Priorities when deciding on participation in early-phase gene therapy trials for Duchenne muscular dystrophy: a best-worst scaling experiment in caregivers and adult patients
Priorities when deciding on participation in early-phase gene therapy trials for Duchenne muscular dystrophy: a best-worst scaling experiment in caregivers and adult patients
复制标题
DOI：
10.1186/s13023-019-1069-6
复制
发表时间：
2019-05-09
影响因子：
3.7
通讯作者：
Peay, Holly L.
中科院分区：
文献类型：
--
作者：
Paquin, Ryan S.;Fischer, Ryan;Peay, Holly L.
目的Duchenne型肌营养不良症的基因治疗试验始于2018年。试验决策是复杂的，有非治愈性的、有时间限制的好处；渐进的、致命的过程；以及高度未得到满足的需求。在这里，照顾者和患者优先考虑影响参与早期基因治疗试验的决策的因素。方法我们在美国照顾者和患有Duchenne的成年人(N=274)中进行了一项最好-最差的评估实验。参与者完成了11个选择集，在决定是否参加假想的基因治疗试验时，选择他们最关心和最不关心的特征。采用序贯条件Logistic回归分析数据。结果受试者在试验决策中优先考虑改善肌肉功能。对参与限制后来使用基因转移和编辑的担忧也很重要，改善肺和心脏功能也是重要的。低死亡风险降至接近中间水平。参与者最不关心肌肉活检和随机服用安慰剂的可能性。与门诊儿童的照顾者相比，患有Duchenne的成人和非门诊儿童的照顾者显著优先考虑改善肺功能。结论我们的数据显示，在基因治疗试验决策中，相对于潜在的危害和程序，我们的数据显示了预期收益和机会成本的优先顺序。这些数据为议定书的制定、教育和宣传工作以及知情同意提供了信息。
PurposeSeveral gene therapy trials for Duchenne muscular dystrophy initiated in 2018. Trial decision making is complicated by non-curative, time-limited benefits; the progressive, fatal course; and high unmet needs. Here, caregivers and patients prioritize factors influencing decision making regarding participation in early-phase gene therapy trials.MethodsWe conducted a best-worst scaling experiment among U.S. caregivers and adults with Duchenne (N=274). Participants completed 11 choice sets, choosing features they cared about most and least when deciding whether to participate in a hypothetical gene therapy trial. We analyzed the data using sequential conditional logistic regression.ResultsParticipants prioritized improved muscle function in trial decision making. Concerns about participation limiting later use of gene transfer and editing were also important, as were improved lung and heart function. Low risk of death fell near the middle. Participants cared least about muscle biopsies and potential for randomization to placebo. Adults with Duchenne and caregivers of non-ambulatory children significantly prioritized improved lung function compared to caregivers of ambulatory children.ConclusionOur data demonstrate prioritization of anticipated benefits and opportunity costs relative to potential harms and procedures in gene therapy trial decision making. Such data inform protocol development, education and advocacy efforts, and informed consent.