Specimen pooling for efficient use of biospecimens in studies of time to a common event

Am J Epidemiol. 2013 Jul 1;178(1):126-35. doi: 10.1093/aje/kws442. Epub 2013 May 2.

Abstract

For case-control studies that rely on expensive assays for biomarkers, specimen pooling offers a cost-effective and efficient way to estimate individual-level odds ratios. Pooling helps to conserve irreplaceable biospecimens for the future, mitigates limit-of-detection problems, and enables inclusion of individuals who have limited available volumes of biospecimen. Pooling can also allow the study of a panel of biomarkers under a fixed assay budget. Here, we extend this method for application to discrete-time survival studies. Assuming a proportional odds logistic model for risk of a common outcome, we propose a design strategy that forms pooling sets within those experiencing the outcome at the same event time. We show that the proposed design enables a cost-effective analysis to assess the association of a biomarker with the outcome. Because the standard likelihood is slightly misspecified for the proposed pooling strategy under a nonnull biomarker effect, the proposed approach produces slightly biased estimates of exposure odds ratios. We explore the extent of this bias via simulations and illustrate the method by revisiting a data set relating polychlorinated biphenyls and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene to time to pregnancy.

Keywords: discrete event time outcome; pooling; pooling for biomarker; pooling for exposure; time to pregnancy.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Biomarkers / analysis
  • Biomarkers / blood
  • Case-Control Studies*
  • Cost-Benefit Analysis
  • Dichlorodiphenyl Dichloroethylene / adverse effects
  • Dichlorodiphenyl Dichloroethylene / analogs & derivatives
  • Dichlorodiphenyl Dichloroethylene / blood
  • Female
  • Humans
  • Logistic Models
  • Models, Statistical
  • Odds Ratio
  • Polychlorinated Biphenyls / adverse effects
  • Polychlorinated Biphenyls / blood
  • Pregnancy
  • Risk Factors
  • Specimen Handling / economics
  • Specimen Handling / methods*
  • Time Factors

Substances

  • Biomarkers
  • Dichlorodiphenyl Dichloroethylene
  • Polychlorinated Biphenyls