An editorial in The New England Journal of Medicine, by its editor Jeffrey M. Drazen, M.D., and Alastair J.J. Wood, M.D. calls attention to the fact that pharmaceutical companies have tampered with the independent function of the DSMB (data safety monitoring board), and have planted promotional reports in The NEJM–and other scientific journals– thereby undermining the integrity of "the whole clinical-trial enterprise."
DSMBs are charged with protecting human subjects, being privy to the ongoing trial data so as to ensure that clinical equipoise is maintained during the course of a clinical trial. That is, the DSMB is supposed to ensure that uncertainty continues to exist about which treatment is safer and effective. If appreciably more subjects in one treatment arm of the trial suffer adverse events, the DSMB may decide that equipoise no longer exists and suspend the trial–so as not to expose human subjects to unjustifiable risk of harm.
Drs. Drazen and Wood cite two cases of commercial sponsor manipulation which undermined the integrity of the reports published by NEJM in 2007 and 2008:
1. GlaxoSmithKline obscured the increased risk of cardiovascular adverse events in the Avandia RECORD trial by jumping the gun and publishing a positive report of the interim data analysis.
2. Merck and Schering-Plough, appear to have interacted with the investigators and the DSMBs in two ongoing trials of ezetimibe (Zetia), the Study of Heart and Renal Protection (SHARP) trial and the Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT), which resulted in the unblinding of data on cancer outcomes in these trials.
The authors acknowledge: "These and other episodes have undermined public confidence in the ability of trials to operate independently of the sponsor. The current way that DSMBs are constituted and report has resulted in a loss of faith."
They propose fundamental changes in the way DSMBs are constituted, are funded, and report, regardless of whether there is a commercial or a public sponsor. They recommend that an independent public body select and convene DSMB members, and that a trial’s sponsors have absolutely no contact with DSMB members.
Better late than never….
Surely, the editor of the NEJM could not have been ignorant until now about corporate-manipulated reports that have been published by the NEJM. May we expect a clinical trial report review followed by a list of tainted retracted reports?
Vera Hassner Sharav
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