This should influence the interpretation of the results of the cumulative meta-analysis, alongside consideration of the possibility that spurious results might arise due to cumulative testing. This may require the use of statistical techniques such as sequential analysis, and the need to consider the statement ‘‘Don’t Ignore Chance Effects’’ when building from early, positive findings. In considering possible limitations of our research,BNS we note that systematic reviews of healthcare interventions are subject to the impact of selective reporting by researchers, in which whole studies might not be published or, even if studies are published, particular findings might be excluded because of the authors’ or editors’ opinions about the findings. This methodological review could also be subject to such biases, where cumulative meta-analyses may have been performed but not reported. In contrast to clinical trials or, more recently, systematic reviews with health outcomes, there is no widely available system to register prospectively methodological research, such as cumulative meta-analysis. This makes it impossible to determine the extent of selective reporting of cumulative metaanalysis, or its potential impact on our conclusions. Furthermore, although there were relatively few examples of cumulative metaanalyses in which benefits appeared for an intervention after the initial trials had shown null or negative results,PFM39 this is not surprising, because awareness of such early results, even without a formal meta-analysis, might discourage future research. By contrast, while early positive results might lead to the conduct of new trials to confirm those results or to test their reproducibility in other settings. Despite these limitations, however, and given that this review found such a breadth of examples, it is likely that our general finding is likely to be valid, namely, that there is a substantial problem of waste in research resulting from unnecessary duplication because existing research has not been reviewed before and after new studies are done.