van Hooff L C, Merz E-M, Kidane Gebremeskel A S, de Jong J A, Burchell G L, Lunshof J E
Department Research & Lab Services, Donor Studies Group, Sanquin Blood Supply Foundation, Amsterdam, the Netherlands.
Department of Sociology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
BMC Med Ethics. 2025 Mar 14;26(1):36. doi: 10.1186/s12910-025-01188-3.
Sickle cell disease (SCD) and Diamond-Blackfan anemia syndrome (DBAS) are two hereditary blood diseases that present significant challenges to patients, their caregivers, and the healthcare system. Both conditions cause severe health complications and have limited treatment options, leaving many individuals without access to curative therapies like hematopoietic stem cell transplantation. Recent advancements in gene and cell therapies offer the potential for a new curative option, marking a pivotal shift in the management of these debilitating diseases. However, the implementation of these therapies necessitates a nuanced understanding of the ethical and social implications.
In this mixed methods systematic review, we explore the responsible development and implementation of gene and cell therapies for SCD and DBAS and aim to sketch a path toward ethically and socially sound implementation. Drawing upon principles of Responsible Research & Innovation and the 4A framework of availability, accessibility, acceptability, and affordability, we thematically analyze existing research to illuminate the ethical and social dimensions of these therapies. Following established PRISMA and JBI Manual guidelines, a search across multiple databases yielded 51 peer-reviewed studies with publication dates ranging from 1991 to 2023.
Our thematic analysis shows that the theme of acceptability is heavily shaped by interactions between patients, caregivers, healthcare professionals and researchers, influencing treatment decisions and shaping the development of curative gene and cell therapies. Despite the generally positive perspective on these therapies, factors like the limited treatment options, financial constraints, healthcare professional attitudes, and (historical) mistrust can impede stakeholder decision-making. While acceptability focuses on individual decisions, the themes of availability, accessibility, and affordability are interconnected and primarily driven by healthcare systems, where high research and development costs, commercialization and a lack of transparency challenge equitable access to these therapies. This diminishes the acceptability for patients, revealing a complex interdependence of the themes.
The findings suggest the need for improved communication strategies in clinical practice to facilitate informed decision-making for patients and caregivers. Policy development should focus on addressing pricing disparities and promoting international collaboration to ensure equitable access to therapies. This review has been pre-registered in PROSPERO under registration number CRD42023474305.
镰状细胞病（SCD）和钻石黑范贫血综合征（DBAS）是两种遗传性血液疾病，给患者、其护理人员和医疗保健系统带来了重大挑战。这两种疾病都会引发严重的健康并发症，且治疗选择有限，导致许多人无法获得造血干细胞移植等治愈性疗法。基因和细胞疗法的最新进展为一种新的治愈选择带来了潜力，标志着这些使人衰弱的疾病管理方面的关键转变。然而，实施这些疗法需要对伦理和社会影响有细致入微的理解。
在这项混合方法的系统评价中，我们探讨了针对SCD和DBAS的基因和细胞疗法的负责任开发与实施，并旨在勾勒出一条通往符合伦理和社会规范实施的道路。借鉴负责任研究与创新原则以及可及性、可获得性、可接受性和可承受性的4A框架，我们对现有研究进行主题分析，以阐明这些疗法的伦理和社会层面。按照既定的PRISMA和JBI手册指南，在多个数据库中进行检索，得到了51项同行评审研究，其发表日期从1991年至2023年不等。
我们的主题分析表明，可接受性主题在很大程度上受到患者、护理人员、医疗保健专业人员和研究人员之间互动的影响，影响治疗决策并塑造治愈性基因和细胞疗法的发展。尽管对这些疗法总体持积极态度，但诸如治疗选择有限、经济限制、医疗保健专业人员态度以及（历史上的）不信任等因素可能会阻碍利益相关者的决策。虽然可接受性侧重于个体决策，但可及性、可获得性和可承受性主题相互关联，主要由医疗保健系统驱动，在该系统中，高昂的研发成本、商业化以及缺乏透明度对公平获得这些疗法构成挑战。这降低了患者的可接受性，揭示了这些主题之间复杂的相互依存关系。
研究结果表明，临床实践中需要改进沟通策略，以促进患者和护理人员做出明智的决策。政策制定应侧重于解决价格差异并促进国际合作，以确保公平获得疗法。本综述已在PROSPERO中预先注册，注册号为CRD42023474305。
