Generalizing Evidence From Randomized Clinical Trials to Target Populations
Generalizing Evidence From Randomized Clinical Trials to Target Populations
复制标题
DOI：
10.1093/aje/kwq084
复制
发表时间：
2010-07-01
影响因子：
5
通讯作者：
Stuart, Elizabeth A.
中科院分区：
文献类型：
--
作者：
Cole, Stephen R.;Stuart, Elizabeth A.
规划合理且实施得当的随机临床试验仍然可能缺乏外部有效性。作者阐述了一种基于模型的方法，利用一项具有重大意义的人类免疫缺陷病毒（HIV）治疗试验，将观察到的试验结果标准化到特定的目标人群，并提供了蒙特卡洛模拟证据来支持该方法。该示例试验于1996年在美国招募了1156名感染HIV的成年男性和女性，将577人随机分配到高效抗逆转录病毒疗法组，579人分配到基本无效的联合疗法组，并对参与者随访了52周。目标人群是美国2006年感染HIV的人群，这是由美国疾病控制与预防中心估计的。在作者已经测量并正确构建了反映治疗效果异质性的选择决定因素模型的假设下，试验结果适用于目标人群，尽管减弱了12%。在治疗效果存在异质性的模拟中，传统的意向性治疗估计存在偏差，置信区间覆盖率较差，但所提出的估计在很大程度上无偏差且具有适当的置信区间覆盖率。所提出的方法将观察到的试验结果标准化到特定的目标人群，从而提供了有关试验结果普遍性的信息。
Properly planned and conducted randomized clinical trials remain susceptible to a lack of external validity. The authors illustrate a model-based method to standardize observed trial results to a specified target population using a seminal human immunodeficiency virus (HIV) treatment trial, and they provide Monte Carlo simulation evidence supporting the method. The example trial enrolled 1,156 HIV-infected adult men and women in the United States in 1996, randomly assigned 577 to a highly active antiretroviral therapy and 579 to a largely ineffective combination therapy, and followed participants for 52 weeks. The target population was US people infected with HIV in 2006, as estimated by the Centers for Disease Control and Prevention. Results from the trial apply, albeit muted by 12%, to the target population, under the assumption that the authors have measured and correctly modeled the determinants of selection that reflect heterogeneity in the treatment effect. In simulations with a heterogeneous treatment effect, a conventional intent-to-treat estimate was biased with poor confidence limit coverage, but the proposed estimate was largely unbiased with appropriate confidence limit coverage. The proposed method standardizes observed trial results to a specified target population and thereby provides information regarding the generalizability of trial results.