# Presentation: 290628

## Human Subjects Protection: Creation and Maintenance of an IRB

***Regulatory Requirements & Recommendations***
***45 CFR part 46***
**Freda E. Yoder**
**Office for Human Research Protections (OHRP) **
**Department of Health and Human Services (HHS)**
**March 30, 2005**
***NARCH Researchers - PI & PD Meeting ***
***	******	******	******	******   ******Indian Health Service ******	******	******	******	******	******      November 9, 2005 ***

## Outline

**Regulatory Background**
**IRB Membership & Responsibilities**
**Written IRB Procedures**
**IRB Records**
**Resources**

## Regulations for Protection of Human Subjects in Research

**HHS regulations at Title 46 CFR part 46**
**Subpart A – common rule or federal ****policy**
**Subparts B, C, & D provide additional protections to certain vulnerable classes of subjects**

## Applicability of Regulations 

**Protections apply to all ****non-exempt human**** ****subject**** ****research **
**conducted or supported by a Federal Department or Agency that has adopted the regulations, **_**OR**_** **
**covered by an Assurance**

## Prerequisite for HHS Conduct or Support of Research

**HHS will conduct or support covered research**
**only if:**
**the institution has an applicable assurance, and only if**
**the institution certifies to the department or agency [conducting/supporting research] that**
**IRB has reviewed and approved the research, and **
**research will be subject to continuing review**
- 							46.103(b)

## Assurance of Compliance

**Documentation of institutional commitment to comply with regulation**
**Principal method of compliance oversight for OHRP**
**Other Federal Departments and Agencies accept a Federalwide Assurance on file with OHRP, in lieu of requiring their own Assurance**

## Assurance of Compliance Includes  

**Statement of principle governing conduct of research**
**Designation of one or more IRB **
**established in accordance with the regulations and **
**for which provisions are made for**
**meeting space**
**sufficient staff to support the IRB’s review and record keeping duties**
**List of IRB members & relevant information **
**Written IRB & institutional procedures**
- 					§46.103(b)

## When is an Assurance Required? 

**	****Each institution ****engaged**** in research, covered by the [Federal] policy, which 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 the policy.**
- 							 §46.103(a)

## 

IRB Membership & Responsibilities

*IRB Membership & Responsibilities*

## Institutional Review Board (IRB)

-     **A committee charged with review of covered human subjects research to assure that the subject’s rights and welfare are adequately protected.**

## IRB Members  

**Regulatory criteria for membership:**
**minimum of 5 members**
**background & expertise appropriate to review research conducted by institution**
**qualification & diversity ... to promote respect for its advice and counsel**
**ability to ascertain acceptability of research in terms of institutional commitments and regulations, applicable law, and standards of professional conduct and practice**
**representation for vulnerable subjects, when appropriate****	**
- 							 §46.107(a)

##   IRB Members (cont)  

**Regulatory criteria for membership:**
**not entirely of same sex and may not consist entirely of members of one profession**
**at least one with primary concerns in scientific areas & at least one in nonscientific areas**
**at least one not affiliated and not immediate family member of anyone affiliated with institution   **
**may not participate in review of any project in which member has a conflicting interest**
**invite other expert to supplement review ****	**					 §46.107(b-f)

## Scientist vs. Non-Scientist

**Scientists include: individuals whose training, background, and occupation would incline them to view scientific activities from the standpoint of a behavioral or biomedical research discipline **
**Non-Scientists include: anyone whose primary concerns are in non-scientific areas**

## IRB Responsibilities, among others

**Review covered research**
**Must be substantive**
**Criteria for approval at §46.111 (and if applicable, subparts B, C, and D) must be satisfied for all covered research**
**Authority to approve, require modifications, or disapprove all covered research   §46.109(a)**
**Authority to suspend or terminate approval of research**
**not conducted in compliance**
**associated with unexpected serious harm to subjects**

## IRB Responsibilities, among others

**Type of Review **
**Review at convened meeting of IRB **
**majority of members present, including non-scientist**
**review & vote on each protocol separately**
**majority present must vote in favor, to approve**
**notify investigators & institution in writing of IRB action/determinations**

## IRB Responsibilities, among others

**Type of Review, cont.**
**Expedited review consistent with §46.110**
**may be used for **
**minor modifications to approved research**
**research no greater than minimal risk & fits category on list (see resource slide)**
**review by chair or by one or more experienced IRB member**
**authority to approve - may not disapprove**
**advise all members of approvals**
**notify investigators & institution in writing of IRB action/determinations**

## IRB Responsibilities, among others (cont)

**When must IRB review research?**
**initial review**
**continuing review**
**prior to initiation of changes to approved research**
**When may expedited review be used?**
**initial review – categories 1 through 7**
**continuing review – categories 8 & 9**
**minor changes to approved research**

## 
 Written IRB Procedures
§46.103(b)(4-5)

OHRP Guidance at:
        http://www.hhs.gov/ohrp/humansubjects/guidance/irbgd702.htm 

* **Written IRB Procedures*
- §***46.103(b)(4-5)***
***OHRP Guidance at:***
***        ***_[http://www.hhs.gov/ohrp/humansubjects/guidance/irbgd702.htm](http://www.hhs.gov/ohrp/humansubjects/guidance/irbgd702.htm)_*** ***

## Required Elements

**Procedures IRB will follow for:**
**conducting initial review of research**
**conducting continuing review of research**
**reporting the IRB’s findings and actions to investigators and the institution**
**	****	****	****	****	****	****	**** **§46.103(b)(4)(i)

## Operational Details

**Initial & continuing review - description of:  **
**any primary reviewer system**
**documents distributed for review & timing**
**expedited review procedure**
**any processes supplementing IRB review**
**range of possible actions by the IRB**

## Operational Details

**Reporting IRB actions - description of:  **
**how notify investigator & how address investigator response**
**which institutional official is notified & how accomplished ****	**			**	****	****	**

## Required Elements

**Procedures for:**
**determining which projects require review more often than annually**
**determining which projects need verification from sources other than the investigator that no material changes have occurred since previous IRB review**	**	****	****	****	****	****	**** ****	****	****	****	**§46.103(b)(4)(ii)

## Required Elements

**Procedures for:**
**ensuring prompt reporting to the IRB of proposed changes in a research activity**
**ensuring that such changes in approved research may not be initiated without IRB review and approval, except when necessary to eliminate apparent immediate hazards to the subject** 	**	**					                       						§46.103(b)(4)(iii)

## Required Elements

**Procedures for:**
**ensuring prompt reporting to the IRB, appropriate institutional officials, the Department of Agency head, and OHRP of any**
**unanticipated problems involving risks to subjects or others**
**any serious or continuing noncompliance**
**any suspension or termination of IRB approval**							 §46.101(b)(5)

## Suggested Additional Elements

**Among others, **
**any further review by institution**
**procedures for determining exemptions**
**procedures for implementing other relevant federal, State, & local laws/regulations**
**training and education programs for IRB members, investigators, & staff**
**procedures for selecting IRB members & chairs**
**procedures for dealing with conflict of interest**

## Suggested Additional Elements (Cont.)

**IRB review of research in emergency situations & settings**
**procedures for ensuring IRB knowledge of local research context**
**description of required elements of informed consent  and criteria for altering or waiving these requirements**
**consideration for date stamping informed consent documents**
**procedures for documenting required IRB  findings/determinations**

## 

IRB Records – Regulatory Requirements 
45 CFR 46.115

*IRB Records – Regulatory Requirements *
*45 CFR 46.115*

## IRB Records - Regulatory Requirements  

**1.****	****Copies of**
**research proposals reviewed**
**scientific evaluations, if any**
**approved sample consent documents**
**progress reports submitted by investigator**
**reports of injuries to subjects**
**	****	****	****	**	 §46.115(a)(1)

## IRB Records - Regulatory Requirements (cont.)

**2.****	****Minutes of IRB meetings  -  in sufficient detail to show **
**attendance at meetings**
**actions taken by the IRB**
**votes on actions [separately for each protocol] **
**basis for requiring changes in or disapproving research, and **
**a written summary of controverted issues & their resolution**
- 					 §46.115(a)(2)

## IRB Records - Regulatory Requirements   (cont.)

**3.****	****Records of continuing review activities**
**4.****	****Copies of all correspondence between the IRB and the investigators**
**List of IRB members in the same detail as described in**** ****§46.103(b)(3)**
**	****	****	****	****	****	****           **§46.115(a)(3–5)

## List of IRB Members

**Members identified by:**
**name**
**earned degree **
**representative capacity**
**indication of experience such as board certification, licenses, etc., sufficient to describe each members expected contribution to IRB deliberations, and**
**any employment or other relationship between each member and the institution**
**	****	****	****	****	****	**** **§46.103(b)(3)

## IRB Records - Regulatory Requirements (cont.)

**6.   Written procedures for the IRB in the same detail as described in §46.103(b)(4) & (5)   **
**7.****	****Statements of significant new findings provided to subjects as required by §46.116(b)(5) **
**	****	****	****	****	****	**** **§46.115(a)(6–7)

## OHRP recommends the IRB records

***OHRP recommends the IRB records***
***also include documentation of any ***
***actions, determinations, findings, or***
***requirements made by the IRB***

## IRB Records - Regulatory Requirements (cont.)

**Retention of records:   **
**	****Records required by the HHS regulations shall be retained for at least 3 years, and records relating to research which is conducted shall be retained for at least 3 years after completion of the research.**
**	****	****	****	****	****	**** **§46.115(b)

## Records Retention (cont.) 

**	****Some state or local jurisdictions,  professional organizations, and institutions may have policies requiring longer retention of research records. **

## IRB Records - Regulatory Requirements (cont.)

**Accessibility**
** ****	****All records shall be accessible for inspection and copying by authorized representatives of the Department or Agency at reasonable times and in a reasonable manner **
**	****	****	****	****	****	**** **§46.115(b)

##        Human Subject Protections

**Subjects**

**Sponsor**

**Advocates**

**IRB**

**Research Team**

**Institutions**

**        **

**Government**

**Public**

**Family**

**Investigator**

## Resources

**Significant Findings of Noncompliance**** **http://www.hhs.gov/ohrp/compliance/findings.pdf
**Expedited review categories:**  http://www.hhs.gov/ohrp/humansubjects/guidance/expedited98.htm
**Institution’s written IRB procedures are posted at web pages** http://www.hhs.gov/ohrp/humansubjects/guidance/irbgd702.htm
**OHRP educational conferences/meetings**
-     http://www.hhs.gov/ohrp/education/conference.html
**IRB Guidebook** http://www.hhs.gov/ohrp/irb/irb_guidebook.htm

## Resources

**Visit OHRP website:****  **_[http://www.hhs.gov/ohrp](http://www.hhs.gov/ohrp)__ __	__	__	__	__	__	__	__	_
**Join List Serve:**** **_[http://www.hhs.gov/ohrp/news/index.html](http://www.hhs.gov/ohrp/news/index.html)_
**E-mail OHRP:****  ****ohrp@osophs.dhhs.gov  **
**Phone #:****   ****	****(240) 453-6900**
**Fax #:****	****(240) 453-6909**