New Drugs Called Riskier Than Old

[Guest guest]

http://www.washingtonpost.com/wp-dyn/articles/A11573-2002Apr30.html

New Drugs Called Riskier Than Old

Study Says Harmful Side Effects Spurred Warnings, Withdrawals

By Marc Kaufman

Washington Post Staff Writer

Wednesday, May 1, 2002; Page A01

Newly approved drugs are riskier than older ones and doctors should avoid

prescribing them when equally effective and long-used medications are

available, according to a study reported in today's Journal of the American

Medical Association.

In a provocative review of a quarter-century of unexpected and harmful side

effects from the most innovative new prescription drugs, the authors found

that more than 10 percent had been taken off the market or required new

warnings against dangerous " adverse reactions. "

" Based on our results and those of others, clinicians should avoid using new

drugs when older, similarly [effective drugs] are available, " the authors

conclude. " Patients who must use new drugs should be informed of the drug's

limited experience and safety record. "

The findings add to the increasingly contentious debate over whether the

Food and Drug Administration is doing enough to protect consumers from the

risks posed by new drugs.

Among the medications taken off the market recently were the nighttime

heartburn drug Propulsid (removed because of fatal heart rhythm

abnormalities), the diabetes drug Rezulin (removed after causing liver

failure) and the irritable-bowel-syndrome treatment Lotronex (removed for

causing fatal constipation and colitis). All three were taken off the market

in 2000.

While the FDA's job is to ensure that drugs coming on the market are safe

and effective, officials there acknowledge that a small number of harmful

side effects undetected during pre-market trials are inevitably discovered

only after a drug has been approved and used by millions of patients.

Because the FDA approved many more drugs during the 1990s than in previous

decades, more unexpected harmful side effects are appearing.

" Our data found that only half of all serious adverse reactions are detected

seven years after a drug enters the market, " said the study's lead author,

E. Lasser. " Millions of patients are exposed to potentially unsafe

drugs each year. "

In an accompanying commentary in the journal, a top official with the FDA's

Center for Drug Evaluation and Research Policy, J. Temple, argues

that the study's assessment of the agency's track record on safety issues is

misleading. He says many of the warnings added after the drugs entered the

market reflected subsequent scientific findings or the discovery that

medications known to be toxic turned out to be more toxic than expected.

" This is a useful study, " Temple said in an interview. " But when I looked

more carefully, many of the problems described are not good reasons to avoid

using a new drug. . . . Patients needn't be nervous about using new drugs

prescribed by their doctors. "

Temple said recent changes in how drugs are developed should help limit the

number of problematic side effects. He also said regulators are now focused,

in particular, on potential liver damage from new drugs -- the cause of some

of the most significant drug withdrawals.

The drug industry trade group Pharmaceutical Research and Manufacturers of

America (PhRMA) yesterday called the JAMA study " misinformed and

misleading. "

" We note that Dr. Lasser et al. state that the benefit/risk ratio of new

medicines sometimes shifts as new information is acquired after marketing,

but they fail to state that it often shifts to the benefit side, " PhRMA said

in a statement. " For example, cholesterol-lowering drugs have been found

after marketing to have significant additional benefits. "

But Sidney Wolfe of Public Citizen's Health Research Group, a coauthor of

the JAMA report, said that despite FDA assurances significant safety

problems remain. " Rather than getting better, we believe the situation is

just as bad, or worse, " he said.

The authors of the study, most from Cambridge Hospital and Harvard Medical

School, used FDA announcements and the Physicians' Desk Reference -- an

annual compendium of drugs on the market -- to study how many medications

were withdrawn and how many required new safety notices to doctors, called

" black box " warnings. Between 1975 and 1999, they report, 548 new chemical

entities were approved by the FDA as prescription drugs, and 56 were either

withdrawn or given new black box warnings.

Because many of the 548 drugs were approved recently, the researchers used a

probability analysis to estimate how many would require FDA action. Based on

experience, they conclude that about 20 percent of the drugs would acquire a

new black box warning over a 25-year period or would be taken off the

market.

A decade ago, the FDA came under intense pressure from the drug industry and

some legislators to speed its drug-approval process. Congress approved a

program in 1992 that allowed the FDA to raise additional funds through a

user fee program supported by the drug industry. Reauthorization of that

program is being debated in Congress, where it has broad bipartisan support.

However, some lawmakers and others argue that the user fees give the drug

industry undue influence over the FDA, and have contributed to the kind of

safety concerns raised in the JAMA article.

But the pressures to speed approvals continue, as illustrated by a poll

conducted by the Competitive Enterprise Institute that was released

yesterday. The institute, a free-market advocacy group, found in its poll

that more than 60 percent of cancer specialists believe the FDA is still

moving too slowly.

© 2002 The Washington Post Company