Berlin Institute of Health at Charité - Universitätsmedizin Berlin, QUEST Center for Responsible Research, Anna-Louisa-Karsch-Str. 2, 10178, Berlin, Germany.
Medizinische Hochschule Hannover, Institute for Ethics, History and Philosophy of Medicine, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
Trials. 2024 Mar 14;25(1):189. doi: 10.1186/s13063-024-08029-5.
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.
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.
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.
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.
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.
各种法规都要求对临床试验进行前瞻性注册。然而，ClinicalTrials.gov 等临床试验注册机构允许随时更新注册信息，并且关键的研究要素（包括开始日期）可能在第一个患者入组之前发生变化。但是，如果试验在开始招募后改变了开始日期，这可能表明存在令人担忧的原因。本研究旨在衡量“回溯前瞻性”试验的发生率。这是指最初是回溯注册的试验，其开始日期早于注册日期，但随后回溯性地将开始日期更改为注册日期之后，使它们看起来像是前瞻性注册的试验。
我们检索了 2015 年在 ClinicalTrials.gov 上注册的所有临床试验的临床试验历史数据（N=11908）。使用自动化分析，我们根据试验的开始日期确定了随时间变化的注册时间点。对于回溯前瞻性试验和一组对照试验，我们手动检查了伴随出版物，以确定它们报告的开始日期以及是否报告了开始日期的更改。
我们发现有 235 项临床试验是回溯前瞻性的，占我们 11908 项试验样本中所有临床试验的 2.0%。在有伴随出版物的 113 项回溯前瞻性临床试验中，有 12 项（10.6%）在出版物中明确表示它们是前瞻性注册的。
回溯前瞻性试验注册在每 50 项试验中就有 1 项。虽然这些开始日期的更改可能是基于最新信息的错误或合法编辑，但也可能表明已经被注册的试验被修改为看起来像是前瞻性注册的试验，这将导致审查员无法察觉的偏见。我们的结果表明需要更透明地报告试验细节的更改，并对临床试验的审查和实施产生影响，我们的完全自动化和免费提供的工具允许审查员或编辑检测到这些更改。
我们研究的预注册方案可通过 https://osf.io/rvq53 获得。方案的最新版本列出了所有偏离原始研究计划的内容，包括更改的理由以及进行的额外分析。
