gms | German Medical Science

Introduction: Meta-analyses for rare binary (e.g., adverse events or safety) outcomes often include studies that have no events in one (“single-zero”) or even both (“double-zero”) treatment arms. A variety of methods to deal with this problem statistically have been proposed. Most of them rely on adding pseudo-observations to the respective studies, or, in case of “double-zero” studies, simple deleting them. However, simply deleting “double-zero” studies might result in biased treatment effects as those studies (with having equal numbers of outcomes in both arms) point to a null effect. We recently gave an example of a meta-analysis where ignoring “double-zero” studies missed a clearly significant and clinically relevant advantage of the off-pump technique on post-operative stroke prevalence in bypass surgery [1]. While it has been reported that about 30 % of all meta-analyses contain at least one “single-zero” study [2], there is no evidence on the frequency of meta-analyses with “double-zero” studies.

Methods: We performed a systematic review on the sample of Cochrane reviews (n = 500) from the Vandermeer [2] study. Two independent reviewers searched the full text of papers for the number of meta-analyses containing at least one “double-zero” study. Disagreement was resolved by repeating the search in the respective review and finding consensus.

Results: In the 500 Cochrane reviews we found 1394 meta-analyses with at least one “double-zero” study. These 1394 meta-analyses originate from 172 of the 500 (= 34.4 %) reviews. The median number of meta-analyses with at least one “double-zero” study in those 172 reviews was 3.5 (Min: 1, Q1: 1, Q3: 9, Max: 102).

Discussion: Meta-analyses with “double-zero” studies occur frequently in Cochrane reviews. In future work we will check if statistical methods that adequately account for those studies (refraining from 1. adding pseudo-observations or 2. simply deleting them) would eventually give clinically different results.