The Role of Expert Opinion in Projecting Long-Term Survival Outcomes Beyond the Horizon of a Clinical Trial

Abstract

Introduction: Clinical trials often have short follow-ups, and long-term outcomes such as survival must be extrapolated. Current extrapolation methods often produce a wide range of survival values. To minimize uncertainty in projections, we developed a novel method that incorporates formally elicited expert opinion in a Bayesian analysis and used it to extrapolate survival in the placebo arm of DAPA-CKD, a phase 3 trial of dapagliflozin in patients with chronic kidney disease (NCT03036150). Methods: A summary of mortality data from 13 studies that included DAPA-CKD-like populations and training on elicitation were provided to six experts. An elicitation survey was used to gather the experts' 10-and 20-year survival estimates for patients in the placebo arm of DAPA-CKD. These estimates were combined with DAPA-CKD mortality and general population mortality (GPM) data in a Bayesian analysis to extrapolate long-term survival using seven parametric distributions. Results were compared with those from standard frequentist approaches (with and without GPM data) that do not incorporate expert opinion.

Algorithmic benchmark modulation: A novel method to develop success rates for clinical studies

“…To account for these pitfalls, prior distributions for assurance calculations can be based on expert opinion informed by existing data. 4 There are, however, other challenges.…”