Health Technology Assessment Of Orphan Drugs : The example of Pompe disease

In recent decades, the development of orphan drugs, i.e. drugs for rare diseases, is stimulated by regulations in various countries. However, the generally high prices of orphan drugs confront policy makers with difficult reimbursement decisions. The orphan disease investigated in this thesis is Pompe disease. Pompe disease is a progressive muscle disease with a wide clinical spectrum. Without specific treatment, patients with the classic-infantile form die within the first year of life. Patients with a milder form of the disease experience progressive muscle weakness and respiratory problems. Since 2006, enzyme replacement therapy (ERT) is available for this disease. ERT treatment is associated with considerable costs.

The first part of the thesis examines the burden of Pompe disease from a financial and economic perspective, the perspective of the patient and the perspective of the informal caregiver. The thesis shows that patients experience a reduced quality of life and are impaired in their ability to work. Informal caregivers provide 18 hours of care per week, which sometimes leads to physical and mental problems, but also gives caregivers fulfilment. Annual cost from healthcare consumption, informal care and productivity losses is estimated to be €22,475 per patient. The second part presents two cost-effectiveness studies. For adult Pompe patients, two scenarios were modelled to resemble uncertainty concerning long-term survival gains. For scenario 1, survival gains were not extrapolated after the observed period; while in scenario 2 survival gains were extrapolated. For both scenarios, substantial survival gains were shown. Incremental costs per QALY were €3.2 million (scenario 1) and €1.8 million (scenario 2). The cost-effectiveness study in infantile patients with Pompe disease showed that ERT led to a survival gain of more than 13 years. Incremental costs per QALY were €1.0 million. The third part of the thesis assessed the extent to which health technology assessment was used in reimbursement decisions on orphan drugs. More transparency is needed to establish the reason for differences in international reimbursement decisions on orphan drugs. For the Netherlands, it was shown that reimbursement criteria were extended for orphan drugs to include limited budget impact, rarity, identifiable patients and absence of alternative treatments.
Finally, the discussion elaborates on the debate on the reimbursement decision from 2012, adaptations needed in orphan drug regulation and pricing, methodological challenges for HTA studies in orphan drugs and directions for further research.