A doctor is thinking of trying a new drug on a 67-year-old
patient because a study shows it works well in men only slightly
younger. But the doctor doesn't know about a clinical trial that
found serious side effects in older patients. Those results were
never published.
John Schneider, a doctor of internal medicine and a member of the
American Medical Association's Council on Scientific Affairs, fears
that that scenario happens all too often.
Because drug companies often do not reveal the contents of
studies that make their drugs look bad, he said, many doctors are
frustrated because they sometimes prescribe medications without
knowing all the information about them and possible side
effects.
Now, the AMA is considering asking the federal government to open
up this secretive world. The group's House of Delegates will vote
during a meeting that starts Saturday on a resolution urging the
U.S. Department of Health and Human Services to create a registry of
all clinical trials and their results.
"No comprehensive system for tracking, organizing and
disseminating information about ongoing clinical trials currently
exists," the Council on Scientific Affairs wrote in a report
supporting the registry resolution.
Last week, New York state's attorney general, Eliot Spitzer, took
another approach when he filed a civil lawsuit accusing
GlaxoSmithKline P.L.C., which has a U.S. headquarters in
Philadelphia, of consumer fraud in its promotion of the
antidepressant Paxil. The suit alleges that, beginning in 1998,
Glaxo failed to disclose negative information from clinical trials
of Paxil in children, and even misinformed its sales staff about the
drug's effectiveness.
Glaxo spokeswoman Mary Anne Rhyne said that the company conducted
eight pediatric clinical trials and that the data from all of them
were communicated in more than 25 presentations at major medical
meetings. Glaxo has never sought regulatory approval to market Paxil
for children, and "the company's policy is not to promote off-label
uses," Rhyne said.
Peter J. Pitts, associate FDA commissioner for external affairs,
said that, under FDA rules, a company seeking approval to sell a new
drug must submit the results of all clinical trials, but the agency
considers that information proprietary. If the drug is the subject
of public FDA hearings, some of the data often become public then
and in labeling information.
When companies are testing a drug for a new use, they must report
any safety problems to the FDA, but they do not have to turn over
all their data until they file for approval.
Eighty percent of the $5.6 billion spent on clinical trials
involving people in 2002 came from pharmaceutical companies or
manufacturers of medical devices, prompting concerns about their
role in designing studies and providing the public with information
about the research, according to the AMA.
"One of the problems with the whole system of reporting is that
the people who design and report the trials are not dispassionate,"
said Dr. Jeffrey Drazen, editor in chief of the New England Journal
of Medicine. "They have a fiduciary interest in it."
When pharmaceutical companies sponsor reseach, they do not have
to seek publication of studies that make their drugs look bad. And
there is evidence that medical journals are more likely to publish
"positive" studies - those that show a drug works - than negative or
inconclusive studies.
Drug industry officials will watch the AMA's debate closely. "We
are examining whether we need to take any new position," said Alan
Goldhammer, associate vice president for regulatory affairs of the
Pharmaceutical Research and Manufacturers of America, the industry
trade group. He said they had not taken up the issue in the
past.
In 1998, Glaxo Wellcome - which merged with SmithKline Beecham in
2000 - provided public summaries of all clinical trial protocols,
Rhyne said. GlaxoSmithKline is working on an expanded version of the
registry that would summarize trial protocols as well as results of
company-sponsored clinical trials, both negative and positive, she
said. The online registry would not provide the underlying data,
only a summary.
The AMA's resolution grew from lobbying by the American
Psychiatric Association and the American Academy of Child and
Adolescent Psychiatry.
"There has been a concern in the psychiatric community about the
accuracy, validity and reliability of the studies in our
literature," said David Fassler, a child and adolescent psychiatrist
in Vermont who is a proponent of a clinical trial registry. While
the possibility that some antidepressants may cause suicidal
thoughts in children has made them the focus of media attention
recently, Fassler said the issue of unpublished drug information
affects all medical specialties.
Prestigious medical journals, such as the Journal of the American
Medical Association and the New England Journal of Medicine, publish
less than 10 percent of the scientific papers submitted to them,
their editors said. In recent years, they have tried to publish more
negative studies, but there are factors that work against that,
Drazen said.
Because of the way statistics work, he said, it often takes fewer
people to prove that a drug does work than to prove it does not.
Several people who support the idea of a registry said it would
be especially helpful for researchers who evaluate all the studies
on a topic. Many doctors use such reports.
"My sense is that it would be extraordinarily useful," said Brian
Strom, an expert on adverse drug reactions at the University of
Pennsylvania Health System.
