title: Choice of study endpoint significantly impacts the results of breast cancer trials evaluating chemotherapy-induced nausea and vomiting.
abstract: Multiple endpoints can be used to evaluate chemotherapy-induced nausea and vomiting (CINV). These endpoints reflect the various combinations of vomiting, nausea and rescue antiemetic use in the acute (0-24 h), delayed (>24-120 h) and overall (0-120 h) periods after chemotherapy. As the choice of outcome measure could potentially change the interpretation of clinical trial results, we evaluated CINV rates using different endpoints on a single dataset from a prospective cohort. Data from 177 breast cancer patients receiving anthracycline and cyclophosphamide-based chemotherapy was used to calculate CINV control rates using the 15 most commonly reported CINV endpoints. As nausea remains such a significant symptom, we explored the frequency at which pharmaceutical and non-pharmaceutical company-funded studies included measures of nausea in their primary study endpoint. CINV control rates ranged from 12.5 %, 95 % (CI 7.6-17.4 %) for total control (no vomiting, no nausea and no rescue medication) in the overall period to 77.4 %, 95 % (CI 71.2-83.6 %) for no vomiting in the overall period. Similar differences were found in the acute and delayed periods. Non-pharmaceutical company-funded trials were more likely to include a measure of nausea in the primary study outcome (9/18, 50 %) than pharmaceutical-funded trials (1/12, 8.3 %). The choice of trial endpoint has an important impact on reported CINV control rates and could significantly impact on interpretation of the results. Primary endpoints of studies, including those mandated by regulatory bodies, should account for nausea to reflect patient experience. Reporting of endpoints should be more comprehensive to allow for cross-trial comparisons.
authors.affiliation: Department of Medicine and Division of Medical Oncology, The Ottawa Hospital and University of Ottawa, 501 Smyth Road, Box 912, Ottawa, ON, K1H8L6, Canada.
authors.forename: Terry
authors.initials: T
authors.lastname: Ng
authors.affiliation: Ottawa Hospital Research Institute, Ottawa, Canada.
authors.forename: Sasha
authors.initials: S
authors.lastname: Mazzarello
authors.affiliation: Ottawa Hospital Research Institute, Ottawa, Canada.|Department of Epidemiology, The Ottawa Hospital, Ottawa, Canada.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Ottawa Hospital Research Institute, Ottawa, Canada.|School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Canada.
authors.forename: Brian
authors.initials: B
authors.lastname: Hutton
authors.affiliation: Statistical Consultant, Toronto, Canada.
authors.forename: George
authors.initials: G
authors.lastname: Dranitsaris
authors.affiliation: Ottawa Hospital Research Institute, Ottawa, Canada.
authors.forename: Lisa
authors.initials: L
authors.lastname: Vandermeer
authors.affiliation: Ottawa Hospital Research Institute, Ottawa, Canada.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Smith
authors.affiliation: Department of Medicine and Division of Medical Oncology, The Ottawa Hospital and University of Ottawa, 501 Smyth Road, Box 912, Ottawa, ON, K1H8L6, Canada. mclemons@toh.on.ca.|Ottawa Hospital Research Institute, Ottawa, Canada. mclemons@toh.on.ca.
authors.forename: Mark
authors.initials: M
authors.lastname: Clemons
mesh_terms: D000328:Adult; D018943:Anthracyclines / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy*; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced*; D011446:Prospective Studies; D014839:Vomiting / Q000139:chemically induced*
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; D003520:Cyclophosphamide
keywords: Antiemetics; Breast cancer; Chemotherapy; Endpoints; Nausea; Vomiting