OBJECTIVES: Spinal muscular atrophy (SMA) is a severe, progressive neuromuscular disease caused by reduced levels of survival of motor neuron protein. The disease spectrum is defined by age of onset and highest achieved motor milestone. The aim of this study is to develop natural history disease models to inform the cost-effectiveness assessment of innovative treatments in this indication.

METHODS: Sources of evidence for the models included (i) de novo systematic review of economic evaluations in SMA and related conditions (conducted in August 2019), (ii) clinician interviews to review current disease management guidelines to define relevant model health states, and to identify appropriate disease-related, treatment-independent adverse events (TIAEs).

RESULTS: Both disease models are based on discrete, motor function milestones reflecting disease severity. Hence, the proposed ‘early onset’ (Type 1) model includes four motor milestones: “not sitting”, “sitting”, “standing”, and “walking”, together with “permanent ventilation” and “death” health states. The ‘later onset’ (Type 2/3) model is identical to that for early onset, apart from the removal of the “not sitting” and “permanent ventilation” health states. Patients can transition between these defined motor function milestones. Our analysis indicates that the newly defined transfer health state (“standing”) is an important preliminary health state which diminishes the reliance on caregivers (increasing caregiver quality of life [QoL] and reducing costs). Each health state includes a “with or without” sub-health state accounting for potential difference in QoL and cost. Finally, each model allows for the application of utility decrements to TIAEs of interest: respiratory, gastrointestinal and orthopedic.

CONCLUSIONS: Use of these natural history models will assist with the cost-effectiveness assessment of novel targeted treatments for SMA. They are based on an extensive review of the literature/clinician opinion and include appropriate health states across disease subtypes, which affect lifetime costs, quality and length of life.