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| PROTOCOL |
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| Year : 2021 | Volume
: 5
| Issue : 1 | Page : 47-53 |
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Efficacy and safety of Ayurveda interventions for acid peptic disease: A protocol for systematic review
Amit Kumar Rai1, Harit Kumari2, Azeem Ahmad1, Richa Singhal1, Bhogavalli Chandrasekhara Rao1, Narayanam Srikanth1
1 Central Council for Research in Ayurvedic Sciences (CCRAS), Ministry of Ayush, Govt. of India, New Delhi, India
2 Regional Ayurveda Research Institute, Lucknow, Uttar Pradesh, India
| Date of Submission | 22-Jul-2021 |
| Date of Acceptance | 03-Sep-2021 |
| Date of Web Publication | 14-Dec-2021 |
Correspondence Address:
Dr. Amit Kumar Rai
Central Council for Research in Ayurvedic Sciences (CCRAS), Ministry of Ayush, Govt. of India, 61−65, Institutional Area, Opposite D-Block, Janak Puri, New Delhi 110058.
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/jras.jras_4_21
Background: Acid peptic disease (APD) has a negative impact on patients’ quality of life and general health status of the individuals. There are a number of case studies and clinical trials on efficacy of Ayurvedic interventions in the management of APD. However, a systematic review of these researches is not available which is needed to evaluate the clinical significance of those studies. Objective: The aim of this study is to conduct a systematic review of the available evidence for the efficacy and safety of Ayurvedic interventions for APD. Methods and Analysis: On the basis of the PRISMA-P statement, a systematic review protocol has been developed. Data from electronic databases such as PubMed, Cochrane Central Register of Controlled Trials, AYUSH Research Portal, DHARA, Shodhganga, Ayurvedic Research Database, Institute for Teaching and Research in Ayurveda, Gujarat Ayurveda University, Jamnagar, Clinical trial registries, and relevant journals will be used to find articles for systematic review. Only studies that have been published in English or Hindi will be considered for inclusion in the systematic review. Data from the selected studies based on study characteristics will be extracted separately by two review authors for data analysis and quality assessment of the studies. The risk of bias in the chosen studies will be evaluated using appropriate available tools. If studies that are qualified for meta-analysis are available during the review, then it will be done. If meta-analysis is not possible, then the findings will be presented in the form of a comprehensive qualitative synthesis. Conclusion: The findings of this study will aid in determining the current state of evidence on the efficacy and safety of Ayurvedic interventions for the treatment of APD. The review will also serve as a source for researchers while planning future studies in order to generate high-quality evidence on the efficacy and safety of Ayurvedic therapies in APD. Study Registration: PROSPERO 2020: CRD42020207484 Keywords: Acid peptic disease, Amplapitta, Ayurveda, systematic review
How to cite this article:
Rai AK, Kumari H, Ahmad A, Singhal R, Rao BC, Srikanth N. Efficacy and safety of Ayurveda interventions for acid peptic disease: A protocol for systematic review. J Res Ayurvedic Sci 2021;5:47-53 |
How to cite this URL:
Rai AK, Kumari H, Ahmad A, Singhal R, Rao BC, Srikanth N. Efficacy and safety of Ayurveda interventions for acid peptic disease: A protocol for systematic review. J Res Ayurvedic Sci [serial online] 2021 [cited 2023 Mar 27];5:47-53. Available from: http://www.jrasccras.com/text.asp?2021/5/1/47/332444 |
| Introduction | |  |
Acid peptic disease (APD) is a collective term used to include several clinical conditions such as gastroesophageal reflux disease (GERD), esophagitis, gastritis, peptic ulcer disease (PUD), and Zollinger−Ellison syndrome (ZES). APD is caused by overlapping but separate disease pathways that result in either excessive acid secretion or weakened mucosal defense.[1] APD has a negative impact on patients’ quality of life and contributes to significant morbidity. According to a survey by the Indian Society of Gastroenterology Task Force, 7.6% of Indian individuals have substantial GERD symptoms, whereas the prevalence rate in western countries is approximately 15%−20%.[2],[3] In the general population, PUD is believed to affect roughly 5%−10% of people.[4]According to an epidemiology study, PUD has a prevalence of 7.8% in India.[5] The annual incidence of PUD that needs treatment ranges from 0.10% to 0.19%.[6] PUD consequences such as bleeding, perforation, and blockage continue to be a cause of considerable number of hospitalizations. The use of Helicobacter pylori eradication medicines and proton pump inhibitors has greatly reduced the prevalence and relapse rate of APD. Evidence has emerged in recent years that 8 weeks or longer use of proton pump inhibitors is connected to adverse drug reactions such as chronic hypergastrinemia with rebound gastric acid hypersecretion, gastric atrophy, and chronic hypochlorhydria.[7] The rising frequency of antibiotic resistance is another barrier to effective management of PUD caused by H. pylori infection. As a result, finding a more promising treatment that is devoid of adverse drug reaction and have better efficacy is the need of hour for treatment of APD.
The clinical features of APD in Ayurveda closely resemble with diseases entitled in Sanskrit as Vidgdhajirna (indigestion), Amlapitta (hyperacidity), Annadravashoola (abdominal colic), and Parinamshoola (duodenal ulcer). Along with diet and lifestyle modification, Ayurveda line of treatment for APD emphasizes on restoring metabolism, body cleansing by medicated vomiting and medicated purgation therapy, and pacifying the involved pathological factors with drugs having a bitter taste and rejuvenation properties such as Yashtimadhu (Glycyrrhiza glabra L.), Amalaki (Phyllanthus emblica L.), and Shatavari (Asparagus racemosus Willd.).[8] Studies indicate that Ayurveda drugs used in APD have actions such as antioxidant, inhibition of excess acid production, and secretion, enhancing mucus formation, stimulation of mucosal proliferation, and inhibition of inflammation.[9],[10],[11],[12],[13],[14],[15] Therefore Ayurvedic interventions have been found to be useful in the management of APD in limited sample size clinical trials and case studies.[16],[17],[18],[19],[20],[21]
However, high-quality evidence addressing the efficacy and safety of Ayurvedic therapy modalities in the management of APD is required for their wider applicability. Hence, the objective of this systematic review is to assess the evidence for the safety and efficacy of Ayurvedic interventions in the treatment of APD.
Review question
Are Ayurveda interventions effective and safe in the treatment of APD?
Objectives
The primary objective of this systematic review is to conduct a comprehensive analysis of published clinical studies in order to determine the efficacy and safety of Ayurvedic therapies in the treatment of APD. The secondary objective is to perform the meta-analysis, if sufficient studies eligible for meta-analysis are available during the review.
| Materials and Methods | | |
This protocol has been drafted using the PRISMA-P (preferred reporting items for systematic review and meta-analysis procedure) statement standards.[22] For methodological considerations, the Cochrane Handbook for Systematic Reviews of Interventions is also referred.[23]
Eligibility criteria
Type of studies
Randomized controlled, non-randomized controlled, quasi-randomized controlled, and multi-arm parallel-group comparative trials in relation to evaluation of the efficacy and safety of Ayurvedic interventions for the treatment of APD are included.
Type of participants
Clinical studies on patients of both sex and regardless of age with diagnosis of Vidgdhajirna (indigestion caused by Pitta), Amlapitta (hyperacidity), Annadravashoola (abdominal colic), and Parinamshoola (duodenal ulcer) explained in classical Ayurveda texts or/and APD such as GERD, esophagitis, gastritis, PUD, non-ulcer dyspepsia considered for this systematic review.
Type of interventions
Ayurveda interventions used in the clinical trials irrespective of medicine type, dosage form, dose, frequency, prescribed diet, and lifestyle modification advices are considered for the present systematic review.
Type of comparators/control
The control or standard group narrated in the collected researches such as standard conventional medicine, non-Ayurveda therapies, placebo, and no treatment will be viewed as comparator/control group.
Outcome measures
Primary outcome: Assessment of improvement in objective and/or subjective criteria related to efficacy of trial interventions.
Secondary outcomes: Incidence of serious adverse event/adverse drug reaction, withdrawals due to adverse events, and improvement in the patient’s health-related quality of life.
Timings: No restrictions will be made to the intervention period or the duration of follow-up. However, an attempt will be made for categorization and assessment of studies based on similar timeline for the treatment of APD.
Information sources
Electronic databases such as PubMed, Cochrane Central Register of Controlled Trials, AYUSH Research Portal, DHARA, Shodhganga, Ayurvedic Research Database (2001−2018), ITRA, Gujarat Ayurveda University, Jamnagar, Clinical trial registries, and clinical studies published in relevant journals will be used for current systematic review. The selected articles references as well as relevant systematic reviews will also be screened. To identify original publications on relevant clinical trials, hand searching will be done for journals that are published only in prints, that is, offline journals, journals not indexed in any electronic database and conference proceedings/reports/compendiums. The information source also includes public domain versions of relevant dissertations and theses. There will be no limitations on the date of publication, or the study setting. However, only research articles published in English or Hindi will be considered. In the case of deficiencies in collected information and where additional information on the study is needed then communication with the authors of respective studies will be done to gather the required information.
Search strategy
Suitable search strategy will be adopted for different electronic databases. Strategy for searching PubMed is shown in [Table 1].
Data collection and analysis
Selection of studies
Two review authors will independently review the titles and abstracts of all accessible articles screened against the inclusion criteria (AKR and HK). In case of disagreement between the two review authors, the disagreement will be settled through involvement and judgement of the third review author (AA). The complete text of the article will also be screened by two review authors (AKR and HK) to determine whether the selected study fits the inclusion criteria. At each level, the justification for the exclusion of research study from the review will be documented. Any disagreements regarding inclusion or exclusion of any study will be handled through discussion among all the review authors. If additional information from the study authors is required to settle any doubts regarding eligibility of the study, then it will be sought through communication with the corresponding author of the relevant work. The full study selection process will be documented according to PRISMA guidelines and it will be shown as PRISMA flow diagram [Figure 1] while presenting the results of the systematic review.[24]
Data extraction
A pre-designed framework will be constructed to extract data from the included studies on study characteristics such as authorship, publication-related information, methodology, participant, intervention, comparator, and outcomes. Two review authors (AKR and HK) will extract data independently from the studies finalized for this systematic review.
Data management
The records and data gathered during the searches will be saved in password-protected folders on a secure computer and also in external data storage device. Only the review authors will have access to the saved data.
Risk of bias (quality) assessment
The risk of bias in the selected studies will be assessed separately by two review authors (AKR and HK). Randomized controlled trials will be assessed with the help of a revised tool to assess the risk of bias in randomized trials (RoB 2), whereas non-randomized trials will be analyzed with the ROBINS-I tool (Risk Of Bias In Non-randomized Studies − of Interventions).[25],[26] The RoB 2 tool is having five domains: randomization, deviations from intended interventions, missing outcome data, outcome measurement, and reporting of outcomes. The seven domains of the ROBINS-I tool are bias due to confounding, bias due to participant selection, bias in intervention classification, bias due to deviation from intended interventions, bias due to missing data, bias in outcome measurement, and bias in the selection of the reported result. With the help of predefined algorithms, a judgement regarding the likely risk of bias on each of the domains of the above-mentioned instruments will be established. As shown in [Figure 2] and [Figure 3], it will be displayed as a traffic light plot and a weighted summary plot.
Measures of treatment effect
The binary variable will be examined using the odds ratio (OR)/risk ratio (RR) with 95% confidence intervals. If the data are continuous, the mean difference (MD)/standard mean difference (SMD) with 95% confidence intervals will be chosen.
Data synthesis
If sufficient studies are clinically similar with comparable study population characteristics, interventions, and outcome measures, methodologically similar in study design and quality, with statistically similar treatment effects, the collected study data will be quantitatively synthesized (meta-analysis).[27] The I2 statistic will be used to evaluate trial heterogeneity.[22] If there is sufficient heterogeneity, a subgroup analysis to investigate the likely causes will be done. The Review Manager 5.4 will be used to conduct the meta-analysis. Summarization and interpretation of results will be done for the included studies as a systematic qualitative synthesis when meta-analysis is not possible due to significant heterogeneity.
Subgroup analysis
Preplanned categories for subgroup analysis will be patient demographics (age and pre-existing co-morbidity), types of intervention and control, and study characteristics (study design, duration of intervention and follow-up, and study quality).
Sensitivity analysis
The impact of including trials with high rates of attrition bias, trials that do not disclose the intention to treat analysis, or have other missing data on the overall treatment outcomes will be assessed using sensitivity analysis.[22]
Assessment of meta-bias
The Cochrane Handbook for Systematic Reviews of Interventions will be referred to assess publication bias and selective reporting of outcomes within the included studies.[23] To detect any publication bias, funnel plots will be generated and examined for any asymmetry.
Confidence of cumulative evidence
The World Health Organization’s Grading of Recommendations for Traditional Medicine will be used to assess the strength of the body of evidence obtained via this systematic review.[28] The evaluation will comprise all of the research studies that have been selected for this systematic review.
Ethics and dissemination
Because no sensitive participant data will be included in this systematic review, no ethical assessment or clearance is required. The findings of this systematic review will be reported in accordance with the PRISMA guidelines,[24] and will be published in an indexed, open-access journal as well as presented at national and/or international conferences to ensure broad dissemination.
| Discussion | | |
In clinical practice and published clinical trials, Ayurvedic interventions have shown encouraging benefits in the management of APD. However, in order to determine the degree and gaps in the available evidences on the safety and efficacy of Ayurvedic care for APD, a thorough review of relevant clinical studies is required. There has never been a systematic review of the efficacy and safety of Ayurvedic interventions for APD; therefore, this work is important in providing the requisite database in view of future recommendations for the management of APD. This systematic review will examine and summarize the available data supporting the efficacy and safety of Ayurvedic interventions for APD management.
| Conclusion | | |
The findings of this study will assist clinicians in patient care and will also provide inputs for future research to provide high-quality evidence on the efficacy and safety of Ayurvedic interventions for their wider use in treatment strategies for APD.
Study registration
This systematic review protocol has been registered with PROSPERO, International Prospective Register of Systematic Reviews (PROSPERO 2020: CRD42020207484).
Acknowledgement
Authors are thankful to Prof. (Vd.) K.S. Dhiman, former Director-General, Central Council for Research in Ayurvedic Sciences, Ministry of AYUSH, Government of India for his valuable guidance and support.
Financial support and sponsorship
This work is supported by Central Council for Research in Ayurvedic Sciences, Ministry of Ayush, Government of India.
Conflicts of interest
There are no conflicts of interest.
Authors’ contribution
AKR contributed to the conception of the study, designing the selection criteria and search strategy, drafting of the protocol, and initial draft of the manuscript. HK assisted in study design and drafting of the manuscript. AA assisted in study design and methodology, and final approval of the manuscript. RS, BCSR, and NS were involved in critical revision and final approval of the manuscript. All authors read, provided feedback, and approved the final version of the manuscript.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1]
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