Gisell Castillo1,2, Manoj Lalu1,2,3, Sarah Asad1,2, Madison Foster1,2, Natasha Kekre1,4, Dean Fergusson1,2,5, Terry Hawrysh6, Harold Atkins1,4, Kednapa Thavorn1,5,7, Joshua Montroy1,2, Stuart Schwartz6, Robert Holt8, Raewyn Broady9, Justin Presseau10,11,12. 1. Clinical Epidemiology Program, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario, K1H 8L6, Canada. 2. Blueprint Translational Research Group, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario, K1H 8L6, Canada. 3. Department of Anaesthesiology and Pain Medicine, University of Ottawa at the Ottawa Hospital General Campus, 501 Smyth Road, Ottawa, Ontario, K1H 8L6, Canada. 4. Blood and Marrow Transplant Program, The Ottawa Hospital, 501 Smyth Road, Ottawa, Ontario, K1H 8L6, Canada. 5. School of Epidemiology and Public Health, University of Ottawa, 600 Peter Morand Crescent, Ottawa, Ontario, K1G 5Z3, Canada. 6. Patient Partners, Ottawa, Canada. 7. Institute for Clinical and Evaluative Sciences (ICES), University of Ottawa, 1053 Carling Ave., Ottawa, Ontario, K1Y 4E9, Canada. 8. BC Cancer Genome Sciences Centre, 100-570 West 7th Avenue, Vancouver, British Columbia, V5Z 4S6, Canada. 9. Leukemia/BMT Program, Vancouver General Hospital, 2775 Laurel St - 10th floor, Vancouver, British Columbia, V5Z 1M9, Canada. 10. Clinical Epidemiology Program, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario, K1H 8L6, Canada. jpresseau@ohri.ca. 11. Blueprint Translational Research Group, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario, K1H 8L6, Canada. jpresseau@ohri.ca. 12. School of Epidemiology and Public Health, University of Ottawa, 600 Peter Morand Crescent, Ottawa, Ontario, K1G 5Z3, Canada. jpresseau@ohri.ca.
Abstract
BACKGROUND: Novel therapies often fail to reach the bedside due to low trial recruitment rates. Prior to conducting one of the first chimeric antigen receptor (CAR) T cell therapy trials in Canada, we used the Theoretical Domains Framework, a novel tool for identifying barriers and enablers to behavior change, to identify physician-related barriers and enablers to screening and recruiting patients for an early phase immunotherapy trial. METHODS: We conducted interviews with hematologists across Canada and used a directed content analysis to identify relevant domains reflecting the key factors that may affect screening and recruitment. RESULTS: In total, we interviewed 15 hematologists. Physicians expressed "cautious hope"; while expressing safety, feasibility, and screening criteria concerns, 14 out of 15 hematologists intended to screen for the trial (domains: knowledge, goals, beliefs about consequences, intentions). Physicians underscored the "challenging contexts," identifying resources, workload, forgetting, and patient wait times to receive CAR T cells as key practical barriers to screening (domains: environmental context and resources, memory, attention and decision-making, behavioral regulation). They also highlighted "variability in roles and procedures" that may lead to missed trial candidates (domain: social and professional role). Left unaddressed, these barriers may undermine trial recruitment. CONCLUSIONS: This study is among the first to use the Theoretical Domains Framework from the physician perspective to identify recruitment challenges to early phase trials and demonstrates the value of this approach for identifying barriers to screening and recruitment that may not otherwise have been elicited. This approach can optimize trial procedures and may serve to inform future promising early phase cancer therapy trials. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03765177 . Registered on December 5, 2018.
BACKGROUND: Novel therapies often fail to reach the bedside due to low trial recruitment rates. Prior to conducting one of the first chimeric antigen receptor (CAR) T cell therapy trials in Canada, we used the Theoretical Domains Framework, a novel tool for identifying barriers and enablers to behavior change, to identify physician-related barriers and enablers to screening and recruiting patients for an early phase immunotherapy trial. METHODS: We conducted interviews with hematologists across Canada and used a directed content analysis to identify relevant domains reflecting the key factors that may affect screening and recruitment. RESULTS: In total, we interviewed 15 hematologists. Physicians expressed "cautious hope"; while expressing safety, feasibility, and screening criteria concerns, 14 out of 15 hematologists intended to screen for the trial (domains: knowledge, goals, beliefs about consequences, intentions). Physicians underscored the "challenging contexts," identifying resources, workload, forgetting, and patient wait times to receive CAR T cells as key practical barriers to screening (domains: environmental context and resources, memory, attention and decision-making, behavioral regulation). They also highlighted "variability in roles and procedures" that may lead to missed trial candidates (domain: social and professional role). Left unaddressed, these barriers may undermine trial recruitment. CONCLUSIONS: This study is among the first to use the Theoretical Domains Framework from the physician perspective to identify recruitment challenges to early phase trials and demonstrates the value of this approach for identifying barriers to screening and recruitment that may not otherwise have been elicited. This approach can optimize trial procedures and may serve to inform future promising early phase cancer therapy trials. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03765177 . Registered on December 5, 2018.
Entities:
Keywords:
Barriers to trial recruitment; Chimeric antigen receptor T cell therapy; Early phase clinical trials; Early phase immunotherapy trials; Physician screening; Theoretical domains framework
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