For patients suffering from rare diseases, it takes on average more than 4 years for them to be diagnosed; nearly 70% of doctors say they do not understand this kind of diseases. The results of the 2020 Comprehensive Social Survey of Rare Diseases in China show that missed diagnosis and wrong diagnosis, weak treatment capacity, and lack of drugs are the three major problems in the diagnosis and treatment of rare diseases worldwide.
“Through the multidisciplinary diagnosis and treatment platform for rare diseases, the time it takes for patients suffering from rare diseases to be diagnosed has been shortened from 4 years to 4 weeks at PUMCH,” said PUMCH President Zhang Shuyang gently but firmly on February 26, 2022, at the venue of the National Rare Disease Diagnosis and Treatment Collaborative Network Work Conference, and her remarks was met with extended applause. PUMCH, a prestigious hospital with a history of 101 years, while leading the national rare disease diagnosis and treatment collaborative network, has built a rare disease diagnosis, treatment and research system for the country, and will continue to work towards the “China solution” to address the difficult problems for the prevention and treatment of rare diseases.
Crack the Hard Nut in Diagnosis: Adopt One-stop Treatment under the Diagnosis and Treatment Collaborative Network
The Government have made comprehensive arrangements for the diagnosis, treatment and research of rare diseases, requiring greater availability and accessibility of rare disease drugs and stronger prevention and control of major diseases, and a series of first-time breakthroughs to be made. In 2018, five national ministries and commissions jointly released the “List of Rare Diseases (First Batch)”, which is of landmark significance and includes specifically 121 rare diseases. The National Health Commission established in 2019 the National Rare Disease Diagnosis and Treatment Collaborative Network that involves 324 hospitals, basically putting in place a three-level rare disease prevention and control system.
PUMCH is the only national-level hospital that takes the leading role in the National Rare Disease Diagnosis and Treatment Collaborative Network. It cooperates with the other 323 hospitals to conduct collective diagnosis and treatment and two-way referrals for patients with rare diseases, which expands the coverage and influence of high-quality medical resources. On February 28, 2019, the PUMCH Rare Disease Multidisciplinary Diagnosis and Treatment Platform was established. It adopts a “one-stop treatment plan” and holds multidisciplinary team consultations for rare diseases (hereinafter referred to as the “rare disease MDT”) every Thursday at noon. As of February 28, 2022, a total of 123 consultations have been held with the attendance of more than 300 experts in various fields, and are open to more than 100 member hospitals of the National Rare Disease Diagnosis and Treatment Collaborative Network; the “PUMCH Case Collection of Multidisciplinary Collaborative Diagnosis and Treatment for Rare Diseases (2021 Edition)” provides cases that doctors in primary hospitals can refer to for improvement in their own rare disease diagnosis and treatment capabilities.
“On the one hand, the rare disease MDT gives hope to rare disease patients. It solves the problems of patients in a ‘one-stop’ way, minimizes misdiagnosis and mistreatment, shortens the waiting time, offers more treatment options for patients, and reduces the burden of referrals and repeated examinations on patients’ family. On the other hand, MDT also empowers doctors. It provides a platform for multidisciplinary academic exchanges and clinical cooperation, which helps improve the comprehensive capabilities of doctors, especially the young doctors, secure new disciplinary advantages, and strengthen scientific research innovation,” said PUMCH President Zhang Shuyang.
PUMCH also conducts remote multidisciplinary consultation, with more than 1,000 patients referred through the National Rare Disease Diagnosis and Treatment Collaborative Network. “Reduction in diagnosis time from 4 years to 4 weeks” and “90% reduction in cost” have become a reality in PUMCH.
Address the Weak Ability in Diagnosis and Treatment: Draw up Guides and Organize Training
“Doctors who can diagnose rare diseases are rarer than patients with rare diseases.” The capabilities of doctors, especially those in primary hospitals with limited ability to identify and diagnose rare diseases, are insufficient for the improvement needed in rare disease diagnosis and treatment. How to solve this problem? PUMCH gave its own answer.
The “The First List of Rare Diseases” was officially released on June 8, 2018. Under the guidance of the National Health Commission, PUMCH organized experts across the country to prepare the “Compendium of China's First List of Rare Diseases” and the first “Guidelines for Rare Disease Diagnosis and Treatment” in China. Based on the List and the Compendium, the 700,000-Chinese-character Guidelines elaborates on the definition, etiology, epidemiology, clinical manifestations, auxiliary examinations, diagnosis, differential diagnosis and treatment of rare diseases, and proposes the diagnosis and treatment procedures. The flow charts in the Guidelines clearly show the diagnosis procedures and treatment principles, which is of great significance for training medical staff and guiding them in rare disease diagnosis.
In 2020, PUMCH took the lead in preparing China’s first systematic textbook on rare diseases, that is the “Textbook on Rare Diseases”; in 2021, President Zhang Shuyang opened the “rare diseases” course in Peking Union Medical College for the first time as the director of the course, filling in the gap in medical education of rare diseases. With the support of relevant parties, PUMCH took the lead in organizing training sessions across the country, covering more than 80 rare diseases and over 50,000 doctors.
Upon the approval of the National Press and Publication Administration, the “Journal of Rare Diseases” sponsored by PUMCH was officially published in 2022. This journal will comprehensively update basic and clinical research on rare diseases, and new developments, progress and achievements in the research and development of orphan drugs to inform policy makers, scientists, and medical staff involved in rare disease-related research.
In addition, PUMCH and Tsinghua University have also jointly developed an AI-assisted diagnosis tool for rare diseases. The preliminary verification shows that its disease prediction accuracy rate is higher than that of doctors. This tool can be implemented in primary hospitals upon optimization to assist doctors in rare disease diagnosis.
Crack the Hard Nut in Treatment: Improve Drug Accessibility
In September 2020, the National Health Commission established the second Expert Committee on Rare Disease Diagnosis, Treatment and Security, with President Zhang Shuyang serving as the chairwoman. In 2020, the National Health Commission gave the nod for PUMCH to establish a national professional quality control center for rare diseases. Following the principle of “putting people and their lives first”, PUMCH has surmounted all obstacles on its path towards continuously improving the accessibility of rare disease drugs and exploring a multi-level medical security system.
PUMCH took the first “ice-breaking” journey for the “one-time import” of mitotane, a clinically urgently needed rare disease drug in China; realized the compassionate drug use for rare diseases for the first time in China within 83 days when Eculizumab Injection ran out; completed the first ultrasound-guided “radiation-free” complex intrathecal injection internationally, marking the first successful drug use for an adult patient with spinal muscular atrophy in China; put into clinical application Aldurazyme targeted at mucopolysaccharidosis for the first time in China; made the first prescription in China for a wild-type ATTR-CA patient after Tafamidis was approved for the treatment of ATTR-CA indications, basically achieving the global synchronization of the medication of ATTR-CA patients. With the support and coordination for rare disease diagnosis and treatment by relevant departments at different levels, PUMCH has established an innovative model for the approval and marketing of more rare disease drugs in China, benefiting more patients.
The research on the medical security system for rare diseases in China led by the China Alliance for Rare Diseases has produced many findings, and those findings serve as a scientific basis for the government in formulating policies of medical services for rare diseases and medical insurance coverage of rare disease drugs. In January 2022, Xiaoyu, who was diagnosed with spinal muscular atrophy (“SMA” for short), was wheeled into a consultation room by her parents. “She could walk before going to the elementary school, and sit without support before junior high school. But now she can’t even sit without the support of the left leg.” Xiaoyu’s mother tried to remain calm, but her voice was obviously trembling. Xiaoyu is unfortunate, but she is also fortunate as Nusinersen Sodium Injection, a drug targeted at SMA, was included in the national basic medical insurance list at the end of 2021, reducing the drug price from RMB 700,000 to RMB 33,000 per injection. “Every group, however small, should not be given up”, said a negotiator in the national centralized drug procurement negotiation, which touched many people. What supports Xiaoyu’s frail body is not only her parents who love her, but also thousands of Chinese doctors who diagnose and treat rare diseases, as well as the commitment of the government to not give up on any disadvantaged group…
Look ahead: Establish the National Rare Disease Clinical Research Collaborative System
With the support of the state, PUMCH has built the State Key Laboratory of Complex, Severe and Rare Diseases, and the National Infrastructures for Translational Medicine. A PUMCH-shaped blueprint for the diagnosis and treatment of rare diseases has gradually become clear. Such efforts will benefit both present and future generations.
In order to find out the “ins and outs” of rare diseases in China, the National Health Commission entrusted PUMCH to develop the “China Rare Disease Diagnosis and Treatment Service Information System”, which will be used to register information of outpatient and inpatient cases suffering from rare diseases on the list (the first batch) in the 324 hospitals in the cooperative network. In the past three years, the number of registered cases in the direct reporting system has exceeded 500,000, covering 121 diseases, and 61 hospitals outside the cooperative network have actively participated in case registry. The establishment of the direct reporting system can offer guidance for case monitoring, diagnosis and treatment data, disease burden, and medical services provision.
In 2016, PUMCH and 19 top domestic hospitals jointly established China National Rare Disease Registry System (NRDRS). The platform conducts registry-based studies on multiple rare diseases and collects clinical data and biological samples of cases, aiming to build a rare disease clinical database and biobank for the Chinese population, thereby supporting rare-disease-related clinical research and new drug or medical device development. By the end of 2021, NRDRS has covered 101 cooperative units in 29 provinces, autonomous regions and municipalities across the country; 188 research cohorts have been established for 171 kinds/categories of rare diseases, and nearly 70,000 rare disease patients have been registered.
The three major research platforms, namely, the NRDRS, the State Key Laboratory of Complex, Severe and Rare Diseases, and the National Infrastructures for Translational Medicine, have supported more than 500 studies in nearly 100 institutions; researchers have formulated more than 100 rare disease-related diagnosis and treatment guidelines and consensus, published hundreds of rare disease research papers, conducted dozens of national multi-center clinical trials, and built one of the largest rare disease resource banks in the world.
A 20-year-old young boy unfortunately passed away due to the rapid progress of heart failure. Ten years ago, his sister, with the same intractable symptoms, met the same fate. The grief-stricken parents wanted desperately to know the cause of death of the sister and brother and begged the attending doctor to send the only remaining specimen to PUMCH. With multi-party cooperation and coordination, it was finally determined that the boy had Danon disease, a rare X-linked dominant genetic disorder, and rapid progress of heart failure was one of the most common symptoms of the disease. If the elder sister who died 10 years ago could have been correctly diagnosed, the fate of her younger brother might have been very likely different. “We really hope that this result can help other patients and let more doctors know about Danon disease,” said the parents. The simple wish of the parents, who, like all of us, never give up despite our differences, is exactly what many rare disease doctors have worked hard and exhaustively for and their life-long pursuit. Even in darkness, light comes in through cracks, which is true for everyone and everything in the world.
Journalist: Chen Xiao and Chen Mingyan
Translator: Liu Haiyan
Editor: Wang Yao