论文标题
通过外部控制数据提高临床试验中的推断效率
Improving efficiency of inference in clinical trials with external control data
论文作者
论文摘要
假设我们对临床试验中的治疗作用感兴趣。由于样本量较小,推理的效率可能受到限制。但是,外部控制数据通常可以从历史研究中获得。由于幽门螺杆菌感染的应用,我们展示了如何从此类数据中借用强度以提高临床试验中的推理效率。在有关潜在结果平均值的交换性假设下,我们表明,通过合并临床试验数据和外部控制,可以降低用于估计平均治疗效果的半参数效率。然后,我们得出双重稳健和局部有效的估计器。效率的提高是显着的,尤其是当外部控制数据集具有较大的样本量和较小的可变性时。我们的方法允许放松的重叠假设,我们说明了临床试验仅包含经过治疗组的情况。我们还开发了双重稳健和局部高效的方法,这些方法将临床试验中的因果关系推断为外部人群和整体人口。我们的结果还为试验设计和数据收集带来了有意义的影响。我们通过模拟评估了提出的估计器的有限样本性能。在幽门螺杆菌感染的应用中,我们的方法表明,组合治疗比三重治疗具有潜在的疗效优势。
Suppose we are interested in the effect of a treatment in a clinical trial. The efficiency of inference may be limited due to small sample size. However, external control data are often available from historical studies. Motivated by an application to Helicobacter pylori infection, we show how to borrow strength from such data to improve efficiency of inference in the clinical trial. Under an exchangeability assumption about the potential outcome mean, we show that the semiparametric efficiency bound for estimating the average treatment effect can be reduced by incorporating both the clinical trial data and external controls. We then derive a doubly robust and locally efficient estimator. The improvement in efficiency is prominent especially when the external control dataset has a large sample size and small variability. Our method allows for a relaxed overlap assumption, and we illustrate with the case where the clinical trial only contains a treated group. We also develop doubly robust and locally efficient approaches that extrapolate the causal effect in the clinical trial to the external population and the overall population. Our results also offer a meaningful implication for trial design and data collection. We evaluate the finite-sample performance of the proposed estimators via simulation. In the Helicobacter pylori infection application, our approach shows that the combination treatment has potential efficacy advantages over the triple therapy.