Rodrigues Craig, Odutayo Ayodele, Patel Sagar, Agarwal Arnav, da Costa Bruno Roza, Lin Ethan, Yeh Robert W, Jüni Peter, Goodman Shaun G, Farkouh Michael E, Udell Jacob A
Women's College Research Institute, Toronto, Canada (C.R., S.P., E.L., J.A.U.).
School of Medicine, Queen's University, Kingston, Canada (C.R.).
Circ Cardiovasc Qual Outcomes. 2021 May;14(5):e007903. doi: 10.1161/CIRCOUTCOMES.120.007903. Epub 2021 May 17.
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.
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.
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.
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.
基于注册登记的随机对照试验允许使用常规健康数据（RHD）来确定结局。虽然这种方法为临床试验成本不断上升和复杂性增加提供了一种潜在解决方案，但与RHD来源相比，通过临床终点委员会（CEC）判定来确定结局的比较分析却很少。在心血管试验中，我们着手系统地比较从RHD与传统临床评估及判定中确定的心血管事件发生率和估计的随机治疗效果。
我们检索了MEDLINE（1976年至2020年8月）中通过RHD和CEC判定两者来确定结局以比较心血管事件发生率和治疗效果的研究。我们得出风险比的比值以比较来自RHD和CEC判定的治疗效果。我们使用逆方差随机效应荟萃分析汇总风险比的比值。
9项研究（1988 - 2020年；32156例患者）涉及10项随机对照试验，比较了心血管疾病患者或有心血管疾病风险患者中RHD与CEC的结局确定情况。对于全因死亡率（一致性百分比：98.4% - 100%，κ值：0.95 - 1.0）和心血管死亡率（一致性百分比：97.8% - 99.9%，κ值：0.66 - 0.99），CEC与RHD结局判定之间存在高度一致性和评估者间可靠性。对于心肌梗死，κ值范围为0.67 - 0.98，对于中风，κ值范围为0.52 - 0.89。相比之下，外周动脉疾病的κ值较低（κ值：0.27）。基于风险比的比值，CEC和RHD对事件的判定所得到的随机治疗效果差异很小，心血管死亡率的风险比汇总比值范围为0.93（95%CI，0.63 - 1.39），中风为1.27（95%CI，0.67 - 2.41）。
使用回顾性获取的RHD进行临床结局判定在识别全因死亡率和心血管结局方面与CEC判定显示出高度一致性。重要的是，从RHD和CEC确定的随机对照试验中的心血管治疗效果产生了相似的点估计值。总体而言，我们的综述支持在心血管试验中使用RHD作为临床结局判定的潜在替代来源。有必要进行前瞻性计划关联的验证研究。
