Using ordinal outcomes to construct and select biomarker combinations for single-level prediction

Biomarker studies may involve an ordinal outcome, such as no, mild, or severe disease. There is often interest in predicting one particular level of the outcome due to its clinical significance. A simple approach to constructing biomarker combinations in this context involves dichotomizing the outcome and using a binary logistic regression model. We assessed whether more sophisticated methods offer advantages over this simple approach. It is often necessary to select among several candidate biomarker combinations. One strategy involves selecting a combination based on its ability to predict the outcome level of interest. We propose an algorithm that leverages the ordinal outcome to inform combination selection. We apply this algorithm to data from a study of acute kidney injury after cardiac surgery, where kidney injury may be absent, mild, or severe. Using more sophisticated modeling approaches to construct combinations provided gains over the simple binary logistic regression approach in specific settings. In the examples considered, the proposed algorithm for combination selection tended to reduce the impact of bias due to selection and to provide combinations with improved performance. Methods that utilize the ordinal nature of the outcome in the construction and/or selection of biomarker combinations have the potential to yield better combinations.