SACHRP recommendation approved March 13, 2018
Points to Consider: Granting Exceptions to Requirements
for Single Institutional Review Board Review for Multi-Site Research
Introduction
Recent initiatives, geared towards both improving efficiency as well as better protecting human subjects in research, have focused on a requirement for single Institutional Review Board (sIRB) review of multi-site research. On June 21, 2016 NIH issued a policy requiring single IRB review for multi-site research funded by the National Institutes of Health, which became effective January 25, 2018. Revisions to the Federal Policy for the Protection of Human Subjects in Research (commonly referred to as the “Common Rule”) were issued as a Final Rule on January 19, 2017, including a requirement of single IRB review for federally funded multi-site research slated to take effect January 20, 2020. At the present time, there is no existing or pending FDA regulation requiring single IRB review of FDA regulated multi-site research.
Exceptions to the Requirement for Single IRB Review of Multi-Site Research
Both the NIH policy and the Final Rule permit certain exceptions to the requirement for single IRB review.
The NIH policy provides:
Exceptions to this policy will be made where review by the proposed sIRB would be prohibited by a federal, tribal, or state law, regulation, or policy. Requests for exceptions that are not based on a legal, regulatory, or policy requirement will be considered if there is a compelling justification for the exception. The NIH will determine whether to grant an exception following an assessment of the need.
The provision in the Final Rule states:
(i) Cooperative research for which more than single IRB review is required by law
(including tribal law passed by the official governing body of an American Indian or
Alaska Native tribe); or
(ii) Research for which any Federal department or agency supporting or conducting the
research determines and documents that the use of a single IRB is not appropriate for the
particular context.
The Final Rule permits the Federal department or agency discretion in requiring single IRB review of multi-site research but does not include the language in the NIH policy that refers to a “compelling justification for the exception.”
Request from OHRP
OHRP has requested that SACHRP consider the criteria that departments and agencies might consider when determining that single IRB review is not appropriate for a particular context in accordance with ___114 (b)(2)(ii) of the Final Rule. OHRP noted that the NPRM utilized the word “study” for this exception, but that the word “study” was changed to “context” in the Final Rule. This topic has been discussed in depth at several SACHRP subcommittee meetings as well as at two SACHRP meetings, and the committee has repeatedly struggled with the intrinsic variability of study designs and populations, and the difficulty of establishing clear criteria which could unambiguously determine the appropriateness of single IRB review. As an alternative, the committee determined that a Points to Consider guidance document would better capture the complexity of the “context” that should determine whether or not single IRB review would decrease regulatory burden while preserving or enhancing participant protections.
Discussion
In comments offered on the proposed revisions to the Common Rule, SACHRP opined on the use of a sIRB in multi-site research and suggested the following exceptions:
• review by a single IRB is unable to meet the needs of specific populations,
• where local IRB review is required by federal, tribal or state laws or regulations,
• research that does not meet the definition of clinical trial,
• research that is not federally funded research,
• research with fewer than 5 sites, and,
• where the funding agency determines that single IRB review is not appropriate.
Two of these suggestions were included in the NIH policy and the Final Rule, which both allow exceptions to the single IRB requirement where local IRB review is required by federal, tribal or state laws or regulations, as well as where the funding agency determines that single IRB review is not appropriate. A third suggestion offered by SACHRP goes without saying: if research is not federally funded, it would not be subject to the Common Rule or NIH policy. After re-review of the proposed exceptions, SACHRP also believes that there is no reason to exempt research that does not meet the definition of clinical trial.
Of the remaining two exceptions previously suggested by SACHRP, we recommend that both continue to be considered. There may be occasions where single IRB review for a particular study involving fewer than five sites could increase the complexity of initial review and ongoing oversight without improving participant protections, and whenever a single IRB is unable to meet the needs of specific populations, additional IRB review should be permitted.
There was considerable discussion at SACHRP as to whether the inclusion of vulnerable populations in research also constituted a distinct reason to except research from the single IRB review requirement. Ultimately, the consensus is that single IRB review may be appropriate even for research with vulnerable populations, and when it is not, this can be captured under the exception for circumstances in which the IRB is unable to meet the needs of specific populations.
These two considerations – number of sites and specific population needs – are demonstrated in the following examples:
1. Research involving surgical placement of a deep brain stimulator in patients with OCD who are treatment refractory, drawn from a single site and evaluated by psychiatry at that site for capacity to consent, treatment refractoriness, and follow-up, with surgery conducted at a different location. Given different research activities at each site, each site’s IRB may be best suited to conduct its own review. In addition, with only two sites, the logistics of organizing single IRB review may be inefficient and unnecessary for participant protection. Exception from the single IRB review requirement would be acceptable in this context.
2. Research that involves an intervention with pregnant women at one site and then follow–up with the neonates at another. Unless a single IRB had adequate expertise in pregnant women, obstetrical practices, and neonatal medicine, human subject protections might best be served by having the elements relevant to pregnant women reviewed by an IRB that has extensive expertise with that area and the elements relevant to the neonates reviewed by a pediatric IRB.
3. A study conducted at multiple sites including both children and adults. For the same reasons as above, it may be most protective of subjects to have inclusion of children reviewed by a separate IRB that is completely pediatric focused. Exception from the single IRB review requirement would be acceptable in this context, as well.
These examples illustrate the difficulty of establishing exception criteria, rather than points to consider. In each of the examples above, a single IRB could also augment its review expertise through the use of consultants and local experts. Thus, the consideration of whether or not single IRB review is appropriate must take into account the full context of the proposed research, including the capabilities and flexibility of the proposed single IRB.
1. In this regard, SACHRP has considered the change from the word “study” in the NPRM to the word “context” in the Revised Common Rule as requested by OHRP. The word “study” means an investigation or analysis of a subject or situation; while the word “context” means “the circumstances that form the setting for an event, statement, or idea, and in terms of which it can be fully understood and assessed.” The use of the word “context” therefore supports consideration of the background, circumstances and factors that more broadly may surround a research study.
2. Accordingly, SACHRP recommends that it would be appropriate to include a third type of exception to the single IRB review requirement, for research that involves political, controversial or sensitive overtones or issues, such that review by local IRBs would better address these concerns or be perceived to better address local sensitivities. The institution would need to present a case that unique political or controversial issues, values or sensitivities warrant review by that institution’s IRB to provide adequate subject protections and that review by an outside IRB would be inappropriate. For example, research involving medical marijuana might best be reviewed by individual IRBs that can best attend to local concerns and attitudes. Another setting in which strong consideration might be given to providing an exception to the single IRB requirement is emergency research studies conducted under the FDA Exception from Informed Consent requirements. Such studies require intensive engagement with the community that might best be performed by a local IRB.
Conclusion
SACHRP supports the goals of single IRB review for multi-site research in improving efficiency and protecting human subjects in research. However, where those goals will not be satisfied by single IRB review, exceptions are appropriate. SACHRP therefore recommends that HHS consider the following categories as potentially appropriate for exception to the single IRB review requirement:
1. Research involving 5 or fewer sites;
2. Research for which review by a single IRB is unable to meet the needs of specific populations; and
3. Research involving political, controversial or sensitive issues such that review by local IRBs would better address those concerns.
