Tsai Jui-Hua, Crossnohere Norah L, Strong Theresa, Bridges John F P
Pharmerit International, Bethesda, Maryland.
Department of Biomedical Informatics, The Ohio State University College of Medicine, Columbus, Ohio.
MDM Policy Pract. 2021 Sep 2;6(2):23814683211039457. doi: 10.1177/23814683211039457. eCollection 2021 Jul-Dec.
Prader-Willi syndrome (PWS) is a rare neurodevelopmental disorder causing quality of life impairments such as insatiable hunger (hyperphagia) and obesity. We explored caregivers' willingness to assume treatment risk in exchange for reduced hyperphagia according to a PWS-validated observer-reported outcome measure. We partnered with PWS patient organizations to develop a discrete-choice experiment exploring caregivers' benefit-risk tradeoffs for emerging PWS treatments. The treatment benefit was a reduction in hyperphagia (as measured by a 0-, 5-, or 10-point change on the Hyperphagia Questionnaire for Clinical Trials [HQ-CT]). Treatment risks included weight gain (none, 5%, 10%), added risk of skin rash (none, 10%, 20%), and risk of liver damage (none, 1 in 1000, 10 in 1000). Preference models were estimated using mixed logistic regression and maximum acceptable risk. We explored differences in preferences across familial caregivers of patients with and without hyperphagia. Four hundred sixty-eight caregivers completed the online survey. The majority of caregivers reported that patients experienced hyperphagia (68%) and half of patients experienced obesity (52%). Caregivers of patients without hyperphagia were willing to accept greater weight gain (16.4% v. 8.1%, = 0.004) and a higher risk of skin rash (11.7% v. 6.2% = 0.008) as compared to caregivers of patients with hyperphagia. Caregivers of patients with hyperphagia would accept a higher risk of liver damage as compared to caregivers of patients without hyperphagia (11.9 out of 1000 v. 6.4 out of 1000, = 0.04). This research demonstrates that caregivers are willing to accept risk in exchange for a five-point improvement on the HQ-CT, a smaller marginal improvement than had been previously classified as meaningful. Patient experience with hyperphagia is a modifier in how much risk caregivers will accept.
普拉德-威利综合征（PWS）是一种罕见的神经发育障碍，会导致生活质量受损，如无法满足的饥饿感（食欲亢进）和肥胖。我们根据一项经PWS验证的观察者报告结局指标，探讨了照料者为换取食欲亢进减轻而承担治疗风险的意愿。我们与PWS患者组织合作开展了一项离散选择实验，以探究照料者对新兴PWS治疗方法的利弊权衡。治疗益处是食欲亢进减轻（通过临床试验用食欲亢进问卷[HQ-CT]上0分、5分或10分的变化来衡量）。治疗风险包括体重增加（无、5%、10%）、皮疹风险增加（无、10%、20%）以及肝损伤风险（无、千分之一、千分之十）。使用混合逻辑回归和最大可接受风险估计偏好模型。我们探讨了有食欲亢进和无食欲亢进患者的家庭照料者在偏好上的差异。468名照料者完成了在线调查。大多数照料者报告称患者有食欲亢进（68%），一半患者有肥胖（52%）。与有食欲亢进患者的照料者相比，无食欲亢进患者的照料者愿意接受更大的体重增加风险（16.4%对8.1%，P = 0.004）和更高的皮疹风险（11.7%对6.2%，P = 0.008）。与无食欲亢进患者的照料者相比，有食欲亢进患者的照料者愿意接受更高的肝损伤风险（千分之11.9对千分之6.4，P = 0.04）。这项研究表明，照料者愿意接受风险，以换取HQ-CT上五分的改善，这一微小的边际改善低于先前被归类为有意义的程度。患者的食欲亢进经历是照料者愿意接受多少风险的一个调节因素。
