The health economics of Duchenne muscular dystrophy

Abstract: Duchenne muscular dystrophy (DMD) is a rare neuromuscular disease characterized by progressive muscle degeneration resulting in loss of independent ambulation, serious multisystem complications, and a mean life expectancy at birth of about 25 years. Several therapies are on the horizon for DMD and it has thus become urgent to better understand the health economic context of the disease to enable assessments of cost-effectiveness and inform decisions regarding reimbursement of new health technologies. However, to date, little is known of the burden of DMD, including cost of illness and impact on health-related quality of life (HRQoL). The aim of this thesis was to estimate and describe the health economics of DMD, develop a tool measuring disease progression, and construct a model framework for economic evaluation of new treatments. Paper I to IV were based on data collected in a cross-sectional, observational study. Patients with DMD from Germany, Italy, the UK, and the US were identified and recruited through the Translational Research in Europe – Assessment and Treatment of Neuromuscular Diseases (TREAT-NMD) network and invited with a caregiver to complete a study questionnaire online. Paper V was a modelling study synthesizing data from the preceding papers. In paper I to III, we estimated direct and indirect costs of DMD and measured patient and caregiver HRQoL and burden using several generic and disease-specific instruments. In paper IV, we developed the Duchenne muscular dystrophy Functional Ability Self-Assessment Tool (DMDSAT), a new rating-scale measuring functional ability in DMD. Item selection for the DMDSAT was led by neuromuscular specialists and the psychometric properties of the instrument were examined using Rasch analysis. In paper V, we synthesized our health economic evidence and developed a decision-analytic model framework for the assessment of the cost-effectiveness of treatments for DMD based on the DMDSAT. For comparison, we also developed two models based on stages of disease as defined in the international DMD clinical care guidelines and patients’ ventilation status, respectively. In paper I, we show that DMD is associated with a substantial cost burden to society and affected households. Across countries, the mean per-patient annual direct cost of illness was found to be 7 to 16 times higher than the mean per-capita health expenditure. Indirect and informal care costs of DMD were substantial, each component constituting between 18% and 43% of total costs. In paper II, we show that HRQoL (as valued by the general population) in DMD is substantially impaired in relation to general population reference values, strongly negatively associated with disease progression, and in good agreement with the caregivers’ subjective rating of patients’ current health and mental status. Still, most children and young adults with DMD were perceived as happy and in good health by their caregivers, indicating that some domains of HRQoL remain intact through the progression of the disease. In paper III, we show that caring for a person with DMD can be associated with a substantial burden and impaired HRQoL. Our findings suggest that caregivers to patients with DMD should be screened for depression and emphasize the need for a holistic approach to family mental health in the context of chronic childhood disease. In paper IV, the administered version of the new rating-scale, the DMDSAT, comprised a total of eight questions covering four domains (arm function, mobility, transfers, and ventilation status). Results from the psychometric analysis show that the DMDSAT is an instrument fit for purpose to measure functional ability in ambulant and non-ambulant patients with DMD. In paper V, we found that model structure and perspective of analysis have a substantial impact on assessments of cost-effectiveness of treatments for DMD. Our results show that the DMDSAT represents a sensitive and clinically relevant option for modelling DMD across the entire trajectory of disease in economic evaluations compared with frameworks based on conventional staging of disease progression. In summary, this thesis provides a description of the previously unknown health economic context of DMD, including a portfolio of cost and utility data, a new tool designed to measure DMD disease severity, and a fully populated decision-analytic model framework for cost-effectiveness analysis. These data and tools should be helpful to inform health technology assessments and health economic programmes of new treatments for DMD.