The starting point for any Cochrane review is the formulation of clinical question (or series of questions). The meeting noted substantial variation in the breadth of questions in relation to the inclusion of multiple interventions in IRs. At one extreme, some reviews include a single specific pair-wise comparison (e.g. a single drug versus placebo). At the other extreme, many reviews address all interventions for a particular clinical condition. Many IRs therefore compare multiple interventions, but this intention is largely implicit rather than explicit. Consequently, the use of formal methods (such as indirect comparisons and MTM) is uncommon.
The meeting decided that the Methods Group should not seek to dictate the breadth of interventions included in any particular IR, since these should be guided by clinical and practical judgements.
The large majority of IRs that involve many interventions present meta-analyses of a series of pair-wise comparisons without a specific plan to integrate the various pieces of evidence. Statistical synthesis using MTM could be performed in many cases, provided that the assumptions of this approach are fulfilled. CRGs should be encouraged to identify existing IRs that compare multiple interventions and consider the feasibility of indirect comparisons and MTM. Further guidance is required to support these considerations. At minimum, authors will need to ensure that the interventions have the same indication, or, in other words, that all interventions could reasonably be randomized against each other in a single trial.
Consideration of these statistical methods applies also to new titles and protocols. When a new IR seeks to compare multiple interventions (i.e. to determine a preferential ordering of three or more competing interventions for a particular outcome), this should be made explicit in the protocol, and appropriate methods should be planned and implemented. Support may be sought from the CMIMG (see Role of the Cochrane CMIMG).
The more interventions that are included in a MTM, the greater the potential gain in precision and the greater the ability to establish whether various sources of evidence ‘agree’ with each other. Therefore, it may sometimes be useful to include interventions that are not current candidates for clinical practice, such as placebo or no treatment, or interventions that are no longer recommended or available (‘legacy treatments’). Guidance is also required on such issues.
Other sections of this report:
Addressing multiple interventions in Cochrane Overviews of Reviews
Clarification of the distinction between Intervention Reviews and Overviews of Reviews
Implications of Overviews for authors and editors of Intervention Reviews
A sequential approach for undertaking reviews that compare multiple-interventions
Role of the Cochrane Comparing Multiple Interventions Methods Group