Secretary’s Advisory Committee on Human Subjects Protections (SACHRP) Summary of Responses on:...

Secretary’s Advisory Committee on Human Subjects Protections (SACHRP)

Summary of Responses on:Advanced Notice of Proposed Rulemaking

(ANPRM) on Holding Institutional Review Boards Directly Accountable

Julie KaneshiroPolicy Team Leader

Division of Policy and AssurancesJuly 21, 2009

Background

SACHRP recommendationCurrent regulatory flexibility

“OHRP, NIH, and FDA should consider holding a workshop focused on central IRB review mechanisms and that SACHRP use the workshop experience and other processes as a means of gathering information and moving forward toward future committee action.”

SACHRP Recommendation (Fall, 2004)

Meetings on Alternative IRB Models

OHRP co-sponsored meetings on alternative IRB models in November 2005 and November 2006

Other sponsors were NIH, the Association of American Medical Colleges, and the American Society of Clinical Oncology


Concluded: Despite existing regulatory flexibilities some institutions remain reluctant to designate external IRBs and rely on cooperative review arrangements.


A key factor: OHRP currently holds institution engaged in human subjects research study accountable for noncompliance on the part of the external IRB designated on FWA to review the research.

Current Regulatory Flexibility

Cooperative review arrangements for multi-site research (45 CFR 46.114):

Joint IRB reviewFacilitated IRB reviewReliance on external IRB

Current Regulatory Flexibility

Designating IRBs on an FWA: Internal IRB External IRB

- IRB of another institution

- Independent or commercial IRB Internal and external IRB IRB composed of members from both

inside and outside of the institution

OHRP Proposal to Hold IRBs Directly Accountable

March 5, 2009, published an ANPRM

Asked whether OHRP should revise 45 CFR part 46 to enable HHS to hold IRBs and IRB organizations (IORGs) directly accountable for compliance

Comments due by June 3, 2009

Comments Received

30 comments received 13 comments were “joint” (e.g., Consortium of

Independent Review Boards, Public Responsibility in Medicine and Research, Association of American Medical Colleges, Council on Governmental Relations, Pharmaceutical Research and Manufacturers of America)

Distributed, as follows:-- 9 from universities/IRBs/investigators-- 11 from non-governmental organizations, private sector-- 10 from individuals

Key Question Asked

: Classifying some comments as “Yes”, “No” or “?” required some interpretation

Should HHS pursue regulatory change to hold IRBs/IORGs directly accountable for compliance with

certain requirements of 45 CFR part 46?

YES NO ?

21 6 3

Note: Classifying some comments as “Yes”, “No” or “?” required interpretation.

Key Question Asked

Should HHS pursue regulatory change to hold IRBs/IORGs directly accountable for compliance with certain requirements of 45 CFR part 46?

IRBs, Investigators

Non-Governmental Organizations

Private Sector

Individuals

YES 7 11 3

NO 2 0 4

? 0 0 3

Questions Asked

ANPRM included 7 specific questions, including the key question discussed previously

Review of Comments – Question 1

Is there sufficient need for HHS to pursue a regulatory change to 45 CFR part 46 to hold IRBs/IORGs directly accountable?


Yes (21) Typical comment: proposed change is desirable and will have

intended effect.Notable comments: Proposal promotes consistency with FDA regulations Regulation not needed—a change in guidance would allow

OHRP to hold IRBs/IORGs directly accountable. Proposal may not increase reliance on external IRBs, but

nevertheless should be pursued.

No (6) Typical comments: proposed change is not desirable and will

not have intended effect; may result in more confusion and administrative burden; guidance is preferable.


Would the proposed regulatory change reduce concerns about regulatory liability and contribute to an increase in collaborative IRB review arrangements?


Yes (14) Typical comments: Proposed change will reduce concerns about

regulatory liability and encourage collaborative IRB review arrangements.

No (3) Typical comments: While proposed change may reduce concerns

about regulatory liability, it will not affect an institution’s decision about whether to rely on an external IRB. Regulatory liability is not the main factor.

Yes & No (4) Typical comments: Will decrease concern about regulatory liability for

institutions considering reliance on an external IRB, but increase liability concerns for external IRBs/IORGs.


Notable comments:

Liability of individual IRB members is a concern. Liability with respect to private parties persists Local context considerations remain Quality of IRB review remains a concern, which could be

mitigated by accreditation


Are there other approaches and strategies that would decrease concern about regulatory liability and increase collaborative IRB review arrangements?


Yes (9)Notable comments: OHRP should eliminate requirement that IRBs be designated

on FWA and permit commitment to use only registered IRBs (relates to SACHRP recommendation)

Mitigate concern about quality of IRB review through voluntary/mandatory accreditation

Consider ways to reduce liability of individual IRB members HHS funding agencies should strongly encourage collaborative

IRB review OHRP should issue guidance and template IRB Authorization

Agreements

No (1)


Would such a regulatory change have the unintended effect of making IRB organizations less willing to have their IRB designated on other institutions’ FWAs or have other unintended effects? If so, would there still be sufficient benefit to pursue the proposed regulatory change? Other possible negative consequences?


Yes (8) Typical comment: The proposal will make IORGs less willing to

serve as external IRBs, but support proposal despite this

Notable comments: Academic medical centers will become less willing to have

their IRBs serve as external IRBs, while “commercial” IRBs would not

IRB members may become less willing to serve if to be held individually accountable

No (4)

Notable comments: No change for IRBs that review FDA-regulated research


If such a regulatory change were pursued, what kinds of administrative actions would be appropriate for OHRP to take against IRBs found to be out of compliance?


Comments (13)

Notable comments: OHRP enforcement should be the same as FDA’s Current OHRP sanctions are insufficient. OHRP

should consider use of fines and seek such authority if it does not currently exist

The same administrative actions against institutions engaged in research should apply to IRBs/IORGs


How should regulatory requirements be categorized? Regulatory requirements seem to fall into three categories of responsibilities:

1. Responsibilities unique to IRBs/IORGs

2. Responsibilities unique to institution engaged in human subjects research

3. Responsibilities that may be fulfilled by either IRBs/IORGs or institutions engaged in human subjects research.

Questions Asked

6a-d.

Are these categories appropriate? Is there a category of responsibilities that are inherently shared by the IRBs/IORGs and engaged institutions? Are the regulatory provisions identified under each category appropriate? How have institutions engaged in research and external IRBs/IORGs divided or shared regulatory responsibilities in the past?


Yes (11) Typical comment: Proposed regulatory categories are

appropriate and the regulatory provisions identified under each of the categories are appropriate.

Notable comments: While no disagreement about the categories, recommends a

simplification to a single category that identifies the minimum regulatory responsibilities of the reviewing IORG.

No (3) Typical comments: There is a category of responsibilities that

are shared by IRBs/IORGs and engaged institutions; there are some regulatory provisions that should be moved to another regulatory category.


7a.

If this regulatory change is pursued, should OHRP use the IRB Authorization Agreement or other forms of agreement to inform its compliance oversight evaluations?

Review of Comments – Question 7a

Yes (8)

Notable comments: Form of agreement used is not important OHRP should develop detailed template IRB

Authorization Agreement

No (1)


7b.

Should there be new provisions that require specific content for agreements between external IRBs and FWA-holding institutions?

Review of Comments – Question 7b

Yes (6) Comments: Some commenters wanted the regulation to

include content for agreements in only the broadest terms, others seemed to prefer more specificity.

No (5) Typical comment: Flexibility is desirable.


7c.

Should the regulation describe which regulatory requirements would need to be met by external IRBs versus institutions engaged in research?

Review of Comments – Question 7c

Yes (7) Typical comment: The regulation should describe which

entity would be held accountable for each regulatory provision.

No (6) Typical comment: Flexibility is desirable, guidance is

preferable.

Additional Information

Reports from 2005 and 2006 meetings on alternative IRB models: http://

www.dhhs.gov/ohrp/sachrp/documents/AltModIRB.pdf

http://www.aamc.org/research/irbreview/irbconf06rpt.pdf

Advanced Notice of Proposed Rulemaking published March 5, 2009 (see http://edocket.access.gpo.gov/2009/pdf/E9-4628.pdf)

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