ABSTRACT
Structured benefit–risk (B–R) assessment has gained increased focus and interest in recent years. Pharmaceutical companies and regulatory agencies are increasingly using structured B–R assessments as part of their internal decision-making processes or for review of regulatory filings. However, amid numerous proposed frameworks, metrics, estimation techniques, and utility survey techniques in B–R assessment, quantitative approaches that separate fact from judgment, aggregate all effects with a common unit, and quantify uncertainties about all effects via a model approach are still lacking. In this chapter, we propose a B–R framework that incorporates efficacy and safety data simultaneously for joint modeling and joint evaluation of clinical proof of concept (POC), optimal dose selection, phase 3 probability of success, and an overall B–R evaluation. Simulation studies were conducted to evaluate the properties of our proposed methods. The proposed 176approach was applied to a real clinical study. On the basis of the true outcome of the clinical study, the assessment based on our proposed approach suggested a reasonable path forward for the clinical programs.
