Statistical Methods In Epidemiology--general

该项目为流行病学开发了新的统计方法，具有广泛的应用，并根据正在进行的流行病学项目，特别是与生殖研究有关的项目，开发了所需的方法。今年的工作涉及几个项目。(1)一个项目涉及在评估围产期结局的风险因素时根据出生时胎龄进行统计调整的普遍做法。由于出生时的胎龄可能是由其他也影响结局的因素造成的，它是一个“碰撞”，这种调整可能会在估计中产生偏差。我们进行了计算，以表明在合理的假设下，这种偏见可能是实质性的，因此生殖流行病学家应该避免这种调整后的病因学推断模型。(2)另一个项目涉及以人体样本为基础的昂贵化验生物标记物的综合评估。早先的工作表明，在病例对照环境中，人们可以从病例集合和对照集合中收集样本，并进行基于集合的分析。通过略微修改的Logistic模型，该分析可以估计个体水平的风险参数，并且与基于个体分析的分析相比几乎没有损失。这意味着，如果暴露是基于昂贵的使用人类样本的测试，那么在测试之前将样本汇集在一起可以显著提高效率。在最近的工作中，我们已经将这些方法扩展到应用于精细匹配的病例对照设计和怀孕时间数据。对于后一种设计，一个人在受孕前定义的地层内汇集标本。同样，与单独的水平分析相比，电力几乎不会受到影响，成本大大降低。总的来说，汇集的另一个巨大好处是它保守地使用了不可替代的人类标本。例如，以3个为一组的集合样本减少了每个样本所需的量的2/3。我们现在正在开发在活动时间设置中的“预期集合”的方法。这种方法应该能够对环境暴露对生存和其他故障时间结果的影响进行有效和廉价的评估。(3)第三个项目开发了改进的方法，用于评估基于生物标记物相对于假阳性和假阴性预测的纵向测量对未来事件预测的准确性。 一篇以设计和分析精细匹配病例对照研究中的合并暴露评估方法为基础的论文正在出版中，一篇关于在环境因素对生育影响的怀孕时间研究中提出和评价使用合并评估的论文正在进行第二次审查。一篇基于对一项涉及生物标志物的纵向研究的预测进行评估的论文发表在《生物统计学》杂志上。

This project develops new statistical methods for epidemiology with broad applications and also methods as needed for ongoing projects in epidemiology, particularly those related to reproductive studies. The work this year involved several projects. (1) One project concerned the common practice of statistically adjusting for gestational age at birth when assessing risk factors for perinatal outcomes. Since gestational age at birth can be caused by other factors that also influence the outcome, it is a "collider" and such adjustment can potentially produce bias in the estimation. We carried out calculations to show that under reasonable assumptions such bias can be substantial and thus reproductive epidemiologists should avoid such adjusted models for etiologic inference. (2) Another project concerns pooled assessment of expensive-to-assay biomarkers based on human samples. Earlier work had shown that in a case-control setting one can pool together specimens from sets of cases and sets of controls and carry out a set-based analysis. With a slightly modified logistic model that analysis can estimate the individual-level risk parameters and loses almost no power compared to analysis based on individual assays. This means that if an exposure is based on an expensive assay that uses human samples, one can markedly improve efficiency by pooling specimens prior to assay. In recent work, we have extended these methods to apply to a fine-matched case-control design and also to time-to-pregnancy data. With the latter design, one pools specimens within strata defined by the time to conception. Again the power suffers almost not at all, compared to individual level assays, and the costs are greatly reduced. Another great benefit to pooling in general is in its conservative use of irreplaceable human specimens. For example, pooling specimens in sets of 3 reduces the amount needed from each specimen by 2/3. We are now developing methods for "prospective pooling" in time-to-event settings. Such methods should allow powerful and inexpensive assessments of the effects of environmental exposures on survival and other failure-time outcomes. (3) A third project developed improved methods for assessing the accuracy of prediction of future events based on longitudinal measures of a biomarker in relation to false positive and false negative predictions. A paper based on methods for design and analysis of pooled exposure assessments in fine-matched case-control studies is in press, and one that proposes and evaluates the use of pooling in time-to-pregnancy studies of fertility effects of environmental factors is undergoing its second review. A paper based on assessing prediction in a longitudinal study involving a biomarker was published in Biometrics.