title: Randomized reverse marker strategy design for prospective biomarker validation.
abstract: We describe a novel study design for validating marker-based treatment strategies meant to select among possible therapeutic options using a biologic marker. Studying existing designs in realistic scenarios, we demonstrate that this design is more than four times more efficient for testing the interaction between a marker and its intended treatment. Our analysis employs a simple parametric framework that uncovers systematic biases in currently proposed designs and suggests how they may be accommodated or enumerated. In the context of markers for choosing a treatment for recurrent ovarian cancer, our proposal requires sample sizes on the order of recently completed phases II and III studies making validation studies for this clinical decision scenario viable.
authors.affiliation: Roswell Park Cancer Institute, Department of Biostatistics and Bioinformatics, Elm and Carlton Streets, Buffalo, NY, 14263, U.S.A.
authors.forename: Kevin H
authors.initials: KH
authors.lastname: Eng
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D056808:Biostatistics; D005260:Female; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000628:therapy; D010051:Ovarian Neoplasms / Q000628:therapy; D011338:Probability Theory; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D018401:Sample Size; D054928:Validation Studies as Topic
chemical_list: D014408:Biomarkers, Tumor
keywords: biomarker validation; interaction; ovarian cancer; randomized trial; trial design