Seth W Linakis1,2, Nathan Kuppermann3, Rachel M Stanley1,2, Hilary Hewes4, Sage Myers5, John M VanBuren4, T Charles Casper4, Matthew Bobinski3, Simona Ghetti6, Walton O Schalick7, Daniel K Nishijima2. 1. Division of Pediatric Emergency Medicine, Nationwide Children's Hospital, Columbus, Ohio, USA. 2. Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA. 3. Department of Emergency Medicine, University of California at Davis School of Medicine, Sacramento, California, USA. 4. Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah, USA. 5. Division of Emergency Medicine, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. 6. Department of Psychology, University of California at Davis, Davis, California, USA. 7. Department of Orthopedics and Rehabilitation, University of Wisconsin, Madison, Wisconsin, USA.
Abstract
BACKGROUND: Federal exception from informed consent (EFIC) procedures allow studies to enroll patients with time-sensitive, life-threatening conditions when written consent is not feasible. Our objective was to compare enrollment rates with and without EFIC in a trial of tranexamic acid (TXA) for children with hemorrhagic injuries. METHODS: We conducted a four-center randomized controlled pilot and feasibility trial evaluating TXA in children with severe hemorrhagic brain and/or torso injuries. We initiated the trial enrolling patients without EFIC. After 3 months of enrollment, we met our a priori futility threshold and paused the trial to incorporate EFIC procedures and obtain regulatory approval. We then restarted the trial allowing EFIC if the guardian was unable to provide timely written consent. We used descriptive statistics to compare characteristics of eligible patients approached with and without EFIC procedures. We also calculated the time delay to restart the trial using EFIC. RESULTS: We enrolled one of 15 (6.7%) eligible patients (0.17 per site per month) prior to using EFIC procedures. Of the 14 missed eligible patients, seven (50%) were not enrolled because guardians were not present or were injured and unable to provide written consent. After obtaining approval for EFIC, we enrolled 30 of 48 (62.5%) eligible patients (1.34 per site per month). Of these 30 patients, 22 (73.3%) were enrolled with EFIC. Of the 22, no guardians refused written consent after randomization. There were no significant differences in the eligibility rate and patient characteristics enrolled with and without EFIC procedures. Across all sites, the mean delay to restart the trial using EFIC procedures was 12 months. CONCLUSIONS: In a multicenter trial of severely injured children, the use of EFIC procedures greatly increased the enrollment rate and was well accepted by guardians. Initiating the trial without EFIC procedures led to a significant delay in enrollment.
BACKGROUND: Federal exception from informed consent (EFIC) procedures allow studies to enroll patients with time-sensitive, life-threatening conditions when written consent is not feasible. Our objective was to compare enrollment rates with and without EFIC in a trial of tranexamic acid (TXA) for children with hemorrhagic injuries. METHODS: We conducted a four-center randomized controlled pilot and feasibility trial evaluating TXA in children with severe hemorrhagic brain and/or torso injuries. We initiated the trial enrolling patients without EFIC. After 3 months of enrollment, we met our a priori futility threshold and paused the trial to incorporate EFIC procedures and obtain regulatory approval. We then restarted the trial allowing EFIC if the guardian was unable to provide timely written consent. We used descriptive statistics to compare characteristics of eligible patients approached with and without EFIC procedures. We also calculated the time delay to restart the trial using EFIC. RESULTS: We enrolled one of 15 (6.7%) eligible patients (0.17 per site per month) prior to using EFIC procedures. Of the 14 missed eligible patients, seven (50%) were not enrolled because guardians were not present or were injured and unable to provide written consent. After obtaining approval for EFIC, we enrolled 30 of 48 (62.5%) eligible patients (1.34 per site per month). Of these 30 patients, 22 (73.3%) were enrolled with EFIC. Of the 22, no guardians refused written consent after randomization. There were no significant differences in the eligibility rate and patient characteristics enrolled with and without EFIC procedures. Across all sites, the mean delay to restart the trial using EFIC procedures was 12 months. CONCLUSIONS: In a multicenter trial of severely injured children, the use of EFIC procedures greatly increased the enrollment rate and was well accepted by guardians. Initiating the trial without EFIC procedures led to a significant delay in enrollment.
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Authors: Daniel K Nishijima; John M VanBuren; Seth W Linakis; Hilary A Hewes; Sage R Myers; Matthew Bobinski; Nam K Tran; Simona Ghetti; P David Adelson; Ian Roberts; James F Holmes; Walton O Schalick; J Michael Dean; T Charles Casper; Nathan Kuppermann Journal: Acad Emerg Med Date: 2022-03-10 Impact factor: 5.221