Unité de Recherche Clinique, Innovation, Pharmacologie, CHU Saint-Etienne, Hôpital Nord, F-42055 Saint-Etienne, France; Unité de Soutien Méthodologique, INSERM, CIC1410, CHU de la Réunion, Saint-Denis, France.
Unité de Recherche Clinique, Innovation, Pharmacologie, CHU Saint-Etienne, Hôpital Nord, F-42055 Saint-Etienne, France; SAINBIOSE U1059, Université Jean Monnet, University of Lyon, INSERM, F-CRIN INNOVTE Network, F-42023 Saint-Etienne, France.
J Clin Epidemiol. 2021 Feb;130:49-58. doi: 10.1016/j.jclinepi.2020.10.013. Epub 2020 Oct 17.
Randomized controlled trials (RCTs) are criticized for including patients who are overselected. Health authorities consequently encourage "real-world" postmarketing cohort studies. Our objective was to determine the differences between RCTs and observational studies as regards their populations and efficacy/safety results.
A systematic review was conducted to identify RCTs and observational studies including patients with venous thromboembolism receiving direct oral anticoagulants or conventional treatment. Ratios of hazard ratio (RHR) comparing epidemiological studies (prospective and retrospective cohort studies and studies using living databases) with RCTs were computed.
Six RCTs (27,121 patients) and twenty observational studies (248,971 patients) were identified and analyzed. Prospective cohort studies seemed to recruit patients who were no less selected than those of RCTs whereas other types of observational studies may reflect the population treated in real life. Among observational studies, prospective cohort studies yielded the most favorable estimates of treatment effect compared with RCTs. These studies were associated with a nonsignificant 33% increase in efficacy estimate (RHR 0.67, [95% CI, 0.39-1.18]) but no effect on safety estimate. Studies using living databases were associated with nonsignificant trends toward a greater effect on efficacy (RHR 0.82, [0.66-1.01]) and a smaller effect on safety (RHR 1.33, [0.96-1.84]).
Overall, in this clinical setting, an exaggeration of the treatment efficacy estimate was seen with observational studies compared with RCTs.
As the presence of residual confounding cannot be excluded, these results should be interpreted cautiously.
随机对照试验（RCT）因纳入过度选择的患者而受到批评。因此，卫生当局鼓励开展“真实世界”的上市后队列研究。我们的目的是确定 RCT 和观察性研究在其人群和疗效/安全性结果方面的差异。
系统检索纳入接受直接口服抗凝剂或常规治疗的静脉血栓栓塞患者的 RCT 和观察性研究。计算比较流行病学研究（前瞻性和回顾性队列研究以及使用活数据库的研究）与 RCT 的风险比（RHR）比值。
共纳入 6 项 RCT（27121 例患者）和 20 项观察性研究（248971 例患者）并进行了分析。前瞻性队列研究似乎招募的患者与 RCT 中的患者一样，选择度不高，而其他类型的观察性研究可能反映了实际生活中治疗的人群。在观察性研究中，前瞻性队列研究与 RCT 相比，对治疗效果的估计最有利。这些研究与疗效估计值增加 33%（RHR 0.67，95%CI，0.39-1.18）但无安全性估计值的影响相关。使用活数据库的研究与疗效效果增大（RHR 0.82，0.66-1.01）和安全性效果减小（RHR 1.33，0.96-1.84）的趋势相关，但均无统计学意义。
总体而言，在这种临床情况下，与 RCT 相比，观察性研究对治疗效果的估计值夸大了。
由于不能排除残余混杂因素的存在，这些结果应谨慎解读。
