Japan's initiative on rare and undiagnosed diseases (IRUD): towards an end to the diagnostic odyssey

Abstract

Japan has been facing challenges relating to specifically defined rare diseases, called Nan-Byo in Japanese (literally 'difficult'+'illness'), and has already taken measures for them since 1972. This governmental support has surely benefited Nan-Byo patients; however, those suffering from medically unidentified conditions do not fall into this scheme and thus still confront difficulty in obtaining an examination, a diagnosis, and a treatment. To identify such rare and often undiagnosed diseases, we must integrate systematic diagnosis by medical experts with phenotypic and genetic data matching. Thus, in collaboration with Nan-Byo researchers and the Japanese universal healthcare system, the Japan Agency for Medical Research and Development launched the Initiative on Rare and Undiagnosed Diseases (IRUD) in 2015. IRUD is an ambitious challenge to construct a comprehensive medical network and an internationally compatible data-sharing framework. Synergizing with existing next-generation sequencing capabilities and other infrastructure, the nationwide medical research consortium has successfully grown to accept more than 2000 undiagnosed registrants by December 2016. We also aim at expanding the concept of microattribution throughout the initiative; that is, proper credit as collaborators shall be given to local primary care physicians, nurses and paramedics, patients, their family members, and those supporting the affected individuals whenever appropriate. As it shares many challenges among similar global efforts, IRUD's future successes and lessons learned will significantly contribute to ongoing international endeavors, involving players in basic research, applied research, and societal implementation.

Figure 1

IRUD’s mission within the existing healthcare delivery architecture in Japan. A disease is referred to as Nan-Byo if it is a rare disease of unknown etiology which requires currently unavailable treatment measures and long-term care for the patient. Research funding has been available for various Nan-Byo projects; and national subsidiary structures have helped offset the cost incurred by patients suffering from eligible Nan-Byo diseases, which had received nomination, consultation, and final authorization by MHLW as designated Nan-Byo. IRUD is positioned to expand the horizon of Nan-Byo research, reaching out to people suffering from unidentified diseases.

Figure 2

Schematic workflow of the IRUD operation. The three major functional modules—Diagnosis Committees and the local collaboration, Data Network, and Analysis Consortium—closely interact with one another and are operated by principal research groups.