Promising New Drugs Deserve Faster Approval : Health: The FDA is determined not to permit drugs that don’t merit approval. But blocking effective ones may be a worse sin.
The United States seems to have a neurotic relationship with its drug-regulatory agency. The Food and Drug Administration is held in high esteem for protecting the public; at the same time, the agency is raked over the coals for serving the public poorly, mostly through bureaucratic foot-dragging. Even the harmonious paean of praise for the FDA’s speedy approval of generic drugs has soured in the face of disclosures of bribes to agency personnel for approving one firm’s drugs more speedily than another’s.
What is wrong with the FDA? Compared to the drug regulatory agencies of other countries, it is huge. Yet it is said to be small for its innumerable responsibilities. Its headquarters in Maryland is cheerless and inadequate in space, wiring and temperature control. These conditions and low pay scales discourage top-notch applicants for staff positions, and many senior posts are unfilled.
Congress maintains relentless oversight of the FDA, with many distracting, often worthless, hearings for which agency leaders must prepare. Hearings used to be about drugs that Congress (in retrospect) believed should not have been approved; of late, the questions have been in the opposite direction: Why is the FDA so slow in making available promising drugs for AIDS?
A key point of the “foot-dragging” controversy is the matter of how much data is enough and who should make that value judgment, which is never a simple mathematical exercise. The FDA believes that its people are the experts, although this is clearly not what Congress had in mind in 1962 when it gave the FDA new controls over the pharmaceutical industry.
One hears repeatedly the disingenuous statement that the FDA is “only carrying out the law.” A comparison between the 1962 statute and its legislative history on the one hand and FDA’s operational behavior on the other shows some striking discrepancies. Consider, for instance, that Congress required only “substantial evidence” for approval--that is, evidence that a few qualified investigators believed a drug to be safe and effective “even though there may be preponderant evidence to the contrary.” Contrast that position with the failure (until recently) to approve ganciclovir for an AIDS-related infection that leads to blindness, despite the verdict by the only two ophthalmologists on a 12-person panel that the drug worked. (The other 10 were not convinced.)
Compounding the trouble is the lack of a speedy, impartial appeals mechanism for judging who is right and who is wrong when a sponsor and the FDA are at loggerheads. American drug companies rarely fight even outrageous FDA demands, fearing retribution in future filings and anticipating inevitable refusal, whatever the merits of their case.
On average, year in and year out, it takes new chemical entities about 2 1/2 years from filing the application to obtaining FDA approval. (This is on top of six to seven years of human study before filing.) Meanwhile, the patent clock is ticking, with loss of income and partial loss of exclusivity time for the sponsoring firm. This is not a trivial consideration when one realizes that to bring a new chemical entity to market in this country requires about $100 million just for the clinical phase costs, exclusive of “discovery” costs (taking account of the failures as well as the successes).
There was little comfort in the record for new drugs taken to FDA advisory committees for votes from 1983 through 1987. For those products approved by the advisory committees without qualification, a mean of 19.7 months elapsed before full agency approval was granted. (A prominent FDA official asserts that this is no longer true, and that approval is now granted “in a matter of weeks” after advisory committee approval. I hope so.)
The agency generally acts as if the worst sin it can commit is to approve a drug that does not merit approval. But for serious diseases where no good remedies exist, surely a sin at least as grievous is to refuse (or even delay) approval for a drug that is effective.
