title: An entropy-based nonparametric test for the validation of surrogate endpoints.
abstract: We present a nonparametric test to validate surrogate endpoints based on measure of divergence and random permutation. This test is a proposal to directly verify the Prentice statistical definition of surrogacy. The test does not impose distributional assumptions on the endpoints, and it is robust to model misspecification. Our simulation study shows that the proposed nonparametric test outperforms the practical test of the Prentice criterion in terms of both robustness of size and power. We also evaluate the performance of three leading methods that attempt to quantify the effect of surrogate endpoints. The proposed method is applied to validate magnetic resonance imaging lesions as the surrogate endpoint for clinical relapses in a multiple sclerosis trial.
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Miao
authors.forename: Yong-Cheng
authors.initials: YC
authors.lastname: Wang
authors.forename: Ashis
authors.initials: A
authors.lastname: Gangopadhyay
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism*; D003198:Computer Simulation / Q000706:statistics & numerical data; D023381:Endpoint Determination / Q000706:statistics & numerical data*; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D015233:Models, Statistical; D009103:Multiple Sclerosis / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology; D016012:Poisson Distribution; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D055502:Secondary Prevention; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D015415:Biomarkers; D016899:Interferon-beta; D000068556:Interferon beta-1a