Health and Human Services (HHS) and Food and Drug Administration (FDA) regulations both include the requirement that IRB membership include “at least one member whose primary concerns are in [the] scientific area[s] and at least one member whose primary concerns are in nonscientific areas.”[1] Despite essentially identical regulatory wording, OHRP and FDA guidance documents differ regarding the definitions and examples of “scientist” and “non-scientist.” OHRP addresses the issue at OHRP IRB Registration FAQ #12 [2]. FDA guidance is found at FAQ #17 of its Clinical Trial Information Sheet Guidance. [3]
[1]HHS regulations at 45 CFR 46.107(c): Each IRB shall include at least one member whose primary concerns are in scientific areas and at least one member whose primary concerns are in nonscientific areas.
FDA regulations at 21 CFR 56.107(c): Each IRB shall include at least one member whose primary concerns are in the scientific area and at least one member whose primary concerns are in nonscientific areas.
[2] [OHRP] The following are some general guidelines to assist you in composing the IRB membership roster.
Scientist/Nonscientist - Members whose training, background, and occupation would incline them to view scientific activities from the standpoint of someone within a behavioral or biomedical research discipline should be considered a scientist, while members whose training, background, and occupation would incline them to view research activities from a standpoint outside of any biomedical or behavioral scientific discipline should be considered a nonscientist. In addition, the IRB must have members with sufficient knowledge of the specific scientific discipline(s) relevant to the research that it reviews.
[3] [FDA] Which IRB members should be considered to be scientists and non-scientists?
21 CFR 56.107(c) requires at least one member of the IRB to have primary concerns in the scientific area and at least one to have primary concerns in the non-scientific area. Most IRBs include physicians and Ph.D. level physical or biological scientists. Such members satisfy the requirement for at least one scientist. When an IRB encounters studies involving science beyond the expertise of the members, the IRB may use a consultant to assist in the review, as provided by 21 CFR 56.107(f).
FDA believes the intent of the requirement for diversity of disciplines was to include members who had little or no scientific or medical training or experience. Therefore, nurses, pharmacists and other biomedical health professionals should not be regarded to have "primary concerns in the non-scientific area." In the past, lawyers, clergy and ethicists have been cited as examples of persons whose primary concerns would be in non-scientific areas.
Some members have training in both scientific and non-scientific disciplines, such as a J.D., R.N. While such members are of great value to an IRB, other members who are unambiguously non-scientific should be appointed to satisfy the non-scientist requirement.
This membership requirement is relevant not only to the composition of the IRB, but also to the review and approval process, since HHS and FDA regulations both specify that a quorum at a convened IRB meeting must include at least one member whose primary concerns are in non-scientific areas.[1]
Recommendation
In the interests of harmonizing OHRP and FDA guidance, and to assist IRBs in appointing appropriately qualified members and adhering to quorum requirements, while still respecting the flexibility implied in the regulatory language, the SACHRP makes the following recommendations regarding the definitions of scientist and non-scientist:
OHRP and FDA should issue a single joint guidance on this issue so that IRBs have a single source of information regarding the agencies’ viewpoint on this issue. This will facilitate compliance and reduce administrative burden on IRBs.
The joint guidance should outline general principles for determining whether an IRB member is to be classified as a “scientific” or “non-scientific” member, regardless of whether the individual is serving on a biomedical or a behavioral/social science IRB, and should also allow reasonable flexibility in the interpretation of an individual’s “primary concerns,” as referenced in the regulations. These principles should indicate that the requirement for having a “nonscientific” member lies in the need to have at least one representative on the IRB who is not self-identified with those conducting research that will be reviewed by the IRB. Examples of scientific members (practicing physician or nurse, Ph.D. level bench scientist, medical laboratory technician, etc.) and clearly-defined non-scientific members (attorney, clergy member, ethicist, etc.) should be given, as well as examples of less well-defined but potentially justifiable assignments. The guidance should reference the expectation that institutions that choose to categorize an individual as a non-scientist, when the rationale for the categorization is not apparent based on occupation or training, should maintain written documentation of the reason for the categorization.
The joint guidance should be included as part of the current FAQs regarding the Electronic Submission System for IRB registration, or should otherwise be posted inconjunction with the IRB registration system, since IRBs that review research regulated by either or both HHS and FDA are required to register using this system. The joint guidance, regardless of how and where it is published, should include an explicit statement(s) that it is both FDA guidance and OHRP guidance. This will ensure that institutions, IRBs, sponsors, and agency employees are aware that it represents the agencies’ current thinking on the topic.
Comment
The existing OHRP FAQ states that an IRB member should be considered a non-scientist if that individual’s training, background, and occupation “would incline [sic] them to view research activities from a standpoint outside of any biomedical or behavioral scientific discipline.” The FDA FAQ is more restrictive, and advises that only individuals with “little or no scientific or medical training or experience”—whether in the biological or the physical sciences—should be classified as non-scientists. In addition, FDA indicates that individuals with advanced or professional training in both scientific and non-scientific areas should not be classified as non-scientists.
The SACHRP believes that the intent of the regulations was to distinguish between two categories of IRB members:
Individuals who are professionally conversant with the scientific method (either by virtue of advanced training or by current occupation in scientific fields), and who might thus be inclined to view a research protocol primarily from the viewpoint of a scientist; and
Individuals who lack professional scientific training and do not work in scientific areas, or who may have past scientific training but who have worked only in areas that do not exercise that training, and might thus be inclined to view a research protocol primarily from the viewpoint of a non-scientist.
SACHRP believes the scientist/non-scientist distinction was designed to ensure a range of intellectual and philosophical perspectives among IRB members. By use of the term “primary concerns,” both OHRP and FDA regulations acknowledge that the concerns of an IRB member are unlikely to lie solely in scientific, or solely in non-scientific, areas.
For instance, an institution might choose to appoint a long-time elementary school teacher with prior advanced training in psychology as a non-scientific member, or an attorney specializing in biomedical intellectual property law as a scientific member. We believe that such appointments, with appropriate justification, are consistent with regulatory intent and should be allowed.
The current FDA guidance states that an IRB member with professional training in both scientific and non-scientific disciplines, such as a J.D., R.N., does not meet the non-scientist requirement. While this analysis would ordinarily prevail, individuals’ circumstances may vary, and we believe that there should not be a flat exclusion of such individuals from the non-scientist category, if the institution has and maintains justification for such an assignment. Similarly, an individual with a bachelor’s or associate degree in a scientific area, but who does not and has not subsequently worked in a scientific area, could appropriately be classified as a non-scientific member.
The current OHRP guidance seems to indicate that for the purpose of IRB member designation, scientists are limited to being either behavioral or biomedical scientists. In accordance with the above discussion, we believe that scientists in fields other than behavioral or biomedical sciences, such as geology or statistics, should be considered scientists for the purpose of IRB membership designation.
Finally, and to reinforce the concept of harmonization, we believe that the joint guidance should clarify that the concepts of scientist and non-scientist should ordinarily not vary from behavioral to medical IRBs. For instance, an anthropologist should be considered a scientist on both a behavioral and a medical IRB, rather than being considered a scientist for a behavioral IRB and a non-scientist for a medical IRB.
We hope that these comments and recommendations will promote regulatory harmonization and reduce administrative burden for the regulated research community, by clarifying a common standard for IRBs reviewing research subject to HHS and FDA oversight, while allowing a reasonable degree of local flexibility in meeting both the requirement and intent of the regulations.
[1] See 45 CFR 46.108(b) and 21 CFR 56.108(c).
