Marc Dooms

Cost-Effectiveness Assessment of Orphan Drugs

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. …

Orphan Drugs for Rare Diseases

Orphan drugs are intended for diseases with a very low prevalence, and many countries have implemented legislation to support market access of orphan drugs. We argue that it is time to revisit the special market access status of orphan drugs. Indeed, evidence suggests that there is no societal preference for treating rare diseases. Although society appears to assign a greater value to severity of disease, this criterion is equally relevant to many common diseases. Furthermore, the criterion of equity in access to treatment, which underpins orphan drug legislation, puts more value on health improvement in rare diseases than in common diseases and implies that population health is not maximized. Finally, incentives for the development, pricing and reimbursement of orphan drugs have created market failures, including monopolistic prices and the artificial creation of rare diseases. We argue that, instead of awarding special market access status to orphan drugs, there is scope to optimize research and development (R&D) of orphan drugs and to control prices of orphan drugs by means of, for example, patent auctions, advance purchase commitments, pay-as-you-go schemes and dose-modification studies. Governments should consider carefully the right incentive strategy for R&D of orphan drugs in rare diseases.

Drugs for rare diseases: influence of orphan designation status on price.

The literature indicates that the expenditure on orphan drugs will be increasing over the coming years. The market for orphan drugs has inherent market characteristics that sometimes result in high prices. The aim of this study was to analyse whether awarding orphan designation status has an influence on the price setting of drugs for rare disease indications. To this effect, prices of designated orphan drugs were compared with other non-designated drugs for rare disease indications. We identified 28 designated orphan drugs and 16 comparable non-designated drugs for rare disease indications for which we collected official hospital prices (per defined daily dose) in Belgium in 2010. Orphan-designated drugs had a higher median price (€138.56 [interquartile range; IQR €406.57]) than non-designated drugs (€16.55 [IQR €28.05]) for rare disease indications (p < 0.01). In conclusion, our results suggest that awarding orphan designation status in itself is associated with higher prices for drugs for rare disease indications. In order to gain full insight into orphan drug pricing mechanisms, future research should focus on collecting information about the different factors influencing orphan drug pricing.

Allergic contact dermatitis from fragrance components in specific topical pharmaceutical products in Belgium

Objectives:  To determine which topical pharmaceutical products marketed in Belgium contain fragrances and to examine the nature of the fragrance allergens in specific pharmaceutical products having caused iatrogenic contact dermatitis.

Computer assisted monitoring of contact dermatitis patients

All contact dermatitis patients are told to avoid their specific allergens. As regards topical pharmaceutical agents, however, it is almost impossible for these patients to identify the products that contain their allergens. In order to provide reliable information for these patients, we have designed a computer assisted data system, The CODEX (COntact DErmatitis indeX) system consists of three computer readable files: a Product File containing the complete composition of the pharmaceutical products an the Belgian market that arc applied on the skin and the mucous membranes, a Patient File with the patients anamnesis, and a Literature File with cross‐referenced material on contact dermatitis. Each patient is given a list of the products that contain his/her allergen(s). The data bases are analyzed statistically and updated periodically. Cosmetics in general are excluded.

Orphan Drugs for Rare Diseases: Grounds for Special Status

Strategy, Management and Health Policy Enabling Technology, Genomics, Proteomics Preclinical Research Preclinical Development Toxicology, Formulation Drug Delivery, Pharmacokinetics Clinical Development Phases I‐III Regulatory, Quality, Manufacturing Postmarketing Phase IV

UV sunlight and patch test reactions in humans

No seasonal influence of UV sunlight on patch test reactions in humans over a period of 9 year, of clinical practice was found in this retrospective study of almost 8OOO patients. Although the mean U V monthly dose varies seasonally, up in the summer and down in the winter, no significant differences could be identified for patch test reactions, either for the mean number of positive test reactions or for the intensity of the skin reaction or for the id‐like spread reactions seen in summer or winter. Furthermore, no short‐term influences of UV exposure during the weekend preceding patch testing could be demonstrated. Therefore, reliable patch‐test results can be expected at any season of the year from a general population, at least in Belgian‐type climates.

Do we need authorized orphan drugs when compounded medications are available

What is known and Objective:  Orphan drugs are used to diagnose, prevent or treat a rare disease. This Commentary aims to present a number of case studies questioning the need for designating compounded medications with a long history of effective use, which is well‐supported by published clinical evidence.

Zinc ricinoleate: sensitizer in deodorants

Isobutyl ketone). Both products were further diluted m acetone (2) to obtam concentrations (50% to 1 %) for testing. Acetone, xylene, butylphenol-formaldehyde resm (I% pet.), formaldehyde (I% aq.) and paratertiary-butylphenol (PTBP) (I% pet.) were also tested. The pigment, methylisobutylketone (MIBK) and ethylene-glycol monoethyl ether were not available. 10 control patients were tested With Chemosil 211 and phenol formaldehyde (8% m MIGK) m the concentrations mdicated m Table I.

Are some orphan drugs for rare diseases too expensive? A study of purchase versus compounding costs

Hospital purchase prices substantially exceed compounding production costs in Belgium for selected orphan drugs that had low costs of research and development and market access procedures. As a result, healthcare payers seem to be paying too much for these orphan drugs and there are arguments for price reductions. Pharmacies can consider compounding, rather than purchasing, these orphan drugs.