FDA - Which side are you on, which side are you on?

The new BMJ features extensive discussion of the serious hoo-hah over licensing of rosiglitazone, brand name Avandia, which was recently reviewed by an FDA advisory panel. A majority of the panel recommended leaving it on the market, albeit with strengthened warnings, for reasons which most of us find inexplicable and which they have not explained very well either.

I think this review of the affair by Deborah Cohen is supposed to be available by subscription only, but as of this writing it appears to be available to the public. So get it while you can.

Without getting fussy over the details, I'll just say that there are three and a half basic issues here. (But who's counting?)

1. Approval of new drugs based on surrogate endpoints. Rosiglitazone was first approved by the FDA on the basis that it lowers glycolated hemoglobin, which is an indicator of high blood sugar. However, there was no evidence that it reduced complications of diabetes, or mortality.
2. As a condition of said approval, the manufacturer (whose name keeps changing during this saga but is currently Glaxo Smith Kline, was supposed to conduct post-marketing studies to determine long term safety and efficacy. It did so (often the companies don't even bother, and such orders are never enforced) but it set up a poor study design, and then interpreted the results in a tendentious way. Although the company still tries to deny it, the best available evidence indicates that the drug increases the risk of cardiovascular complications and probably death
3. The only reason we know point 2 is because, as a result of an unrelated lawsuit, GSK was required to post results of previously secret studies to a publicly accessible web site.
4. The most important complication of Type 2 diabetes, and the principal way it kills people, is heart disease. What earthly reason could there be to prescribe a drug to people with diabetes that increases the risk of the most important complication? Given this apparent no-brainer, what could possibly be going on in the heads of physicians who voted to leave the drug on the market?

What is going on in their heads, and in the heads of pharmaceutical regulators in general, is that they have a first duty to protect the proprietary interests of drug manufacturers, rather than the interests of the public. They seem to think it would be unfair to GSK to revoke the license without absolute proof that the drug does more harm than good and that there is no sub-group of patients for whom there might be some plausible argument for taking it. Of course any confusion about these questions results entirely from GSK's deliberately obfuscating conduct of research and efforts to withhold any negative information from public or regulatory scrutiny.

Actually, they are supposed to be on our side. As GP Iona Heath discusses in the same issue (and this is properly hidden from your view, alas), the culture of medicine, and the popular culture surrounding it, is infected by fantasies of omnipotence and rescue. There is a powerful bias to do something and to believe that what we do is for the best. Often, however, we don't have good responses to chronic diseases, but interventions that are useless or harmful are still undertaken because of an unexamined assumption that action must be better than inaction. In the case of Type 2 diabetes, trying to tightly control hyperglycemia with drugs appears to do more harm than good, at least given the drugs we have now.

Eating right (that would be vegetables), exercising, and losing weight, does work, but it isn't a miraculous heroic medical intervention. So we give up on it very early on, and start pushing pills. It just doesn't seem to change.