Docket Management
Docket: 01N-0322 - Institutional Review Boards
Comment Number: EC -15

Accepted - Volume 1

Comment Record
Commentor Dr. Robert Schooley Date/Time 2002-06-04 18:36:16
Organization University of Colorado/AIDS Clinical Trials Group
Category Academic

Comments for FDA General
1. General Comments Re: Docket No. 01N-0322 - Institutional Review Boards: Requiring Sponsors and Investigators to Inform IRBs of any Prior IRB Reviews Dear Sirs and Madams: We are writing on behalf of the Adult AIDS Clinical Trials Group (ACTG), a multicenter clinical trials cooperative group supported by the National Institutes of Health to conduct clinical and translational research directed at reducing and ultimately eliminating morbidity and mortality due to HIV-1 infection. Our Group was founded in 1987 and has enrolled thousands of study volunteers into hundreds of clinical trials directed at HIV and its complications. The ACTG is composed of clinical trials sites located at 34 major academic medical centers, a Statistical Center at the Harvard School of Public Health and an Operations Center in Bethesda. We wish to respond to several of the questions raised in the proposal to institute regulations that are designed at the theoretical problem of so-called IRB shopping. 1. How significant is the problem of IRB shopping? Although it was stated that the OIG had heard of a few situations of IRB shopping. It is not at all clear to us that this is a situation that occurs in more than isolated circumstances. Before instituting a regulation that would affect every clinical investigator in the country, the existence or non-existence of IRB shopping must be ascertained. Multicenter clinical trials, such as those conducted by the Adult AIDS Clinical Trials Group (AACTG), are generally conducted at academic institutions and must use the institution's formally designated IRB, as listed on the FDA Form 1572. Investigators at academic medical centers do not generally have the option to use IRB's other than the one designated by the institution. Therefore, we believe that IRB shopping does not occur within the AACTG (and is not likely to be a common event within any academic medical center). AACTG protocols and consent forms receive extensive ethical and regulatory review from the investigators, NIAID staff and FDA regulatory officials before even being submitted to local IRB's. Individual site IRBs may request modifications or clarification before final approval, but outright disapproval of a protocol is extremely rare. 2. Who should make these disclosures? If investigator X was required to inform his IRB about the disapproval of investigator Y's protocol, the distribution and tracking of these IRB reviews would create an unmanageable paperwork tangle, multiplied by the number of sites conducting the protocol. In our case in which we have 34 participating Universities and another 40 or 50 subsites - not all of which use the same IRB, keeping every IRB apprised of the action of every other IRB about every protocol would rapidly melt down the internet. This would be particularly true if the proposal is expanded to require disclosure of both positive and negative comments as well as to provide background information about every IRB member on each participating IRB. 3. Who should receive the disclosures? For better or worse, the current concept of IRB review is that local IRB's are in the unique position of being best able to judge the merits of a study for the clinical trials location(s) they regulate. Flooding IRB's with information about other IRB actions would undermine the independence of the process. Suppose, for example, one of the 50 or 60 IRB's involved in reviewing ACTG protocols is inundated with 58 notifications that study x had been approved by other IRB's. This would both overwhelm the IRB with information (much o which is not that helpful in our view) and could predispose a review result. Any IRB, regardless of whether it is a prior or new IRB, should be doing an unbiased review of the protocol. 4/5/6. What information should be disclosed? If a proposal would not require disclosure of all prior IRB decisions, what information should be disclosed? To permit a subsequent IRB to assess the value of a prior IRB decision, should information about the basis for the prior decision be disclosed? None. The disclosure of favorable reviews to all other investigators serves no purpose other than to create a paper file. Although the disclosure of only unfavorable reviews might ensure awareness of relevant issues, it would not insure that the new IRB makes the correct decision about protocol approval or disapproval. As we have already stated, we believe this approach is fundamentally flawed and would overwhelm local IRB's with information that they could not possible assess. The assumption that every IRB must know what every other IRB has done suggests that none of them are competent to review any protocol. 7. How should FDA enforce the requirement? The amount of generated paperwork would lead to the classic case of not being able to see the forest for the trees. The FDA is already extremely taxed dealing with much more important issues and is both understaffed and underfunded. A better question would be What would you prefer the FDA NOT do if this regulation is implemented as policy? 8. Are there other ways to deal with IRB shopping? NO. There is no need to institute a regulation, if a problem has not been documented to exist beyond the current anecdotal nature of the thinking that appears to be behind this proposal. If rigorous and quantitative data can be generated about this issue, it would make it possible to conduct a risk/benefit analysis as to whether the net effect of such regulations would benefit or harm research volunteers. Without such data, imposition of policies such as those suggested here would be a reckless action that we believe would be more likely, on balance, to harm patients than to help them. Protecting research subjects is something the research community cares deeply about and poorly thought out regulations may actually harm the welfare of research subjects. We hope that the person or persons who proposed this will make a more concerted effort to evaluate the need for such a program, do some research in the area and present a more cogent case for the need for such a program before it is reflexively adopted without thought in the name of protecting patients. Sincerely, Constance A. Benson, M.D. Chair, AIDS Clinical Trials Group Robert T. Schooley, M.D. Vice Chair, AIDS Clinical Trials Group

EC -15