Multilevel Bayesian Models for Survival Times and Longitudinal Patient-Reported Outcomes With Many Zeros

Regulatory approval of new therapies often depends on demonstrating prolonged survival. Particularly when these survival benefits are modest, consideration of therapeutic benefits to patient-reported outcomes (PROs) may add value to the traditional biomedical clinical trial endpoints. We extend a popular class of joint models for longitudinal and survival data to accommodate the excessive zeros common in PROs, building hierarchical Bayesian models that combine information from longitudinal PRO measurements and survival outcomes. The model development is motivated by a clinical trial for malignant pleural mesothelioma, a rapidly fatal form of pulmonary cancer usually associated with asbestos exposure. By separately modeling the presence and severity of PROs, using our zero-augmented beta (ZAB) likelihood, we are able to model PROs on their original scale and learn about individual-level parameters from both presence and severity of symptoms. Correlations among an individual's PROs and survival are modeled ...