title: Pooling Bio-Specimens in the Presence of Measurement Error and Non-Linearity in Dose-Response: Simulation Study in the Context of a Birth Cohort Investigating Risk Factors for Autism Spectrum Disorders.
abstract: We sought to determine the potential effects of pooling on power, false positive rate (FPR), and bias of the estimated associations between hypothetical environmental exposures and dichotomous autism spectrum disorders (ASD) status. Simulated birth cohorts in which ASD outcome was assumed to have been ascertained with uncertainty were created. We investigated the impact on the power of the analysis (using logistic regression) to detect true associations with exposure (X₁) and the FPR for a non-causal correlate of exposure (X₂, r = 0.7) for a dichotomized ASD measure when the pool size, sample size, degree of measurement error variance in exposure, strength of the true association, and shape of the exposure-response curve varied. We found that there was minimal change (bias) in the measures of association for the main effect (X₁). There is some loss of power but there is less chance of detecting a false positive result for pooled compared to individual level models. The number of pools had more effect on the power and FPR than the overall sample size. This study supports the use of pooling to reduce laboratory costs while maintaining statistical efficiency in scenarios similar to the simulated prospective risk-enriched ASD cohort.
authors.affiliation: Department of Environmental and Occupational Health, Dornsife School of Public Health, Drexel University, Philadelphia, PA 19104, USA. karynkh@aol.com.
authors.forename: Karyn
authors.initials: K
authors.lastname: Heavner
authors.affiliation: A.J. Drexel Autism Institute, Dornsife School of Public Health, Drexel University, Philadelphia, PA 19104, USA. cjn32@drexel.edu.
authors.forename: Craig
authors.initials: C
authors.lastname: Newschaffer
authors.affiliation: Department of Public Health Sciences, University of California at Davis, Davis, CA 95616, USA. ihp@phs.ucdavis.edu.
authors.forename: Irva
authors.initials: I
authors.lastname: Hertz-Picciotto
authors.affiliation: Department of Public Health Sciences, University of California at Davis, Davis, CA 95616, USA. dhbennett@phs.ucdavis.edu.
authors.forename: Deborah
authors.initials: D
authors.lastname: Bennett
authors.affiliation: Department of Environmental and Occupational Health, Dornsife School of Public Health, Drexel University, Philadelphia, PA 19104, USA. cjn32@drexel.edu.|A.J. Drexel Autism Institute, Dornsife School of Public Health, Drexel University, Philadelphia, PA 19104, USA. cjn32@drexel.edu.|Department of Epidemiology and Biostatistics, Dornsife School of Public Health, Drexel University, Philadelphia, PA 19104, USA. cjn32@drexel.edu.
authors.forename: Igor
authors.initials: I
authors.lastname: Burstyn
mesh_terms: D000067877:Autism Spectrum Disorder / Q000209:etiology*; D015982:Bias; D015331:Cohort Studies; D003198:Computer Simulation; D004781:Environmental Exposure; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D015201:Meta-Analysis as Topic; D015233:Models, Statistical; D012107:Research Design; D012307:Risk Factors; D018401:Sample Size
keywords: autism spectrum disorders; measurement error; pooling