title: The Imperative for a New Approach to Toxicity Analysis in Oncology Clinical Trials.
abstract: A consistent system for reporting adverse events (AEs) is paramount in cancer clinical trials and is crucial to ensure the safety and tolerability of chemotherapy. The shift towards individualized medicine in oncology over the last decade has brought with it an impressive array of novel, targeted therapies and increasingly complex clinical trials to investigate them. Many of the newer drugs are oral agents that are taken continuously over protracted periods of time. They stand sharply in contrast to conventional cytotoxic intravenous chemotherapy given over a prefixed number of cycles. With its narrow emphasis on high-grade events, the consensus method for reporting of AEs in current cancer trials has not evolved to reflect the longitudinal toxicity profiles of the newer agents. Current methods do not incorporate patient-reported outcomes, which are of rising importance when therapy lasts for months or even years in a patient's life. Additionally, tables focusing on worst-grade events do not depict evolution of toxicity over time and therefore cannot offer patients and clinicians information about the onset or duration of a given AE. Most importantly, current methods do not capture lower-grade but longer-lasting toxicity that may have important ramifications on patients' quality of life. The failure to include any time-related information in our current methods of toxicity reporting provides an incomplete and even inaccurate depiction of AEs. To remain in step with the advancing science of cancer and the vast array of new therapies with extended treatment durations, our consensus method of AE analysis in oncology clinical trials must modernize to include the dimension of time.
authors.affiliation: Department of Medical Oncology (GT, JH, AG) and Alliance Statistics and Data Center (JAS), Mayo Clinic, Rochester, MN. thanarajasingam.gita@mayo.edu.
authors.forename: Gita
authors.initials: G
authors.lastname: Thanarajasingam
authors.affiliation: Department of Medical Oncology (GT, JH, AG) and Alliance Statistics and Data Center (JAS), Mayo Clinic, Rochester, MN.
authors.forename: Joleen M
authors.initials: JM
authors.lastname: Hubbard
authors.affiliation: Department of Medical Oncology (GT, JH, AG) and Alliance Statistics and Data Center (JAS), Mayo Clinic, Rochester, MN.
authors.forename: Jeff A
authors.initials: JA
authors.lastname: Sloan
authors.affiliation: Department of Medical Oncology (GT, JH, AG) and Alliance Statistics and Data Center (JAS), Mayo Clinic, Rochester, MN.
authors.forename: Axel
authors.initials: A
authors.lastname: Grothey
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems / Q000639:trends; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D002986:Clinical Trials as Topic; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D011788:Quality of Life; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents