title: Adverse symptom event reporting by patients vs clinicians: relationships with clinical outcomes.
abstract: BACKGROUND
  In cancer treatment trials, the standard source of adverse symptom data is clinician reporting by use of items from the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE). Patient self-reporting has been proposed as an additional data source, but the implications of such a shift are not understood.
  
  
  METHODS
  Patients with lung cancer receiving chemotherapy and their clinicians independently reported six CTCAE symptoms and Karnofsky Performance Status longitudinally at sequential office visits. To compare how patient's vs clinician's reports relate to sentinel clinical events, a time-dependent Cox regression model was used to measure associations between reaching particular CTCAE grade severity thresholds with the risk of death and emergency room visits. To measure concordance of CTCAE reports with indices of daily health status, Kendall tau rank correlation coefficients were calculated for each symptom with EuroQoL EQ-5D questionnaire and global question scores. Statistical tests were two-sided.
  
  
  RESULTS
  A total of 163 patients were enrolled for an average of 12 months (range = 1-28 months), with a mean of 11 visits and 67 (41%) deaths. CTCAE reports were submitted by clinicians at 95% of visits and by patients at 80% of visits. Patients generally reported symptoms earlier and more frequently than clinicians. Statistically significant associations with death and emergency room admissions were seen for clinician reports of fatigue (P < .001), nausea (P = .01), constipation (P = .038), and Karnofsky Performance Status (P < .001) but not for patient reports of these items. Higher concordance with EuroQoL EQ-5D questionnaire and global question scores was observed for patient-reported symptoms than for clinician-reported symptoms.
  
  
  CONCLUSIONS
  Longitudinally collected clinician CTCAE assessments better predict unfavorable clinical events, whereas patient reports better reflect daily health status. These perspectives are complementary, each providing clinically meaningful information. Inclusion of both types of data in treatment trial results and drug labels appears to be warranted.
authors.affiliation: Health Outcomes Group, Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, 307 East 63rd St, New York, NY 10065, USA. basche@mskcc.org
authors.forename: Ethan
authors.initials: E
authors.lastname: Basch
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Jia
authors.forename: Glenn
authors.initials: G
authors.lastname: Heller
authors.forename: Allison
authors.initials: A
authors.lastname: Barz
authors.forename: Laura
authors.initials: L
authors.lastname: Sit
authors.forename: Michael
authors.initials: M
authors.lastname: Fruscione
authors.forename: Mark
authors.initials: M
authors.lastname: Appawu
authors.forename: Alexia
authors.initials: A
authors.lastname: Iasonos
authors.forename: Thomas
authors.initials: T
authors.lastname: Atkinson
authors.forename: Shari
authors.initials: S
authors.lastname: Goldfarb
authors.forename: Ann
authors.initials: A
authors.lastname: Culkin
authors.forename: Mark G
authors.initials: MG
authors.lastname: Kris
authors.forename: Deborah
authors.initials: D
authors.lastname: Schrag
mesh_terms: D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D002986:Clinical Trials as Topic / Q000379:methods; D015986:Confounding Factors, Epidemiologic; D003248:Constipation / Q000139:chemically induced / Q000175:diagnosis; D003627:Data Interpretation, Statistical; D003643:Death; D004636:Emergency Service, Hospital / Q000706:statistics & numerical data; D005260:Female; D006304:Health Status; D006801:Humans; D017567:Karnofsky Performance Status; D008137:Longitudinal Studies; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000175:diagnosis; D017063:Outcome Assessment, Health Care / Q000379:methods; D017060:Patient Satisfaction / Q000706:statistics & numerical data*; D010820:Physicians / Q000706:statistics & numerical data*; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D016896:Treatment Outcome