Letters for “Prospects for the future of clinical efficacy evaluation of traditional Chinese Medicine—Emphasis on original theory and clinical practice”

Yaolong Chen,Kehu Yang,Xinfeng Guo,Darong Wu,Ling Zhao,Bo Li

Clinical Efficacy Evaluation of Traditional Chinese Medicine is Moving in the Right Direction

To the Editor:On the basis of affirming the outstanding contribution of Traditional Chinese Medicine (TCM) to the world,Professor Shang and his team analyzed the current bottlenecks in the development of TCM.They proposed two important approaches for the future research of TCM around the theme of evaluation of clinical efficacy of TCM.

The first one is to pay attention to the integration of original theories and ideas of TCM into the TCM clinical efficacy evaluation system,so that we can ensure its compliance with clinical practice of TCM.The authors objectively summarized the differences between TCM and Western medicine.If we copy the evaluation system of Western medicine to produce the research evidence of TCM,which will not be in line with the clinical practice of TCM.Therefore,from the perspective of the research object,the authors described how we should combine the TCM model of diagnosis and treatment with the evaluation system of Western medicine,and to produce the evidence of clinical efficacy evaluation for TCM diagnosis and treatment environment.Finally,it can provide guidance for designing and conducting high-quality TCM clinical research in accordance with the environment of TCM diagnosis and treatment.

The second is to pay attention to the integration of thinking mode,mechanism,and diagnosis and treatment mode in TCM clinical practice.Moreover,we need to combine new methods and technologies to improve and verify the TCM practice mode.The authors combined specific examples of different diseases with the same mechanism,the same disease with different mechanism to illustrate how to optimize and integrate the theory of TCM in the practice process.In the absence of practical experience,we can adopt new methods and techniques to evaluate the efficacy of TCM.However,we need to think about its compatibility with clinical practice,so that the theories and ideas of TCM will be consolidated in the clinical process.

The establishment of the TCM clinical efficacy evaluation system,which focuses on the combination of original TCM theory and clinical practice,will play an important role in the implementation of One Belt,One Road and Healthy China strategies.It will be a critical step for TCM to be widely accepted,promoted,and used around the world.

Yaolong Chen,MD,PhD

Kehu Yang,MD,PhD

Author Affiliations:Evidence Based Medicine Centre of Lanzhou University,Gansu,China.

Corresponding to:Yaolong Chen,Evidence Based Medicine Centre of Lanzhou University,Gansu 730000,China.Email:chenyaolong@lzu.edu.cn

Kehu Yang,Evidence Based Medicine Centre of Lanzhou University,Gansu 730000,China.Email:yangkh@lzu.edu.en

About the Author:Yaolong Chen is the professor of Evidence Based Medicine Centre of Lanzhou University,the co-director of WHO Collaborating Centre for Guideline Implementation and Knowledge Translation,the chair of GIN Asia,and the director of Chinese GRADE centre.

Kehu Yang is the professor and director of the center for evidence-based medicine of lanzhou university,the director of the key laboratory of evidence-based medicine and clinical transformation of gansu province,the co-director of the WHO guidance implementation and knowledge transformation cooperation center,and vice chairman of the committee of evidence-based medicine of Chinese medical doctor association.

Discussing the Principles,Methods and Strategies of TCM Clinical Efficacy Evaluation from Another Perspective

To the Editor:For traditional Chinese medicine(TCM) researchers,they must not only understand the methods and techniques of clinical trial methodology,but also grasp the scientific research principles behind them,and use appropriate scientific research methods to solve various and specific scientific problems.

When it comes to TCM ontology knowledge and original theory,more attentions should be paid regarding to its research complexity.There are many levels of ontological knowledge and original theories of TCM,ranging from the Yin-Yang theory at the highest philosophical level from Yellow Emperor's Internal Classic,the eight syndrome-differentiation principles of later generations,to TCM doctrine,pathogenesis,treatment methods,and prescription interventions.The more difficult it is to verify or disprove high-level theories,some levels even go beyond the scope of natural scientific research.When studying original theories of TCM,it is important to clearly understand its characteristics and to recognize the limitations of general clinical research,especially when conducting clinical trials of clinical efficacy evaluation.Many theories of the Yellow Emperor's Internal Classic belong to the philosophical level(such as solitary yin and yang do not grow),they are principled,directional,difficult to measure and operate,thus difficult even impossible to verify or falsify; intermediate-level knowledge and theories(like various TCM doctrines) can never be solved by one or a small number of clinical research institutes.It requires a long period of accumulation of a large number of different types of research,mutual certification,and logical self-consistent etc.Other ontological knowledge at the level of TCM experience itself may be right or wrong,If you don't get the expected conclusion,you need to explore the possible reasons from the level of the research design,confounding,data accuracy,analyzing method limitations,etc.If there are no special reasons or major problems in research design,implementation and analysis,you should accept the fact that some previous TCM theory and experience are wrong or no longer applicable.TCM will lose the opportunities for theoretical improvement and self-renewal if without such denies of former knowledge.

So,are modern clinical trial methods suitable for evaluating the efficacy of TCM? The answer is yes.Scientificity,innovation,importance,accuracy,repeatability,and generalization are generally accepted scientific research principles,while randomization,control,and blinding are the most commonly used methods and techniques to ensure the accuracy of research results,especially clinical trials for efficacy evaluation.In terms of specific clinical trial design,if perfect comparability between groups can be ensured(like the identical twin newborns),then randomized allocation may not be required theoretically.If the stability of the research subjects can be guaranteed(the diagnosis and prognosis do not change with time,place,social conditions,etc.,the method and accuracy of data collection are the same etc.),the research results with historical control can also be recognized.If you can ensure that the clinical trial outcomes are completely free from subjective psychological influence(the placebo effect and the Hawthorne effect can completely be avoided),the subject may not be blinded.If it is guaranteed that the researchers are completely unaffected by the group allocation (all patients receive the same care and medical measures without implementation bias),then there is no need to blind the clinical researchers etc.However,the fact is that clinical trials involving humans can hardly meet any of the above conditions,therefore the accuracy of the research results cannot be guaranteed without using commonly used methods such as randomization,control and blinding (internal accuracy,usually considered to be the basis of scientific research).In practice,treatment based on syndrome-differentiation,dynamic and tailoring adjustment of treatment plans,and random allocation of subjects are not incompatible: it is difficult but not impossible to implement double-blind methods for many TCM interventions.There is no logistical problem in using the randomized controlled trial for syndrome-differentiated treatment.What need to be solved are the accepted definitions of basic concepts of TCM syndromes,operationalization of diagnosis criteria,repeatability etc.,and then come challenges of clinical trial implementation,management and data analysis,conclusion derivation and generalization.

As for the shortcomings of "homogeneity" of TCM randomized controlled trials,the TCM community needs to dialectically see the commonality and personality of TCM diagnosis and treatment,common rules of syndrome management and individualized tailoring and treatment,and cannot be misled.Any knowledge system that can be passed on must be based on common laws,not individual experiences.TCM is a very complicated system.When there is a clear and main etiology and pathogenesis,single herb and acupoint (such as artemisinin for malaria,Zhiyin/BL67 moxibustion for malposition) can be used.Diseases (stages) with a core pathogenesis can adopt the traditional clinical trial design that has one fixed prescription in one trial from the start to the end.Some ancient TCM doctors did not reject it either.Xu Lingtai once said that "there must be one main formula for one disease,and one predominant herb in one formula."

Such experience is easier to verify or falsify using classic randomized controlled trials,and their research results are easier to apply and generalize.They should be given research priority in case of limited research funding and capacity of clinical researchers;while the verification of therapies and treatments with complex interventions,tailoring and dynamic adjustments is much more complicated,requiring more research funding and more complex research methods and highly competent researchers,thus should not be encouraged too much at the current stage,when research resources and researchers' research capabilities are both limited.

As for the design of the study,it is not difficult to randomly assign participants to different groups,what the researchers need to do is to set detailed,objective,and repeatable standards for the adjustment of the treatment plan,the prescription,dose,and the change in the method of administration,and to set a reasonable control group corresponding to the specific purpose of the trial; choose universally accepted primary endpoint as the outcome indicator; try best use of other bias control methods when it is difficult to implement double-blinding,such as independent efficacy assessor,etc.Scientific research will inevitably make appropriate compromises from scientific to feasibility.At this time,we must pay attention to the rigor of conclusion derivation.

In summary,TCM clinical research priorities should be set more to clinical,treatment and efficacy,but less to theory,mechanisms and diagnosis.

Xinfeng Guo,MD,PhD

Author Affiliations:Guangdong Provincial Hospital of Chinese Medicine,The Second Medical College of Guangzhou University of Chinese Medicine,Guangzhou,China.

Corresponding to:Xinfeng Guo,Guangdong Provincial Hospital of Chinese Medicine,The Second Medical College of Guangzhou University of Chinese Medicine,Guangzhou 510120,China.Email:guoxinfeng@gzucm.edu.cn

About the Author:Dr.Xinfeng Guo is a research professor of Traditional Chinese Medicine,PI and Director of EBM & Clinical Research Service Group,Guangdong Provincial Academy of Chinese Medical Sciences,and also the Evidence-based clinical Chinese medicine project facilitator of China-Australia International Research Centre for Chinese Medicine,an joint research centre initiated by Royal Melbourne Institute of Technology (RMIT),Australia,and Guangdong Provincial Academy of Chinese Medical Sciences.

TCM clinical efficacy evaluation shall be based on inheritance and development

To the Editor:Zhao C,et al.published an article in regards of the prospects for the future of clinical efficacy evaluation of traditional Chinese Medicine.It is well recognized that inheritance and development are two critical steps for the development progress of TCM.For inheritance,it shall be based on a comprehensive understanding of the theories as well as the content of TCM.These theories and contents are considered as TCM basic characteristics,and are closely connected with the efficacy and effectiveness of TCM.Either clinical practice or researches,such as efficacy evaluation studies,shall follow these characteristics.

For development,there are several aspects,for instance,the development of TCM clinical practice,the development of the clinical research methodologies in the area of TCM,or the development research methods for ancient books ’content analysis,etc.All the above aspects cannot be carried out or moved forward without introducing innovative methods or technologies.

In this paper,the author emphasized that TCM clinical efficacy evaluation should follow the characteristics of TCM,including the original TCM theories and the content of TCM thinking,which meets the inheritance aspect of TCM development progress.The author also mentioned that to introduce innovative methods and technologies would be helpful in improving TCM clinical practice,which hits the development aspect.

It can be anticipated that the development of TCM will be strongly enhanced and facilitated while constantly optimizing clinical practice on the basis of findings from high quality clinical researches.

Darong Wu,MD,PhD

Author Affiliations:The Second Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou,China.

Corresponding to:Darong Wu,Program for Outcome Assessment in TCM,The Second Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510120,China.Email:darongwu@gzucm.edu.cn

About the Author:Dr.Darong Wu is the professor of traditional Chinese medicine (TCM),at the 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine in Guangzhou,China.

Looking forward more“Chinese guidelines”,“Chinese evidence”and “Chinese voices”

To the Editor:Chen Zhao and colleagues conducted a comment entitled “Prospects for the future of clinical efficacy of Traditional Chinese medicine” from two aspects: original TCM theories and improving TCM clinical practice.This comment is important and valuable for the future orientation,design and implementation of clinical efficacy evaluation in TCM field.

Firstly,this comment recommended to represent TCM thinking in a proper clinical mode from a macroscopic perspective.It’s an insightful suggestion.Western Medicine diagnostic criteria,therapy ideas,and evaluation standards were widely adopted in TCM clinical trials to make the results can be recognized internationally.However,it ignores the most important treatment based on syndrome differentiation principles of individualization in original TCM theories.This maybe a critical factor to underestimate the clinical efficacy of TCM.

Secondly,this comment considers it is important to discuss the compatibility of the new method with clinical practice.Among them,the newly introduction of Narrative-based Medicine (NBM),because it has shares similarity with classic TCM case reports that include both narrations and comments,is expected to facilitate the clinical efficacy evaluation of TCM.However,we cannot ignore the reliability of the objective indicators based on Western Medicine for the evaluation of clinical efficacy.We should consider how to integrate the advantages of TCM with the outcome indicators of Western Medicine,and develop some evaluation methods that is more in line with the clinical characteristics of TCM.

We look forward to formulating more “Chinese guidelines” in clinical efficacy evaluation,generating more “Chinese evidence”,and sending more“Chinese voices”around the world in the field of TCM.

Ling Zhao,MD,PhD

Author Affiliations:School of Acupuncture and T uina,Chengdu University of Traditional Chinese Medicine,Sichuan,China.

Corresponding to:Ling Zhao,School of Acupuncture and Tuina,Chengdu University of Traditional Chinese Medicine,Sichuan 610075,China.Email:zhaoling@cdutcm.edu.cn

About the Author:Ling Zhao is the professor of Chengdu University of Traditional Chinese Medicine,doctoral supervisor,vice president of acupuncture and massage college,Chengdu University of Traditional Chinese Medicine,Sichuan,China.

The future of doctors and patients co-construction

To the Editor:Standing at the beginning of 2020,looking back at the evaluation of the efficacy of Chinese medicine in 2019,there are several things that can have an impact on the future,as suggestions for exchange and discussion:

The rising of narrative medicine.Both traditional Chinese medicine and western medicine have expectations in terms of humane care,but they are difficult to implement.However,in terms of diagnosis and treatment evaluation,the introduction of narrative medicine is a historical necessity,which will make medicine more warm and return to the origin of medicine.

The role of participatory action diagnosis and treatment.The medical community has generally recognized the importance of the relationship between human psychology and people and the environment in the medical process,and has begun to focus on the benefits of patient values and patient participation in diagnosis and treatment decisions and treatment effects.Participatory action research emphasizes cooperation and practice,which helps inspire participants to develop critical thinking,and to some extent fits the concept of medical guidance for patients to develop"health awareness".

The practice of doctor-patient co-construction diagnosis and treatment model.From theory to practice,combined with evidence-based medicine,narrative medicine,and practical clinical and scientific experience,we strive to further advocate the model of doctor-patient co-construction,accurate diagnosis and treatment,and more practically solve patients' pain.Medicine is science,diagnosis and treatment is art,and the joint construction of doctors and patients can make a perfect combination of science and art,and promote common health.

In short,a healthy future,more emphasis on teamwork,not only cooperation between doctors,will gradually expand to the cooperation between doctors and patients.Facing disease,doctors and patients build a future together.

Bo Li,MD

Author Affiliations:Beijing Hospital of Traditional Chinese Medicine,Capital Medical University,Beijing Institute of Traditional Chinese Medicine,Beijing,China.

Corresponding to:Bo Li,Beijing Hospital of Traditional Chinese Medicine,Capital Medical University,Beijing Institute of Traditional Chinese Medicine,Beijing 100010,China.Email:dr.libo@vip.163.com

About the Author:Dr.Bo Li is the Chief in EBM Centre,and the associate senior doctor in Gastroenterology Department,Beijing Hospital of Traditional Chinese Medicine.

Executive Editor:Chaoyong Wu

Submitted:13 January 2020,Accepted: 24 January 2020,Online:29 January 2020.