NEJM editors were “not fully aware” of GSK and Merck manipulation of Avandia and Vytorin DSMBs

Prior to publication of key papers on rosiglitazone (Avandia) and ezetimibe (Vytorin) in the New England Journal of Medicine, the editors of the journal were not aware that trial sponsors had “manipulated” the Data and Safety Monitoring Boards (DSMBs) of the trials, according to information contained in an editorial in NEJM by its editor, Jeffrey Drazen, and Alastair JJ Wood.

In response to the incidents , Drazen and Wood “propose fundamental changes in the way DSMBs are constituted, are funded, and report,” and say that DSMBs “should be chosen and convened under the aegis of an independent public body.”

The editorialists write that the problem represented by these two episodes “puts the integrity of the whole clinical-trial enterprise at risk.”

In the first incident, Drazen and Wood report that GlaxoSmithKline “went around the steering committee and the DSMB” of the RECORD trial. Publication of an interim analysis of RECORD in NEJM was used by GSK in an attempt to refute the Nissen meta-analysis. Drazen and Wood write that “we published that analysis in June 2007 but were not fully aware of GlaxoSmithKline’s manipulations” until the publication of a senate report detailing the episode in February of this year.

In the second incident, following a finding in the SEAS trial suggesting an excess of cancer deaths in patients taking ezetimibe and simvastatin, Merck and Schering-Plough “appear to have interacted with the investigators and the DSMBs” of two ongoing trials of ezetimibe, SHARP and IMPROVE-IT, “which resulted in the unblinding of data on cancer outcomes in these trials.” Again, the editorialists report, “we published the outcome of this analysis but were not fully aware of the role of the trial sponsors and the extent of the interactions that had occurred among the sponsors, the DSMBs, and the trial investigators.” (The editorial doesn’t dwell on the fact that this information came out in an article by Califf, Harrington, and Blazing published in NEJM.)

In both cases, according to Drazen and Wood, “a commercial entity decided to unblind aspects of trial data rather than let the DSMBs exercise their important and appropriate responsibilities both to the trial participants and to the wider community.”


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