论文标题
通过使用未靶向的HPV菌株评估HPV疫苗接种功效时，提高效率并降低偏差
Increasing efficiency and reducing bias when assessing HPV vaccination efficacy by using non-targeted HPV strains
论文作者
论文摘要
疫苗疗效的研究通常记录靶向疫苗靶向病毒菌株的发生率（主要结果）和非靶向菌株的发生率（次要结果）。但是，靶向菌株疫苗功效的标准估计值忽略了非靶向菌株的数据。假设未靶向菌株不受疫苗接种的影响，我们将次级结果视为阴性对照结果，并表明使用此类数据可以（i）在随机试验中提高针对靶向菌株的估计疫苗疗效的精度，并且（ii）在观察研究中减少了相同估计值的混杂偏差。对于客观（i），我们通过二级结果的函数增强了主要结果估计方程，该方程是零偏见的。对于客观（II），我们共同估计对主要和次要结果的治疗效果。如果对两种类型的结果所引起的偏见相似，那么影响一般感染风险的因素是合理的，那么我们可以对次要结果使用估计的疗效来消除对主要结果的估计功效中的偏见。我们证明了这些方法在仅针对一些高度致癌菌株的HPV疫苗研究中的实用性。在此示例中，在随机试验中使用非靶向菌株的精度提高了精度，但在观察性研究中降低了偏差。
Studies of vaccine efficacy often record both the incidence of vaccine-targeted virus strains (primary outcome) and the incidence of non-targeted strains (secondary outcome). However, standard estimates of vaccine efficacy on targeted strains ignore the data on non-targeted strains. Assuming non-targeted strains are unaffected by vaccination, we regard the secondary outcome as a negative control outcome and show how using such data can (i) increase the precision of the estimated vaccine efficacy against targeted strains in randomized trials, and (ii) reduce confounding bias of that same estimate in observational studies. For objective (i), we augment the primary outcome estimating equation with a function of the secondary outcome that is unbiased for zero. For objective (ii), we jointly estimate the treatment effects on the primary and secondary outcomes. If the bias induced by the unmeasured confounders is similar for both types of outcomes, as is plausible for factors that influence the general risk of infection, then we can use the estimated efficacy against the secondary outcomes to remove the bias from estimated efficacy against the primary outcome. We demonstrate the utility of these approaches in studies of HPV vaccines that only target a few highly carcinogenic strains. In this example, using non-targeted strains increased precision in randomized trials modestly but reduced bias in observational studies substantially.
