Specify characteristics in advance

Authors should, whenever possible, pre-specify characteristics in the protocol that later will be subject to subgroup analyses or meta-regression. Pre-specifying characteristics reduces the likelihood of spurious findings, first by limiting the number of subgroups investigated and second by preventing knowledge of the studies’ results influencing which subgroups are analysed. True pre-specification is difficult in systematic reviews, because the results of some of the relevant studies are often known when the protocol is drafted. If a characteristic was overlooked in the protocol, but is clearly of major importance and justified by external evidence, then authors should not be reluctant to explore it. However, such post hoc analyses should be identified as such.