A discriminant function approach to adjust for processing and measurement error when a biomarker is assayed in pooled samples

Robert H. Lyles, Dane Van Domelen, Emily M. Mitchell, Enrique F. Schisterman

Research output: Contribution to journalArticlepeer-review

Abstract

Pooling biological specimens prior to performing expensive laboratory assays has been shown to be a cost effective approach for estimating parameters of interest. In addition to requiring specialized statistical techniques, however, the pooling of samples can introduce assay errors due to processing, possibly in addition to measurement error that may be present when the assay is applied to individual samples. Failure to account for these sources of error can result in biased parameter estimates and ultimately faulty inference. Prior research addressing biomarker mean and variance estimation advocates hybrid designs consisting of individual as well as pooled samples to account for measurement and processing (or pooling) error. We consider adapting this approach to the problem of estimating a covariate-adjusted odds ratio (OR) relating a binary outcome to a continuous exposure or biomarker level assessed in pools. In particular, we explore the applicability of a discriminant function-based analysis that assumes normal residual, processing, and measurement errors. A potential advantage of this method is that maximum likelihood estimation of the desired adjusted log OR is straightforward and computationally convenient. Moreover, in the absence of measurement and processing error, the method yields an efficient unbiased estimator for the parameter of interest assuming normal residual errors. We illustrate the approach using real data from an ancillary study of the Collaborative Perinatal Project, and we use simulations to demonstrate the ability of the proposed estimators to alleviate bias due to measurement and processing error.

Original languageEnglish (US)
Pages (from-to)14723-14740
Number of pages18
JournalInternational Journal of Environmental Research and Public Health
Volume12
Issue number11
DOIs
StatePublished - Nov 18 2015
Externally publishedYes

Keywords

  • Epidemiology
  • Errors-in-variables
  • Odds ratio
  • Pooling

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

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