title: Statistical and practical considerations for clinical evaluation of predictive biomarkers.
abstract: Predictive biomarkers to guide therapy for cancer patients are a cornerstone of precision medicine. Discussed herein are considerations regarding the design and interpretation of such predictive biomarker studies. These considerations are important for both planning and interpreting prospective studies and for using specimens collected from completed randomized clinical trials. Specific issues addressed are differentiation between qualitative and quantitative predictive effects, challenges due to sample size requirements for predictive biomarker assessment, and consideration of additional factors relevant to clinical utility assessment, such as toxicity and cost of new therapies as well as costs and potential morbidities associated with routine use of biomarker-based tests.
authors.affiliation: Affiliations of authors: Biometric Research Branch (M-YCP, BF, ELK, LMS), Cancer Diagnosis Program (BAC), and Cancer Treatment and Evaluation Program (JSA), Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Mei-Yin C
authors.initials: MY
authors.lastname: Polley
authors.forename: Boris
authors.initials: B
authors.lastname: Freidlin
authors.forename: Edward L
authors.initials: EL
authors.lastname: Korn
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Conley
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Abrams
authors.forename: Lisa M
authors.initials: LM
authors.lastname: McShane
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000378:metabolism; D015254:DNA Modification Methylases / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000378:metabolism; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D066246:ErbB Receptors / Q000235:genetics; D000077156:Gefitinib; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy; D006801:Humans; D007191:Indazoles; D015850:Interleukin-6 / Q000378:metabolism; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics; D008745:Methylation; D058990:Molecular Targeted Therapy; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D057285:Precision Medicine / Q000639:trends*; D011237:Predictive Value of Tests; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use; D011799:Quinazolines / Q000494:pharmacology / Q000627:therapeutic use; D018714:Radiotherapy, Adjuvant; D016032:Randomized Controlled Trials as Topic; D018401:Sample Size; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use; D000077204:Temozolomide; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D007191:Indazoles; D015850:Interleukin-6; D011743:Pyrimidines; D011799:Quinazolines; D013449:Sulfonamides; D025521:Tumor Suppressor Proteins; D003606:Dacarbazine; C516667:pazopanib; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D066246:ErbB Receptors; D045643:DNA Repair Enzymes; D000077156:Gefitinib; D000077204:Temozolomide