Senate investigation revealing new details in Avandia case, WSJ reports

Senator Grassley’s investigation into the Avandia case is turning up new, potentially embarrassing details about GSK’s internal responses to the controversy, according to a story in the Wall Street Journal.  In response to the forthcoming Nissen meta-analysis, a GSK consultant wrote: “The numbers are the numbers, the analysis is very similar to our own.”

The WSJ article quotes an email from Moncef Slaoui, GSK’s director of research: “FDA, Nissen and GSK all come to comparable conclusions regarding increased risk for ischemic events, ranging from 30% to 43%!” In response, a GSK spokeman said that Slaoui “used imprecise language” and that he “was more precise in written testimony to Congress when he said that the company didn’t agree with Dr. Nissen’s conclusions and thought that his methodology had significant limitations.”

When it comes to big controversies like this (the same applies for ezetimibe and Vioxx) it often seems to me that the fundamental problem isn’t a disagreement over data but a disagreement over perspective and fundamental assumptions. The WSJ story quotes the FDA’s Janet Woodcock as saying that Avandia had been “convicted without a trial.” 

Woodcock is undoubtedly correct, but others would disagree with the underlying, unstated assumption that Avandia should be accorded a presumption of innocence. Until recently, at least, surrogate trials were sufficient to gain a drug FDA approval and a presumption of clinical benefit. As we achieve much greater granularity in the details of clinical reality, these previous assumptions are now subject to much greater scrutiny, and there is no general agreement on underlying fundamental assumptions.