TY - JOUR T1 - Integrating Quality of Life and Survival Outcomes Cardiovascular Clinical Trials: Results from the PARTNER Trial JF - bioRxiv DO - 10.1101/513895 SP - 513895 AU - Jacob V. Spertus AU - Laura A. Hatfield AU - David J. Cohen AU - Suzanne V. Arnold AU - Martin Ho AU - Philip G. Jones AU - Martin Leon AU - Bram Zuckerman AU - John A. Spertus Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/01/12/513895.abstract N2 - Background Survival and health status (e.g., symptoms and quality of life) are key outcomes in clinical trials of heart failure treatment. However, health status can only be recorded on survivors, potentially biasing treatment effect estimates when there is differential survival across treatment groups. Joint modeling of survival and health status can address this bias.Methods and Results We analyzed patient-level data from the PARTNER 1B trial of transcatheter aortic valve replacement (TAVR) versus standard care. Health status was quantified with the Kansas City Cardiomyopathy Questionnaire (KCCQ) at randomization, 1, 6, and 12 months. We compared hazard ratios for survival and mean differences in KCCQ scores at 12 months using several models: the original growth curve model for KCCQ scores (ignoring death), separate Bayesian models for survival and KCCQ scores, and a Bayesian joint longitudinal-survival model fit to either 12 or 30 months of survival follow-up. The benefit of TAVR on 12-month KCCQ scores was greatest in the joint model fit to all survival data (mean difference = 33.7 points; 95% CrI: 24.2, 42.4), followed by the joint model fit to 12 months of survival follow-up (32.3 points; 95% CrI: 22.5, 41.5), a Bayesian model without integrating death (30.4 points; 95% CrI: 21.4, 39.3), and the original growth curve model (26.0 points; 95% CI: 18.7, 33.3). At 12 months, the survival benefit of TAVR was also greater in the joint model (hazard ratio = 0.50; 95% CrI: 0.32, 0.73) than in the non-joint Bayesian model (0.54; 95% CrI: 0.37, 0.75) or the original Kaplan-Meier estimate (0.55; 95% CI: 0.40, 0.74).Conclusions In patients with severe symptomatic aortic stenosis and prohibitive surgical risk, the estimated benefits of TAVR on survival and health status compared with standard care were greater in joint Bayesian models than other approaches. ER -