Bounds for direct and indirect effects with application to perinatal epidemiology

描述(由申请人提供)：卫生科学研究人员经常感兴趣的是检查治疗对某些结果的影响在多大程度上是由中间变量调节的。经常使用各种统计技术来进行这种中介分析。然而，为了将这种统计分析的结果解释为因果关系，也就是说，作为特定处理的直接和间接影响，必须对混淆做出某些强有力的假设。中介分析中所需的不可测量的混杂假设比研究治疗的总体效果时所需的假设更强。为了估计受控的直接影响，不仅不能有治疗-结果关系的不可测量的混杂因素，而且也不能有介体-结果关系的不可测量的混杂因素。此外，为了将总影响分解为直接影响和间接影响，还必须假定治疗-调解人关系中没有不可测量的混杂因素，也不存在混淆调解人-结果关系的治疗结果。在许多观察性研究中，这些没有测量的混杂假设将不成立。这项研究的目的是在观察研究中获得并应用关于直接和间接影响的界限的结果，当识别所需的无不可测-混杂的假设失败时。将主要通过对未测量的混杂变量与感兴趣的治疗、调解人和结果之间的关系施加单调性假设来取得进展。这一结果将应用于围产期流行病学中的一个问题。在过去的二十年里，美国对产前护理的利用有所增加；然而，早产率也有所增加；剖腹产率有所增加；婴儿死亡率有所下降。对这些趋势的一种可能的解释是，产前护理允许及早发现怀孕问题，对这些问题的适当反应是早产、剖腹产或医学引产。这将导致更大比例的早产，但最终会产生更健康的婴儿。这项研究将考察医学诱导的早产在多大程度上影响产前护理对婴儿死亡率的影响。这种分析所需的无不可测-混淆的假设不太可能在国家卫生统计中心将被分析的出生证明和婴儿死亡率文件中得到满足，因此，方法学研究中得出的结果将被用来确定产前护理对婴儿死亡率的影响部分的界限，这部分影响是通过医学诱导的早产来调节的。 公共卫生相关性：在拟议的研究中开发的统计方法将有助于评估一个变量对另一个变量的影响在多大程度上受到某种中介的影响。这些方法将被用来确定产前护理对婴儿死亡率的影响程度，允许及早发现妊娠问题，对其适当的反应是早产、剖腹产或引产。

DESCRIPTION (provided by applicant): It is often of interest to investigators in the health sciences to examine the extent to which the effect of a treatment on some outcome is mediated by an intermediate variable. Various statistical techniques are often employed to carry out this mediation analysis. However, in order to interpret the results of such statistical analysis causally, that is, as direct and indirect effects of a particular treatment, certain strong assumptions must be made about confounding. The nounmeasured- confounding assumptions required in mediation analysis are stronger than those required in studies of the total effect of a treatment. In order to estimate controlled direct effects there must not only be no unmeasured confounders of the treatment-outcome relationship but there also must be no unmeasured confounders of the mediator-outcome relationship. Furthermore, for the decomposition of a total effect into a direct and an indirect effect, one must also assume that there are no unmeasured confounders of the treatment-mediator relationship and that there is no consequence of treatment that confounds the mediator-outcome relationship. In many observational studies these no-unmeasured-confounding assumptions will not hold. The purpose of this research is to obtain and apply results concerning bounds for direct and indirect effects in observational studies when the no-unmeasured-confounding assumptions required for the identification fail. Progress will be made principally by imposing monotonicity assumptions on the relationship between the unmeasured confounding variables and the treatment, mediator and outcome of interest. The results will be applied to a problem in perinatal epidemiology. Over the last twenty, utilization of prenatal care has increased in the United States; preterm birth rates, however, have also increased; c-section rates have increased; infant mortality has decreased. One possible explanation for these trends is that prenatal care allows for the early detection of pregnancy problems for which the appropriate response is preterm c-section or medically-induced labor. This would result in a greater proportion of preterm births but ultimately healthier infants. The research will examine the extent to which the effect of prenatal care on infant mortality is mediated by medically induced preterm birth. The no-unmeasured-confounding assumptions required for such an analysis are unlikely met in the National Center for Health Statistics Linked Birth Certificate and Infant Mortality files that will be analyzed and thus the results derived in the methodological research will be employed to determine bounds for the portion of the effect of prenatal care on infant mortality that is mediated by medically-induced preterm birth. PUBLIC HEALTH RELEVANCE: The statistical methodology developed in the proposed research will be useful in studies assessing the extent to which the effect of one variable on another is mediated by some intermediate. The methods will be employed to determine the extent to which prenatal care affects infant mortality by allowing for the early detection of pregnancy problems for which the appropriate response is a preterm c-section or induced labor.