Analysis of Benefit-risk Balance in Decision-making of the Food and Drug Administration for Premarket Approval of Therapeutic Medical Devices

Compared to the evaluation of new pharmaceutical drugs, the assessments of the design and results of clinical trials for medical devices are not well established. For medical devices, the definition of the benefit-risk balance assessed during approval by regulatory agencies is not clear, which may result in subjectivity of the decision-making process. It is possible to hypothesize that the newly approved medical device should be superior in both risk and efficacy to the already existing device, which is used as control. To test this hypothesis, we performed an independent analysis of the premarket approvals (PMA) of therapeutic medical devices based on assessment review of reports of a regulatory agency, the Food and Drug Administration (FDA). A total of 74 studies that tested various medical devices for PMA were selected. For each clinical trial, the study design was evaluated with particular emphasis on its nature (retrospective or prospective). presence of a control arm, randomization, and masking. We performed an objective analysis of the benefit-risk balance between effectiveness and safety in the test arm compared to that in the control arm, using an original method for data evaluation. Of the 74 studies, 56 (76%) were prospective, 1 was purely retrospective (1%). 15 were mixed (20%), and 2 (3%) did not specify the nature of study. Only 46 studies (62%) included a comparative control group, 26 of which (57%) demonstrated "equivalence" but not "superiority" of the primary effectiveness measure. Depending on the evaluation criteria (mortality, complications, adverse effects, others) the results of safety assessment revealed advantage of the test arm in only 16-38% of comparative studies. The designs of the protocols for testing therapeutic medical devices and the criteria of objective evaluation during approval for broad clinical practice are not standardized. For PMA approval, FDA does not ultimately require better effectiveness and/or safety of the new device compared to the existing control device.