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
move.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
marketing."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 patients.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 aneurysms."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 occurred.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.