Graafland Charlotte H, Seelaar Harro, Panman Jessica L, Jiskoot Lize C, Kleefstra Tjitske, Poos Jackie M, Richard Edo, Schermer Maartje H N, van Swieten John C, Donker Kaat Laura, Bunnik Eline M
Department of Public Health, section Medical Ethics, Philosophy and History of Medicine, Erasmus University Medical Centre, Rotterdam, The Netherlands.
Department of Neurology and Alzheimer Centre, Erasmus University Medical Centre, Rotterdam, The Netherlands.
Alzheimers Res Ther. 2025 May 6;17(1):99. doi: 10.1186/s13195-025-01749-z.
Onset-predictive biomarker tests (OPBT) in genetic frontotemporal dementia (FTD) may be used to recruit mutation carriers into preventive clinical trials before symptoms manifest. This would require disclosure of OPBT results to potential participants. This study investigates the perspectives of Dutch presymptomatic mutation carriers and individuals at 50% risk of genetic FTD on disclosure of OPBT results. It focuses on their willingness to receive OPBT results, what impacts they foresee from disclosure, and their preferences for the process of disclosure.
Semi-structured interviews were conducted with presymptomatic mutation carriers and individuals at 50% risk of developing genetic FTD (n = 25), who had received genetic counselling or participate in a longitudinal cohort study. The interview transcripts were analysed using thematic inductive analysis.
Main themes were: willingness to undergo biomarker testing, foreseen impact of test results, preferences regarding biomarker test features, and understanding of biomarker testing. Most participants would be willing to receive OPBT results in the context of clinical trial recruitment. Participants would also be willing to receive OPBT results without access to clinical trial participation, as they perceived utility from these results. They would use positive OPBT results to prepare for the future, e.g. by planning for care, drawing up advance care directives, retiring early, and spending final healthy years well. At the same time, they thought positive OPBT results might also have negative psychological impacts on self-image or social dynamics with others. Implications of positive OPBT results for self-image as healthy or ill differed between participants. Negative OPBT results would provide relief and not lead to life changes.
Dutch presymptomatic mutation carriers and individuals at 50% risk of developing genetic FTD tend to be willing to receive OPBT results. The results would allow for participation in a clinical trial and preparation for onset through personal life planning. At the same time, disclosure of OPBT results might have negative psychological consequences. This study provides valuable input for developing ethical guidance and an appropriate counselling process to ensure responsible disclosure of OPBT results with clinical trial recruitment.
在遗传性额颞叶痴呆(FTD)中,发病预测生物标志物检测(OPBT)可用于在症状出现之前招募突变携带者进入预防性临床试验。这需要向潜在参与者披露OPBT结果。本研究调查了荷兰有症状前突变携带者以及有50%遗传FTD风险的个体对OPBT结果披露的看法。研究重点在于他们接受OPBT结果的意愿、他们预见的披露会带来的影响以及他们对披露过程的偏好。
对有症状前突变携带者以及有50%发生遗传FTD风险的个体(n = 25)进行了半结构化访谈,这些个体接受过遗传咨询或参与了一项纵向队列研究。使用主题归纳分析法对访谈记录进行了分析。
主要主题包括:接受生物标志物检测的意愿、检测结果的预期影响、对生物标志物检测特征的偏好以及对生物标志物检测的理解。大多数参与者愿意在临床试验招募的背景下接受OPBT结果。参与者也愿意在无法参与临床试验的情况下接受OPBT结果,因为他们认为这些结果有用。他们会利用阳性OPBT结果为未来做准备,例如通过规划护理、制定预先护理指示、提前退休以及充分利用最后的健康时光。与此同时,他们认为阳性OPBT结果也可能对自我形象或与他人的社会关系产生负面影响。阳性OPBT结果对自我形象是健康还是患病的影响在参与者之间存在差异。阴性OPBT结果会带来解脱感,不会导致生活改变。
荷兰有症状前突变携带者以及有50%发生遗传FTD风险的个体倾向于愿意接受OPBT结果。这些结果将有助于参与临床试验并通过个人生活规划为发病做准备。与此同时,披露OPBT结果可能会产生负面心理后果。本研究为制定伦理指导和适当的咨询流程提供了有价值的参考,以确保在临床试验招募中负责任地披露OPBT结果。