Classification of clinical outcomes using high-throughput informatics: Part 1 - nonparametric method reviews

It is widely recognized that many cancer therapies are effective only for a subset of patients. However clinical studies are most often powered to detect an overall treatment effect. To address this issue, classification methods are increasingly being used to predict a subset of patients which respond differently to treatment. This study begins with a brief history of classifi- cation methods with an emphasis on applications involving melanoma. Nonparametric methods suitable for predicting subsets of patients responding differently to treatment are then reviewed. Each method has different ways of incorporating continuous, categorical, clinical and high-throughput covariates. More recent methods have built-in dimension reduction methods for high throughput data. Pre-validation is one method of assessing the added value of high-throughput data to clinical covariates. The way in which treatment interactions are incorporated is important if the goal is to predict a subset of patients which respond differently to treatment. For nonparametric methods, distance measures specific to the method are used to make classification decisions. Approaches are outlined which employ these distances to measure treatment interactions. It is hoped that this study will stimulate more development of nonparametric methods to predict subsets of patients responding differently to treatment.