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

• Published in: Advances in therapy 2023-06, Vol.40 (6), p.2741-2751
• Main Authors: Willigers, Bartholomeus J. A., Ouwens, Mario, Briggs, Andrew, Heerspink, Hiddo J. L., Pollock, Carol, Pecoits-Filho, Roberto, Tangri, Navdeep, Kovesdy, Csaba P., Wheeler, David C., Garcia Sanchez, Juan Jose
• Format: Article
• Language: English
• Subjects: Bayes Theorem; Cardiology; Endocrinology; Humans; Internal Medicine; Medicine; Medicine & Public Health; Oncology; Original Research; Pharmacology/Toxicology; Renal Insufficiency, Chronic - drug therapy; Rheumatology; Surveys and Questionnaires
• ISSN: 0741-238X; 1865-8652; 1865-8652
• DOI: 10.1007/s12325-023-02503-3

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. Results The group expert-elicited estimate for 20-year survival was 31% (lower estimate, 10%; upper estimate, 40%). In the Bayesian analysis, the 20-year extrapolated survival across the seven distributions was 14.9–39.1%, a range that was 2.4- and 1.6-fold smaller than those produced by the frequentist methods (0.0–56.9% without and 0.0–39.2% with GPM data). Conclusions Using expert opinion in a Bayesian analysis provided a robust method for extrapolating long-term survival in the placebo arm of DAPA-CKD. The method could be applied to other populations with limited survival data.