Llewellyn-Bennett Rebecca, Edwards Danielle, Roberts Nia, Hainsworth Atticus H, Bulbulia Richard, Bowman Louise
MRC Population Health Research Unit, Clinical Trial Service Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Richard Doll Building, Roosevelt Drive, Oxford, OX3 7LF, UK.
Bodleian Health Care Libraries, University of Oxford, Roosevelt Drive, Oxford, OX3 7LF, UK.
Trials. 2018 May 30;19(1):298. doi: 10.1186/s13063-018-2653-0.
Randomised controlled clinical trials typically have a relatively brief in-trial follow-up period which can underestimate safety signals and fail to detect long-term hazards, which may take years to appear. Extended follow-up after the scheduled closure of the trial allows detection of both persistent or enhanced beneficial effects following cessation of study treatment (i.e. a legacy effect) and the emergence of possible adverse effects (e.g. development of cancer).
A systematic review was conducted following PRISMA guidelines to qualitatively compare post-trial follow-up methods used in large randomised controlled trials. Five bibliographic databases, including Medline and the Cochrane Library, and one trial registry were searched. All large randomised controlled trials (more than 1000 adult participants) published from March 2006 to April 2017 were evaluated. Two reviewers screened and extracted data attaining > 95% concordance of papers checked. Assessment of bias in the trials was evaluated using the Cochrane Risk of Bias tool.
Fifty-seven thousand three hundred and fifty-two papers were identified and 65 trials which had post-trial follow-up (PTFU) were included in the analysis. The majority of trials used more than one type of follow-up. There was no evidence of an association between the retention rates of participants in the PTFU period and the type of follow-up used. Costs of PTFU varied widely with data linkage being the most economical. It was not possible to assess associations between risk of bias during the in-trial period and proportions lost to follow-up during the PTFU period.
Data captured during the post-trial follow-up period can add scientific value to a trial. However, there are logistical and financial barriers to overcome. Where available, data linkage via electronic registries and records is a cost-effective method which can provide data on a range of endpoints.
Not applicable for PROSPERO registration.
随机对照临床试验的试验期随访通常相对较短，这可能会低估安全信号，无法检测到可能需要数年时间才会出现的长期危害。在试验按计划结束后进行延长随访，能够检测到研究治疗停止后持续或增强的有益效果（即遗留效应）以及可能出现的不良反应（如癌症的发生）。
按照PRISMA指南进行系统评价，以定性比较大型随机对照试验中使用的试验后随访方法。检索了包括Medline和Cochrane图书馆在内的五个文献数据库以及一个试验注册库。对2006年3月至2017年4月发表的所有大型随机对照试验（超过1000名成年参与者）进行了评估。两名评审员筛选并提取数据，对所检查论文的一致性达到95%以上。使用Cochrane偏倚风险工具评估试验中的偏倚。
共识别出57352篇论文，65项有试验后随访（PTFU）的试验纳入分析。大多数试验使用了不止一种随访类型。没有证据表明PTFU期间参与者的保留率与所使用的随访类型之间存在关联。PTFU的成本差异很大，数据链接是最经济的。无法评估试验期间的偏倚风险与PTFU期间失访比例之间的关联。
试验后随访期间收集的数据可为试验增加科学价值。然而，存在后勤和财务方面的障碍需要克服。在可行的情况下，通过电子注册库和记录进行数据链接是一种具有成本效益的方法，可提供一系列终点的数据。
不适用于PROSPERO注册。
