Harvard Prof Analyzes Avandia Controversy

In what amounts to the best brief analysis of the Avandia controversy—that is, whether to keep the antidiabetic drug on the market—Daniel Carpenter, professor of government at Harvard, defines the major divisive issues that inform the FDA's upcoming review of the product. His BEST GUEST PHARMA BLOG POST PROBABLY EVER can be found at today's Pharmalot.

The battles, as defined by the prof:

• "The War Over Method"—meaning, should we continue to overwhelmingly favor the results of randomized controlled trials, which have generally downplayed Avandia's cardiac risks, or should we cling to the findings of less rigorous and inherently problematic observational studies (eg, meta-analyses), which emphasize the drug's cardiac risks? Inextricably tied to this debate is the fact that the Avandia RCTs are uniformly funded by GlaxoSmithKline, the maker of Avandia, while the most press-worthy observational studies have been conducted by an attention-loving academic (Steve Nissen) and an FDA maverick (David Graham)—both of whom may have their own axes to grind with GSK and the FDA, respectively.
• A complicating subissue in The War Over Method (although Carpenter defines this as a separate issue) is what to do with a new report from FDA reviewer Thomas Marciniak, who publicly maligned the design and analysis of GSK's RECORD trial (a trial that was intended to assess Avandia's cardiac risks). With his report, Marciniak cast a very long shadow over the integrity of all GSK-sponsored RCTs.
• The third issue that Carpenter defines is Reputation and Power—which, in my mind, is so strong an undercurrent in the Avandia debate that it merits upfront discussion. And while Carpenter primarily directs this topic at the FDA (an emphasis, not coincidentally, that markets his new book, Reputation and Power: Organizational Image and Pharmaceutical Regulation at the FDA), the issue can also be applied to the motives and integrity of individual parties—like Steve Nissen and David Graham.