Drugs for exceptionally rare diseases: do they deserve special status for funding?

Abstract

Ultra-orphan drugs are medicines used to treat exceptionally rare diseases that are chronically debilitating or life-threatening. Low patient numbers make it difficult for pharmaceutical companies to recoup research and development costs, and consequently these medicines are generally expensive on a per patient basis. European Union (EU) regulations promote the development of orphan drugs; but to contain costs, some EU healthcare systems assess the cost-effectiveness of therapies when deciding if they should be funded. As ultra-orphan drugs are invariably cost-ineffective, factors in addition to cost-effectiveness need to be considered if ultra-orphan drugs are to be provided by public health services. Health service funding of ultra-orphan drugs, which varies across the EU and within the UK, has led to geographical inequities in patients' access to treatment. In some instances, support for these drugs would appear to have been approved on the basis that diseases that are rare and severe are a special case. We explore whether ultra-orphan drugs merit special status by considering efficiency, effectiveness and equity criteria. Mechanisms are discussed for creating a policy that would reduce geographical inequalities in provision across Europe.

A discrete choice experiment investigating preferences for funding drugs used to treat orphan diseases: an exploratory study

“…2 Such policies require that "orphan treatments" be defined. The Orphan Designation procedure at the EMEA, states that to qualify a medicine must meet two conditions: a) the medicinal product is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition that either affects less than 1 in 2,000 individuals; or that without incentives is unlikely to generate sufficient return on investment to justify the expenditure and b) there is an absence of solution or the drug brings a significant benefit compared to the present situation (Denis et al, 2009). even if treatment does not offer the largest health gain for its cost (Hughes et al, 2005). The rule-of-rescue principle asserts that society should come to the aid of those facing immediate, often life-threatening danger.…”

“…Hughes et al (Hughes et al, 2005), argue that orphan diseases are not inherently life-threatening, although many are debilitating and reduce life-expectancy. McCabe et al (2006) characterize arguments based on the rule-of-rescue as emotional reactions to identifiable individuals in catastrophic events, but that unknown patients will become identifiable in the future and hence it is an ethically invalid principle for policy-making.…”

“…But perhaps the most common objection to setting higher costeffectiveness thresholds for orphan drugs derive from the principle of maximizing the health gain achieved with society's limited health care resources (Schlander, 2008). The opportunity cost of such a policy is larger health losses among those who suffer from common, highly prevalent diseases (Dear et al, 2006;Hughes et al, 2005;McCabe et al, 2006). This debate has proceeded in a virtual vacuum of evidence regarding the views of the public regarding such a special status for drugs used to treat orphan diseases.…”

Economic evaluation in the context of rare diseases: is it possible?

“…Still, these policies do not guarantee demand, since they do not require reimbursement for treatment at any price offered by the companies. Each country has clear rules on the incorporation of the technologies into their social protection systems, and some consider incremental cost-effectiveness ratios in addition to clinical evidence 19 .…”

Using Value-of-Information Methods when the Disease Is Rare and the Treatment Is Expensive—The Example of Hemophilia A

“…Furthermore, in some cases, even when cost-effectiveness is near acceptable threshold values, there is a great deal of parameter uncertainty, and a drug or technology may receive conditional funding with the option to revise as new evidence becomes available. 3,4 Considering the difficulties in conducting research in rare diseases, future trials should be designed to maximize the difference between the expected value of the information provided by the results and the expected costs of the trial. The traditional tests of hypothesis and power considerations …”