Broomfield Jonathan, Hill M, Chandler F, Crowther M J, Godfrey J, Guglieri M, Hastie J, Larkindale J, Mumby-Croft J, Reuben E, Woodcock F, Abrams K R
University of Leicester, Leicester, UK.
GlaxoSmithKline, Middlesex, UK.
Pharmacoecon Open. 2024 Jan;8(1):79-89. doi: 10.1007/s41669-023-00450-x. Epub 2023 Nov 29.
The aim of this study was to pool multiple data sets to build a patient-centric, data-informed, natural history model (NHM) for Duchenne muscular dystrophy (DMD) to estimate disease trajectory across patient lifetime under current standard of care in future economic evaluations. The study was conducted as part of Project HERCULES, a multi-stakeholder collaboration to develop tools to support health technology assessments of new treatments for DMD.
Health states were informed by a review of NHMs for DMD and input from clinicians, patients and caregivers, and defined using common outcomes in clinical trials and real-world practice. The primary source informing the NHM was the Critical Path Institute Duchenne Regulatory Science Consortium (D-RSC) database. This was supplemented with expert input obtained via an elicitation exercise, and a systematic literature review and meta-analysis of mortality data.
The NHM includes ambulatory, transfer and non-ambulatory phases, which capture loss of ambulation, ability to weight bear and upper body and respiratory function, respectively. The NHM estimates patients spend approximately 9.5 years in ambulatory states, 1.5 years in the transfer state and the remainder of their lives in non-ambulatory states. Median predicted survival is 34.8 years (95% CI 34.1-35.8).
The model includes a detailed disease pathway for DMD, including the clinically and economically important transfer state. The NHM may be used to estimate the current trajectory of DMD in economic evaluations of new treatments, facilitating inclusion of a lifetime time horizon, and will help identify areas for further research.
本研究的目的是汇总多个数据集，构建以患者为中心、基于数据的杜氏肌营养不良症（DMD）自然史模型（NHM），以在未来经济评估中按照当前护理标准估计患者一生的疾病轨迹。该研究是大力神项目的一部分，大力神项目是一个多利益相关方合作项目，旨在开发支持DMD新疗法卫生技术评估的工具。
通过对DMD的NHM进行回顾以及临床医生、患者和护理人员的意见，确定健康状态，并使用临床试验和实际临床中的常见结果进行定义。NHM的主要信息来源是关键路径研究所杜氏监管科学联盟（D-RSC）数据库。通过专家意见征集、系统文献综述和死亡率数据的荟萃分析对该数据库进行补充。
NHM包括行走、转移和非行走阶段，分别反映行走能力丧失、负重能力以及上肢和呼吸功能。NHM估计患者在行走状态下约花费9.5年，在转移状态下花费1.5年，其余时间处于非行走状态。预测中位生存期为34.8年（95%CI 34.1-35.8）。
该模型包含DMD详细的疾病路径，包括具有临床和经济意义的转移状态。NHM可用于在新疗法的经济评估中估计DMD的当前轨迹，便于纳入终身时间范围，并将有助于确定进一步研究的领域。
