Yelland Lisa N, Kahan Brennan C, Dent Elsa, Lee Katherine J, Voysey Merryn, Forbes Andrew B, Cook Jonathan A
1 South Australian Health and Medical Research Institute, Adelaide, SA, Australia.
2 School of Public Health, The University of Adelaide, Adelaide, SA, Australia.
Clin Trials. 2018 Jun;15(3):278-285. doi: 10.1177/1740774518761627. Epub 2018 Apr 11.
Background/aims In clinical trials, it is not unusual for errors to occur during the process of recruiting, randomising and providing treatment to participants. For example, an ineligible participant may inadvertently be randomised, a participant may be randomised in the incorrect stratum, a participant may be randomised multiple times when only a single randomisation is permitted or the incorrect treatment may inadvertently be issued to a participant at randomisation. Such errors have the potential to introduce bias into treatment effect estimates and affect the validity of the trial, yet there is little motivation for researchers to report these errors and it is unclear how often they occur. The aim of this study is to assess the prevalence of recruitment, randomisation and treatment errors and review current approaches for reporting these errors in trials published in leading medical journals. Methods We conducted a systematic review of individually randomised, phase III, randomised controlled trials published in New England Journal of Medicine, Lancet, Journal of the American Medical Association, Annals of Internal Medicine and British Medical Journal from January to March 2015. The number and type of recruitment, randomisation and treatment errors that were reported and how they were handled were recorded. The corresponding authors were contacted for a random sample of trials included in the review and asked to provide details on unreported errors that occurred during their trial. Results We identified 241 potentially eligible articles, of which 82 met the inclusion criteria and were included in the review. These trials involved a median of 24 centres and 650 participants, and 87% involved two treatment arms. Recruitment, randomisation or treatment errors were reported in 32 in 82 trials (39%) that had a median of eight errors. The most commonly reported error was ineligible participants inadvertently being randomised. No mention of recruitment, randomisation or treatment errors was found in the remaining 50 of 82 trials (61%). Based on responses from 9 of the 15 corresponding authors who were contacted regarding recruitment, randomisation and treatment errors, between 1% and 100% of the errors that occurred in their trials were reported in the trial publications. Conclusion Recruitment, randomisation and treatment errors are common in individually randomised, phase III trials published in leading medical journals, but reporting practices are inadequate and reporting standards are needed. We recommend researchers report all such errors that occurred during the trial and describe how they were handled in trial publications to improve transparency in reporting of clinical trials.
背景/目的 在临床试验中，在招募、随机分组和为参与者提供治疗的过程中出现错误并不罕见。例如，不符合条件的参与者可能会被无意中随机分组，参与者可能会被随机分到错误的分层中，当只允许单次随机分组时参与者可能会被多次随机分组，或者在随机分组时可能会无意中向参与者发放错误的治疗。这些错误有可能在治疗效果估计中引入偏差并影响试验的有效性，然而研究人员几乎没有动力去报告这些错误，而且不清楚它们发生的频率。本研究的目的是评估招募、随机分组和治疗错误的发生率，并回顾在主要医学期刊上发表的试验中报告这些错误的当前方法。
方法 我们对2015年1月至3月发表在《新英格兰医学杂志》《柳叶刀》《美国医学会杂志》《内科学年鉴》和《英国医学杂志》上的个体随机、III期随机对照试验进行了系统评价。记录报告的招募、随机分组和治疗错误的数量和类型以及它们是如何处理的。对于纳入评价的试验随机抽取样本，联系相应的作者，要求他们提供有关试验期间发生的未报告错误的详细信息。
结果 我们识别出241篇潜在符合条件的文章，其中82篇符合纳入标准并被纳入评价。这些试验中位数涉及24个中心和650名参与者，87%涉及两个治疗组。82项试验中有32项（39%）报告了招募、随机分组或治疗错误，错误中位数为8个。最常报告的错误是不符合条件的参与者被无意中随机分组。在82项试验中的其余50项（61%）中未发现提及招募、随机分组或治疗错误。基于联系的15位相应作者中9位关于招募、随机分组和治疗错误的回复，试验中发生的错误有1%至100%在试验出版物中被报告。
结论 在主要医学期刊上发表的个体随机、III期试验中，招募、随机分组和治疗错误很常见，但报告做法不充分，需要报告标准。我们建议研究人员报告试验期间发生的所有此类错误，并在试验出版物中描述它们是如何处理的，以提高临床试验报告的透明度。
