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.

α-突触核蛋白病多系统萎缩症 (MSA) 和帕金森病 (PD) 的疾病缓解疗法正处于临床测试的早期阶段。在监管审批过程中，越来越多地考虑患者的偏好，包括治疗开发初始阶段与治疗相关的风险意愿。在我们对 49 名 MSA 和 38 名 PD 患者进行的研究中，针对不同严重程度的潜在药物或手术副作用，使用经过验证的标准赌博场景来量化与治疗相关的风险意愿。风险意愿呈现非高斯分布，组内和组间差异显着。 MSA 患者接受中位 1% 的猝死风险 [四分位范围： 0.001–25%]，治愈机会为 99% [四分位范围： 99.999–75%]，而 PD 患者报告中位风险为 0.055% [四分位范围： 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，但不愿意接受治疗相关风险的增加。对生活状况、情绪和非运动疾病负担的满意度与 MSA 患者的风险意愿相关，而 PD 患者则与年龄和疾病持续时间相关。针对 MSA 和 PD 患者的个体化方法至关重要，因为从疾病（阶段）直接推断与治疗相关的风险意愿是不可行的。监管机构可以在其审批流程中考虑此类研究，以患者为中心的方式协助权衡安全方面的权重。 对患者风险意愿和相关特征的系统定量评估可以通过促进治疗方案的风险和益处的沟通，帮助医生对患有 MSA 或 PD 的患者进行个体咨询。