Professor Zhang Shuyang: From macro layout to micro construction, outline the rare disease diagnosis and treatment service system with Chinese characteristics

*For medical professionals only

The state, societies and hospitals collaborate to enhance the sense of acquisition of rare disease patients!

Rare diseases refer to a type of disease with a very low incidence, with serious disease, difficult diagnosis, high misdiagnosis rate, low cure rate and other characteristics, which is one of the medical fields that need to be paid attention to and urgently need to be overcome. In recent years, driven by policies and technologies, the field of rare diseases has received widespread attention from all walks of life. At present, what is the current status of the development of rare diseases in China, and what role does the state, medical institutions and other organizations play in it?

In this issue of "Meet rare", Professor Zhang Shuyang, President of Peking Union Medical College Hospital and Secretary General of the Secretariat of the China Rare Disease Alliance, is specially invited to tell you about the achievements and challenges of the development of China's rare disease cause in combination with the development process of concord in the past century...

Multi-pronged approach to help the development of rare diseases

▌ The five-year construction of NRDRS has achieved initial results

Since its establishment in 2016, NRDRS has grown a lot after more than five years of construction, while continuously realizing the original intention of construction:

The project cooperation unit has covered 101 medical institutions and universities from 29 provinces, autonomous regions and municipalities directly under the central government, and the number has reached five times that of the initial stage of project construction;

NRDRS registered a total of 171 rare diseases/classes, established 188 clinical research cohorts, registered 68,137 patients with rare diseases, and tracked the survival status of 19,845 of them, establishing long-term and close contact with patients;

With the informed consent of patients, NRDRS collected and preserved biological samples and related information of 16,987 patients with rare diseases, which will accumulate valuable data resources for the exploration of the pathogenesis of rare diseases and the development and screening of emerging therapeutic drugs.

As The first standardized super-large, multi-center, multi-disease rare disease registration research platform in China, NRDRS has realized the standardization and unification of rare disease registration research in China, and its extensive coverage and huge data volume have also laid a solid foundation for the development of clinical research, epidemiological research and related medical product clinical trials of rare diseases in China. At the same time, the long-term and continuous operation of NRDRS will also become the best and most reliable mode for breaking through the bottleneck of rare disease research and development, and building a communication between the pharmaceutical industry, doctors (researchers) and patients.

▌In response to challenges, many parties have made efforts to improve the level of diagnosis and treatment and protection of rare diseases in China

Professor Zhang Shuyang: At present, the challenges faced by rare diseases in China mainly include three aspects: diagnosis and treatment level, drug accessibility and treatment affordability, and the specific analysis is as follows:

Rare disease diagnosis and treatment level: rare diseases often involve multiple systems and tissues throughout the body, diagnosis and treatment is difficult, the rate of missed diagnosis and misdiagnosis is high, "rare disease doctors are rarer than patients" is a problem that must be solved to improve the ability of rare disease diagnosis and treatment.

Accessibility of drugs: lack of effective treatment drugs after the diagnosis of the disease; or there are drugs that can be treated but have not yet been marketed in China; or although the drugs are listed in China, they have not been approved for rare disease indications.

Affordability of treatment: Some rare diseases have drugs to treat, but they have not yet been included in the scope of medical insurance reimbursement, or "ultra-indication drugs" lead to medical insurance can not be reimbursed, increasing the economic burden of patients.

Regarding rare diseases, the questions we urgently need to know are: What are the rare diseases in China? How many patients with rare diseases are there, where are they distributed, and what is the prevalence and annual incidence of each disease? What are the difficulties in the diagnosis and treatment of various rare diseases, and what are the effective treatment methods? How to establish the standard diagnostic process and clinical pathway for rare diseases? What is the current status of the development of advantageous disciplines and clinical teams in the diagnosis and treatment of rare diseases in China? How to plan and implement the training and network for rare disease diagnosis and treatment? What is the current status of medical expenses for each disease and the medical burden of patients with rare diseases?

In view of the above challenges and urgently clear questions, the objectives of China's rare disease protection work are: to determine the definition of rare diseases in China; to clarify the disease and distribution of rare diseases; to formulate targeted support policies and prevention strategies to provide reference for the research and development of orphan drugs and related diagnosis and treatment methods; to shorten the diagnosis time, reduce the rate of misdiagnosis, and improve the effect of diagnosis and treatment; to provide accurate and effective medical guidance for rare disease patients; to support the effective operation of the national rare disease collaboration network; and to support the rapid listing of national orphan drugs and other policy formulation Provide a reference for medical insurance support policies for the cost of diagnosis and treatment of patients with rare diseases.

In recent years, the state and the government have attached great importance to the diagnosis and treatment of rare diseases. The National Health Commission has established an expert committee on rare disease diagnosis, treatment and protection, a national rare disease diagnosis and treatment cooperation network and a national rare disease quality control center. Through the joint efforts of the government and many parties in society, the diagnosis and treatment and protection of rare diseases in China have developed rapidly.

Among them, the accessibility and affordability of drugs for rare diseases have been effectively improved. The 2019 edition of the Medicare Catalogue contains 22 drugs for rare diseases (rare diseases covering 13 diseases), while the 2020 edition of the Medicare Catalogue increases the number of drugs for rare diseases to 45 (rare diseases covering 22 diseases). In the recently updated 2021 National Medical Insurance Drug List, 7 new drugs for the treatment of rare diseases (including Nosinasin sodium injection for the treatment of spinal muscular dystrophy, ammydine extended-release tablets for the treatment of multiple sclerosis, agasacidase α for injection of concentrated solution for the treatment of Fabre disease, human coagulation factor IV. for the treatment of hemophilia, Etibant acetate injection for the treatment of hereditary angioedema, ilojumab injection for the treatment of homozygous familial hypercholesterolemia and soft capsules of clobenzozolic acid for the treatment of transthyroxin amyloidosis cardiomyopathy).

The increasing number of drugs available for rare disease medical insurance and the expansion of disease coverage indicate that the supply guarantee mechanism and medical security mechanism for rare disease drugs in China are becoming more and more sound, and the medical security of rare disease patients has been further improved. In addition, as more rare disease drugs are included in medical insurance, more patients can use rare disease drugs, and clinicians will accumulate valuable clinical drug experience, which will help improve the ability of doctors to identify, diagnose and treat rare diseases, thereby improving the overall diagnosis and treatment capabilities of rare diseases in China and benefiting more rare disease patients.

Let the standardized diagnosis and treatment of rare diseases in China have a basis for evidence

Professor Zhang Shuyang: Rare diseases are a general term for a large category, in which the diagnosis and treatment of each disease has its own characteristics. For example, transthyroxin protein amyloid cardiomyopathy (ATTR-CA) is an infiltrating myocardial lesion, the clinical manifestations of the disease lack specificity, not only clinicians do not understand the disease, the disease diagnosis and treatment also lacks a standardized process; in addition, the previous ATTR-CA diagnosis relies on pathological biopsy, and clinical development is more difficult. Therefore, there is a serious underdiagnosis and misdiagnosis of ATTR-CA.

In recent years, with the increasing number of ATTR-CA-related studies and the increasing standardization of the diagnostic process, the academic community generally believes that the prevalence of the disease may be underestimated; and the emergence of non-invasive diagnostic methods and effective prognostic drugs has made us continuously standardize and update the clinical manifestations, diagnostic processes and treatment methods of ATTR-CA:

In 2020, the Galen Prize, known as the "Nobel Prize" of the medical community, awarded the best biotechnology product award to drugs that treat ATTR: Paritisiran, Inotersen and chlorobenzolic acid. The advent of these drugs has greatly changed the situation that ATTR is incurable. Among them, clobenzozolic acid is an oral small molecule drug, which can inhibit TTR amyloid fiber formation, and can significantly reduce the all-cause death and cardiovascular-related hospitalization rate of ATTR-CA patients. In 2019, 80 mg of clobenzazolic acid was approved by the FDA for the treatment of ATTR-CA. China's State Drug Administration (NMPA) also approved chlorobenzazolic acid (61 mg after changing the dosage form) for the treatment of ATTR-CA in October 2020. Clobenzazolic acid is the only drug with current evidence to improve prognosis in patients with ATTR-CA;

In April 2021, the Cardiovascular Disease Branch of the Chinese Medical Association published the "National Consensus on the Diagnosis and Treatment of Transthyroxine Cardiac Amyloidosis", which provides a reliable basis for the diagnosis and treatment of ATTR-CA in China.

In the diagnosis and treatment of difficult and rare diseases in China, Concord comes first

Professor Zhang Shuyang: Peking Union Medical College Hospital has taken the diagnosis and treatment of difficult and rare diseases as its mission since its establishment, and the case of one of the three treasures of Concord has witnessed the milestone progress of rare disease diagnosis and treatment in China:

It records the first diagnosis of rare diseases in China and even in the world: the first case of multiple sclerosis in China in 1922; the first case of pheochromocytoma in China in 1929; the first case of Wilson's disease in China in 1931; the first name of "renal osteodystrophy" in the world in 1935; the first case of hereditary angioedema (HAE) in China in 1981; and the first case of mitochondrial disease in China in 1993.

It has pioneered many firsts in the treatment of rare diseases in China: in 1922, the first case of spinal cord tumor resection in China; in 1924, the first case of sigmoidoscopy in China; in 1934, the first case of insulinoma resection in China; in 1938, the first case of adrenal tumor resection in China; in 1983, the establishment of China's first neonatal ward and intensive care department; in 1984, the first case of cochlear implantation in China was carried out for the first time.

Peking Union Medical College Hospital has been inherited and developed for a hundred years, and its sound disciplinary foundation has provided important academic support for the leapfrog development of rare diseases in China and played a leading role in the whole country; in addition, Peking Union Medical College Hospital has set the National Guidance Center for Diagnosis and Treatment of Difficult and Severe Diseases designated by the National Health Commission, the State Key Laboratory of Difficult and Severe Diseases and Rare Diseases, the National Center for Translational Medicine, the National Center for Quality Control of Rare Diseases and the only national center of the National Rare Disease Diagnosis and Treatment Collaboration Network, which will be based on the diagnosis and treatment research system. Work with colleagues across the country to promote the development of the transformation of clinical and research results of rare diseases in China, and benefit patients with rare diseases.

Doctors are in a key position in the diagnosis and treatment of rare diseases, and young doctors are not only the reserve army of national doctor resources, but also a new force for clinical work. In view of the current shortage of rare disease professional resources and insufficient doctors' diagnosis and treatment capacity, in 2021, Peking Union Medical College Hospital compiled China's first postgraduate national planning textbook "Rare Diseases" and opened courses at Union Medical College. We carry out rare disease training offline or online every year, and have trained more than 100,000 doctors or medical students nationwide.

Peking Union Medical College Hospital will uphold the spirit of "rigorous refinement, diligent dedication", continue to improve the training system for rare disease talents, fill the gap in rare disease higher education (undergraduate and above), and will also provide opportunities for rare disease professionals across the country to learn, further study and practice in the rare disease diagnosis and treatment research platform of Peking Union Medical College Hospital, and welcome young doctors and grass-roots doctors to actively participate in rare disease-related training and knowledge popularization, and improve the overall diagnosis and treatment level of rare disease doctors.

Expert Profiles

Professor Zhang Shuyang

President of Peking Union Medical College Hospital, Vice President of Peking Union Medical College, Chief Physician, Professor, Doctoral Supervisor, Chinese Academy of Medical Sciences and Peking Union Medical College.

Chairman of the Expert Committee on Rare Disease Diagnosis and Treatment and Protection of the National Health Commission

Director of the National Center for Quality Control of Rare Diseases

Vice Chairman and Secretary General of China Rare Disease Alliance

Director, World Medical Association

Standing Director of Chinese Medical Association

Member of the Standing Committee and Secretary-General of the Cardiology Branch of the Chinese Medical Association

President-designate of cardiovascular physician branch of the Chinese Medical Doctor Association

Source: Rare Diseases Channel of the Medical Community

Editor-in-charge: Wan Shunshun

Proofreader: Zang Hengjia

Plate making: Xue Jiao