The randomized controlled trial (RCT) is the gold standard for estimating the average treatment effect (ATE) of a medical intervention but requires 100s-1000s of subjects, making it expensive and difficult to implement. While a cross-over trial can reduce sample size requirements by measuring the treatment effect per individual, it is only applicable to chronic conditions and interventions whose effects dissipate rapidly. Another approach is to replace or augment data collected from an RCT with external data from prospective studies or prior RCTs, but it is vulnerable to confounders in the external or augmented data. We propose to simulate the cross-over trial to overcome its practical limitations while exploiting its strengths. We propose a novel framework, SECRETS, which, for the first time, estimates the individual treatment effect (ITE) per patient in the RCT study without using any external data by leveraging a state-of-the-art counterfactual estimation algorithm, called synthetic intervention. It also uses a new hypothesis testing strategy to determine whether the treatment has a clinically significant ATE based on the estimated ITEs. We show that SECRETS can improve the power of an RCT while maintaining comparable significance levels; in particular, on three real-world clinical RCTs (Phase-3 trials), SECRETS increases power over the baseline method by $\boldsymbol{6}$-$\boldsymbol{54\%}$ (average: 21.5%, standard deviation: 15.8%).

提出了一种名为 SECRETS 的新框架，利用合成干预的算法来模拟交叉试验，可以在不使用任何外部数据的情况下估计 RCT 研究中每个患者的个体治疗效果，并使用新的假设检验策略来确定治疗是否具有临床意义的ATE。

SECRETS: 使用合成干预实现主体高效临床随机对照试验