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Title: Bayesian meta-analytical methods to incorporate multiple surrogate endpoints in drug development process
Authors: Bujkiewicz, Sylwia
Thompson, John R.
Riley, R. D.
Abrams, Keith R.
First Published: 3-Nov-2015
Publisher: Wiley
Citation: Statistics in Medicine, 2016, 35 (7), pp. 1063-1089
Abstract: A number of meta-analytical methods have been proposed that aim to evaluate surrogate endpoints. Bivariate meta-analytical methods can be used to predict the treatment effect for the final outcome from the treatment effect estimate measured on the surrogate endpoint while taking into account the uncertainty around the effect estimate for the surrogate endpoint. In this paper, extensions to multivariate models are developed aiming to include multiple surrogate endpoints with the potential benefit of reducing the uncertainty when making predictions. In this Bayesian multivariate meta-analytic framework, the between-study variability is modelled in a formulation of a product of normal univariate distributions. This formulation is particularly convenient for including multiple surrogate endpoints and flexible for modelling the outcomes which can be surrogate endpoints to the final outcome and potentially to one another. Two models are proposed, first using an unstructured between-study covariance matrix by assuming the treatment effects on all outcomes are correlated and second using a structured between- study covariance matrix by assuming treatment effects on some of the outcomes are conditionally independent. While the two models are developed for the summary data on a study level, the individual-level association is taken into account by the use of the Prentice’s criteria (obtained from individual patient data) to inform the within study correlations in the models. The modelling techniques are investigated using an example in relapsing remitting multiple sclerosis where the disability worsening is the final outcome, while relapse rate and MRI lesions are potential surrogates to the disability progression.
DOI Link: 10.1002/sim.6776
ISSN: 0277-6715
eISSN: 1097-0258
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2015 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. This is an open-access article distributed under the terms of the Creative Commons Attribution License ( ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Appears in Collections:Published Articles, Dept. of Health Sciences

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