A summary of ODs definitions is provided based on the country
| Country, frequency | # of articles; (%) | (RD) definition | Date | |
| EU/UK (22) | 19 (20%) | EMA | If the drug is intended for the diagnosis, prevention, or treatment of a life-threatening or chronically and seriously debilitating condition affecting not more than 5 in 10 000 EU people or that it is unlikely that marketing the drug in the EU would generate sufficient benefit for the affected people and for the drug manufacturer to justify the investment. | |
| NICE | The current NICE appraisal system means orphan drugs that do not meet HST criteria go through the standard technology appraisal (TA) process, with a cost-effectiveness threshold of £30 k/QALY, or £50 k/QALY when end-of-life criteria are met. | |||
| EURORDIS | Drugs used in the treatment of rare diseases address significant unmet medical needs and are referred to as orphan drugs because the pharmaceutical industry has little interest under normal market conditions in developing and marketing drugs intended for only a small number of patients suffering from very rare condition. | (2011c) | ||
| The Orphan Medicinal Product Regulation | Defines Orphan Medicinal Products (OMPs) as products for diagnosis, prevention, or treatment of life-threatening or very serious conditions that affect no more than 5 in 10 000 people in the European Union. | |||
| The Netherlands | Defines orphan drug‚ as either having an official EU orphan designation or if it targets a disease with a prevalence of <1 in 150 000 and shows a clinically proven therapeutic benefit and no other registered medicine exists. | |||
| Poland | There is no specific formal threshold for orphan designations, there is only a general cost-effectiveness threshold that equals 3× GDP per capita for ICUR/QALY (for CUA) or ICER/LYG (for CEA), which in 2014 is approximately €26 800. | |||
| USA (9) | 8 (9%) | FDA | The defines an OD as ‘one intended for the treatment, prevention or diagnosis of a rare disease or condition, which is one that affects less than 200 000 persons in the USA’ (which equates to approximately 6 cases per 10 000 population) ‘or meets cost recovery provisions of the act’. | |
| Orphan Drug Act (ODA) | Orphan drug on the basis of unprofitability: one intended for the diagnosis, treatment, or prevention of a rare disease or condition in the United States, such that there was no reasonable expectation that the costs of developing the drug would be recovered from its sales in the United States. This definition was amended in 1984 to provide, in addition, a prevalence threshold of 200 000 persons affected by the disease. condition of interest in the United States as a surrogate for the lack of profitability. | |||
| Orphan product‚ as one that is intended to treat a rare disease or condition that affects fewer than 200 000 people in the United States OR as a product which will not be profitable within seven years of approval by the FDA. | ||||
| Korea (2) | 2 (2%) | the Orphan Drug Centre | Supplies medicines for diseases affecting fewer than 1 in 20 000. | |
| the Korea Ministry of Food and Drug Safety formulates ODs | Drugs used for a disease with 20 000 or fewer patients (population with the disease) and diseases for which adequate treatments or drugs have not yet been developed, or drugs that significantly improve safety or efficacy compared to existing alternatives, are designated as OD. | |||
| China (2) | 2 (2%) | Orphan drugs are defined by their availability as pharmaceutical products or active ingredients not developed, imported, or registered owing to low commercial returns and unfavorable marketing conditions. |
CEA, cost-effectiveness analysis; CUA, cost-utility analysis; EMA, European Medicines Agency; EU, European Union; EURORDIS, European Organisation for Rare Diseases; FDA, Food and Drug Administration; GDP, gross deomestic product; HST, Highly Specialised Technologies; ICER, incremental cost-effectiveness ratio; ICUR, incremental cost-utility ratio; LYG, life years gained; NICE, National Institute for Health and Care Excellence; ODs, orphan drugs; QALY, quality- adjusted life year.