Out of sight but not out of mind: how to search for unpublished clinical trial evidence.

Systematic reviews of randomised trials play a key role in guiding patient care and health policy. Their validity depends to a large extent on reviewers’ ability to retrieve relevant information from all existing trials. Unfortunately, about half of clinical trials remain unpublished after receiving ethics approval—particularly those with statistically non-significant findings. Even when published, most journal articles do not report all of the outcome data or key methodological information. 3 The overall result is that the published literature tends to overestimate the efficacy and underestimate the harms of a given intervention, while providing insufficient information for readers to evaluate the risk of bias. It is thus important that systematic reviewers adopt a comprehensive strategy to search beyond the published literature. The optimal systematic review would have complete information about every trial—the full protocol, final study report, raw dataset, and any journal publications and regulatory submissions. The eligibility and risk of bias for each trial could then be evaluated, regardless of its publication status. There are several potential sources of unpublished information on trial methods and results (table⇓). These sources can help to identify the existence and results of unpublished trials, as well as unreported outcomes within published trials. They can also provide methodological information that facilitates assessment of risk of bias, including the detection of discrepancies between unpublished and published methods. 6 Systematic reviewers should consider using all potential information sources as part of their search strategy, while keeping in mind the strengths and limitations of each source (table⇓). Trial registries and results databases