In biomedical studies, estimating drug effects on chronic diseases requires a long follow-up period, which is difficult to meet in randomized clinical trials (RCTs). The use of a short-term surrogate to replace the long-term outcome for assessing the drug effect relies on stringent assumptions that empirical studies often fail to satisfy. Motivated by a kidney disease study, we investigate the drug effects on long-term outcomes by combining an RCT without observation of long-term outcome and an observational study in which the long-term outcome is observed but unmeasured confounding may exist. Under a mean exchangeability assumption weaker than the previous literature, we identify the average treatment effects in the RCT and derive the associated efficient influence function and semiparametric efficiency bound. Furthermore, we propose a locally efficient doubly robust estimator and an inverse probability weighted (IPW) estimator. The former attains the semiparametric efficiency bound if all the working models are correctly specified. The latter has a simpler form and requires much fewer model specifications. The IPW estimator using estimated propensity scores is more efficient than that using true propensity scores and achieves the semiparametric efficient bound in the case of discrete covariates and surrogates with finite support. Both estimators are shown to be consistent and asymptotically normally distributed. Extensive simulations are conducted to evaluate the finite-sample performance of the proposed estimators. We apply the proposed methods to estimate the efficacy of oral hydroxychloroquine on renal failure in a real-world data analysis.
翻译:在生物医学研究中,估计药物对慢性疾病的影响需要很长的后续期,这在随机临床试验中很难达到。使用短期替代物来取代评估药物影响的长期结果,取决于经验研究往往无法满足的严格假设。在肾病研究的推动下,我们调查药物对长期结果的影响,方法是将RCT结合起来,而不观察长期结果,进行观察性研究,观察性研究,观察性研究可以观察到长期结果,但可能存在不测的混乱。在比以往文献弱的平均值交换假设下,我们确定RCT的平均治疗效果,并得出相关的高效影响功能和半对称效率的约束。此外,我们提出一个当地高效的加倍估算值和偏差加权估量(IPW)估算值。如果所有工作模型都得到正确说明,前者就具有半负比值,后者的形式比较简单,需要少得多的模型规格。使用估计性偏差分数的IPW估测算器在RCT中,我们确定平均的治疗效果,并得出相关的有效影响和半对准性效率。我们提出的精确性测测测测测算方法,在精确测测测测测测算后,其为我们测测测测测定性测算性测测测测测测测测测测测的精确度的精确度的精确度的精确性测测算方法是测测测测测测测测测测测测测测测测测测测测为测测测为测的精确性。