By Susan F. Wood, PhD
Two things appear to be major bones of contention in determining the final version of what is now named the “FDA Revitalization Act of 2007″ (FDARA). And they both related to public transparency and public accountability.
The first is the limitation of financial conflicts of interest by FDA Advisory Committee members. The House has adopted language that limits the ability of FDA to grant waivers to members of Advisory Committees (AC) who have financial conflicts to only 1 waiver per meeting of a committee. This was identical to an amendment offered on the Senate floor by Senator Durbin, which was defeated on a tie vote 47-47. Interestingly, Sen. Spector has since written a letter stating that his vote was mis-counted – he had intended to vote in favor of the amendment. Thus the amendment should have passed on a vote of 48-46. So you would think there would be strong agreement to include strong restrictions on financial conflicts of interest for AC members.
But apparently not so. Concerns have been floated about how this would limit access to qualified AC members, or that in some circumstances there are only a few experts in a particular field and these individuals have needed expertise but have financial conflicts.
A few days ago a group of notable scientists and physicians wrote a letter to Senators Kennedy and Dodd, who both voted against the conflict of interest amendment.
From their letter:
According to its January 2007 report to Congress, the FDA granted waivers to 24 percent of the 928 members of its 47 advisory committees that met during the 14-month period November 10, 2005 through January 4, 2007.
Allowing conflicted members of an advisory committee to vote can have serious public health consequences. For example, in early 2005 a FDA advisory committee reviewed the safety of COX-2 inhibitors and concluded that all three of these drugs, including Vioxx, were safe enough to keep on the market. Ten of 32 scientists on that panel had financial ties to manufacturers of the drugs. Had their votes been eliminated, two of the three drugs in that class would have ben voted down by the panel. (Vioxx was, of course, voluntarily withdrawn from the market by Merck in September 2004 because of safety concerns).
It is possible to find unconflicted experts. The FDA could choose its committee members from among the 123,000 faculty at the 125 medical schools in the United States and public health experts at other federal agencies such as the National Institutes of Health (“NIH”), the Centers for Disease Control, and the Veterans Administration. The NIH’s Office of Medical Applications of Research and the Agency for Healthcare Research and Quality’s U.S. Preventive Services Task Force bar any conflicted scientists from serving on the panels that developconsensus statements on the implications of clinical trial evidence. The Center for Evidence-Based Policy at Oregon Health Sciences University bars any conflicted expert from its analysis of clinical trial evidence to determine what drugs, biologics, and devices provide the best medical outcomes; this evidence is then turned over to states for use in establishing what Medicaid will pay for, among other uses.
The second issue is regarding the establishment of a clinical trials results database. The idea behind this is that not only should ongoing studies be registered (as in clinicaltrials.gov) so that patients can find them and potential participate, but that the public should have access to the information and data that is generated from these studies.
Both for ethical reasons – people should have access to the information generated on studies that they participated in – and for scientific and medical reasons – if the studies aren’t published or the date publicly available then there is the inability to learn from them or identify possible safety or efficacy questions.
Recently reported is that the White House is circulating an informal statement of Administration Policy (SAP)
from Inside Health Policy (requires subscription):
The unofficial statement of administration policy (SAP) notes that NIH already is preparing to study approaches to summarizing and presenting trial results, and says Congress should not require a results databaseuntil the NIH study is done.
Having two results databases is “unrealistic,” the administration writes, and the legislation does not give FDA nearly enough time to implement them. The White House complains there would be a lot of overlapping information in the databases, and that the technical database should not include demographic information or primary and secondary outcomes information.
Requiring lay summaries of trial results is particularly troubling, the SAP states. The administration also dislikes technical summaries.
“While trial results (without interpretative text) are inherently technical and data driven, narrative summaries are, in contrast, highly subjective and present the greatest likelihood for bias (intentional or unintentional),” the SAP states.
The administration also complains that the bill’s process for publishing results data is complicated. The NIH typically does not receive trial results data from FDA when products are approved or denied, but the bill requires NIH to post such information contingent on certain FDA regulatory actions.
“It would be infeasible, and inordinately burdensome, to have FDA notify NIH each time a triggering action either occurred or did not occur, and setting up some type of automated system will be incredibly complicated,” the SAP states. “More importantly, it is not appropriated for NIH to possess scientific information that it is not permitted to post.”
The administration also complains that the definitions of preapproval and post-approval trials differ from the way FDA uses those terms. And the bill has different requirements for post-approval trials and trials that are “seeking approval of a new use,” even though trials could fall into both categories.
The administration also questions the rationale for releasing preapproval trial results because the results pertain to products not on the market.
These are the arguments we hear from the industry and now hear from the White House. But these arguments don’t hold water and the principle of transparency and public access to all data is critical if we want FDA and the academic and medical research community to be able to identify both potential problems as well a potential benefits from medical products on the market – that are being used by people daily.
Susan F. Wood, PhD is Research Professor at George Washington University School of Public Health and Health Services, where she is part of the Project on Scientific Knowledge and Public Policy (SKAPP). She also served as Director of the FDA Office of Women’s Health from 2000-2005