12:00 AM
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Jun 11, 2007
 |  BioCentury  |  Politics, Policy & Law

Incomplete RECORD

Companies that experience the kind of drug safety-related public relations disaster that recently hit GlaxoSmithKline plc rarely get a chance to quickly turn perceptions around. GSK thought it had such an opportunity last week, but it proved evanescent, as an independent board decided to release interim results of the RECORD safety study of Avandia rosiglitazone to the journal that had already made itself the platform for the drug's detractors.

Given another opportunity in The New England Journal of Medicine last week, the critics put the RECORD in the most alarming light possible, even though it arguably is inconclusive at this point and even suggests it is possible the safety signals are too faint to show a significant risk for Avandia versus its comparators.

The treatment was not unlike the paper that started the outcry on May 21, when NEJM published a meta-analysis of the cardiac safety of Avandia by Steven Nissen and Karen Wolski of the Cleveland Clinic. Their paper noted limitations to the analysis, but nonetheless urged patients and physicians to consider its results when making treatment decisions.

Instead of soliciting commentary from experts with differing viewpoints, the journal chose authors with the same viewpoint as Nissen/Wolski, who used the paper to indict both GlaxoSmithKline (LSE:GSK; GSK, London, U.K.) and FDA.

As a result, some of the major shortcomings of the Nissen paper - the omission of trials with no cardiovascular events, the lack of a time-to-event analysis, the very low rate of events overall, and especially the lack of robustness of meta-analyses - were given short shrift.

The uncertainty around Avandia's cardiac effects has been discussed in the medical literature since it was approved in 1999, as has its effectiveness in helping diabetics control their blood sugar levels. But NEJM portrayed the story as big news, and it was treated that way by the media and by drug safety reformers in Congress(see Cover Story).

GSK executives were in the unenviable position of having to tell the world that it would have to wait for definitive data on Avandia's safety until 2009, when the RECORD results would be available.

RECORD - the Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes trial - is a 4,400-patient randomized, open-label trial comparing cardiovascular outcomes in patients treated with Avandia as add-on therapy to either metformin or sulfonylurea to cardiovascular outcomes in patients who receive metformin and a sulfonylurea.

The trial, which was designed and launched in 2000 to fulfill a post-marketing commitment to EMEA, is designed as a noninferiority trial. Avandia could...

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