Background:Registry-based randomized controlled trials allow for outcome ascertainment using routine health data (RHD). While this method provides a potential solution to the rising cost and complexity of clinical trials, comparative analyses of outcome ascertainment by clinical end point committee (CEC) adjudication compared with RHD sources are sparse. Among cardiovascular trials, we set out to systematically compare the incidence of cardiovascular events and estimated randomized treatment effects ascertained from RHD versus traditional clinical evaluation and adjudication.Methods:We searched MEDLINE (1976 to August 2020) for studies where outcome ascertainment was performed by both RHD and CEC adjudication to compare the incidence of cardiovascular events and treatment effects. We derived ratios of hazard ratios to compare treatment effects from RHD and CEC adjudication. We pooled ratios of hazard ratios using an inverse variance random-effects meta-analysis.Results:Nine studies (1988–2020; 32 156 patients) involving 10 randomized control trials compared outcome ascertainment with RHD and CEC in patients with or at risk of cardiovascular disease. There was a high degree of agreement and interrater reliability between CEC and RHD outcome determination for all-cause mortality (agreement percentage: 98.4%–100% and κ: 0.95–1.0) and cardiovascular mortality (agreement percentage: 97.8%–99.9% and κ: 0.66–0.99). For myocardial infarction, the κ values ranged from 0.67–0.98, and for stroke the values ranged from 0.52–0.89. In contrast, the κ value for peripheral artery disease was low (κ: 0.27). There was little difference in the randomized treatment effect derived from CEC and RHD ascertainment of events based on the ratios of hazard ratio, with pooled ratios of hazard ratios ranging from 0.93 (95% CI, 0.63–1.39) for cardiovascular mortality to 1.27 (95% CI, 0.67–2.41) for stroke.Conclusions:Clinical outcome ascertainment using retrospectively acquired RHD displayed high levels of agreement with CEC adjudication for identifying all-cause mortality and cardiovascular outcomes. Importantly, cardiovascular treatment effects in randomized control trials determined from RHD and CEC resulted in similar point estimates. Overall, our review supports the use of RHD as a potential alternative source for clinical outcome ascertainment in cardiovascular trials. Validation studies with prospectively planned linkage are warranted.

中文翻译：

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来自常规健康数据的心血管试验结果确定和治疗效果估计的准确性：系统评价和荟萃分析

背景：基于注册的随机对照试验允许使用常规健康数据 (RHD) 确定结果。虽然这种方法为临床试验的成本和复杂性不断上升提供了潜在的解决方案，但与 RHD 来源相比，临床终点委员会 (CEC) 裁决对结果确定的比较分析很少。在心血管试验中，我们开始系统地比较心血管事件的发生率和从 RHD 与传统临床评估和裁决确定的随机治疗效果估计值。 RHD 和 CEC 裁决比较心血管事件的发生率和治疗效果。我们推导出风险比的比率来比较 RHD 和 CEC 裁决的治疗效果。我们使用逆方差随机效应荟萃分析汇总了风险比。 结果：九项研究（1988-2020 年；32156 名患者）涉及 10 项随机对照试验，将结果确定与 RHD 和 CEC 在患有或有心血管风险的患者中进行比较疾病。在全因死亡率（一致百分比：98.4%–100% 和 κ：0.95–1.0）和心血管死亡率（一致百分比：97.8%–99.9% 和κ：0.66–0.99）。对于心肌梗塞，κ 值的范围为 0.67-0.98，而对于中风，该值的范围为 0.52-0.89。相反，外周动脉疾病的κ值较低（κ：0.27）。基于风险比的 CEC 和 RHD 事件确定的随机治疗效果几乎没有差异，风险比的汇总比范围从心血管死亡率的 0.93（95% CI，0.63-1.39）到 1.27（95 % CI, 0.67–2.41) 中风。结论：使用回顾性获得的 RHD 确定临床结果与 CEC 裁决在确定全因死亡率和心血管结果方面高度一致。重要的是，根据 RHD 和 CEC 确定的随机对照试验中的心血管治疗效果导致了相似的点估计。总体而言，我们的审查支持使用 RHD 作为心血管试验中临床结果确定的潜在替代来源。有必要进行具有前瞻性计划联系的验证研究。