Sometimes the Silence Can Be like the Thunder: Access to Pharmaceutical Data at the FDA
Lurie, Peter, Zieve, Allison, Law and Contemporary Problems
According to the advocates of greater corporate involvement in clinical science, the increasingly entwined relationship between corporations, academia and government is the very definition of a "win-win" situation. Corporations can benefit from the knowledge of scientists in academia or government, and the public benefits from the more rapid movement of beneficial products into commerce.
That argument, however, ignores a fundamental clash of cultures. Progress in science is based on the free publication of study results and on the public release of data, allowing scientists to build on the experiences of others. In contrast, the governing ethic in the corporate sector is secrecy--the withholding of any information from which a competitor might benefit. There is perhaps no realm in which these competing viewpoints are presented more starkly than in the area of access to pharmaceutical data at the Food and Drug Administration (FDA).
Those committed to the free exchange of scientific information have long complained about various restrictions on access to these pharmaceutical data and the resultant restrictions on open discourse. Such restrictions include the selective publication of favorable results, (2) gag orders on corporate-funded research, (3) and misleading presentations of data. (4) Only in the last several years have these concerns penetrated public consciousness. Two recent examples demonstrate the problems these restrictions create:
The first example involves the selective publication of data on the efficacy of selective serotonin reuptake inhibitor (SSRI) antidepressants in children. Despite objective evidence demonstrating that SSRI's are, at best, moderately effective in children, (5) published studies generally exaggerated the benefits of these drugs, while certain negative studies provided to FDA were never published. Industry-funded academic scientists withheld from publication some studies that failed to demonstrate drug efficacy, (6) the inclusion of which would have altered the risk-benefit profile of the drugs. (7) Despite these efforts, an FDA analysis of published and unpublished pediatric SSRI trials ultimately led to the addition of a black box to the FDA-approved label that warned of the increased risk of suicidal ideation in children and adolescents. (8)
In another revealing example, the Journal of the American Medical Association published a report in 2001 claiming that, after six months of therapy, the COX-2 inhibitor celecoxib (Celebrex) was associated with a reduced incidence of gastrointestinal ulcers compared to two other pain medications. (9) If true, this outcome would have represented a significant advantage over other approved pain medications. However, the authors of the study failed to disclose that at the time of publication they had already received data for the full twelve-month period for which the study was originally designed. (10) The twelve-month data showed no advantage for Celebrex over other drugs. Although the FDA, armed with the twelve-month data, has never allowed the company to claim reduced ulcer incidence, the published study helped drive the massive Celebrex market.
Together, these two cases underscore the harms resulting from the ability of pharmaceutical companies to withhold data from the view of physicians and patients. Moreover, even when such data are available to the FDA, for reasons described below, the agency may fail to disclose the data publicly, further limiting the public's access to accurate information.
Some observers have suggested that a registry of clinical trials would shed more light on the drug-approval process. In theory, companies (or others) forced to register their studies at the point-of-study initiation and ultimately to disclose their results would be more accountable to regulators, researchers, and patients. However, a review of open-government procedures and litigation at the FDA demonstrates that the need for transparency at the agency extends well beyond the reach of any clinical trial registry. …