Concordance between European medicine agency good clinical practice inspections and medical literature: a meta-research survey

Abstract Background Health authorities, such as the European Medicines Agency (EMA), inspect clinical sites performing clinical trials and occasionally find evidence of substantial departures from Good Clinical Practice (GCP). However, if the findings are not transposed in the medical literature, publication of those trials may convey inaccurate messages. Methods Objective to describe the differences between EMA GCP inspection reports and medical literature on drugs with withdrawn or refused applications. Design a retrospective study comparing studies included in European Public Assessment Reports (EPARs) and the corresponding articles published in the medical literature. Data sources—we screened all EPARs released by the EMA from inception to April 2024 for drugs that were refused or had a withdrawn application. Data extracted — two reviewers independently gathered information on the GCP inspections and their findings. The reviewers checked related publications for mentions of the inspection and any subsequent correction, retraction, or expressions of concern related to its findings. Main outcome measures — the main outcome was the mention of the GCP inspection findings in the publication of the inspected studies. We also assessed whether there was any mention of these findings in a correction, retraction or expression of concern. Results Out of 285 EPARs screened, 57 (20%) mentioned a GCP inspection. Fifty-eight distinct studies with inspections had 61 publications. In most of the cases ( n = 47, 77%), the study was published before the EPARs. Only 1 publication (2%) addressed the inspection findings. Moreover, there were no corrections, retractions or expressions of concern related to inspection findings. Among the 61 publications, 26 (43%) were related with 24 distinct studies that had an inspection that casted doubts on data reliability, but none mentioned the inspections at or after the time of publication. Conclusions This meta-research survey indicates that health authorities’ GCP inspections are not reflected in the medical literature, even when the inspections have put the data reliability in doubt. This study raises the question of responsibility for any corrections that may be necessary in medical literature following the publication of EPARs.