Enrollment of individual patients into more than one study has been poorly evaluated. The objective of this study was to describe the characteristics of patients, researchers and centers involved in coenrollment, studies precluding coenrollment, and the prevalence, patterns, predictors, and outcomes of coenrollment in a randomized clinical trial.
We conducted an observational study nested within the OSCILLation for Acute Respiratory Distress Syndrome Treated Early Trial, which compared high-frequency oscillatory ventilation to conventional ventilation. We collected patient, center, and study data on coenrollment in randomized patients. Multilevel regression examined factors independently associated with coenrollment, considering clustering within centers. We examined the effect of coenrollment on safety and the trial outcome.
Overall, 127 of 548 randomized patients (23.2%) were coenrolled in 25 unique studies. Coenrollment was reported in 17 of 39 centers (43.6%). Patients were most commonly coenrolled in one additional randomized clinical trial (76; 59.8%). Coenrollment was less likely in older patients (odds ratio, 0.87; 95% CI, 0.76–0.997), and in ICUs with greater than 26 beds (odds ratio, 0.56; 95% CI, 0.34–0.94), and more likely by investigators with more than 11 years of experience (odds ratio, 1.73; 95% CI, 1.06–2.82), by research coordinators with more than 8 years of experience (odds ratio, 1.87; 95% CI, 1.11–3.18) and in Canada (odds ratio, 4.66; 95% CI, 1.43–15.15). Serious adverse events were similar between coenrolled high-frequency oscillatory ventilation and control patients. Coenrollment did not modify the treatment effect of high-frequency oscillatory ventilation on hospital mortality.
Coenrollment occurred in 23% of patients, commonly in younger patients, in smaller centers with more research infrastructure, and in Canada. Coenrollment did not influence patient safety or trial results.
1Department of Medicine, McMaster University, Hamilton, ON, Canada.
2Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.
3Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada.
4Department of Medicine, University of Toronto, Toronto, ON, Canada.
5Department of Physiology, University of Toronto, Toronto, ON, Canada.
6Division of Respirology, Department of Medicine, University Health Network, University of Toronto, Toronto, ON, Canada.
7Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
8Department of Critical Care Medicine, Sunnybrook Health Science Centre, Toronto, ON, Canada.
9Department of Critical Care Medicine, Orlando Regional Medical Center, Orlando, FL.
10Department of Critical Care, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
11Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, ON, Canada.
12Adult Critical Care Department, University Hospital of Wales, Cardiff, United Kingdom.
13Department of Critical Care, University of British Columbia, Vancouver, BC, Canada.
* See also p. 485.
This work was performed at McMaster University, Hamilton, ON, Canada.
Drs. Cook, Ferguson, Hand, Austin, Matte, Clarke, Smith, and Meade contributed to conception and design. Drs. Cook, Ferguson, Hand, Austin, Danesh, Matte, Clarke, Smith, and Meade contributed to collection and assembly of data. Drs. Zhou and Hanna provided statistical expertise. Drs. Cook, Ferguson, Hand, Austin, Zhou, Adhikari, and Meade contributed to drafting of the article. All authors contributed to critical revision of the article for important intellectual content and final approval of the article.
This study was funded by the Canadian Institutes for Health Research (CIHR). Dr. Cook holds a Chair of the CIHR. Dr. Ferguson was supported by a New Investigator Award from the CIHR. Dr. Zhou disclosed “work for hire.” Dr. Adhikari’s institution received grant support from the CIHR. Dr. Danesh received support for travel (reimbursement for travel expense). Her institution received grant support from Orlando Health (OSCILLation for ARDS Treated Early [OSCILLATE] Trial). Ms. Matte’s institution received grant support (Institution was paid for the main study. This is a substudy using data that were previously captured) and received support for travel (Attended one meeting for substudies related to main OSCILLATE trial. Travel expenses were reimbursed to the institution). Ms. Smith received support for travel from the CIHR. Her institution received grant support from the CIHR. Dr. Wise received support for travel from McMaster University (Hamilton, ON, Canada); served as a board member on the Bard Advisory Board (relevant to hypothermia) and on the Merck Advisory Board (relevant to nutrition); is employed by National Institute for Social Care and Health Research, Academic Health Sciences Collaboration (NISCHR AHSC) Research Fellowship (research fellowships funds); lectured for Fisher & Paykel (lecturing at educational meeting); received royalties from Wiley Publishing (book chapters for textbook); received support for travel from International Symposium on Intensive Care and Emergency Medicine, Eli Lilly, British Thoracic Society, and the Intensive Care Society; and received support from CareFusion (loaned electrical impedance tomography equipment for research) and from Sage Products (gifted oral care products for research). His institution received grant support from NISCHR AHSC Clinical Research Fellowship (research fellowships funds). Dr. Meade’s institution received grant support from the CIHR. The remaining authors have disclosed that they do not have any potential conflicts of interest.
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