Abstract: In 2021, CDE and FDA released guidance documents related to real-world data evaluation. In a healthcare industry where policy plays a key driving role, the policy overlays new landing breakthroughs, anchoring the real-world research track into a new windfall.
By Guo Yilin Yu Na Beijing, China Times (www.chinatimes.net.cn)
From drugs to electronic health records, real-world research is poised for even broader applications.
In recent years, "real-world research" has emerged as a "trendy term" in the field of big data in healthcare. In layman's terms, real-world research is the process by which data scientists and healthcare practitioners analyze real data collected in order to provide conclusions and recommendations for treatment.
In 2021, the Center for Drug Evaluation of the State Drug Administration of China (CDE) and the U.S. Food and Drug Administration (FDA) issued guidance documents related to real-world data evaluation, and in this medical industry, where policy is a key driver, policy overlays and new breakthroughs on the ground have pushed the real-world research track into a new windfall.
The ClinicalTrials website shows that the number of real-world studies is increasing every year. By 2020, according to incomplete statistics, more than 1,700 studies have been registered under the keyword "Real world," which is twice as many as in 2016. It is expected that there will be a spurt of real-world research findings from 2018 to 2022.
Will domestic real-world research companies ride this spring breeze and quickly usher in a bending period? In this regard, Feng Sheng, chief data scientist of Zero Krypton Technology, said in an interview with the Huaxia Times, "It is an extremely long process from RWD to RWE, and at this stage the country has to use real hardcore innovations such as statistics, epidemiology, and machine learning methods to drive real-world research to work quickly."
Compared to traditional clinical trials, which demonstrate the effectiveness and safety of drugs in an ideal environment, RWS is a study of drugs in a real environment, which has more practical implications for clinical decision making and guidance. Therefore, although the traditional randomized controlled trial (RCT) is still the gold standard, RWS has also gained more attention in recent years.
The ClinicalTrials website shows that the number of real-world studies is increasing every year. By 2020, according to incomplete statistics, more than 1,700 studies were registered under the keyword "Real world", which is twice as many as in 2016. Until 2018-2022, there will be a spurt of real world research findings.
Although the development of RWS in China is a fledgling stage, many industry insiders reflect that its stock market has not yet been fully tapped, and along with policy support and the growth of demand from pharmaceutical companies, the RWS market will continue to expand. 2020 statistics show that 18.91% of the real-world studies that continue to heat up are conducted in China. Among them, the percentage of research projects in active status is 68%, which is more than 15% higher than the global average.
Domestic and foreign companies have laid out, corresponding alliances, associations and platform centers have been established, and five new drugs based on RWS research have been launched globally. Although the RWS market is bustling with activity, everything is just beginning, and policy, data quality and compliance issues are still constraints to the development of the industry.
Feng Sheng believes that although China is already conducting practices including fast-tracking real-world research in Boao, Hainan, RWE for pediatric use, drug development for rare diseases and clinical co-medication, China should have its own original innovation in the field of real-world research.
In fact, along with the development of AI technology and natural language processing (NLP) technology, the existing clinical research model has been gradually changing. In RWS, with the help of such technologies, data can be processed efficiently on the one hand, and RWE can be quickly mined from RWD on the other. "This makes the impact of real-world data on clinical endpoints and how genetic testing affects the survival benefit profile of oncology patients worthy of further exploration by the industry." Feng Sheng said.
In addition, from the technical side, how can real-world data be transformed into real-world evidence in real-world research? This is where the relevance, reliability, traceability of data and its key. The large number of medical treatments in China, coupled with the different hospitals and geographic areas visited, make it easy to form information silos and no complete system. At the same time, the data standardization is insufficient, and the types of multiple records are incomplete. How to build to break the data barriers, form a comprehensive data chain with more multi-dimensional data, and build a data standardization system has been an important issue that needs to be urgently discussed and solved.
In this context, medical industry associations are also actively using the advantages of their associations to try to break through the data barriers through projects, such as the first real-world research project on stage I-IIIA non-small cell lung cancer (NSCLC) co-sponsored by the National Cancer Center and the Beijing Oncology Society, which targets a total of 30 provincial oncology hospitals across China to comprehensively collect data on the treatment of patients under different economic conditions, different living environments and different treatment concepts.
Behind the attention boom, it is inseparable from the strong support of the policy.
In 2021, CDE and FDA released the Real World Data (RWD) Guidelines for Generating Real World Evidence (RWE) (Pilot) and Real World Data: Evaluating Electronic Health Records and Medical Claims Data to Support Regulatory Decision Making for Drugs and Biologics, respectively. Thus unveiling the discussion of the regulation of RWS (real world research) in China, the US and Europe.
In addition, back in 2016, the U.S. explored the use of "real-world evidence" (RWE) to approve new indications for existing drugs and related research through the release of the 21st Century Medicine Act, and with it, the RWS quickly exploded. In China, policies related to RWS began with the State Council's No. 42 in 2017 and the Real World Research Guidelines released in 2018, entering a period of accelerated development. Hainan Lecheng, which took the lead in piloting the project, has also become the hotbed of RWS at the moment.
With the gradual improvement of policy and breakthrough in technology, more research projects are bound to form RWD into RWE. how can RWD become more valuable RWE? More and more companies are trying to implement post-market research with RWS to solve the problems of the traditional model. In Feng Sheng's view, the guidelines are not an integral part of the path to this as far as real world research is concerned.
"Through practice we tend to find that we are simply too rich in data. Therefore, I don't think the presence or absence of guidelines is a measure of a country's level of development in real-world research. Countries like Israel and the Nordic countries, which have high levels of RWD and RWE research, do not have corresponding guidelines; these countries have smaller populations and owe much of their success in real-world research to the integrated healthcare systems they have." Feng Sheng added.
In the process of acquiring real-world data, a data system needs to be constructed so that the source data can be converted to a research database," admits Xia Jielai, a professor at the Air Force Medical University. And then studies are conducted through prospective or retrospective methods in order to control bias and realize the transformation from real-world data to research evidence. The transformation from real-world evidence to real-world research cannot be achieved without scientific and rigorous design. The entire process must be based on protocol design, organization of the study, and quality control for data collection, data management, and statistical analysis.RWS and RCT complement each other although they differ in terms of study purpose, study population, sample size, study duration, study design, and implementation scenarios."
Liu Shusen, Chief Medical Officer of Linkstar Biologics, suggested that RWD can also play a unique advantage in the early development of innovative drugs, one is to discover new targets, mechanisms and drug resistance genes, and the other is to develop new Biomarkers and pinpoint target patients. To achieve the above purposes, multidimensional and high quality RWD is the foundation.
In his view, RWD-driven innovative drug development is about coming from the clinic to the clinic. "Because we know what kind of patients are more likely to benefit from some of these new targets. Then such a new R&D pathway can make traditional drug development more rapid and effective, and improve the success rate of drug development."
In the case of genetic testing, for example, this demand is based on clinical diagnosis and treatment. Some patients will undergo various genetic tests, and for patients who have undergone genetic tests, if they are continuously followed up to understand their treatment and clinical outcomes, and then integrate these collected patient follow-up data and public health data, they can be used as the basis of RWD. We can then use AI and big data mining technologies to find out which potential genes may become new targets for drugs to facilitate and guide new drug development. At the same time, these data can also guide future clinical benefits.
Therefore, the key to reaching this goal is to improve data quality and relies on regulatory, clinical and industrial academia working together. With good data collection, governance and scientific analysis under the framework of relevant guidelines and norms, real-world studies are able to produce convincing evidence. At this stage, in rare diseases, orphan drugs or research areas where RCTs are less feasible, using RWE to improve research efficiency and shorten the development cycle as much as possible can undoubtedly benefit patients earlier.
As of today, the number of RWS-type medical projects that Zero Krypton Technologies participates in is approximately 300 per year. For example, a drug that was prioritized for use in the BoaoLeCheng Advance Zone in Hainan has accumulated a large amount of treatment data during the course of its use. In order to expand to a broader population of drug users in mainland China, the sponsor has adopted the RWS research results designed and executed by Zero Krypton's lead, which has helped the sponsor submit an interim summary report to the regulator within the optimal time window and has been approved by the regulator.
"In the future, we can see RWS and the evidence it generates helping to get drugs prescribed and used more quickly and better in a wider region of China." Feng Sheng admits.