Survey on patients with undiagnosed diseases in Japan: potential patient numbers benefiting from Japan’s initiative on rare and undiagnosed diseases (IRUD)

Abstract

BackgroundThere is now an international partnership to establish global programs for patients with rare and undiagnosed diseases, involving interdisciplinary expert panels and phenotype-driven genetic analyses utilizing next-generation sequencing and analytics. Whereas it is crucial to have data such as the actual number of undiagnosed patients, to help inform the implementation plan with such programs, there have been no systematic studies to quantitate the numbers of patients principally because of the inherent difficulty in most health systems to identify patients whose condition has not yet been diagnosed and coded. Our national experience with a rare disease program, Nan-Byo which was established in 1972, and the more recently expanded Initiative on Rare and Undiagnosed Diseases (IRUD), provided a unique opportunity to design a cross-sectional study to ascertain the undiagnosed patients in Japan based on the IRUD referral criteria.ResultsTwo rounds of online surveys were performed: one survey targeting physicians affiliated with general hospitals (GH) and family clinics (FC) (the response rate: 30.6% (242/792)) and one nationwide survey targeting university hospitals (UH) in Japan (47.1% (839/1781)). A high percentage of doctors needing IRUD was seen in pediatrics at GH, FC, while there was a clear demand for IRUD in most departments at UH. We calculated the number of undiagnosed patients in Japan, as the “percentage of doctors needing IRUD” × “number of patients who would be referred to IRUD per doctor needing IRUD (cases/person)” × “total number of doctors in the relevant facilities in Japan (persons)”, resulting in 3681 cases in pediatrics/pediatric surgery and 33,703 cases in other departments, for a total of 37,384 cases.ConclusionsOur study revealed the extant demand for IRUD in most departments and 37,000+ potential patients with undiagnosed diseases in the Japanese health system. These data inform the establishment of an equitable, sustainable, efficient and effective outpatient-based IRUD. These findings would serve as a valuable reference for undiagnosed diseases programs in different international jurisdictions and for countries and regions who also share vision(s) for societal implementation that help to advance international efforts to support patients with rare diseases who are direly waiting for diagnosis, subsequent treatment and care.

Importance of Quality Assessment in Clinical Research in Japan

“…Research in the field of rare and incurable diseases has made great progress due to this wave of government support. The Japan Agency for Medical Research and Development invested in rare and incurable diseases’ research (Japan Agency for Medical Research and Development (AMED), 2017), and the Initiative on Rare and Undiagnosed Diseases was created as a platform for research and treatment of these conditions (Adachi et al, 2017; Adachi et al, 2018), thus generating a relatively large amount of new research in the field.…”

How to Design a Registry for Undiagnosed Patients in the Framework of Rare Disease Diagnosis – Suggestions on Software, Data Set and Coding System

“…(12)(13)(14)(15) To improve timely and correct diagnosis for patients with rare diseases, the development of a 'registry for undiagnosed patients' was also recommended by the German National Action Plan, taking into account that a high percentage of these 'undiagnosed patients' eventually are diagnosed to have a rare disease. 17; the "Nan-Byo" (which translates as "di cult and illness"), which was established in 1972 in Japan and extended in 2015 as Japan's Initiative on Rare and Undiagnosed Diseases (18); Just recently, in February 2020, the Australian government announced to provide funding for activities to implement the National Strategic Action Plan for Rare Diseases, which was developed by Rare Voices Australia. (19) Registries for Rare Diseases Registries in general and especially in the eld of rare diseases can help to connect data from multiple health care providers (HCP), thus enlarging the data base for research questions, including epidemiology of rare diseases.…”

“…Some international examples are: The National Institutes of Health Undiagnosed Diseases Program, which started in 2008(17); the "Nan-Byo" (which translates as "di cult and illness"), which was established in 1972 in Japan and extended in 2015 as Japan's Initiative on Rare and Undiagnosed Diseases(18); Just recently, in February 2020, the Australian government announced to provide funding for activities to implement the National Strategic Action Plan for Rare Diseases, which was developed by Rare Voices Australia (19). …”

How to design a registry for undiagnosed patients in the framework of rare disease diagnosis: suggestions on software, data set and coding system

“…Similar National strategies have been developed in most member states of the European Union as well as Norway, Switzerland and the UK [ 24 ] Some international examples are: The National Institutes of Health Undiagnosed Diseases Program, which started in 2008 [ 25 ]; the “Nan-Byo” (which translates as “difficult and illness”), which was established in 1972 in Japan and extended in 2015 as Japan’s Initiative on Rare and Undiagnosed Diseases [ 26 ]; In February 2020, the Australian government announced to provide funding for activities to implement the National Strategic Action Plan for Rare Diseases, which was developed by Rare Voices Australia [ 27 ].…”