|
 
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| EDITORIAL |
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| Year : 2021 | Volume
: 4
| Issue : 2 | Page : 41-45 |
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Ayush research strategies and designs: An epitome
Eugene Wilson, Arumugam Rajendra Kumar
Central Council for Research in Siddha, Ministry of Ayush, Government of India, Chennai, Tamil Nadu, India
| Date of Submission | 26-Oct-2022 |
| Date of Acceptance | 18-Nov-2022 |
| Date of Web Publication | 23-Jan-2023 |
Correspondence Address:
Dr. Eugene Wilson
Central Council for Research in Siddha, Ministry of Ayush, Government of India, Tambaram Sanatorium, Chennai, Tamil Nadu
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/jrsm.jrsm_30_22
How to cite this article:
Wilson E, Rajendra Kumar A. Ayush research strategies and designs: An epitome. J Res Siddha Med 2021;4:41-5 |
| Preamble | |  |
“Much of outcomes research is a systematic attempt to exploit what is known and make it better”—Kevin Kelly
Ayush systems of medicine are categorized as whole medical systems, which are complete systems of theory and practice that have evolved over time in different cultures.[1] Ayush systems, in addition to internal medicines, provide dietary advice, discuss lifestyle choices, and perhaps also use external treatment packages such as thokkanam (massage), varmam (manual techniques), etc., as component parts of whole system of healthcare.[2] Siddha medicine, the science of holistic health, emphasizes on maximizing the body’s inherent healing ability, addressing physical, mental, and spiritual attributes of a disease, and placing a strong emphasis on preventive medicine. The inventors of Siddha science/medicine—Siddhars have pioneered research in domains pertaining to basic science, drug research, and clinical medicine much before the dawn of industrial revolution and advent of sophisticated laboratory and instrumentation technology available today.[3] The role of ancient Siddhars as clinicians as well as researchers is noteworthy and commendable in facets such as philosophy, pharmacy, pharmacognosy, pharmacology, pharmaceutics, pathology (also subtle), diagnostics, nosology, omics (individualized treatment), toxicology, nanotechnology, etc. Siddhars used a 10-fold approach without any bias for full-proof evaluation and validation known as “alavai.”[3]
The coronavirus disease (COVID-19, an infectious disease caused by the SARS-CoV-2 virus) pandemic has brought out the efficacy of Siddha formulations in mitigating mild-to-moderate COVID illness validated through double-blind placebo-controlled trials—the gold standard of evidence-based medicine. Central Council for Research in Siddha (CCRS, an autonomous organization under the Ministry of Ayush, Government of India is an apex body for conducting research in Siddha system of medicine) has published the findings of its clinical trials in peer-reviewed journals.[4] Significant research in India has recognized a poly-herbal medicated powder (Madhumega chooranam) for non-insulin dependent diabetes mellitus–PURSE HIS cohort, RAN therapy for human immuno deficiency virus pandemic—nonrandomized controlled study, Orthosiphon stamineus Benth (Poonai meesai) for renal insufficiency—case report, etc.[5],[6],[7] Moreover, the clinical use of Andrographis paniculata Nees. potion, etc., for chikungunya and dengue epidemics has been justified by in vitro studies.[8] Even the antiviral activity of Kabasura kudineer and Nilavembu kudineer for COVID-19 was equivalent to remdesivir in in vitro studies.[9] Long-term research on Wrightia tinctoria (Roxb.) R. Br has yielded dividends in the form of patents and trademark protection in the management of psoriasis (777 oils).[10],[11] Globally systematic research on Ayush therapies has provided wider acceptance and promoted many components of Ayush therapies as complementary and alternative medicine, which are becoming an integral part of the complementary and integrative medicine (CIM). Aatharam (six subtle basic centers—wheel/chakras), meditation (mind–body medicine), thokkanam (massage), attai vidal (leech therapy), panchakarma (Ayurveda), yogasanam (Yoga), cupping (Unani), etc., are some of CIM practices popular in India.[12]
Even though Ayush systems are inherently evidence-based (long history of use, tradition, faith, popularity, and anecdotal reports), it is important to recognize the need for research in Ayush systems. Since Ayush remedies are already in the public domain, the main motive to perform clinical research on Ayush treatments is for justification purpose.[13] Research should emerge from positive experience in clinical practice and ideally address “effectiveness gaps,” resulting from either the suboptimal management conditions by allopathic medicine or where the use of allopathic medications is expensive and/or likely to result in drug reactions and side effects for the subject.[14] Appropriate methodologies and clinical protocols for evaluating safety and efficacy of Ayush systems remain crucial, even more so in the case of research and evaluation of traditional procedure-based therapies. Pragmatic or whole system clinical trials (black box approach) may be better suited for Ayush. In this regard, the World Health Organization has published General Guidelines for Methodologies on Research and Evaluation of Traditional Medicine (2000).[15] The Department of Ayush (currently the Ministry of Ayush) has published Good Clinical Practice (GCP) for Clinical Trials in Ayurveda, Siddha and Unani (2013) based on the GCP Guidelines for Clinical Trials on Pharmaceutical Products (2001) published by Central Drugs Standard Control Organization (CDSCO).[16]
Considering the above facts, the research strategies to encourage R&D in Ayush sector is briefed below.
| Research Strategies And Research Designs | | |
When is a treatment said to be effective? A treatment is said to be effective only if the patient is better with the intervention than without. How do we know that a treatment is effective? The theory predicts that it should be effective, plus the practitioners experience and expertise of vaittiyars/teachers indicate it has been effective, and evidence from earlier studies shows it has been effective (if any). How can we assess effectiveness? We can assess effectiveness by a simple pre–post comparison that is before treatment and after treatment, for example, comparison using visual analog scale (VAS) for pain intensity.[17] Again, we have to ask questions, like: Is the pre–post difference a good indicator for effectiveness? And is the pre–post difference a valid estimate of the treatment effect or is it biased. So, whenever there is potential bias like natural history, prognosis, and regression to the mean arise, the remedy is to include a control or comparison group whenever possible, because the consequence from having a control group focuses on group differences (not pre–post comparison).[18]
Groups probably differ in factors relevant to prognosis (severity of symptoms, chronicity, socioeconomic status, health behavior, beliefs, etc.), which may lead to selection bias/confounding. Other potential biases are prognostic and baseline difference, and the remedy is randomization using random allocation whenever possible.[19] Potential biases also occur in a controlled study, and the remedy is blinding, whenever possible.[20] Further, high attrition rates/missing data can make studies uninterpretable because of variety of factors. The remedy is to do careful follow-up/analyses. Moreover, nonspecific effect is yet another major problem, and many report that isn’t it all a placebo effect? To overcome this, we may use placebo controls, whenever possible.[21]
| Research Question | | |
The fundamental starting point is to define the research question from which the rest of the research design will follow.[22] Different questions require different research models to provide the answers. [Table 1] details appropriate research methodology to answer specific research question.
| Research Design | | |
Individualized
Each subject is given an individualized prescription that may change over time. Constitutional factors that underpin the health of each person, such as the state/strength of their digestive system, subjective sense of vitality, etc., are taken into account. These subtle changes are considered important to enhance the effectiveness and reduce any unwanted adverse effects. Case studies/reports and case series both retrospective and prospective may be helpful in the development of hypothesis/protocol for a clinical trial with semi-standardized research design.[23] For example, N-of-1 trial could represent a way to make the traditional use of a case study more rigorous and scientifically acceptable.[24]
Semi-standardized
Constitutional framework of the subject (udal iyal/prakriti) and diagnosis of disease by pulse (nadi), tongue (naa) examination, urine-ghee sign (neer-nei kuri), etc., are used to notify treatment or inclusion/exclusion into a clinical trial so as to provide broadly targeted treatment. This will ensure external validity of the study similar to clinical practice, e.g., observational studies.[23]
Standardized
Single remedy is used for all subjects in a trial. It has the advantage of making the findings of the trial more generalizable, but it may not conform to the generally held principles of Ayush practice, as the internal validity of the study is safeguarded and may not mimic clinical practice, e.g., randomized controlled trial.[23]
| Superiority Over Placebo | | |
Ayush treatment is based on proper history taking, pulse, and tongue diagnosis, etc. Hence, an additional Ayush diagnosis with the conventional diagnosis could be used for choosing the appropriate Ayush drug. In this direction, Ayush diagnosis and an appropriate treatment could be used for stratification within the randomization process [Figure 1]. This is especially useful for pilot trials or smaller studies to prove Ayush as an individualized treatment system. This trial design allows for an individual Ayush treatment according to the Ayush diagnosis.[25] | Figure 1: Example of placebo-controlled trial design to evaluate Ayush drugs
Click here to view |
| Noninferiority Or Superiority Over Standard Care | | |
The second possibility is to see the diagnostic procedure as a part of the Ayush treatment, and the diagnostic procedure is used only on the Ayush group after randomization [Figure 2]. Study designs shown in [Figure 1] and [Figure 2] are used to answer different research questions. The first option focuses on the treatment effects of the drug, whereas the second option provides a broader picture and evaluates Ayush as a whole treatment system, which consists of both the diagnostic procedure and the drug treatment.[26] | Figure 2: Example of standard care-controlled trial to evaluate Ayush as a whole treatment system
Click here to view |
| Diagnostic Studies | | |
Reliability studies
The reliability of a diagnostic test depends on the accuracy and reproducibility of the test results. The accuracy is defined by comparing the test results with a final true diagnosis. The predictive values are here the most important clinical measures. Since it may be impossible to establish a final true diagnosis the reliability must in some cases be measured by a determination of reproducibility. More importantly, it must be ensured that diagnostic agreement is achieved between different observers as well as at different time points.[27]
Validity studies
Validity measures the extent to which the diagnostic test actually does what it is supposed to do. More precisely, validity is determined by measuring how well a test performs against the gold standard. The best method to establish a diagnosis is by comparing a new diagnostic test with the gold standard.[28],[29]
| Research Planning | | |
“PICO” represents an acronym for patient, intervention, control, and outcome. These four components are the essential elements to clarify the research question on effectiveness and eventually guides to plan a study as depicted in [Table 2].[30]
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
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[Figure 1], [Figure 2]
[Table 1], [Table 2]
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