Cost-Effectiveness Assessment of Orphan Drugs

Abstract

In September 2012, the Dutch Healthcare Insurance Board issued advice not to reimburse orphan drugs that target lysosomal storage disorders: agalsidase alfa and agalsidase beta for Fabry disease and alglucosidase alfa for Pompe disease [1, 2].With respect to the former, the Healthcare Insurance Board concluded that enzyme replacement therapy offered an added therapeutic value compared with symptomatic treatment of Fabry disease [1]. However, enzyme replacement therapy was not cost effective at an incremental cost of euro3.3 million per quality-adjusted life-year gained. The unfavourable cost effectiveness originated from the limited additional therapeutic value (as a result of the slow progression of the disease) and high costs: enzyme replacement therapy costs euro200,000 per patient per year, resulting in a total budget impact of euro11 million per year for the Netherlands. The Healthcare Insurance Board argued that continued reimbursement of enzyme replacement therapy for Fabry disease would imply that limited resources are not available to reimburse other, more cost effective health technologies.With respect to the latter, the Healthcare Insurance Board recommended to restrict reimbursement of alglucosidase alfa for Pompe disease to patients who suffer from the classic form of the disease and to patients who show symptoms of the (non-)classic disease during their infancy [2]. Alglucosidase alfa was found to generate an added therapeutic value over best supportive care, was cost effective at an incremental cost of euro0.3-0.9 million per quality-adjusted life-year gained in the classic form of Pompe disease, but was not cost effective at an incremental cost of euro15 million per quality-adjusted life-year gained in the non-classic form of Pompe disease. The annual cost of treating a patient with alglucosidase alfa amounted to euro0.4-0.7 million.1 A Scientific ConundrumThese two examples highlight some of the scientific challenges involved in assessing the cost effectiveness of orphan drugs.Uncertainty tends to surround the safety and effectiveness of orphan drugs at the time of market launch. This clinical uncertainty may result from difficulties involved in recruiting a sufficient number of patients across countries, the lack of randomized controlled trials, and the use of surrogate efficacy measures [3]. As a result, there is an urgent need for the development of methodological guidelines about the assessment of the (cost) effectiveness of orphan drugs for (ultra-)rare diseases. In England and Wales, the National Institute for Health and Clinical Excellence (NICE) will be responsible for assessing orphan drugs from April 2013 onwards and has committed itself to developing methods to guide such an assessment [4].Dutch physicians who are involved in treating patients with these lysosomal storage disorders have argued that the Healthcare Insurance Board is not able to issue an informed advice due to the lack of long-term data on safety and effectiveness [5]. For instance, on the occasion of the public hearing of the Dutch Healthcare Insurance Board on 21 September 2012, Professor Hollak stressed that the main challenge with enzyme replacement therapy is that effectiveness is different across patient subgroups [6]. While a clear benefit was shown in some patients, in others, such as those with end-renal or cardiac disease, a lesser benefit was observed. No conclusions can nonetheless be drawn as the overall amount of data remains too small, resulting from the low number of Dutch patients. To address this issue, the idea has been proposed to launch a compulsory Europeanwide registry following marketing authorization of an orphan drug [5]. The establishment of such registries for rare diseases is supported by the European Medicines Agency and by many member states, although registries are not without methodological limitations [3].The ethical principle underlying economic evaluation is that scarce resources are allocated to the most cost-effective health technologies with a view to maximizing population health. …