# Presentation: 664212

## Issues Surrounding Human Research Subject Protections

* *
*	**	**	**	**  **Freda E. Yoder, MA    *
- Division of Education
* **Office for Human Research Protections (OHRP)*
*  **Department of Health & Human Services (HHS)*
*NIH – Acquisition Management *
*Committee (AMC) Symposium*
*Hershey, PA*
*October 24, 2006*

## Human Subject Protections 

- Background
- Determining Applicability of the Regulations
- Protections Afforded by the Regulations
- Resources/Contacting OHRP

##             Human Subject Protections

**Subjects**

**Sponsor**

**Advocates**

**IRB**

**Research Team**

**Institutions**

**        **

**Government**

**Public**

**Family**

**Investigator**

## Historical Precedents

- Nazi biomedical studies & trials
- US studies – e.g.,
- Tuskegee – Syphilis (1932-1972)
- Willowbrook (1950s) – hepatitis virus
- Milgram (1960s) – obedience
- Beecher article (1966)
- PHS Policy (1966)
- National Research Act (1974)

##             The Belmont Report

**Ethical Principles and Guidelines for the Protection of Human Subjects of Research**
- The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research
- April 18, 1979

## Ethical Principles

- Three Basic Ethical Principles:
- Respect for Persons
- Beneficence
- Justice

## Regulation for Protection of Human Subjects 

- HHS regulations:  Title 45 CFR part 46
- Subpart A – basic HHS Policy - “The Common Rule” or Federal Policy
- -   Basis IRB & informed consent requirements
- -   Other federal departments & agencies have adopted – FDA has its own
- 	Departments of Agriculture, Energy, Commerce, HUD, Justice, Defense, Education, Veterans Affairs,  Transportation, HHS, & Home land Security.  NSF, NASA, EPA, AID, Social Security Administration*, CIA, and the Consumer Product Safety Commission
-          *only in part

- 6

## Additional HHS Protections

- Subpart B - Pregnant Women, Human Fetuses, and Neonates
- Subpart C - Prisoners
- Subpart D - Children

## 

Determining Applicability of Regulations

*Determining Applicability of Regulations*

## Determining Applicability of Regulations

- Prerequisite:
- Research involving human subjects conducted or supported by HHS and that is not otherwise exempt
- 				OR
- Non-exempt human subject research covered by Assurance of Compliance** **

## Determining Applicability

- Does activity involve Research?
- Does research involve Human Subjects?
- Is human subjects research exempt?

## Does Activity Involve Research?

*Research* - a systematic investigation designed to develop or contribute to generalizable knowledge
- includes research development, testing, and evaluation
**	****	**					 §46.102(c)

## Does Research Involve Human Subjects?

*Human Subject* - a living individual about whom an investigator conducting research obtains
- data through intervention or interaction with the individual, or
- identifiable private information
**	****	****	****	****	****	****	**** ****	****	****	****	**				§46.102(f)

## Identifiable Private Information

- 	Private information must be individually identifiable (i.e., identity of subject is or may readily be ascertained by the investigator or associated with the subject) in order for obtaining the information to constitute research involving human subjects.
- 							    §46.102(f)

## Normal educational practices in established educational settings
Educational tests, surveys, interviews, or observation of public behavior unless identified and sensitive **
Research on elected or appointed public officials or candidates for public office
	*  exception for prisoners **exception for children

- Normal educational practices in established educational settings
- Educational tests, surveys, interviews, or observation of public behavior unless identified _and_ sensitive **
- Research on elected or appointed public officials or candidates for public office
**	***  exception for prisoners **exception for children

- Research using existing data, if publicly available _or_ recorded without identifiers
- Evaluation of public benefit service programs
- Taste and food quality evaluation and consumer acceptance studies
**	****	****	**

** ****Research that is “exempt” includes *******

- §46.101(b)

## Applicability of Regulations 

- Bottom line:  *HHS Regulations protecting human subjects apply to all non-exempt human subject research conducted or supported by HHS (or covered by an Assurance)*
- Decision Charts:*  http://www.hhs.gov/ohrp/humansubjects/guidance/decisioncharts.htm *

## 

Protections Afforded by the Regulations

*Protections Afforded by the Regulations*

## HHS Regulations  (45 CFR part 46)

- HHS will conduct or support non-exempt
- human subject research only if:
- the institution has an OHRP-approved assurance, and
- the institution has certified to HHS
- research was reviewed and approved by IRB, and
- the research will be subject to continuing review**	**
**	****	****	****	****	****	****   **§46.103(b) & (f)
**	****	****	****	****	****	**

##   Basic Protections Afforded by Regulations 

-   Basic Protections Afforded by Regulations

** ****Institutional Assurance**

**IRB Review**

**Informed**** ****Consent**

*Institutional Assurance*

## Institutional Assurance

- “Each institution engaged in research which is covered by this policy and which is conducted or supported by a Federal Department or Agency shall provide written assurance ... that it will comply with the requirements set forth in this policy.”    §46.103(a)
- See OHRP guidance on engagement in research:
- http://www.hhs.gov/ohrp/humansubjects/assurance/engage.htm

## Institutional Assurance, cont’d 

- Negotiated and approved by OHRP
- Terms of Assurance
- Federalwide Assurance (FWA) – only option
- Method of compliance oversight for OHRP
- Generally recognized by other federal departments & agencies
- Registering IRB and filing Federalwide Assurance  (FWA): http://www.hhs.gov/ohrp/assurances
-     http://www.hhs.gov/ohrp/assurances/assurances_index.html

## Who is covered by an Institution’s Assurance? 

- Employees and agents, including students,   involved in the conduct of research covered by the FWA.
- May be extended to collaborating individual investigators in limited circumstances

## Assurance Applications – Extending FWA

- Individual Investigator Agreement (IIA)
- independent investigators
- investigators at another institution
- Assured institution responsible for oversight of research
- Individual investigator must adhere to *Terms* of the IIA
- Guidance available at: http://www.hhs.gov/ohrp/humansubjects/assurance/guidanceonalternativetofwa.htm
- Sample Agreement:  http://www.hhs.gov/ohrp/humansubjects/assurance/unaflsup.rtf

## Assurance Applications –   Relying on External IRB

- Institution responsibility
- Written agreement
- IRB Authorization Agreement
- 	http://www.hhs.gov/ohrp/humansubjects/assurance/iprotsup.rtf
- Designate IRB in FWA
- Ensure research conducted per IRB approved plan
- Procedures for reporting to OHRP

## Institutional Responsibilities

- Institutions bear full responsibility for all research involving human subjects covered by their Assurance
- All requirements of 45 CFR 46 must be met for ***all HHS-conducted or supported*** research
- OHRP strongly encourages institutions to embrace the HHS regulations regardless of sponsorship, and to commit to this standard in their Assurance.

*IRB Review and Approval*

## Institutional Review Board (IRB):  
   A committee charged with the review of human subject research to ensure that the rights and welfare of research subjects are adequately protected.
Why do we need IRB review? 

- Institutional Review Board (IRB):
*   **A committee charged with the review of human subject research to ensure that the rights and welfare of research subjects are adequately protected.*
- Why do we need IRB review?

##  IRB Review

- Ensure rights & welfare of subjects are protected
- Review by IRB designated in assurance
- Must be substantive
- Sufficient information to make required findings at  §46.111 and relevant subpart(s)
- Members with conflicting interest may not participate

*Informed Consent**** ***

## Legally effective informed consent
Each prospective subject or legally authorized representative  
In accordance with and to extent required by §46.116 	
Waiver/alteration consistent with §46.116(c) or (d), § 46.408(c),  or §46.101(i)		

- Legally effective informed consent
- Each prospective subject or legally authorized representative
- In accordance with and to extent required by §46.116
- Waiver/alteration consistent with §46.116(c) or (d), § 46.408(c),  or §46.101(i)	**	**

## Key principles of the informed consent
process:
Full disclosure of the nature of the research and the subject's participation, 
Adequate comprehension on the part of the potential subjects
The subject's voluntary choice to participate

- Key principles of the informed consent
- process:
- Full disclosure of the nature of the research and the subject's participation,
- Adequate comprehension on the part of the potential subjects
- The subject's voluntary choice to participate

## IRB Decision Matrix

- Risk/Benefit Analysis
- Experimental Design
- Qualifications of PI

- Subject selection
- Inclusion/exclusion
- Recruitment

- J. Cooper, Albany Medical Center

## 

OHRP Resources & Guidance

*OHRP Resources & Guidance*

## Reporting Adverse Events & Unanticipated Problems (draft of Oct. 13, 2005 under revision)
Procedures for Reporting Incident to OHRP
Use of Coded Private Information or Biological Specimens
Conflict of Interest
407 Review Process

- Reporting Adverse Events & Unanticipated Problems (draft of Oct. 13, 2005 under revision)
- Procedures for Reporting Incident to OHRP
- Use of Coded Private Information or Biological Specimens
- Conflict of Interest
- 407 Review Process

## IRB Review of Clinical Trial Websites
OHRP’s Compliance Oversight Procedures for Evaluating Institutions
Human Subject Regulations Decision Charts
International Compilation of Human Subject Research Protections 

- IRB Review of Clinical Trial Websites
- OHRP’s Compliance Oversight Procedures for Evaluating Institutions
- Human Subject Regulations Decision Charts
- International Compilation of Human Subject Research Protections

## Engagement of Institutions in Research (revision)
Informed Consent for Subjects Who Do Not Understand English
What Is Research?
Definition of Human Subject
Exempt Human Subject Research  

- Engagement of Institutions in Research (revision)
- Informed Consent for Subjects Who Do Not Understand English
- What Is Research?
- Definition of Human Subject
- Exempt Human Subject Research

## 45 CFR 46
IRB Registration 
Federalwide Assurance
Subpart D
Informed Consent
Investigator Responsibilities

- 45 CFR 46
- IRB Registration
- Federalwide Assurance
- Subpart D
- Informed Consent
- Investigator Responsibilities

## OHRP Web page:  http://www.hhs.gov/ohrp 
Main Phone Number: 240-453-6900
	Toll Free:  1-866-447-47771-866-HHS-HRPP
New Staff Phone Numbers:  http://www.hhs.gov/ohrp/about/staff.html 
IRB Registration & Assurance Staff:   http://www.hhs.gov/ohrp/daqi-staff.html 
E-mail:   ohrp@hhs.gov
Join Listserv: http://www.hhs.gov/ohrp/news/index.html

- OHRP Web page:  http://www.hhs.gov/ohrp
- Main Phone Number: 240-453-6900
- 	Toll Free:  1-866-447-47771-866-HHS-HRPP
- New Staff Phone Numbers:  http://www.hhs.gov/ohrp/about/staff.html
- IRB Registration & Assurance Staff:   http://www.hhs.gov/ohrp/daqi-staff.html
- E-mail:   _[ohrp@hhs.gov](mailto:ohrp@hhs.gov)_
- Join Listserv: http://www.hhs.gov/ohrp/news/index.html

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