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Bibliographic Details
Main Authors: Phillippo, David M., Dias, Sofia, Ades, A. E., Welton, Nicky J.
Format: Preprint
Published: 2024
Subjects:
Online Access:https://arxiv.org/abs/2401.12640
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author Phillippo, David M.
Dias, Sofia
Ades, A. E.
Welton, Nicky J.
author_facet Phillippo, David M.
Dias, Sofia
Ades, A. E.
Welton, Nicky J.
contents Network meta-analysis combines aggregate data (AgD) from multiple randomised controlled trials, assuming that any effect modifiers are balanced across populations. Individual patient data (IPD) meta-regression is the "gold standard" method to relax this assumption, however IPD are frequently only available in a subset of studies. Multilevel network meta-regression (ML-NMR) extends IPD meta-regression to incorporate AgD studies whilst avoiding aggregation bias, but currently requires the aggregate-level likelihood to have a known closed form. Notably, this prevents application to time-to-event outcomes. We extend ML-NMR to individual-level likelihoods of any form, by integrating the individual-level likelihood function over the AgD covariate distributions to obtain the respective marginal likelihood contributions. We illustrate with two examples of time-to-event outcomes, showing the performance of ML-NMR in a simulated comparison with little loss of precision from a full IPD analysis, and demonstrating flexible modelling of baseline hazards using cubic M-splines with synthetic data on newly diagnosed multiple myeloma. ML-NMR is a general method for synthesising individual and aggregate level data in networks of all sizes. Extension to general likelihoods, including for survival outcomes, greatly increases the applicability of the method. R and Stan code is provided, and the methods are implemented in the multinma R package.
format Preprint
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publishDate 2024
record_format arxiv
spellingShingle Multilevel network meta-regression for general likelihoods: synthesis of individual and aggregate data with applications to survival analysis
Phillippo, David M.
Dias, Sofia
Ades, A. E.
Welton, Nicky J.
Methodology
Network meta-analysis combines aggregate data (AgD) from multiple randomised controlled trials, assuming that any effect modifiers are balanced across populations. Individual patient data (IPD) meta-regression is the "gold standard" method to relax this assumption, however IPD are frequently only available in a subset of studies. Multilevel network meta-regression (ML-NMR) extends IPD meta-regression to incorporate AgD studies whilst avoiding aggregation bias, but currently requires the aggregate-level likelihood to have a known closed form. Notably, this prevents application to time-to-event outcomes. We extend ML-NMR to individual-level likelihoods of any form, by integrating the individual-level likelihood function over the AgD covariate distributions to obtain the respective marginal likelihood contributions. We illustrate with two examples of time-to-event outcomes, showing the performance of ML-NMR in a simulated comparison with little loss of precision from a full IPD analysis, and demonstrating flexible modelling of baseline hazards using cubic M-splines with synthetic data on newly diagnosed multiple myeloma. ML-NMR is a general method for synthesising individual and aggregate level data in networks of all sizes. Extension to general likelihoods, including for survival outcomes, greatly increases the applicability of the method. R and Stan code is provided, and the methods are implemented in the multinma R package.
title Multilevel network meta-regression for general likelihoods: synthesis of individual and aggregate data with applications to survival analysis
topic Methodology
url https://arxiv.org/abs/2401.12640