Background

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.

Aims

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

Methods

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.

Results

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.

Conclusion

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.

中文翻译：

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在基于生物标志物的研究中有效组合重复尿液样本的策略比较

背景

在基于生物标志物的研究中，收集每位参与者重复的生物样本可以减少测量误差，特别是对于显示出受试者内部高变异性的生物标志物。不存在合并此类重复生物样本的指南。

宗旨

比较依赖重复生物样本估计 7 天暴露的几种设计的效率。

方法

我们在 7 天内从 8 个个体收集的所有尿液（N = 427）中量化了三氯生和双酚 A (BPA)。我们估计了一周内收集的所有尿液样本的体积加权浓度，并将这些黄金标准与等体积池（尿液稀释标准化或未标准化）、不等体积池（基于样本体积或肌酐浓度）获得的浓度进行比较)，以及在每个点样本中测量的肌酐标准化浓度的平均值。

结果

对于这两种化学品，等体积和不等体积混合设计与黄金标准的相关性相似。仅对于 BPA，在对等体积池中估计的比重或肌酐浓度进行标准化后，相关系数显着降低。与非标准化合并设计获得的那些相比，在每个点样本中测量的平均 BPA 肌酐标准化浓度也导致与金标准的相关性较低。

结论

对于 BPA 和三氯生，在合并时考虑单个尿样体积或肌酐浓度是不必要的，因为等体积合并足以估计金标准中的浓度。在等体积池中评估的浓度的比重或肌酐标准化以及在每个单独的点样本中测量的平均肌酐标准化浓度不适用于 BPA。这些结果为如何在流行病学研究中结合重复的生物样本提供了一个实用的框架。