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Users' Guides to the Medical Literature |

How to Use an Article Reporting a Multiple Treatment Comparison Meta-analysis

Edward J. Mills, PhD, MSc; John P. A. Ioannidis, MD, DSc; Kristian Thorlund, PhD, MSc; Holger J. Schünemann, MD, PhD, MSc; Milo A. Puhan, MD, PhD; Gordon H. Guyatt, MD, MSc
JAMA. 2012;308(12):1246-1253. doi:10.1001/2012.jama.11228.
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Multiple treatment comparison (MTC) meta-analysis uses both direct (head-to-head) randomized clinical trial (RCT) evidence as well as indirect evidence from RCTs to compare the relative effectiveness of all included interventions. The methodological quality of MTCs may be difficult for clinicians to interpret because the number of interventions evaluated may be large and the methodological approaches may be complex. Clinicians and others evaluating an MTC should be aware of the potential biases that can affect the interpretation of these analyses. Readers should consider whether the primary studies are sufficiently homogeneous to combine; whether the different interventions are sufficiently similar in their populations, study designs, and outcomes; and whether the direct evidence is sufficiently similar to the indirect evidence to consider combining. This article uses the existing Users' Guides format to address study validity, interpretation of results, and application to a patient scenario.

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Figure 1. Examples of Possible Network Geometry
Graphic Jump Location

The figure shows 4 network graphs. In each graph, lines show where direct comparisons exist from one or more trials. The star shows a network for which all interventions have a single mutual comparator. A single closed loop involves 3 interventions and can provide data to calculate both direct comparisons and indirect comparisons. A well-connected network in which all interventions have been compared against each other in multiple randomized controlled trials (RCTs). The complex network has multiple loops and arms that may have sparse connections.

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Figure 2. A Simple Indirect Comparison and Simple Closed Loop
Graphic Jump Location

A, In an indirect comparison, there is direct evidence from paroxetine compared with placebo and direct evidence of lorazepam compared with placebo. Therefore, the indirect comparison can be applied to determine the effect of paroxetine compared with lorazepam, even if no direct head-to-head comparison exists for these 2 agents. B, In the closed loop, there is direct evidence that compares nicotine replacement therapy with both varenicline and also bupropion. There is also direct evidence comparing bupropion with varenicline. Therefore, enough information exists to evaluate whether the results are coherent between direct and indirect evidence.

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Figure 3. Treatment Network for the Drugs Considered in the Example Multiple Treatment Comparison on Generalized Anxiety Disorder
Graphic Jump Location

The lines between treatment nodes indicate the comparisons made throughout randomized clinical trials (RCTs). The numbers on the lines indicate the number of RCTs informing a particular comparison. (The figure is based on Baldwin et al.1)



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