Value Assessment of Orphan Drugs and Treatments for Rare Diseases

Thesis (Master's)--University of Washington, 2016-06

OBJECTIVES: In 1983 the US Orphan Drug Act was passed to facilitate commercialization of drugs to treat rare diseases. The market value for orphan drugs in the US reached $90 billion annually in 2014, with worldwide sales forecast at $176 billion. Payers and policymakers need robust methodology for evaluation of health technology in this growing landscape of expensive treatments for rare diseases. Here I present a systematic review of current practices in value-based evaluation of orphan drugs from a global perspective. I also propose a potential new framework to be developed as new metric for assessing the value of orphan drugs, the Orphan Drug Index Estimate (ODIE). METHODS: For the systematic review, searches were conducted in December 2015 in PubMed®, EMBASE®, and Web of Science® databases using the following keywords: orphan drug, rare disease treatment, economics, resource utilization, cost, cost effectiveness, questionnaire, and value. Only references published in English were included. Manuscripts that solely reported one of the following were excluded: clinical or patient care, policy or legislation on orphan drugs particularly relating to research incentive, opinion or editorial, preclinical studies, drug-development, unrelated to rare diseases or healthcare, reviews other than systematic reviews for health technology assessment. RESULTS: A total of 2513 unique references were obtained, and screened by title and abstract according to exclusion criteria. After exclusion, 333 references remained for full evaluation. Of those, an additional 296 were excluded, but 51 additional studies were included from the reference lists of included articles. A total of 88 articles were included in the complete analysis. Overall, the methodology employed for conducting cost-effectiveness assessments followed traditional techniques including decision analysis and Markov modeling techniques. The reported incremental cost effectiveness ratios (ICERs) ranged from dominant treatments to a high of €6.1 million per quality adjusted life year (QALY). Interpretation of the results was more challenging, with 43% of studies reporting ICERs that would not be considered cost-effective under a willingness-to-pay threshold of $50,000 per QALY. In spite of the lack of cost-effectiveness, the majority of authors agreed that since the treatment under review is for a rare condition, there is an obligation to cover the costs. In light of these analyses, there is an evident need for a method of analysis that is more comprehensive than the ICER, and more appropriate for addressing the uniqueness of orphan drugs, including variables related to the rarity and severity of disease, and a broader societal perspective on costs, including societal burden and identifiable opportunity costs. In response, here I propose a potential new metric based on multicriteria decision analysis (MCDA) techniques to provide a more comprehensive evaluation of orphan drugs. CONCLUSIONS: There is a global consensus of a need to develop appropriate methodology, analysis techniques, and related policies to address management of expensive treatments. It is not yet clear how best to evaluate the value of orphan drugs. More thorough evaluation and validation of novel modeling techniques, analytic rationale and proactive policy changes are needed to redefine the status quo of health technology assessment of rare disease treatments. I propose a new metric to overcome some limitations of the ICER in evaluation of rare diseases. Continued research is needed in detailed development of a valid, quantifiable, and reproducible metric; however, the work presented here provides a foundation for the development process.