Trials that turn from retrospectively registered to prospectively registered: A cohort study of ‘retroactively prospective’ clinical trial registration using history data

Abstract

Background.Prospective clinical trial registration is a methodological best practice, a moral requirement under the Declaration of Helsinki, and in many cases legally required. The US clinical trials register ClinicalTrials.gov allows for changes to a clinical trial registry entry at any time, including changes to the clinical trial start date, making it possible for a trial that was registered after the enrolment of the first patient (retrospective registration) to retroactively change its start date to a later one, making it appear to be prospectively registered.Methods.Using the novel R package cthist, we downloaded clinical trial history data for all clinical trials with a first registration date in the year 2015.Findings.We found 235 clinical trials to be retroactively prospective, comprising 2.0% of all clinical trials first registered on ClinicalTrials.gov in 2015 and 3.9% of all prospectively registered trials. Among the 113 retroactively prospective clinical trials with an accompanying publication, 10.6% explicitly stated in the publication that they had been prospectively registered.Interpretation.While the rate of retroactively prospective trial registration is lower than hypothesized, the existence of this issue has implications for the review and conduct of clinical trials, and it can be detected using fully automated and freely available tools. This is the first analysis of the potentially questionable research practice that we call retroactively prospective trial registration.