A meeting of the Circulatory System Devices Panel was held on July 23, 2009. The Panel discussed and made recommendations pertaining to clinical trial issues for cardiovascular adhesion barriers. The meeting was closed to the public from 8:45 a.m. until 12:30 p.m. to permit discussion of and review of trade secret and/or confidential information.
Many adhesion products have been approved by FDA for obstetric, gynecological, and abdominal use and then occasionally been used off-label during cardiac surgery. There are currently no approved adhesion barriers for use in adult patients in the cardiovascular region and only one approved adhesion barrier for pediatric, cardiovascular use.
The purpose of this meeting was to discuss the characteristics of clinical trial designs that would generate valid scientific evidence to support premarket approval (PMA) for the use of adhesion barriers in adults. Specifically, FDA wanted the Panel to make recommendations on overall trial design issues as well as study endpoint considerations.
Call to Order
Dr. Borer called the meeting to order at 8:00 a.m. James Swink, Executive Secretary for the Circulatory System Devices Advisory Panel, read the conflict of interest statement into the record. All members and consultants were in compliance. Based on the agenda and all financial interests reported by the Panel members and consultants, no conflict of interest waivers were issued in accordance with 18 U.S.C. Section 208 (b)(3). Copies of this information may be obtained by visiting the Agency’s website at http://www.fda.gov/ RegulatoryInformation/Dockets/default.htm or by submitting a written request to the Agency’s Freedom of Information Office, Room 6-30 of the Parklawn Building.
FDA opened the meeting with a presentation that outlined the regulatory history of adhesion barriers, provided an overview of an earlier panel meeting during which the only approved cardiac adhesion barrier was reviewed, summarized the existing clinical data, and detailed the various trial design issues related to collecting adequate data to eventually support an adult indication.
In the afternoon, the Panel was given the opportunity to address FDA’s questions. In general, the Panel offered the following recommendations in response to the FDA questions:
- There is not enough known about the biology of adhesion formation/lysis to definitively assess the pediatric population as an appropriate surrogate for adults.
- However, pediatric patients undergoing staged reoperations may represent the most practical group in which to assess effectiveness. Other potential populations were also discussed (e.g., younger patients receiving bioprosthetic valves, homograft replacement, etc.).
- Determination of device benefit in adult patients will be difficult given low percentage of patients requiring a reoperation coupled with the inability to determine a priori which patients will have severe adhesions.
- Development of non-invasive imaging modalities by which to assess adhesion severity may make it more feasible to collect effectiveness data in adults.
- Patients implanted with ventricular assist devices represent a population with a critical need for this device type; creative trial designs could be considered for evaluating device safety/effectiveness in this patient group.
- A composite endpoint is appropriate for evaluating safety of adhesion barriers.
- In terms of effectiveness endpoints, many panelists believed that an assessment of clinical benefit would be critical, citing that they were unclear as to the exact benefit inferred by a reduction in the percentage of severe adhesions. Suggested endpoints included injury upon reentry and anesthesia time.
- Given the difficulty in directly determining effectiveness with much certainty in an adult population, the Panel felt that a stringent safety hypothesis that rules out any substantial increase in risk would be needed in order to support approval of an adult indication.
Contact: James Swink, Executive Secretary,
(301) 796- 6313 James.Swink@fda.hhs.gov
Transcripts may be purchased from: (written requests only)
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