All Times EDT
Keywords: Quantitative, Benefit-Risk Assessment
A favorable benefit-risk (B-R) profile is the basis for regulatory approval of a medicinal product. While sometimes straightforward, the actual decision-making can be a complex task. B-R evaluation is often viewed a qualitative process relying on quantitative data with some level of uncertainty, which is further complicated by stakeholders having differing perspectives on the clinical importance of events and what level of B-R tradeoff is acceptable.
The VOYAGER PAD (Efficacy and Safety of Rivaroxaban in Reducing the Risk of Major Thrombotic Vascular Events in Subjects With Symptomatic Peripheral Artery Disease Undergoing Peripheral Revascularization Procedures of the Lower Extremities) trial randomized patients to rivaroxaban 2.5 mg twice daily plus aspirin or aspirin alone. For the current B-R assessment, efficacy endpoints (benefits) were acute limb ischemia, major amputation of a vascular cause, myocardial infarction, ischemic stroke, and cardiovascular death; safety endpoints (risks) were fatal, non-fatal critical organ, and other major bleeding. The B-R balance was quantified using a structured approach by calculating the between-treatment rate differences in efficacy and safety endpoints, respectively, presented as the excess number of events along with 95% CI per 10,000 patients treated. Between-treatment differences in benefits and risks based on Kaplan-Meier estimates were also plotted to highlight B-R balance over time. Because benefits and risks may reflect different clinical importance, a Multi-Criteria Decision Analysis (MCDA) was applied, using weights based on utility values for the relevant health states from a literature review. Results demonstrated both a positive B-R profile overall and a temporal trend towards improved B-R balance over time.