Ethan Basch1,2, Amylou C Dueck3, Lauren J Rogak2, Lori M Minasian4, William Kevin Kelly5,6, Ann M O'Mara7, Andrea M Denicoff7, Drew Seisler8, Pamela J Atherton8, Electra Paskett9, Lisa Carey1, Maura Dickler10, Rebecca S Heist11, Andrew Himelstein12, Hope S Rugo13, William M Sikov14,15, Mark A Socinski16, Alan P Venook13, Douglas J Weckstein17, Diana E Lake10, David D Biggs12, Rachel A Freedman18, Charles Kuzma19, Jeffrey J Kirshner20, Deborah Schrag21. 1. Department of Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill. 2. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York. 3. Alliance Statistics and Data Center, Division of Health Sciences Research, Mayo Clinic, Scottsdale, Arizona. 4. Division of Cancer Prevention, National Cancer Institute (NCI), Rockville, Maryland. 5. Department of Medical Oncology and Urology, Division of Solid Tumor, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania. 6. Clinical Research and Prostate Cancer Program, Sidney Kimmel Cancer Center, Philadelphia, Pennsylvania. 7. Division of Cancer Treatment and Diagnosis, NCI, Rockville, Maryland. 8. Alliance Statistics and Data Center, Division of Health Sciences Research, Mayo Clinic, Rochester, Minnesota. 9. Division of Cancer Prevention and Control, Department of Internal Medicine, Division of Epidemiology, College of Public Health, The Ohio State University, Columbus. 10. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. 11. Department of Thoracic Oncology, Harvard Medical School, Massachusetts General Hospital, Boston. 12. Delaware/Christiana Care NCI Community Oncology Research Program (NCORP), Helen F. Graham Cancer Center & Research Institute, Newark. 13. Department of Medicine, University of California at San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco. 14. Program in Women's Oncology, Department of Obstetrics & Gynecology, Women and Infants Hospital of Rhode Island, Providence. 15. Department of Medicine, Warren Alpert Medical School of Brown University, Providence, Rhode Island. 16. Thoracic Oncology Program, Florida Hospital Cancer Institute, Orlando. 17. New Hampshire Oncology Hematology, Hooksett. 18. Department of Medical Oncology, Harvard Medical School, Dana-Farber Cancer Institute, Boston, Massachusetts. 19. Southeast Clinical Oncology Research Consortium, Winston-Salem, North Carolina. 20. Hematology Oncology Associates of Central New York, East Syracuse. 21. Division of Population Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts.
Abstract
IMPORTANCE: In cancer clinical trials, symptomatic adverse events (AEs), such as nausea, are reported by investigators rather than by patients. There is increasing interest to collect symptomatic AE data via patient-reported outcome (PRO) questionnaires, but it is unclear whether it is feasible to implement this approach in multicenter trials. OBJECTIVE: To examine whether patients are willing and able to report their symptomatic AEs in multicenter trials. DESIGN, SETTING, AND PARTICIPANTS: A total of 361 consecutive patients enrolled in any 1 of 9 US multicenter cancer treatment trials were invited to self-report 13 common symptomatic AEs using a PRO adaptation of the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) via tablet computers at 5 successive clinic visits. Patient adherence was tracked with reasons for missed self-reports. Agreement with clinician AE reports was analyzed with weighted κ statistics. Patient and investigator perspectives were elicited by survey. The study was conducted from March 15, 2007, to August 11, 2011. Data analysis was performed from August 9, 2013, to March 21, 2014. RESULTS: Of the 361 patients invited to participate, 285 individuals enrolled, with a median age of 57 years (range, 24-88), 202 (74.3%) female, 241 (85.5%) white, 73 (26.8%) with a high school education or less, and 176 (64.7%) who reported regular internet use (denominators varied owing to missing data). Across all patients and trials, there were 1280 visits during which patients had an opportunity to self-report (ie, patients were alive and enrolled in a treatment trial at the time of the visit). Self-reports were completed at 1202 visits (93.9% overall adherence). Adherence was highest at baseline and declined over time (visit 1, 100%; visit 2, 96%; visit 3, 95%; visit 4, 91%; and visit 5, 85%). Reasons for missing PROs included institutional errors in 27 of 48 (56.3%) of the cases (eg, staff forgetting to bring computers to patients at visits), patients feeling "too ill" in 8 (16.7%), patient refusal in 8 (16.7%), and internet connectivity problems in 5 (10.4%). Patient-investigator CTCAE agreement was moderate or worse for most symptoms (most κ < 0.05), with investigators reporting fewer AEs than patients across symptoms. Most patients believed that the system was easy to use (234 [93.2%]) and useful (230 [93.1%]), and investigators thought that the patient-reported AEs were useful (133 [94.3%]) and accurate (119 [83.2%]). CONCLUSIONS AND RELEVANCE: Participants in multicenter cancer trials are willing and able to report their own symptomatic AEs at most clinic visits and report more AEs than investigators. This approach may improve the precision of AE reporting in cancer trials.
IMPORTANCE: In cancer clinical trials, symptomatic adverse events (AEs), such as nausea, are reported by investigators rather than by patients. There is increasing interest to collect symptomatic AE data via patient-reported outcome (PRO) questionnaires, but it is unclear whether it is feasible to implement this approach in multicenter trials. OBJECTIVE: To examine whether patients are willing and able to report their symptomatic AEs in multicenter trials. DESIGN, SETTING, AND PARTICIPANTS: A total of 361 consecutive patients enrolled in any 1 of 9 US multicenter cancer treatment trials were invited to self-report 13 common symptomatic AEs using a PRO adaptation of the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) via tablet computers at 5 successive clinic visits. Patient adherence was tracked with reasons for missed self-reports. Agreement with clinician AE reports was analyzed with weighted κ statistics. Patient and investigator perspectives were elicited by survey. The study was conducted from March 15, 2007, to August 11, 2011. Data analysis was performed from August 9, 2013, to March 21, 2014. RESULTS: Of the 361 patients invited to participate, 285 individuals enrolled, with a median age of 57 years (range, 24-88), 202 (74.3%) female, 241 (85.5%) white, 73 (26.8%) with a high school education or less, and 176 (64.7%) who reported regular internet use (denominators varied owing to missing data). Across all patients and trials, there were 1280 visits during which patients had an opportunity to self-report (ie, patients were alive and enrolled in a treatment trial at the time of the visit). Self-reports were completed at 1202 visits (93.9% overall adherence). Adherence was highest at baseline and declined over time (visit 1, 100%; visit 2, 96%; visit 3, 95%; visit 4, 91%; and visit 5, 85%). Reasons for missing PROs included institutional errors in 27 of 48 (56.3%) of the cases (eg, staff forgetting to bring computers to patients at visits), patients feeling "too ill" in 8 (16.7%), patient refusal in 8 (16.7%), and internet connectivity problems in 5 (10.4%). Patient-investigator CTCAE agreement was moderate or worse for most symptoms (most κ < 0.05), with investigators reporting fewer AEs than patients across symptoms. Most patients believed that the system was easy to use (234 [93.2%]) and useful (230 [93.1%]), and investigators thought that the patient-reported AEs were useful (133 [94.3%]) and accurate (119 [83.2%]). CONCLUSIONS AND RELEVANCE: Participants in multicenter cancer trials are willing and able to report their own symptomatic AEs at most clinic visits and report more AEs than investigators. This approach may improve the precision of AE reporting in cancer trials.
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