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Incorporating alternative design clinical trials in network meta-analyses

Authors Thorlund K, Druyts E, Toor K, Jansen J, Mills EJ

Received 9 July 2014

Accepted for publication 24 October 2014

Published 23 December 2014 Volume 2015:7 Pages 29—35

DOI https://doi.org/10.2147/CLEP.S70853

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 6

Editor who approved publication: Professor Henrik Toft Sorensen


Kristian Thorlund,1–3 Eric Druyts,1,4 Kabirraaj Toor,1,5 Jeroen P Jansen,1,6 Edward J Mills1,3

1Redwood Outcomes, Vancouver, BC, 2Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada; 3Stanford Prevention Research Center, Stanford University, Stanford, CA, USA; 4Department of Medicine, Faculty of Medicine, 5School of Population and Public Health, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada; 6Department of Public Health and Community Medicine, Tufts University, Boston, MA, USA


Introduction: Network meta-analysis (NMA) is an extension of conventional pairwise meta-analysis that allows for simultaneous comparison of multiple interventions. Well-established drug class efficacies have become commonplace in many disease areas. Thus, for reasons of ethics and equipoise, it is not practical to randomize patients to placebo or older drug classes. Unique randomized clinical trial designs are an attempt to navigate these obstacles. These alternative designs, however, pose challenges when attempting to incorporate data into NMAs. Using ulcerative colitis as an example, we illustrate an example of a method where data provided by these trials are used to populate treatment networks.
Methods: We present the methods used to convert data from the PURSUIT trial into a typical parallel design for inclusion in our NMA. Data were required for three arms: golimumab 100 mg; golimumab 50 mg; and placebo. Golimumab 100 mg induction data were available; however, data regarding those individuals who were nonresponders at induction and those who were responders at maintenance were not reported, and as such, had to be imputed using data from the rerandomization phase. Golimumab 50 mg data regarding responses at week 6 were not available. Existing relationships between the available components were used to impute the expected proportions in this missing subpopulation. Data for placebo maintenance response were incomplete, as all induction nonresponders were assigned to golimumab 100 mg. Data from the PURSUIT trial were combined with ACT-1 and ULTRA-2 trial data to impute missing information.
Discussion: We have demonstrated methods for converting results from alternative study designs to more conventional parallel randomized clinical trials. These conversions allow for indirect treatment comparisons that are informed by a wider array of evidence, adding to the precision of estimates.

Keywords: adaptive, network meta-analysis, indirect treatment comparison, ulcerative colitis, golimumab

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