A recent editorial in the New York Times suggests that more needs to
be done to allow the FDA to tighten its regulation on drugs that are
already on the market. It calls for more authority on the part of the
FDA to require additional testing, put conditions on, or pull from the
market, drugs that are post-approval but look risky. The issue of
post-approval regulation came to the fore when in 2004 Merck withdrew
from the market its anti-inflammatory drug Vioxx, approved in 1999,
when data showed it was increasing the risk of heart attack and
stroke. Though we applaud the merit behind the editorial's words, we
point out that applying them will require more than giving the FDA
sharper claws. There are high costs associated with testing drugs, and
they will be harder to meet post-approval.
Out of about 5000 exploratory compounds, five will pass the
pre-clinical phase and be tested in humans. Of those, only one can be
expected to gain FDA approval and enter the market. This process takes
an average of 12 years ( https://www.allp.com/drug_dev
1993). Patient safety is paramount throughout this entire process, and
trial drugs must satisfy increasingly rigorous requirements before
advancing to the next stage. Therefore, by the time a trial drug
reaches phase 3, where it is tested in about 1000 to 3000 volunteer
patients, its relative effectiveness and potential side effects are
already known. Phase 3 also tends to be longer; after all, it is meant
to monitor adverse effects after long-term use.
So what makes post-marketing testing different from pre-marketing? The
difference is in the data. During clinical trials, every patient must
keep a careful record of concomitant medication, vital signs, and
adverse effects. Additionally, they must regularly see their physician
to relay the results. This needs to be done in order to give the
clearest picture of the drug's effects, and only the drug's effects.
However, the cost of maintaining and analyzing this information is
non-trivial, as going through thousands of patient files takes both
time and money.
Who then should pay to collect, input, store, and analyze the data of
millions of customers after the drug has been launched? Would you be
willing to keep track of every change in your medicine cabinet for
years on end? These details are crucial for the same reasons they are
crucial in the trial phases, to isolate the effects of the drug. And
then there are the privacy issues that inevitably occur when the
personal data of millions is recorded.
Should the FDA keep an eye out on long-term effects of drugs on the
market? Absolutely. But it likely won't come as cheaply or easily as it
New York Times, February 5, 2007 – Editorial Desk
The Food and Drug Administration is making encouraging moves to
strengthen its regulation of drugs that are already on the market. But
the changes fall far short of what's needed to protect millions of
unsuspecting patients whose adverse effects may show up only after
years of use.
The agency has traditionally focused on the drug-approval process to
determine if a drug is safe and effective. Unfortunately, by that time
a drug has typically been tested in only a few hundred or a few
thousand patients — too few for many kinds of adverse effects to
become apparent. Once the drug is being used by millions, the agency
has limited powers to halt sales that begin to look risky.
Last September, the Institute of Medicine, part of the National
Academy of Sciences, issued a report decrying the big imbalance
between premarketing and postmarketing regulation. The report, which
had been requested by the F.D.A., made some 25 recommendations for
strengthening the agency.
The F.D.A had already been moving to strengthen its safety assessments
but now has developed a more comprehensive approach. One notable
venture is a pilot program to assess the safety of a few breakthrough
drugs about 18 months after they are marketed. The F.D.A. will
collaborate with the Department of Veterans Affairs, the Medicare and
Medicaid programs, and other groups to track drugs in use. It will
publish results on its Web site. Such steps should greatly improve the
agency's ability to monitor the use of drugs in the real world.
Even so, Congress needs to give the agency more money and more teeth:
including explicit powers to impose conditions on drugs that begin to
look risky, to require additional testing and even to yank drugs from