29: Benefit-Risk Assessment with Complex Patient Trajectories

Music City Center 

Assessment of benefit-risk for different subgroups/strata of patients is a long-standing challenge and is of great interest for patients, industry, and regulators. More comprehensive assessments of risk and benefit
can be obtained by characterizing the joint distribution of multiple safety and efficacy outcomes and their change over time. To this end, we propose a Bayesian multivariate, discrete-time survival model for capturing the relationship between a collection of potentially recurrent safety and efficacy events. Our model can estimate overall measures of utility that tradeoff efficacy and safety for more complex forms of patient outcomes, and our model can also be used to characterize variation in these utility measures across key patient subgroups. For subgroup analyses, our Bayesian formulation generates more stable shrinkage estimates of subgroup-specific utility measures and protects against spurious subgroup findings. We demonstrate the utility of our approach with an analysis of the TIMI 50 vorapaxar cardiovascular outcomes study, which contains both primary efficacy endpoints and recurrent thrombotic adverse events.

benefit-risk assessment;

stratified medicine

multivariate discrete regression

potential outcomes

Bayesian posterior inference 

Biopharmaceutical Section