Guest Authorship, Mortality Reporting, and Integrity in Rofecoxib Studies

Abstract

To the Editor: The study by Drs Psaty and Kronmal and the accompanying Editorial by Drs DeAngelis and Fontanarosa regarding rofecoxib illustrate the recurring problem of discretionary or data-driven analysis. Given the possibility of selective analysis based on observed data and the risk of positive results due to chance alone, it is critical to know in detail which analyses were prespecified and when the prespecification occurred. This can only be done via a full protocol repository, as we suggested in 2002. Our proposal would establish a secure real-time repository for protocols, amendments, and statistical analysis plans. The material would be kept confidential for intellectual property reasons during the clinical trial and its analysis and then made public at the time of publication. The proposal has yet to be implemented, although the Food and Drug Administration (FDA) Act of 2007 (US HR3580), which provides for a Web site for results of all phase 2, 3, and 4 trials, also requires posting the protocol. The rofecoxib data reported in the study by Psaty and Kronmal illustrate that the ascertainment of even a hard end point like mortality can be modulated by varying the appropriate window of time used to capture the event of interest. With other end points, especially composite end points, the situation is rife with possibilities of changing results by discretionary ascertainment. This is why one of the last aspects of the protocol to be finalized is often the statistical analysis plan. However, with no protocol or a timeline documentation of its provenance, these details are never made public so that it is not possible to see how published analyses compare with protocol-specified analyses. This transparency is needed to be confident in the validity of the results.