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Every year on February 28, the global community comes together to observe Rare Disease Day, a day dedicated to raising awareness and understanding for the millions of individuals who live with rare disorders. While individual rare diseases may seem uncommon, their collective impact is significant, affecting the lives of countless families and communities worldwide. This day serves as a crucial platform to amplify the voices of those affected, advocate for increased research and support, and inspire hope for a future where rare diseases can be prevented, diagnosed earlier, and effectively treated., Competing Interests: Declaration of interests The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Rare diseases (RDs) affect millions of people worldwide, and these diseases can severely impact the health-related quality of life (HRQoL) of those affected. Despite this, there is a lack of research measuring HRQoL using the EQ-5D-5L, which is one of the most widely used generic preference-based instruments to measure HRQoL in populations living with RDs., Objective: This study aimed to measure HRQoL using the EQ-5D-5L in a large number of patients with various types of RDs in China, and to examine the relationship between respondents' socioeconomic characteristics and preference-based health utility scores., Methods: The data used in this study were obtained from a web-based survey conducted in China. The survey aimed to explore and understand the health and socioeconomic status of patients with RDs in China. We recruited registered and eligible members, including patients or their primary caregivers, from 33 RD patient associations to complete the questionnaires via their internal social networks. HRQoL was measured using the EQ-5D-5L utility score, which was calculated based on an established Chinese value set. Utility scores have been presented based on demographics and disease-related information. Univariate linear regression analysis was used to assess the differences in the EQ-5D-5L utility scores between subgroups., Results: A total of 12,502 respondents completed the questionnaire and provided valid responses, including 6919 self-completed respondents and 5583 proxy-completed respondents. Data from 10,102 participants over the age of 12 years were elicited for analysis. Among patients with RDs, 65.3% (6599/10,102), 47.5% (4799/10,102), 47.0% (4746/10,102), 24.8% (2506/10,102), and 18.4% (1855/10,102) reported no problems for "self-care," "usual activities," "mobility," "pain/discomfort," and "anxiety/depression," respectively. A full health state was reported by 6.0% (413/6902) and 9.2% (295/3200) of self- and proxy-completed patients, respectively. Among self-completed patients, 69.9% (4826/6902) and 50.4% (3478/6902) reported no problems for "self-care" and "usual activities," respectively, whereas only 17.7% (1223/6902) reported problems for "anxiety/depression." Proxy-completed respondents showed a higher proportion of reporting extreme problems than self-completed respondents in all 5 dimensions. The mean utility scores reported by self- and proxy-completed respondents were 0.691 and 0.590, respectively. Different types of caregivers reported different utility scores, and among them, proxy-completed (mother) respondents reported the highest mean utility score., Conclusions: The establishment of a normative profile for RD patients can facilitate patients' adaptation and assess the effectiveness of interventions to improve the HRQoL and well-being of this population. Differences between self- and proxy-completed HRQoL assessed by the EQ-5D-5L have been identified in this study. This finding highlights the importance of incorporating perspectives from both patients and their proxies in clinical practice. Further development of the patient cohort is necessary to assess long-term changes in HRQoL in the RD population., (©Richard Huan Xu, Shamay S M Ng, Nan Luo, Dong Dong, Shuyang Zhang. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 31.10.2023.)

Background: Genetic testing can facilitate the diagnosis and subsequent therapeutic management of rare diseases. However, there is a lack of data on the use of genetic testing for rare diseases. This study aims to describe the utilization rate and troubles encountered by clinicians in treating rare diseases with genetic testing., Methods: A cross-sectional electronic questionnaire survey was conducted between June and October 2022 among the medical staff from the hospitals covering all provinces, municipalities, and autonomous regions of China. The survey on genetic testing focused on whether genetic testing was used in the diagnosis and treatment of rare diseases, the specific methods of genetic testing, and the problems encountered when using genetic testing., Results: A total of 20,132 physicians who had treated rare diseases were included, of whom 35.5% were from the central region, 36.7% were from the eastern region, and 27.8% were from the western region. The total utilization rate of genetic testing for rare diseases was 76.0% (95%CI: 75.4-76.6). The use of genetic testing was highest in the Eastern region (79.2% [95% CI: 78.3-80.1]), followed by the Central (75.9% [95% CI: 74.9-76.9]) and Western regions (71.9% [95% CI: 70.7-73.1]). More than 90% (94.1% [95%CI: 93.4-94.8]) of pediatricians had used genetic testing to treat rare diseases, with surgeons having the lowest use of genetic testing (58.3% [95% CI: 56.6-60.0]). Physicians' departments and education levels affect the use of genetic testing. Most physicians have used a variety of genetic tests in the management of rare diseases, the most popular methods were "Whole-exome sequencing (Proband)" and "Whole-exome sequencing (families of three or more)". Doctors have encountered many problems with the use of genetic testing in the diagnosis and treatment of rare diseases, among which the high price was the main concern of medical workers., Conclusion: Three-quarters of physicians used genetic testing in rare disease practice, and there were regional differences in the use of genetic testing. Recognition of the utilization of genetic testing can help identify patterns of resource utilization in different regions and provide a more comprehensive picture of the epidemiology of rare diseases in jurisdictions., (© 2023. Institut National de la Santé et de la Recherche Médicale (INSERM).)

Background: There are about 7000 rare diseases worldwide, of which only 5% of the diseases can be treated with medicines, showing that it's important to improve patient access to orphan drugs. Recently, China has actively worked to set up a national system for rare diseases to improve the diagnosis and treatment capabilities and ensure the accessibility of drugs. However, the benefits of the system have yet not to be measured. This study aimed to provide an overview of orphan drug access based on the Compendium of China's First List of Rare Diseases and National Network to Collaborate on Diagnosis and Treatment of Rare Diseases, expecting to map a blueprint for orphan drug access in China., Methods: Framework of China's national system for rare diseases was summarized. We surveyed the availability and affordability of 79 approved orphan drugs based on the Compendium of China's First List of Rare Diseases in 30 leading provincial institutions from 2017 to 2020. The availability was measured annually at 3 levels (market, hospital and drug), and affordability was reflected by comparing costs of daily defined dose with per capita income of urban and rural residents, with the National Basic Medical Insurance considered., Results: The market availability of orphan drugs in China showed an upward trend. As of 2020, the median hospital-level availability was 41.1% (increased by 1.5 times), highly available drugs increased by 16.5%. There were 64/74 orphan drugs that were affordable to rural/urban residents with the National Basic Medical Insurance considered (an increase of 14.1%), and the urban-rural gap of affordability ratio was narrowed (down by 6.0%). Comprehensive analysis showed the proportions of drugs with better availability and affordability in urban and rural areas by 2020 were 39.4% and 32.3%, respectively, which had increased but were still at a low level., Conclusions: China's national system for rare diseases has made great progress in orphan drug access, indicating that it's been functioning under the joint reformation of medical treatment, medical insurance and medicines supply. The list of rare diseases will be updated and collaboration in networks will be enhanced to further improve the system., (© 2022. The Author(s).)

Background: China has made tremendous progresses in serving the needs of its people living with rare diseases in the past decade, especially over the last 5 years. The Chinese government's systematic approach included a series of coordinated initiatives, amongst these are: forming the Rare Disease Expert Committee (2016), funding the "Rare Diseases Cohort Study" (2016-2020), and publishing its first "Rare Disease Catalog" (2018). Herein, we present the National Rare Diseases Registry System (NRDRS)-China's first national rare diseases registry, and the analysis of cases registered in the first 5 years ending Dec 31, 2020., Results: The total 62,590 cases covered 166 disease/disease types, forming 183 disease cohorts. The data from nearly 22% of them (13,947 cases) is also linked to valuable biological samples. The average age of definitive diagnosis was 30.88 years; 36.07% of cases were under 18 years of age. Regional distribution analysis showed 60% of cases were from the more developed, wealthier East and North China, suggesting the local availability of quality care and patients' financial status were key access factors. Finally, 82.04% of cases were registered from the five clinical departments: Neurology, Endocrine, Hematology, Cardiovascular, and Nephrology, suggesting that either these are most affected by rare diseases, or that there were disease non-specific ascertainment factors., Conclusions: The preliminary analysis of the first 5-year's data provides unique and valuable insight on rare disease distribution in China, and higlights the directions for enhancing equity, scale and utility., (© 2021. The Author(s).)

Rare diseases are major challenges in healthcare and medical research and are the basis of national development strategies in many countries. However, inadequate definition of rare diseases and lags in orphan drug development in China hinder rare disease research. In response, the first National Rare Diseases Registry System of China (NRDRS) was established, and various cohort studies have been launched since 2016. More than 20 top academic institutions in China are currently participating in this joint effort to carry out nationwide registration of rare diseases. The primary objectives are to establish standardization for the registration platform, build biobanks of genomic data, and create partnerships for data sharing and research collaboration. Innovative informatics technologies have been implemented to develop the NRDRS, including employment of ontological and knowledge bases to render standardization and support standard of care. Development of informatics analysis tools will facilitate accurate and more efficient diagnoses for rare diseases. Long-term research collaboration is encouraged to create additional national rare disease networks for research translation and to benefit patients with rare diseases. The NRDRS of China and related cohort studies are anticipated to enlighten rare disease research significantly in China.

The diagnosis and treatment of rare diseases have long been significant challenges in the medical practice. With the rapid development of genomics and genetics, medical genetics has been widely applied in the diagnosis and treatment of rare diseases. Systematic medical genetics training courses are essential for enhancing the professional level of clinicians in diagnosing and treating rare diseases. This paper aims to analyze the current status of medical genetics training, discuss the principles and methods of curriculum design, and propose strategies to optimize training effectiveness, in order to enhance their comprehensive capabilities in the diagnosis and treatment of rare diseases.

Objective This study aims to sort out the rare disease drugs in the China′s Second List of Rare Diseases, to provide reference for the management of rare disease drug treatment. Methods Up to December 31, 2023, based on the China′s Second List of Rare Diseases, we sorted out the drugs approved in China with the drug label, or approved by the U.S. Food and Drug Administration(FDA) and the European Medicines Agency (EMA) for the treatment of the above diseases, and developed the second batch of rare disease drug catalog in China. The accessibility, localization and coverage of the national medical insurance were also analyzed. Results From the point of view of diseases, a total of 37 diseases in the China′s Second List of Rare Diseases have drug indications approved in China, and 10 diseases have drugs listed by the U.S. FDA/EMA and approved in China, but for off-label use. From the point of view of drugs, there are 55 drug indications approved for the treatment of the China′s Second List of Rare Diseases, and 22 drugs listed in the U.S. FDA/EMA and approved in the China, but for off-label use. Among the above-mentioned drugs with domestic approved rare disease indications or approved numbers, 39 drugs have at least one domestic approval number for a dosage form, covering 30 rare diseases; 37 drugs used for at least one rare disease are included in the national medical insurance catalog and are covered by reimbursement, covering 29 rare diseases. Conclusions The list of rare disease drugs in the China′s Second List of Rare Diseases was established. The number of rare disease drugs and covered diseases approved by China and the U.S. FDA/EMA has increased, and the number of rare disease drugs and covered diseases that are localized and included in the medical insurance catalog has also continued to increase.

In the past few years, China has pushed forward the availability of diagnosis and treatment of rare diseases. However, only 5% of patients receive effective treatment in the world. In China, the difficulties in having access to drugs against rare disease is still one of the major problems in medical service and the main cause of patients complaints for " difficulties in getting treatment" and " difficulties in getting drugs". The availability of the medication for rare disease is a coordinating mechanism involving multiple such points in the chain as in research and development, production, circulation, usage, way of payment, technology innovation and so forth. It also relates to the actors in supply, demand, and policy decision-makers. The complexity is different from that of common drugs. This article provides a brief overview of the current status of availability policies of medication for rare diseases in China and in other countries, as well as the technology in drug development. In addition, the article points out the problems, challenges and expectations for future possibilities.

The establishment of the Department of Rare Diseases at Peking Union Medical College Hospital (PUMCH) is a landmark in the disciplinary development of the rare diseases. The establishment of the department will booster the prominence of the influence and leading position of the PUMCH in the field of rare diseases. In addition, the department is instrumental in the development of the hospital of high-quality. The department aims at delivery of better medical care for patients with rare diseases, the training of specialists in rare diseases, and avancement of the preventing and treating rare diseases in China.This paper preliminarily discusses the working basis, significance and discipline development plan of the department of rare diseases at PUMCH.

This article combs and summarizes the entire process of rare disease selection and priority theme determination, including the application and preliminary review of rare diseases, standardization of disease theme information, the evaluation methods of evidence sorting and disease selection for priority selection of disease themes, and other aspects of the content were analyzed in depth. It is expected to provide reference for the subsequent selection of rare diseases, improve the fairness, rationality and scientificity of rare disease selection, and further promote research and decision-making in China′s rare disease-related fields.

Although the incidence of rare diseases is extremely low, 6% to 8% of the global population are affected by more than 7000 rare diseases. Rare diseases guidelines are playing an increasingly important role as guiding documents in improving the health outcomes of patients with rare diseases. Therefore, we aim to systematically elaborate on the status quo, challenges and opportunities of rare disease guidelines at home and abroad, and put forward thoughts and suggestions on promoting the development of rare diseases guidelines in the future.

The onset of rare cardiovascular diseases is early and the mortality is high. The patients of the disease face a long time of hardship in diagnosis and a low treatment rate. As a result, it is urgent to improve the diagnosis and treatment level of rare diseases and to accelerate the selection and R&D of drugs of rare cardiovascular diseases. In recent years, with the rapid development of new technology and basic research, the diagnosis and treatment of rare cardiovascular diseases have made breakthroughs. The article summarizes the research progress in diagnosis and treatment of rare cardiovascular diseases and looks into the future of the research.

Health security for rare diseases has aroused much attention in the society nowadays, In this article, we analyzed in-depth the construction of rare diseases health security in China by studying the literature reviews, expert interviews, and reports of pilot policy investigations. We conclude in the study that it is an important step to constructing a multiple health security system for the rare disease making the basic health security as the cornerstone. For rare medications and treatments that cannot be covered by the current national health insurance, it is necessary to build an specific funding for rare disease funding as a means of safeguard. Finally, for those who are financially disadvantages, the system should involve relief and philanthropy to help them. By constructing a multiple health security system, rare diseases patients in our country will get a well-covered health care.

Rationale: Oral treprostinil improves exercise capacity in patients with pulmonary arterial hypertension (PAH), but the effect on clinical outcomes was unknown.Objectives: To evaluate the effect of oral treprostinil compared with placebo on time to first adjudicated clinical worsening event in participants with PAH who recently began approved oral monotherapy.Methods: In this event-driven, double-blind study, we randomly allocated 690 participants (1:1 ratio) with PAH to receive placebo or oral treprostinil extended-release tablets three times daily. Eligible participants were using approved oral monotherapy for over 30 days before randomization and had a 6-minute-walk distance 150 m or greater. The primary endpoint was the time to first adjudicated clinical worsening event: death; hospitalization due to worsening PAH; initiation of inhaled or parenteral prostacyclin therapy; disease progression; or unsatisfactory long-term clinical response.Measurements and Main Results: Clinical worsening occurred in 26% of the oral treprostinil group compared with 36% of placebo participants (hazard ratio, 0.74; 95% confidence interval, 0.56-0.97; P = 0.028). Key measures of disease status, including functional class, Borg dyspnea score, and N-terminal pro-brain natriuretic peptide, all favored oral treprostinil treatment at Week 24 and beyond. A noninvasive risk stratification analysis demonstrated that oral treprostinil-assigned participants had a substantially higher mortality risk at baseline but achieved a lower risk profile from Study Weeks 12-60. The most common adverse events in the oral treprostinil group were headache, diarrhea, flushing, nausea, and vomiting.Conclusions: In participants with PAH, addition of oral treprostinil to approved oral monotherapy reduced the risk of clinical worsening.Clinical trial registered with www.clinicaltrials.gov (NCT01560624).

Rare diseases refer to diseases characterized by very low prevalence rate but causing serious public health problem in the society. The diagnosis and treatment of the diseases pose great challenges.During the period of 13th Five-Year, China has accelerated the pace in all aspects targeting on policy support and scientific research in the rare diseases and on patients having the diseases. The efforts include establishing the cataglog for rare disease, introducing a series of policies to accelerate the R & D of drugs, upgrading the standardization of the diagnosis and treatment competences and so forth. In addtion, the establishment of National Rare Diseases Registry System(NRDRS) has been instrumental in knowing the burden of the diseases and enhancing the scientific research to rare diseases.

Rare diseases have been a major challenge for clinical medicine and public health challenge in China. One of the effective measures is to conduct proactive research on rare diseases to deal with the disease burden of the diseases. However, low prevalence, disperse distribution of patients, lack of knowledge about the disease course, and phenotype heterogeneity hamper the development of research for rare diseases. Recently, it has been found that patients registry is effective in understanding the course of the disease and accu- mulating the cases and data of clinical research or clinical trial design. At present, most of developed countries or regions in the world have promoted clinical research and clinical trials of new medications on rare diseases by using the registration of rare disease. In 2016, Peking Union Medical College Hospital established China's first registry system at the national level-National Rare Disease Registry System of China(NRDRS). NRDRS has accumulated 68 137 cases data registered by the researchers from China's 101 collaborating hospitals in 29 provinces/municipalities/autonomous regions, covering 171 different, and forming 188 cohorts. To date, NRDRS complete the initial stage of resources buildup.Nex stage will be focused on clinical research and clinical trials related to rare diseases based on NRDRS. This article is on the process of building NRDRS, the potential support for conducting clinical research and clinical trials related to rare diseases, and the challenges will be faced.

Background: Rare diseases have become a major public health concern worldwide. However, detailed epidemiological data are lacking. With the development of the Internet, search queries have played an important role in disease surveillance. In this study, we explored a new method for the epidemiological research on rare diseases, using large-scale online search queries and reported case data. We distilled search logs related to rare diseases nationwide from 2016 to 2019. The case data were obtained from China's national database of rare diseases during the same period. Results: A total of 120 rare diseases were included in this study. From 2016 to 2019, the number of patients with rare diseases estimated using search data and those obtained from the case database showed an increasing trend. Rare diseases can be ranked by the number of search estimated patients and reported patients, and the rankings of each disease in both search and reported case data were generally stable. Furthermore, the disease rankings in the search data were relatively consistent with the reported case data in each year, with more than 50% of rare diseases having a ranking difference of -20 to 20 between the two systems. In addition, the relationship between the disease rankings in the two systems was generally stable over time. Based on the relationship between the disease rankings in the search and reported case data, rare diseases can be classified into two categories. Conclusion: Online search queries may provide an important new resource for detecting rare diseases. Rare diseases can be classified into two categories to guide different epidemiological research strategies. [ABSTRACT FROM AUTHOR]

Background: In China, there are severe unmet medical needs of people living with rare diseases. Relatedly, there is a dearth of data to inform rare diseases policy. This is historically partially due to the lack of informatics infrastructure, including standards and terminology, data sharing mechanisms and network; and concerns over patient privacy protection. Objective: This study aims to introduce the progress of China's rare disease informatics platform and knowledgebase, and to discuss critical enablers of rare disease informatics innovation, including: data standardization; knowledgebase construction; national policy support; and multi-stakeholder participation. Methods: A systemic national strategy, delivered through multi-stakeholder engagement, has been implemented to create and accelerate the informatics infrastructure to support rare diseases management. This includes a disease registry system, together with more than 80 hospitals, to perform comprehensive research information collection, including clinical, genomic and bio-sample data. And a case reporting system, with a network of 324 hospitals, covering all mainland Chinese provinces, to further support reporting of rare diseases data. International standards were incorporated, and privacy issues were addressed through HIPAA compliant rules. Results: The National Rare Diseases Registry System of China (NRDRS) now covers 166 rare diseases and more than 63,000 registered patients. The National Rare Diseases Case Reporting System of China (NRDCRS) was primarily founded on the National Network of Rare Diseases (NNRD) of 324 hospitals and focused on real-time rare diseases case reporting; more than 400,000 cases have been reported. Based on the data available in the two systems, the National Center for Health Technology Assessment (HTA) of Orphan Medicinal Products (OMP) has been established and the expert consensus on HTA of OMP was produced. The largest knowledgebase for rare disease in Chinese has also been developed. Conclusion: A national strategy and the coordinating mechanism is the key to success in the improvement of Chinese rare disease clinical care and drug accessibility. Application of innovative informatics solutions can help accelerate the process, improve quality and increase efficiency. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the psychometric properties of the EQ-5D-5L and SF-6D, and to compare their performance among patients living with haemophilia in China.Methods: A total of 875 Chinese patients completed the EQ-5D-5L, SF-6D, and Haem-A-QoL questionnaires. Construct validity of the EQ-5D-5L and SF-6D dimensions and indices was assessed by testing hypotheses relating these measures to Haem-A-QoL and clinical measures. The Spearman correlation coefficient was used to assess convergent validity, and one-way analysis of variance (F statistic) was used to assess the known-groups validity (discriminatory power). The agreement between EQ-5D-5L and SF-6D indices was assessed using the intraclass correlation coefficient (ICC) and the Bland-Altman plot.Results: Both the EQ-5D-5L and SF-6D indices showed acceptable ceiling and floor effects. As hypothesised, both EQ-5D-5L and SF-6D were significantly correlated with Haem-A-QoL (both dimensions and overall score). EQ-5D-5L and SF-6D indices as well as EQ-VAS differentiated patients are known to differ in severity of haemophilia, bleeding status, disabling levels, and comorbidity. The F statistics in the known-groups comparisons suggested that the EQ-5D-5L was slightly more discriminative than the SF-6D. ICC (0.41) and Bland-Altman plot confirmed that the agreement between the EQ-5D-5L and SF-6D indices was poor.Conclusion: Both EQ-5D-5L and SF-6D showed satisfactory construct validity in the measurement of the HRQoL among patients with haemophilia. However, the two instruments may not be used interchangeably in this patient population due to their poor agreement and differing discriminatory power. [ABSTRACT FROM AUTHOR]

Objectives: Three hundred million people living with rare diseases worldwide are disproportionately deprived of in-time diagnosis and treatment compared with other patients. This review provides an overview of global policies that optimize development, licensing, pricing, and reimbursement of orphan drugs.Methods: Pharmaceutical legislation and policies related to access and regulation of orphan drugs were examined from 194 World Health Organization member countries and 6 areas. Orphan drug policies (ODPs) were identified through internet search, emails to national pharmacovigilance centers, and systematic academic literature search. Texts from selected publications were extracted for content analysis.Results: One hundred seventy-two drug regulation documents and 77 academic publications from 162 countries/areas were included. Ninety-two of 200 countries/areas (46.0%) had documentation on ODPs. Thirty-four subthemes from content analysis were categorized into 6 policy themes, namely, orphan drug designation, marketing authorization, safety and efficacy requirements, price regulation, incentives that encourage market availability, and incentives that encourage research and development. Countries/areas with ODPs were statistically wealthier (gross national income per capita = $10 875 vs $3950, P < .001). Country/area income was also positively correlated with the scope of the respective ODP (correlation coefficient = 0.57, P < .001).Conclusions: Globally, the number of countries with an ODP has grown rapidly since 2013. Nevertheless, disparities in geographical distribution and income levels affect the establishment of ODPs. Furthermore, identified policy gaps in price regulation, incentives that encourage market availability, and incentives that encourage research and development should be addressed to improve access to available and affordable orphan drugs. [ABSTRACT FROM AUTHOR]