Ethical Prioritization of Patients to CAR T-Cell Therapies: Tool Development and Process

Abstract

Introduction: CAR T-cell therapy is a novel and expensive anti-cancer treatment marked by limited availability and an expanding eligible patient population. This situation requires an ethical framework and priority-setting process to guide fair allocation of limited healthcare resources. The purpose of this health services and quality initiative was to develop an ethical prioritization tool to support oncology clinicians in making fair and equitable decisions about patient prioritization to CAR T-cell therapies. Methods: Accountability for reasonableness (A4R) is a well-developed ethical approach to resource allocation when there are values-disagreements between stakeholders about the principles that should govern priority setting. A4R supports a democratic decision-making process, enabling stakeholders to agree on what is legitimate and fair, rather than articulating principles that should govern decision-making a priori. Key elements of the process include: transparency about the rationale for decisions, rationales and evidence that all can accept as relevant to meeting health needs fairly, and procedures for revisiting decisions. Following the A4R approach, we engaged a strong multi-disciplinary team to form a CAR T-cell therapy Ethics Working Group that included physicians, nurses, patients, coordinators, social work, managers, operations, flow, quality, bioethics, and fellows/trainees. Stakeholders from the myeloma, lymphoma and leukemia programs were represented. Through two deliberative events and one patient focus group we established an ethical framework, prioritization tools based on the ethical framework, and an assessment process to support fair and equitable decision making. Results: Stakeholders agreed the following ethical principles are relevant to the decision-making process: beneficence, non-maleficence, equity/consistency, stewardship, autonomy, evidence-informed, and utility. Beneficence and non-maleficence were identified as inherent to the process and equity/consistency and stewardship were also identified as extremely important, especially as more patients become eligible for CAR-T cell therapy. Stakeholders then identified prioritization criteria and categorized them into four major themes: medical benefit, safety/risk of complications, medical urgency, and psychosocial factors. Although the relative weights were not determined, the sequence of application of these criteria were deemed important. Determination of medical benefit was primary, as no patient should proceed further if they did not have any potential for medical benefit. Safety/Risk and psychosocial evaluation would follow using existing tools (e.g., ECOG) and allowing for summative objectives, when possible. Lastly, medical urgency as defined by rapid pace of disease progression, refractoriness to prior therapy, and development of serious disease-related complications, was considered critical in prioritizing patients for therapy. However, stakeholders agreed and cautioned that medical urgency does not equate medical benefit, as patients with rapidly expanding disease and acute deterioration frequently have dismal outcomes, despite all attempts to expedite their treatment course. Recognizing the importance of sequencing in the assessment of criteria, stakeholders developed a 3-Step assessment process: (1) Medical Benefit Assessment, (2) Safety/Risk and Psychosocial Assessment and (3) referral to the Cell Therapy Review Committee for review and prioritization based on medical urgency. Patients who may gain medical benefit, have reasonable risk of toxicity, and have adequate psychosocial capacity and support from Steps 1 and 2, proceed to 3 where consensus decisions are documented on an existing intake form. Conclusions: An ethical framework to support CAR T-cell priority-setting is necessary to ensure transparent and equitable decision making, thus allowing fair patient access to these important therapies. It also enhances the cancer care experience for all by promoting public trust and confidence in the healthcare system and therapeutic relationships by ensuring that decisions are based on sound rationales and that individual clinician biases are minimized.