title: Boomerang: A method for recursive reclassification.
abstract: While there are many validated prognostic classifiers used in practice, often their accuracy is modest and heterogeneity in clinical outcomes exists in one or more risk subgroups. Newly available markers, such as genomic mutations, may be used to improve the accuracy of an existing classifier by reclassifying patients from a heterogenous group into a higher or lower risk category. The statistical tools typically applied to develop the initial classifiers are not easily adapted toward this reclassification goal. In this article, we develop a new method designed to refine an existing prognostic classifier by incorporating new markers. The two-stage algorithm called Boomerang first searches for modifications of the existing classifier that increase the overall predictive accuracy and then merges to a prespecified number of risk groups. Resampling techniques are proposed to assess the improvement in predictive accuracy when an independent validation data set is not available. The performance of the algorithm is assessed under various simulation scenarios where the marker frequency, degree of censoring, and total sample size are varied. The results suggest that the method selects few false positive markers and is able to improve the predictive accuracy of the classifier in many settings. Lastly, the method is illustrated on an acute myeloid leukemia data set where a new refined classifier incorporates four new mutations into the existing three category classifier and is validated on an independent data set.
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, New York 10065, U.S.A.. devlins@mskcc.org.
authors.forename: Sean M
authors.initials: SM
authors.lastname: Devlin
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, New York 10065, U.S.A.
authors.forename: Irina
authors.initials: I
authors.lastname: Ostrovnaya
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, New York 10065, U.S.A.
authors.forename: Mithat
authors.initials: M
authors.lastname: Gönen
mesh_terms: D000465:Algorithms; D015415:Biomarkers; D002965:Classification / Q000379:methods*; D003198:Computer Simulation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics; D008722:Methods; D009154:Mutation; D011237:Predictive Value of Tests; D011379:Prognosis; D018401:Sample Size
chemical_list: D015415:Biomarkers
keywords: Predictive accuracy; Prognostication; Reclassification; Recursive partitioning; Survival analysis