Eliciting Unreported Subgroup-Specific Survival from Aggregate Randomized Controlled Trial Data

Oguzhan Alagoz, Prianka Singh, Matthew Dixon and Murat Kurt
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Oguzhan Alagoz: Department of Industrial and Systems Engineering and Department of Population Health Sciences, University of Wisconsin–Madison, Madison, WI, USA
Prianka Singh: Bristol-Myers Squibb, Princeton, NJ, USA
Matthew Dixon: Bristol-Myers Squibb, Princeton, NJ, USA
Murat Kurt: Bristol-Myers Squibb, Princeton, NJ, USA

Medical Decision Making, 2026, vol. 46, issue 2, 250-264

Abstract: Introduction Subgroup analyses are vital components of health technology assessments, but randomized controlled trials (RCTs) do not commonly report survival distributions for subgroups. This study developed an analytical framework to elicit unreported subgroup-specific survival curves from aggregate RCT data. Methods Assuming exponentially distributed subgroup survival durations, we developed an optimization model that approximates the restricted mean survival time (RMST) for the overall population via the weighted average of the RMSTs of 2 subgroups in each arm. Reported hazard ratios from the forest plots between the arms were used to enforce the relationship among subgroups’ hazard rates in the model. The performance of the model was tested in a real-life test set of 8 RCTs in advanced-stage gastrointestinal tumors, which also reported KM curves for overall survival (OS) for 40 subgroups as well as in 42 synthetic test cases with 168 subgroups as a benchmark. For each subgroup, predicted median survival, OS rates, and the RMSTs were compared against their actual counterparts as well as their 95% confidence intervals (CIs). Results Predicted median survivals and RMSTs were within the 95% CIs of the reported values in 32 (80%) and 34 (85%) of 40 subgroups in real-life test cases and in 163 (97%) and 146 (87%) of 168 subgroups in synthetic test cases, respectively. Across all cases, on average, the predicted survival curves laid within the 95% CIs of reported KM curves 71% and 97% of the time in real-life and synthetic test cases, respectively. Discussion Our study offers a useful and scalable method for extracting subgroup-specific survival from aggregate RCT data to enable subgroup-specific indirect comparisons, and cost-utility and meta-analyses. Higlights Most randomized controlled trials report survival curves for the overall patient population but do not provide subgroup-specific survival curves, which are crucial for cost-effectiveness analyses and meta-analyses focusing on these subgroups. This study developed an optimization modeling approach to elicit unreported subgroup-specific survival curves from aggregate trial data. The proposed modeling approach accurately predicted the reported subgroup-specific survival curves in 42 simulated test cases with 168 subgroups overall, in which each subgroup-specific survival curve was assumed to followed an exponential distribution. The performance of the proposed modeling approach was sensitive to the assumptions when it was tested using a real-life test set of 8 oncology trials, which also reported survival curves for a total of 40 subgroups.

Keywords: optimization; restricted-mean survival; subgroup-specific survival; survival rates; forest plots (search for similar items in EconPapers)
Date: 2026
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Persistent link: https://EconPapers.repec.org/RePEc:sae:medema:v:46:y:2026:i:2:p:250-264

DOI: 10.1177/0272989X251388464

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