Department of Clinical and Organizational Ethics, University Health Network, Toronto, ON, Canada.
Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
Blood. 2023 Oct 12;142(15):1263-1270. doi: 10.1182/blood.2023020703.
Manufacturing capacity and institutional infrastructure to deliver chimeric antigen receptor T-cell therapies (CAR-T) are pressured to keep pace with the growing number of approved products and expanding eligible patient population for this potentially life-saving therapy. Consequently, many cell therapy programs must make difficult decisions about which patient should get the next available treatment slot. This situation requires an ethical framework to ensure fair and equitable decision-making. In this perspective, we discuss the application of Accountability for Reasonableness (A4R), a priority-setting framework grounded in procedural justice, to the problem of limited CAR-T slots at our institution. We formed a multidisciplinary working group spanning several hematological malignancies. Through multiple rounds of partner engagement, we used A4R guiding principles to identify 4 main criteria to prioritize patients for CAR-T: medical benefit, safety/risk of complications, psychosocial factors, and medical urgency. Associated measures/tools and an implementation process were developed. We discuss further how ethical principles of fairness and equity demand a consistent approach within health systems that does not disadvantage medically underserved or underrepresented populations and supports overcoming barriers to care. In our commitment to transparency and collaboration, we make our tools available to others, ideally to be used to engage in their own A4R process, adapting the tools to their unique environments. Our hope is that our preliminary work will support the advancement of further study in this area globally, aiming for justice in resource allocation for all potential CAR-T candidates, wherever they may seek care.
制造嵌合抗原受体 T 细胞疗法 (CAR-T) 的能力和机构基础设施承受着跟上越来越多已批准产品和扩大这一潜在救命疗法的合格患者群体的压力。因此，许多细胞治疗项目必须就哪些患者应该获得下一个可用的治疗名额做出艰难的决定。这种情况需要一个伦理框架来确保公平和公正的决策。在这篇观点文章中，我们讨论了将合理性问责制 (A4R) 应用于我们机构的有限 CAR-T 插槽问题，A4R 是一种基于程序正义的优先排序框架。我们组成了一个跨越多个血液恶性肿瘤领域的多学科工作组。通过多轮合作伙伴参与，我们使用 A4R 指导原则确定了优先考虑 CAR-T 患者的 4 个主要标准：医疗效益、并发症的安全性/风险、心理社会因素和医疗紧迫性。制定了相关的措施/工具和实施流程。我们进一步讨论了公平和平等的伦理原则如何要求医疗系统内部采取一致的方法，不使医疗服务不足或代表性不足的人群处于不利地位，并支持克服护理障碍。在我们对透明度和合作的承诺中，我们向其他人提供了我们的工具，理想情况下是为了让他们参与自己的 A4R 过程，根据其独特的环境调整工具。我们希望我们的初步工作将支持全球在这一领域进一步研究的推进，旨在为所有潜在的 CAR-T 候选者的资源分配实现正义，无论他们在哪里寻求护理。
