Personalized Medicine Where Traditional Chinese Medicine and Western Medicine Can Meet

Transcription

1 Personalized Medicine Where Traditional Chinese Medicine and Western Medicine Can Meet Dr. Jean Paul Collet MD, PhD, Prof. - University of British Columbia - Child and Family Research Institute - BC Children s Hospital jpcollet@gmail.com WFCMS Sravan Jaggumantri, PhD student Arianne Toleno 4th International Conference on the Modernization of Traditional Chinese Medicine Chengdu, China Sept 26-27, 2013

2 Outline 1. Evidence-based Medicine approach 2. Traditional Chinese Medicine approach 3. Development of Patient Centred Medicine approach in Western Medicine 4. Could Patient Centred Medicine be used to evaluate TCM?

3 Basic Research Knowledge WFCMS Western Approach: A Snapshot Clinical Trials Phase 1-3 Efficacy Knowledge Pragmatic trials & Comparative Effectiveness Cohort Case Control Effectiveness Knowledge HTA Good Practice Evidence Based Knowledge Genetic? Clinical Assessment Personalized Outcomes Utility Individualized treatment Personalized Treatment Useful Treatment! Patient Oriented Research Useful Practice: patient s view

4 Western Approach: Evidence-Based Western Medicine Evaluation standard: based on Randomized Trials - On average, the treatment gives better results than the placebo - For public health and economic reasons, we recommend the use of treatment - Assuming average effect and good compliance economic models can demonstrate the positive effects of using drugs

5 Western Approach: Evidence-Based WFCMS Patients treated by beta-blockers death after myocardial infarction have a 20% risk reduction of death (fictitious example to illustrate the point) The risk of death in 1230 subjects treated by beta-blockers was 12%, while the risk in the 1240 subjects treated by placebo the risk was 15% (15% - 12%) / 15% = 20% However, the true risk reduction is 15% - 12%= 3%

6 Western Approach: Evidence-Based Western Approach of Evidence: - Population-based evaluation - For public health decisions Perspective: - Public Health Policy Maker - Pharmaceutical Industry WFCMS Evidence-Based Medicine Clinical Practice Guidelines Practice of Medicine Based on what has been observed as average effect at population level NO SURPRISE: PATIENTS ARE NOT HAPPY!

7 Traditional Chinese Medicine Therapeutic Diagram Yin/Yang balance Qi/Blood pattern Organ identification External factors identification TCM Diagnosis TCM Syndrome Differentiation WFCMS Inspection Interrogation Palpation Listening and Smelling TCM Intervention Multifactorial Herbal treatment Acupuncture/pressure Energy based (Qigong/Tai chi) According to Chinese Syndromes

8 Yin-Yang Balance Yin-Yang balance Yin-Yang imbalance Health Disease Balance Yin deficiency WFCMS TCM Therapeutic Diagram Yin Yang Yang deficiency Yin excess Yang excess

9 From Symptoms to Syndromes and Treatment food and taste stools and urine body energy sleep tongue pulse complexion Heart-and-Spleen-Qi Deficiency Heart-Blood Deficiency Yin Deficiency Yang Deficiency Four-Gentlemen Decoction - basic herb formula Four-Gentlemen Decoction modified by herbs: A,B,D,F Four-Gentlemen Decoction modified by herbs : B,D,F,G,H Four-Gentlemen Decoction modified by herbs : A,C,E Prescription is tailored to patients' syndrome, not to specific clinical symptoms TCM is Patient Centred with main goal to improve clinical outcomes and patients wellbeing

10 Clinical Status TCM Diagnosis Syndrome 1 Prescription 1 Clinical Status 2 Clinical Status 3 WFCMS TCM Action: A Cascade of Effects to Rebuild Energy, Balance and Circulation TCM Diagnosis TCM Diagnosis Syndrome 2 Syndrome 3 Prescription 2 Prescription 3 «Tailored and adaptative» Repair

11 SUMMARY: Western vs TCM Approach Western Approach of Evidence: - Population-based evaluation - For public health decisions Perspective: - Public Health Policy Maker - Pharmaceutical Industry TCM Approach of Evidence: - Individual-based evaluation - For individual decisions Perspective: - Individual subject - Physician ASSESSING IMPACT Individual Level Public Health Level TCM +/- Western Med +/-

12 Development of Patient Centred Medicine WHY? WHAT?

13 Goal setting and attainment in Alzheimer s disease patients treated with donepezil jnnp.bmj.com on May 6, month phase 4 trial, 108 patients with mild to moderate disease Physicians and Caregivers set goals particularly in domains of functionality : autonomy, leisure, social interaction Patient/career global global goal scores correlated moderately with the physician s CIBIC + at week 12 and 52 (r=.52 and.56, respectively); and not with ADA-cog. Disease Assessment Scale-Cognitive (ADAS-cog), and the Clinician s Interview-Based Impression of Change-Plus (CIBICplus)

14 EXAMPLE FABRY DISEASE WFCMS Rare X-linked recessive disease Deficiency of enzyme alpha galactosidase A due to mutation Accumulation of a glycolipid within the blood vessels, other tissues, and organs: Sphingolipidosis Pain: Full body or localized, GI Renal involvement: Proteinuria, kidney insufficiency Cardio-vascular manifestations: Hypertension, cardiomyopathy, aneurysm, Dermatological manifestations: Angiokeratomas, anhidrosis, Raynaud s dis. Ocular manifestations: Keratopathy, macular edema, optic atrophy, cataract Neurological manifestations: Neuropathy Other manifestations: Fatigue, stroke, vertigo, tinnitus, diarrhea, vomiti In practice drug efficacy was assessed on the change of sphingolipid accumulation in the skin biopsy

15 Patient insights in trial Parents are fighting to keep a drug to treat autism and fragile X syndrome that failed clinical trials on the market because it has helped their children. design

16 Methodological Development Outcome has to be personal, specific and important - Which ones? - How to find? Measurement - Measuring outcomes? - Measuring changes? - How to assess utility of a change? - Validity reliability Design - N-of-1 type of design Validity external and internal Impact Patient Centred Medicine

17 Goal Attainment Scaling Step 1: Establishment of personal important outcomes in each individual. Mutual agreement is a key component of PCM, guided by specific tools adapted from the GAS approach. Treatment effectiveness will be assessed by changes in the PSOI. Step 2: Determining the expected change over the treatment course. This process forces a precise definition of the PSOI and the criteria to assess the changes; it is often a source of insightful discussions with the family. The entire process is facilitated by the communication tools. Step 3: Scaling the observed change. The change in PSOI is assessed at the end of the treatment course. The scaling process follows a very precise rule that transforms the change into a score of success (between -2 to +2) Step 4: Determining utility and making decision by integrating information from both the traditional clinical endpoints and PSOI. A utility analysis of all the outcomes is conducted with the use of a Bayesian methodology by updating the decision on treatment effectiveness as additional evidence is acquired using the model.

18 Goal Attainment Scaling

19 Phase 1 Literature Review Conceptualizing the structural & functional framework of the PCM model Development of an adaptive GAS approach to establish PSOI Draft Internal protocols & procedures Knowledge trasfer Phase 2 Test feasbility of the PCM model Knowledge transfer Phase 3 Evaluate the PCM model on a large scale Plan for an RCT of PCM against traditional medical model Knowledge transfer Phase 4 Larger/Broader Knowledge Transfer

20 IS PATIENT CENTERED APPROACH SCIENTIFIC? Can we evaluate the PCM approach? Yes, based on patients satisfaction with regard to personal outcomes and expectations: RCTs are possible Is it possible to use PSOI to evaluate drug effects? Yes, to show that the effect is not only determined through statistical analysis (Can it?) Can drug development benefit from PCM approach? Yes, because the effect in few will be diluted in the population Market for few is scary for both pharma and public health agency Can PCM informs public health impact of the drug? Yes, accumulation of data regarding drug utility at individual level gives information on the added value the drug at societal level Can PCM enable comparing different strategies to treat a condition? Yes, by comparing the success rate at individual level and aggregating the number of success by group.

21 Conclusion 1 Traditional Chinese Medicine has a tradition behind patient centred approaches However, TCM lacks systematic evaluation WFCMS Although conducting RCTs of TCM should continue There is also the possibility to conduct Patient Centred Medicine, based on Patient Oriented Research To identify treatment utility at individual level In a systematic, rigorous and formal way To justify the Public Health utility of TCM With the PCM design Western and Traditional Chinese Medicines can joined their effort to support patients

22 PCM: Future Direction Conducting Patient Centred Medicine studies For assessing treatment of Chronic Diseases For assessing treatment is situation of Rare Diseases Validity & Reliability Consolidating tools and technology around PCM BCCH N-of-1 platform Goal Attainment Scaling tools (to assess PSOI, for scaling) WFCMS Developing new IT support for patient centred medicine Web applications Automatizing the GAS algorithms Automatizing the symptom capture Automatizing the utility assessment

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24 CHARACTERISTICS Ev. B MEDICINE PC B MEDICINE MODEL Evidence-based Patient Centred DOMAIN Policy, GCP Patient s opinion EVIDENCE DECISION BASED ON Obtained at population level Published data Obtained at individual level Individual s decision QUALITY ASSESSMENT Audit Satisfaction IMPLEMENTATION QI and KT for CPG implementation Clinical practice approach TOOLS QI techniques Goal Attainment Scaling