Access to orphan drugs in western Europe: can more systematic policymaking really help to avoid different decisions about the same drug?

When the Scottish government recently launched a £21 million fund to provide patients with rare diseases access to treatment, Alex Neill, the Scottish Health Secretary, stated that 'it was only right that Scottish patients with rare conditions had access to innovative medicines which were clinically justified, and that they were not disadvantaged due to the very high cost of these treatments'. This statement raises questions about the criteria that play a role in reimbursement decisions on orphan drugs. This editorial examines the criteria that were used in the decisions about the reimbursement of an orphan drug for Pompe disease and explores methods to improve the transparency and consistency of reimbursement decisions for orphan drugs in general.

[Shift of focus in the financing of Hungarian drugs. Reimbursement for orphan drugs for treating rare diseases: financing of enzyme replacement therapy in Hungary]. / Hangsúlyeltolódások a hazai gyógyszerek finanszírozásában. A ritka betegségek kezelésére szolgáló árva gyógyszerek támogatása. Enzimpótló kezelések finanszírozása hazánkban.

Focusing on the benefits of patients with rare disease the authors analysed the aspects of orphan medicines financed in the frame of the Hungarian social insurance system in 2012 in order to make the consumption more rational, transparent and predictable. Most of the orphan drugs were financed in the frame of compassionate use by the reimbursement system. Consequently, a great deal of crucial problems occurred in relation to the unconventional subsidized method, especially in the case of the highest cost enzyme replacement therapies. On the base of the findings, proposals of the authors are presented for access to orphan drugs, fitting to the specific professional, economical and ethical aspects of this unique field of the health care system. The primary goal is to provide a suitable subsidized method for the treatment of rare disease patients with unmet medical needs. The financial modification of orphans became indispensible in Hungary. Professionals from numerous fields dealing with rare disease patients' care expressed agreement on the issue. Transforming the orphan medicines' financial structure has been initiated according to internationally shared principles.

Newborn screening for pompe disease? a qualitative study exploring professional views.

BACKGROUND: Developments in enzyme replacement therapy have kindled discussions on adding Pompe disease, characterized by progressive muscle weakness and wasting, to neonatal screening. Pompe disease does not fit traditional screening criteria as it is a broad-spectrum phenotype disorder that may occur in lethal form in early infancy or manifest in less severe forms from infancy to late adulthood. Current screening tests cannot differentiate between these forms. Normally, expanding screening is discussed among experts in advisory bodies. While advisory reports usually mention the procedures and outcome of deliberations, little is known of the importance attached to different arguments and the actual weighing processes involved. In this research we aim to explore the views of a wide range of relevant professionals to gain more insight into the process of weighing pros and cons of neonatal screening for Pompe disease, as an example of the dilemmas involved in screening for broad-spectrum phenotype disorders. METHODS: We conducted 24 semi-structured interviews with medical, lab, insurance and screening professionals, and executive staff of patient organisations. They were asked about their first reaction to neonatal screening for Pompe disease, after which benefits and harms and requirements for screening were explored in more detail. RESULTS: Advantages included health gain by timely intervention, avoiding a diagnostic quest, having a reproductive choice and gaining more knowledge about the natural course and treatment. Being prepared was mentioned as an advantage for the later manifesting cases. Disadvantages included treatment costs and uncertainties about its effect, the timing of treatment in later manifesting cases, the psychological burden for the patient-in-waiting and the family. Also the downsides of having prior knowledge as well as having to consider a reproductive option were mentioned as disadvantages. CONCLUSION: When weighing pros and cons, interviewees attach different importance to different arguments, based on personal and professional views. Professionals expect benefits from neonatal screening for Pompe disease, especially for early-onset cases. Some interviewees valued screening in later manifesting cases as well, while stressing the need for adequate support of pre-symptomatic patients and their families. Others considered the psychological burden and uncertainties regarding treatment as reasons not to screen.

Swiss national guideline for reimbursement of enzyme replacement therapy in late-onset Pompe disease.

Glycogen storage disease type II is a rare multi-systemic disorder characterised by an intracellular accumulation of glycogen due a mutation in the acid alpha glucosidase (GAA) gene. The level of residual enzyme activity, the genotype and other yet unknown factors account for the broad variation of the clinical phenotype. The classical infantile form is characterised by severe muscle hypotonia and cardiomyopathy leading to early death. The late-onset form presents as a limb girdle myopathy with or without pulmonary dysfunction. Enzyme replacement therapy (ERT) with recombinant human GAA (rhGAA) in infants is life saving. In contrast, therapeutic efficacy of rhGAA in the late-onset form is modest. High expenses of rhGAA, on-going infusions and poor pharmacokinetic efficacy raised a discussion of the cost effectiveness of ERT in late-onset Pompe disease in Switzerland. This discussion was triggered by a Swiss federal court ruling which confirmed the reluctance of a health care insurer not to reimburse treatment costs in a 67-year-old female suffering from Pompe disease. As a consequence of this judgement ERT was stopped by all insurance companies in late-onset Pompe patients in Switzerland regardless of their clinical condition. Subsequent negotiations lead to the release of a national guideline of the management of late-onset Pompe disease. Initiation and limitation of ERT is outlined in a national Pompe registry. Reimbursement criteria are defined and individual efficacy of ERT with rhGAA is continuously monitored.

The cost-effectiveness of enzyme replacement therapy (ERT) for the infantile form of Pompe disease: comparing a high-income country's approach (England) to that of a middle-income one (Colombia).

OBJECTIVES: Determining the cost-effectiveness of enzyme replacement therapy (ERT) for the classical infantile form of Pompe disease (complete acid a-glucosidase deficiency-related) in two different settings: England and Colombia. Pompe disease is very rare (1:40,000 births incidence). METHODS: A literature review was made and historic databases searched for National Health Service (NHS) reimbursed costs in England and by health insurers in Colombia; expert opinion was elicited. Two Markov models were constructed for comparing both countries; alive with symptoms and dead were the transition states used. Patients aged < 6 months receiving ERT were assumed to have 75 % survival rate and better health-related quality of life (HR-QoL) compared to those without treatment (0.700 HR- QoL using the EQ-5D scale). RESULTS: The incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) gained was £234,307.7 for England and £109,991 for Colombia. Uncertainty about Anal HR-QoL with ERT, disease progression and cost from palliative care had the biggest impact on the ICER in both models. If ERT costs were reduced to 10,000 times per dose and HR-QoL was 0.750-0.820 ICER, then £165,000 could be attainable for England and £65,000 for Colombia. Transaction costs per case in Colombia were high. CONCLUSIONS: ERT was more effective than no ERT in treating infantile Pompe disease, but high levels of uncertainty still remain about survival and progression rates and QoL in the long-run. ICERs were high compared to CE thresholds. Manufacturers' ERT costs and monopoly had a major impact on Anal CEA results.

[The 'Myozyme' decision of the Federal Supreme Court of Switzerland and German Law: a constitutional rights and health insurance law perspective]. / Die Myozyme-Entscheidung des Schweizerischen Bundesgerichts aus der Perspektive des deutschen Verfassungs- und Krankenversicherungsrechts.

In November 2010, the Federal Supreme Court of Switzerland dismissed a plea seeking reimbursement for treatment of glycogen storage disease type II - a very rare genetic metabolic disease also referred to as acid maltase deficiency (AMD) or Pompe disease -with a drug called 'Myozyme'. The Court held that the medication was not sufficiently effective or, alternatively, there was insufficient evidence for its effectiveness. The Court argued that the cost was out of balance with respect to the effects of the drug and concluded that it would be against the principle of legal equality if taxpayers were required to defray excessive expenses benefiting only an extremely small fraction of the population. Cost-effectiveness, however, cannot be accepted as a standard criterion governing the allocation of health insurance benefits because diversity of individual health must be regarded as a risk which nature has distributed equally among the members of the population. Therefore, it is a manifestation, rather than a violation, of the principle of legal equality that a public health insurance provider should pay for medical treatment in a particular case even if such treatment could not necessarily be administered to all other insured parties as well. At the same time, if cost-effectiveness in public health care is taken into account carefully, the risk of irrational resource allocation may be minimised. (As supplied by publisher).

The cost-effectiveness of enzyme replacement therapy (ERT) for the infantile form of Pompe disease: comparing a high-income country's approach (England) to that of a middle-income one (Colombia) / Costo-Efectividad de la terapia del reemplazo enzimático (TRE) para la forma infantil de la enfermedad Pompe: perspectiva económica comparativa de un país ingresos altos (Inglaterra) vs uno de ingresos medios (Colombia)

Objectives Determining the cost-effectiveness of enzyme replacement therapy (ERT) for the classical infantile form of Pompe disease (complete acid a-glucosidase deficiency-related) in two different settings: England and Colombia. Pompe disease is very rare (1:40,000 births incidence). Methods A literature review was made and historic databases searched for National Health Service (NHS) reimbursed costs in England and by health insurers in Colombia; expert opinion was elicited. Two Markov models were constructed for comparing both countries; alive with symptoms and dead were the transition states used. Patients aged < 6 months receiving ERT were assumed to have 75 % survival rate and better health-related quality of life (HR-QoL) compared to those without treatment (0.700 HR- QoL using the EQ-5D scale). Results The incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) gained was £234,307.7 for England and £109,991 for Colombia. Uncertainty about Anal HR-QoL with ERT, disease progression and cost from palliative care had the biggest impact on the ICER in both models. If ERT costs were reduced to 10,000 times per dose and HR-QoL was 0.750-0.820 ICER, then £165,000 could be attainable for England and £65,000 for Colombia. Transaction costs per case in Colombia were high. Conclusions ERT was more effective than no ERT in treating infantile Pompe disease, but high levels of uncertainty still remain about survival and progression rates and QoL in the long-run. ICERs were high compared to CE thresholds. Manufacturers' ERT costs and monopoly had a major impact on Anal CEA results.

Objetivo Determinar la costo-efectividad de la TRE como indicación para la forma clásica de la enfermedad de Pompe (relacionada con deficiencia completa de a-glucosidasa ácida) desde dos perspectivas, Inglaterra y Colombia. La enfermedad de Pompe es muy rara (incidencia 1:40000 nacimientos). Métodos Revisiónbibliográfica y bases de datos para calcular costosasociados al tratamiento en NHS en Inglaterra, aseguradores de salud en Colombia y opinión de expertos. Dos procesos de Markov fueron construidos para comparar entre países; los estados de transición fueron: vivo sintomático y fallecido. En pacientes de < 6 meses de edad con TRE, se asume un incremento de 75 % de sobrevida y mejor calidad de vida comparada con los que no reciben TRE (HR-QoL 0.700 usando EQ-5D). Resultados Inglaterra alcanzo ICER por QALY ganado £234307, 7 y Colombia £109991. Incertidumbre sobre HR-QoL con TRE, progresión de enfermedad y costo de cuidado paliativo tuvieron el mayor impacto en losICERs;sí el costo de TREfuera 10.000 menor y la HR-QoLalcanzara 0.750-0.820 ICERs de £165000y £65000 podrían obtenerse para Inglaterra y Colombia respectivamente. Los costos transaccionales en Colombia son representativos. Conclusiones La TRE es más efectiva que no dar tratamiento, pero incertidumbre sobre tasas desobrevida, progresión y HR-QoLpermanecen en el largo plazo. Los ICERsson altos comparados a los umbrales establecidos de CE. Los costos de TRE y el podermonopolístico del fabricante tienen un impacto importante en los resultados Anales de CEA. Investigación adicional debe realizarsea futuro.

Burden of illness of Pompe disease in patients only receiving supportive care.

BACKGROUND: Pompe disease is an orphan disease for which enzyme replacement therapy (ERT) recently became available. This study aims to estimate all relevant aspects of burden of illness--societal costs, use of home care and informal care, productivity losses, and losses in health-related quality of life (HRQoL)--for adult Pompe patients only receiving supportive care. METHODS: We collected data on all relevant aspects of burden of illness via a questionnaire. We applied a societal perspective in calculating costs. The EQ-5D was used to estimate HRQoL. RESULTS: Eighty adult patients (87% of the total Dutch adult Pompe population) completed a questionnaire. Disease severity ranged from mild to severe. Total annual costs were estimated at 22,475 (range 0-169,539) per adult Pompe patient. Patients on average received 8 h of home care and 19 h of informal care per week. Eighty-five percent of the patients received informal care from one or more caregivers; 40% had stopped working due to their disease; another 20% had reduced their working hours. HRQoL for Pompe patients who only received supportive care was estimated at 0.72, 17% lower than the Dutch population at large. CONCLUSIONS: Adult Pompe disease is associated with a considerable burden of illness at both the societal and patient levels. The disease leads to substantial costs and dependency on medical devices, home care, and informal care, and has a high impact on the patient's social network. In addition, patients are limited in their ability to work and have significantly reduced HRQoL.