title: An efficient basket trial design.
abstract: The landscape for early phase cancer clinical trials is changing dramatically because of the advent of targeted therapy. Increasingly, new drugs are designed to work against a target such as the presence of a specific tumor mutation. Because typically only a small proportion of cancer patients will possess the mutational target, but the mutation is present in many different cancers, a new class of basket trials is emerging, whereby the drug is tested simultaneously in different baskets, that is, subgroups of different tumor types. Investigators desire not only to test whether the drug works but also to determine which types of tumors are sensitive to the drug. A natural strategy is to conduct parallel trials, with the drug 's effectiveness being tested separately, using for example, the popular Simon two-stage design independently in each basket. The work presented is motivated by the premise that the efficiency of this strategy can be improved by assessing the homogeneity of the baskets ' response rates at an interim analysis and aggregating the baskets in the second stage if the results suggest the drug might be effective in all or most baskets. Via simulations, we assess the relative efficiencies of the two strategies. Because the operating characteristics depend on how many tumor types are sensitive to the drug, there is no uniformly efficient strategy. However, our investigation demonstrates that substantial efficiencies are possible if the drug works in most or all baskets, at the cost of modest losses of power if the drug works in only a single basket. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, 485 Lexington Ave. 2nd Floor, New York City, 10017, NY, U.S.A.
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Cunanan
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, 485 Lexington Ave. 2nd Floor, New York City, 10017, NY, U.S.A.
authors.forename: Alexia
authors.initials: A
authors.lastname: Iasonos
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, 485 Lexington Ave. 2nd Floor, New York City, 10017, NY, U.S.A.
authors.forename: Ronglai
authors.initials: R
authors.lastname: Shen
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, 485 Lexington Ave. 2nd Floor, New York City, 10017, NY, U.S.A.
authors.forename: Colin B
authors.initials: CB
authors.lastname: Begg
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, 485 Lexington Ave. 2nd Floor, New York City, 10017, NY, U.S.A.
authors.forename: Mithat
authors.initials: M
authors.lastname: Gönen
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D056808:Biostatistics; D002986:Clinical Trials as Topic / Q000379:methods* / Q000706:statistics & numerical data; D017322:Clinical Trials, Phase II as Topic / Q000379:methods / Q000706:statistics & numerical data; D003198:Computer Simulation; D006801:Humans; D058990:Molecular Targeted Therapy; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D012984:Software
chemical_list: D000970:Antineoplastic Agents
keywords: basket trials; multiple comparisons; phase II clinical trials; power