The US Food and Drug Administration (FDA) watches over prescription and over-the-counter drugs, medical devices, dietary supplements and most foods — all together about 25% of the US economy. It is therefore quite troublesome to see how often its decisions are questioned, its authority undermined and its need for reform highlighted. The latest instance — the storm over the diabetes drug Avandia — is another serious blow for an agency that desperately needs to recover its credibility.

The Avandia controversy began on 21 May with the publication in The New England Journal of Medicine (NEJM) of a meta-analysis that pointed to an increased risk of myocardial infarction in people taking the drug. On 5 June, the same journal published an interim analysis of a clinical trial supported by GlaxoSmithKline (GSK, the manufacturer of Avandia), which failed to show conclusive evidence that the drug increases the risk of heart attacks.

Editorials in NEJM and in other scientific and nonscientific publications accompanied both papers, extensively exposing the limitations of the two studies — the meta-analysis had limited statistical power and included studies that did not have the same endpoints, whereas the clinical trial was designed to finish in 2009 and was therefore unlikely to give a meaningful answer at the time of the interim analysis.

Then, the plot started to thicken. There were allegations of competing financial interests against one of the authors of the NEJM meta-analysis, and the authors of the NEJM editorials were accused of presenting inaccurate and extreme views. It emerged that a GSK meta-analysis with the same bottom line as the one published by the NEJM had already been submitted to the FDA and to the European Medicines Agency in August 2006. However, only the latter had changed the label of the drug, warning against possible cardiovascular effects, while the FDA began an internal re-analysis of the data. Finally, Rosemary Johann-Liang, a supervisor at the FDA, stepped forward to claim that she had approved a recommendation that Avandia carry a stronger safety warning, but had been ordered by other officials who dealt more closely with GSK to withdraw her approval and lost her power to approve such assessments.

Meanwhile, the number of Avandia prescriptions dropped markedly, as did the value of GSK's shares. This prompted shareholders to sue the company for allegedly failing to let investors know in a timely fashion the results of the meta-analysis that the GSK submitted to the FDA nearly a year ago.

The FDA, in turn, was humiliated in the US Congress, which accused it of negligence. Officials from the agency pledged to investigate Johann-Liang's accusations. And FDA Commissioner Andrew von Eschenbach said that the agency has asked GSK to place a more prominent warning on Avandia to highlight the heart risks associated with its use, a request that was made just two days after the publication of the NEJM meta-analysis.

What's wrong with this picture? Why were the results of two studies with such evident limitations given so much visibility so quickly? And if these studies were manifestly inconclusive, then why did the FDA act so promptly to request the new warning? Was the FDA bullied into action by the first publication in NEJM (its shortcomings notwithstanding), by the accompanying editorial and by the reaction it elicited in the popular press, or did the agency realize that it could not sit for any longer on the data it received last year and on the recommendations from its own staff? It's hard to choose which of these two possibilities is the less reprehensible.

Much has been written about the limitations of meta-analyses and about how they cannot replace a carefully designed clinical trial to answer questions about drug safety (see page 767). Alas, few postmarketing trials currently take place, and those that do tend to focus on efficacy, not on monitoring side effects. As a result there have been repeated calls to give the FDA the power to compel companies to carry out more safety studies of drugs on the market. Indeed, a bill that would inject more money into the FDA to achieve this goal is making its way through the US Congress.

Unfortunately, most of the additional funds would come from the drug companies themselves, creating a paradoxical situation in which the pharmaceutical industry might actually acquire more influence over the FDA. Even so, we should in principle regard this bill as a positive development. However, cases like the Avandia affair, which expose the lack of leadership and good judgment at the FDA and undermine the public's confidence in the ability of the agency to do its job, beg the question of whether bestowing more power on the FDA is a good idea.

In this context, the recent announcement that the FDA will appoint a panel to advise the agency on how to tell the public about the risks and benefits of drugs is noteworthy. In the words of an FDA official, the advisory committee will “help improve FDA's communication of the science-based information about product risks and benefits that the public needs to make informed decisions.” Judging from the handling of the Avandia case, one wouldn't think that it is the public who needs to learn how to make informed decisions.