Urban Luisa, Haller Nina, Pieper Dawid, Mathes Tim
Department of Medical Statistics, University Medical Center Göttingen, Humboldtallee 32, Göttingen 37073, Germany.
Department of Medical Statistics, University Medical Center Göttingen, Humboldtallee 32, Göttingen 37073, Germany.
J Clin Epidemiol. 2025 Feb;178:111614. doi: 10.1016/j.jclinepi.2024.111614. Epub 2024 Nov 17.
Registry-based randomized controlled trials (RRCTs) can provide internally valid results in a real-world context at relatively low effort and cost. However, the main characteristics, the extent to which the registry is utilized (eg, proportion of data from registry) and registry-related limitations are not well characterized. This methodological review of RRCTs aims to analyze the trial design features, investigate potential usage options, and identify possible limitations of using registry data for randomized controlled trials (RCTs).
A systematic search in PubMed for ongoing and published RRCTs was conducted up to February 2, 2023. Studies that reported at least one outcome derived from a registry were included. Study selection was independently performed by two reviewers. All data were extracted into a standardized table, and descriptive statistics were generated.
We included 162 RRCTs (41 protocols and 121 studies). Most RRCTs were multicenter trials (n = 127; 78.4%) comprising a large number of participants (median = 1787; range = 41 to 683,927) and a long follow-up period (median = 60 months; range = 1 to 367 months) with a minimal loss to follow-up. The inclusion criteria of participants were mostly broadly defined. Types of interventions ranged from surgical procedures to behavioral interventions, and almost half of the interventions (46.9%) had a preventive purpose. The main registry outcome was mostly a clinical endpoint (40.1%) or a composite endpoint of major clinical events (30.9%) that was objectively measurable. We found different degrees of registry utilization, ranging from the exclusive use of long-term monitoring of previously published data to the more comprehensive registry utilization for patient recruitment, endpoint collection, and long-term follow-up. Limitations related to the use of registry data comprised potential coding errors or incomplete data (eg, due to under-recording of mild cases). In addition, technical challenges must be considered (eg, failed linkages or time-delayed data entry).
A broad spectrum of potential usage options and usage extent of registry data exist. Our analysis suggests that in many cases, the potential of using registry data and thus their benefits were not fully utilized. In addition, the study illustrates that there is not a single, unified methodology for designing RRCTs but that registries can support RCTs in various ways. Therefore, future RRCTs should specify for what purposes and to what extent registries were utilized. Moreover, a clear definition and taxonomy of RRCTs appears necessary for facilitating future dialogue and research on RRCTs.
基于注册库的随机对照试验（RRCT）能够以相对较低的工作量和成本在真实世界背景下提供内部有效的结果。然而，其主要特征、注册库的利用程度（例如来自注册库的数据比例）以及与注册库相关的局限性尚未得到充分描述。本对RRCT的方法学综述旨在分析试验设计特征、研究潜在的使用方式，并识别将注册库数据用于随机对照试验（RCT）的可能局限性。
截至2023年2月2日，在PubMed中对正在进行和已发表的RRCT进行了系统检索。纳入至少报告了一项源自注册库的结果的研究。由两名审阅者独立进行研究选择。所有数据被提取到一个标准化表格中，并生成描述性统计数据。
我们纳入了162项RRCT（41项方案和121项研究）。大多数RRCT是多中心试验（n = 127；78.4%），包含大量参与者（中位数 = 1787；范围 = 41至683,927），随访期较长（中位数 = 60个月；范围 = 1至367个月），失访率极低。参与者的纳入标准大多定义宽泛。干预类型从外科手术到行为干预不等，几乎一半（46.9%）的干预具有预防目的。主要的注册库结局大多是临床终点（40.1%）或主要临床事件的复合终点（30.9%），且这些终点是可客观测量的。我们发现注册库利用程度各不相同，从仅使用先前发表数据的长期监测到更全面地利用注册库进行患者招募、终点收集和长期随访。与使用注册库数据相关的局限性包括潜在的编码错误或数据不完整（例如由于轻症病例记录不足）。此外，还必须考虑技术挑战（例如链接失败或数据录入延迟）。
注册库数据存在广泛的潜在使用方式和使用程度。我们的分析表明，在许多情况下，使用注册库数据的潜力及其益处未得到充分利用。此外，该研究表明设计RRCT不存在单一、统一的方法，但注册库可以通过多种方式支持RCT。因此，未来的RRCT应明确说明使用注册库的目的和程度。此外，为促进未来关于RRCT的对话和研究，似乎有必要对RRCT进行清晰的定义和分类。
