Participants Left Uninformed in Some Halted Medical Trials
Posted: October 30, 2007
By Barry Meier
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 ClinicalTrials.gov, 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.