Japan Agency for Medical Research and Development (AMED), 22F Yomiuri Shimbun Bldg., 1-7-1 Otemachi, Chiyoda-ku, Tokyo, 100-0004, Japan.
Orphanet J Rare Dis. 2018 Nov 20;13(1):208. doi: 10.1186/s13023-018-0943-y.
There 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.
Two 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.
Our 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.
目前，国际社会正在建立全球性计划，为患有罕见和未确诊疾病的患者提供服务，该计划涉及跨学科专家小组和表型驱动的基因分析，利用下一代测序和分析技术。虽然拥有未确诊患者的实际数量等数据对于帮助制定此类计划的实施计划至关重要，但由于大多数卫生系统在识别尚未确诊和编码的患者方面存在固有困难，因此尚未进行系统研究来量化患者数量。我们在日本的一项罕见疾病计划 Nan-Byo 的国家经验（该计划成立于 1972 年）和最近扩大的罕见和未确诊疾病倡议（IRUD）提供了一个独特的机会，设计了一项横断面研究，根据 IRUD 的转诊标准确定日本的未确诊患者。
进行了两轮在线调查：一轮针对附属综合医院（GH）和家庭诊所（FC）的医生（回应率：30.6%（242/792）），另一轮针对日本大学医院（UH）的全国性调查（47.1%（839/1781））。GH 和 FC 的儿科医生需要 IRUD 的比例较高，而 UH 的大多数科室都明确需要 IRUD。我们根据“需要 IRUD 的医生比例”ד每位需要 IRUD 的医生将转诊到 IRUD 的患者数量（例/人）”ד日本相关医疗机构的医生总数（人）”计算了日本未确诊患者的数量，结果显示儿科/小儿外科有 3681 例，其他科室有 33703 例，总计 37384 例。
我们的研究表明，IRUD 在大多数科室都有需求，日本卫生系统中有 37000 多名患有未确诊疾病的潜在患者。这些数据为建立公平、可持续、高效和有效的基于门诊的 IRUD 提供了信息。这些发现将为不同国际司法管辖区和有社会实施愿景的国家和地区的未确诊疾病计划提供宝贵的参考，有助于推进支持那些迫切需要诊断、后续治疗和护理的罕见疾病患者的国际努力。
