SU M M A R Y Background: Consumers want to know the recent evidences on Ayurveda treatments despite of over 10,000 written volumes (Bhagel MS 2009). Progress in any discipline of science often judged by the number of publications (Arunachalam S 2002). English language journals always highlight the difficulty in locating research publication on Ayurveda. Unpublished research works (e.g. theses) and journal volumes are scattered all over India denying easy accessibility. Since funding agencies list the name of projects that they support there ought to have many publication on Ayurveda. However no attempts were made to systematically search and collect research publications on Ayurveda. This helps to conduct systematic reviews and offer recommendations for patient treatment and further research. Objective: 1. To develop a search strategy to identify vast majority of published and unpublished clinical studies in any subject on Ayurveda 2. To develop structured protocol to conduct systematic reviews on research publications to recommend on treatment & further research 3. To E-publish search methodologies, protocols, systematic reviews and journal abstracts Methods: The first meeting of Local Project Advisory Committee (LPAC) decided to structure a model to implement the project objectives over one disease: Switra (called Vitiligo or Leucoderma). The project was implemented in three steps: 1. Developed protocol and search strategy to identify research publications 2. Conducted systematic review of pooled research works. Recommendations are made on the basis of available publications for evidence based treatment of Switra 3. E published the outcome o f project work with a scope to expand the database to provide easy access to the information on evidence based treatment in Ayurveda. We searched all articles (1975-2008) pertaining to one disease: Switra. The Protocol was developed ( Page No 74 to 111).We are grateful to Prof Shreekumaran Nair (Manipal), 3
Dr. Unnikrishnan (Mangalore ) and Dr. Muralidharan (Kasaragod) for their continuous guidance during protocol development. Search strategy to identify research works included developing a PICO table (Page No 41) listing controlled vocabulary of Sanskrit ( AyuSH - Ayurveda Subject Headings) as key words (Page no 207) Hand Searching was achieved the through Baghel MS (2006). During the search strategy we had to list the databases that host Ayurveda articles. At this stage search strategy was supported by search option and descriptions of various web sites (page No 39). We also visited the offices o f a few o f them to learn on their experiences. Pooled research publications were reviewed independently by PI- allopathy (Dr. S R Narahari) and SRF - Ayurveda (Dr. Guruprasad Aggithaya). Both attempted to extract the data through integrated data extraction sheet ( Page No 104). A standard methodology article against which the reviews could be compared did not exist. Hence at this stage we synthesized clinical trial methodology out o f Ayurvedic principles and structured that using CONSORT model. Based on the review a questionnaire was developed to assess the knowledge level of Ayurveda investigators. This was sent to four referees. The questionnaire was then further improved through pre-testing in two Ayurveda Medical colleges: SDM College Udupi, Karnataka (Dr. Muralidhara Sharma & Colleagues), Parassinikkadavu Ayurveda Medical College, K.annur, Kerala (Dr. Rashmitha & Colleagues). This questionnaire was sent through email (1631) and by post (445). 58 investigators participated. (Page No 308) Summary of the project activities are then E-published (www.systematicreviewinayurveda.org) Results: 41 databases were identified that host authentic research publication from Ayurveda. Baghel MS (2006) listed 71 theses works on Switra in 27 institutions. This formed 0.9 % of total theses work all Ayurveda Medical Colleges in the country during 1975-2008.34 Articles were identified in 41 databases and 64% could be procured. We could procure 32.4 % of theses on Switra. Many studies identified in Ayurveda Medical Colleges could not be procured despite a personal visit or sending an emissary. 112 combinations or single formulations to treat Switra were listed from classical literature. 39 of them were studied through 24 clinical trials till 2008. Each of 39 medicines has undergone only one trial. Most of them had methodological issues and of small sample size. Case series studies were eleven. 4
Five trials used industrial products that are not described in classical Ayurveda. One classical formulation (Katuki) was used along with biomedical drugs. This was classified as integrative medicine trial. Details of the trials conducted and medicines used are described in tables (Page No 278)Trials on industrial products gave no details on conducting mandatory preclinical tests. 20.7 % studies performed after 2000 AX) obtained ethical approval. A questionnaire based assessment of knowledge level of investigators on Ayurveda was done. 58 responses were obtained from 2076 people contacted. 60% did not know the correct method of literature search. None developed a search strategy. They frequently accessed PUBMED for research studies. None mentioned Baghel MS (2006) for hand searching. Percentage of incorrect answers to important issues in clinical trials were listed ( Page No316, Table no 4) 74% of investigators on Ayurveda who receive grants for their research did not receive training for research. Discussion: Kessler C, Hannover Medical School, Germany observed that many Ayurvedic publications are retrievable only by hand search as a comprehensive electronic database for Ayurvedic publications do not exists. Popular western databases such as PUBMED and CAM databases list only a small number of Ayurvedic studies. Ayurvedic systematic reviews often quote CCRAS database to search for publications. Two systematic reviews on vitiligo published from Europe did not contain any Ayurveda research papers. Western scientists commonly search AMED for CAM articles. This could not be accessed from India. Facilities to search Ayurveda journal abstracts in the similar was as far biomedical journal abstracts (PubMed) is not available in world wide web as far we could find. This as background the project had the objective to develop protocols for evidence based Ayurveda to treat dermatology and sexually transmitted disease. Creating a search strategy, for ayurveda databases and publications, hand searching for unpublished research work, systematic review of the pooled literature all formed the part o f the work elements. Since there was no previous experience in the field, we developed each area de novo. To achieve this we have used the framework o f Cochrane protocols. Comparative clinical trials used classical Ayurveda medicines on intervention and comparison arms. However there was no mention of the non inferiority margin. Non inferiority trials (NIT) test the hypothesis that one therapy is not worse than the other. One o f the trials (Perugu 1992) compared Shamanoushadha with two arms o f shodhana 5
karma (virechana and jalaukavacharana). Shamana group and virechana group were given to 19 patients each. Jalaukavacharana was given 14 patients. All showed repigmentation except one patient in jalaukavacharana group. This study resembled equivalence trial (ET). However these publications did not mentioned about NIT or ET. NIT and ET are of recent development and therefore Ayurveda studies may not discuss these designs in their methodology. Since comparative trials resembled NIT we call them quazi non inferiority trials. There needs an elaborate discussion to develop clear guidelines on use of non inferiority trials on Indian Systems of Medicine before its adaptation to systematic reviews of Ayurveda. We found that in most trials non hairy areas of the body had shown repigmentation. Ayurveda and biomedicine claim that depigmentation affecting non hairy areas is mostly not treatable. The findings in these primary studies give a lead that repigmentation process may be influenced by factors other than melanocytes cell count done. Total of 105 research works were undertaken on Switra during 1975-2008. 55/105 (52.4%) could be procured. Among the procured studies 29/55 (52.7%) were eligible for analysis. Our recommendation (Page No 8 to 11) are When shamanoushadha alone is used dhatryadi chuma or dhatryadi yoga is to be given along with avalguja beejadi lepa on the basis o f individualized patient selection Any of the following Shamanoushadha can be used along with virechana on the basis of individualized patient selection 1. shwetha aparajitha mula (oral) + Chitraka root (topical) 2. Gajalinda Kshara (oral) + Bakuchi beeja (topical) As the part of the project knowledge level of investigators on Ayurveda were assessed. 60.3% of the responders were Ayurvedic doctors, No one in 58 obtained full marks on MCQ section of the questionnaire. MCQ questions dealt on available clear cut guidelines with no scope for ambiguity. Incorrect answers to them indicate that clinical studies carried out by such investigators are likely to have lower evidence level because of the possibility of confounders. 60% of the investigators did not know the correct method of literature search. None accessed all databases discussed in the project. There was no search strategy. No one was aware of hand searching through Baghel MS (2006). Among responders 77.6% were currently conducting research studies receiving funding 6
from India s major grant making agencies. However 74.1% am ong investigators did not receive any structured training. The above project used Switra as a model disease. This m ay be replicated to any disease. We expect that in other diseases e.g. Kitibha, Amavatha, Vatarakta etc clinical studies are likely to be more common on these diseases than vitiligo as latter is a difficult to cure (Asadhya/ Kastasadhya) disease. References: 1. Bhagel MS, Kori VK. International catalogue of Ayurvedic publications; Institute for Postgraduate Teaching and Research in Ayurveda, Gujrat Ayurveda University, Jamnagar; 2009. 2. Bhagel MS. Researches in Ayurveda 2005. Gandhinagar; M ridu Ayurvedic Publication and Sales, 2006. 3. Perugu 1992 Evaluation of kakodumbaradi yoga in the management of shvitra Department o f kayachikitsa, Govt. Ayurvedic M edical College Mysore. 4. Subbiah Arunachalam. Is science in India on the decline? Current science, 2002; 83:107-108. 7