Harvard Medical Sees Pressure Rising for Higher Standards in FDA Drug Approval Process

Jerry Avorn, professor of medicine at Harvard Medical School and chief of the Division of Pharmacoepidemiology and Pharmacoeconomics at Brigham and Women's Hospital, Boston, this week writes in The New England Journal of Medicine that the FDA should ask tougher questions in its drug-approval process.

The acceleration of the discovery and development of new drugs is one of the keystones of the new biology economy. Molecular biology tools are increasingly seen as levers to shortening the lengthy and expensive process of bringing new drugs to the market by narrowing the pool of patients that may benefit from their use (pharmacogenomics), or by failing compounds earlier in the development process.

Avorn looks at the end of the pipeline, saying that the government supports a minimal standard for evidence for approval for a new drug that would be “unacceptable anywhere else in research.” It's not a sloppy process, he says, but one with a low standard of “proving that a new medication is superior to a usually irrelevant comparison treatment (such as placebo) in achieving a potentially irrelevant outcome (such as a surrogate measure),” he said.

“Beyond overly simple surrogate measures and the failure to demand relevant comparison trials,” he cites the recent approval of the BiDil brand of hydralazine and isosorbide dinitrate for use in treating congestive heart failure in black patients as an example of the FDA's low standards of approval, saying this drug's approval was based on a “post hoc analysis of racial subgroups enrolled in a larger trial in which the combination did not perform particularly well,” he writes.

So, instead of testing the racial-difference hypothesis in a trial with blacks and whites, the drug passed regulatory minimal standards, and was approved, he said.

“The racial-difference assumption was embraced as fact, and the new pivotal study enrolled only blacks; it found that adding BiDil to their regimens worked better than adding placebo,” Avorn said.

He concludes that the rising concern about the efficacy–risk–cost trade-offs of drugs, and the potential mass purchasing power of Medicare in 2006, may convince Congress to change today's regulatory frameworks.

"The idea that government approval should be based on what a new drug really does for patients may soon come into its own,” he writes.

Tags -- [Drug disovery, drug development, regulation, approval, FDA]