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Main Authors: Glynn, David, Saramago, Pedro, Singh, Janharpreet, Bujkiewicz, Sylwia, Dias, Sofia, Palmer, Stephen, Soares, Marta
Format: Preprint
Published: 2025
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Online Access:https://arxiv.org/abs/2502.13844
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author Glynn, David
Saramago, Pedro
Singh, Janharpreet
Bujkiewicz, Sylwia
Dias, Sofia
Palmer, Stephen
Soares, Marta
author_facet Glynn, David
Saramago, Pedro
Singh, Janharpreet
Bujkiewicz, Sylwia
Dias, Sofia
Palmer, Stephen
Soares, Marta
contents A growing number of oncology treatments, such as bevacizumab, are used across multiple indications. However, in health technology assessment (HTA), their clinical and cost-effectiveness are typically appraised within a single target indication. This approach excludes a broader evidence base across other indications. To address this, we explored multi-indication meta-analysis methods that share evidence across indications. We conducted a simulation study to evaluate alternative multi-indication synthesis models. This included univariate (mixture and non-mixture) methods synthesizing overall survival (OS) data and bivariate surrogacy models jointly modelling treatment effects on progression-free survival (PFS) and OS, pooling surrogacy parameters across indications. Simulated datasets were generated using a multistate disease progression model under various scenarios, including different levels of heterogeneity within and between indications, outlier indications, and varying data on OS for the target indication. We evaluated the performance of the synthesis models applied to the simulated datasets, in terms of their ability to predict overall survival (OS) in a target indication. The results showed univariate multi-indication methods could reduce uncertainty without increasing bias, particularly when OS data were available in the target indication. Compared with univariate methods, mixture models did not significantly improve performance and are not recommended for HTA. In scenarios where OS data in the target indication is absent and there were also outlier indications, bivariate surrogacy models showed promise in correcting bias relative to univariate models, though further research under realistic conditions is needed. Multi-indication methods are more complex than traditional approaches but can potentially reduce uncertainty in HTA decisions.
format Preprint
id arxiv_https___arxiv_org_abs_2502_13844
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle Methods of multi-indication meta-analysis for health technology assessment: a simulation study
Glynn, David
Saramago, Pedro
Singh, Janharpreet
Bujkiewicz, Sylwia
Dias, Sofia
Palmer, Stephen
Soares, Marta
Methodology
Applications
A growing number of oncology treatments, such as bevacizumab, are used across multiple indications. However, in health technology assessment (HTA), their clinical and cost-effectiveness are typically appraised within a single target indication. This approach excludes a broader evidence base across other indications. To address this, we explored multi-indication meta-analysis methods that share evidence across indications. We conducted a simulation study to evaluate alternative multi-indication synthesis models. This included univariate (mixture and non-mixture) methods synthesizing overall survival (OS) data and bivariate surrogacy models jointly modelling treatment effects on progression-free survival (PFS) and OS, pooling surrogacy parameters across indications. Simulated datasets were generated using a multistate disease progression model under various scenarios, including different levels of heterogeneity within and between indications, outlier indications, and varying data on OS for the target indication. We evaluated the performance of the synthesis models applied to the simulated datasets, in terms of their ability to predict overall survival (OS) in a target indication. The results showed univariate multi-indication methods could reduce uncertainty without increasing bias, particularly when OS data were available in the target indication. Compared with univariate methods, mixture models did not significantly improve performance and are not recommended for HTA. In scenarios where OS data in the target indication is absent and there were also outlier indications, bivariate surrogacy models showed promise in correcting bias relative to univariate models, though further research under realistic conditions is needed. Multi-indication methods are more complex than traditional approaches but can potentially reduce uncertainty in HTA decisions.
title Methods of multi-indication meta-analysis for health technology assessment: a simulation study
topic Methodology
Applications
url https://arxiv.org/abs/2502.13844