Department of Global Health and Population, Harvard TH Chan School of Public Health, Boston, MA, USA; Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA.
Centro Español de Investigación Farmacoepidemiológica, Madrid, Spain.
J Clin Epidemiol. 2018 Apr;96:12-22. doi: 10.1016/j.jclinepi.2017.11.021.
To emulate three target trials: single treatment vs. no treatment, joint treatment vs. no treatment, and head-to-head comparison of two treatments, we explain how to estimate the observational analogs of intention-to-treat and per-protocol effects, using hazard ratios and survival curves. For per-protocol effects, we describe two methods for adherence adjustment via inverse-probability weighting.
Prospective observational study using electronic medical records of individuals aged 55-84 with coronary heart disease from >500 practices in the United Kingdom between 2000 and 2010.
The intention-to-treat mortality hazard ratio (95% confidence interval) was 0.90 (0.84, 0.97) for statins vs. no treatment, 0.88 (0.73, 1.06) for statins plus antihypertensives vs. no treatment, and 0.91 (0.77, 1.06) for atorvastatin vs. simvastatin. When censoring nonadherent person-times, the per-protocol mortality hazard ratio was 0.74 (0.64, 0.85) for statins vs. no treatment, 0.55 (0.35, 0.87) for statins plus antihypertensives vs. no treatment, and 1.13 (0.88, 1.45) for atorvastatin vs. simvastatin. We estimated per-protocol hazard ratios for a 5-year treatment using different dose-response marginal structural models and standardized survival curves for each target trial using intention-to-treat and per-protocol analyses.
When randomized trials are not available or feasible, observational analyses can emulate a variety of target trials.
通过模拟三个目标试验：单一治疗与无治疗、联合治疗与无治疗以及两种治疗方法的头对头比较，我们解释了如何使用风险比和生存曲线来估计意向治疗和方案治疗效果的观察类似物。对于方案治疗效果，我们描述了两种通过逆概率加权进行依从性调整的方法。
这是一项前瞻性观察性研究，使用了 2000 年至 2010 年间英国 500 多家诊所中年龄在 55-84 岁的冠心病患者的电子病历。
与无治疗相比，他汀类药物的意向治疗死亡率风险比（95%置信区间）为 0.90（0.84，0.97），他汀类药物加抗高血压药物的风险比为 0.88（0.73，1.06），阿托伐他汀与辛伐他汀的风险比为 0.91（0.77，1.06）。当对不依从的个体时间进行删失时，与无治疗相比，他汀类药物的方案治疗死亡率风险比为 0.74（0.64，0.85），他汀类药物加抗高血压药物的风险比为 0.55（0.35，0.87），阿托伐他汀与辛伐他汀的风险比为 1.13（0.88，1.45）。我们使用不同的剂量-反应边缘结构模型估计了 5 年治疗的方案治疗风险比，并使用意向治疗和方案分析为每个目标试验生成了标准化的生存曲线。
当随机试验不可用或不可行时，观察性分析可以模拟各种目标试验。
