G.K. Raju, Karthik Gurumurthi, Reuben Domike, Dickran Kazandjian, Ola Landgren, Gideon M. Blumenthal, Ann Farrell, Richard Pazdur, Janet Woodcock

Drug regulators around the world make decisions about drug approvability based on qualitative benefit-risk analysis. In this work, a quantitative benefit-risk analysis approach captures regulatory decision-making about new drugs to treat multiple myeloma (MM). MM assessments have been based on endpoints such as time to progression (TTP), progression-free survival (PFS), and objective response rate (ORR) which are different than benefit-risk analysis based on overall survival (OS) due to an increased focus on quality of life instead of quantity of life. Twenty-two FDA decisions on MM drugs submitted to FDA between 2003 and 2015 were identified and analyzed. The benefits and risks were quantified relative to comparators (typically the control arm of the clinical trial) to estimate whether the median benefit-risk was positive or negative. A sensitivity analysis was demonstrated using ixazomib to explore the magnitude of uncertainty. FDA approval decision outcomes were consistent and logical using this benefit-risk framework. This article is protected by copyright. All rights reserved.