Improving the design of epidemiology studies that use biomonitoring for exposure assessment: a SciPinion panel recommendation

Abstract Background Epidemiological studies that rely on biomarkers of exposure typically estimate each subject’s exposure from measurements on that individual. If repeated measurements of biomarkers of exposure are obtained on an individual, they are typically averaged. This averaging helps to reduce error from within-person variability if average exposure is a better measure of the biologically effective dose than the instantaneous one. However, these analyses then often ignore the residual within-person variation in the averages of measurements. Not considering this variation can bias effect estimates and lead to inaccurate risk assessment. Methods We developed software (“calculators”) that help design studies of continuous and binary outcomes that rely on biomarkers of exposure. An independent panel of experts was employed to peer review the models and answer questions regarding their use and best practices for the design of epidemiology studies that utilize biomonitoring data for the exposure assessment. Results Web-based tools were developed to estimate the required sample sizes, number of repeated measurements, and the trade-offs between power and bias in simple linear and logistic regression models under classical (independent, additive, normally distributed, homogeneous variance) measurement error assumptions. Application of the calculators was illustrated in case studies of investigation of the associations between urinary levels of bisphenols during pregnancy and fetal growth, and urinary levels of triclosan and neurodevelopment in children. Best practices are recommended for the design of epidemiology studies that utilize biomonitoring data for the exposure assessment. Conclusions Calculators have been developed and vetted by a panel of experts. They are designed to estimate sample size (number of individuals sampled and number of samples per individual), power and bias in epidemiological studies that use biomonitoring to assess each subject’s exposure in the presence of classical measurement errors. These user-friendly tools account for measurement error and allow researchers to design more accurate and appropriately powered studies, ultimately improving quality of public health research.