In the pioneer area of medical tourism in Lecheng, Boao, Hainan, medical workers are conducting real-world research on fluocinonide intravitreal implants. This drug is the first imported registered drug approved by China based on overseas clinical trial data and real-world data of domestic patients. (Photo courtesy of the interviewee)
The "real-world research" based on the clinical effectiveness of medical products and various data of patients plays an important role in empowering enterprises to develop new drugs and accelerating the examination and approval of medical equipment. China has a large population base and a relatively high level of medical information development, which has accumulated a huge amount of medical data and provided a good soil for real-world research.
Recently, the Economic Information Daily reporter learned from the second Boao International Conference on Real-world Research of Medical Instruments that real-world research has attracted the attention of global pharmaceutical companies and regulatory agencies. In recent years, China has launched a real-world data application pilot, and some cities have also begun the layout of related industries. At the same time, more than 10 innovative medical equipment products, such as glaucoma drainage tube and platini, have been listed in China with the help of real-world data, which not only benefits patients more widely, but also promotes the new development of China's medical equipment industry.
"Rising Star" of Evidence-based Medicine
What is real-world research? Professor Kang Deying of China Evidence-based Medicine Center once used "fishing" to explain the relationship between traditional randomized controlled trials and real-world research: the former is fishing in a highly controlled artificial environment, with a fishing rod, a pool and a cage; The latter is fishing in rivers and lakes in the natural environment.
In other words, when a drug is doing a randomized controlled trial, many restrictions similar to "laboratory" are set in advance, and it will select the test objects and means. The real-world research verifies the clinical effectiveness of drugs, and the samples cover a wider patient population.
In real-world research, the collected data come from complex and huge sources, including medical records, visiting information, follow-up records, electronic health cards, and even medical insurance databases. By analyzing these data, the basis of proving the effectiveness of drugs is obtained, which is called real-world evidence.
As a "rising star" of evidence-based medicine research, in the opinion of experts, real-world research is less difficult, lower in cost and more realistic and comprehensive in evaluation.
In addition, after a drug is approved for clinical use, it is much more complicated to have an "out-of-specification" dose and use other drugs in combination than when it is developed and tested, so it is necessary to continue safety monitoring and evaluation. Zhao Jun, reviewer of the Drug Evaluation Center of the State Food and Drug Administration, said that compared with traditional experiments, real-world research has absolute advantages in operation and time.
At present, the speed of global medical device innovation is accelerating, and real-world research has attracted the attention of global drug regulatory agencies and medical machinery enterprises. Many countries, including the United States, Britain, the European Union and China, have formulated policies around strengthening real-world research.
As early as 2015, the joint meeting of the British Academy of Medical Sciences and the Pharmaceutical Industry Association proposed that real-world evidence should be more widely used in drug research and development, approval and other aspects. In 2016, the US 21st Century Cure Act made it clear that regulators can use real-world evidence as the basis for approval. In August this year, the US Food and Drug Administration reiterated that "there is no need to apply for clinical research of new drugs for real-world research".
China is also at the forefront of the world in promoting real-world research. In 2018, China released the first real-world research guide. In June 2019, the State Food and Drug Administration and the Hainan Provincial Government jointly launched a real-world data application pilot in Boao Lecheng International Medical Tourism Pioneer Zone.
David Moeny, an expert of the US Food and Drug Administration, believes that with the development of artificial intelligence, 5G and other technologies, real-world data collection and processing will be more convenient, and the "real-world era" may accelerate.
A "new tool" to drive the medical machinery industry
In June this year, China's first real-world research project on anti-Covid-19 drugs on the market was launched in Beijing. The study, involving 30 provincial regions, more than 100 large hospitals and primary medical institutions, will include the real data of nearly 40,000 patients in COVID-19.
"This shows that real-world research has broad application prospects in drug safety evaluation." Eric Barrette, senior director of Medtronic, said that because real-world research can speed up the approval of medical devices and product monitoring after listing, pharmaceutical giants have regarded it as a "new tool" and a "new weapon" for industrial expansion.
Roche acquired two tumor big data companies; Bristol-Myers Squibb incorporated real-world research into strategic planning; The real-world evidence platform developed by Sanofi has hundreds of millions of patient data, covering more than 300 disease fields; AstraZeneca has made great efforts to deploy real-world research under the background of a perfect clinical trial framework ... "We are both participants in the whole process and beneficiaries of the results in the practice of real-world research." Ma Liqiao, president of Qiming Medical Devices Co., Ltd. said that real-world research allows enterprises to know and ensure the safety of patients at the first time when there is a problem with the product status. As a result, iterative products and innovative products can emerge continuously.
"Real-world evidence has gradually replaced traditional clinical evidence and greatly reduced the research and development cost of medical equipment." Gao Guobiao, deputy director of National Medical Products Administration Medical Device Evaluation Center, admitted that the cost of large-scale clinical randomized controlled trials of some rare diseases is rising, and real-world research just makes up for this defect.
The most important thing for medical machinery enterprises is that real-world research can accelerate the approval and listing of new drugs.
In April, 2021, OCV announced that its new drug, fluoxetine vitreous implant, was approved for marketing. This is the first time that the State Drug Administration has accepted a drug declaration based entirely on real-world data, shortening the time to market of this new drug by at least 18 months. In Lecheng, Hainan, Boston Scientific's prostate thermal steam ablation system, a pilot application of real-world data research, took only about 4 months from registration acceptance to approval, two and a half years earlier than the traditional process. Penny Peng, head of the project, said that at present, more than 100 hospitals have introduced this ultra-minimally invasive technology, and many patients have benefited from it.
Up to now, 13 pilot varieties, such as glaucoma drainage tube, femtosecond laser eye treatment system and Platini, have been approved to be listed in China by using the real world data of Lecheng.
"Real-world research has brought more opportunities for the development of pharmaceutical companies." Zhao Jun said that through real-world research, pharmaceutical companies can systematically understand the broad population characteristics and clinical medication characteristics of products, so as to better identify and manage market segments and collect high-quality product promotion information.
Join hands in racing the future track.
China has a large population base and a relatively high level of medical information development, and has accumulated a huge amount of medical data, which provides a good soil for real-world research. However, experts in the industry generally believe that China's real-world research is still in the development stage of climbing the hill.
"Data is a valuable treasure." According to Alvin Wong, director of Statistics and Clinical Pharmacology Department of Drug Evaluation Center of State Food and Drug Administration, there is a bottleneck in the real world research practice in China.
The pilot experience shows that real-world data research and application are faced with five key problems: low data quality and inapplicability, inconsistent data standards and inability to integrate; It is difficult to protect patients' personal information; Multi-party rights cannot be taken into account and the level of data industrialization is not high; And it is difficult to ensure the quality, intensity and scientific supervision of evidence.
Xu Jinghe, deputy director of the State Food and Drug Administration, believes that to effectively solve the above problems, it is necessary to cooperate with many departments such as health, medical insurance, drug supervision and informatization, join hands with clinical institutions, medical equipment manufacturers, scientific research institutes and other units, learn from foreign advanced experience, make full use of information technologies such as artificial intelligence, big data, Internet of Things and blockchain, and continue to promote real-world research, cooperation and sharing with the concept of scientific supervision.
Experts in the industry suggest that, first, we should break the data barrier and establish a unified national data standard; Second, we should explore the ethical review and informed consent model that conforms to the characteristics of real-world data utilization, and clarify data property rights; Third, we should promote the organic integration of medical big data, improve the quality and applicability of data, promote the circulation and use of data and realize industrialization.
Jia Ning, director of Hainan Boao Lecheng Medical Tourism Pioneer Zone Administration, said that Hainan Province will continue to expand the scope of pilot varieties by using the Lecheng pilot platform, guide the whole process with one enterprise and one policy, continuously improve the communication mechanism, and promote the listing of innovative medical equipment. At the same time, we will continue to explore data application products and promote real-world evidence to play a greater role in all aspects of the product life cycle, such as pre-market evaluation and post-market monitoring.
"It is necessary to unify the technical requirements of research." David Moni said that the medical regulatory agencies in the United States, China and many other countries are issuing real-world research guides one after another, which makes the accumulation and processing of relevant data safer, and also facilitates unified supervision and better decision-making.
Geng Zhongyu, Assistant Director of Device Safety in China Office of the US Food and Drug Administration, emphasized "transnational cooperation": "The global real-world data and evidence can be shared through a national cooperation network, and the health data of more countries and organizations can be integrated to race this future track together." (Reporter Chen Kaizi)
Source: Economic Information Daily