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Background

It would not be an overstatement to say that the 21st Century will be the era of pluralism in Health Care. The human population, the world over, is grappling with new age health problems and not getting viable solutions for all their needs in anyone single medical system. Therefore the search and growing acceptance of complementary systems of health care.

Ayurveda and Yoga are evidence based health sciences (pramana shastra) which have evolved and matured over the last two millennia. They therefore have the potential to be significant contributors in the global search for complementary health care. The following examples may serve as illustrations of the quality of Ayurvedic knowledge. The plant Curcuma longa (nisha, rajani, haridra) is advised in Ayurveda for harvest after sunset for realising its optimum therapeutic potential. Recent studies reveal that the chemistry & bio-activity of the day and night collections is different. 1 In respect of the processing of products which use Piper longum, Ayurveda prescribes extraction of the piper in milk or ghee instead of the usual aqueous extract. A study has shown that piper extract in milk or ghee (fatty medium) is 27 times more bioactive than the aqueous extract.2 With respect to efficacy, for treatment of .diabetes (prameha) Ayurvedic pharmacology texts advise that prolonged use bitter herbs should avoided when the patient is lean (Vata type) but they are advocated for use in the case of an obese person. 3

All such advice and prescriptions are precise and not hypothetical; they are based on sound clinical evidence and grounded in A yurvedic logic. All the codified fields of knowledge in Ayurveda like Dravyaguna Shastra (Pharmacology), Bhaisaj Kalpana (Pharmaceutics), Nidan (Diagnosis) and Chikitsa (Management principles) are all based on validated knowledge. Similarly is the case with the design and application of asanas, mudras and kriya in the domain of yoga. It is necessary to therefore assert that A yurveda and Yoga are I evidence based knowledge systems'. The issue at hand is that the evidence base in Ayurvedic Pharmacognosy, Pharmacology, Pharmaceutics and
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1 Need to develop inter-cultural standards for quality, safety and efficacy of traditional Indian Systems of Medicine. Darshan Shankar, P.M. Unnikrishnan and Padma Venkatasubramanian Current Science VaIn No. 11, June 2007, 1499-1505

2 Bioactivity of traditional preparation of Piper longum L(Piperaceae). V.B. Preethi Sudha, U.G. Geeta, P.Venkatasubramanian. Journal of Tropical Medicinal Plants. Vol. 5 No.2,December 2004

3 Char aka Samhita - Chikitsa Sthana - 6th Chapter deals with the management of prameh, where in prolonged use of Bitter drugs has been contra-indicated for lean (vata type) people suffering from prameha.

Clinical Practice is constructed on the systemic parameters of the A yurvedic discipline and not in terms of structural parameters of western bio-medicine.

Thus the evidence available is disciplinary (rooted in Ayurvedic discipline) and not 'trans-disciplinary'. Generating trans-disciplinary evidence is a complex task because it requires assimilation of the disciplinary knowledge of Ayurveda (which is a holistic systemic theory) and its translation and correlation with western bio-medicine (which is a reductionist and structural theory). Cross cultural interpretation of knowledge systems requires understanding of their foundations, world-views and epistemic frameworks. The correlation between two knowledge systems can certainly be discovered because the whole is related to its part, but the key is to appreciate that a systemic and structural theory cannot share a one to one correlation.

The challenge in designing clinical trials will be to develop an assessment strategy that takes into consideration the multiple facets of Traditional Health Care intervention which is not based upon the predominant one drug suits all paradigm of conventional western bio-medicine. This multiplicity in approach is what sets apart, A yurvedic Clinical management, from that of western bio-medicine. The multiple facets of A yurvedic Management of health and disease are:

a. Customised intervention that varies according to individual constitutional frame
work (prakriti) and the stage & phase of disease.
b. Multi-component intervention involving drug, diet, lifestyle, pancha-karma and
yoga.
c. A systemic cleansing of body (shodhana Chikitsa) using techniques of Pancha­
karma that is unique to A yurveda
d. A treatment approach that has homeostasis or restoration of balance as its end
point. In this approach stress is given to two things:
(1) Apunarbhavatva: Achieving a stable state of homeostasis that does not go
back to the prior diseased stage (non-recurring).
(2) Yonyamanyamudeerayet: Achieving homeostasis without causing any
disturbance to any other systems (without side-effects).

Another important point to be noted while developing a study design for clinical trials in Ayurveda is its three fold management strategy. These are outlined below:

1. Hetu-viparita or Hetu-viparitarthakari: This is an, approach that involves an intervention that is designed to tackle the cause of the disease rather than the specific type of imbalance of homeostasis or dosha. Such interventions would be individual specific and cannot be generalised. To illustrate the point, Hareetaki (Terminalia Chebula) is a drug used for many conditions, one of which is constipation, but it is specifically contra-indicated in certain people and in certain conditions (E.g. An exhausted and physically drained person, a person who has lost a lot of fluids, a very lean person, pregnant women, children etc). This implies that if one were to undertake a clinical trial to study the action of Hareetaki (Terminalia Chebula) in constipation then it should be a trial for only individuals for whom it is indicated and not for constipation in general.

2 Vyadhi-viparita or Vyadhi-viparitarthakari: This is an approach that involves an intervention that is designed to tackle a specific disease entity irrespective of the nature of imbalances of homeostatis or dosha. These are interventions that are disease specific. For example, the plant Patha (cissampleous pareira) is advised as a drug of choice in diarrhoea. It could be used in all kinds of diarrhoea, except in a condition called amatisara.4

Ubhaya-viaparita or Ubhaya- viparitarthakari: This is an approach that involves a strategy that is designed to tackle the disease as well as its cause, the imbalance in homeostatis or dosha. For example the herbal formulation, Dashamoola Kwatha (a decoction made from the roots of ten medicinal plants) is advised in vataja shotha (a specific kind of inflammation). Dashamoola acts on both, the specific type of imbalance (vata dosha) which is the cause for the disease, as well as, on the inflammation (shotha) which is the actual manifestation of the disease.

The basis of usual statistical design of clinical trials is randomization of eligible subjects to two or more comparator groups (in a blinded manner) and comparison between these comparator groups. The comparison is based on a clinical outcome which in most cases is a single outcome variable rather than a clinical outcome which is more holistic in nature. In addition the interpretation of results, especially in the confirmatory trials, is done to either prove or dis­prove a hypothesis which is set-up before the start of the trial.

In order to combine the knowledge systems of A yurveda and adapt the existing statistical approaches to design and analyze the data, we will have to address the following issues:

How do you select eligible subjects for A yurveda trials? Do you need to stratify all trials by the type of dosha. ?

How do you select the appropriate comparator group? Do you want to compare to a Placebo? How do you design a placebo which can be blinded? If this cannot be done, then how can we avoid a bias in interpreting the results? Do you want to use the existing/ approved western bio-medicine as a comparator?

4 In amatisara, a particular stage of diarrhoea described in Ayurveda, the purge is allowed to continue until the body is cleared of all ama (unhealthy metabolites resulting from faulty digestive process). The logic is that the purge is part of a curative mechanism of the body to rid itself of accumulated toxins and should not be stopped using medicines.

How do you define a quantifiable/objective end-point? Is there a systematic approach to turning a holistic, Ayurveda based, clinical end-point into an objective and quantifiable endpoint?

Do you want to conduct the A yurveda clinical trial as a confirmation trial? If no, are there alternative ways of doing a clinical trial and still come up with results which help in furthering the science. For example, instead of testing a pre­specified hypothesis, the first step could be to conduct a clinical trial to estimate the magnitude of the effect. .

Are the Ayurvedic treatments that are being tested quantifiable? If not, can the different treatment levels be put on an ordinal scale? For example, if in addition to the Ayurvedic medicine, yoga is also required. In this case can different levels of yoga asana to be done be quantified based on the intensity of yogic exercises.

In order to brainstorm these issues and many others which will help us adapt the existing, theoretically very powerful statistical design and analyses techniques, IIAIM proposes to organise a National Workshop involving Ayurveda Vaidyas, Yoga Experts, Clinical Pharmacologists, Economists, Epidemiologist, Social scientists and Bio-Statisticians. This will be a precursor to an international conference involving important CAM players including representatives of regulatory bodies to discuss and disseminate the outputs of the workshop.

Objectives of the Workshop

(1) To raise awareness about specific issues which need to be factored in order to design an Ayurvedic clinical trial

(2)To formulate guidelines for design of Management-Trials, sensitive to the multi-component interventions and end points of Ayurveda.

Participants

Around thirty persons (listed below) representing Ayurveda clinicians, Post graduate institutions, Research centers, Yoga Experts, Clinical Pharmacologists, Epidemiologist, Social scientists and Bio-Statisticians:

1. Prof. Ranjith Roy Choudhury, INCLEN, New Delhi
2. Dr. MS Valiathan
3. Dr. MUR Naidu, NIMS, Hyderabad
4. Dr. Bhushan Patwardhan, MUL, Bangalore
5. Dr. Urmila Thatte,KEM, Mumbai
6. Dr. Tanaz Birdi, FMR, Mumbai
7. Dr. Nagaraj, Director NIMHANS
8. Vaidya Vilas Nanal, Pune
9. Vaidya Ramesh Nanal, Mumbai
­10. Vaidya Gangadhran,Bangalore
11. Vaidya RH Singh, Varanasi
12. Vaidya Dilip Gadgil, rune
13. Dr. Jayaprakash Narayan, Bangalore
14 Dr. Ashwini Mathur, Hyderabad
15. Mr. A V Balasubramanian, Chennai
16. Dr. Nagendra, VY ASA, Bangalore
17. Mangal Teertham Saraswathi (Dr. AK Ghosh), Bihar School of Yoga
18. Dr. Ishwar Murthy, Director, MD National Institute of Yoga, Delhi
19. Dr. Lavekar, Director, CCRAS
20. Dr. Ram Manohar, AVATAR
21. Dr. Ramesh, A VN, Madurai
22. Dr. Rangesh Paramesh, Himalaya Drug Company Limited
23 Dr. Shailesh Nadkarni, Dhootpapeshwar, Mumbai
24. Dr. Narendra Bhat, Mumbai
25 Dr. MS Baghel, GAU, Jamanagar
26. Director, NIA, Jaipur
27. Dean, BHU, Varanasi
28. Dean, Tilak A yurveda Vidyapeeth, rune
29. Principal, Government A yurvedic College, Trivandrum
30. Principal, VPSV AMC, Kottakkal
31. Dr. Murlidhar Sharma, SDM, Udupi
32. Director, National Institute of Unani Medicine, Bangalore
33. Director, Amrita College of Ayurveda, Kerala
34. Dr. Asok vaidya.
35. Dr. L. Mahadevan
36. Director,National Institute of Sidha Medicine, Chennai
37. Dr. Ravi Narayan, Bangalore