With heighted interest in causal inference based on real‐world evidence, this empirical study sought to understand differences between the results of observational analyses and long‐term randomized clinical trials. We hypothesized that patients deemed “eligible” for clinical trials would follow a different survival trajectory from those deemed “ineligible” and that this factor could partially explain results. In a large observational registry dataset, we estimated separate survival trajectories for hypothetically trial‐eligible vs ineligible patients under both coronary artery bypass surgery (CABG) and percutaneous coronary intervention (PCI). We also explored whether results would depend on the causal inference method (inverse probability of treatment weighting vs optimal full propensity matching) or the approach to combine propensity scores from multiple imputations (the “across” vs “within” approaches). We found that, in this registry population of PCI/CABG multivessel patients, 32.5% would have been eligible for contemporaneous RCTs, suggesting that RCTs enroll selected populations. Additionally, we found treatment selection bias with different distributions of propensity scores between PCI and CABG patients. The different methodological approaches did not result in different conclusions. Overall, trial‐eligible patients appeared to demonstrate at least marginally better survival than ineligible patients. Treatment comparisons by eligibility depended on disease severity. Among trial‐eligible three‐vessel diseased and trial‐ineligible two‐vessel diseased patients, CABG appeared to have at least a slight advantage with no treatment difference otherwise. In conclusion, our analyses suggest that RCTs enroll highly selected populations, and our findings are generally consistent with RCTs but less pronounced than major registry findings.

中文翻译：

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实证使用因果推理方法来评估现实世界登记中的生存差异与随机临床试验中发现的生存差异。


由于人们对基于现实世界证据的因果推断产生了浓厚的兴趣，这项实证研究试图了解观察分析结果与长期随机临床试验结果之间的差异。我们假设被认为“有资格”参加临床试验的患者将遵循与那些被认为“不合格”的患者不同的生存轨迹，并且这个因素可以部分解释结果。在大型观察登记数据集中，我们估计了假设的符合试验资格和不符合试验资格的患者在冠状动脉搭桥手术（CABG）和经皮冠状动脉介入治疗（PCI）下的单独生存轨迹。我们还探讨了结果是否取决于因果推理方法（治疗加权的逆概率与最佳完全倾向匹配）或组合多重插补倾向得分的方法（“跨”与“内”方法）。我们发现，在 PCI/CABG 多支血管患者的登记人群中，32.5% 符合同期随机对照试验的条件，这表明随机对照试验招募了选定的人群。此外，我们发现 PCI 和 CABG 患者之间的倾向评分分布不同，导致治疗选择偏倚。不同的方法论并没有得出不同的结论。总体而言，符合试验资格的患者似乎表现出比不符合试验资格的患者至少稍微好一点的生存率。按资格进行的治疗比较取决于疾病的严重程度。在符合试验资格的三支病变患者和不符合试验资格的两支病变患者中，CABG 似乎至少具有轻微优势，其他方面没有治疗差异。 总之，我们的分析表明，随机对照试验招募了经过精心挑选的人群，我们的研究结果总体上与随机对照试验一致，但不如主要注册研究结果那么明显。