Using mixed treatment comparisons and meta‐regression to perform indirect comparisons to estimate the efficacy of biologic treatments in rheumatoid arthritis

Richard M. Nixon · Nick J Bansback · Alan Brennan

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Meta-analysis and systematic reviews Rheumatoid Arthritis Research and Therapies Statistical Methods in Clinical Trials

Abstract

Mixed treatment comparison (MTC) is a generalization of meta-analysis. Instead of the same treatment for a disease being tested in a number of studies, a number of different interventions are considered. Meta-regression is also a generalization of meta-analysis where an attempt is made to explain the heterogeneity between the treatment effects in the studies by regressing on study-level covariables. Our focus is where there are several different treatments considered in a number of randomized controlled trials in a specific disease, the same treatment can be applied in several arms within a study, and where differences in efficacy can be explained by differences in the study settings. We develop methods for simultaneously comparing several treatments and adjusting for study-level covariables by combining ideas from MTC and meta-regression. We use a case study from rheumatoid arthritis. We identified relevant trials of biologic verses standard therapy or placebo and extracted the doses, comparators and patient baseline characteristics. Efficacy is measured using the log odds ratio of achieving six-month ACR50 responder status. A random-effects meta-regression model is fitted which adjusts the log odds ratio for study-level prognostic factors. A different random-effect distribution on the log odds ratios is allowed for each different treatment. The odds ratio is found as a function of the prognostic factors for each treatment. The apparent differences in the randomized trials between tumour necrosis factor alpha (TNF- alpha) antagonists are explained by differences in prognostic factors and the analysis suggests that these drugs as a class are not different from each other.

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2002How should meta‐regression analyses be undertaken and interpreted?2004Combination of direct and indirect evidence in mixed treatment comparisons 2002Network meta‐analysis for indirect treatment comparisons

Cited by

2008Biologic drugs for rheumatoid arthritis in the medicare program: A cost‐effectiveness analysis 2010Mixed treatment comparison analysis provides internally coherent treatment effect estimates based on overviews of reviews and can reveal inconsistency 2015A Bayesian missing data framework for generalized multiple outcome mixed treatment comparisons 2014Balancing benefit and risk of medicines: a systematic review and classification of available methodologies 2007Modelling the cost effectiveness of TNF- antagonists in the management of rheumatoid arthritis: results from the British Society for Rheumatology Biologics Registry 2013Incorporating data from various trial designs into a mixed treatment comparison model 2007Meta‐analysis of mixed treatment comparisons at multiple follow‐up times 2012Mixed treatment comparisons using aggregate and individual participant level data

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