TESTICULAR IMPLANT FAILURES SHOULD BE ASSESSED IN PMAs

TESTICULAR IMPLANT FAILURES SHOULD BE ASSESSED IN PMAs submitted to FDA after finalization of a call for premarket approval applications for the devices. In a proposal outlining a call for PMAs for the pre-1976 Class III devices, the agency says that in order for it to perform a risk/benefit analysis, long-term effectiveness data must be included in the PMA submissions. To date, the agency adds, elements of these data such as "the incidence of implant failure and attendant causes, as well as the incidence of reoperations required, have not been clearly identified." FDA identifies extrusion and erosion of testicular implants through the scrotal wall as the most common potential risks associated with the devices. In addition to information on implant failures, FDA seeks data on the incidence of capsular contracture, noting that "it is not clear what methods are used in the prevention and treatment of capsular contracture..., nor is it clear how these approaches may reduce the risks associated with use of this device." FDA says information on risks of gel leakage and migration is needed for the gel-filled implants. Specifically, such data "should include consideration of gel cohesiveness, envelope thickness/strength," and "diffusion of the gel through the envelope (gel 'bleed')." Data on potential long-term effects of the implants, such as cancer and immune-related connective disorders, as well as information on incidence of rupture or fracture, are also lacking, the agency adds. The proposal relates to solid and silicone gel-filled prostheses, which are "implanted surgically to resemble a testicle." The agency notes that some testicular implants covered with polyurethane foam have been marketed and would also be covered by the proposal. However, the agency adds that use of foam, which "is known to degrade over time" into a potentially carcinogenic compound, "may have been discontinued." Testicular implants are "used to correct congenital anomalies in young males who are born without one or both testicles" or are implanted subsequent to removal of one or both testes due to cancer or testicular trauma. The agency notes these disorders may lead to depression or, in young males, "feelings of inferiority." The implants "may help to alleviate such feelings in males of all ages, thereby improving quality of life." FDA says that PMAs must include studies of factors such as patient satisfaction, improved self-image and improved psychological outlook. The studies should make use of "well-established standardized tests." As in the Jan. 8 proposed call for saline-filled breast implant PMAs (see related story, p. 2), FDA is requiring that sponsors of testicular implant PMAs carry out long-term post- approval followup on implanted patients in order to assess risks of cancer and immune-related connective tissue disorders. The proposal adds that "because young males, including infants, are the recipients of a significant percentage of these implants, information regarding the chronic toxic effects, including possible reproductive and teratogenic effects of silicone, could be of substantial importance in determining the risk to these patients." The proposal requires that animal studies be performed to evaluate "chronic toxicity, carcinogenicity, reproductive toxicity, teratogenicity and later effects on offspring" as well as the toxicity to animals of each chemical that can be extracted from the finished device. Clinical data must include well-controlled studies with "explicit patient inclusion/exclusion criteria," control/comparison groups and "detailed long-term followup." In addition, "detailed patient demographic analyses and characterizations should be presented, and should show that the patients included in the study are representative of the population intended to receive the device." FDA notes that appropriate statistical techniques must be used to analyze all hypotheses stated in the PMA. "A sufficient number of patients needs to be followed for a sufficient length of time to adequately support all statistical claims in any PMA submission," the proposal concludes. When the proposal becomes final, manufacturers of testicular implants will have 90 days to submit PMAs to FDA. The agency is accepting comments on the proposal for 60 days after publication, which is slated for the Jan. 12 or Jan. 13 Federal Register. Requests for reclassification will be accepted for 15 days following publication of the proposal.