Bounds for direct and indirect effects with application to perinatal epidemiology

描述（由申请人提供）：健康科学研究者通常感兴趣的是检查治疗对某些结局的影响在多大程度上是由中间变量介导的。通常采用各种统计技术来进行这种中介分析。然而，为了从因果关系上解释这种统计分析的结果，也就是说，作为特定治疗的直接和间接影响，必须对混杂因素做出某些强有力的假设。在中介分析中所需的不可测量的混杂假设比在治疗的总效果研究中所需的假设更强。为了估计受控的直接效应，不仅必须没有治疗-结局关系的不可测量的混杂因素，而且必须没有中介-结局关系的不可测量的混杂因素。此外，为了将总效应分解为直接效应和间接效应，还必须假设治疗-中介关系不存在不可测量的混杂因素，并且不存在混淆中介-结果关系的治疗后果。在许多观察性研究中，这些无未测量混杂的假设将不成立。本研究的目的是获得和应用的结果时，识别所需的无不可测的混杂假设失败的观察性研究中的直接和间接影响的界限。将主要通过对未测量的混杂变量与治疗、中介和关注结果之间的关系施加单调性假设来取得进展。结果将被应用于围产期流行病学的问题。在过去的20年里，美国对产前护理的利用率有所上升;然而，早产率也有所上升;剖腹产率有所上升;婴儿死亡率有所下降。对这些趋势的一个可能的解释是，产前护理可以早期发现妊娠问题，适当的反应是早产剖腹产或药物诱导分娩。这将导致更大比例的早产，但最终婴儿更健康。这项研究将检查产前护理对婴儿死亡率的影响在多大程度上是由医学诱导的早产引起的。这种分析所需的无未测量混杂假设不太可能在将要分析的国家卫生统计中心关联出生证明和婴儿死亡率文件中得到满足，因此将采用方法学研究中得出的结果来确定产前护理对婴儿死亡率的影响部分的界限，该影响部分由医学诱导的早产介导。 公共卫生相关性：在拟议的研究中开发的统计方法将是有用的研究评估在何种程度上一个变量对另一个变量的影响是介导的一些中间。这些方法将用于确定产前护理对婴儿死亡率的影响程度，通过早期发现妊娠问题，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.