Developing a Natural History Model for Duchenne Muscular Dystrophy.

Area of Science:

• Biomedical Informatics
• Disease Modeling
• Health Economics

Background:

• Duchenne muscular dystrophy (DMD) requires robust tools for health technology assessments.
• Existing models lack a comprehensive, patient-centric view of disease trajectory.
• Project HERCULES aims to develop data-informed models for DMD treatment evaluation.

Purpose of the Study:

• To develop a patient-centric, data-informed natural history model (NHM) for Duchenne muscular dystrophy (DMD).
• To estimate the lifetime disease trajectory of DMD patients under current standard of care.
• To support future economic evaluations and health technology assessments for novel DMD therapies.

Main Methods:

• Pooled multiple datasets, including the Critical Path Institute Duchenne Regulatory Science Consortium (D-RSC) database.
• Defined health states based on clinical trial outcomes, real-world practice, and expert input.
• Supplemented data with expert elicitation and a systematic literature review and meta-analysis of mortality.

Main Results:

• The NHM incorporates ambulatory, transfer, and non-ambulatory phases, detailing functional decline.
• Patients spend approximately 9.5 years in ambulatory states, 1.5 years in the transfer state.
• Median predicted survival for DMD patients is estimated at 34.8 years.

Conclusions:

• The developed NHM provides a detailed disease pathway for DMD, including the critical transfer state.
• This model can enhance economic evaluations by incorporating a lifetime time horizon for DMD.
• The NHM will aid in identifying future research priorities for Duchenne muscular dystrophy.