OTC ADVISORY COMMITTEE SUBMISSIONS: "LESS" INFORMATION MAY BE "MORE"

OTC ADVISORY COMMITTEE SUBMISSIONS: "LESS" INFORMATION MAY BE "MORE" valuable to advisory committee members, Nonprescription Drugs Advisory Committee Chairman Randy Juhl, PhD, University of Pittsburgh, suggested at the Nonprescription Drug Manufacturers Association annual research and scientific conference in Washington, D.C. on Nov. 18. Referring to a recent submission that was "a foot high," Juhl noted that although the committee was "dedicated to the task, . . . that is more information than most humans can readily digest and synthesize" in a limited period of time. Juhl observed that the Institute of Medicine's 1992 report on FDA advisory committees contains recommendations that "will be helpful in that regard" and that FDA is in the "process of implementing [the IoM] recommendations." Commissioned by FDA, the IoM report found the FDA advisory committee system "fundamentally sound" but in need of some improvements. Among its recommendations, the report suggested advance annual scheduling of meetings and agendas. Juhl noted that the committee is beginning to "deal with an agenda that is somewhat in advance and that would be very helpful." Juhl asked that companies provide the advisory committee with meeting packets no less than three weeks before an advisory committee meeting, as suggested by the IoM report. NDAC committee member Louis Cantilena, MD/PhD, Uniformed Services, also asked for earlier submission of the information to be considered at the meetings. "We have had quite a range so far," Cantilena said, noting that packets usually arrive two weeks before the meeting. However, he noted that "in one case" committee members received part of a submission the day before the meeting. Cantilena outlined several recommendations for OTC advisory committee submissions during his presentation. "I would like to see one binder with summary type information but fairly detailed," he said, asking also for "clearly-labeled" back-up material that includes the "primary information so that, if needed," committee members can refer to it. Cantilena said that the IoM recommendations for a 20 to 25-page summary "could work for some issues that come before us," but suggested that the "executive summary approach would not satisfy all situations" because some of the issues that "come before us are quite old and come from a variety of sources." Reliance on "old data" was highlighted by both Juhl and Cantilena as one of the issues the committee has had to grapple with at past meetings. "There is nothing inherently bad about old data," Juhl offered. However, he warned that when it is "old data that was in dispute 20 years ago, in all likelihood it is going to be in dispute now." Juhl reported that he has had "people from the science side of companies" approach him after meetings "and say: 'I'm really sorry we don't have good data but marketing took all the money.'" Juhl commented: "I'd like to give my push to keep your products up to date." Committee members "cringe" when they see data that have been to FDA "for a third or fourth statistical review because you think you have found a way to get significance," Juhl said. Juhl also warned OTC manufacturers that there are clues that "let [us] know that there are going to be problems with the presentations." When a statistical review is "about yea thick," he cautioned, that would "suggest to us that there is a statistical argument between the sponsor and FDA." Most recently, NDAC rejected a switch recommendation for SmithKline Beecham's Tagamet (cimetidine) because of unproven efficacy ("The Tan Sheet" Sept. 13, p. 1). FDA and the committee members primarily focused their questions on SmithKline's study methodology and the one-tailed statistical analyses of the data. SmithKline is currently in discussions with FDA to determine whether or not the existing data can be re-evaluated to demonstrate effectiveness. Cantilena observed that the committee has occasionally felt restricted in its discussions of an issue by the meeting questions prepared beforehand by FDA. He suggested that the panel be given some leeway so that "if our discussion evolves, we can pursue it." With regard to data presentations, Juhl recalled at one meeting, committee member Marcus Reidenberg, MD, brought up the topic of the "Pinocchio effect." Juhl explained that Reidenberg "called into question some of the information that the committee had received from consultants" that had been brought before the committee. "Put in the positive," Juhl offered, "my suggestion would be to emphasize to the academic presenters that you bring in . . . that they be able to speak to the broad items that are going to be asked of them and not to stray or hesitate on an item that would be about side effects." Otherwise, he added, it "destroys the credibility of their entire presentation." Reidenberg, Juhl noted, plans to publish a journal editorial called the "Pinocchio Effect." Oncology and Pulmonary Drug Products Division Director Gregory Burke, MD/PhD pointed to what he called "ostrich effect." Burke said that "the worst thing a company can do is to minimize the uncertainties [that] everyone with half a brain in the room already knows exist." He noted that "a frank, open discussion of the uncertainties is much preferable" to claiming that there is "no problem." Burke also recommended that switch sponsors look at the NDAC meeting as an "ongoing process" and not as an "event." Burke suggested that Rx-to-OTC switches be approached in a manner similar to the "proactive" approval process for new prescription drugs beginning with "what we call the 'end of Phase II conference.'" At this point, Burke explained, "we usually try to identify a consultant to the division who is a member of the advisory committee." With the consultant, "sponsor companies [could] try to work out a development plan for collecting the information that needs to be presented and make a reasonable decision about whether or not a product can go OTC," he noted. "I think that by having an advisory committee member involved as a consultant at that stage [who] links back to the advisory committee . . . ensures that this, in fact, [is] an ongoing process of interchange," Burke said. Moreover, he suggested that the consultant "act as the primary reviewer when the OTC switch is actually presented at the advisory committee meeting."