Yaseen M Arabi1, Deborah J Cook2,3, Qi Zhou3, Orla Smith4, Lori Hand3, Alexis F Turgeon5,6, Andrea Matte7, Sangeeta Mehta8,9, Russell Graham10, Kristin Brierley11, Neill K J Adhikari8,12, Maureen O Meade2,3, Niall D Ferguson7,13,14,15,16. 1. 1 Intensive Care Department, King Saud Bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. 2. 2 Department of Medicine and. 3. 3 Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Ontario, Canada. 4. 4 Critical Care Department & Keenan Research Center, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Canada. 5. 5 Division of Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, and. 6. 6 Population Health and Optimal Health Practices Research Unit, Research Center of the CHU de Québec, Université Laval, Québec City, Québec, Canada. 7. 7 University Health Network, Toronto, Canada. 8. 8 Interdepartmental Division of Critical Care Medicine. 9. 13 Department of Medicine. 10. 14 Department of Physiology, and. 11. 15 Institute for Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada. 12. 9 Department of Medicine, Mount Sinai Hospital, Toronto, Canada. 13. 10 Memorial Hermann, Texas Medical Center, Houston, Texas. 14. 11 University of Michigan Health System, Ann Arbor, Michigan. 15. 12 Department of Critical Care Medicine, Sunnybrook Health Science Centre, Toronto, Canada; and. 16. 16 Division of Respirology, Department of Medicine, Mount Sinai Hospital, Toronto, Canada.
Abstract
RATIONALE: Patients eligible for randomized controlled trials may not be enrolled for various reasons. Nonenrollment may affect study generalizability and lengthen the time required for trial completion. OBJECTIVES: To describe characteristics and outcomes of eligible nonenrolled (ENE) patients in a multicenter trial of mechanical ventilation strategies. METHODS: Within the OSCILLATE trial of high-frequency oscillation (HFO) versus conventional ventilation (CV) in adults with adult respiratory distress syndrome, and with approval from research ethics boards, we collected a minimal dataset on patients who satisfied eligibility criteria but were not enrolled. We categorized ENE patients as ENE-HFO and ENE-CV based on receipt of HFO at any time. We used multivariable logistic regression to assess the association between ENE status and mortality. MEASUREMENTS AND MAIN RESULTS: A total of 548 patients were randomized, and 546 were ENE. The most common reasons for ENE were no consent (42%), physician refusal (24%), missed randomization window (15%), and current HFO use (14%). Compared with randomized patients in respective arms of the trial, ENE-HFO patients were younger and had worse lung injury, whereas ENE-CV patients had lower illness severity. ENE status was independently associated with mortality (adjusted odds ratio, 1.39; 95% confidence interval, 1.06-1.84; P = 0.02), with no significant interaction with ventilation treatment group. CONCLUSIONS: Nonenrollment was common, with approximately one ENE patient for every randomized patient. Our study suggests that enrollment in trials of mechanical ventilation may be associated with improved outcomes compared with standard care and highlights the need for prospective tracking and transparent reporting of ENE patients as part of trial management.
RCT Entities:
RATIONALE: Patients eligible for randomized controlled trials may not be enrolled for various reasons. Nonenrollment may affect study generalizability and lengthen the time required for trial completion. OBJECTIVES: To describe characteristics and outcomes of eligible nonenrolled (ENE) patients in a multicenter trial of mechanical ventilation strategies. METHODS: Within the OSCILLATE trial of high-frequency oscillation (HFO) versus conventional ventilation (CV) in adults with adult respiratory distress syndrome, and with approval from research ethics boards, we collected a minimal dataset on patients who satisfied eligibility criteria but were not enrolled. We categorized ENE patients as ENE-HFO and ENE-CV based on receipt of HFO at any time. We used multivariable logistic regression to assess the association between ENE status and mortality. MEASUREMENTS AND MAIN RESULTS: A total of 548 patients were randomized, and 546 were ENE. The most common reasons for ENE were no consent (42%), physician refusal (24%), missed randomization window (15%), and current HFO use (14%). Compared with randomized patients in respective arms of the trial, ENE-HFO patients were younger and had worse lung injury, whereas ENE-CV patients had lower illness severity. ENE status was independently associated with mortality (adjusted odds ratio, 1.39; 95% confidence interval, 1.06-1.84; P = 0.02), with no significant interaction with ventilation treatment group. CONCLUSIONS: Nonenrollment was common, with approximately one ENE patient for every randomized patient. Our study suggests that enrollment in trials of mechanical ventilation may be associated with improved outcomes compared with standard care and highlights the need for prospective tracking and transparent reporting of ENE patients as part of trial management.
Authors: Padmanabhan Ramnarayan; Alvin Richards-Belle; Laura Drikite; Michelle Saull; Izabella Orzechowska; Robert Darnell; Zia Sadique; Julie Lester; Kevin P Morris; Lyvonne N Tume; Peter J Davis; Mark J Peters; Richard G Feltbower; Richard Grieve; Karen Thomas; Paul R Mouncey; David A Harrison; Kathryn M Rowan Journal: JAMA Date: 2022-07-12 Impact factor: 157.335
Authors: Padmanabhan Ramnarayan; Alvin Richards-Belle; Laura Drikite; Michelle Saull; Izabella Orzechowska; Robert Darnell; Zia Sadique; Julie Lester; Kevin P Morris; Lyvonne N Tume; Peter J Davis; Mark J Peters; Richard G Feltbower; Richard Grieve; Karen Thomas; Paul R Mouncey; David A Harrison; Kathryn M Rowan Journal: JAMA Date: 2022-04-26 Impact factor: 157.335
Authors: Ken Kuljit S Parhar; Karolina Zjadewicz; Gwen E Knight; Andrea Soo; Jamie M Boyd; Danny J Zuege; Daniel J Niven; Christopher J Doig; Henry T Stelfox Journal: Crit Care Explor Date: 2021-05-17
Authors: Jessica A Palakshappa; Brian J Anderson; John P Reilly; Michael G S Shashaty; Ryo Ueno; Qufei Wu; Caroline A G Ittner; Anna Tommasini; Thomas G Dunn; Dudley Charles; Altaf Kazi; Jason D Christie; Nuala J Meyer Journal: Crit Care Date: 2016-03-16 Impact factor: 9.097
Authors: Colin H Holtze; Elizabeth A Freiheit; Susan L Limb; John L Stauffer; Karina Raimundo; Wayne T Pan; Kevin R Flaherty; Hyun J Kim Journal: Respir Res Date: 2020-02-10