Abstract Body: Purpose: Recruiting participants for acute ischemic stroke trials is challenging due to difficulties in obtaining written informed consent in urgent settings. Alternative consent methods, like deferred consent and Exemption from Informed Consent (EFIC), have been proposed to facilitate timely intervention and improve trial feasibility. This review examines the impact of these methods on recruitment efficiency in both ischemic stroke and ICH trials.

Methods: A scoping review of trials on acute ischemic stroke and ICH interventions (enrollment ≤24 hours from onset) published between January 2013 and March 2023 was conducted. Studies were categorized by consent methods, and trial characteristics were analyzed to compare recruitment efficiency. The review protocol was pre-registered on the Open Science Framework (https://osf.io/5rkc2).

Results: A total of 170 trials met our inclusion criteria. Of these, 118 trials used conventional written informed consent (Conventional group), while 52 trials (30.6%) adopted alternative consent methods including deferred consent and EFIC (Alternative group). In univariable analysis, the Alternative group had a significantly shorter maximum allowable time from onset/LKW to randomization/enrollment compared to the Conventional group (6 hours [IQR 4-12] vs. 9 hours [IQR 5-24], p=0.03). There were no significant differences between the groups in terms of the number of participating countries, sites, or overall enrollment duration. However, the number of withdrawals (in counts) was significantly higher in the Alternative group (2.8 ± 5.8 vs. 9.3 ± 13, p<0.001). Additionally, alternative consent strategies were more frequently used in pre-hospital settings, where patients were often enrolled before a clinical diagnosis was confirmed. In the multivariable regression analysis, adjusting for operational factors (number of participating countries, sites, patients) and trial design elements (blinding, randomization, intervention), the Alternative group showed no significant difference in enrollment duration compared to the Conventional group (β = -0.32 weeks, 95% CI: -8.1 to 7.4, p = 0.93).

Conclusions: Alternative consent methods, used in approximately 30% of acute stroke trials, allow quicker enrollment without significantly impacting overall enrollment duration. However, these methods are linked to higher dropout rates. These strategies require careful implementation to balance speed and trial feasibility.