Background and Purpose— The ESCAPE trial (The Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times) was a multicentre, randomized controlled trial of endovascular thrombectomy versus standard care for patients with acute ischemic stroke that allowed patients to be enrolled with deferred consent. We investigated the knowledge and opinions of these patients or their authorized third parties about the consent process. Methods— All patients (or their authorized third parties) enrolled with deferral of consent in ESCAPE were invited to complete a 12-question survey within the first 4 days of enrollment and again at 90 days. Questions investigated knowledge of the ESCAPE trial and opinions on deferral of consent. Results— Of 56 patients enrolled with deferred consent, 33 (59%) completed the initial survey, and of these, 27 (81%) completed the 90-day follow-up. Enrollment with deferred consent was not associated with a significant difference in door-to-randomization times (50.5 versus 57 minutes; P =0.29) but allowed these 56 patients to participate in the trial. Only 52% of respondents understood that patients could be randomized to thrombectomy or standard care, although most understood the other basic principles of the trial. At baseline and at 90 days, respondents disagreed or strongly disagreed with deferred consent in acute stroke trials generally (82% and 78%) and in the ESCAPE trial specifically (93% and 91%). Conclusions— Respondents generally disagreed with the use of deferred consent for enrollment in the ESCAPE trial and in stroke trials more generally.

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IntroductionRandomised controlled trials (RCTs) are widely viewed to generate the most reliable medical knowledge. However, RCTs are not always scientifically necessary and therefore not always ethical. Unfortunately, it is not clear when an RCT is not necessary or how this should be established. This study seeks to systematically catalogue justifications offered throughout the medical and ethics literature for performing randomisation within clinical trials.Methods and analysisWe will systematically search electronic databases of the medical literature including MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Clinical Trials Register, Web of Science Proceedings, ClinicalTrials.gov; databases of philosophical literature including Philosopher’s Index, Phil Papers, JSTOR, Periodicals Archive Online, Project MUSE, National Reference Centre for Bioethics; the library catalogue at the University of Ottawa; bibliographies of retrieved papers; and the grey literature. We will also pursue suggestions from experts in the fields of medical ethics, philosophy and clinical trial methodology. Article screening, selection and data extraction will be performed by two independent reviewers based on prespecified inclusion/exclusion criteria. A third reviewer will be consulted to resolve any discrepancies. We will then extract the reasons given to justify randomisation using methodology established to extract data in a defensible, systematic manner. We will track the reasons given, their frequency of use and changes over time. Finally, using grounded theory, we will combine the reasons into broader themes. These themes will form the foundation of our subsequent analysis from qualitative and quantitative perspectives. This review will map existing arguments that clinicians, ethicists and philosophers use to ethically justify randomisation in clinical trials.Ethics and disseminationNo research ethics board approval is necessary because we are not examining patient-level data. This protocol complies with the reported guidance for conducting systematic scoping reviews. The findings of this paper will be disseminated via presentations and academic publication. In a subsequent phase of this research, we hope to engage with stakeholders and translate any recommendations derived from our findings into operational guidelines.

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