Human Subjects Protection: Creation and Maintenance of an IRB

Regulatory Requirements & Recommendations45 CFR part 46

Freda E. YoderOffice 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 BackgroundRegulatory Background IRB Membership & IRB Membership &

ResponsibilitiesResponsibilities Written IRB ProceduresWritten IRB Procedures IRB RecordsIRB Records ResourcesResources

Regulations for Protection of Human Subjects in Research 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 researchonly 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 Statement of principle governing conduct of

researchresearch Designation of one or more IRB Designation of one or more IRB

– established in accordance with the regulations established in accordance with the regulations and and

– for which provisions are made forfor which provisions are made for meeting spacemeeting space sufficient staff to support the IRB’s review and sufficient staff to support the IRB’s review and

record keeping dutiesrecord keeping duties List of IRB members & relevant information List of IRB members & relevant information Written IRB & institutional proceduresWritten IRB & institutional procedures

§46.103(b)§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

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:Regulatory criteria for membership: minimum of 5 membersminimum of 5 members background & expertise appropriate to background & expertise appropriate to

review research conducted by institutionreview research conducted by institution qualification & diversity … to promote qualification & diversity … to promote

respect for its advice and counselrespect for its advice and counsel ability to ascertain acceptability of research ability to ascertain acceptability of research

in terms of institutional commitments and in terms of institutional commitments and regulations, applicable law, and standards of regulations, applicable law, and standards of professional conduct and practiceprofessional conduct and practice

representation for vulnerable subjects, when representation for vulnerable subjects, when appropriateappropriate

§46.107(a)§46.107(a)

IRB Members (cont)

Regulatory criteria for membership:Regulatory criteria for membership: not entirely of same sex and may not consist not entirely of same sex and may not consist

entirely of members of one professionentirely of members of one profession at least one with primary concerns in scientific at least one with primary concerns in scientific

areas & at least one in nonscientific areasareas & at least one in nonscientific areas at least one not affiliated and not immediate at least one not affiliated and not immediate

family member of anyone affiliated with family member of anyone affiliated with institution institution

may not participate in review of any project in may not participate in review of any project in which member has a conflicting interestwhich member has a conflicting interest

invite other expert to supplement review invite other expert to supplement review §46.107(b-f) §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

Required Elements

Procedures IRB will follow for:Procedures IRB will follow for: conducting initial review of researchconducting initial review of research conducting continuing review of conducting continuing review of

researchresearch reporting the IRB’s findings and actions reporting the IRB’s findings and actions

to investigators and the institutionto investigators and the institution

§46.103(b)§46.103(b)(4)(i)(4)(i)

Operational Details

Initial & continuing review - Initial & continuing review - description of: description of: any primary reviewer systemany primary reviewer systemdocuments distributed for review & documents distributed for review & timingtimingexpedited review procedureexpedited review procedureany processes supplementing IRB any processes supplementing IRB reviewreviewrange of possible actions by the IRBrange of possible actions by the IRB

Operational Details

Reporting IRB actions - Reporting IRB actions - description of: description of:

how notify investigator & how how notify investigator & how address investigator responseaddress investigator response

which institutional official is which institutional official is notified & how accomplished notified & how accomplished

Required Elements

Procedures for:Procedures for: determining which projects require determining which projects require

review more often than annuallyreview more often than annually determining which projects need determining which projects need

verification from sources other than the verification from sources other than the investigator that no material changes investigator that no material changes have occurred since previous IRB have occurred since previous IRB

reviewreview §46.103(b)(4)(ii)§46.103(b)(4)(ii)

Required Elements

Procedures for:Procedures for: ensuring prompt reporting to the IRB of ensuring prompt reporting to the IRB of

proposed changes in a research activityproposed changes in a research activity ensuring that such changes in approved ensuring that such changes in approved

research may not be initiated without IRB research may not be initiated without IRB review and approval, except when review and approval, except when necessary to eliminate apparent immediate necessary to eliminate apparent immediate

hazards to the subjecthazards to the subject §46.103(b)(4)(iii)§46.103(b)(4)(iii)

Required Elements

Procedures for:Procedures for: ensuring prompt reporting to the IRB, ensuring prompt reporting to the IRB,

appropriate institutional officials, the appropriate institutional officials, the Department of Agency head, and OHRP of anyDepartment of Agency head, and OHRP of any

– unanticipated problems involving risks to unanticipated problems involving risks to subjects or otherssubjects or others

– any serious or continuing noncomplianceany serious or continuing noncompliance

– any suspension or termination of IRB any suspension or termination of IRB approvalapproval §46.101(b)(5)§46.101(b)(5)

Suggested Additional Elements

Among others, Among others, any further review by institutionany further review by institution procedures for determining exemptionsprocedures for determining exemptions procedures for implementing other relevant procedures for implementing other relevant

federal, State, & local laws/regulationsfederal, State, & local laws/regulations training and education programs for IRB training and education programs for IRB

members, investigators, & staffmembers, investigators, & staff procedures for selecting IRB members & chairsprocedures for selecting IRB members & chairs procedures for dealing with conflict of interestprocedures for dealing with conflict of interest

Suggested Additional Elements (Cont.)

IRB review of research in emergency IRB review of research in emergency situations & settingssituations & settings

procedures for ensuring IRB knowledge of procedures for ensuring IRB knowledge of local research contextlocal research context

description of required elements of description of required elements of informed consent and criteria for altering informed consent and criteria for altering or waiving these requirementsor waiving these requirements

consideration for date stamping informed consideration for date stamping informed consent documentsconsent documents

procedures for documenting required IRB procedures for documenting required IRB findings/determinationsfindings/determinations

IRB Records – Regulatory Requirements 45 CFR 46.115

IRB Records - Regulatory Requirements1.1. Copies ofCopies of

– research proposals reviewedresearch proposals reviewed

– scientific evaluations, if anyscientific evaluations, if any

– approved sample consent documentsapproved sample consent documents

– progress reports submitted by progress reports submitted by investigatorinvestigator

– reports of injuries to subjectsreports of injuries to subjects

§46.115(a)(1)§46.115(a)(1)

IRB Records - Regulatory Requirements (cont.)

2.2. Minutes of IRB meetings - in sufficient Minutes of IRB meetings - in sufficient detail to show detail to show

– attendance at meetingsattendance at meetings

– actions taken by the IRBactions taken by the IRB

– votes on actions [separately for each votes on actions [separately for each protocol] protocol]

– basis for requiring changes in or basis for requiring changes in or disapproving research, and disapproving research, and

– a written summary of controverted issues a written summary of controverted issues & their resolution& their resolution

§46.115(a)(2)§46.115(a)(2)

IRB Records - Regulatory Requirements (cont.)

3.3. Records of continuing review activitiesRecords of continuing review activities

4.4. Copies of all correspondence between Copies of all correspondence between the IRB and the investigatorsthe IRB and the investigators

5.5. List of IRB members in the same detail List of IRB members in the same detail as described in §46.103(b)(3)as described in §46.103(b)(3)

§46.115(a)(3–5)§46.115(a)(3–5)

List of IRB Members

Members identified by:Members identified by: namename earned degree earned degree representative capacityrepresentative capacity indication of experience such as board indication of experience such as board

certification, licenses, etc., sufficient to certification, licenses, etc., sufficient to describe each members expected contribution describe each members expected contribution to IRB deliberations, andto IRB deliberations, and

any employment or other relationship between any employment or other relationship between each member and the institutioneach member and the institution

§46.103(b)(3)§46.103(b)(3)

IRB Records - Regulatory Requirements (cont.)

6. Written procedures for the IRB in the 6. Written procedures for the IRB in the same detail as described in §46.103(b)same detail as described in §46.103(b)(4) & (5) (4) & (5)

7.7. Statements of significant new findings Statements of significant new findings provided to subjects as required by provided to subjects as required by §46.116(b)(5) §46.116(b)(5)

§46.115(a)(6–7)§46.115(a)(6–7)

OHRP recommends the IRB recordsalso include documentation of any actions, determinations, findings, orrequirements made by the IRB

IRB Records - Regulatory Requirements (cont.)

Retention of records: Retention of records:

Records required by the HHS Records required by the HHS

regulations shall be retained for at least regulations shall be retained for at least

3 years, and records relating to 3 years, and records relating to

research which is conducted shall be research which is conducted shall be

retained for at least 3 years after retained for at least 3 years after

completion of the research.completion of the research.

§46.115(b)§46.115(b)

Records Retention (cont.)

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

IRB Records - Regulatory Requirements (cont.)

AccessibilityAccessibility

All records shall be accessible for All records shall be accessible for

inspection and copying by authorized inspection and copying by authorized

representatives of the Department or representatives of the Department or

Agency at reasonable times and in a Agency at reasonable times and in a

reasonable manner reasonable manner

§46.115(b)§46.115(b)

Human Subject Protections

Subjects

Sponsor

Advocates

IRB

Research Team

Institutions

Government Public

Family

Investigator

Resources

Significant Findings of Noncompliance Significant Findings of Noncompliance http://www.hhs.gov/ohrp/compliance/findings.pdfhttp://www.hhs.gov/ohrp/compliance/findings.pdf

Expedited review categories:Expedited review categories: http://www.hhs.gov/ohrp/humansubjects/guidance/exphttp://www.hhs.gov/ohrp/humansubjects/guidance/expedited98.htm edited98.htm

Institution’s written IRB procedures are posted Institution’s written IRB procedures are posted at web pagesat web pages http://www.hhs.gov/ohrp/humansubjects/guidance/irbghttp://www.hhs.gov/ohrp/humansubjects/guidance/irbgd702.htm d702.htm

OHRP educational conferences/meetingsOHRP educational conferences/meetings

http://www.hhs.gov/ohrp/education/conference.html http://www.hhs.gov/ohrp/education/conference.html IRB GuidebookIRB Guidebook

http://www.hhs.gov/ohrp/irb/irb_guidebook.htm http://www.hhs.gov/ohrp/irb/irb_guidebook.htm

Resources

Visit OHRP website:Visit OHRP website: http://www.hhs.gov/ohrp http://www.hhs.gov/ohrp

Join List Serve:Join List Serve: http://www.hhs.gov/ohrp/news/index.htmlhttp://www.hhs.gov/ohrp/news/index.html

E-mail OHRP:E-mail OHRP: ohrp@osophs.dhhs.gov ohrp@osophs.dhhs.gov

Phone #:Phone #: (240) 453-6900(240) 453-6900

Fax #:Fax #: (240) 453-6909(240) 453-6909