Interpreting indirect treatment comparisons and network meta-analysis for health-care decision making: report of the ISPOR Task Force on Indirect Treatment Comparisons Good Research Practices: part 1.

Mapi Values, Boston, MA, USA.
Value in Health (Impact Factor: 2.89). 06/2011; 14(4):417-28. DOI: 10.1016/j.jval.2011.04.002
Source: PubMed

ABSTRACT Evidence-based health-care decision making requires comparisons of all relevant competing interventions. In the absence of randomized, controlled trials involving a direct comparison of all treatments of interest, indirect treatment comparisons and network meta-analysis provide useful evidence for judiciously selecting the best choice(s) of treatment. Mixed treatment comparisons, a special case of network meta-analysis, combine direct and indirect evidence for particular pairwise comparisons, thereby synthesizing a greater share of the available evidence than a traditional meta-analysis. This report from the ISPOR Indirect Treatment Comparisons Good Research Practices Task Force provides guidance on the interpretation of indirect treatment comparisons and network meta-analysis to assist policymakers and health-care professionals in using its findings for decision making. We start with an overview of how networks of randomized, controlled trials allow multiple treatment comparisons of competing interventions. Next, an introduction to the synthesis of the available evidence with a focus on terminology, assumptions, validity, and statistical methods is provided, followed by advice on critically reviewing and interpreting an indirect treatment comparison or network meta-analysis to inform decision making. We finish with a discussion of what to do if there are no direct or indirect treatment comparisons of randomized, controlled trials possible and a health-care decision still needs to be made.

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    ABSTRACT: 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. 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. 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.
    Clinical Epidemiology 01/2015; 7:29-35.
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    ABSTRACT: Network meta-analysis (NMA) has emerged as a useful analytical tool allowing comparison of multiple treatments based on direct and indirect evidence. Commonly, a hierarchical Bayesian NMA model is used, which allows rank probabilities (the probability that each treatment is best, second best, and so on) to be calculated for decision making. However, the statistical properties of rank probabilities are not well understood. This study investigates how rank probabilities are affected by various factors such as unequal number of studies per comparison in the network, the sample size of individual studies, the network configuration, and effect sizes between treatments. In order to explore these factors, a simulation study of four treatments (three equally effective treatments and one less effective reference) was conducted. The simulation illustrated that estimates of rank probabilities are highly sensitive to both the number of studies per comparison and the overall network configuration. An unequal number of studies per comparison resulted in biased estimates of treatment rank probabilities for every network considered. The rank probability for the treatment that was included in the fewest number of studies was biased upward. Conversely, the rank of the treatment included in the most number of studies was consistently underestimated. When the simulation was altered to include three equally effective treatments and one superior treatment, the hierarchical Bayesian NMA model correctly identified the most effective treatment, regardless of all factors varied. The results of this study offer important insight into the ability of NMA models to rank treatments accurately under several scenarios. The authors recommend that health researchers use rank probabilities cautiously in making important decisions.
    Clinical Epidemiology 01/2014; 6:451-60.
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    ABSTRACT: Network meta-analyses (NMAs) are complex methodological approaches that may be challenging for non-technical end-users, such as policymakers and clinicians, to understand. Consideration should be given to identifying optimal approaches to presenting NMAs that help clarify analyses. It is unclear what guidance researchers currently have on how to present and tailor NMAs to different end-users. A systematic review of NMA guidelines was conducted to identify guidance on how to present NMAs. Electronic databases and supplementary sources were searched for NMA guidelines. Presentation format details related to sample formats, target audiences, data sources, analysis methods and results were extracted and frequencies tabulated. Guideline quality was assessed following criteria developed for clinical practice guidelines. Seven guidelines were included. Current guidelines focus on how to conduct NMAs but provide limited guidance to researchers on how to best present analyses to different end-users. None of the guidelines provided reporting templates. Few guidelines provided advice on tailoring presentations to different end-users, such as policymakers. Available guidance on presentation formats focused on evidence networks, characteristics of individual trials, comparisons between direct and indirect estimates and assumptions of heterogeneity and/or inconsistency. Some guidelines also provided examples of figures and tables that could be used to present information. Limited guidance exists for researchers on how best to present NMAs in an accessible format, especially for non-technical end-users such as policymakers and clinicians. NMA guidelines may require further integration with end-users' needs, when NMAs are used to support healthcare policy and practice decisions. Developing presentation formats that enhance understanding and accessibility of NMAs could also enhance the transparency and legitimacy of decisions informed by NMAs.
    PLoS ONE 12/2014; 9(12):e113277. · 3.53 Impact Factor

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