An Evidence-Based Approach to TCM Patient Class Definition and Differentiation

An Evidence-Based Approach to TCM Patient Class Definition and Differentiation

اسلاید 1: Page 1www.tabaye.ir

اسلاید 2: An Evidence-Based Approach to TCM Patient Class Definition and DifferentiationNevin L. ZhangThe Hong Kong Univ. of Sci. & Tech.http://www.cse.ust.hk/~lzhangJoint Work with：HKUST: Yuan Shihong, Chen Tao, Wang Yi, Liu Tengfei, Poon Kin Man, Liu Hua Beijing TCM U: Wang Tianfang, Zhao Yan, Xu Wenjie, Wang QingguoShanghai TCM U: Xu Zhaoxia, Wang YiqingAcademy of TCM: Zhou Xuezhong, Zhang Runshun, Gong Yanbin, He Liyun, Wang Jie, Liu BaoyanBeijing Dongfang Hospital: Zhang Yongling, Chen Boxing, Fu Chen

اسلاید 3: TCM is Worthy of ResearchTraditional Chinese Medicine (TCM) is important to the Chinese people.Culture traditionHealth careIt is used by many others. WHO report:Global herbal medicine market: US$60 billionTraditional medicine treatment at least once in life90% of Canadian, 49% of French people, 48% of Australians, 42% of Americans. Page 3

اسلاید 4: Spectrum of TCM ResearchPage 4A visit to TCM DoctorPatient Information Collection:Inspection (望))Auscultation & Olfaction (闻))Inquiry (问))Palpation (切))Patient Classification:Syndrome differentiation (辨证)Determine pattern of disharmonyTreatment:Herbal medicineAcupunctureTui Na, Cupping, Qigong, .., etc

اسلاید 5: Spectrum of TCM ResearchPage 5A visit to TCM DoctorResearchPatient Information Collection:Inspection (望))Auscultation & Olfaction (闻))Inquiry (问))Palpation (切))Instruments:…….Patient Classification:Syndrome differentiation (辨证)Determine pattern of disharmonyTreatment:Herbal medicineAcupunctureTui Na, Cupping, Qigong, .., etc

اسلاید 6: Spectrum of TCM ResearchPage 6A visit to TCM DoctorResearchPatient Information Collection:Inspection (望))Auscultation & Olfaction (闻))Inquiry (问))Palpation (切))Instruments:…….Patient Classification:Syndrome differentiation (辨证)Determine pattern of disharmonyTreatment:Herbal medicineAcupunctureTui Na, Cupping, Qigong, .., etcEfficacyEffective component of herbsAction mechanism Safety….

اسلاید 7: Spectrum of TCM ResearchPage 7A visit to TCM DoctorResearchPatient Information Collection:Inspection (望))Auscultation & Olfaction (闻))Inquiry (问))Palpation (切))Instruments:…….Patient Classification:Syndrome differentiation (辨证)Determine pattern of disharmonySupervised learningLabeled Data: Symptoms & signs, class labels assigned by expertTreatment:Herbal medicineAcupunctureTui Na, Cupping, Qigong, .., etcEfficacyEffective component of herbsAction mechanism Safety….

اسلاید 8: Spectrum of TCM ResearchPage 8A visit to TCM DoctorResearchPatient Information Collection:Inspection (望))Auscultation & Olfaction (闻))Inquiry (问))Palpation (切))Instruments:…….Patient Classification:Syndrome differentiation (辨证)Determine pattern of disharmonySupervised learningLabeled Data: Symptoms & signs, class labels assigned by expertOur work: cluster analysis Unlabeled Data: symptoms & signs Treatment:Herbal medicineAcupunctureTui Na, Cupping, Qigong, .., etcEfficacyEffective component of herbsAction mechanism Safety….

اسلاید 9: Western Medicine vs TCM: A Layman viewWestern Medicine (Modern Biomedical Medicine )Human body: A machine with different parts, viewed at different levels: anatomic, biochemical, geneticDisease: malfunction of some partTCMHuman body: Dynamic system of energy and functions, holistic viewDisease: Disharmony Among yin, yang, qi, xuĕ, zàng-fǔ, meridians etc. and/orBetween of the human body and the environmentPage 9

اسلاید 10: Patient ClassesBoth Modern Medicine and TCM divide patients into classesPatient classes in modern medicineCorrespond to diseases at certain stages: E.g., Stage 4 COPD Clearly definedHave gold standard for differentiationPatient classes in TCMCorrespond to pattern of disharmony (syndrome): Yang DeficiencyNot clearly definedDifferentiation heavily influenced by subjectivityPage 10

اسلاید 11: Data-Driven Research on Syndrome DifferentiationSupervised learningLabeled Data: Symptoms & signs, class labels assigned by expertsProvides quantitative summarization of experts’ know-howsConducive to the improvement of TCM service. Reduce variance.However, it does not solve the subjectivity problem.Our work: cluster analysis Unlabeled Data: symptoms & signs onlyAim at finding natural clusters among patient population, whichCan be used as objective evidence for patient class definition.Page 11

اسلاید 12: Our ObjectiveIn clinic practice, syndrome differentiation is heavily influenced by objectivity.Our objective to provide evidence to make syndrome differentiation as objective as possible.Page 12Status QuoOf Syndrome DifferentiationSubjectiveIdeal CaseObjective Gold StandardOur GoalReference StandardObjective Evidence +Subjective Judgment

اسلاید 13: OutlineIntroductionStatistical validation of TCM postulatesProviding evidence for TCM patient class definition and differentiationConcluding remarksPage 13

اسلاید 14: TCM PostulatesTCM has postulates to explain occurrence of symptoms:Kidney yang is the basis of all yang in the body. When kidney yang is in deficiency, it cannot warm the body and the patient feels cold, resulting in intolerance to cold, cold limbs, and cold lumbus and back.Key question:Do concepts such as “kidney yang deficiency” have scientific contents or are pure subjective notion?Efforts to provide objective evidence would be in vain in the latter case.Page 14

اسلاید 15: Research on Objectivity of TCM SyndromeFor more than 50 years, researchers have tried to show that TCM syndrome factors correspond to real entities by means of biomedical laboratory tests, (recently genetic method also)but there has been little success. We take a data-analysis approachPage 15

اسلاید 16: TCM syndromes are latent variablesTCM postulate:Kidney yang is the basis of all yang in the body. When kidney yang is in deficiency, it cannot warm the body and the patient feels cold, resulting in intolerance to cold, cold limbs, and cold lumbus and back.Manifest variables：Directly observedFeel cold, cold limbs, intolerance to cold.Latent variable: Not directly observedKidney Yang deficiencySimilar to concepts such as “intelligence”Latent StructureRelationships between latent variables and manifest variablesPage 16

اسلاید 17: Collective CognitionHow did concepts such as “Intelligence” come into being?Conjecture: From correlation between observed variables.How do we possibly prove this?LampPrinciple applet interactive demo …Shows that human beings tend to introduce latent variables to explain co-occurrence in observationsConjecture about TCM the formation postulatesCo-occurrence of cold symptoms => Kidney Yang deficiencyPage 17

اسلاید 18: Statistical Validation of TCM PostulatesPage 18

اسلاید 19: Data Analysis ToolPage 19Latent tree models:Each node represents a discrete random variableArrows represent dependenceLeaves observed (manifest variables)Internal nodes latent (latent variables)Links quantify by probability distributions: P(Y1), P(Y2|Y1), P(X1|Y2), P(X2|Y2), …

اسلاید 20: Data Analysis ToolLearning latent tree models: DetermineNumber of latent variablesCardinality of each latent variableModel StructureConditional probability distributions

اسلاید 21: Data Analysis ToolPage 21How to learn latent tree models from dataStatistical Principle (BIC score) + Search

اسلاید 22: Case StudyKidney dataPopulation: Seniors aged 60 or above from residential communitiesVariables: 34 symptoms associated with kidney deficiencySample size: 2600Page 22

اسلاید 23: Latent structure matches relevant TCM postulatesWe have not shown “yang deficiency” corresponds to real entity We have shown that the postulate of a “yang deficiency” entity would explain the co-occurrence patterns observed in data well.Page 23

اسلاید 24: Page 24Match between Model and TCM PostulatesTCM Kidney yang deficiency,failing to warm bodyintolerance to cold, cold limbs, cold lumbus and back,  Spleen disorders loose stools, indigested grain in the stoolModelGood Match

اسلاید 25: Page 25Match between Model and TCM PostulatesTCMWhen kidney fails to control the urinary bladder, frequent urination, urine leakage after urination, frequent nocturnal urination, (in severe cases) urinary incontinence and nocturnal enuresis. ModelGood Match

اسلاید 26: Page 26Match between Model and TCM PostulatesTCMkidney essence insufficiency premature baldness, tinnitus, deafness, poor memory, trance, declination of intelligence, fatigue, weakness, and so on.ModelGood Match

اسلاید 27: Page 27Match between Model and TCM PostulatesTCMkidney yin deficiency dry throat, tidal fever or hectic fever, fidgeting, hot sensation in the five centers,insomnia, yellow urine, rapid and thready pulse, and so on.ModelGood Match

اسلاید 28: Results on other Data Sets from a 973 ProjectPage 28

اسلاید 29: SummaryWe have analyzed many data setsLatent variables obtained match the relevant TCM postulates in all casesConclusion:TCM syndrome concepts do have scientific contents.We have not shown that TCM syndromes corresponds to real entities. We have shown that the postulate of the existence of such entities would explain the co-occurrence patterns observed in data.Page 29

اسلاید 30: Value of Work in View of OthersD. Haughton and J. Haughton. Living Standards Analytics: Development through the Lens of Household Survey Data. Springer. 2012Zhang et al. provide a very interesting application of latent class models to diagnoses in traditional Chinese medicine (TCM). The results tend to confirm known theories in Chinese traditional medicine. This is a significant advance, since the scientific bases for these theories are not known.The model proposed by the authors provides at least a statistical justification for them.Page 30

اسلاید 31: Value of Work in View of Others[Review of a recent paper] I am very interested in what these authors are trying to do. They are dealing with an important epistemological problem.To go from the many symptoms and signs that patients present, to construct a consistent and other-observer identifiable constellation, is a core task of the medical practitioner. A kind of feedback occurs between what a practitioner is taught/finds listed in books, and what that practitioner encounters in the clinic. The better the constellation is understood, the more accurate the clustering of symptoms, the more consistent is the identification of syndromes among practitioners and through time. While these constellations have been worked into widely-accepted ‘disease constructs’ for biomedicine for some time which are widely accepted as ‘real,’ this is not quite as true for TCM constellations. This latent variable study is interesting not only in itself, but also as providing evidence that what TCM ‘says’ is so, shows up during analysis as demonstrably so.Page 31

اسلاید 32: OutlineIntroductionStatistical validation of TCM postulatesProviding evidence for TCM patient class definition and differentiationConcluding remarksPage 32

اسلاید 33: Integration of TCM and Western MedicineCommon practice in ChinaPatients of a WM disease subdivided into several TCM classesExample:WM disease: DepressionTCM Classes: Liver-Qi Stagnation (肝气郁结), Stagnation of liver qi and spleen deficiency (肝郁脾虚), Deficiency of both heart and spleen (心脾两虚), Liver depression forming fire (肝郁化火), ….No agreed sub-classing standard5 different standards proposed by different organizations/groupsBased experts’ opinionsCan we provide evidence for the TCM sub-typing of WM diseases?Page 33

اسلاید 34: The IdeaImagine sub-typing Western medicine disease D from TCM perspectiveAlso providing a basis for defining syndrome Z and for differentiating syndrome Z patients from other D patientsPage 34

اسلاید 35: Cluster AnalysisGrouping of objects into clusters so that objects in the same cluster are similar in some sensePage 35

اسلاید 36: How to Cluster Those?Page 36

اسلاید 37: How to Cluster Those?Page 37Style of picture

اسلاید 38: How to Cluster Those?Page 38Type of object in picture

اسلاید 39: How to Cluster Those?Page 39Multidimensional clustering / Multi-ClusteringHow to partition data in multiple ways?Latent tree models

اسلاید 40: Latent Tree Models & Multidimensional ClusteringModel relationship betweenObserved / Manifest variablesMath Grade, Science Grade, Literature Grade, History GradeLatent variablesAnalytic Skill, Literal Skill, IntelligenceEach latent variable gives a partitionIntelligence: Low, medium, highAnalytic skill: Low, medium, high

اسلاید 41: LTM for a Depression Data SetPage 41

اسلاید 42: Page 42Partition given by Y15

اسلاید 43: What is the Z?We now have the empirical partition.What is the Z?In TCM, the symptoms “shortness of breath” etc. characterize Qi movement disorder in chest (胸膈气机不畅).So, Z should be “whether Qi movement disorder in chest”Page 43

اسلاید 44: Patient Class Definition and DifferentiationPreviously, no clear definition for the classQi movement disorder in chest (胸膈气机不畅).Empirical partition gives us a clear definitions1: Qi movement disorder in chest (胸膈气机不畅), s0: no Qi movement disorder in chest (无胸膈气机不畅)Sizes of the classes: 48%，52%；Class differentiation: Bayes rule, importance of symptoms indicated by ratiosPage 44

اسلاید 45: Easy-to-Operate Differentiation StandardsFor clinic convenience, differentiation standards are usually given by a scoring system:Current work: Derive such scoring systems from results of latent tree analysis, particularly the probability ratios.Page 45

اسلاید 46: Concluding RemarksLatent tree analysis is tool for Systematically identifying co-occurrence patterns of symptomsIntroduce latent structure to explain the patternsProvide evidence in support of TCM postulates about symptom occurrenceTool for multidimensional clusteringEach latent variable represents a partition of dataProvide evidence for TCM patient class definition and differentiationPage 46

اسلاید 47: Application of LTM in BioinformaticsPage 47

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اسلاید 49: Thank You！