As a bispecific antibody program for the secondary prevention of stroke, the "Efficacy Study of Clopidogrel in High-risk Groups of Acute Non-disabling Cerebrovascular Disease Events" completed by the Chinese research team has been recommended as the highest level of evidence by authoritative guidelines for cerebrovascular diseases in the United States, Europe, Canada and other countries and regions.
Reporter Dai Xiaopei.
This year marks the 20th anniversary of The Lancet Neurology. A few days ago, the journal reviewed 15 major advances that have changed the clinical practice of stroke in the past 20 years, including the "Efficacy Study of Clopidogrel in People at High Risk of Acute Non-disabling Cerebrovascular Disease" (hereinafter referred to as the CHANCE Study) completed by the team of Professor Wang Yongjun of the National Clinical Research Center for Neurological Diseases in China, which also became the only study selected in Asia.
In 2001, the Temple of Heaven International Conference on Cerebrovascular Diseases (hereinafter referred to as the Temple of Heaven Conference) was born. This has promoted the integration of cerebrovascular disease research in China with international standards.
In 2002, the stroke unit was introduced into China, which greatly shortened the distance between the clinical practice of cerebrovascular diseases in China and the world. In the following 20 years, from the World Stroke Organization participating in the hosting of the Temple of Heaven to the establishment of the Chinese Stroke Society, China's cerebrovascular disease research has grown from weak to strong, from small to large, and the "highlight moment" is CHANCE research.
CHANCE research opens up a new path for short-range bispecific antibodies.
For a long time, it has been generally believed in the industry that antithrombotic (anticoagulant or antiplatelet) drugs for patients with ischemic cerebrovascular disease are the mainstay.
Although a single antiplatelet (i.e., aspirin monotherapy**) can reduce the risk of ischemic cerebrovascular disease** and death, the three-month** rate is still more than 10%, which poses a heavy burden on the patient, the patient's family and society.
Therefore, it has been proposed to reduce the risk of stroke with aspirin and clopidogrel in combination with antiplatelet drugs** (bispecific antibodies**). Theoretically, bispecific antibodies** can have a synergistic effect to enhance antiplatelet efficacy and prevent stroke**. However, three related international large-scale clinical trials failed.
In this regard, Wang Yongjun raised three key questions: Which patients may benefit from the use of bispecific antibodies**? How long should I take the medication? What should be the dosage?
In order to answer these three questions, with the support of the National Major New Drug Creation Science and Technology Project, Wang Yongjun led the team to start the CHANCE study.
In terms of suitable populations, we found through previous big data analysis that patients with transient ischemic attack and mild ischemic stroke are more suitable for bispecific antibodies**; With regard to drug dose, we found the optimal loading dose through basic research on platelet activity. "Chance study participant.
1. Jing Jing, deputy chief physician of the National Clinical Research Center for Nervous System Diseases, told science and technology reporters.
Questions about the length of medication are the most difficult to answer. Authoritative guidelines in Europe and the United States have previously considered that patients who use bispecific antibodies** for 90 days benefit the most. "But after repeated research, especially big data analysis, it took us several years to determine that 21 days of bispecific antibodies** can benefit patients the most. Wang Yongjun said that the 21-day plan is the key to victory.
Wang Yongjun's team creatively proposed that within 24 hours after the onset of stroke patients, initiating a low- and medium-dose aspirin and clopidogrel dual-target combination antiplatelet drug** for 21 days can reduce the risk of stroke in high-risk patients by 32% without increasing the risk of bleeding. "This is completely the original work of Chinese researchers. Jing Jing said.
In February 2013, CHANCE's findings were published in the New England Journal of Medicine. As a bispecific antibody** regimen for the secondary prevention of stroke, this study has been recommended as the highest level of evidence by authoritative guidelines for cerebrovascular diseases in the United States, Europe, Canada and other countries and regions. The 21-day rule has become the gold standard for bispecific antibodies for ischemic cerebrovascular disease**. For the first time, the European Medicines Agency has also rewritten the instructions of clopidogrel based on the trial initiated by Chinese scholars.
This is the first international standard set in the field of cerebrovascular disease in China, and it is a major breakthrough in the field of secondary prevention of stroke in China. Wang Yongjun said that CHANCE research has broken through the bottleneck of clinical evaluation of major new drug creation in China and established confidence in clinical research in China.
According to relevant data, this new drug use program has cumulatively reduced hundreds of thousands of cerebrovascular disease cases in China, and reduced the hospitalization cost of patients by more than 10 billion yuan. The programme is widely used worldwide and is expected to reduce the number of strokes** globally by 300,000 per year. Wang Yongjun said.
China's stroke clinical research system is improving day by day.
Wang Yongjun told reporters that the greatest significance of CHANCE research is to lead the reform of domestic clinical research methodology, which can provide a good reference for future research work.
First, we must do a good job in top-level design. "Gradually turning clinical problems into research questions, and then into research hypotheses, study designs, and standard operating procedures, is a huge test for clinicians in China. Wang Yongjun said that CHANCE research has made a breakthrough in top-level design and accumulated experience in dialogue with top international teams.
Second, it is necessary to continuously improve the research system. "Before the CHANCE study, there was no project management system for clinical research in China, and there was a lack of mature professional methodology team. CHANCE Research has left behind a very professional team, and its design, statistics, data, logistics, projects, funds, archives and other links are managed by the most professional people. Wang Yongjun said that at that time, there were 114 hospitals across the country that participated in the CHANCE study, and more hospitals have since joined the CHANCE series of studies (CHANCE2 study, CHANCE3 study). Up to now, there are more than 2,000 members of the National Cerebrovascular Disease Clinical Research Cooperation Network, and the clinical research cooperation system of cerebrovascular diseases in China has been continuously improved.
Third, there should be professional training. "For a long time, there was no academic education for clinical trials in China. The CHANCE study exposed the shortcomings of clinical research in China, so we established the first clinical trial department in China at Capital Medical University to cultivate talents in clinical trials. Wang Yongjun said.
In recent years, the level of stroke research in China has been continuously improved and has begun to influence the world. At present, there are two flashpoints in stroke research in China: one is antithrombosis and the other is intra-arterial intervention. Wang Yongjun believes that this is due to the fact that China's overall scientific and technological environment is getting better and better, scientific and technological innovation has been highly valued, and investment in clinical research has been increasing.
At present, the clinical research system of stroke in China is gradually improving. The National Clinical Research Center for Neurological Diseases has established the world's largest collaborative network of hospitals with research capabilities. The members of the collaborative network usually participate in the training uniformly, and share the same standards, ethical system and management methods when there is a research project, which improves the speed and quality of research. Wang Yongjun said that with the blessing of a strong system, China can always have the best results in international multi-center clinical trials.
The future of finding new drugs for cerebrovascular diseases depends on big data.
Wang Yongjun believes that at present, the research on cerebrovascular diseases in China is still relatively weak in basic research. "In order to achieve transcendence in basic research on cerebrovascular diseases, China needs to find another way. He said.
Wang Yongjun introduced that in the past, finding new drugs was driven by knowledge, that is, after figuring out the physiological and pathological effects of a molecule, experiments were carried out on animals, and if animal experiments proved effective, they began to enter clinical trials.
The so-called alternative way is to rely on data-driven to find new drugs, that is, to find patterns from the data of clinical cohorts, and once the patterns are found, they will go back to cells and animals to determine their physiological and pathological effects. In this mode, the new drug discovery process is to first build a large cohort, measure the multi-omics data of the samples (blood, urine, feces, etc.) in the large cohort, and use the biometric information analysis of multiple groups to lock the target molecules related to clinical problems.
If the calculation finds a molecule that is related in the data, it is listed as a potential drug target, and then it is verified in the laboratory to find intervention methods, and then it enters animal experiments and clinical trials in turn. This is the data-driven model of finding new drug targets from clinical big data. Wang Yongjun said.
Wang Yongjun said that there are three key points to realize the whole chain of new drug transformation: first, high-quality queues; the second is a big data platform based on multi-omics; The third is to have a team that is familiar with the analysis of multiple groups of student biometric information. "China has innate advantages in this field, and has also established stromics, the world's largest multi-omics platform for cerebrovascular diseases, and the discovery and research and development of new drug targets have been greatly accelerated. Wang Yongjun said.
In addition, the National Clinical Research Center for Neurological Diseases carries out the "Physician Scientist" program every year to train doctors-scientists, and the Chinese Stroke Society is also promoting the "Future Leadership in Stroke Research" program.
Editor in charge: Zhi Yanrong).
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