ImportanceThe use of real-world data (RWD) external control arms in prospective studies is increasing. The advantages, including the immediate availability of a control population, must be balanced with the requirements of meeting evidentiary standards.ObjectiveTo address the question of whether and to what extent the methods of RWD studies compare to standard methods used in randomized clinical trials.Evidence ReviewA systematic search across 4 electronic databases and Google Scholar was conducted from January 1, 2000, to October 23, 2023. Studies were included in the systematic review if they compared an intervention arm in a clinical trial to an RWD control arm in patients with hematological cancers and if they were published between 2000 and 2023.FindingsThirty-two prospective intervention studies incorporating external control data from RWD sources of patients with hematological cancers were identified. A total of 4306 patients from intervention arms and 10 594 from RWD control arms were included across all studies. Only 2 studies (6%) included prospectively collected RWD. The complete trial inclusion criteria were applied to the RWD cohort in 7 studies (22%). Four studies (13%) published the statistical analysis plan and prespecified use of RWD. A total of 23 studies (72%) applied matching algorithms for trial and RWD cohorts, including matching for demographic, disease, and/or therapy-related characteristics. The end point criteria were the same as the trial in 8 studies (25%). In contrast, 12 studies (38%) used different end points, and 12 (38%) did not provide an end point definition for the RWD. Twelve studies (38%) had a median follow-up difference of less than a year between arms. Eight studies (25%) reported toxic effect data for the trial arm, of which 5 studies reported toxic effect data for the RWD arm.Conclusions and RelevanceIn this systematic review, limitations were observed in the application of clinical trial eligibility criteria to RWD, statistical rigor and application of matching methods, the definition of end points, follow-up, and reporting of adverse events, which may challenge the conclusions reported in studies using RWD.

中文翻译：

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在血液癌患者中使用真实世界数据的外部对照研究


重要性在前瞻性研究中真实世界数据 （RWD） 外部控制臂的使用正在增加。这些优势，包括立即获得对照人群，必须与满足证据标准的要求相平衡。目的解决 RWD 研究的方法是否以及在多大程度上与随机临床试验中使用的标准方法进行比较的问题。证据综述从 2000 年 1 月 1 日至 2023 年 10 月 23 日对 4 个电子数据库和 Google Scholar 进行了系统检索。如果研究将临床试验中的干预组与血液癌患者的 RWD 对照组进行比较，并且如果它们在 2000 年至 2023 年之间发表，则这些研究被纳入系统评价。所有研究共纳入干预组 4306 例患者和 RWD 对照组 10 594 例患者。只有 2 项研究 （6%） 纳入前瞻性收集的 RWD。在 7 项研究 （22%） 中，将完整的试验纳入标准应用于 RWD 队列。四项研究 （13%） 发表了统计分析计划和预先指定的 RWD 使用。共有 23 项研究 （72%） 对试验和 RWD 队列应用了匹配算法，包括对人口统计学、疾病和/或治疗相关特征的匹配。终点标准与 8 项研究 （25%） 的试验相同。相比之下，12项研究（38%）使用了不同的终点，12项研究（38%）没有提供RWD的终点定义。12 项研究 （38%） 的组间中位随访差异不到一年。 8 项研究 （25%） 报告了试验组的毒性作用数据，其中 5 项研究报告了 RWD 组的毒性作用数据。结论和相关性在本系统综述中，观察到临床试验资格标准对 RWD 的应用、统计严谨性和匹配方法的应用、终点的定义、随访和不良事件报告方面的局限性，这可能会挑战使用 RWD 的研究中报告的结论。