The PRISMA Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-analyses of Health Care Interventions: Checklist and Explanations

Systematic reviews and meta-analyses are fundamental tools for the generation of reliable summaries of health care information for clinicians, decision makers, and patients. Systematic reviews provide information on clinical benefits and harms of interventions, inform the development of clinical recommendations, and help to identify future research needs. In 1999 and 2009, respectively, groups developed the Quality of Reporting of Meta-Analyses (QUOROM) statement (1) and the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement (2, 3) to improve the reporting of systematic reviews and meta-analyses. Both statements have been widely used, and coincident with their adoption, the quality of reporting of systematic reviews has improved (4, 5). Systematic reviews and meta-analyses often address the comparative effectiveness of multiple treatment alternatives. Because randomized trials that evaluate the benefits and harms of multiple interventions simultaneously are difficult to perform, comparative effectiveness reviews typically involve many studies that have addressed only a subset of the possible treatment comparisons. Traditionally, meta-analyses have usually compared only 2 interventions at a time, but the need to summarize a comprehensive and coherent set of comparisons based on all of the available evidence has led more recently to synthesis methods that address multiple interventions. These methods are commonly referred to as network meta-analysis, mixed treatment comparisons meta-analysis, or multiple treatments meta-analysis (68). In recent years, there has been a notable increase in the publication of articles using these methods (9). On the basis of our recent overview (10) of reporting challenges in the field, as well as findings from our Delphi exercise involving researchers and journal editors, we believe that reporting guidance for such analyses is sorely needed. In this article, we describe the process of developing specific advice for the reporting of systematic reviews that incorporate network meta-analyses, and we present the guidance generated from this process. Development of the PRISMA Network Meta-analysis Extension Statement We followed an established approach for this work (11). We formed a steering committee (consisting of Drs. Hutton, Salanti, Moher, Caldwell, Chaimani, Schmid, Thorlund, and Altman); garnered input from 17 journal editors, reporting guideline authors, and researchers with extensive experience in systematic reviews and network meta-analysis; and performed an overview of existing reviews of the reporting quality of network meta-analyses to identify candidate elements important to report in network meta-analyses (10). We also implemented an online Delphi survey of authors of network meta-analyses in mid-2013 (215 invited; response rate, 114 [53%]) by using Fluid Surveys online software (Fluidware, Ottawa, Ontario, Canada) to determine consensus items for which either a new checklist item or an elaboration statement would be required, and to identify specific topics requiring further discussion. Next, we held a 1-day, face-to-face meeting to discuss the structure of the extension statement, topics requiring further consideration, and publication strategy. After this meeting, members of the steering committee and some of the meeting participants were invited to contribute specific components for this guidance. All participants reviewed drafts of the report. Scope of This Extension Statement This document provides reporting guidance primarily intended for authors, peer reviewers, and editors. It may also help clinicians, technology assessment practitioners, and patients understand and interpret network meta-analyses. We also aim to help readers develop a greater understanding of core concepts, terminology, and issues associated with network meta-analysis. This document is not intended to be prescriptive about how network meta-analyses should be conducted or interpreted; considerable literature addressing such matters is available (6, 1251). Instead, we seek to provide guidance on important information to be included in reports of systematic reviews that address networks of multiple treatment comparisons. For specific checklist items where we have suggested modification of instructions from the PRISMA statement, we have included examples of potential approaches for reporting different types of information. However, modified approaches to those presented here may also be feasible. How to Use This Document This document describes modifications of checklist items from the original PRISMA statement for systematic reviews incorporating network meta-analyses. It also describes new checklist items that are important for transparent reporting of such reviews. We present an integrated checklist of 32 items, along with elaborations that demonstrate good reporting practice. The elaboration (Appendix,) describes each item and presents examples for new or modified items. Although new items have been added in what was deemed the most logical place in the core PRISMA checklist, we do not prescribe an order in which these must be addressed. The elaboration also includes 5 boxes that highlight methodological considerations for network meta-analysis. The Table presents the PRISMA network analysis checklist that authors may use for tracking inclusion of key elements in reports of network meta-analyses. The checklist has been structured to present core PRISMA items and modifications of these items where needed, as well as new checklist items specific to network meta-analysis. Checklist items are designated "New Item" in the main text if they address a particular aspect of reporting that is novel to network meta-analyses; these are labeled S1 through S5. The heading "Addition" indicates discussion of an issue that was covered by the original PRISMA statement but requires additional considerations for reviews incorporating network meta-analyses. Examples with elaborations have been provided for checklist items in these 2 categories. Table.Checklist of Items to Include When Reporting a Systematic Review Involving a Network Meta-analysis What Is a Treatment Network? Systematic reviews comparing the benefits and harms of multiple treatments are more complex than those comparing only 2 treatments. To present their underlying evidence base, reviews involving a network meta-analysis commonly include a graph of the network to summarize the numbers of studies that compared the different treatments and the numbers of patients who have been studied for each treatment (Figure 1). This network graph consists of nodes (points representing the competing interventions) and edges (adjoining lines between the nodes that show which interventions have been compared among the included studies). The sizes of the nodes and the thicknesses of the edges in network graphs typically represent the amounts of respective evidence for specific nodes and comparisons. Sometimes, additional edges are added to distinguish comparisons that may be part of multigroup studies that compare more than 2 treatments. Figure 1. Overview of a network graph. A network graph presenting the evidence base for a hypothetical review of 4 interventions is shown. Treatments are represented by nodes and head-to-head studies between treatments are represented by edges. The sizes of edges and nodes are used to visually depict the available numbers of studies comparing interventions and the numbers of patients studied with each treatment. The graphs also allow readers to note particular features of the shape of a treatment network. This includes the identification of closed loops in the network; a closed loop is present in a treatment network when 3 or more comparators are connected to each other through a polygon, as in Figure 1 for treatments A, B, and C. This shows that treatments A, B, and C have all been compared against each other in existing studies, and thus each comparison in the closed loop (AB, AC, BC) is informed by both direct and indirect evidence (see the Box for definitions of direct and indirect evidence and Figure 2 for a graphical representation of terms in the Box). Box. Terminology: Reviews With Networks of Multiple Treatments Terms are discussed further in the Box. Top. Adjusted indirect treatment comparison of treatments B and C based on studies that used a common comparator, treatment A. Middle. A network of 8 treatments and a common comparator, with a mix of comparisons against the control treatment and a subset of all possible comparisons between active treatments. Bottom. A treatment network similar to that shown in the middle panel, but with study data available for an additional 4 comparisons in the network which form closed loops. Figure 2. Graphical overview of the terminologies that are related to the study of treatment networks. Discussion All phases of the clinical research cycle generate considerable waste, from posing irrelevant questions to inappropriate study methods, bad reporting, and inadequate dissemination of the completed report. Poor reporting is not an esoteric issue. It can introduce biased estimates of an intervention's effectiveness and thus affect patient care and decision making. Journals regularly publish new evidence regarding some aspect of inadequate reporting (52). Improving the completeness and transparency of reporting research is a low-hanging fruit to help reduce waste, and possibly explains the rise in developing reporting guidelines (53, 54) and such initiatives as the EQUATOR Network. The PRISMA statement was aimed at improving the reporting of traditional pairwise systematic reviews and meta-analyses; it has been endorsed by hundreds of journals and editorial groups. Some extensions have been developed, including PRISMA for reporting abstracts (55) and equity (56). Other extensions are in various stages of development, including those for individual patientdat