The term rare disease is defined as diseases with a very low incidence rate. They are generally chronic and serious diseases that often endanger human life. Rare disease does not refer particularly to a certain disease. Instead, it is a general designation of a large category of rare diseases scattered in various disease areas. Rare disease is in essence a social definition and a relative concept. It is also a variable social perception that can be redefined in the dimension of time. As human researches on diseases deepen gradually, some rare diseases may turn to be common diseases, while cases of new rare diseases are reported each year. Therefore, at a global level, there is no unified and generally accepted definition for rare diseases.
Currently, rare diseases are defined as follows in some countries or regions:
•The United States issued the Rare Disease Act in 2002, which defines rare diseases as “any disease or condition that affects less than 200,000 persons”. There are now about 25 ~ 30 million rare disease patients in the United States, over half of whom are children [1].
• The EU defines rare diseases as chronic and progressive life-threatening diseases with an incidence of less than 1/2,000. In Europe, there are about 24 ~ 36 million rare disease patients, accounting for 6%~8% of the total population of the 25 nations of the EU [2].
• In Japan, the legal definition of rare diseases is those diseases with a patient number of less than 50,000 or an incidence of less than 1/2,500[3].
•Taiwan adopted the Law on the Prevention, Treatment and Drugs of Rare Diseases in 2000, which defines rare diseases as diseases that have an incidence of less than 1/10,000 or are included through examination and approval [4].
•Allegedly, the World Health Organization (WHO) defines rare diseases as “diseases or pathological conditions afflicting 0.065%~0.1% of the whole population”. This definition, which is extensively cited by Chinese researchers, does not exist in fact, for WHO has yet to give its official definition of rare diseases [5].
According to the statistics of the US Food and Drug Administration (FDA), there are more than 7,000 known rare diseases around the globe, accounting for 10% of the total number of human diseases; the number of global rare disease patients has exceeded 250 million, with children accounting for nearly 50% of them; only less than 10% of the known 7,000 plus rare diseases have approved treatment drugs or plans [6]. Most rare diseases threaten the lives of patients or seriously affect their survival quality. But, given the availability of drug treatment, the progress of some rare diseases can be brought under control gradually until they become chronic diseases through management.
Currently in China, there is no clear legal interpretation of rare diseases:
• On May 17, 2010, the Medical Genetics Branch of the Chinese Medical Association held an expert seminar on the definition of China’s rare diseases in Shanghai. The participating experts proposed that the rare diseases in China should be defined as diseases with an incidence of less than 1/500,000 or an incidence of less than 1/10,000 in newborns [6]. Based on this, the number of Chinese rare diseases patients is about 16.8 million [7], while it is not a commonly accepted definition.
• In May 2018, five national departments, including the National Health Commission (“NHC”), Ministry of Science & Technology, Ministry of Industry and Information Technology, National Medical Products Administration (“NMPA”) and State Administration of Traditional Chinese Medicine, jointly issued the Catalogue of First Batch of Rare Diseases” (“121 Catalogue”) [8], which includes 121 rare diseases. This is the first time that the Chinese government has defined rare diseases in the form of a catalogue of diseases. According to the calculation based on epidemiological literature reports and other public data, the 121 rare diseases affect about 3 million patients in mainland China.
Aside of the number perspectives, the term “rare disease” also implies the vision on what the challenge the society encounters, and what the potential solutions are. Essentially, the term “rare disease” is an expansion from its clinical definition to its social impact in specific region.
Firstly, the term “rare” is a relative concept, a variable social perception that can be redefined in the dimension of time. Rare disease does not refer particularly to a certain disease. Instead, it is a general designation of a large category of rare diseases scattered in various disease areas. The definition is stemmed from clinical perception resulted from general society environment. Essentially, with more research and understanding some “rare disease” will become “common” such as AIDS, while new “rare disease” will be reported. Moreover, the development of genetic diagnosis empowers precision medicine that continuously reshape the histology-based disease understanding to genomic view. Especially in oncology, the redefinition on disease and emerging of “rare” subtype is becoming prevalent. Lung cancer as an example, has been redefined to numerous genetic subtypes such as ALK, EGFR, NTRK, RET, etc, in which some low-incidence subtypes are definitely “rare disease” in some countries and regions. In fact, many orphan drug designations granted by FDA are rare subtypes in oncology.
Secondly, it is the regional diversity in relative concept and social perception that make unfeasible a globalized unified and generally accepted definition for rare diseases. Regionally diversified disease spectrum, together with the social demand at certain historical period, results in difference in the legal meaning and policy framework for rare disease. For China nowadays, mechanical copy of any country or region for rare disease definition will be highly disputable.
Finally, the definition of “rare disease” ought be framed by regional development strategy and directed by resource allocation. The legal meaning of “rare disease” is, ultimately, to serve policy making purpose, in which the definition of a certain community will endorse the resource allocation accordingly. Consequently, diversified definitions across different countries and regions are necessary to precisely manage the resource allocated to “rare disease” patients, considering some low-incidence disease patients have been included in other already-built policy framework. For example, Taiwan has not included hemophilia and rare oncology in its rare disease legislation, because individual policies have been established to support drug development and reimbursement of these diseases.
Resource: <China Rare Disease Drug Accessibility Report 2019>