Basel Institute for Clinical Epidemiology and Biostatistics, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.
Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom.
JAMA Netw Open. 2021 Nov 1;4(11):e2128898. doi: 10.1001/jamanetworkopen.2021.28898.
Clinical trial registries are important for gaining an overview of ongoing research efforts and for deterring and identifying publication bias and selective outcome reporting. The reliability of the information in trial registries is uncertain.
To assess the reliability of information across registries for trials with multiple registrations.
For this systematic review, 360 protocols of randomized clinical trials (RCTs) approved by research ethics committees in Switzerland, the UK, Canada, and Germany in 2012 were evaluated. Clinical trial registries were searched from March to September 2019 for corresponding registrations of these RCTs. For RCTS that were recorded in more than 1 clinical trial registry, key trial characteristics that should be identical among all trial registries (ie, sponsor, funding source, primary outcome, target sample size, trial status, date of first patient enrollment, results available, and main publication indexed) were extracted in duplicate. Agreement between the different trial registries for these key characteristics was analyzed descriptively. Data analyses were conducted from May 1 to November 30, 2020. Representatives from clinical trial registries were interviewed to discuss the study findings between February 1 and March 31, 2021.
The analysis included 197 RCTs registered in more than 1 trial registry (151 in 2 registries and 46 in 3 registries), with 188 trials in ClinicalTrials.gov, 185 in the European Union Drug Regulating Authorities Clinical Trials Database (EudraCT), 20 in ISRCTN, and 47 in other registries. The agreement of key information across all registries was as follows: 178 of 197 RCTs (90%; 95% CI, 85%-94%) for sponsor, 18 of 20 (90%; 95% CI, 68%-99%) for funding source (funding was not reported on ClinicalTrials.gov), 154 of 197 (78%; 95% CI, 72%-84%) for primary outcome, 90 of 197 (46%; 95% CI, 39%-53%) for trial status, 122 of 194 (63%; 95% CI, 56%-70%) for target sample size, and 43 of 57 (75%; 95% CI, 62%-86%) for the date of first patient enrollment when the comparison time was increased to 30 days (date of first patient enrollment was not reported on EudraCT). For results availability in trial registries, agreement was 122 of 197 RCTs (62%; 95% CI, 55%-69%) for summary data reported in the registry and 91 of 197 (46%; 95% CI, 39%-53%) for whether a published article with the main results was indexed. Different legal requirements were stated as the main reason for inconsistencies by representatives of clinical trial registries.
In this systematic review, for a substantial proportion of registered RCTs, information about key trial characteristics was inconsistent across trial registries, raising concerns about the reliability of the information provided in these registries. Further harmonization across clinical trial registries may be necessary to increase their usefulness.
临床试验注册机构对于全面了解正在进行的研究工作以及防止和识别发表偏倚和选择性结果报告非常重要。试验注册机构中信息的可靠性尚不确定。
评估具有多个注册的试验在各个注册机构中的信息可靠性。
在这项系统评价中，评估了 2012 年在瑞士、英国、加拿大和德国获得伦理委员会批准的 360 项随机临床试验（RCT）的方案。从 2019 年 3 月至 9 月，对这些 RCT 的相应注册进行了临床试验注册机构的检索。对于在多个临床试验注册机构记录的 RCT，应从所有临床试验注册机构中提取相同的关键试验特征（即赞助商、资金来源、主要结局、目标样本量、试验状态、首例患者入组日期、结果是否可用以及主要出版物索引），并进行重复提取。对这些关键特征在不同临床试验注册机构之间的一致性进行描述性分析。数据分析于 2020 年 5 月 1 日至 11 月 30 日进行。代表临床试验注册机构的人员在 2021 年 2 月 1 日至 3 月 31 日之间讨论了研究结果。
分析包括在超过 1 个临床试验注册机构中注册的 197 项 RCT（151 项在 2 个注册机构中，46 项在 3 个注册机构中），其中 188 项在 ClinicalTrials.gov 中，185 项在欧盟药品监管机构临床试验数据库（EudraCT）中，20 项在 ISRCTN 中，47 项在其他注册机构中。所有注册机构之间关键信息的一致性如下：197 项 RCT 中有 178 项（90%；95%CI，85%-94%）为赞助商，20 项 RCT 中有 18 项（90%；95%CI，68%-99%）为资金来源（ClinicalTrials.gov 未报告资金情况），197 项 RCT 中有 154 项（78%；95%CI，72%-84%）为主要结局，197 项 RCT 中有 90 项（46%；95%CI，39%-53%）为试验状态，194 项 RCT 中有 122 项（63%；95%CI，56%-70%）为目标样本量，57 项 RCT 中有 43 项（75%；95%CI，62%-86%）为首例患者入组日期（EudraCT 未报告首例患者入组日期）。当比较时间延长至 30 天时，试验注册机构中结果可用性的一致性为 197 项 RCT 中有 122 项（62%；95%CI，55%-69%）为注册中报告的汇总数据，91 项 RCT 中有 197 项（46%；95%CI，39%-53%）为是否索引主要结果的已发表文章。临床试验注册机构的代表表示，不同的法律要求是不一致的主要原因。
在这项系统评价中，对于相当一部分已注册的 RCT，关键试验特征的信息在各个临床试验注册机构之间不一致，这引发了对这些注册机构中提供信息的可靠性的担忧。可能需要在临床试验注册机构之间进一步协调，以提高其有用性。
