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  • Studies were eligible if they included a cumulative meta-analysis of studies of the relative effects of alternative healthcare interventions. Ideally, the cumulative meta-analysis would be presented as a graph showing the summary estimates as each study's result was added to the meta-analyses in the order this had been published or became available in some other way. However, studies were eligible if these graphs or the separate summary estimates were not available, but the general findings or implications of the cumulative meta-analyses were reported. Studies were eligible if a single cumulative meta-analysis was presented, or if a meta-epidemiological project had been done in which numerous systematic reviews or meta-analyses were included. Eligible cumulative meta-analyses had sometimes been done as part of the planning process for a new study to explore how the evidence base had evolved. Studies were not included if only surrogate outcome measures were used unless - like blood pressure and severe anaemia, for example - these were unambiguously important. The searches also identified cumulative meta-analysis in other types of health research (including observational epidemiology and genetics) but these were not eligible for this review. We wished to identify published reports containing graphs of cumulative meta-analyses. An initial search of Pubmed Clinical Queries using the term ‘cumulative meta-analysis’ retrieved 822 records. The selected papers were screened by one author (IC), who selected a set of 23 records which were added to a set of core articles that had been previously identified as part of this author's general interest in this area. This full set of papers were then analysed to obtain ideas for free-text search terms and index or MeSH terms for use in a final search strategy. Searches were then run on the following databases: MEDLINE, OVID (1946–2012, In-Process and other non-indexed citations); EMBASE, OVID (1947–2012); the Cochrane Methodology Register (2012); and Science Citation Index (2012). No language or publication date restrictions were applied. The following search strategy was used for MEDLINE: cumulative adj10 meta?analys$.mp. OR (cumulative.mp. and meta-analysis.pt.). The search of the Cochrane Methodology Register combined the output of a simple search for the word ‘cumulative’ in the abstract with that for a search for records that had been assigned the term ‘Meta-analysis updating and cumulative meta-analysis’ by the compilers of the Register. The searches were conducted in June 2012. The reference lists of relevant systematic reviews and other publications were checked to identify additional articles [11]. A search was undertaken in Google Scholar to identify relevant terms in the full text of articles where relevant concepts had not been located in bibliographic databases using searches of titles, abstracts and index terms. Assessment of studies, data extraction and analysis: Records were exported from Endnote to Sente for first screening by one of the authors (AB). This screening was deliberately over-inclusive, and all potentially eligible articles or unclear articles were checked by a second author (IC). The eligibility of all studies arising from this process was then confirmed by a third author (MC) before their inclusion in this review. The process of data extraction was piloted in ten records and emerging themes identified. A final data extraction form was then agreed. All eligible papers were read, and passages of text commenting on the details of the cumulative meta-analysis and the implications of the completed cumulative meta-analyses were identified and extracted. This was done by one author (AB) and the data extracted were checked against the original articles by the other authors (IC and MC). No attempts were made to combine the results of the included studies, because the aim of this review is to present a range of examples and identify themes across the cumulative meta-analyses identified, rather than to attempt to generate a statistical finding. Similarly, this review does not seek to estimate the incidence or prevalence of trials that have been conducted unnecessarily, since that would be done better with a comprehensive study of large cohorts of trials addressing the same or similar questions. Instead, it seeks to identify and report a range of examples to examine whether cumulative meta-analyses might have led to different choices in the conduct of new research.
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