1/23/01 • Fuzzy Math In Drug Studies?

http://healthwatch.medscape.com/medscape/p/gcommunity/HNews/HnewsPrint.asp?RecID=232469

By Eric Sabo

Jan. 23 (CBSHealthWatch)--How safe are those medications you're taking?
Researchers who test these drugs in clinical trials are the first to find
any troubles, but two new reports charge that many investigators do a poor
job of divulging all the risks.

The bad reactions from an experimental treatment, which doctors ultimately
rely on to prescribe new medications, are sometimes downplayed if not
skimmed over, possibly making the drug seem safer than it really is. In
fact, researchers who publish their results in medical journals often devote
more ink to their academic affiliations than they do to explaining the
nature and severity of a drug's side effects, claims a new study in the
Journal of American Medical Association.

"Important information is not adequately reported," says study author Joseph
Lau, MD, of the New England Medical Center. "In real clinical practice, side
effects are far more common than what appears in these studies."

Lau and John Ioannidis of Tufts University reviewed close to 200 trials of
drugs used to treat various diseases, including AIDS, arthritis and
hypertension. The severity of the side effects, according to their analysis,
was poorly explained in more the 60% of the studies.

Moreover, less than half of the published findings listed how frequent these
problems were in patients who stopped taking the drugs. Reporting just the
basic drawbacks allows for more discussion of other important issues in the
study, but Lau says that drug side effects deserve greater attention.

"When a drug may be of a small benefit, and you begin to take into
consideration the side effects, then the overall benefit may no longer be in
your favor," he says. "You need to have a good understanding of both the
benefits and side effects to make a good decision."

And skipping over the bad news may start even before study results are
published, claims one expert. Based on records made available through the
Freedom of Information Act, Adil Shamoo, MD, of the University of Maryland
contends in a soon to be released study for Accountability in Research that
investigators are not always up front with government regulators. Over the
last 10 years, Shamoo found that the National Institutes of Health (NIH)
received less than 900 reports of serious adverse events, including just 8
deaths.

"There's only eight reported deaths in ten years? It doesn't make any
sense," he says. Out of the 70 million or so subjects who were involved in
clinical trials, Shamoo estimates that about 51,000 are likely to die in a
one-month period. The only explanation, he argues, is that researchers are
not reporting all the problems they should.

"Thousands of patients have died in research settings and no one has said
anything," Shamoo says.

These allegations come at time when the Food and Drug Administration (FDA)
is calling for greater scrutiny of studies involving high-tech treatments
like gene therapy and xenotransplantion. Just last week, the FDA proposed
new rules that would make once confidential safety information from these
trials open to the public. Industry groups are deeply opposed.

"Disclosing data on all adverse events in clinical trials without first
investigating the causes could unnecessarily frighten patient sand the
public," said Carl Feldbaum of the Biotechnology Industry Organization, in a
statement. "The vast majority of adverse events in clinical trials are
related to the patients' underlying diseases, not the experimental
medicines."

But for long-time government watchdogs like Shamoo, the FDA should go
further. "It's positive step," he says. "But just because these trials have
more publicity doesn't mean all others don't need it."

Indeed, Shamoo says that the scandal-tainted research has brought other
potential dangers to light. Before Jesse Gelsinger died in a gene therapy
trial nearly two years ago, there were fewer than 50 adverse events reported
with similar type drugs in an 8-year period. During the next 4 months after
his death, Shamoo says that more than 900 serious events popped up.

Lau points to many reasons for why drug side effects might get less press:
Journal articles need to cut for space, researchers tend to care more about
treatment benefits rather than how a patient handles the medication, and
drug companies like to see their products in the best possible light.

"I think everyone is at fault," Lau says.

Shamoo places the blame on money. "It's the conflict of interests," he says.
"If I have a small company, and the stock goes up or down based the news of
the data, than it's human tendency not report these problems."