The final editorial in the NEJM’s three-part series on FDA reform takes
it’s title from a line in the Institute of Medicine report: The Future of
Drug Safety: “This [is] a golden moment of opportunity to
improve fundamentally the way FDA regulation
considers and responds to the evolving understanding
of risks and benefits of drugs.”
In the editorial, the authors are particularly concerned with the
vexing issue of assessing the safety of drugs after
they are marketed. The reason for concern is simple math.
Premarketing testing typically involved a few thousand
individuals. Once a drug is on the market, it typically is
given to millions of people. It simply is not possible to
anticipate how the risks will present in a population that is both
larger, and less carefully selected.
Reauthorization — Drug Safety’s Golden Moment of Opportunity?
Pharm.D., Ph.D., and Brian L. Strom, M.D., M.P.H.
the more easily remediable shortcomings identified by the IOM are the
severe underfunding of the FDA, the particularly poor funding for
postapproval monitoring of safety, and the “troubling imbalance”
between these resources and those available for preapproval review.
This disparity is particularly disturbing because inherent limitations
in the knowledge gained in the preapproval drug-testing process are
responsible for the fact that 20% of drugs receive black-box warnings
after approval2 and that 4% of drugs are ultimately withdrawn from the
market for safety reasons.3 A principal goal of our postapproval
drug-safety system should be to minimize the delay between approval and
the discovery of these serious risks…
..We believe that the FDA’s January 16, 2007, recommendations to
Congress for the reauthorization of PDUFA risk squandering this key
opportunity by providing grossly inadequate PDUFA funds for
postapproval drug safety in general and studies of specific drug-safety
issues in particular.
They point out that Congress is expected to authorize only $29 million
to the problem, despite the fact that the pharmaceutical industry
grosses over $118 billion per year, and spends almost $12 billion on
advertising. In contrast, the IOM estimates that it would
cost up to $60 million to investigate ten “safety signals” per year.
(That refers to an indication tha there might be a safety
What they don’t say, which would admittedly be difficult to estimate,
is how much money could be saved by improving the postmarketing
surveillance system. Large safety problems, such as the Vioxx
situation, are enormously costly. I know that budget cutting
is popular in Washington right now, but failing to fund adequate drug
safety programs seems like a poor tradeoff.