Bernhardt Alexander Maximilian, Oeller Marc, Friedrich Isabel, Kocakavuk Emre, Nachman Eliana, Peikert Kevin, Roderigo Malte, Rossmann Andreas, Schröter Tabea, Wilhelm Lea Olivia, Prell Tino, van Riesen Christoph, Nieweler Johanna, Katzdobler Sabrina, Weiler Markus, Jacobi Heike, Warnecke Tobias, Claus Inga, Palleis Carla, Breimann Stephan, Falkenburger Björn, Brandt Moritz, Hermann Andreas, Rumpf Jost-Julian, Claßen Joseph, Höglinger Günter, Gandor Florin, Levin Johannes, Giese Armin, Janzen Annette, Oertel Wolfgang Hermann
Department of Neurology, Ludwig-Maximilians-Universität München, Munich, Germany.
German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
NPJ Parkinsons Dis. 2024 Aug 15;10(1):158. doi: 10.1038/s41531-024-00764-5.
Disease-modifying therapeutics in the α-synucleinopathies multiple system atrophy (MSA) and Parkinson's Disease (PD) are in early phases of clinical testing. Involving patients' preferences including therapy-associated risk willingness in initial stages of therapy development has been increasingly pursued in regulatory approval processes. In our study with 49 MSA and 38 PD patients, therapy-associated risk willingness was quantified using validated standard gamble scenarios for varying severities of potential drug or surgical side effects. Demonstrating a non-gaussian distribution, risk willingness varied markedly within, and between groups. MSA patients accepted a median 1% risk [interquartile range: 0.001-25%] of sudden death for a 99% [interquartile range: 99.999-75%] chance of cure, while PD patients reported a median 0.055% risk [interquartile range: 0.001-5%]. Contrary to our hypothesis, a considerable proportion of MSA patients, despite their substantially impaired quality of life, were not willing to accept increased therapy-associated risks. Satisfaction with life situation, emotional, and nonmotor disease burden were associated with MSA patients' risk willingness in contrast to PD patients, for whom age, and disease duration were associated factors. An individual approach towards MSA and PD patients is crucial as direct inference from disease (stage) to therapy-associated risk willingness is not feasible. Such studies may be considered by regulatory agencies in their approval processes assisting with the weighting of safety aspects in a patient-centric manner. A systematic quantitative assessment of patients' risk willingness and associated features may assist physicians in conducting individual consultations with patients who have MSA or PD by facilitating communication of risks and benefits of a treatment option.
针对α-突触核蛋白病（多系统萎缩症（MSA）和帕金森病（PD））的疾病修饰疗法正处于临床试验的早期阶段。在监管审批过程中，越来越多地追求在治疗开发的初始阶段纳入患者的偏好，包括与治疗相关的风险意愿。在我们对49例MSA患者和38例PD患者的研究中，使用经过验证的标准博弈情景对不同严重程度的潜在药物或手术副作用的治疗相关风险意愿进行了量化。风险意愿呈非高斯分布，在组内和组间有显著差异。MSA患者接受99%[四分位间距：99.999 - 75%]的治愈机会时，突然死亡的中位风险为1%[四分位间距：0.001 - 25%]，而PD患者报告的中位风险为0.055%[四分位间距：0.001 - 5%]。与我们的假设相反，相当一部分MSA患者尽管生活质量严重受损，但仍不愿意接受增加的治疗相关风险。与PD患者不同，生活状况满意度、情绪和非运动疾病负担与MSA患者的风险意愿相关，而年龄和病程是与PD患者风险意愿相关的因素。对MSA和PD患者采取个体化方法至关重要，因为从疾病（阶段）直接推断治疗相关风险意愿是不可行的。监管机构在审批过程中可能会考虑此类研究，以协助以患者为中心对安全方面进行权衡。对患者风险意愿及相关特征进行系统的定量评估，可能有助于医生与患有MSA或PD的患者进行个体化咨询，促进对治疗方案风险和益处的沟通。
