The multicriteria decision analysis approach piloted works and could be developed for use by payers and health technology assessment bodies.

Legislative incentives enacted in Europe through the Regulation (EC) No. 141/2000 to incentivize orphan drug development have over the last 12 years constituted a powerful impetus toward R&D directed at the rare diseases population.However, despite therapeutic promises contained in these projects and significant economic impact linked to burgeoning R&D expenditures, the affordability and value of OMPs has become a topic of health policy debate in Europe fueled by the perception that OMPs have high acquisition costs, and by misconceptions around pricing dynamics and rare-diseases business models. In order to maintain sustainable patient access to new and innovative therapies, it is essential to address these misconceptions, and to ensure the successful continuation of a dynamic OMPs R&D within rare-diseases public health policy.Misconceptions abound regarding the pricing of rare diseases drugs and reflect a poor appreciation of the R&D model and the affordability and value of OMPs.Simulation of potential financial returns of small medium sized rare diseases companies focusing on high priced drugs show that their economic returns are likely to be close to their cost of capital. Research in rare diseases is a challenging endeavour characterised by high fixed costs in which companies accrue substantial costs for several years before potentially generating returns from the fruits of their investments. Although heavily dependent upon R&D capabilities of each individual company or R&D organization, continuous flow of R&D financial investment should allow industry to increasingly include efficiencies in research and development in cost considerations to its customers. Industry should also pro-actively work on facilitating development of a specific value based pricing approach to help understanding what constitute value in rare diseases. Policy makers must reward innovation based upon unmet need and patient outcome. Broader understanding by clinicians, the public, and policy makers of the complexity of clinical programs to deliver OMPs to market is required to better comprehend the decisions needed and made by industry. In parallel, an overt effort to consider the impact of public policies on R&D investments is key to enable policy makers to better reconcile the incentives provided by public policy decisions and companies investments decisions in a more positive manner.

The purpose of this research is to identify the attributes to include in an orphan medicinal product (OMP) value framework, determine their relative importance via a multi-criteria decision analysis (MCDA) process, and test whether an MCDA approach can practically support decision making. MethodsThe project included literature searches on the natural history and burden of 40 rare diseases and how payers assess treatment value as well as three workshops. Workshops also were held: the first with GlaxoSmithKline managers working on OMPs, the second with EU clinical and health economics experts, and the third with representatives of rare diseases patient groups in the European Union. Participants refined the attributes, weighted them, scored two case study OMPs in terms of those attributes, and tested the sensitivity of the overall ratings to changes in weights and scores. ResultsEight non-monetary attributes were agreed: four concern the disease being treated and four the treatment itself. Workshop participants agreed consensus weights for the attributes. The patient group representatives and the clinical and health economics experts both attributed about half of the weight to attributes reflecting the disease being treated, and half to attributes of the treatment. Patient group representatives gave greater weight than the experts to patients' quality of daily life and less weight to clinical factors. The weighted attributes were readily applied by workshop participants to two example OMPs and yielded distinct ratings of their respective values. ConclusionsAn OMP value framework with agreed attributes and weights is a viable proposition using an MCDA approach, and could improve clarity and transparency in decision making about the value of OMPs.

OBJECTIVES:To ensure rapid access to new potentially beneficial medicines and affordability, payers are adopting innovative approaches called Managed Entry Agreement(MEAs). AIFA has pioneered in the design and implementation of MEAs for the last two decades. The objective is to describe and quantify AIFA's MEAs used to support decision-making in situations of uncertainty. METHODS: Data on MEAs were retrieved from the AIFA monitoring registries and databases, and analyzed between August 1st 2011 and December 15th 2011. RESULTS: The management of uncertainty of new medicines/therapeutic indications(TI) is performed through arrangements based on access with evidence development i.e. "AIFA monitoring registries" which can be associated with outcome based schemes: "Payment by Results(PbR)" or "Risk-Sharing(RS)". To manage utilization, AIFA set "Restricting Notes for Prescription"(RNP), a tool to restrict NHS reimbursability of medicines for a particular condition/disease, and the "Therapeutic Plans"(TP), which guarantee reimbursement only under specialist monitoring. To achieve management of budget impact, financial-oriented schemes are in place: The "Volume-based Agreements"(VbA), a negotiation of volume of sales between AIFA and manufacturers, and the Cost-sharing(CS), a discount on the initial therapy cycle(s) for all eligible patients. The AIFA Registries include 78 TI: 44 refer to oncology, 15 to rare diseases, 7 to diabetes and the remaining to other therapeutic areas. Among 78 TI, 14 were PbR, 12 CS and 2 RS. For the remaining 50 indications, no scheme for reimbursement was applied, but registries were used to monitor post-marketing safety and effectiveness. Furthermore AIFA implemented 32 RNP and a total of 85 VbA and TP for more than 350 medicines. CONCLUSIONS: Unlike other European authorities which base reimbursement decisions on thresholds, AIFA implemented an extensive range of strategies to allow health care access and budget sustainability. These strategies ensure proper utilization of standard therapies and guarantee access to most recent innovative medicines.BACKGROUND: Recent recommendations from the EU commission have given countries the responsibility to develop national strategies for rare diseases, including plans for inventorying of rare diseases and development of centers of excellence (CoE). In France, patients are required to consult or obtain their prescription from a CoE in order for reimbursement of orphan drugs to be granted. As CoE and rare disease registries are developed throughout the EU member states, increased awareness, education, and data collection will lead to better management of orphan diseases, monitoring of long-term outcomes and cost and opportunities for

OBJECTIVES:To ensure rapid access to new potentially beneficial medicines and affordability, payers are adopting innovative approaches called Managed Entry Agreement(MEAs). AIFA has pioneered in the design and implementation of MEAs for the last two decades. The objective is to describe and quantify AIFA's MEAs used to support decision-making in situations of uncertainty. METHODS: Data on MEAs were retrieved from the AIFA monitoring registries and databases, and analyzed between August 1st 2011 and December 15th 2011. RESULTS: The management of uncertainty of new medicines/therapeutic indications(TI) is performed through arrangements based on access with evidence development i.e. "AIFA monitoring registries" which can be associated with outcome based schemes: "Payment by Results(PbR)" or "Risk-Sharing(RS)". To manage utilization, AIFA set "Restricting Notes for Prescription"(RNP), a tool to restrict NHS reimbursability of medicines for a particular condition/disease, and the "Therapeutic Plans"(TP), which guarantee reimbursement only under specialist monitoring. To achieve management of budget impact, financial-oriented schemes are in place: The "Volume-based Agreements"(VbA), a negotiation of volume of sales between AIFA and manufacturers, and the Cost-sharing(CS), a discount on the initial therapy cycle(s) for all eligible patients. The AIFA Registries include 78 TI: 44 refer to oncology, 15 to rare diseases, 7 to diabetes and the remaining to other therapeutic areas. Among 78 TI, 14 were PbR, 12 CS and 2 RS. For the remaining 50 indications, no scheme for reimbursement was applied, but registries were used to monitor post-marketing safety and effectiveness. Furthermore AIFA implemented 32 RNP and a total of 85 VbA and TP for more than 350 medicines. CONCLUSIONS: Unlike other European authorities which base reimbursement decisions on thresholds, AIFA implemented an extensive range of strategies to allow health care access and budget sustainability. These strategies ensure proper utilization of standard therapies and guarantee access to most recent innovative medicines.BACKGROUND: Recent recommendations from the EU commission have given countries the responsibility to develop national strategies for rare diseases, including plans for inventorying of rare diseases and development of centers of excellence (CoE). In France, patients are required to consult or obtain their prescription from a CoE in order for reimbursement of orphan drugs to be granted. As CoE and rare disease registries are developed throughout the EU member states, increased awareness, education, and data collection will lead to better management of orphan diseases, monitoring of long-term outcomes and cost and opportunities for