Trials that turn from retrospectively registered to prospectively registered: a cohort study of “retroactively prospective” clinical trial registration using history data

Abstract

Background Prospective registration of clinical trials is mandated by various regulations. However, clinical trial registries like ClinicalTrials.gov allow registry entries to be updated at any time, and key study elements, including the start date, may change before the first patient is enrolled. If a trial changes its start date after recruiting began, however, it may indicate a reason for concern. This study aimed to measure the rate of “retroactively prospective” trials. This refers to trials that are originally registered retrospectively, with the start date before the registration date, but that retroactively change their start date to be after the registration date, making them appear as if they were prospectively registered. Methods We retrieved clinical trial history data for all clinical trials registered on ClinicalTrials.gov with a first registration date in the year 2015 (N = 11,908). Using automated analyses, we determined the timepoints of registration in relation to the start date of the trial over time. For retroactively prospective trials and a set of control trials, we manually checked the accompanying publications to determine which start date they report and whether they report changes to the start date. Results We found 235 clinical trials to be retroactively prospective, comprising 2.0% of all clinical trials in our sample of 11,908 trials. Among the 113 retroactively prospective clinical trials with an accompanying publication, 12 (10.6%) explicitly stated in the publication that they had been prospectively registered. Conclusions Retroactively prospective trial registration happens in one in 50 trials. While these changes to the start date could be mistakes or legitimate edits based on the most up-to-date information, they could also indicate a retrospectively registered trial that has been made to appear as a prospectively registered trial, which would lead to biases unapparent to reviewers. Our results point to the need for more transparent reporting of changes to a trial’s details and have implications for the review and conduct of clinical trials, with our fully automated and freely available tools allowing reviewers or editors to detect these changes. Trial registration The preregistered protocol of our study is available via https://osf.io/rvq53. The most recent version of the protocol lists all deviations from the original study plan, including the rationale behind the changes, and additional analyses that were conducted.