Full article reprinted from 'The Gray Sheet" - July 27, 2009
Panelists advising FDA officials on how to design clinical trials for cardiovascular adhesion barriers said that until they better understand the benefits of these devices, they are reluctant to expose heart patients to more than the slightest of risks. Read more...
FDA Panel Is Wary Of Cardiovascular Adhesion Barrier Trials
Full article reprinted from 'The Gray Sheet" - July 27, 2009
Panelists advising FDA officials on how to design clinical trials for cardiovascular adhesion barriers said that until they better understand the benefits of these devices, they are reluctant to expose heart patients to more than the slightest of risks.
"Given that we really can't in a direct way measure the benefit, it's very hard to conceive of allowing for approvability a risk that is substantially greater than none at all," said Jeffrey Borer, M.D., Cornell Medical College, and chair of the Circulatory System Devices Panel.
The panel met July 23 in Gaithersburg, Md., for a public discussion on trial design for cardiovascular adhesion barriers, devices that help prevent post-surgery fibrotic tissue growth on heart muscle or surrounding vessels, which can make it difficult for surgeons to re-operate. Similar products are approved and used in obstetric, gynecological and abdominal procedures, and off label in some heart surgeries.
The panel also met behind closed doors with FDA officials and SyntheMed, which wants to expand the market for its Repel-CV cardiac adhesion barrier, approved in March for children, to the adult population.
SyntheMed CEO Robert Hickey would not elaborate on the closed-door discussions, but said the talks gave additional clarity on requirements for a clinical trial.
Trials In Need Of Dependable Endpoints
During the public discussion, panelists failed to settle on solid primary endpoints, with some committee members arguing that measuring the severity of post-surgical adhesions was not a demonstrable surrogate for clinical outcomes.
"It's too random, and it doesn't tell you anything as a primary endpoint," said Craig Selzman, M.D., University of Utah.
To complicate matters, measuring the severity of cardiac adhesions poses practical challenges, namely the need to re-open the chest of a study patient to get a close look.
Borer urged trial sponsors to find ways to validate methodology for using non-invasive imaging techniques to measure the severity of post-surgical adhesions.
Magnetic resonance imaging may be more appropriate than computed tomography because it would not have the same radiation risks, he added.
The panel also debated the practicality of identifying a subset of heart patients most likely to undergo a second procedure, who would then be candidates to help measure the safety and effectiveness of adhesion barriers.
Specifically, panelists discussed the pros and cons of enrolling ventricular assist device patients in trials for circulatory adhesion devices, including to what extent the data could be extrapolated to the general adult population.
Benefits Of Reducing Adhesions Hard To Quantify
Borer recognized that cardiac surgeons believe there is a benefit to preventing adhesions with barrier devices. However, "unless we have a good sense of what the benefit truly is, we really cannot be anything less than very stringent about the allowable risk for that ill-defined benefit," he said.
The mechanism for a barrier device in preventing adhesions is not fully known, said panel member Michael Mitchell, M.D., DRI Medical College of Wisconsin. He worries that using a barrier device could compromise the system in ways not yet understood.
Eugene Blackstone, M.D., Cleveland Clinic, pushed the panel to consider the possibility that other sponsors may bring different cardiac adhesion barrier technologies to trial, and wants FDA to consider safety issues such as allergic reactions.
Blackstone suggested secondary endpoints might also include the amount of blood loss during and following a second cardiac procedure, risk to dissection and the overall duration of a procedure.
Borer said an adjunct endpoint could also be to look at a surgeon's "entry into areas we didn't want to go" during a secondary procedure due to adhesions.
"Injury of the heart - that is the point," Sheridan said. "I would hate to leave the meeting with the idea that injury to the heart is anything less than a primary endpoint."
- Monica Hogan
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