Part 3 of 3 — Making Amends in Clinical Investigation Requirements: Aligning FDA Regulations with the Common Rule – Comment Period Extended until December

Part 3 of 3 — Making Amends in Clinical Investigation Requirements: Aligning FDA Regulations with the Common Rule – Comment Period Extended until December

In Part 2 of this series, we discussed FDA’s first proposed rule, “Protection of Human Subjects and Institutional Review Boards.” Part 3 will break down the second proposed rule, “Institutional Review Boards; Cooperative Research.”

This proposed rule recommends a requirement for single Institutional Review Board (sIRB) review of research that is conducted in the U.S., with some exceptions, and addresses a related recordkeeping requirement. This would harmonize FDA regulations with the revised Common Rule’s sIRB requirements, as well as similar policies enacted by the National Institutes of Health (NIH).

Under current FDA regulations, sIRB review for cooperative research is voluntary. Despite FDA policies encouraging sIRB review, there has been a reluctance to do so, for reasons such as fear of losing local context and concerns regarding quality of review. FDA proposes to replace its current regulatory provision on voluntary use of a single IRB review multisite studies with a new mandatory requirement. FDA argues that decentralized IRB reviews for multisite studies carry administrative burdens and inefficiencies, while single IRB review would streamline the review process and increase efficiencies for oversights without compromising protection for human subjects. FDA also believes that, in many cases, mandatory sIRB review would decrease administrative burdens created by multiple IRB reviews for institutions, investigators, and sponsors.

The revised Common Rule already requires all U.S. institutions engaged in cooperative research that are subject to the Common Rule to rely on sIRB review, subject to two exceptions. NIH has similarly adopted a policy that single IRB review generally will be used for multisite research funded by NIH.

The two exceptions are:

1. Cooperative research where more than an sIRB review is required by law (including tribal law passed by the official governing body of an American Indian or Alaska Native tribe)
2. Research where any federal department or agency supporting or conducting the research determines and documents that the use of sIRB review is not appropriate for the particular context

FDA proposes to adopt the first exception, but not the second, which FDA believes could increase administrative burden because certain FDA-regulated research does not require interaction with FDA before it begins. Instead, FDA proposes three additional exceptions that could better reflect circumstances where requiring sIRB review may not be appropriate:

1. Cooperative research involving highly specialized, FDA-regulated medical product that requires unique, localized expertise
2. Cooperative research on drugs that are exempt from investigational new drug regulations
3. Cooperative research on medical devices that meets the abbreviated requirements for a nonsignificant study or exempted investigations

FDA invites comments on whether the Common Rule’s second exception should be added into their final rule, or whether FDA’s three substitutions are more applicable.

Another difference worth mentioning between the proposed rule and the revised Common Rule is that the latter requires the reviewing IRB to be “identified by the Federal Department or Agency supporting or conducting the research, or to be proposed by the lead institution subject to the acceptance of the Federal Department or Agency supporting the research.” FDA says it is not logical for them to assume this responsibility given that most FDA-regulated research is not conducted or supported by FDA or by any federal department or agency.

Finally, FDA proposes a new IRB recordkeeping requirement. For research that takes place at an institution where IRB oversight is conducted by an IRB not operated by the institution, the institution must retain documentation specifying the institution’s reliance on the IRB and the responsibilities each entity will undertake to ensure compliance. This proposed requirement is consistent with the revised Common Rule.

FDA proposes that the effective date of the final rule would be one year from the date of publication, and research initially approved by an IRB on or after the effective date would be required to comply with any new requirements.

In addition to the proposals mentioned above, FDA also requests comments on the following issues:

• Whether FDA should include two other exceptions:
  1. Cooperative research where use of an sIRB is unable to meet the needs of specific populations
  2. Cooperative research with a small number of investigational sites
• Whether an sIRB would generally be able to supplement its members’ knowledge and experience with additional information or expertise to account for this situation, and any data on the frequency of how often this situation my occur
• Any impact of the discrepancies between FDA’s proposed rule and the revised Common Rule regarding exceptions to the use of single IRB review
• Whether there are unique challenges to the use of sIRB review for FDA-regulated cooperative research that could not be addressed by the proposed exceptions

FDA is accepting comments on this proposal until December 28, 2022, and while some commenters have expressed their support for this proposal, like the Association for Clinical Oncology, many have voiced their concern for the consequences that this proposal could have, if finalized.

One commenter expressed their concern about how many sites have policies that require a local IRB application—regardless of use of an sIRB record reliance agreement. This was supported by another commenter, who argued that for many academic research centers, a compliance review is required at the local level, which could result in investigators interacting with two different IRBs. This supposed streamlining would create duplicative work for staff and could delay start-up at the site.

Another commenter explained that this proposal might reduce the IRB committee workload, but it would in fact increase administrative workload: “Most institutions…find the reliance process lengthy, inconsistent, and fraught with administrative glitches. Every reviewing IRB has a different way of requesting reliance and managing documents.” This commenter also argued that the Common Rule’s requirements are not necessarily adaptable to FDA regulations because the NIH and the Common Rule typically deal with university or academic medical center IRBs, while the FDA mandate will lead to industry sponsors relying on commercial, for-profit IRBs for most industry sponsored research. Another commenter had similar thoughts, explaining that “it is likely that industry sponsors will utilize commercial or for-profit IRBs as the IRB of record,” which in turn might weaken protection for human subjects.

You can submit comments electronically at www.regulations.gov. Comments on this proposed rule will inform FDA on how to proceed with these potential changes for Institutional Review Boards, and whether additional changes need to be made. For more information, review the published proposal in the Federal Register: Institutional Review Boards; Cooperative Research.

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