Statistical Methods In Epidemiology--general

本项目发展具有广泛应用的流行病学新统计方法，并发展流行病学正在进行的项目所需的方法，特别是与生殖研究有关的项目。今年的工作涉及几个项目。(1)一个项目涉及使用美国新生儿的双变量出生体重和妊娠长度数据来估计和纠正使用最后一次月经来估计妊娠长度的测量误差。我们的最终目标是制定更好的出生体重标准和妊娠周的差异，并纠正种族和产妇年龄类别中估计的早产率。我们还希望在这些类别中改进对出生体重、妊娠期长短和围产期死亡风险之间关系的评估。(2)另一个项目涉及基于人类样本的昂贵生物标志物的综合评估。早期的工作表明，在病例对照环境中，可以将来自病例组和对照组的标本汇集在一起，并进行基于病例组的分析。通过稍微修改的逻辑模型，分析可以估计个人水平的风险参数，并且与基于个人分析的分析相比几乎没有损失。这意味着，如果暴露是基于使用人类样本的昂贵化验，则可以通过在化验前汇集标本来显着提高效率。在最近的工作中，我们将这些方法扩展到适用于精细匹配的病例对照设计和怀孕时间数据。在后一种设计中，人们将标本放入由时间定义的地层中。再一次，与个体水平的分析相比，功率几乎没有受到任何影响，而且成本大大降低。总的来说，汇集的另一个巨大好处是它对不可替代的人类标本的保守使用。例如，以3个样本为一组将每个样本所需的数量减少了2/3。(3)第三个项目开发了基于与假阳性和假阴性预测相关的生物标志物的纵向测量来评估未来事件预测准确性的改进方法。

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 using the bivariate birth weight and gestational length data for US births to estimate and correct for measurement errors in use of last menstrual period for estimating gestational length. Our goal is ultimately to develop improved standards for birth weights and variances for each completed week of gestation and also to correct the estimated rates of preterm birth within ethnic and maternal age categories. We also hope to improve the assessment of the relationship between birth weight, gestational length and risk of perinatal mortality within those categories. (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. (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 currently undergoing review, and one that proposes and evaluates the use of pooling in time-to-pregnancy studies of fertility effects of environmental factors is soon to be submitted. A paper based on improving birth weight standards for specific gestational ages is currently in preparation. A paper based on assessing prediction in a longitudinal study involving a biomarker was published in Biometrics and another in this area is undergoing review.