F.D.A. APPROVAL IS JUST THE FIRST STEP

PHILADELPHIA -- A study published in the Journal of the American Medical
Association a week ago found that more than 100,000 Americans die each
year from adverse reactions to medication. If the report is accurate,
these reactions are the fourth leading ca use of death in this country --
just behind strokes and ahead of pulmonary disease and accidents. And the
problem might even be worse than that: the study took into account only
hospitalized patients. Plenty of people have reactions to medication at
home.

We haven't known just how bad the problem is because so little money and
effort are devoted to monitoring or researching the safety of drugs after
they have been approved by the Food and Drug Administration. Since 1992,
the F.D.A. has increased spending b y $335 million to speed up the
approval of new drugs. But it has provided little additional money to
monitor drugs after approval.

Medications are tested on only 3,000 to 4,000 volunteers during clinical
trials. Much of what we need to know about a drug's safety can be
determined only once it has been approved and is taken by hundreds of
thousands of patients under varied circumstanc es.

The F.D.A. has been able to speed up approvals because pharmaceutical
manufacturers must now pay six-figure "user fees" along with their drug
applications. But when the companies agreed in 1992 to pay these fees,
they also tacked on a rule that none of th e money generated -- about $36
million this year -- could be used to track adverse reactions after the
drugs were approved.

The F.D.A. currently allots only $140,000 a year from its budget for the
Medwatch system, which is responsible for monitoring reactions to all
drugs sold in the United States. Until last fall, Medwatch wasn't even
computerized; it was run "pretty much lik e a library card catalogue,"
according to Dr. Murray Lumpkin, the deputy director of the F.D.A. Center
for Drug Evaluation and Research.

Moreover, doctors are not required by law to report their patients' drug
sensitivities to the F.D.A., and they rarely do. The F.D.A. estimates that
less than 10 percent of all drug reactions are ever reported.

Once a new safety problem is discovered, it is difficult to get unbiased
research on the subject. The F.D.A.'s own small budget for studying drug
reactions has shrunk even though the number of new drugs approved has
increased. That leaves manufacturers as the main source of financing to
study problems with their own drugs.

Last year, Congress passed legislation creating a pilot program to conduct
independent research on adverse drug reactions and provide safety
information to doctors and patients. But the current White House budget
proposal allocates only a third of the $3 million needed to create the
first center.

There have been exciting discoveries in predicting which patients will
react badly to certain drugs -- particularly in the new field of
pharmacogenetics, in which DNA analysis is used to identify genetic
predispositions to medical sensitivities. The techn ology that allows
doctors to analyze a drop of blood for DNA markers already exists. But we
need to finance research to find the markers that indicate possible drug
sensitivities, or the technology will be wasted.

Pharmaceutical companies have given us plenty of good news about the
benefits of their products, especially since a change in the F.D.A.
television advertising rules last August unleashed a deluge of new "ask
your doctor" advertisements. It is important f or us to learn not only
what these drugs can do for us, but also what they can do to us.

Stephen Fried is the author of "Bitter Pills: Inside the Hazardous World
of Legal Drugs."

Copyright 1998 The New York Times Company