Approaches for Enhanced Extrapolation of Long-Term Survival Outcomes Using Electronic Health Records of Patients With Cancer

• Published in: Value in health 2022-02, Vol.25 (2), p.230-237
• Main Authors: Wang, Xiaoliang, Adamson, Blythe J., Briggs, Andrew, Tan, Katherine, Bargo, Danielle, Ghosh, Shuhag, Baxi, Shrujal, Ramsey, Scott
• Format: Article
• Language: English
• Subjects: Aged; Anastrozole - therapeutic use; Antineoplastic Agents - therapeutic use; Breast Neoplasms - drug therapy; Breast Neoplasms - mortality; cancer treatment; clinical trial; Cohort Studies; Databases, Factual; Electronic Health Records; Female; Humans; Letrozole - therapeutic use; Middle Aged; Progression-Free Survival; Randomized Controlled Trials as Topic; real-world data; survival extrapolation; Survival Rate
• ISSN: 1098-3015; 1524-4733
• DOI: 10.1016/j.jval.2021.08.013

This study aimed to demonstrate enhanced survival extrapolation methods using electronic health record-derived real-world data (RWD). The study population included patients diagnosed of ER+/HER2− metastatic breast cancer who started first-line treatment with anastrozole or letrozole between November 18, 2014, and November 18, 2015. Two patient cohorts were constructed: a clinical trial cohort from digitized MONARCH-3 clinical trial results and a RWD cohort from a deidentified electronic health record-derived database. RWD patients were weighted to trial baseline covariate distributions. Standard parametric approaches were applied to trial data and a “best-fit” model was selected. We demonstrate traditional and enhanced hybrid (pooling with weighted RWD at start, 75%, or end of trial) extrapolation approaches. Observed and estimated 5-year progression-free survival (PFS) rates in extrapolating the trial control arm (n = 165) were comparable across all methods. Compared with the observed 5-year mean PFS in the RWD cohort (n = 118) of 20.4 months (95% confidence interval [CI] 16.9-23.8), there was some variation among studied methods. Best-fit standard parametric model (log-normal) had 5-year mean PFS of 21.3 months (95% CI 18.2-24.9), and for the hybrid methods in order of estimate conservativeness was start of trial (20.8 months; 95% CI 18.5-23.2), 75% of trial (21.3 months; 95% CI 18.1-24.5), and end of trial (21.8 months; 95% CI 18.8-25.2). Our study leverages RWD to enhance long-term survival extrapolation. Future use cases should include applying patient eligibility criteria, weighting on baseline characteristics, and choice of time window to add RWD to trial data. •Standard extrapolation methods using clinical trial data only estimate outcomes beyond the trial observation period and may not accurately represent longer-term survival outcomes.•Using electronic health record-derived real-world data (RWD) with sufficient clinical depth and longitudinality, we were able to generate a RWD cohort similar to the trial patients by carefully applying selection criteria, enrollment windows, and weighting on baseline characteristics.•This study illustrates different approaches to incorporate RWD to enhance survival extrapolation from clinical trial data. It demonstrates the strengths and limitations of several enhanced survival extrapolation methods for supplementing trial data with RWD data at various time points.