Biomarker evaluation and comparison using the controls as a reference population

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Abstract
The classification accuracy of a continuous marker is typically evaluated with the receiver operating characteristic (ROC) curve. In this paper, we study an alternative conceptual framework, the “percentile value.” In this framework, the controls only provide a reference distribution to standardize the marker. The analysis proceeds by analyzing the standardized marker in cases. The approach is shown to be equivalent to ROC analysis. Advantages are that it provides a framework familiar to a broad spectrum of biostatisticians and it opens up avenues for new statistical techniques in biomarker evaluation. We develop several new procedures based on this framework for comparing biomarkers and biomarker performance in different populations. We develop methods that adjust such comparisons for covariates. The methods are illustrated on data from 2 cancer biomarker studies.