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Uncertainty in the Bayesian meta-analysis of normally distributed surrogate endpoints

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journal contribution
posted on 01.09.2015, 09:02 by Sylwia Bujkiewicz, John R. Thompson, Enti Spata, Keith R. Abrams
We investigate the effect of the choice of parameterisation of meta-analytic models and related uncertainty on the validation of surrogate endpoints. Different meta-analytical approaches take into account different levels of uncertainty which may impact on the accuracy of the predictions of treatment effect on the target outcome from the treatment effect on a surrogate endpoint obtained from these models. A range of Bayesian as well as frequentist meta-analytical methods are implemented using illustrative examples in relapsing-remitting multiple sclerosis, where the treatment effect on disability worsening is the primary outcome of interest in healthcare evaluation, while the effect on relapse rate is considered as a potential surrogate to the effect on disability progression, and in gastric cancer, where the disease-free survival has been shown to be a good surrogate endpoint to the overall survival. Sensitivity analysis was carried out to assess the impact of distributional assumptions on the predictions. Also, sensitivity to modelling assumptions and performance of the models were investigated by simulation. Although different methods can predict mean true outcome almost equally well, inclusion of uncertainty around all relevant parameters of the model may lead to less certain and hence more conservative predictions. When investigating endpoints as candidate surrogate outcomes, a careful choice of the meta-analytical approach has to be made. Models underestimating the uncertainty of available evidence may lead to overoptimistic predictions which can then have an effect on decisions made based on such predictions.

Funding

This work was funded by the Medical Research Council (grant no. MR/L009854/1 awarded to SB). KRA is supported by the UK National Institute for Health Research (grant no. NF-SI-0512-10159).

History

Citation

Statistical Methods in Medical Research, August 13, 2015 0962280215597260

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Health Sciences

Version

VoR (Version of Record)

Published in

Statistical Methods in Medical Research

Publisher

SAGE Publications (UK and US)

issn

0962-2802

eissn

1477-0334

Acceptance date

24/06/2015

Copyright date

2015

Available date

01/09/2015

Publisher version

http://smm.sagepub.com/content/early/2015/08/11/0962280215597260

Language

en