FDA's Approval of Anti-Scarring Device for Children is Another in a Long Line of Questionable Decisions
March 9, 2009
Peter Lurie, M.D., M.P.H., Deputy Director, Public Citizen's Health Research Group
The approval on March 6 of SyntheMed’s REPEL-CV bioresorbable cardiac adhesion barrier for pediatric patients once again demonstrates the Food and Drug Administration’s (FDA) low standard for approving medical devices. On the heels of the FDA’s clearance of ReGen’s Menaflex implant, this approval further documents the Agency’s willingness to approve a device that has failed to demonstrate any clinical benefit.
REPEL-CV is intended to help reduce the severity of post-surgical adhesions (scarring) in children following open-heart surgery. These scars may complicate subsequent heart surgeries because the scars would need to be broken up, potentially increasing operative time.
At best, this device demonstrated a modest decrease in the severity of adhesions; it had no impact on the fraction of patients who had adhesions nor on the percentage of the operative area that had adhesions. Even this “benefit” depended on the use of a rating scale that has never been validated. In addition, because remnants of the REPEL-CV implant were seen in 34 percent of patients in the REPEL-CV group, significant unblinding could bias the results in the direction of apparent device effectiveness.
Given that the apparent purpose of adhesion prevention is the facilitation of follow-up surgeries, the only endpoint with a resemblance to clinical significance is adhesion dissection time. Yet this endpoint was not influenced by REPEL-CV (25.9 minutes to break up adhesions in the treatment group vs. 25.0 minutes in the control group). The lack of a positive result for the only clinical endpoint calls into question the usefulness of the device.
In the trial, there were also signs of possible dangers associated with REPEL-CV, including trends toward higher risks of death and mediastinal (chest) infection. These differences were not statistically significant, but the consistent direction of the adverse effects observed, even if non-significant, is concerning. Because the trial was so small, we can only be assured that there was not more than a three-fold increase in mortality and not more than a 10-fold increase in mediastinal infections for patients implanted with the device. This is hardly reassuring.
The approval of REPEL-CV bears an eerie resemblance to another device, Intergel, an anti-adhesion device intended for pelvic surgeries that also demonstrated reduced adhesions without clinically validated endpoints. That trial was also underpowered for safety and showed a consistent but non-statistically significant increase in infection rates. Less than two years after Intergel was approved, the company removed the product from the market due to reports of post-operative pain, foreign body reactions, and tissue adhesions requiring repeat surgery, including three deaths among women who received it. This history should have given the FDA pause before once again approving an adhesion barrier with only surrogate endpoints and a questionable safety record.
Dr. Daniel Schultz, director of FDA’s medical device center, described the approval as “an example of FDA’s commitment to work with regulated industry.” The approval of REPEL-CV is more appropriately characterized as the latest in a string of ineffective devices approved by the FDA, including vagus nerve stimulation, transcranial magnetic stimulation, and the Menaflex collagen scaffold. The public has a reasonable expectation that only safe and effective devices will come to market. Yet again, these expectations have been dashed.