Patient-Centered Clinical Trial Design for Heart Failure Devices via Bayesian Decision Analysis
As part of its heart failure project, MDIC’s multi-stakeholder group of experts published this manuscript in addition to this Methods Report to advance robust discussion about opportunities to incorporate the views of patients in clinical development of medical devices. This paper specifically reviews the potential to use a novel statistical and design approach for clinical trials called Bayesian decision analysis (BDA). BDA provides a means by which it may be possible to conduct smaller, faster clinical trials using endpoints and outcome measures that have been found to be meaningful for patients through patient preference studies. A key element of this approach is to calculate the willingness of patients to accept a greater risk of potential harm associated with a device in exchange for the potential that the device may bring benefits of perceived value. Patients may be interested in reviewing this paper to better understand how BDA works and how it can be used in medical device clinical trial design.
This paper adds to the growing body of published literature about how novel statistical methods and innovative trial design may be incorporated into medical device clinical development programs. In this paper, experts describe a process by which Bayesian decision analysis (BDA) was applied to heart failure device studies in an effort to choose an optimal significance threshold that maximizes the expected net benefit to patients across both the null and alternative hypotheses. The paper describes how results from a discrete-choice experiment (DCE) study focusing on heart failure patients’ preferences (specifically patients’ willingness to accept therapeutic risks in exchange for quantifiable benefits with alternative hypothetical medical device performance characteristics) were used to adjust the optimal statistical significance threshold for a potential device trial. The paper also describes how the benefit-risk tradeoff allowed for estimation of the impact from the patient perspective of a false positive or false negative pivotal trial result. The paper presents the results from this effort, including a description of the willingness of heart failure patients to bear additional uncertainty in effectiveness of the investigational device in exchange for its benefits, concluding that BDA provides a systematic, transparent, and repeatable process for combining clinical and statistical significance, explicitly incorporating burden of disease and patient preferences into the risk evaluation of a medical device by manufacturers.