Ayush GCP-Need for Guidelines: Ethical perspective

1. Ayush GCP-Need for Guidelines: Ethical perspective N.SRIKANTH & RAMESH BABU ASSISTANT DIRECTOR DIRECTORGENERAL CENTRAL COUNCIL FOR RESEARCH IN AYURVEDIC SCIENCES Department of AYUSH Ministry of Health & Family Welfare Government of India

2. BackgroundLargest network • India enjoys the distinction of having the largest network of AYUSH health care, which are functional with a structure of • Practitioners • Academic Institutions • Research Institutions • Licensed Pharmacies

3. BackgroundResurgence • A resurgence of interest in Ayurveda and other AYUSH systems has resulted from the preference of health seekers towards • holistic approach • products of natural origin • About 65-80 % of population in India utilize AYUSH and LHTs to help meet their primary health requirements

4. Health Seeking attitude Role of Ayush/TM • The most prevalent users of Traditional Medicine are individuals who have • Refractory conditions • Non–life-threatening conditions that may be chronic viz. neurological disorders, arthritis etc. • The second largest group of users are those struggling with • Chronic, potentially life-threatening diseases, such as Cancer and HIV/AIDS etc

5. Health Seeking attitude Role of Ayush/TM • Both groups turn to TM/AYUSH systems for a variety of reasons, such as • Management as main treatment option • to improve immune functioning • to improve overall functioning • to improve quality of life • to cope with side effects from conventional therapies, and • to relieve symptoms related to their illness

6. BackgroundMainstreaming and Integration • Growing recognition of AYUSH/ TM in India and across the globe and emerging market potential (trillion USD) have driven for • mainstreaming of their core potential • physical and functional integration of medical systems • fulfillment of the limitations and unmet needs

7. Need for EvidenceQUALITY ,SAFETY ,EFFICACY AND RATIONAL USE • At this juncture owing to vibrant changes towards these systems the • quality • safety • efficacy • rational use of AYUSH/TM therapies have become important concerns both for policymakers and consumers as well.

8. Need for Guidelines • This necessitated Health authorities the promotion of evidence based use • substantiated by research studies • espousal of suitable guidelines & ethics

9. Historical account • The observance of Good Clinical Practices (GCPs) and ethical guidelines have been in vogue since Vedic period, traces back to 5000BC • Systematically codified during Samhita period 1000-700 B.C.

10. Historical account • Code of ……. • ethics • practice ………. in ancient India holds a salutary position in the history of medicine………….. ‘No other gift is better than the gift of life’ -Chrakasamhita

11. Historical account • Ayurvedaapproaches enormously contributed in • developing • integrating a strong code of medical ethics into the practice as an integral part of • medical practice • research

12. Code of ethicsCharaka’s view • Four ethical principles : • friendship • sympathy towards the sick • interest in cases according to one’s capabilities • no attachment with the patient after his recovery

13. IntegritySusruta’s view • ‘The patient may doubt………….. • his relatives • his sons • even his parents but he has full faith in the physician……..’ • The patient gives himself up in the doctor’s hand and has no misgivings about him • Therefore, it is the physician’s duty to look after him as his own son

14. Historical accountAncient Vs Current • Commitment • Integrity • Respect • Excellence

15. Historical accountSafety -paramount • Ethical concepts are ever-present and an ethical undercurrent runs through the major texts of Ayurveda • These comprehensive guidelines emphasize the • ‘safety of patient’ as paramount subject and also focus on related aspects viz. • societal • environmental • regulatory

16. Historical accountAncient Vs Current • Embodied with inherent primary ethics , ancient guidelines fulfill essentials of Clinical Research with emphasis on ………… • innovation • validation • reproducibility • compliance to fundamental textual principles / baseline

17. Historical accountAncient Vs Current • The process of learning, research and clinical practice in Ayurveda are scientific and evidence based. • Evolved through most suitable approaches and tools (Paramanas) • Pratyaksha (direct perception) • Anumana (logical inference) • Upamana (analogy:Comparative /control design • Aptopadesa(authentic documentary testimony/evidence base ) • Yukti (experimental evidence & reproducibility )

18. Agama or AptaVachanaEstablished guidelines • Basic idea and guidelines of clinical experimentation evolved during Samhita period • Scientific planning and experimentation with reproducible evidence forms the foundation of codified Knowledge of samhitas

19. GuidelinesRoots of Clinical Experimentation SUSRUTA’SAPPROACH:REVERSE INNOVATION • Research ideas / concepts for devising treatment for diseases/syndromes (Talllingatwat) through Reverse Pharmacology approach with a bottom-line of system validation (Agamatsya) • Designing the trial and observing the success/results of empirical treatment/ test drug (Dristhaphalatwat) • Analyzing the data/ inferences with textual /documented principles of Ayurveda (Agamatsya) and drawing logical conclusions .

20. GuidelinesRoots of Clinical Experimentation CHARAKA’S APPROACH: METICULOUS DESIGN & EMPHASIS ON REPRODUCIBILITY • Emphasizes on reproducibility and methodical study plan with …. • Feasible ideology / Hypothesis (Budhipasyathiyabhavan) • Multi dimensional approach in planning & assessment (Bahukarayanayogajaan) • Appropriate design (Yukti-Yogna) …… and outcome of such planed studies valid perpetually and reproducible (Yuktitrikalasagneya)

21. Currant scenario

22. Currant scenarioinadequate application of Core Concepts • In most of the clinical trials designed to examine the • safety • efficacy of AYUSH therapies/approaches, the fundamental aspects of holistic systems are inadequately positioned

23. Modern Medicine Understanding the differences • AYUSH • While designing the research trials it would be appropriate to understand differences in designing of the trials between

24. Understanding the differences • Differences are mainly due to the • basic approach to health and disease perceptions • epistemological • AYUSH is holistic in approach in • diagnosis • prognosis • management

25. AYUSH Vs Conventional • This holistic approach is its ‘strength’ as well as ‘Challenge ’ • Holistic’ approach of AYUSH is indeed good in clinical practice • For ‘research’, however, this approach poses considerable difficulties to devise parameters and design suitable models for clinical studies/trials.

26. Challenges • Diverse concepts • Complex approaches • Clinical Trial Design • Diagnosis & Therapy • Clinical Efficacy • Outcome measures • Drug interaction • Harmonization

27. Challenges • Complexity of too many “variables” of in terms of ‘objective’ parameters as in case of “Prakriti” in clinical trials. • Clinical investigations in Ayurveda are made difficult by factors such as use of complex, individualized treatments

28. Challenges • Their problems include difficulties in accruing, randomizing, and retaining patients and in identifying appropriate placebo interventions. • Strong commitment is required from the research community to create evidence and provide information to the public and health professionals.

29. Limitations

30. Need for AYUSH GCP • Owing to the ………………………. • diversity of approaches • fundamental differences in between traditional medical systems and contemporary modern medicine ……………… several experts endorse the need for specific guidelines for AYUSH /TM

31. Ethics are local…. • “This basis of Western medicine upon research stands in contradistinction to certain non-Western medical traditions whose foundation is principally textual or traditional. • For example, ……………………………. • the literate Asian systems (Ayurveda) look backwards to their basic texts for knowledge • whereas Western medicine looks forward, through research, for knowledge

32. Ethics are local…. • While ‘traditional’ thought has been characterized as trying to annual the passage of time • ‘scientific’ thought often seems to be frantically trying to hurry it up by devising artificial situation, experiments, that would otherwise take a long time to take place naturally. • The epistemology of Western as compared with these non-Western contemporary medical systems is often fundamentally different.” (Ethics are local: Engaging cross-cultural variation in the ethics for clinical research, Soc. Sci. Med., Vol. 35, No 9, pp 1079-1091, 1992).

33. Need for AYUSH GCP • Relatively little consideration has heretofore been given to the interaction between Western clinical research ethics and non-Western ethical expectations • Conflicts over research ethics may be expected to exacerbate the traditional conflicts that arise when the Western medical tradition is transposed into a non-Western cultural setting. Council for International Organizations of Medical Sciences (CIOMS)

34. cross-cultural medical ethics • The lack of consideration of cross-cultural medical ethics is also unfortunate given three current trends in the practice of Western medicine: • the worldwide salience of Western medicine and its ever increasing spread into non-Western settings • the increasing movement of Western medical investigators across cultural boundaries • the increasing application of Western research methodologies (by both Western and non-Western physicians) to medical problems in the developing world.

35. Research Guidelines in Vogue

36. Guidelines in Vogue M/o Environment and Forests, Govt. of India 2010 Indian council of medical research 2006 M/o Health & F.W. Govt. of India 2001

37. Ethics, Law& guidelines LAW ETHICS • Category • Requirements Guidelines + • ASU • Herbal……? • Need not ASU

38. Specific Regulations ASU Drug Trials/Product approvals Rule158(B)(Amendment) of Drugs and Cosmetic Act- 1945 vide Gazette Number 441 in Augest2010

39. Specific Regulations ASU Drugs

40. ICMR categorization • The ASU drugs include herbal and herbo-mineral formulations. The herbal products can belong to one of the three categories given below: Category 1. A lot is known about the use of a plant or its extract, metals, minerals andanimal products in the ancient Ayurveda, Siddha or Unani literature or the plant may actually be regularly used by physicians of the traditional systems ofmedicine Category 2. When an extract of a plant or a compound isolated from the plant and any compound formulation having plants, metals, minerals and animal products as ingredients has to be clinically evaluated for a therapeutic effect not originally described in the texts of traditional systems or, the method of preparation is different, it has to be treated as a new substance or new chemical entity (NCE) Category 3. An extract or a compound isolated from a plant and any compound formulation having plants, metals, minerals and animal products as ingredients which has never been in use before and has not ever been mentioned in ancient literature, should be treated as a new drug, and therefore, should undergo all regulatory requirements before being evaluated clinically.

41. B.B .Gaintode, Research, Drug development and manufacture of herbal drugs; Traditional Medicine in Asia ,2002 WHO pp.251.

42. Type of evidence General Guidelines on Methodologies of Research and Evolution in Traditional Medicine WHO;2000

43. Institutional Vs Industrial • Similar guidelines and ethics for different levels of AYUSH Clinical Research involving HUMAN PARTICIPANTS • Academic • Institutional • Industrial

44. More clarityNO confusion

45. Need for AYUSH GCP • There is a need to have the will to break down barriers where they exist. • The single drug, molecular approach adopted over the last many years needs a paradigm shift, not abandoning it altogether but by an infusion of comparative clinical studies to evaluate the effectiveness whole system approach. • The present research orients itself to drug constituents rather that at clinical protocols, which may enrich pharmacopeia not factual pharmaco-therapeutics with credible translational potential.

46. Need for AYUSH GCP • AYUSH specific guidelines are the essential requirement of the day for designing trials/research plans satisfying it’s • core fundamentals • philosophies • The inappropriate trial designs may lead to wrong conclusions may not signify system validation

47. Need for AYUSH GCP • The demarcation of medical system would become a challenge in the perspective of medical ethics ………………. • while conducting RCTs & testing the safety & efficacy of AYUSH with conventional medicine • Safety and efficacy of add-on/ adjuvant therapies ……….wherein more than one medical systems are involved

48. Key technical issues • Holistic and individualistic • Procedure based • Selection and assessment parameters • Diet and lifestyle • Blinding • Difficulty in adopting gold standards • Use of crude ingredients and extracts • Non chemical entities • Preclinical Safety/ toxicity/ efficacy

49. General issues • Separate Guidelines for Methodology of research • Orientation of the researcher • Interdisciplinary integration • Research database/AYUSH Research portal •  Clinical trial registry

50. Guidelines are pivotalclinical research- key to system development • Clinical research is the key to the development of the system. • Good clinical practices is an ethical and scientific quality standard for designing, conducting and recording trials and compliance with this standard provides assurance of protection of subjects • We may face certain difficulties in adopting GCP in the trials involving Ayurvedic principles but the solution exists for each problem.