US: Despite Vow, Drug Makers Still Withhold Data

Publisher Name: 
New York Times


 

 

When the drug industry came under fire last summer for failing to
disclose poor results from studies of antidepressants, major drug
makers promised to provide more information about their research on new
medicines. But nearly a year later, crucial facts about many clinical
trials remain hidden, scientists independent of the companies say.

Within the drug industry, companies are sharply divided about how
much information to reveal, both about new studies and completed
studies for drugs already being sold. The split is unusual in the
industry, where companies generally take similar stands on regulatory
issues.

Eli Lilly and some other companies have posted hundreds of trial
results on the Web and pledged to disclose all results for all drugs
they sell. But other drug makers, including Merck and Pfizer, release less information and are reluctant to add more, citing competitive pressures.

As a result, doctors and patients lack critical information about
important drugs, academic researchers say, and the companies can hide
negative trial results by refusing to publish studies, or by
cherry-picking and highlighting the most favorable data from studies
they do publish.

"There are a lot of public statements from drug companies saying
that they support the registration of clinical trials or the
dissemination of trial results, but the devil is in the details," said
Dr. Deborah Zarin, director of clinicaltrials.gov, a Web site financed by the National Institutes of Health that tracks many studies.

Journal editors and academic scientists have pressed big drug makers
to release more information about their studies for years. But the
calls for more disclosure grew stronger after reports last year that
several companies had failed to publish studies that showed their
antidepressants worked no better than placebos.

In August, GlaxoSmithKline
agreed to pay $2.5 million to settle a suit by Eliot Spitzer, the New
York attorney general, alleging that Glaxo had hidden results from
trials showing that its antidepressant Paxil might increase suicidal
thoughts in children and teenagers. At a House hearing in September,
Republican and Democratic lawmakers excoriated executives from several
top companies, including Pfizer and Wyeth, for hiding study results. In response, many companies promised to do better.

At the same time, Merck and Pfizer have been criticized for failing
to disclose until this year clinical trial results that indicated that
cox-2 painkillers like Vioxx might be dangerous to the heart.

Drug makers test their medicines in thousands of trials each year,
and federal laws require the disclosure of all trials and trial results
to the F.D.A. While too complex for many patients to understand, the
trial results are useful to doctors and academic scientists, who use
them to compare drugs and look for clues to possible side effects. But
companies are not required to disclose trial results to scientists or
the public.

Some scientists and lawmakers say new rules are needed, and a bill
that would require the companies to provide more data was introduced in
the Senate in February. So far no hearings have been scheduled on the
legislation. The bill's prospects are uncertain, said a co-sponsor,
Senator Christopher J. Dodd, Democrat of Connecticut.

The drug makers have been criticized both for failing to provide
advance notice of clinical trials before they begin and for refusing to
publish completed trial results for medicines that are already being
sold.

The two issues are related, because companies cannot easily hide the
results of trials that have been disclosed in advance, said Dr. Alan
Breier, chief medical officer of Lilly, the company that has gone
furthest in disclosing results.

"You're registering a trial - at some point, the results have got to
show up," Dr. Breier said. He added that disclosing trial results was
important both to give doctors and patients as much information as
possible and to improve the industry's reputation, which has been
damaged by several recent withdrawals of high-profile drugs.

"Fundamentally, what we're doing is in the interest of patients, and
I think that that is the winning model, for academia, for industry and
for the future," he said.

In September, Pharmaceutical Research and Manufacturers of America,
an industry lobbying group known as PhRMA, said it would create a site
for companies to post the results of completed trials. Then, under
pressure from the editors of medical journals, the major drug companies
in January agreed to expand the number of trials registered on
clinicaltrials.gov, the N.I.H. site, which was originally created so
patients with life-threatening diseases could find out about clinical
trials.

But Merck, Pfizer and GlaxoSmithKline, three of the six largest drug
companies, have met the letter but not the spirit of that agreement,
Dr. Zarin said.

The three companies have filed only vague descriptions of many
studies, often failing even to name the drugs under investigation, Dr.
Zarin said. For example, Merck describes one trial as a "one-year study
of an investigational drug in obese patients."

Drug names are crucial, because the clinicaltrials.gov registry is
designed in part to prevent companies from conducting several trials of
a drug, then publicizing the trials with positive results while hiding
the negative ones. If the descriptions do not include drug names, it is
hard to tell how many times a drug has been studied.

"If you're a systematic reviewer trying to understand all the
results for a particular drug, you might never know," Dr. Zarin said.
"You don't know whether you're seeing the one positive result and not
the four negative results - you don't have context."

Pfizer, Merck and GlaxoSmithKline say that they disclose their
largest trials, which determine whether a drug will be approved. Though
they would not discuss their policies in detail, executives and press
representatives at the companies said generally that disclosing too
much information about early-stage trials might reveal business or
scientific secrets.

Rick Koenig, a spokesman for Glaxo, said the company understood the
concerns about disclosure and planned to add more information to
clinicaltrials.gov. He declined to be more specific, saying Glaxo and
other companies were discussing the issue with regulators and medical
journal editors.

In contrast, Lilly has registered all but its smallest trials at
clinicaltrials.gov. Dr. Breier of Lilly said the company believed that
it could protect its intellectual property and still increase the
amount of information it released.

Lilly has also posted the results of many completed studies to clinicalstudyresults.org,
the Web site created last September by PhRMA. That site now contains
some information on nearly 80 drugs that are already on the market.
Both Lilly and Glaxo have posted detailed summaries of hundreds of
studies.

Pfizer, on the other hand, has posted only a few, and Merck has posted none.

All the companies were meeting the group's guidelines for the site,
said Dr. Alan Goldhammer, associate vice president for regulatory
affairs at PhRMA. The lobbying group requires only that its members
post a notice that a trial has been completed and a link to a published
study or a summary of an unpublished study, he said. Studies completed
before October 2002 are exempt from the requirements, and PhRMA has not
set penalties for companies that do not comply.

"We're seeing pretty regular posting on a weekly basis, and as best
we can assess right now, things are on track for meeting the goal we
and our members set for ourselves," Dr. Goldhammer said.

The continued gaps in disclosure have caused some lawmakers to call
for new federal laws. The bill introduced in February by Mr. Dodd and
Senator Charles E. Grassley, Republican of Iowa, would convert
clinicaltrials.gov into a national registry for both new trials and
results and impose civil penalties of up to $10,000 a day for companies
that hide trial data. But Mr. Dodd said that the chances the bill would
pass in this Congress were even at best.

"I haven't had that pat on the back saying, 'This is a great idea, let's get going on this as fast as we can,' " Mr. Dodd said.

Dr. David Fassler, a psychiatry professor at the University of
Vermont and a longtime proponent of more disclosure, said that trial
reporting had improved in the last two years. But he said that a
central federally run site, as opposed to the current mix of government
and industry efforts, was the only long-term solution.

AMP Section Name:Health