FDA SILICONE BREAST IMPLANT RECONSTRUCTION "OPEN PROTOCOL" MONITORING

FDA SILICONE BREAST IMPLANT RECONSTRUCTION "OPEN PROTOCOL" MONITORING will include inspections of 10% of the 3,000 clinical investigators who are expected to participate in the study "over the course of the program," FDA says in a Jan. 6 document. The document responds to a House Government Operations human resources subcommittee draft staff report on the agency's regulation of silicone gel-filled breast implants. FDA says that the investigator monitoring program will result in about 50 to 60 inspections per year. The open availability study is the second part of a three- stage program under which FDA is allowing distribution of silicone gel-filled breast implants ("The Gray Sheet" April 20, p. 1). The study, which began on Dec. 1, allows silicone breast prostheses to be implanted in women who have had a mastectomy or have deformities resulting from a serious trauma to a breast, or a disease or congenital disorder. The first study phase, which expired when the second stage began, allowed for implantation in a smaller group of women deemed to have "urgent need" for the devices. The third phase is a limited study of the implants for breast augmentation. Mentor is the only firm currently supplying breast implants for the open availability protocol. McGhan, which continues to be out of compliance with good manufacturing practices regulations, has FDA clearance to distribute a limited number of implants to women who have the firm's temporary tissue expander in place ("The Gray Sheet" Nov. 2, p. 7). As part of its open protocol monitoring, FDA will "inspect Mentor to ensure that they can adequately manage and implement the program" and will "continue to inspect Mentor on a periodic basis to ensure compliance with the program." The agency's "open availability" protocol monitoring effort also will include inspections of 20% of the local institutional review boards overseeing investigators, resulting in about 12 inspections per year. In addition, the agency plans to inspect the "national" IRB "at least once a year." Set up by Mentor in August when the firm initiated physician recruitment for the reconstruction protocol ("The Gray Sheet" Aug. 10, p. 1), the national IRB can be used by surgeons who do not have a local IRB or wish to bypass their local IRB. The agency says that its monitoring strategy "will enable FDA to identify trends that may signal physician abuses, particularly performing augmentation surgeries under the guise of 'correcting a deformity.'" In the draft report, the subcommittee staff claims that "FDA has had virtually no role in monitoring the open protocol since it began enrolling patients in September." The staff says that it is concerned that FDA will not assure that certification and informed consent forms will be gathered by Mentor; the staff maintains that there have been irregularities in obtaining these forms during the urgent need protocol. In a press release issued with the report, subcommittee chairman Donald Payne (D-N.J.), who assumed leadership of the subcommittee following the death of Rep. Ted Weiss in September, stated: "When the FDA was under intense scrutiny regarding breast implants,...they were more careful about their regulatory efforts. When attention was focused elsewhere, it was business as usual at FDA." The staff maintains that during a December inspection of Mentor ("The Gray Sheet" Jan. 4, In Brief), FDA found that many urgent need patient files lacked patient informed consent and physician certification forms. An FDA "examination of 37 closed patient files [at Mentor] revealed that 12 (32%) did not have informed consent forms and five (14%) had incomplete urgent need certifications," the report says, adding that "an examination of 32 working patient files revealed 26 (81%) urgent need certifications were missing and two (6%) were incomplete, and seven (22%) consent forms were missing." FDA counters that the allegations about the Mentor inspection are "not true." The inspection of Mentor "revealed that all closed patient files contained the required, physician-signed certification attesting that the patient met the 'urgent need' criteria and that the patient had signed the required informed consent form" [emphasis FDA's]. The agency explains that under the urgent need protocol, Mentor was required to "maintain copies of these [physician certifications] in each file" but was not required "to receive or maintain actual copies of the multi- page informed consent form for each patient." In addition to FDA's monitoring of the protocols, the subcommittee also targeted the content of the patient informed consent forms used in the studies. Faulting FDA's "capitulation to criticisms of informed consent forms," the subcommittee notes that the agency "deleted many of the statements in the... form[s]" that had been objected to by the American Society of Plastic and Reconstructive Surgery. For example, the report asserts that FDA weakened warnings about closed capsulotomy procedures, gel migration and breast feeding. Defending the consent form, FDA proclaims: "The informed consent form for silicone gel-filled breast implants is one of the most extensive and complete documents of its kind ever to be approved by FDA." The agency adds: "As with all groups, FDA took the advice of ASPRS where it improved the accuracy or clarity of the material, but the agency did not accept many of ASPRS's suggestions" [emphasis FDA's].