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.
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