To adjust or not to adjust in living systematic reviews? It's all about the context.

With each update of meta-analyses from living systematic reviews, treatment effects and their confidence intervals are recalculated. This often raises the question whether or not multiplicity is an issue and whether a method to adjust for multiplicity is needed. It seems that answering these questions is not that straightforward. We approach this matter by considering the context of systematic reviews and pointing out existing methods for handling multiplicity in meta-analysis. We conclude that multiplicity is not a relevant issue in living systematic reviews when they are planned with the aim to provide up-to-date evidence, without any direct control on the decision over future research. Multiplicity might be an issue, though, in living systematic reviews designed under a protocol involving a "stopping decision", which can be the case in living guideline development or in reimbursement decisions. Several appropriate methods exist for handling multiplicity in meta-analysis. Existing methods, however, are also associated with several technical and conceptual limitations, and could be improved in future methodological projects. To better decide whether an adjustment for multiplicity is necessary at all, authors and users of living systematic reviews should be aware of the context of the work and question whether there is a dependency between the effect estimates of the living systematic review and its stopping/updating or an influence on future research.