From: Myrl on

Oct 30, 2007
Participants Left Uninformed in Some Halted Medical Trials

Christina Rafsky, left, and Barbara Padgett were in a trial of a
breast implant model that was halted.

Melissa Lyttle for The New York Times

Drug and medical device makers will not be forced to disclose the
results of clinical trials on some products that never reached the


When Congress passed a bill last month requiring makers of drugs and
medical devices to disclose the results of clinical trials for all
approved products, advocates of greater study disclosure applauded the

But a provision that would have mandated disclosures for another group
of products never made it into the final version of the bill. It would
have covered products tested on patients, but dropped before

"Trial sponsors can still choose to keep information about some trials
confidential, creating serious ethical concerns," said Dr. Deborah A.
Zarin, the director of, a Web site run by the
National Library of Medicine.

Many experts said the recent Congressional debate underscored a
troubling fact: some patients in clinical studies never learn about
test results. The problem may be particularly relevant to those
implanted with medical devices that stay with them long after a trial
is over.

For manufacturers and researchers alike, "there is a tremendous
incentive to go on, to forget about the old and move on to the new,"
said Drummond Rennie, a deputy editor at The Journal of the American
Medical Association, who has written critically about clinical trials.

There are no data available for the number of patients who participate
in studies of drugs and medical devices that never make it to the
marketplace, though it is likely that the number runs into the
thousands. A product may not reach the market for a variety of reasons
- it may not perform well in trials, for example, or it may be
rejected by regulators.

Although researchers conducting clinical studies are not required to
disclose test results to study participants, they must alert patients
taking part in a test to emerging product dangers.Companies also have
to keep promises made to regulators at the time a trial began, like
agreements to follow the health of study patients. Such promises are
often required to get approval to begin trials in the first place.

But researchers and manufacturers do not always fulfill even those
minimal requirements. And such failing may be particularly acute in
trials of implanted devices, since those products remain inside

In August, for example, the Food and Drug Administration sent a
warning to Boston Scientific after investigators discovered the
company's diligence in following up with patients faltered around the
time it dropped a product under development.

The product being tested was an experimental stent intended to prevent
the rupturing of an aneurysm in the major abdominal artery.Among other
things, agency investigators found that Boston Scientific, which
halted development of the stent last year after a study showed it
frequently fractured, had neglected to tell patients in that trial
about the problem's scope.

Researchers involved said such a fracture, while not dangerous in
itself, could cause a stent device to shift position, thus rendering
it useless in treating an aneurysm, a weakening of a blood vessel that
can burst with fatal consequences.Paul Donovan, a spokesman for Boston
Scientific, said that the company was moving to address the F.D.A.'s
concerns. While six patients involved in the study have died, Mr.
Donovan said
that the company did not believe that those deaths were related to
either the stent or burst

"There were instances of reporting that was not done in a complete and
timely manner, and we are addressing these shortcomings," Mr. Donovan
said.Because of loopholes in the recently passed Congressional bill,
device makers like Boston Scientific will still have discretion
whether to publicly reveal the results of studies like that of the
failed stent.Under the law, device producers will have to report such
"premarketing" studies and their results to the F.D.A. But that data
will remain in a confidential "black box" until a product is approved;
if a device is rejected or dropped, a company will not have to
disclose those results or even publicly acknowledge that the trials

Device makers lobbied against mandating disclosure for failed
products, arguing that releasing such data would be confusing to
patients and would give away valuable information to a company's
competitors about devices under development that might succeed in
subsequent trials.

"Such disclosures could have the unintended consequence of eliminating
many small device makers from the marketplace," Stephen J. Ubl, chief
executive of the Advanced Medical Technology Association trade group,
testified before Congress in June.

The new bill does allow for a mechanism under which the secretary of
the Health and Human Services Department could release trial data
about unapproved products if a public health issue exists, but such
moves would be argued case by case."This was a
disappointment," said Dr. Steven E. Nissen, the chairman of the
cardiology department at the Cleveland Clinic, who helped draft the
House version of the bill.

"The problem is that if you don't tell people about failed trials, you
can make the same mistake again and again.

"As a result, patients who were in failed trials may find out about
the consequences only by chance.That apparently is what happened last
year when two women struck up a conversation at a hospital in Tampa,
Fla., and found out that they were both there for the same reason:
severe pain, related to their breast implants.As they talked, the
women, Christina Rafsky and Barbara Padgett, learned they had more in
common. Both had seen the same doctor in Tampa, who had persuaded them
to participate in a clinical trial he was overseeing of a new type of
silicone-filled implant made by Inamed Aesthetics, now a unit of
Allergan.Next, a curious Ms. Rafsky called Allergan and learned for
the first time that Inamed had halted that trial in 2005 because the
implant model she had received was rupturing."I was angry and
frustrated," said Ms. Rafsky, who lives in Tampa.

A spokeswoman for Allergan, Caroline Van Hove, said that Inamed
alerted physicians involved in the study in 2005 including the women's
physician, Dr. Gerard Mosiello of Tampa, and suggested that they
contact patients about the rupture issue.

But when Ms. Rafsky contacted Dr. Mosiello, he claimed not to have
received the letter. "He said he did not know anything about the
product being recalled," she said.Ms. Rafsky then filed a complaint
with a panel at the University of South Florida that oversaw the
implant trial, which took place at the H. Lee Moffitt Cancer Center
and Research Institute in Tampa. Such panels, which are known as
institutional review boards, or I.R.B.'s, help ensure, among other
things, that trials are properly conducted.After a lengthy
investigation, the panel found that Dr. Mosiello had failed, among
other things, to follow up on the health of study participants like
Ms. Rafsky and Ms. Padgett.

"It was the consensus of the I.R.B. that there was sufficient evidence
to support that there were lapses in participant care and follow-up,"
the group wrote in a July letter that Ms. Rafsky made available to The
New York Times. Dr. Mosiello declined to be interviewed for this
article.Recently, Ms. Rafsky and Ms. Padgett retained Alan Milstein, a
lawyer who specializes in representing patients involved in clinical
trials.As to whether Dr. Mosiello received the Inamed letter in 2005,
the University of South Florida panel, which interviewed both Dr.
Mosiello and an Allergan official, found that "there was no
documentation or recordkeeping regarding who had been contacted and
when," its letter states.

Ms. Van Hove, the Allergan spokeswoman, said that Inamed had followed
up to make sure researchers like Dr. Mosiello had received the
company's letter. But she acknowledged that it had not checked back to
see what physicians like Dr. Mosiello had told patients, if
anything."The actual communication between a health care provider and
his or her patient is left to the physician exercising his or her
medical judgment," Ms. Van Hove said in a statement.