目的是量化成人和镰状细胞病（SCD）儿童的父母/照顾者中潜在基因疗法的利益-风险权衡。开发了一项离散选择实验（DCE）调查，受访者在一系列实验对照的假设基因疗法对和“无基因疗法”选项中选择了他们首选的治疗方案。基因治疗替代方案是根据消除 SCD 症状的机会、预期寿命的预期延长、治疗相关的死亡风险以及终生癌症风险的潜在增加来定义的。受访者根据他们当前疾病​​的严重程度以及对疾病恶化的预期做出选择。三个临床中心和一个患者组织招募了 174 名成年患者和 109 名 SCD 儿童家长来完成这项调查。成年人和家长受访者普遍愿意选择基因疗法，但成年人比父母需要更高的预期疗效水平（即消除症状的机会更高）才能选择死亡率风险为 10% 或更高的基因疗法。当成人和症状不太严重的儿童的父母被要求考虑疾病严重程度较高的情况时，风险承受能力增加，具有死亡风险的基因疗法的最低可接受疗效水平下降了 50% 以上。基线 SCD 症状是基因治疗可接受性的主要驱动力。症状较轻的患者的成人和父母可能更喜欢其他治疗选择；然而，症状恶化的预期引发了对这项新技术可接受的效益-风险平衡的强烈重新评估。版权所有 © 2023 美国血液学会。

Objective is to quantify benefit-risk tradeoffs pertaining to potential gene therapies among adults and parents/caregivers of children with sickle-cell disease (SCD). A discrete-choice experiment (DCE) survey was developed in which respondents selected their preferred treatment alternatives in a series of experimentally-controlled pairs of hypothetical gene therapies and a "no gene therapy" option. Gene therapy alternatives were defined based on the chance of eliminating SCD symptoms, expected increases in life expectancy they could offer, treatment-related risk of death and potential increases in lifetime cancer risk. Respondents made selections based on their current disease severity and in the context of expectations of worsened disease. Three clinical sites and one patient organization recruited 174 adult patients and 109 parents of children with SCD to complete the survey. Adult and parent respondents were generally willing to choose gene therapies, but the adults required higher expected levels of efficacy (i.e., higher chance of eliminating symptoms) than parents to choose gene therapies that conferred mortality risks of 10% or more. When adults and parents of children with less severe symptoms were asked to consider scenarios of higher levels of disease severity, the risk tolerance increased, and the lowest acceptable level of efficacy for gene therapies with mortality risks dropped by more than 50%. Baseline SCD symptoms are a major driver of gene therapy acceptability. Adults and parents of patients with milder symptoms may prefer other treatment options; however, an expectation of symptoms deterioration triggers strong reassessment of the acceptable benefit-risk balance of this novel technology.Copyright © 2023 American Society of Hematology.