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An Empirical Validation of the Within-subject Biospecimens Pooling Approach to Minimize Exposure Misclassification in Biomarker-based Studies

Abstract : Background: Within-subject biospecimens pooling can theoretically reduce bias in dose-response functions from biomarker-based studies when exposure assessment suffers from classical-type error. However, collecting many urine voids each day is cumbersome. We evaluated the empirical validity of a within-subject pooling approach and compared several options to avoid sampling each void. Methods: In 16 pregnant women who collected a spot of each urine void over several nonconsecutive weeks, we compared concentrations of 10 phenols in daily, weekly, and pregnancy within-subject pools. We pooled either three or all daily samples. In a simulation study using these data, we quantified bias in dose-response functions when using one to 20 urine samples per subject to assess methylparaben (a compound with moderate within-subject variability) and bisphenol A (high variability) exposures. Results: Correlations between exposure estimates from pools of all and of only three voids per day were above 0.80 for all time windows and compounds, except for benzophenone-3 and triclosan in the daily time window (correlations, 0.57-0.68). With one spot sample to assess pregnancy exposure, correlations were all below 0.74. Using only one biospecimen led to attenuation bias in the dose-response functions of 29% (methylparaben) and 69% (bisphenol A); four samples for methylparaben and 18 for bisphenol A decreased bias to 10%. Conclusions: For nonpersistent chemicals, collecting and pooling three samples per day instead of all daily samples efficiently estimates exposures over a week or more. Collecting around 20 biospecimens can strongly limit attenuation bias for nonpersistent chemicals such as bisphenol A.
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https://www.hal.inserm.fr/inserm-03156679
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Submitted on : Wednesday, March 3, 2021 - 10:10:13 AM
Last modification on : Tuesday, May 11, 2021 - 11:36:39 AM

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Céline Vernet, Claire Philippat, Lydiane Agier, Antonia Calafat, Xiaoyun Ye, et al.. An Empirical Validation of the Within-subject Biospecimens Pooling Approach to Minimize Exposure Misclassification in Biomarker-based Studies. Epidemiology, Lippincott, Williams & Wilkins, 2019, 30 (5), pp.756-767. ⟨10.1097/EDE.0000000000001056⟩. ⟨inserm-03156679⟩

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