Center for the Evaluation of Value and Risk in Health, Tufts Medical Center, Boston, Massachusetts.
Department of Biomedical Informatics, The Ohio State University Wexner Medical Center, Columbus, Ohio.
Clin Ther. 2021 Jul;43(7):1164-1178.e4. doi: 10.1016/j.clinthera.2021.05.013. Epub 2021 Jun 27.
Prader-Willi syndrome (PWS) is a rare disease associated with cognitive impairment, hypotonia, hyperphagia (an insatiable hunger), and obesity. Therapies that target hyperphagia are in development, but understanding the value of these therapies to inform patient-focused drug development (PFDD) requires valid data on disease burden. We estimated disease burden by measuring and comparing quality-adjusted life-years (QALYs) for 3 PWS health states relevant to current PFDD initiatives.
Time trade-off (TTO) and a visual analog scale (VAS) were used to elicit PWS caregivers' values for 3 fixed health states for a standardized patient described with (1) untreated PWS, (2) PWS with controlled obesity, and (3) PWS with controlled obesity and hyperphagia. We excluded participants who left at least 1 TTO or VAS question blank or incomplete (noncompleters) and respondents who reported the same answer for all TTO scenarios (nontraders). The remaining group of respondents (traders) were used for all primary analyses. We assessed validity and bias of QALY estimates by comparing differences in health state valuations, treatment priorities, and characteristics among respondents who did and did not complete the TTO.
A total of 458 respondents completed the survey, including 226 traders, 93 nontraders, and 139 noncompleters. Traders valued untreated PWS at 0.69 QALYs, PWS with controlled obesity at 0.79 QALYs, and controlled hyperphagia/obesity at 0.91 QALY (P < 0.01 for differences among health state values). Reported VAS ratings were similar for traders versus nontraders for untreated PWS (38.64 vs 38.95, P = 0.89) and PWS with controlled obesity (57.36 vs 55.14, P = 0.35) but varied for PWS with controlled obesity and hyperphagia (70.70 vs 64.46, P = 0.02). Exclusion of noncompleters did not introduce obvious bias because traders and noncompleters were similar in treatment priorities and characteristics. The exclusion of nontraders did not meaningfully alter mean or distribution of valuations.
This study found that avoiding hyperphagia decreases the burden of PWS and that these results are robust, even once imposing strict inclusion criteria. Use of fixed health states to estimate QALYs addresses many of the complexities of measuring disease burden in rare and pediatric conditions, indicating the potential value of this approach to inform premarket decision makers in identifying outcome importance.
普拉德-威利综合征（PWS）是一种罕见疾病，与认知障碍、低张力、贪食（无法满足的饥饿感）和肥胖有关。针对贪食症的治疗方法正在开发中，但要了解这些疗法对以患者为中心的药物开发（PFDD）的价值，就需要有关疾病负担的有效数据。我们通过测量和比较与当前 PFDD 计划相关的 3 种 PWS 健康状况的质量调整生命年（QALY）来估计疾病负担。
时间权衡（TTO）和视觉模拟量表（VAS）用于引出标准化患者的 3 种固定健康状况的 PWS 护理人员的价值，该患者（1）未经治疗的 PWS，（2）肥胖得到控制的 PWS，以及（3）肥胖和贪食得到控制的 PWS。我们排除了至少留下 1 个 TTO 或 VAS 问题空白或不完整的参与者（非完成者）和对所有 TTO 场景报告相同答案的受访者（非交易员）。所有主要分析都使用了剩余的应答者（交易员）。我们通过比较完成和未完成 TTO 的受访者在健康状况评估、治疗优先级和特征方面的差异，评估了 QALY 估计的有效性和偏差。
共有 458 名受访者完成了调查，其中包括 226 名交易员、93 名非交易员和 139 名非完成者。交易员对未经治疗的 PWS 的估值为 0.69 QALY，对肥胖得到控制的 PWS 的估值为 0.79 QALY，对肥胖和贪食得到控制的 PWS 的估值为 0.91 QALY（健康状况值之间的差异具有统计学意义，P < 0.01）。交易员与非交易员相比，对未经治疗的 PWS 的报告 VAS 评分相似（38.64 对 38.95，P = 0.89）和肥胖得到控制的 PWS（57.36 对 55.14，P = 0.35），但对肥胖和贪食得到控制的 PWS 的评分不同（70.70 对 64.46，P = 0.02）。非完成者的排除并没有引入明显的偏差，因为交易员和非完成者在治疗优先级和特征方面相似。非交易员的排除并没有显著改变或改变估值的均值或分布。
这项研究发现，避免贪食症会降低 PWS 的负担，并且即使在实施严格的纳入标准后，这些结果也是可靠的。使用固定健康状况来估计 QALY 解决了在罕见和儿科疾病中测量疾病负担的许多复杂性，表明这种方法有可能为识别上市前决策者的结果重要性提供信息。
