Making drugs safer saves lives. It also lowers health care costs.
The Food and Drug Administration later this year will impanel an advisory committee to consider whether to pull GlaxoSmithKline’s diabetes drug Avandia off the market. An internal FDA report leaked to The New York Times in February suggested the drug is causing in excess of 800 heart failure and heart attack cases a month, with one in eight leading to premature death.
The Avandia problem is not new. Between 1999, when the drug came on the market, and 2007, the year its sales plunged after its dangerous side effects were brought to light by a study in The New England Journal of Medicine, an estimated 41,000 to 205,000 diabetics may have suffered unnecessary heart attacks and heart failures, according to Steven E. Nissen, a cardiologist at the Cleveland Clinic who co-authored the analysis.
The safety controversy swirling around the drug has been accompanied by allegations of scientific skullduggery. They include charges that a peer reviewer leaked the NEJM manuscript to Glaxo officials prior to publication, and Glaxo prematurely halted a study designed to show if Avandia was safe.
Capitol Hill has also jumped into the controversy. A Senate Finance committee report issued in February blasted the FDA’s handling of Avandia over the years and alleged that Glaxo attempted to intimidate researchers who had sought to bring the drug’s safety problems to light. The company denied those charges. And last week, a spokeswoman said the company will mount a vigorous defense of the drug at the FDA’s July hearing. “Six large randomized controlled clinical trials have looked at the cardiovascular safety of Avandia and none show a connection,” she said.
The Real Cost
Drug safety generates lots of headlines, and the FDA advisory committee will no doubt focus exclusively on that issue. But drug safety is also a cost issue. If the FDA’s internal reviewers are accurate, those 800 excess heart failures a month are costing the health care system nearly a half-billion dollars a year (conservatively estimating the cost of treating a single heart attack including follow-up care at about $50,000 a year). Safer alternatives that work just as well at the primary task of lowering blood sugar in diabetics — and several are available — would not only save lives, they would eliminate that unnecessary expenditure.
What Works, What Doesn’t
The recently enacted health care reform bill calls for investing more money in comparative effectiveness research, which will show which health care interventions work best for a particular disease. Obviously, such studies will take both the benefits and risks of competing treatments into account. The Obama administration’s $787 billion stimulus package includes a $1.1 billion down payment on the program.
But by its very nature, comparative effectiveness research cannot appear until years after competing treatments have come on the market. The original industry-funded clinical trials that lead to a drug’s or device’s approval usually contain no comparisons, since the law requires they only be compared to placebo. Follow-up studies that compare various approaches only appear gradually. In the interim, the health care system can waste billions, and harm thousands. How can the process be shortened? One way is to generate better information about the safety of drugs on the front end of the approval process.
A Possible Solution
The FDA on Monday held its first public hearing on the 2012 reauthorization of the Prescription Drug User Fee Act, which occurs every five years. Under PDUFA, originally passed in 1992, drug and device companies pay fees to the FDA in exchange for more rapid review of their new drug applications. About one-half of the $1 billion Center for Drug Evaluation and Research budget now comes from industry user fees.
The last time Congress reauthorized PDUFA (in the wake of the painkiller Vioxx’s withdrawal from the market for its heart attack problems), it gave the FDA more power to demand that companies implement risk management plans when new drugs show hints of safety problems in their original approval trials. The plans usually involve closely monitoring the patients who take the drugs immediately after they go on the market. Had such a program been in place in 1999, Avandia would have no doubt been subjected to a Risk Evaluation and Mitigation Strategy (REMS), since there was an elevated but statistically insignificant increase in heart problems in its first clinical tests.
The industry plans to use the hearing to push the FDA to streamline the REMS approval process and make it less onerous. “Implementation of . . . REMS has led to a breakdown in FDA’s review process and has eroded some of the positive progress derived from earlier PDUFA agreements,” David Wheadon, senior vice president at the Pharmaceutical Research and Manufacturers of America, testified. Consumer groups, meanwhile, pushed for more controls over direct-to-consumer advertising and better access to the results of early stage clinical trials.
But no one is pushing the FDA to require companies to conduct comparative clinical trials when they are developing new drugs for diseases for which there are already existing treatments. The trials would need to be large enough to test not only which drug was better for the condition, but which drug was safer.
If someone pushed for such a reform, the companies would complain bitterly that it would raise the cost of developing new drugs. That is true. But it would actually be a win-win-win reform.
It would be better for patients and physicians since they would more quickly learn which are the safer and more effective treatments. It would be better for insurers and their customers since it would save the health care system money. And it would be better for the drug and device industries, since it would force companies to focus their research on truly innovative products. And that would be more profitable, at least for the winners, since they would be able to charge higher prices and gain greater market share.