Docket Management
Docket: 01N-0322 - Institutional Review Boards
Comment Number: EC -11

Accepted - Volume 1

Comment Record
Commentor Mr. Michael Werner Date/Time 2002-06-04 16:36:54
Organization Biotechnology Industry Organization
Category Association

Comments for FDA General
Questions
1. General Comments June 4, 2002 Dockets Management Branch (HFA-305) Food and Drug Administration 5630 Fishers Lane Room 1061 Rockville, Maryland 20852 Re: Institutional Review Boards—Requiring Sponsors and Investigators to Inform IRBs of Any Prior IRB Reviews (Docket No. 01N-0322) Dear Sir or Madam: The Biotechnology Industry Organization (“BIO”) appreciates the opportunity to submit the following comments concerning the March 6, 2002, advance notice of proposed rulemaking issued by the Food and Drug Administration (“FDA”) which seeks public comment on whether the agency should modify its human subject protection regulations to require research sponsors and/or investigators to inform institutional review boards (“IRBs”) of prior IRB reviews. 67 Fed. Reg. 10,115 (March 6, 2002). BIO represents more than 1,000 biotechnology companies, academic institutions, state biotechnology centers, and related organizations in all fifty states and thirty-three foreign nations. BIO’s members conduct and sponsor research designed to discover medicines, diagnostics, and innovative new forms of therapy. Our members provide a home base for researchers who are committed to finding ways to use science to meet unmet medical needs. For most of our members, research is their business; only a handful have products approved for marketing. They are sustained by their prospective patients’ hope and faith in their research enterprise, and by Americans’ willingness to invest in that hope. BIO’s members have long endorsed the principle of respect for participants in human subjects research and have supported appropriate legal safeguards that promote the safety and well-being of those who voluntarily participate in our research activities. Our members recognize that we must do all we reasonably can to ensure that these volunteers have the utmost confidence they will be protected throughout the research process. In this instance, however, BIO believes that the disclosure requirement under consideration by the FDA is not a necessary—or even appropriate—means of furthering these goals. BIO is not aware of the scope of the practice of “IRB shopping,” as characterized by the Department of Health and Human Services Office of Inspector General (“OIG”) in its 1998 report on IRBs (Office of Inspector General, Department of Health and Human Services, Institutional Review Boards: A Time for Reform 14 (1998)), or the extent to which such a practice may have occurred in a way that runs counter to the best interests of research participants. We are unaware of any data, empirical or otherwise, on this point. We find it telling, though, that the OIG indicated that it had only “heard of a few” instances of this practice and, as noted by the FDA, failed to provide any “quantitative estimate” of the nature of the purported problem. The report’s treatment of this matter suggests that, to the extent it occurs at all, “IRB shopping” is limited in nature, especially in relation to the vast amount of important human subjects research that occurs today. As a result, a disclosure requirement strikes us as a solution in search of a problem. BIO is even more concerned, though, that as a “solution,” a disclosure requirement, although well-intentioned, is ill-advised. Nothing currently prohibits IRBs from soliciting information about prior reviews, but the FDA’s request for comments itself contains a virtual laundry list of prospective difficulties associated with implementing a requirement to disclose such information. The agency obviously is aware of the potential for these problems and we need not repeat them all here. We wish, however, to point out that some of these problems are so significant that we do not believe a disclosure scheme, regardless of its design, could be implemented in a way that would overcome them. In particular, we note that the administrative burden imposed on IRBs by a disclosure requirement (as well as on investigators and/or sponsors) would be considerable. For a disclosure scheme to be of real value for human subjects, IRBs would have to spend untold hours of time and expend inestimable precious resources querying, and responding to inquiries from, other IRBs in an effort to understand the meaning behind protocol approvals and/or denials—effectively lengthening the review process and delaying potentially significant research (this is in addition to delays caused by IRBs postponing decisions until they have heard from other IRBs reviewing the same protocol as part of a multi-site study). This problem might be minimized to some degree if IRBs provide much more detailed explanations at the time they approve or disapprove a protocol, but this in itself would impose a substantial administrative burden on review boards. In either event, boards would begin to drown in a sea of paper and information. The FDA undoubtedly is aware that IRBs already are overburdened by the sheer number of protocols they must review. The imposition of a disclosure requirement, regardless of design, would only add to the burden on IRBs (and investigators and/or sponsors) and, given the apparent absence of a material problem of “IRB shopping” in the first instance, would not be a cost-effective means of enhancing protection for human subjects. In fact, the extra administrative burden associated with learning about and understanding prior decisions with respect to certain protocols may necessarily result in less critical review of others, thereby potentially increasing risk for research participants. We note that in the same report cited by FDA, the OIG specifically recommended that FDA lessen or eliminate some of the existing procedural requirements applicable to IRBs, stating that “[t]he aim here should be to enable IRBs . . . to concentrate their attention on those research practices posing the greatest risks to human subjects” and noting that “[t]oo much of [IRBs’] attention now focuses on perfunctory review responsibilities yielding little protective value.” Office of Inspector General, at 11. BIO submits that, for the reasons stated above, the disclosure requirement under consideration is exactly the kind of procedural requirement that the OIG recommended FDA consider for elimination. In addition, we are greatly concerned by the likelihood that some IRBs will, perhaps unconsciously, over time begin to fail in their responsibility to make independent judgments as to the potential risks and benefits of protocols submitted for review, with the result(s) that risk to human subjects increases and/or that potentially valuable biomedical research is delayed. BIO believes that, given the extent to which many IRBs already are pressed for time and resources, it is inevitable that some review boards will, even unwittingly, allow the judgment of another IRB to affect or, at the extreme, substitute for their own. The consequences of such bias could be damaging regardless of the outcome of a prior review. If a prior approval is not well-founded, the second IRB’s decision to approve might only expose additional research participants to unacceptable levels of risk; if a prior disapproval is not well-founded, the second IRB’s decision to disapprove would only delay further potentially beneficial research. This problem is exacerbated where the first IRB is affiliated with a “prestigious” institution, as subsequent IRBs will be more likely to accept the first decision at face value or with little independent review. We do not see how the FDA could implement a disclosure scheme in such a way as to surmount this serious problem. In sum, while BIO is unaware of the extent of IRB shopping or the problems such a practice may have caused, we have no reason to believe that it is commonplace, and we are not persuaded to the contrary by the OIG’s pronouncement that it heard of a “few” instances of the practice. More importantly, to the extent IRB shopping is a problem, we do not believe the disclosure requirement under consideration by the FDA is a well-advised solution. Although such a requirement would spring from good intentions, its primary effects would be to impose additional burdens on already-overtaxed review boards and to increase the risk of bias in subsequent protocol reviews. Ironically, in its effort to protect research participants, the agency’s action likely would do more harm than good. We suggest as an alternative that, to the extent the FDA learns of individual abuses of the review process, the agency use its existing enforcement powers to address the problem. Thank you again for this opportunity to share our views on this important issue. Sincerely, Michael J. Werner, Esq. Vice President, Bioethics Biotechnology Industry Organization 1225 Eye Street, N.W., Suite 400 Washington, DC 20005 (202) 962-9200




EC -11