Objectives Spontaneous reporting schemes show an increase in adverse drug events, while at the same time accelerated and conditional approval procedures for early marketing of drugs were intensified over recent years, illustrating the need to strengthen drug safety and efficacy evaluation in post-authorization studies (PAS). The European Medicines Agency (EMA) mandates and supervises post-authorization safety and efficacy studies (PASS/PAES) on approved drugs. However, unpublished study documents and results so far hamper the systematic scientific evaluation of these PAS. Developing a translational framework for the evaluation of PAS thus is an important challenge in regulatory research. The project’s objective is to develop a TRAnslational framework for regulatory research through Critical appraisal and Evaluation of Post-Authorisation Safety and Efficacy Studies (TRACE-PASS/PAES).

Method TRACE-PASS/PAES will set up a database of PAS that have been registered in Germany since 2010, and it will follow up these PAS identifying study protocols and reports in public databases and obtaining access to unpublished reports using freedom of information (FOI) requests. Based on these documents from multiple data sources, the project will systematically evaluate: 1) the consistency of study set-up as described in study protocols and registration databases, 2) the transparency and consistency of reporting in journal articles and registration databases, 3) the transparency and consistency of conduct in documents held by EMA, and 4) the transparency and consistency of progress through examination of all available documents. Concerning these four aspects, the project will critically appraise documents using established, adapted, and bespoke study instruments and statistical analyses. Further, it will apply an open peer review process and open data access evaluating the four aspects across all documents.

Results We recently investigated PAS registered from 2008 to 2010 in Germany (Spelsberg et al. BMJ 2017; 356:j337). This study was the first to examine PAS using unpublished data obtained through FOI requests. Systematic evaluation of -set-up, reporting, conduct, and progress was beyond its scope. However, the study examined PASS 1160.84 on dabigatran etexilate (Pradaxa®) using multiple data sources and showed inconsistent and non-transparent aspects in study set-up, reporting, and progress, potentially affecting the scientific quality and validity of PASS 1160.84. Detection of these inconsistencies and lack of transparency through evaluation of different data sources relating to PASS 1160.84 represents a proof of concept for the proposed project.

Conclusions Follow-up of PAS through multiple data sources proved successful in identifying shortcomings with regard to methods, reporting, and progress of a particular PAS. This concept represents an expedient strategy for the translational framework proposed by TRACE-PASS/PAES. We thus aim to extend this systematic evaluation of PAS using multiple data sources to larger samples of PAS conducted in Germany and Europe with the aim of fostering regulatory research for improved evidence and health care.