title: Focusing on Core Patient-Reported Outcomes in Cancer Clinical Trials: Symptomatic Adverse Events, Physical Function, and Disease-Related Symptoms.
abstract: Cancer clinical trials have relied on overall survival and measures of tumor growth or reduction to assess the efficacy of a drug. However, benefits are often accompanied by significant symptomatic toxicities. The degree to which a therapy improves disease symptoms and introduces symptomatic toxicity affects how patients function in their daily lives. These concepts are important contributors to health-related quality of life (HRQOL). In this article, we discuss patient-reported outcome (PRO) assessment in cancer trials and challenges relying solely on static multi-item HRQOL instruments. We propose focusing on three separate measures of well-defined concepts: symptomatic adverse events, physical function, and disease-related symptoms, which are key contributors to the effect of a therapy on HRQOL. Separate measures of these three concepts may facilitate the incorporation of emerging contemporary instruments that can tailor the PRO assessment strategy to different trial contexts. Irrespective of the PRO measures used, continued improvement in trial design and conduct is crucial to decrease missing data and optimize the quality of PRO information. International stakeholder collaboration and continued research into optimal practices for PRO and other clinical outcome assessments are necessary to advance a common framework for generating and reporting rigorous patient-centered data from cancer clinical trials.
authors.affiliation: Office of Hematology and Oncology Products, Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland. paul.kluetz@fda.hhs.gov.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Kluetz
authors.affiliation: Clinical Outcome Assessment Staff, Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Ashley
authors.initials: A
authors.lastname: Slagle
authors.affiliation: Clinical Outcome Assessment Staff, Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Elektra J
authors.initials: EJ
authors.lastname: Papadopoulos
authors.affiliation: Office of Biostatistics, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Laura Lee
authors.initials: LL
authors.lastname: Johnson
authors.affiliation: Office of Hematology and Oncology Products, Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Martha
authors.initials: M
authors.lastname: Donoghue
authors.affiliation: Office of Hematology and Oncology Products, Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Virginia E
authors.initials: VE
authors.lastname: Kwitkowski
authors.affiliation: Clinical Outcome Assessment Staff, Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Wen-Hung
authors.initials: WH
authors.lastname: Chen
authors.affiliation: Office of Biostatistics, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Rajeshwari
authors.initials: R
authors.lastname: Sridhara
authors.affiliation: Office of Hematology and Oncology Products, Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Ann T
authors.initials: AT
authors.lastname: Farrell
authors.affiliation: Office of Hematology and Oncology Products, Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Patricia
authors.initials: P
authors.lastname: Keegan
authors.affiliation: Office of Hematology and Oncology Products, Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Kim
authors.affiliation: Office of Hematology and Oncology Products, Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Richard
authors.initials: R
authors.lastname: Pazdur
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D006801:Humans; D009369:Neoplasms / Q000175:diagnosis / Q000401:mortality / Q000628:therapy; D063868:Patient Outcome Assessment; D000071066:Patient Reported Outcome Measures; D011788:Quality of Life