To pool or not to pool, from whether to when: applications of pooling to biospecimens subject to a limit of detection

Authors

  • Enrique F. Schisterman,

    1. Division of Epidemiology, Statistics and Prevention Research, National Institute of Child Health and Human Development, National Institutes of Health, Rockville, MD, USA
    Search for more papers by this author
  • Albert Vexler

    1. Division of Epidemiology, Statistics and Prevention Research, National Institute of Child Health and Human Development, National Institutes of Health, Rockville, MD, USA
    Search for more papers by this author

Enrique F. Schisterman, Division of Epidemiology, Statistics and Prevention Research, National Institute of Child Health and Human Development, 6100 Executive Boulevard, 7B03N, Rockville MD 20852, USA.
E-mail: schistee@mail.nih.gov

Summary

Pooling of biological specimens has been utilised as a cost-efficient sampling strategy, but cost is not the unique limiting factor in biomarker development and evaluation. We examine the effect of different sampling strategies of biospecimens for exposure assessment that cannot be detected below a detection threshold (DT). The paper compares use of pooled samples to a randomly selected sample from a cohort in order to evaluate the efficiency of parameter estimates.

The proposed approach shows that a pooling design is more efficient than a random sample strategy under certain circumstances. Moreover, because pooling minimises the amount of information lost below the DT, the use of pooled data is preferable (in a context of a parametric estimation) to using all available individual measurements, for certain values of the DT. We propose a combined design, which applies pooled and unpooled biospecimens, in order to capture the strengths of the different sampling strategies and overcome instrument limitations (i.e. DT). Several Monte Carlo simulations and an example based on actual biomarker data illustrate the results of the article.

Ancillary