Network meta-analysis with competing risk outcomes.
BACKGROUND
Cost-effectiveness analysis often requires information on the effectiveness of interventions on multiple outcomes, and commonly these take the form of competing risks. Nevertheless, methods for synthesis of randomized controlled trials with competing risk outcomes are limited.


OBJECTIVE
The aim of this study was to develop and illustrate flexible evidence synthesis methods for trials reporting competing risk results, which allow for studies with different follow-up times, and that take account of the statistical dependencies between outcomes, regardless of the number of outcomes and treatments.


METHODS
We propose a competing risk meta-analysis based on hazards, rather than probabilities, estimated in a Bayesian Markov chain Monte Carlo (MCMC) framework using WinBUGS software. Our approach builds on existing work on mixed treatment comparison (network) meta-analysis, which can be applied to any number of treatments, and any number of competing outcomes, and to data sets with varying follow-up times. We show how a fixed effect model can be estimated, and two random treatment effect models with alternative structures for between-trial variation. We suggest methods for choosing between these alternative models.


RESULTS
We illustrate the methods by applying them to a data set involving 17 trials comparing nine antipsychotic treatments for schizophrenia including placebo, on three competing outcomes: relapse, discontinuation because of intolerable side effects, and discontinuation for other reasons.


CONCLUSIONS
Bayesian MCMC provides a flexible framework for synthesis of competing risk outcomes with multiple treatments, particularly suitable for embedding within probabilistic cost-effectiveness analysis.
Ades
A E
AE
Department of Community Based Medicine, University of Bristol, Cotham Hill, Bristol, UK. t.ades@bristol.ac.uk
Mavranezouli
Ifigeneia
I
Dias
Sofia
S
Welton
Nicky J
NJ
Whittington
Craig
C
Kendall
Tim
T
D001499:Bayes Theorem; D003362:Cost-Benefit Analysis; D055317:Evidence-Based Practice / Q000191:economics*; D006801:Humans; D008390:Markov Chains; D015201:Meta-Analysis as Topic; D015233:Models, Statistical; D009010:Monte Carlo Method; D018570:Risk Assessment