Comparison of strategies to efficiently combine repeated urine samples in biomarker-based studies

In biomarker-based studies, collecting repeated biospecimens per participant can decrease measurement error, particularly for biomarkers displaying high within-subject variability. Guidelines to combine such repeated biospecimens do not exist.

To compare the efficiency of several designs relying on repeated biospecimens to estimate exposure over 7 days.

We quantified triclosan and bisphenol A (BPA) in all urine voids (N = 427) collected over seven days from eight individuals. We estimated the volume-weighted concentrations for all urine samples collected during a week and compared these gold standards with the concentrations obtained for equal-volume pools (standardized or not for urine dilution), unequal-volume pools (based on sample volume or creatinine concentration), and for the mean of the creatinine-standardized concentrations measured in each spot sample.

For both chemicals, correlations with gold standards were similar for equal- and unequal-volume pooling designs. Only for BPA, correlation coefficients were markedly lower after standardization for specific gravity or creatinine of concentrations estimated in equal-volume pools. Averaging BPA creatinine-standardized concentrations measured in each spot sample led also to lower correlations with gold standards compared to those obtained for unstandardized pooling designs.

For BPA and triclosan, considering individual urine sample volume or creatinine concentrations when pooling is unnecessary because equal-volume pool adequately estimates concentrations in gold standards. Standardization for specific gravity or creatinine of the concentrations assessed in equal-volume pool as well as averaging creatinine-standardized concentrations measured in each individual spot sample are not suitable for BPA. These results provide a practical framework on how to combine repeated biospecimens in epidemiological studies.