Prospects for the future of clinical efficacy evaluation of traditional Chinese medicine
——Emphasis on original theory and clinical practice

Chen Zhao,Wei Mu,Hongcai Shang

1Institute of Basic Research in Clinical Medicine,China Academy of Chinese Medical Sciences,Beijing,China;

2Department of Clinical Pharmacology,Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin,China;

3Key Laboratory of Chinese Internal Medicine of Ministry of Education,Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine,Beijing,China.

Abstract

Keywords:Traditional Chinese medicine,Clinical efficacy evaluation,Original theory,Clinical practice

Background

The China Center for Evidence-based Traditional Chinese Medicine (CCEBTCM) was established in 2019.Also in this year,TCM terminology was included in the 11th revision of the International Statistical Classification of Diseases (ICD-11) and the study of ‘innovative methods and technologies for TCM clinical efficacy evaluation’ was acknowledged as one of the country’s 20 major scientific,engineering and technological challenges.It is time to contemplate on the limitations in previous research and embrace the new challenge of changing integration needs and ways of definition,in order to associate TCM clinical evaluation with the unique characteristics of TCM.The current study proposed a rational prospect for the future of TCM clinical efficacy evaluation research.

The approach to TCM evaluation is distinctly divergent from that to the evaluation of western medicine (WM) for the following reasons.First,researchers tend to regard TCM ontology knowledge as unverified and form clinical questions drawing on ways of thinking used in western medicine.This way of analysing clinical questions as static and separable elements is incompatible with the analysis of pattern and pathogenesis using original TCM theories featuring continuous and integrated critical thinking and debate.However,clinical practice will not benefit from this if the TCM ontology knowledge thus acquired contradicts with clinical experience.The other way round is to validate the knowledge further in clinical research after adjusting the dosage,treatment duration,regimen,or reducing the control level.The prevalent neglecting of TCM clinical questions,clinical thinking and mode of practice makes it hard to unite different research teams to facilitate research activities because their work has different backgrounds.This further weakens the role of basic TCM clinical concepts in supporting research,although they have been recognised by ICD-11.

The significance of performing clinical evaluation lies in impacting health care in a systematic way,i.e.,by optimizing diagnosis and treatment with high-quality evidence,or by using validated data to guide practice,drug manufacture and medical insurance policy-making.It is important to keep the uniqueness of TCM when forming a clinical question for evaluation,in order to generate evidence for the TCM way of thinking,i.e.,administrating treatment based on pattern differenciation.It will be meaningless to make a conclusion that is from but being inferior to clinical practice,which is neither accepted by WM nor used by TCM practitioners.

With regard to the object of clinical efficacy evaluation,three rules should be followed to keep the uniqueness of TCM in this process.First,clinical questions should originate from original TCM theories.Second,the content of TCM thinking,treating patients according to a pattern in particular,needs to be enriched and deepened.Third,it is recommended to introduce innovative methods and technologies to facilitate TCM practice.In summary,the prospects for the future of TCM clinical evaluation lie in an emphasis on original theories and thinking,and a consolidated basis for clinical practice.

Emphasis on original TCM theories and thinking

In Chinese history,TCM has made an indelible contribution to the living and breeding of the Chinese nation.With the spread of western studies into the East in modern times,western medicine was widely introduced in China.The TCM academia has well absorbed its experimental methods and way of doing research,as well as the standardized clinical evaluation methodology,eagerly and humbly.The Chinese TCM researchers have also successfully contributed efficacy-proven therapies including artemisinin[1],arsenic trioxide[2] and acupuncture[3-5] for mankind.This builds up great confidence in us to explore further into the treasures of TCM using clinical evaluation tools,in the hope of providing evidence for optimal TCM practice.

On 20thFebruary 2019,an expert panel organized by the China Association of Chinese Medicine proposed “the scientific study of the TCM original theories” as a major scientific question high on the TCM development agenda[6].Abstract in nature,the concepts and the relations among different concepts in original TCM theories are symbolized principles summarized from long-term practices.Nowadays,these theories still serve as a useful guide for clinical practice after long years of absorption from practitioners’medical experiences and Chinese culture.They are mandatorily studied and widely used by college students in TCM higher education institutes.The inclusion of these basic concepts and definitions in ICD-11 signifies they have gained growing international recognition although having not been completely understood or interpreted in basic research.Thus,it is recommended to represent TCM thinkings in a proper clinical mode from a macroscopic perspective and invite speculation and debate on them while preserving the essentials.Clinical questions that are characteristic of TCM should be the target of clinical evaluation.

For example,it is recommended to define the research population by either TCM or WM criteria for diseases such as rib fracture,which has simple and clear diagnostic criteria and pathological factors shared by both TCM and WM.If a TCM indication fits in the WM definitions of disease and patients with TCM patterns (for which TCM interventions are indicated) dominates in the patient population diagnosed by WM criteria,then a combination of disease and pattern diagnosis could be used to define the population.Examples are the“fire excess from Yin deficiency” syndrome in diabetes,and the cold syndrome in dysmenorrhea.For some indications of TCM interventions which meet the WM definition of a variety of diseases,it is recommended to define the population with an umbrella TCM pattern covering different WM diseases on condition that these diseases are pathologically correlated.For example,stomach cold syndrome may cover diseases such as superficial gastritis,gastric ulcer,duodenal ulcer,and stomach cramps.For comprehensive TCM interventions that are indicated for complex clinical conditions such as intermingling syndromes,it is inappropriate to simply define by one disease or one syndrome.It is recommended to draw on clinical experience to reveal the truth of the syndrome,quantitatively or qualitatively define and analyse the pathogenesis,and exploratorily validate the TCM explanations of the pathogenesis using human biomedical indicators and in basic research.An example of this is the coexistence of the sputum,stasis and deficiency syndrome in patients with chest stuffiness and pain.

Improving TCM clinical practice

Practice is the basis and starting point of TCM clinical efficacy evaluation.A consensus on practice is critical to fulfill CCEBTCM’s task of systematic integration of evaluation research findings from research teams,each with their own strengths.The clinical question,the way of thinking,and the model of diagnosis and treatment together with their minor details need to attain a certain degree of maturity in order for the evaluated question to fit in clinical context and for the findings to be readily used in practice.It will be especially useful to introduce innovative methods,concepts and technologies that could improve the clinical form of the TCM thinkings that have been previously widely evaluated.In particular for TCM ontology knowledge to be a subject of evaluation,it is necessary to combine the subject with certain new knowledge from other sources following proper discussion on the practical situation and feasibility,and apply the new subject in clinical practice.It is good for clinical efficacy evaluation only after the new subject has formed into a mature and stable clinical model.

Currently,many original thinkings based on the TCM ontology knowledge that may potentially optimize the subject of clinical evaluation have not been widely validated in research.For example,the therapeutic principles of “treating different diseases sharing common or similar pathogenesis with the same formula” and “treating the same disease with common symptoms caused by probably different pathogenesis in individuals” may lead to the homogeneity of randomized controlled trials (RCTs)in TCM research.As a result,the new way of“using a syndrome to cover several diseases” is gaining acceptance as a potential replacement of the old way of“using a disease to cover several syndromes”due to more accurate representation of the TCM clinical form by the former method[7].This concept is originally from TCM ontology knowledge.Still,discussions on the consistency in pathogenesis between the syndrome and diseases,the similarity in the stage of the disease and also the course of the disease should be made before using this model of thinking for a specific clinical efficacy evaluation question.

New methods and technologies are largely foreign to TCM research.In the absence of practical experiences,the evaluation of a subject newly formed after integrating new methods may adversely impact on the subsequent acceptability of the better method and increase the risk of influencing the TCM model of practice.It is,therefore,important to discuss the compatibility of the new method with clinical practice.The following are a few examples.The dosage and the method of taking herbal medicine need to be checked against the routine clinical practice in an efficacy trial.The standard operating practice of a special diagnosis and treatment technic should be examined to see if it highlights individual differences while retaining original functions.Feasibility of the method of clinical treatment and data collection should be tested in the demonstration evaluation of a TCM clinical question using new methods and technologies.The nature of each critical timing and the mode of change need to be evidenced in clinical practice while performing mathematical fitting of the pattern differenciation and development rules such as the “six meridians pattern differenciation” and the “warm disease pattern differenciation” method.Moreover,the degree of applicability needs to be examined before a new model of clinical practice is ready for evaluation.

Another example is the recent introduction of Narrative-based Medicine (NBM) which promotes the effective communication of the doctor and the patient,encourages doctors to understand the pains of the patient with empathy and a sense of responsibility,and asks them to keep a narrative record of this reflective process[8].Researchers have formed a new subject based on the current NBM model of practice,i.e.,a method of patient-centered clinical efficacy evaluation that analyses words instead of clinical data[9].This method is expected to facilitate the clinical efficacy evaluation of TCM because it shares similarity with classic TCM case reports that include both narrations and comments.The introduction of NBM to TCM research has led to a series of studies on theoretical debate,clinical application and exploratory trials,contributing to the birth of promising TCM practice models including TCM parallel medical records[10],the joint development of evidence-based medical records by doctors and patients[11],and the patients’medical profile on chronic disease management using TCM[12].A breakthrough in the clinical efficacy evaluation research of TCM will be made possible through the subsequent development of the above and other studies.

Also,the rise of Narrative-Evidence Based Medicine and Real World Research echoes the needs for highlighting clinical application in medical research.To make this happen,TCM research featuring individualized practice needs to highlight practical questions as well as clinical questions characteristic of the TCM original thinkings.This also sends the message to TCM researchers that a model of“using findings from evaluation studies,and evaluating clinical questions requiring answers” needs to be implemented in order to constantly optimize clinical practice.