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Background Systematic reviews should provide trustworthy guidance to decision-makers, but their credibility is challenged by the selective reporting of trial results and outcomes. Some trials are not published, and even among clinical trials that are published partially (e.g., as conference abstracts), many are never published in full. Although there are many potential sources of published and unpublished data for systematic reviews, there are no established methods for choosing among multiple reports or data sources about the same trial. Methods We will conduct systematic reviews of the effectiveness and safety of two interventions following the Institute of Medicine (IOM) guidelines: (1) gabapentin for neuropathic pain and (2) quetiapine for bipolar depression. For the review of gabapentin, we will include adult participants with neuropathic pain who do not require ventilator support. For the review of quetiapine, we will include adult participants with acute bipolar depression (excluding mixed or rapid cycling episodes). We will compare these drugs (used alone or in combination with other interventions) with placebo or with the same intervention alone; direct comparisons with other medications will be excluded. For each review, we will conduct highly sensitive electronic searches, and the results of the searches will be assessed by two independent reviewers. Outcomes, study characteristics, and risk of bias ratings will be extracted from multiple reports by two individuals working independently, stored in a publicly available database (Systematic Review Data Repository) and analyzed using commonly available statistical software. In each review, we will conduct a series of meta-analyses using data from different sources to determine how the results are affected by the inclusion of data from multiple published sources (e.g., journal articles and conference abstracts) as well as unpublished aggregate data (e.g., “clinical study reports”) and individual participant data (IPD). We will identify patient-centered outcomes in each report and identify differences in the reporting of these outcomes across sources. Systematic review registration CRD42015014037, CRD42015014038

Background Clinical trial (and other) data from the European Medicines Agency (EMA) offers the best available opportunity to address the extensive reporting bias in pharmaceutical trial literature. Data are requested via freedom of information requests, but 5 years on, little is known about how the system is working. Methods Case series of 12 requests for regulatory data (clinical study reports and other regulatory data) relating to 29 different compounds. We logged start and end dates for correspondence with and data releases from the EMA, the need for additional correspondence and appeal of initial negative decisions, and inspected data releases for redaction. We measured: time from initial request to first substantive response from the EMA, to final decision from the EMA (in case of appeal), to initial receipt of documents, and to completion of request; number of data transmission batches generated; number of pages received for each request; average number of pages per batch over time (for releases in multiple batches); judgment as to whether the request was satisfied. Results We found great variability in time to receive an initial decision from the EMA (1 to 13 weeks). Additional correspondence with the EMA was necessary in 10 of 12 requests. Four of 12 were initially refused but 3 of 4 were allowed on appeal after 3 to 33 additional weeks. One request was denied despite appeal. Time to final decision was 1 to 43 weeks. We received data for 11 of 12 requests in 98 batches. While two requests remain outstanding as at June 2015 the remaining nine requests took a median 43 weeks to completion (range: 17 to 186 weeks). Despite redaction in 10 of 11 releases (mainly of researcher and participant identifying information), 8 requested were wholly satisfied. Conclusions The EMA is the only regulator in the world that is routinely releasing original clinical trial data, but release can take considerable time to occur and often only after a lengthy correspondence. Given its importance for research and significance for transparency we suggest ways in which the process could be made more efficient. Electronic supplementary material The online version of this article (doi:10.1186/s13063-016-1194-7) contains supplementary material, which is available to authorized users.