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Abstract:
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Cost-effective yet efficient designs are critical to the success of biomarker validation research. Two-phase sampling designs, under which expensive exposures are only measured on a subsample of cases and a fraction of non-cases, are useful in novel biomarker evaluation for preserving study samples and minimizing cost of biomarker assaying. In this manuscript, we investigate a variety of two-phase design options and provide statistical approaches aimed at improving efficiency of simple IPW estimators by incorporating auxiliary information available for the entire cohort. Drawn on the idea of augmentation previously proposed in the context of relative risk estimation, we consider accuracy summary estimators that accommodate auxiliary information in the context of evaluating the incremental values of novel biomarkers over existing prediction tools and provide formal theoretical justifications in terms of consistency and weak convergence. In addition, we evaluate the relative efficiency of a variety of sampling and estimation options under both types of two-phase studies, to shed light on issues pertaining to both the design and analysis of biomarker validation studies. We apply o
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