiable private information. 

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. 


asabaliauskas on DSK5VPTVN1PROD with PROPOSALS
54058 Federal Register / Vol. 80, No. 173 / Tuesday, September 8, 2015 / Proposed Rules 

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

Carolyn W. Colvin, 

Acting Commissioner of Social Security. 

AGENCY FOR INTERNATIONAL 

DEVELOPMENT 

22 CFR Part 225 

List of Subjects in 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 proposes to revise 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 Protection of biospecimens and 

identifiable private information. 

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. 

Wade Warren, 

Senior Deputy Assistant Administrator for 

Global Health, U.S. Agency for International 

Development. 

DEPARTMENT OF JUSTICE 

28 CFR Part 46 

AG Order No. 3553–2015 

List of Subjects in 28 CFR Part 46 

Human research subjects, Reporting 

and record-keeping requirements, 

Research. 

For the reasons stated in the 

preamble, the Department of Justice 

proposes to revise 28 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 Protection of biospecimens and 

identifiable private information. 

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; 28 U.S.C. 509– 

510. 

Sally Quillian Yates, 

Deputy Attorney General. 

DEPARTMENT OF LABOR 

29 CFR Part 21 

List of Subjects in 29 CFR Part 21 

Human research subjects, Reporting 

and record-keeping requirements, 

Research. 

For the reasons stated in the 

preamble, the Social Security 

Administration proposes to add 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 Protection of biospecimens and 

identifiable private information. 

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. 


asabaliauskas on DSK5VPTVN1PROD with PROPOSALS
Federal Register / Vol. 80, No. 173 / Tuesday, September 8, 2015 / Proposed Rules 54059 

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

Christopher P. Lu, 

Deputy Secretary of Labor. 

DEPARTMENT OF DEFENSE 

32 CFR Part 219 

List of Subjects in 32 CFR Part 219 

Human research subjects, Reporting 

and record-keeping requirements, 

Research. 

For the reasons stated in the 

preamble, the Department of Defense 

proposes to revise 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 Protection of biospecimens and 

identifiable private information. 

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. 

Patricia L. Toppings, 

OSD Federal Register Liaison, Officer, 

Department of Defense. 

DEPARTMENT OF EDUCATION 

34 CFR Part 97 

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 

proposes to amend 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. 

■ 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 Protection of biospecimens and 

identifiable private information. 

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. 

Arne Duncan, 

Secretary of Education. 

DEPARTMENT OF VETERANS 

AFFAIRS 

38 CFR Part 16 

List of Subjects in 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 proposes to revise 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 Protection of biospecimens and 

identifiable private information. 

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. 


asabaliauskas on DSK5VPTVN1PROD with PROPOSALS
54060 Federal Register / Vol. 80, No. 173 / Tuesday, September 8, 2015 / Proposed Rules 

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

7331, 7334. 

Robert L. Nabors II, 

Chief of Staff, U.S. Department of Veterans 

Affairs, 

ENVIRONMENTAL PROTECTION 

AGENCY 

40 CFR Part 26 

List of Subjects in 40 CFR Part 26 

Human research subjects, Reporting 

and record-keeping requirements, 

Research. 

For the reasons stated in the 

preamble, the Environmental Protection 

Agency proposes to amend 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. 

■ 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 Protection of biospecimens and 

identifiable private information. 

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. 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

45 CFR Part 46 

List of Subjects in 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 proposes to amend 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. 

■ 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 Protection of biospecimens and 

identifiable private information. 

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 

45 CFR Part 690 

List of Subjects in 45 CFR Part 690 

Human research subjects, Reporting 

and record-keeping requirements, 

Research. 

For the reasons stated in the 

preamble, the National Science 

Foundation proposes to revise 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 Protection of biospecimens and 

identifiable private information. 

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. 


asabaliauskas on DSK5VPTVN1PROD with PROPOSALS
Federal Register / Vol. 80, No. 173 / Tuesday, September 8, 2015 / Proposed Rules 54061 

Authority: 5 U.S.C. 301. 

Lawrence Rudolph, 

General Counsel. 

DEPARTMENT OF 

TRANSPORTATION 

49 CFR Part 11 

List of Subjects in 49 CFR Part 11 

Human research subjects, Reporting 

and record-keeping requirements, 

Research. 

For the reasons stated in the 

preamble, the Department of 

Transportation proposes to revise 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 Protection of biospecimens and 

identifiable private information. 

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. 

Anthony R. Foxx, 

Secretary of Transportation. 

[FR Doc. 2015–21756 Filed 9–2–15; 11:15 am] 

BILLING CODE 4150–36–P 


asabaliauskas on DSK5VPTVN1PROD with PROPOSALS