title: Case-control data analysis for randomly pooled biomarkers.
abstract: Pooled study designs, where individual biospecimens are combined prior to measurement via a laboratory assay, can reduce lab costs while maintaining statistical efficiency. Analysis of the resulting pooled measurements, however, often requires specialized techniques. Existing methods can effectively estimate the relation between a binary outcome and a continuous pooled exposure when pools are matched on disease status. When pools are of mixed disease status, however, the existing methods may not be applicable. By exploiting characteristics of the gamma distribution, we propose a flexible method for estimating odds ratios from pooled measurements of mixed and matched status. We use simulation studies to compare consistency and efficiency of risk effect estimates from our proposed methods to existing methods. We then demonstrate the efficacy of our method applied to an analysis of pregnancy outcomes and pooled cytokine concentrations. Our proposed approach contributes to the toolkit of available methods for analyzing odds ratios of a pooled exposure, without restricting pools to be matched on a specific outcome.
authors.affiliation: Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, Bethesda, MD, 20892, USA. perkinsn@mail.nih.gov.
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Perkins
authors.affiliation: Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, Bethesda, MD, 20892, USA.
authors.forename: Emily M
authors.initials: EM
authors.lastname: Mitchell
authors.affiliation: Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, 30322, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Lyles
authors.affiliation: Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, Bethesda, MD, 20892, USA.
authors.forename: Enrique F
authors.initials: EF
authors.lastname: Schisterman
mesh_terms: D015415:Biomarkers / Q000032:analysis*; D016022:Case-Control Studies; D003198:Computer Simulation; D016207:Cytokines / Q000097:blood; D003627:Data Interpretation, Statistical; D005260:Female; D006801:Humans; D008954:Models, Biological; D016017:Odds Ratio; D011247:Pregnancy; D011256:Pregnancy Outcome
chemical_list: D015415:Biomarkers; D016207:Cytokines
keywords: Biomarkers; Gamma distribution; Odds ratio; Pooled specimens; Skewness
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