The Importance of Considering Differences in Study Design in Network Meta-analysis: An Application Using Anti-Tumor Necrosis Factor Drugs for Ulcerative Colitis

Abstract

Background and Aims. Adaptive trial designs present a methodological challenge when performing network meta-analysis (NMA), as data from such adaptive trial designs differ from conventional parallel design randomized controlled trials (RCTs). We aim to illustrate the importance of considering study design when conducting an NMA. Methods. Three NMAs comparing anti-tumor necrosis factor drugs for ulcerative colitis were compared and the analyses replicated using Bayesian NMA. The NMA comprised 3 RCTs comparing 4 treatments (adalimumab 40 mg, golimumab 50 mg, golimumab 100 mg, infliximab 5 mg/kg) and placebo. We investigated the impact of incorporating differences in the study design among the 3 RCTs and presented 3 alternative methods on how to convert outcome data derived from one form of adaptive design to more conventional parallel RCTs. Results. Combining RCT results without considering

Systematic review and network meta‐analysis: first‐ and second‐line biologic therapies for moderate‐severe Crohn's disease

“…There were no head‐to‐head trials, and all comparative efficacy and safety analyses were based on indirect comparisons. Approaches to conducting network meta‐analyses when study designs are different have been proposed, but it is difficult to assess their validity . We did not examine overall and comparative efficacy of different biologics for achieving endoscopic remission; however, most trials in patients with Crohn's disease do not consistently report endoscopic outcomes.…”

Systematic review with network meta‐analysis: first‐ and second‐line pharmacotherapy for moderate‐severe ulcerative colitis

“…A thorough comparative analysis across all agents was limited to trials of induction therapy; due to differences in trial design of maintenance therapy, we had conduct two separate network meta‐analyses limiting comparative assessments. Approaches to conducting network meta‐analyses when study designs are different have been proposed, but it is difficult to assess their validity . Most of the included trials relied on local investigators for endoscopic reading of endoscopic disease activity for trial recruitment and outcome assessment, whereas trials of tofacitinib included blinded central readers, which can influence absolute event rates of clinical remission and mucosal healing; additional the efficacy outcome in OCTAVE trials of tofacitinib were more robust, with requirement of a rectal bleeding subscore of 0 .…”

The Adaptive designs CONSORT Extension (ACE) statement: a checklist with explanation and elaboration guideline for reporting randomised trials that use an adaptive design

“…Secondary analyses (for example, health economic evaluation) may also be affected if appropriate adjustments are not made 219220. Cameron et al221 discuss methodological challenges in performing network meta-analysis when combining evidence from randomised trials with ADs and fixed designs. Statistical methods for estimating the treatment effect and its precision exist for some ADs68222223224225226227228229230231 and implementation tools are being developed 82232233234.…”