Permissibility & Necessity in the Ethical Justification of RCTs: The Four Quadrants Framework and the Case of Endovascular Thrombectomy Trials for Acute Ischemic Stroke.

Abstract

Objective: This study seeks to propose a novel framework for the ethical justification of randomized controlled trials (RCTs).

Study design and setting: This paper develops a novel framework to the ethical evaluation of RCTs, explored through the example of trials of endovascular thrombectomy for acute ischemic stroke. We propose that RCTs can be categorized into four quadrants, where justification in each quadrant relates to different thresholds for permissibility (the ethical defensibility of the trial) and necessity (the social and scientific importance of conducting the trial).

Results: Trials can be situated within four quadrants based on the interventions being compared: standard vs standard treatment in the alpha quadrant, standard vs novel treatment in the beta quadrant, standard vs no treatment in the gamma quadrant, and no treatment vs novel treatment in the delta quadrant. In each quadrant, the thresholds to establish permissibility and necessity will differ. The controversies that surrounded trials of thrombectomy for acute stroke can be understood as representing differing points of view about whether those trials should have been situated in the beta or delta quadrant. These differing conclusions highlight the importance of using a quadrant-based analysis in assessing ethical permissibility and necessity of RCTs.

Conclusion: The proposed four quadrants framework provides a comprehensive and preise approach to assessing the ethical justification of RCTs. Implementing this framework could improve regulatory evaluations of RCTs and reduce unnecessary harm to trial participants while balancing the objectives of scientific advancement.