Justification of deferral of consent in the ACT-GLOBAL adaptive platform trial in stroke

Launched in August 2024, the ACT-GLOBAL (a multifactorial, multiarm, multistage, randomized, global adaptive platform) trial is the first multinational adaptive platform trial for acute stroke. Because it proposes to enroll participants by deferral of consent, the ACT-GLOBAL trial seeks to publish an explicit justification for this practice.

Following a standardized protocol for establishing whether it is justified to use deferral of consent, all active domains of the ACT-GLOBAL platform adaptive trial were considered according to six questions: (1) Is there evidence-based uncertainty about the research question?; (2) is the standard of care treatment included in the trial, meaning that patients are unlikely to be disadvantaged by their participation?; (3) is the trial of sufficient methodological rigor that it can result in a change of practice?; (4) Are patients eligible for enrollment in the trial likely to be incapable of providing their own consent?; (5) Will seeking to obtain consent from a surrogate decision-maker meaningfully delay treatment and impact outcomes?; and (6) Are steps taken to mitigate the compromise to individual autonomy?

The leadership of the ACT-GLOBAL trial is able to answer affirmatively the six questions outlined above in relation to each of the trial's current domains. The results of this analysis suggest that the use of deferral of consent in the ACT-GLOBAL trial is ethically justified, where permitted by law.

This exercise demonstrates the utility of following an accepted protocol for determining whether alterations to standard consent practices such as deferral of consent are ethically justified in acute stroke research.