The unexpected lesson of the Avandia debacle.
Also in Slate: Eliot Spitzer writes about the FDA's failed efforts to regulate drug companies.
Let's assume that the FDA tightened regulations so that all of the current drama around the RECORD trial was eliminated. In the end, if the results confirmed "non-inferiority," Avandia would have been a me-too drug, no better than cheaper alternatives. If it was worse—as it appears to be—diabetics are no worse off than they were with their generics.
Ultimately, the main problem with trials like RECORD isn't that they may collect biased results. It's that they can cost hundreds of millions of dollars, monopolize the best minds from major academic medical centers, and don't do anything useful for patients. Drug companies are not charities, and they expect a return on their massive investments. They design clinical trials with the goal of selling their product, not to advance the health and knowledge of the global population. They don't ask the questions about drugs for which we most need answers.
Because federal agencies like the National Institutes of Health rarely shoulder the costs of large drug trials, the pharma companies are the only ones throwing in money. They are the sugar daddies for many cubs at academic centers and health centers. Pharma companies pay lavishly and, in return, buy the right to design trials with very narrow aims.
Consider another recent example: the controversy over the 2008 AstraZeneca-funded trial of the cholesterol-lowering drug Crestor, known as JUPITER. That study concluded that even adults with normal cholesterol levels (but other risk factors like high blood pressure or obesity) should take Crestor if they had an abnormally high "C-reactive protein," or CRP. The kicker is that CRP can be measured only by a "high-sensitivity" blood test patented by the study's lead author. Last month, the Archives of Internal Medicine published several articles accusing the study authors of misclassifying data and succumbing to commercial biases to promote the drug's benefits.
As with the Avandia trial, this fixation on supposed data-manipulation misses the larger point. The Crestor trial was specifically designed, for better or for worse, to push an agenda (in this case, widespread CRP testing). Most observers believe the study should have included a comparison group of high-risk people with hypertension and obesity but normal CRP levels; this would have allowed them to compare responses to Crestor and evaluate the utility of the CRP test. The public's chance to learn the answer has been lost.
Had it been conducted perfectly, the Avandia trial still wouldn't have helped people with Type 2 diabetes avoid any long-term problems. More regulations on research are likely to drive up research costs, which will incentivize pharma companies to narrow their studies' goals further. That isn't in the best interests of our health.
The alternative is for the government to invest directly in more useful clinical trials. Currently, the FDA approves drugs for sale without any cost-benefit analysis—it looks only at safety and efficacy—and Medicare later foots the bill. The FDA effectively acts as the nation's largest pharmaceutical purchaser; its approval of Avandia in 1999 meant Medicare soon would spend billions more. Why not, then, invest $100 million up front to decide that's a good buy?
Darshak Sanghavi is Slate's health care columnist. He is chief of pediatric cardiology and associate professor of pediatrics at the University of Massachusetts Medical School as well as the author of A Map of the Child: A Pediatrician's Tour of the Body. Follow him on Twitter.
Photograph of Avandia by Joe Raedle/Getty Images.