Need for good clinical trials in Ayurveda:
Double-blind randomized placebo-controlled trials have been long regarded as the gold standards that provide evidence regarding the efficacy of any intervention, and hence, one cannot afford to ignore this trend. When there are sufficient numbers of such double-blind trials, there will be room for meta-analyses and systematic reviews which will form the best possible evidence. However, when one considers Ayurveda interventions, it becomes obvious that there are no good meta-analyses in the literature because of a paucity of good clinical trials. On PubMed search, for instance, we get roughly 130 clinical trials when the search term ‘Ayurveda’ is entered. Therefore, there cannot be an argument against the need for good clinical trials in Ayurveda.
Why conducting good clinical trials in Ayurveda is difficult?
Ayurveda is a complex system that considers multiple clinical and other parameters while deciding a specific line of treatment. These parameters include individual constitution (Prakriti), digestive strength (Agnibala), nature of bowel evacuation (Koshtha), Saama-Niraama state (metabolically immature and mature state) and many more. Further, the diagnosis of a disease in Ayurveda too is complex one. For example, different individuals suffering from the same clinical condition, noninfective gastroenteritis for example, may be diagnosed by different names such as Visuchika, Atisara, Grahani, Ajirna, Adhoga Amlapitta, Shula etc. Further, there could be external factors such as seasons (Ritu) and Desha (place of residence) that might differ in each of these individuals. This in fact leads to many possible permutations and combinations in interventions. In a nutshell, different patients suffering from same disease may receive different interventions according to Ayurveda.
This situation poses a challenge in designing a good clinical trial because the generally accepted method of conducting clinical trial involves comparing the efficacy of one intervention against either placebo or another intervention. Mostly, a linear cause-effect relationship is assumed in such trials. For example, it may be one antibacterial agent vs another antibacterial agent in case of infective conditions, and one analgesic versus another analgesic in conditions that are associated with pain. This model may be sufficient to guide biomedical clinical practice because this is how biomedicine is practiced. However, this model of clinical trials is not suitable in the context of Ayurveda because multiple algorithms are involved in decision-making by Ayurveda practitioners. This is the reason why available literature on Ayurveda clinical trials is grossly insufficient: these protocols are blind copies of the clinical trials involving biomedical interventions. Therefore, there is a huge gap between how Ayurveda is practiced and how it is researched!
Recent attempts:
It is important to note that during the past few years there have been a few sincere attempts at designing right kind of Ayurveda clinical trials in a manner that is true to the principles of Ayurveda. In one of these trials on rheumatoid arthritis, the autonomy of a physician in the form of individualizing the complex interventions was preserved. Because this study was published in one of the leading journals of rheumatology, it was expected that many such studies would be attempted at. However, it is strange to see that researchers have not yet considered this as the right template for building up evidence in favor of Ayurveda interventions. One of the reasons for this is that Ayurveda academia does not take up serious kind of research in general. Another factor may be that most of the Ayurveda teachers are ignorant of these attempts and hence, this model has not yet probably percolated into Ayurveda colleges and research institutions.
Suggested algorithm:
I suggest that the complexity involved in deciding interventions must be considered at an early stage while designing a good clinical trial. All possible permutations and combinations of parameters and diagnoses must be enumerated in the beginning itself and the individualization methods must be made clear. It is a good idea to include a panel of clinically successful Ayurveda practitioners to deliberate and finalize this. Such a trial would prove fruitful in testing the “whole system” against either standard of care or a placebo, as the case may be. A good protocol for Ayurveda clinical trial must at the beginning itself have clear-cut flowcharts designed and individualization methods finalized. A flowchart involving the following factors must be prepared and each intervention at every possibility must be pre-decided:
- The factors related to the individual could be Prakriti, Agnibala, Koshtha, Dhatu Sarata, occupation of the individual, lifestyle, dietary habits, etc
- The factors related to the disease could be Saama-Niraama stage, Nava-Purana State, Stage of the disease (Kriyakala), the diagnosis of the condition, accompanying conditions such as obesity, hypertension etc.
- The factors related to environment: Ritu, Desha etc.
While reporting, though conventional biomedical diagnosis must also go in the title, I suggest that a detailed algorithm followed while deciding the intervention may also be provided.
Limitations of this approach and available alternatives:
Yes, this approach may be too complex and it may be difficult to enumerate all possible permutations and combinations beforehand. Conducting such complex studies with the limited available resources may be another problem. This is especially true because as the number of permutations and combinations increase, the number of formulations and other interventions too would increase. Standardization of raw materials, standardization of pharmaceutical processes etc would consume lot of time and resources. In such cases, I suggest that a study can be limited to one set of possibilities. For example, a study could be framed something like "Effectiveness of Ayurveda intervention in the young-adult population of Pitta Prakriti with acid-peptic disease presenting as Vidagdhajirna in Sharad Ritu". Though such an alternative would require excluding many cases of the same disease, still would prove to be practical.
Science versus non-science dilemma:
Most of the hardcore science lovers have a bias against alternative therapies and often call such methods ‘pseudo-medicine’ or ‘pseudoscience’. It is high time that Ayurveda researchers come up with right kind of clinical trial protocols and start publishing the results. This would in a long run help everyone of us to understand what Ayurveda actually is. Till that time Ayurveda will continue to be perceived by scientists based on the trials that are poorly designed and that ignore core principles.
References:
1. Manohar PR. Consideration of Ayurvedic diagnostics in design of clinical trials. Ancient Science of Life. 2013;33(1):1-3. doi:10.4103/0257-7941.134553.
2. Witt CM, Michalsen A, Roll S, et al. Comparative effectiveness of a complex Ayurvedic treatment and conventional standard care in osteoarthritis of the knee – study protocol for a randomized controlled trial. Trials. 2013;14:149. doi:10.1186/1745-6215-14-149.
3. Furst DE, Venkatraman MM, Krishna Swamy BG, McGann M, Booth-Laforce C, Ram Manohar P, Sarin R, Mahapatra A, Krishna Kumar PR. Well controlled, double-blind, placebo-controlled trials of classical Ayurvedic treatment are possible in rheumatoid arthritis. Ann Rheum Dis. 2011 Feb;70(2):392-3. doi:10.1136/ard.2010.136226. Epub 2010 Aug 24. PubMed PMID: 20736391.
4. Furst DE, Venkatraman MM, McGann M, Manohar PR, Booth-LaForce C, Sarin R, Sekar PG, Raveendran KG, Mahapatra A, Gopinath J, Kumar PR. Double-blind, randomized, controlled, pilot study comparing classic ayurvedic medicine, methotrexate, and their combination in rheumatoid arthritis. J Clin Rheumatol. 2011 Jun;17(4):185-92. doi: 10.1097/RHU.0b013e31821c0310. Erratum in: J Clin Rheumatol. 2011 Oct;27(7):407. PubMed PMID: 21617554.
8 comments:
Dear Vd.Kishor, first of all let me appreciate your relentless enthusiasm on matters related to Ayurvedic education and research. I wish your blogpost will bring in some good discussion in the subject matter. I always used to worry about the type of research we do and the type of evidence we try to generate. We hire some or other method to research ayurveda from a different school of thought and try to prove/disprove what is told in the classical literature. The terminology and methodology used always conflicts with what is intended. Has this sort of research ever helped Ayurvedic corpus or practice to improve further? Keep the matter of research away. Do we have a proper methodology to teach ayurveda under the centralised curriculum? I am afraid, the answer is no. Ayurveda has some integrity in its theoretical platform and it is somewhat universal. But that is not the case with its practice. It changes from time to time and from place to place. These practices are not standardised. They are not monolithic as well. And there is no sense in hoping it to be so. This is not the case with the systems or streams whose tools we hire to teach or to do research. At present ayurveda academies all over the country and abroad, are engaged in an exercise of making ayurveda 'scientific'. The learned members of the academies feel that there is something in the Ayurvedic corpus which may be regarded as 'row information' of the past. They consider these informations as the crude representation of the primitive understanding of the Indian subcontinent. If researched upon and refined, these information can be used as leads for proper works and further product development which suits the needs of modern society. With this attitude they work hard to make ayurveda refined and scientific. After 4 decades of concerted effort, a stage prevails at present wherein the Ayurvedic teaching, learning and practice have become very complex and research have become a puppetry. The diverse practices of ayurveda are almost extinct. Everything herbal, including tribal practices/grandma's kit/backyard remedies/practice of shamans, are labelled as ayurveda. From contraceptive to curry powder, everything is sold with the label of ayurveda. The philosophy and logic of the system lost. Homas and other religious practices getting more and more tied up to Ayurvedic billboard. 'Panchakarma' has become the buzzword to sell ayurveda. We should understand the loss that society has suffered through all these 'scientific' twists and turns that the system has gone through. Society has all the rights to enjoy the benefits of a traditional system of healing and healthcare. But the academies made the system UN-available/affordable/acceptable. So with all the humility, let me express my concerns about making the system further 'scientific' . Instead, let's plan something original, something which is in tune with the original logic and philosophy of the system, to reinvent it with proper learning/teaching techniques and giving the benefits of its contents to the society with all the advantages of the present day technology. Let's stop filling the heads of our students with unwanted, irrelevant information out of our overenthusiasm to get marked as 'scientific'. And let's stop our faculty members and researchers from publishing papers for the academic incerements and emoluments. After all let's stop ourself from dancing to the tunes which do not match our pitches. I again express my hope that your post will ignite, as always, some good discussion in this regard.
With lots of love and regards
Vd. M. Prasad
sunethriayurveda@gmail.com
Hi,
Nice article. I want to comment the following:
1. I feel the complexity of Ayurvedic diagnosis of disease is because of the absence of classification of disease based on the site of disease and symptoms; everything seems to be mixed up. If we can simplify the diagnosis through a structured approach (like in shalakya netra roga), it may bring down the ambiguities and treatment may also become more rational and straight forward
2. Even randomized controlled trials or modern research methodology has several shortcomings. It also keeps changing, for example, for example, p-value slowly losing its value.
3. Can we develop our own Ayurvedic research methodology? - may be based on Pramana and Vaadamaarga; we may evan have to look outside Ayruvedic text books for the same
4. Specialized research units are missing in Ayurveda. If we develop 10 specialized research units, each focusing on 1 disease/subject, we can specialize in that area within a matter of 25 years and we may be able to replace modern medicine with Ayurveda in that particular disease area.
5. We lack marketing skills and communication skills; we need to focus on that part to ensure our success spreads to remaining Ayurvedic doctors as well as patients.
I totally agree and especially endorse your view on a clinical trial on RA which, according to me should be weighed in gold standards and be set as an example in designing research protocols for clinical trials in Ayurveda.
Dear Kishor,
A thought provoking article.
I have some questions and some possible answers. I would like to read your responses.
1. ....similar clinical condition may be diagnosed with different names - Is this a problem in ayurveda diagnosis framework or of the physician? If it is of the physician, then development of sound diagnostic protocols is the solution. I feel diagnostic framework using right algorithms (algorithms are computer assisted) should solve the issue. So the specific condition will be diagnosed specific name. But if the problem lies in the framework (which I doubt) then challenging the framework is the key.
2. 'linear cause effect relationship' - if you refer to the discussion on 'satkaryavad', relationship between types of causes and their outcomes is elaborated. 3 types of causes and two types of relationships one to one or one to many and vice versa. Similar basis of reasoning is explained as principle of modern clinical research. Therefore the component of controlling maximum possible variations to ascertain linear cause effect relation began, making it reductionistic. We can use both approaches reductionist and comprehensive.
3. I would share the example of whole system clinical research by Kalpana Joshi and T near for asthma. as you rightly pointed out such designs are possible in ayurvedic teaching/ academic hospitals with minimal funds but involvement of PG students. The clinical work happens every day in academic institutions. Change in Approach is needed towards documentation.
Thanks for these constructive comments.
Asmita madam, what I have understood about the same clinical condition being diagnosed by different names is not a problem related to the diagnostic skills, rather, this is how Ayurveda looks at diseases. Our diseases are often classified based on presenting symptoms. The same disease, for example gastroenteritis, may present as pain abdomen (Shula ?) in one case and as diarrhoea (Atisara ?) in another case. That determines our diagnosis, and even the line of treatment. However, it is not the case with conventional medicine. Their diagnosis is mostly based on the cause or the pathogenesis, but not on clinical presentation. What I am trying to say here is that possibly we need to discuss and identify the different possible presentations of the same disease beforehand, and decide our interventions.
'One cause and one effect' is the reductionist approach to understanding any disease. Ayurveda framework provides multi-factorial approach to such an understanding, and that is the basis of "systems thinking" too. The fields of genomics and molecular biology have already started adopting such "systems biology approach" to understand human biology.
Thanking you,
Kishor
Hello sir .such a nice article you have written and i am very impressed by your blog.Thanks for sharing.
Thank you Kishor.
Good to see that we are on the same page with difference of expression.
Keep writing.
Dear Kishor,
You have realy raised a valid and essential issue. It is true that a single disease entity is looked differently and managed differently according to principles of Ayurveda. Ayurved does not give much importance to the name of disease.
"Vikaro Nama Akushalo Na Jihiviyat Kadachana.
Na hi Sarva Vikaranam Namato asti Dhruvan Sthiti".
But every condition can be classfied down the line starting from Santarpanottha Apatarpanottha to condition of Dosha, Dhatu, Agni, Dhatvagni etc. One has to consider the Anshansh Kalpana. We have to take up research studies on our basic tenets. For examples we can take up studies on effect of a particular dravya on Ama. Comaprative study of Amapacaka effect. A drvaya acting on particualr Dhatvagni. We all know that similar conditions will not exist. A patient suffering from R.A. may have issue with Rasa dhatvagni while another patient of R.A. my be having problem with Mamasa Dhatvagni. They will require different treatments. Still a single Amapacaka dravya will work for them in initial stage whereas their Dhatvagnis will have to be addressed at a later stage. Therefore we have to fractionalize the treatment protocols and subject them to stagewise assessment. This is a complex process but I think that is what is required for Ayurved research.
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