The State Food and Drug Administration issued a document, the opportunity for the development of Chinese medicine is here!

Chinese medicine, development opportunities are here!

On May 29, the Center for Drug Evaluation of the State Food and Drug Administration issued the "Notice on Public Solicitation of "Basic Considerations for Drug Development Supported by Real World Evidence"." This is how real-world evidence is used in drug research and development, and it was first presented in official documents.

What is real world research?

The term "real world research" has become more and more exposed in the medical field in recent years. What is real world research?

To put it simply, Real World Study (RWS) is a clinical trial that originated from practicality. It is characterized by selecting treatment measures based on the patient’s actual condition and willingness based on a larger sample size, conducting long-term evaluations, and conducting long-term evaluations. Focus on treatment with meaningful outcomes. Real-world research is to dig out information from multiple data sets other than traditional evidence-based clinical research, and adopt non-random, open, and placebo-free research. The form of RWS includes observation queue, registration and management database.

Some people believe that the real world lacks strict methodological control, and the research results are quite biased, so the real world evidence is completely ignored. In fact, this understanding is one-sided, and the best research evidence of evidence-based medicine does not necessarily come from RCTs (randomized controlled trials).

Professor Kang Deying from West China Hospital of the Chinese Center for Evidence-Based Medicine once used an vivid example to explain the relationship between RWS and traditional RCT: RCT is fishing in an ideal state, such as a fish pond or a net cage, which is a highly controlled artificial Environment; while real-world research is fishing in reality, real rivers and lakes, this is the natural environment. In other words, real-world research is the process of comparing and selecting different medical methods under real clinical conditions and real environments; it is an evaluation study of specific medical interventions and actual operations and their results in the actual medical environment.

Six situations, real world evidence can be used

According to the Draft for Comments issued by the Drug Evaluation Center of the National Medical Products Administration, it lists 6 situations in which real-world evidence supports drug development and regulatory decision-making.

1. Rare disease treatment drugs

In addition to the scarcity of cases and difficulty in recruiting clinical trials of drugs for the treatment of rare diseases, the biggest challenge is the choice of controls, because rare diseases usually have no or few alternative treatments. Therefore, real-world data formed by natural disease cohorts can be used as external controls.

2. Revise indications or range of combination medication

For the expanded indications of drugs already on the market, randomized controlled clinical trials (RCT) are usually used to support the expanded indications. However, when RCTs are not feasible or the evidence generated is not optimal, practical clinical trials (PCT) are very important. Good choice. In the field of pediatric medication, there are often cases of off-label medication in domestic clinical practice. Using real-world evidence to support the expansion of the indicated population is also a strategy for drug research and development.

Using real-world evidence to support the expansion of typical cases of combination medication:

The vascular endothelial growth factor (VEGF) humanized monoclonal antibody preparation Bevacizumab (Bevacizumab) was approved in China in 2015 for combined chemotherapy (carboplatin and paclitaxel) for unresectable advanced, metastatic or recurrent non- First-line treatment for patients with squamous non-small cell lung cancer. In the real world, the combined chemotherapy regimens for patients are not limited to carboplatin and paclitaxel, but also include pemetrexed combined with platinum, gemcitabine combined with cisplatin and so on. In October 2018, the drug was approved to expand the treatment plan to a combined platinum-based chemotherapy regimen. The results of three real-world studies provided strong supporting evidence. These three studies retrospectively analyzed the patient data of the three hospitals, and all showed that the combination of bevacizumab on the basis of platinum-containing dual-agent chemotherapy significantly prolonged PFS and OS compared with chemotherapy alone, which is consistent with global population data, and did not find New security issues. In addition, relevant real-world studies also provided efficacy data in different patient subgroups such as EGFR mutations and brain metastases, confirming the effectiveness and safety of bevacizumab combination therapy from multiple angles.

3. Re-evaluation of post-marketing drugs

This is the most frequently mentioned application in the industry before discussing real-world evidence. Drugs approved based on RCT evidence usually have limited safety information, uncertain efficacy conclusions, and medication regimens due to the small number of cases, short research time, strict entry conditions for trial subjects, and standardized interventions. , Lack of economic benefits and other deficiencies, it is necessary to use real-world data to conduct a more comprehensive assessment of the effectiveness, safety, medication plan, and economic benefits of drugs in natural populations, and continue to make decisions based on real-world evidence Adjustment.

4. Clinical research and development of hospital preparations of Chinese medicine

For hospital preparations of traditional Chinese medicine that have been widely used clinically for a long time but have not been approved for marketing, it is also possible to explore the application of real-world evidence to support research and development.

5. Guiding clinical research design

not only includes the real-world evidence generated by retrospective observational research in Case 4, but also provides a basis for the next stage of research design. More generally, real-world evidence can provide an effective reference for the selection and exclusion criteria, the parameters of sample size estimation, and the determination of non-inferiority thresholds.

6. Precisely locate the target group

Through detailed analysis of real-world data, the benefits and risks of different subgroups can be fully investigated, and real-world evidence can be obtained to support more precise target population positioning. This is critical for the identification of biomarkers in preclinical and early clinical studies of targeted therapeutic drugs. Using real-world data such as omics data in the population cohort, public gene bank information, and related clinical data, real-world evidence can be obtained through a variety of machine learning targeted analysis technologies, which can support the precise population of targeted therapy drugs Positioning.

The opportunity for the development of Chinese medicine is here

It is well known that Chinese medicine has been criticized by the industry in terms of clinical research, and many Chinese patent medicines are simply linked with the concept of adjuvant medication.

There are some problems with the outcome indicators of many clinical trials of traditional Chinese medicine: the indicators are not scientific enough, which makes the research results not widely recognized; the indicators lack practicality, which causes the research results to fail to reflect the needs of patients, clinicians or policy makers; indicators vary widely , Leading to similar research results can not be horizontally compared or combined analysis.

The National Health Commission’s "Notice on the Implementation of Drug Use Monitoring and Comprehensive Clinical Evaluation Work" clarified that drug use monitoring and clinical comprehensive evaluation are the basic work to promote the return of drugs to clinical value, and are important measures to consolidate and improve the essential drug system. The specific requirements of the drug supply guarantee system.

How to reasonably carry out clinical trials and accurately evaluate the clinical effects and safety of traditional Chinese medicine interventions to prevent and treat diseases is a problem that needs to be solved urgently, and it is also a problem that must be solved for the development of Chinese medicine itself and the international trend.

With the development of real-world research, opportunities for the development of Chinese medicine have come.

Recently, the kick-off meeting of the real-world research project of Chinese medicine based on family doctors sponsored by the Guangdong Family Doctor Association was held in Guangzhou.

At the meeting, He Liyun, the current director of the Clinical Evaluation Center of the Chinese Academy of Chinese Medical Sciences and the chairman of the Real World Research Committee of the World Federation of Chinese Medicine Societies, said that the era of big data, computer technology, and multimedia technology have injected new vitality into evidence-based medicine and brought new vitality to the real world. Research provides good conditions. In fact, in real-world research, every Chinese medicine practitioner has the responsibility to record the medical activities that he engages in every day. The vast number of grassroots doctors are the people who have the most say and the most foundation in generating evidence.

President Zhang Shousheng of Guangdong Family Doctors Association believes that compared with traditional clinical trial methods, real-world research is more compatible with the characteristics of individualized diagnosis and treatment of Chinese medicine and overall efficacy evaluation, and is likely to become the mainstream mode of clinical research of Chinese medicine.

The Honorary Director-General of the World Health Organization, Margaret Chan, recently stated at the establishment ceremony of the China Center for Evidence-Based Medicine in Traditional Chinese Medicine that Chinese medicine is China’s national treasure and the safety and effectiveness of Chinese medicine should be affirmed. It is hoped that Chinese medicine can serve the Chinese people at the same time. , To provide the World Health Organization with more evidence on the efficacy of traditional Chinese medicine.

Generally speaking, the traditional RCT (Randomized Controlled Trial) evaluation methodology conducts research in strictly selected specific populations to ensure that the research results are not affected by various external interference factors, thereby providing clinical effectiveness and safety. Evidence is the main method for pre-marketing clinical research of new drugs. However, RCT's rigorous research design and strict entry criteria also lead to its research results that may not be suitable for direct large-scale application in clinical practice.

Traditional Chinese medicine emphasizes individualized treatment. The evaluation of curative effects emphasizes holistic, complex, and multiple influences, and emphasizes the interrelationship of viscera and meridians, as well as the interdependence of patients and the environment. At present, it is difficult to meet the requirements of RCT objective and absolute control of conditions. The characteristics of medicine are difficult to reflect in RCT.

In addition, in terms of safety evaluation, clinical safety studies designed by RCTs are difficult to observe accidental or rare, delayed, overdose, and combined drug adverse reactions and their influencing factors, and the monitoring information is basically lacking. .

"The characteristics of traditional Chinese medicine determine that it is difficult to conduct clinical evaluation using RCT methods. Therefore, RWS (real world research) has become an important choice." An industry expert said.