Optimal allocation of resources in a biomarker setting

• Published in: Statistics in medicine Vol. 34; no. 2; pp. 297 - 306
• Main Authors: Rosner, Bernard, Hendrickson, Sara, Willett, Walter
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 30.01.2015; Wiley Subscription Services, Inc
• Subjects: Ascorbic Acid - blood; Bias; biomarker; Biomarkers; Biomarkers - blood; Computer Simulation; Data Interpretation, Statistical; Diet Records; Energy Intake; Europe; Humans; measurement error; Measurement errors; method of triads; Nutrition Assessment; Nutrition research; Oncology; Prospective Studies; Research Design; Resource allocation; Resource Allocation - economics; Resource Allocation - standards; Vitamin C; Europe; biomarker; method of triads; measurement error
• ISSN: 0277-6715; 1097-0258; 1097-0258
• DOI: 10.1002/sim.6327

Nutrient intake is often measured with substantial error both in commonly used surrogate instruments such as a food frequency questionnaire (FFQ) and in gold standard‐type instruments such as a diet record (DR). If there is a correlated error between the FFQ and DR, then standard measurement error correction methods based on regression calibration can produce biased estimates of the regression coefficient (λ) of true intake on surrogate intake. However, if a biomarker exists and the error in the biomarker is independent of the error in the FFQ and DR, then the method of triads can be used to obtain unbiased estimates of λ, provided that there are replicate biomarker data on at least a subsample of validation study subjects. Because biomarker measurements are expensive, for a fixed budget, one can use a either design where a large number of subjects have one biomarker measure and only a small subsample is replicated or a design that has a smaller number of subjects and has most or all subjects validated. The purpose of this paper is to optimize the proportion of subjects with replicated biomarker measures, where optimization is with respect to minimizing the variance of ln(λ̂). The methodology is illustrated using vitamin C intake data from the European Prospective Investigation into Cancer and Nutrition study where plasma vitamin C is the biomarker. In this example, the optimal validation study design is to have 21% of subjects with replicated biomarker measures. Copyright © 2014 John Wiley & Sons, Ltd.