what should be done on the issue of orphan drugs to combat high costs without viable alternatives

Orphanet J Rare Dis. 2011; vi: 42.

Pricing and reimbursement of orphan drugs: the demand for more transparency

Steven Simoens

¹Inquiry Middle for Pharmaceutical Care and Pharmaco-economics, Katholieke Universiteit Leuven, O&N2 bus 521, Herestraat 49, 3000 Leuven, Kingdom of belgium

Received 2011 Feb 22; Accustomed 2011 Jun 17.

Abstract

Pricing and reimbursement of orphan drugs are an issue of loftier priority for policy makers, legislators, wellness care professionals, industry leaders, academics and patients. This study aims to conduct a literature review to provide insight into the drivers of orphan drug pricing and reimbursement.

Although orphan drug pricing follows the same economic logic every bit drug pricing in general, the monopolistic power of orphan drugs results in high prices: a) orphan drugs do good from a period of marketing exclusivity; b) few culling health technologies are available; c) tertiary-party payers and patients have limited negotiating power; d) manufacturers attempt to maximise orphan drug prices within the constraints of domestic pricing and reimbursement policies; and e) substantial R&D costs need to be recouped from a pocket-size number of patients.

Although these conditions apply to some orphan drugs, they do not apply to all orphan drugs. Indeed, the minor number of patients treated with an orphan drug and the limited economic viability of orphan drugs can exist questioned in a number of cases. Additionally, manufacturers have an incentive to game the arrangement by artificially creating monopolistic market place conditions.

Given their high toll for an often modest effectiveness, orphan drugs are unlikely to provide value for money. However, additional criteria are used to inform reimbursement decisions in some countries. These criteria may include: the seriousness of the disease; the availability of other therapies to treat the disease; and the cost to the patient if the medicine is non reimbursed. Therefore, the maximum toll per unit of measurement of outcome that a health care payer is willing to pay for a drug could exist fix higher for orphan drugs to which society attaches a high social value.

There is a need for a transparent and evidence-based approach towards orphan drug pricing and reimbursement. Such an approach should exist targeted at demonstrating the relative effectiveness, cost-effectiveness and economic viability of orphan drugs with a view to informing pricing and reimbursement decisions.

Background

A rare disease is a illness with a very low prevalence. In the European Union (EU), rare diseases are defined as life-threatening or chronically debilitating diseases with a prevalence of 5 out of x,000 individuals or less [1]. The European union defines an orphan drug as either a medicinal production intended for a life-threatening or chronically debilitating rare affliction or a medicinal product that would not be developed without incentives considering its sales are unlikely to generate sufficient render on investment. An additional requirement to qualify as an orphan drug is that no satisfactory method exists to diagnose, prevent or care for the disease or, if such a method exists, that the medicinal product will exist of significant benefit to those affected by that disease [1].

The EU implemented specific policies in 2000 to stimulate innovation in the field of orphan drugs [1]. Manufacturers that accept an orphan designation (i.e. the accolade of orphan status to a drug) for a medicinal product benefit from: a) protocol help (scientific advice during the product evolution phase); b) straight access to the European Drugs Bureau (EMA) Centralised Procedure with respect to registration; c) ten-year marketing exclusivity starting from the date of marketing authority (i.due east. the approving to market place a drug); and d) fiscal incentives (fee reduction or exemptions, possible assistance with research and development). Orphan drug policies can be considered a success as the number of orphan designations and marketing authorizations granted by EMA increased from 270 designations and 22 authorizations by the end of 2005 to 805 designations and 61 authorizations past April 2011 [2].

Whereas decisions surrounding orphan designation and marketing authorization of orphan drugs are taken at the EU level, decisions governing pricing and reimbursement of orphan drugs are a member land responsibleness. As a outcome, evidence requirements, pricing and reimbursement policies governing orphan drugs differ between countries; thereby creating differences in admission to, prices and utilization of orphan drugs between countries [3].

Although a detailed discussion of differences between drugs for rare diseases and for mutual diseases falls outside the scope of this article, the reader should annotation that the features of rare diseases and orphan drugs brand them an outcome of high priority for policy makers, researchers, legislators, health care professionals, manufacture leaders, patients and involvement groups. For instance, the present EU organization of orphan designation allows for drugs for non-orphan diseases to be designated as orphan drugs. The economic factors underlying orphan designation can be questioned in some cases as a low prevalence of a certain indication does not equal a low render on investment for the drug across its indications. High-quality evidence near clinical added value of orphan drugs is rarely available at the time of marketing authorization due to the low number of patients. Moreover, economic evaluations tend to notice that orphan drugs are not price-constructive considering the incremental toll for the additional wellness benefit provided past the orphan drug is usually high. Finally, given the loftier price of orphan drugs, policy makers are faced with an increasing proportion of pharmaceutical expenditure being spent on orphan drugs [4]. The aim of this study is to acquit a review of the international scientific literature to provide insight into two policy aspects surrounding rare diseases and orphan drugs, i.e. the pricing and reimbursement of orphan drugs. In dissimilarity with a recent study from the industry perspective [5], this review addresses pricing and reimbursement of orphan drugs mainly from the health care payer perspective.

Pricing

Pricing of orphan drugs follows the aforementioned economic logic equally drug pricing in full general: the toll of an orphan drug is fix by a manufacturer in an effort to compensate research and development (R&D) costs and to accomplish a certain profit margin. Additionally, the price takes into business relationship the value of the product to the patient, market place conditions (e.g. the existence of culling health technologies) and the regulatory pricing and reimbursement environment in a country. However, the market for orphan drugs has inherent marketplace failures, thus resulting in high prices due to a number of reasons.

Monopoly

In the Eu, orphan drugs benefit from a period of marketing exclusivity following marketing authorization. Marketing exclusivity gives a monopoly to the manufacturer equally no other company is allowed to market place the orphan drug during the exclusivity menstruation. The monopolistic power is strengthened by the fact that no alternative health technology exists for many orphan drugs. Additionally, marketing can farther heave marketplace power. Under these conditions, manufacturers have an incentive to charge the maximum cost for an orphan drug that the marketplace is able to bear. Health intendance payers have limited negotiating ability, often lack data about the cost structure of orphan drugs, and are under pressure from patient advocacy groups and media to accommodate new orphan drugs [half-dozen]. Every bit a result, health intendance payers are often forced to accept the price offered by the manufacturer.

For instance, a contempo study compared prices of 28 designated orphan drugs with prices of xvi comparable non-designated drugs for rare disease indications [7]. Cost data were based on official hospital prices (per defined daily dose) in Belgium in 2010. Orphan-designated drugs had a higher median price (€ 138.56 - IQR € 483.06) than non-designated drugs (€ sixteen.55 - IQR € 28.67) for rare illness indications (p < 0.01). The authors ended that awarding orphan designation status in itself is associated with college prices for drugs for rare affliction indications.

Manufacturers can attempt to create a monopoly market by splitting upwards a disease into several sub-diseases that qualify as rare diseases (a practice chosen 'disease sub-setting', 'salami-slicing' or 'disease stratification') [viii]. In other words, artificial sub-sets of a common disease are created with a view to qualifying as several rare diseases. The domains of for instance pharmacogenomics and oncology are prime targets for creating new rare diseases [9]. Disease stratification may take many benefits for a manufacturer: the company can benefit from measures to stimulate the development of its products, the company creates a monopolistic market where chronically ill patients receive long-term treatment with its orphan drug, the visitor incurs lower marketing costs as it needs to accomplish fewer medical specialists, marketing exclusivity erases the possibility of 'me-too' competitors, and the small market place reduces the economic viability for generic drugs [10].

The touch on of monopolistic market place power on prices tin too exist witnessed in the observation of toll increases when a drug with a common indication receives a second, orphan indication. This can be illustrated with the example of sildenafil in Kingdom of belgium: the orphan drug Revatio^®for pulmonary arterial hypertension was more than than six times more expensive than Viagra^®for erectile dysfunction in 2011.

In the EU, multiple orphan drugs can be authorised to diagnose, foreclose or treat a specific rare disease. As a issue, the monopolistic power of an orphan drug is sometimes offset past the availability of other products and competitive pressures may reduce prices. For instance, advanced renal cell carcinoma and cystic fibrosis each have x drugs with designated orphan condition [11]. Using available data on the annual cost per patient of reimbursed orphan drugs in Belgium and the availability of alternative health technologies [4], 13 orphan drugs with an alternative had a lower annual cost per patient than 9 orphan drugs without an alternative, although this finding was not statistically pregnant (independent samples t-examination; p = 0.183).

Price variation betwixt countries

A study compared prices of ten orphan drugs betwixt 25 European union countries [3]. Price data originated from pharmaceutical industry, wellness government, retail or hospital pharmacies, and national databases. The authors noted that some domestic pricing and reimbursement policies provide incentives to maximise prices of orphan drugs. Countries that adhere to free market place pharmaceutical pricing generally accept higher drug prices and, thus, college prices for orphan drugs (e.g. Germany) than countries that regulate prices (east.thou. Portugal, Spain). Prices of orphan drugs distributed through the hospital pharmacy are not regulated in most European countries, but are negotiated betwixt the manufacturer and an individual hospital. To accept a stronger negotiating position, some hospitals jointly purchase orphan drugs from manufacturers. Also, countries such equally Kingdom of belgium, Hellenic republic and Italy have imposed price controls on orphan drugs distributed through the hospital pharmacy. Manufacturers are free to set prices of orphan drugs in the Britain, although the Pharmaceutical Price Regulation Scheme (which regulates industry profitability rather than drug prices) [12] and pharmaco-economic guidelines exert downward pressure on prices of orphan drugs. Although the National Institute for Health and Clinical Excellence in England does non frequently assess orphan drugs, the Scottish Medicines Consortium and the All Wales Medicines Strategy Group do assess orphan drugs, with the latter for example having specific guidelines for appraising orphan drugs and ultra-orphan drugs [thirteen]. In France, the system of authorization for temporary utilize allows manufacturers to freely set and maximise the price for an orphan drug which will exist fully reimbursed.

Costs of R&D and market access

The high price of orphan drugs as well derives from the cost of the R&D process and of market access procedures. R&D of drugs is a very expensive process associated with a high attrition charge per unit of potential products. Furthermore, in the case of orphan drugs, these R&D costs need to exist recouped from a small number of patients, thus resulting in high conquering costs per patient [14]. A European analysis of orphan drug prices in 25 countries found that the cost of an orphan drug is higher for a disease with a lower prevalence [3]. Using published data on the annual cost per patient of an orphan drug in Belgium [4] and the prevalence of the rare disease as derived from Orphanet [15], Effigy 1 points to a negative clan between the cost of an orphan drug and the prevalence of the affliction (y = 26230x^-0,5316; R²= 0.468). A like inverse association has too been observed using Italian data [16].

An external file that holds a picture, illustration, etc. Object name is 1750-1172-6-42-1.jpg

Association between annual Belgian price per patient of an orphan drug and disease prevalence.

However, the need to recoup substantial R&D costs from a small number of patients does not apply to all orphan drugs. Some orphan drugs were approved on the basis of historical apply, where the manufacturer was not required to produce new evidence on efficacy to proceeds marketing potency. In such cases, R&D costs are pocket-sized. The provision to license drugs without much industry-investment in clinical trials tin can be illustrated with the case of amifampridine (iii,4-diaminopyridine phosphate), which is approved for Lambert-Eaton syndrome. The clinical evidence underpinning this orphan drug primarily referred to the literature on the costless base of operations form of iii,4-diaminopyridine [17].

With respect to market access procedures, a recent written report showed that orphan drugs were less likely to gain marketing authorization from EMA than other drugs [eighteen]. Furthermore, manufacturers take to comply with different pricing and reimbursement procedures in each member land, thereby raising the price of orphan drugs [ten]. Another commuter of orphan drug prices occurs following marketing say-so. As many orphan drugs are fast-tracked to market say-so (due to, for instance, the life-threatening nature of the illness and the absence of culling health technologies), regulatory authorities tend to impose expensive postal service-marketing surveillance programmes.

Many orphan drugs target few patients as they are used to treat rare or ultra-rare diseases, the prevalence of which is by and large sick-researched. Also, not all patients are diagnosed or need treatment [5]. Nevertheless, the assertion that orphan drugs target few patients does not utilize to all cases [xix]. First, certain orphan drugs have proved to be effective confronting multiple rare diseases and, thus, target a larger number of patients. Examples are sorafenib, which has been approved by the EMA to treat patients with hepatocellular carcinoma and advanced renal cell carcinoma; and imatinib, which has half-dozen designated orphan indications in the European union. Second, the use of an orphan drug for a rare illness may subsequently be extended to a mutual illness. Bosentan, an orphan drug for the treatment of pulmonary arterial hypertension, may besides be effective to treat eye failure [twenty]. Third, a drug for a common affliction may subsequently develop an indication for a rare disease. An case is sildenafil, whose initial indication of erectile dysfunction was afterward extended to include pulmonary artery hypertension and chronic thromboembolic pulmonary hypertension. Fourth, while a disease may authorize equally a rare affliction in 1 land, it may be more mutual in other countries (eastward.g. drugs to treat tropical diseases). Furthermore, a common disease in 1 land (eastward.m. Balkan nephropathy) may qualify equally a rare illness at EU level [11]. Finally, although these diseases are individually rare, rare diseases collectively touch on approximately 30 1000000 Europeans [6].

Economical viability

Legislation in the EU attempts to address the issue of the price and the economic viability of orphan drugs. Eu legislation is in place to reduce the period of marketing exclusivity if an orphan drug turns out to be sufficiently profitable [1]. However, information technology is not clear what is meant by 'sufficiently profitable' and this legislation has never been put into practise. The lack of economic viability of orphan drugs can be questioned in certain cases. Some orphan drugs probably exercise not crave a loftier level of investment to market place the drug. For instance, the costs of extending the indication of sildenafil to pulmonary avenue hypertension and chronic thromboembolic pulmonary hypertension are probable to be limited to conducting clinical trials and to marketing.

Orphan biopharmaceuticals

Many orphan drugs (in evolution) are made by or derived from living organisms using biotechnology. A study focused on ex-manufacturer prices of biopharmaceuticals in 5 European countries (France, Germany, Italy, Spain, and the United kingdom), Australia, Canada, Japan, Mexico, and the United States [21]. The authors argued that biopharmaceutical prices may exist less regulated and higher than those of chemically-derived drugs given that: a) some countries exclude biopharmaceuticals used in hospital from toll regulation; b) price comparisons with other products in a therapeutic class are less likely to occur for biopharmaceuticals with a novel mechanism of action or indication; c) informal cost-effectiveness thresholds may be higher for biopharmaceuticals that address unmet clinical needs or that treat rare diseases; and d) some countries have in place industrial policies to support the evolution of biopharmaceuticals.

When the 20-year patent on a biopharmaceutical expires, less expensive versions of the drug, so-chosen biosimilar drugs or follow-on biologics, can enter the market. Orphan biopharmaceuticals tend to confront express contest from biosimilars due to difficulties in and the costs of demonstrating bio-similarity. To substantiate the claim of biosimilarity in Europe, the manufacturer must deport a direct and extensive comparability exercise between the biosimilar and the reference biopharmaceutical, with a view to demonstrating that the two products accept similar quality, safety and efficacy.

Reimbursement

Economic evaluation of orphan drugs

Testify derived from economical evaluations is used to inform pharmaceutical reimbursement (and/or pricing) decisions in many countries. The economic evaluation of orphan drugs is inhibited by the being of oftentimes limited and weak clinical data at launch fourth dimension. In the context of rare diseases, it may prove hard to recruit a sufficient number of patients and medical centers in clinical trials, thus raising costs. Orphan drug trials (in for example the field of oncology) may be halted early on upstanding grounds when an interim analysis demonstrates clinical superiority of the orphan drug in terms of an intermediate outcome mensurate such as progression-free survival. It has been recommended to allow greater use of surrogate outcome measures for orphan drugs if clinical data are incomplete, but impose at the same time a commitment to continue research [22].

A primal component of this approach is the commitment to ongoing evaluation through, for example, patient registries of rare diseases designed to collect the necessary information to follow up and evaluate uncertainties surrounding the longer-term effectiveness and cost-effectiveness of orphan drugs used in the treatment of rare diseases [23]. Setting up patient and affliction registries is part of Eu policy and is an action line in rare disease plans that many member states accept in place or are setting up. The use of patient registries would support the controlling process, inform clinical practice, and could provide information almost long-term agin events.

All the same, patient registries of rare diseases have their limitations. A patient registry may be biased if the patient etiology and illness severity change over time. Too, patient registries tend to collect data on a specific orphan drug used in the handling of a rare illness, but non on alternative treatments, thus providing partial data to summate the cost-effectiveness of the orphan drug relative to an alternative treatment. Furthermore, new treatment strategies may become available during the menstruum covered past the registry. Therefore, patient registries of rare diseases need to exist set in a flexible way to collect sufficient data and to account for the evolution in patient population and treatment strategies over their lifecycle.

Societal considerations

Given their high cost for an oftentimes modest effectiveness, orphan drugs are unlikely to provide value if their cost-effectiveness ratio is compared to a fixed threshold value (e.m. the threshold of £20,000-£30,000 per QALY used by Nice in England and Wales [24]) [14]. This raises the question of whether club needs to provide incentives to pharmaceutical industry to develop orphan drugs when the costs surpass the value that society attaches to the health benefits produced by orphan drugs [25]? In order to reply this question, it has been argued that other societal considerations may thing when evaluating an orphan drug, such as the observation that orphan drug reimbursement conforms to the principle of social solidarity in which vulnerable groups receive support; that orphan drugs tend to target life-threatening diseases for which there may exist no alternative therapy; and that orphan drugs take a considerable bear upon on patients' wellness care expenditures if they would have to incur the drug costs themselves. For example, the Pharmaceutical Benefits Advisory Committee in Australia is reported to take into account such societal considerations [26].

How can these various considerations be aggregated? In other words, how tin can the often loftier cost-effectiveness ratio, weak clinical data, small health benefit, loftier cost and absence of an alternative therapy for orphan drugs be taken into account in a payer's conclusion to cover such a drug? Information technology has been argued that the threshold ICER should be college for drugs to which guild attaches a high social value [14]. Alternatively, equity weights could be applied to outcome measures according to disease prevalence [27]. Methodological guidance issued by NICE in January 2009 stated that weights should consider the uncertainty surrounding the evidence of the drug'southward clinical effectiveness and the value that patients place on additional months of life [28]. Weighted outcomes would increase the health gain achieved by an orphan drug, so that there is a higher probability that an orphan drug has an ICER below the threshold value. Nonetheless, to the best of the author's knowledge, this arroyo has non been practical in practice yet.

Orphan drugs may attract a loftier social value, although more research is needed to elicit social values ascribed to orphan drugs and to rare diseases [25]. A literature review has indicated that society attaches a higher value to health improvements experienced by patients who have worse lifetime wellness prospects [29]. In 2005, Squeamish in England and Wales set up a Denizen's Council with a view to identifying criteria that the National Health Service may use to value orphan drugs more than highly [30]. The height 3 criteria were the caste of severity of the disease, whether treatment achieved more than than but stabilize the disease, and whether the illness was life-threatening. Fourscore percentage of the Council indicated that illness severity might be a reason to pay a premium for drugs, but affliction rarity was not. A Norwegian report explored whether a societal preference existed for giving priority to the handling of rare diseases and for accepting a higher threshold ICER for orphan drugs [31]. Although respondents supported equal treatment rights for patients with rare diseases, no societal preference for rarity existed if treatment of rare diseases implied that patients with common diseases could not be treated in the context of a finite budget.

The relevance of societal considerations tin be illustrated with several orphan drug decisions made by the Medicine Reimbursement Committee in Belgium and Overnice in England and Wales. A Belgian study reviewed reimbursement dossiers of 26 orphan drugs submitted between January 2002 and June 2008 [four]. Reimbursement was awarded to 22 orphan drugs. The Medicine Reimbursement Commission brash to reimburse 19 drugs and reimbursement was approved by the Minister of Social Affairs. Although the Commission did not result an advice relating to one drug, reimbursement was approved by the Minster of Social Affairs. For the remaining two orphan drugs, the dossiers indicated that both the Medicine Reimbursement Committee and the manufacturer proposed a number of elements for negotiation - including a toll decrease, employment opportunities, restrictions on the size of the patient population, the funding of diagnostic tests past the company, a reduction of the dosage - which may accept played a role in awarding reimbursement. The rationale for not granting reimbursement to iv orphan drugs may exist related to the high cost of these drugs in comparison with alternative drugs or the existence of other non-orphan indications of the drug.

Despite an unfavorable cost-effectiveness ratio, Squeamish approved imatinib for the treatment of chronic myeloid leukaemia with an ICER of £37,000 per QALY in the chronic phase, £38,400 per QALY in the accelerated phase and £49,000 per QALY in the smash phase in the absenteeism of any effective alternative therapy (except for bone marrow transplantation) and on equity grounds [32]. A second example relates to enzyme replacement therapy for Fabry's affliction. An economic evaluation stated that, although the ICER of enzyme replacement therapy is at to the lowest degree six times higher than the threshold value adopted by Overnice, clinicians and manufacturers argued that the National Health Service had no pick but to provide this therapy considering Fabry's illness is a rare disease [33].

Innovative mechanisms accept been proposed for the reimbursement of orphan drugs. Risk-sharing arrangements are schemes in which the manufacturer shares the take chances with the health care payer that the product may not be constructive for a particular patient. If the product does non take the expected effect, the company may loose some or all product revenue, or needs to provide a replacement product [34]. Such arrangements are instituted at the level of a defined patient population, may require physicians to be trained in the advisable utilize of the drug, and necessitate the implementation of a tracking system to follow up its use. For case, the Scottish Medicines Consortium has in place an Orphan Medicines Take chances Share scheme [35]. Medicines included in the risk share scheme are agalsidase alpha and beta for Fabry's disease; imiglucerase and miglustat for type 1 Gaucher's illness; and iloprost for pulmonary arterial hypertension. In England and Wales, NICE has instituted a risk-sharing scheme for the supply of interferon beta and glatiramer acetate which incorporated agreed target handling furnishings for patients with multiple sclerosis [36]. If handling effects were not accomplished, the scheme included the selection to reduce the drug price to guarantee its cost-effectiveness at a threshold value of £36,000 per QALY. However, some concerns with this scheme accept recently been identified [37] and some take argued that the money should be better allocated to funding a randomized controlled trial of interferon beta [27].

Discussion

In general, the monopolistic power granted to orphan drugs results in high prices. Although these atmospheric condition apply to some orphan drugs, it should be emphasised that they do non use to all orphan drugs. This study has demonstrated that the small number of patients treated with an orphan drug and the limited economic viability of orphan drugs can be questioned in a number of cases. Additionally, manufacturers have an incentive to game the system by artificially creating monopolistic market conditions.

Therefore, there is a demand to assess orphan drugs on an private basis to make up one's mind whether their specific features warrant high prices. This cess should take into account current and planned indications, the existence of alternative wellness technologies, the total number of patients beyond registered and off-label indications, and R&D costs. Health care payers could impose the requirement to justify the toll based on detailed information about the R&D costs and return on investment at a global level. This could exist accompanied by regular monitoring throughout the product's lifecycle. Such an approach necessitates that health intendance payers brand a subjective judgement well-nigh an appropriate level of return on investment.

A number of mechanisms to optimise R&D of orphan drugs and to control prices of orphan drugs have been proposed [38]. Auctions of patents take been suggested equally a way to reward manufacturers for successfully developing a new orphan drug. Advance buy commitments entail that the health care payer agrees to pay a specific toll for a specified number of units of an orphan drug, thereby guaranteeing a minimum reward for the innovator. Nether pay-equally-you lot-go schemes, the health care payer provides additional rewards as a potential drug candidate progresses through the R&D process. Authorities should consider carefully the correct incentive strategy for R&D of orphan medicines in rare diseases.

Several European countries have put in place government intervention in rare illness and orphan drug markets with a view to continue downward prices, restrict public reimbursement and promote a toll-effective utilise of orphan drugs [4]. For instance, Belgium, French republic, Italy and the Netherlands compare the price requested by the manufacturer with the price in other countries. The Great britain has set up a organisation of profit control to constrain prices (although this system will be abolished in favour of a value-based pricing arroyo from 2013/fourteen) and Sweden uses a system of public procurement at the regional level in order to maximise price contest.

To gain reimbursement, a formal economical evaluation needs to be performed in some, but not all European countries. Information technology should exist noted that national authorities tend to demand data on the effectiveness of orphan drugs in a real-globe setting rather than on their efficacy in a structured setting. Also, equally the cost-effectiveness of an orphan drug is calculated relative to a relevant comparator, there is a demand for comparative data. Both factors have implications for the blueprint of patient and disease registries. For orphan drugs that provide a first-in-class therapy for unmet clinical needs, the cost-effectiveness tin be calculated on the basis of studies comparing the orphan drug with placebo. For orphan drugs that are marketed in the presence of competitor health technologies, in that location is a need to compute the cost-effectiveness based on head-to-head studies of the orphan drug relative to a relevant comparator.

Conclusions

This study has identified and discussed several factors affecting pricing and reimbursement of orphan drugs. There is a demand for a transparent and bear witness-based approach towards pricing and reimbursement of orphan drugs. Such an approach should be targeted at demonstrating the relative effectiveness, cost-effectiveness, cost construction and economic viability of orphan drugs with a view to informing pricing and reimbursement decisions.

Competing interests

The author has no conflicts of interest that are relevant to the content of this manuscript.

Authors' contributions

SS designed the study, carried out the literature review and drafted the manuscript.

Acknowledgements

Fiscal support for this inquiry projection was received from the Royal Baudouin Foundation. The sponsor was not involved in the design of the study; the conduct of the literature review; or the writing of the manuscript. The publication of the study was non contingent on the sponsor'due south approval or censorship of the manuscript.

References

European Commission. Regulation (EC) No 141/2000 of the European Parliament and the Quango of 16 December 1999 on orphan medicinal products. Official Journal of the European Communities. 2000. L 18/1.
Orphanet. The portal for rare diseases and orphan drugs. Orphanet. 2011. pp. ix–5. 2011. Ref Type: Electronic Commendation.
Alcimed. Report on orphan drugs. Phase I: overview of the conditions for marketing orphan drugs in Europe. Koning Boudewijnstichting. 2006. pp. xviii–3. 2010. Ref Type: Electronic Citation.
Denis A, Simoens S, Fostier C, Mergaert L, Cleemput I. Wellness technology assessment policy governing orphan diseases and orphan medicines. Brussels, Belgian Health Care Cognition Centre; 2009. Ref Type: Report. [Google Scholar]
Tambuyzer E. Rare diseases, orphan drugs and their regulation: questions and misconceptions. Nat Rev Drug Discov. 2010;9:921–929. doi: 10.1038/nrd3275. [PubMed] [CrossRef] [Google Scholar]
Rinaldi A. Adopting an orphan. EMBO Rep. 2005;six:507–510. doi: 10.1038/sj.embor.7400450. [PMC gratuitous article] [PubMed] [CrossRef] [Google Scholar]
Picavet E, Dooms One thousand, Cassiman D, Simoens S. Drugs for rare diseases - orphan designation condition influences price. Appl Health Econ Health Policy. 2011;9:1–5. doi: 10.2165/11531800-000000000-00000. [CrossRef] [Google Scholar]
Hollis A. In: Health services restructuring in Canada: new evidence and new directions. Embankment C, editor. Montreal: McGill-Queen's University Press; 2006. Drugs for rare diseases: paying for innovation. [Google Scholar]
Loughnot D. Potential interactions of the Orphan Drug Act and pharmacogenomics: a flood of orphan drugs and abuses? Am J Law Med. 2005;31:365–380. [PubMed] [Google Scholar]
Boon Westward, Moors E. Exploring emerging technologies using metaphors--a study of orphan drugs and pharmacogenomics. Soc Sci Med. 2008;66:1915–1927. doi: 10.1016/j.socscimed.2008.01.012. [PubMed] [CrossRef] [Google Scholar]
Love JW, Lilitkarntakul P, Webb DJ. Are rare diseases still orphans or happily adopted? The challenges of developing and using orphan medicinal products. Br J Clin Pharmacol. 2006;62:264–271. doi: 10.1111/j.1365-2125.2006.02654.x. [PMC free commodity] [PubMed] [CrossRef] [Google Scholar]
Department of Health. Pharmaceutical Price Regulation Scheme. London, Department of Health; 2010. pp. 18–three. 2010. Ref Blazon: Written report. [Google Scholar]
All Wales Medicines Strategy Group. AWMSG policy on ultra-orphan drugs. All Wales Medicines Strategy Group. 2011. pp. 21–2. 2011. Ref Type: Electronic Commendation.
Drummond MF, Wilson DA, Kanavos P, Ubel P, Rovira J. Assessing the economical challenges posed by orphan drugs. Int J Technol Assess Health Intendance. 2007;23:36–42. [PubMed] [Google Scholar]
Orphanet. The portal for rare diseases and orphan drugs. Orphanet. 2010. pp. 11–half-dozen. 2010. Ref Type: Electronic Citation.
Messori A, Cicchetti A, Patregani L. Orphan drugs. Relating price determination to affliction prevalence. BMJ. 2010;341:c4615. doi: 10.1136/bmj.c4615. [PubMed] [CrossRef] [Google Scholar]
Ferner RE, Hughes DA. The problem of orphan drugs. BMJ. 2010;341:c6456. doi: 10.1136/bmj.c6456. [PubMed] [CrossRef] [Google Scholar]
Regnstrom J, Koenig F, Aronsson B, Reimer T, Svendsen 1000, Tsigkos S. et al.Factors associated with success of market authorisation applications for pharmaceutical drugs submitted to the European Medicines Bureau. Eur J Clin Pharmacol. 2010;66:39–48. doi: 10.1007/s00228-009-0756-y. [PubMed] [CrossRef] [Google Scholar]
Maeder T. The orphan drug backfire. Sci Am. 2003;288:lxxx–87. [PubMed] [Google Scholar]
Attina T, Camidge R, Newby DE, Webb DJ. Endothelin antagonism in pulmonary hypertension, heart failure, and beyond. Center. 2005;91:825–831. doi: 10.1136/hrt.2004.053991. [PMC free commodity] [PubMed] [CrossRef] [Google Scholar]
Danzon PM, Furukawa MF. Prices and availability of biopharmaceuticals: an international comparing. Health Aff (Millwood) 2006;25:1353–1362. doi: ten.1377/hlthaff.25.v.1353. [PubMed] [CrossRef] [Google Scholar]
Clarke JT. Is the electric current approach to reviewing new drugs condemning the victims of rare diseases to decease? A phone call for a national orphan drug review policy. CMAJ. 2006;174:189–190. doi: ten.1503/cmaj.050706. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
Owen A, Sprinks J, Meehan A, Robb T, Hardy Yard, Kwasha D. A new model to evaluate the long-term toll effectiveness of orphan and highly specialised drugs post-obit list on the Australian Pharmaceutical Benefits Scheme: the Bosentan Patient Registry. Journal of Medical Economics. 2008;xi:235–243. [PubMed] [Google Scholar]
Rawlins Doc, Culyer AJ. National Institute for Clinical Excellence and its value judgments. BMJ. 2004;329:224–227. doi: x.1136/bmj.329.7459.224. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
McCabe C, Claxton Yard, Tsuchiya A. Orphan drugs and the NHS: should we value rarity? BMJ. 2005;331:1016–1019. doi: 10.1136/bmj.331.7523.1016. [PMC costless article] [PubMed] [CrossRef] [Google Scholar]
George B, Harris A, Mitchell A. Cost-effectiveness analysis and the consistency of decision making: testify from pharmaceutical reimbursement in australia (1991 to 1996) Pharmacoeconomics. 2001;19:1103–1109. doi: 10.2165/00019053-200119110-00004. [PubMed] [CrossRef] [Google Scholar]
Hughes DA, Tunnage B, Yeo ST. Drugs for exceptionally rare diseases: do they deserve special status for funding? QJM. 2005;98:829–836. doi: 10.1093/qjmed/hci128. [PubMed] [CrossRef] [Google Scholar]
National Plant for Health and Clinical Excellence. Appraising life-extending, terminate of life treatments. London: National Institute for Health and Clinical Excellence; 2009. [Google Scholar]
Dolan P, Shaw R, Tsuchiya A, Williams A. QALY maximisation and people's preferences: a methodological review of the literature. Health Econ. 2005;fourteen:197–208. doi: 10.1002/hec.924. [PubMed] [CrossRef] [Google Scholar]
National Found for Health and Clinical Excellence. Citizens Quango Report Ultra Orphan Drugs. National Institute for Wellness and Clinical Excellence. 2005. pp. xix–3. 2010. Ref Type: Electronic Citation.
Desser AS, Gyrd-Hansen D, Olsen JA, Grepperud S, Kristiansen IS. Societal views on orphan drugs: cross sectional survey of Norwegians aged 40 to 67. BMJ. 2010;341:c4715. doi: x.1136/bmj.c4715. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
Littlejohns P, Garner S, Doyle N, Macbeth F, Barnett D, Longson C. x years of Prissy: still growing and all the same controversial. Lancet Oncol. 2009;ten:417–424. doi: 10.1016/S1470-2045(09)70077-4. [PubMed] [CrossRef] [Google Scholar]
Connock Yard, Juarez-Garcia A, Frew Eastward, Mans A, Dretzke J, Fry-Smith A. et al.A systematic review of the clinical effectiveness and cost-effectiveness of enzyme replacement therapies for Fabry's disease and mucopolysaccharidosis type 1. Health Technol Assess. 2006;ten:iii–113. [PubMed] [Google Scholar]
Cook JP, Vernon JA, Manning R. Pharmaceutical take chances-sharing agreements. Pharmacoeconomics. 2008;26:551–556. doi: 10.2165/00019053-200826070-00002. [PubMed] [CrossRef] [Google Scholar]
Scottish Medicines Consortium. Orphan Drugs Risk Share. Scottish Medicines Consortium. 2010. pp. 19–3. 2010. Ref Type: Electronic Commendation.
Department of Wellness. Cost effective provision of illness modifying therapies for people with multiple sclerosis. 2002. pp. 19–3. 2010. Ref Type: Study.
Raftery J. Multiple sclerosis risk sharing scheme: a costly failure. BMJ. 2010;340:c1672. doi: 10.1136/bmj.c1672. [PubMed] [CrossRef] [Google Scholar]
Maurer SM. Choosing the correct incentive strategy for research and evolution in neglected diseases. Bull World Health Organ. 2006;84:376–381. doi: ten.2471/BLT.06.029835. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Articles from Orphanet Periodical of Rare Diseases are provided here courtesy of BioMed Central

marchandannital.blogspot.com

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3132155/