title: Adaptive clinical trial designs for simultaneous testing of matched diagnostics and therapeutics.
abstract: A critical challenge in the development of new molecularly targeted anticancer drugs is the identification of predictive biomarkers and the concurrent development of diagnostics for these biomarkers. Developing matched diagnostics and therapeutics will require new clinical trial designs and methods of data analysis. The use of adaptive design in phase III trials may offer new opportunities for matched diagnosis and treatment because the size of the trial can allow for subpopulation analysis. We present an adaptive phase III trial design that can identify a suitable target population during the early course of the trial, enabling the efficacy of an experimental therapeutic to be evaluated within the target population as a later part of the same trial. The use of such an adaptive approach to clinical trial design has the potential to greatly improve the field of oncology and facilitate the development of personalized medicine.
authors: Department of Medicine, Genitourinary Oncology Service, Memorial Sloan-Kettering Cancer Center, and Weill Cornell Medical College, New York, New York, USA. scherh@mskcc.org
authors: Howard I
authors: HI
authors: Scher
authors: Shelley Fuld
authors: SF
authors: Nasso
authors: Eric H
authors: EH
authors: Rubin
authors: Richard
authors: R
authors: Simon
mesh_terms: D000465:Algorithms; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D017326:Clinical Trials, Phase III as Topic / Q000379:methods*; D003627:Data Interpretation, Statistical; D023381:Endpoint Determination; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy / Q000379:methods; D009369:Neoplasms / Q000175:diagnosis* / Q000188:drug therapy*; D057285:Precision Medicine / Q000379:methods; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000188:drug therapy
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor