title: The application of group sequential stopping boundaries to evaluate the treatment effect of an experimental agent across a range of biomarker expression.
abstract: Using stopping boundaries developed for group sequential trials, we control the overall type 1 error for a series of tests that evaluate the treatment effect of an experimental agent in each of several predefined marker subgroups. We then go on to present a procedure based on these group sequential stopping boundaries that provides strong control of type 1 error for testing a series of hypothesis regarding the treatment effect over a range of marker expression. Finally this use of group sequential procedures to control the type 1 error in biomarker subset testing will be compared with some other benchmark procedures in a simulation.
authors.affiliation: Oncomed Pharmaceuticals, Biostatistics, 800 Chesapeake Drive, United States. Electronic address: eric.holmgren@oncomed.com.
authors.forename: Eric
authors.initials: E
authors.lastname: Holmgren
mesh_terms: D000465:Algorithms; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015415:Biomarkers; D017322:Clinical Trials, Phase II as Topic / Q000379:methods*; D018572:Disease-Free Survival; D015507:Drugs, Investigational; D006801:Humans; D015233:Models, Statistical; D009369:Neoplasms / Q000188:drug therapy*; D012107:Research Design; D018401:Sample Size
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D015507:Drugs, Investigational
keywords: Biomarker; Group sequential boundary; Phase 2; Strong control