Figures
Abstract
Background
Many randomised controlled trials (RCTs) of herbal interventions have been conducted in the ASEAN Communities. Good quality reporting of RCTs is essential for assessing clinical significance. Given the importance ASEAN placed on herbal medicines, the reporting quality of RCTs of herbal interventions among the ASEAN Communities deserved a special attention.
Objectives
To systematically review the quality of reporting of RCTs of herbal interventions conducted in the ASEAN Plus Six Countries.
Methods
Searches were performed using PubMed, EMBASE, The Cochrane Library, and Allied and Complementary Medicine (AMED), from inception through October 2013. These were limited to studies specific to humans and RCTs. Herbal species search terms were based on those listed in the National List of Essential Medicines [NLEM (Thailand, 2011)]. Studies conducted in the ASEAN Plus Six Countries, published in English were included.
Results
Seventy-one articles were identified. Thirty (42.25%) RCTs were from ASEAN Countries, whereas 41 RCTs (57.75%) were from Plus Six Group. Adherence to the recommended CONSORT checklist items for reporting of RCTs of herbal interventions among ASEAN Plus Six Countries ranged from 0% to 97.18%. Less than a quarter of the RCTs (18.31%) reported information on standardisation of the herbal products. However, the scope of our interventions of interest was limited to those developed from 20 herbal species listed in the NLEM of Thailand.
Citation: Pratoomsoot C, Sruamsiri R, Dilokthornsakul P, Chaiyakunapruk N (2015) Quality of Reporting of Randomised Controlled Trials of Herbal Interventions in ASEAN Plus Six Countries: A Systematic Review. PLoS ONE 10(1): e108681. https://doi.org/10.1371/journal.pone.0108681
Editor: Daniele Fanelli, Université de Montréal, Canada
Received: January 21, 2014; Accepted: September 2, 2014; Published: January 29, 2015
Copyright: © 2015 Pratoomsoot et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This research received funding support from The Department for Development of Thai Traditional Medicine and Alternative Medicine, Ministry of Public Health, Thailand. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Introduction
Traditional Medicine is recognised as part of historical and cultural heritage in the communities of the Association of Southeast Asian Nations (ASEAN) Member States. The role and contribution of traditional medicine has been highlighted by the ASEAN Socio-cultural Community (ASCC) Blueprint under section B4: Access to healthcare and promotion of healthy lifestyles [1]. Under which, the strategic objectives were to ensure access to adequate and affordable healthcare, medical services and medicine, and promote healthy lifestyles for the people of ASEAN. Specific actions include the facilitation of research and cross-country exchange of experience in promoting the integration of safe, effective and quality Traditional Medicine, Complementary and Alternative Medicine (TM/CAM) into the national healthcare system, notably, the strengthening of the evidence base for herbal medicines and products.
ASEAN’s external relations with other nations led to the formation of an economic partnership known as the ASEAN Plus Six Group, which comprised of the members of the ASEAN plus Australia, China, India, Japan, New Zealand, and South Korea. This regional framework signifies the promotion of cooperation, prompting economic ties, increasing market scale and resource supply capacity [2].
It has been demonstrated that randomised controlled trials (RCTs) of herbal interventions seldom provide adequate methodological information, and the quality of reporting is poor [3]–[5]. Gagnier and colleagues (2006) studied the quality of reporting of RCTs of herbal medicine interventions, and observed that less than half (45%) of the consolidated standards of reporting trials’ (CONSORT) checklist items was reported across the 206 included RCTs [5]. In addition, many study reports overlooked the importance of the detailed information on the herbal products being investigated, and often, specific characteristics of the herbal interventions were omitted [6].
The significance of adequate and transparent reporting of herbal interventions cannot be overstated as it is necessary to elicit clinical significance. An Elaborated CONSORT Statement was developed to provide recommendations for the reporting of herbal medicine trials [7], which serve as an aid to editors and reviewers in assessing the internal/external validity and reproducibility of herbal medicine trials, thereby an accurate assessment of safety and efficacy can be achieved [8].
The purpose of the current study was to strengthen the evidence base for herbal medicines and products specific to the ASEAN Community. To date, no systematic assessments of the quality of reporting of RCTs of herbal interventions in ASEAN Communities have been published. Adequate reporting is considered crucial for the audience of the reports to reliably interpret the outcomes of the trials. In order to strengthen the evidence base for herbal medicines specific to the ASEAN Community as outlined in the ASCC Blueprint, specific study within the Community of ASEAN Plus six is called for. ASEAN Plus Six allowed for larger pool of the available evidence in herbal interventions as opposed to ASEAN alone. Thus, the aim of the present study was to assess the reporting quality of RCTs of herbal interventions in ASEAN Plus Six Countries using the Elaborated CONSORT Statement.
Methods
Electronic searches for randomised controlled trials of herbal interventions from ASEAN Plus Six Countries were conducted in the following databases: PubMed, EMBASE, The Cochrane Library, and Allied and Complementary Medicine (AMED). Searches were performed from inception through October 2013, and were limited to studies specific to humans and randomised controlled trials with the use of the term “random*”.
There were seven countries within the ASEAN Plus Six Groups where herbal medicines are listed as part of the National List of Essential Medicines or National Essential Drugs List [9]–[24]. These were China [10], Japan [12], South Korea [14], Lao PDR [18], Philippines [21], Thailand [23] and Vietnam [24]. However, the lists from China and Japan were written in Chinese and Japanese, respectively. Thus, the information was not readily available in English to us at the time of the study. In addition, we were unable to access the lists from South Korea and Lao PDR. The list from Philippines included herbal medicines from the several species including Cassia alata Linn. Vietnam has included thyme oil and ginko biloba in the list. Thailand has a long history of traditional and herbal medicine use. Over 70 herbal medicine products are listed under the National List of Essential Medicine (2011) [23]. This list was available to us at the time of the study. Of these herbal medicine products, we were interested in the products that were developed from single herbal species instead of the multi-herb preparations as this enabled us to limit the scope of the present study. There were 20 herbal medicine products developed and manufactured from 20 herbal species that were included in the list. These 20 herbal species thus formed the basis for the search terms in the present study (Table S1). An electronic search strategy for a database (EMBASE) is given in Table S2.
Screening
One researcher (CP) performed the searches and screened the titles and abstracts of the identified studies. The following inclusion criteria were applied:
- The studies were of herbal interventions of interest, single or combination preparations that included any of 20 species of herbs listed in the search terms
- The studies were randomised controlled trials in human subjects
- The randomised controlled trials were performed in ASEAN Plus Six Countries (ASEAN: Brunei, Cambodia, Indonesia, Laos, Malaysia, Myanmar, Philippines, Singapore, Thailand and Vietnam. Plus six: Australia, China, India, Japan, New Zealand, and South Korea). Locations of the studies were assessed by the information provided under the Patients and Methods Sections of the studies. Any randomised controlled trials of herbal interventions of interest that were performed outside ASEAN Plus Six Countries were not included
- The studies were published in English
Data extraction and assessment of quality of reporting
Full text articles were retrieved; three reviewers (CP, RS, and PD) screened the content and performed data extraction using an electronic standardised extraction form (Data available on request). Discussions were held to resolve any disagreement or discrepancies.
For each randomised controlled trial, we extracted information on the reporting characteristics according to the 22-item Elaborated CONSORT statement of recommendations for reporting randomised controlled trials of herbal interventions [8]. An assessment of the quality of reporting was carried out whereby each CONSORT checklist item was assigned a yes or no response depending on whether the item was included in the study report under the recommended section of the report. Furthermore, additional items which were not part of the CONSORT checklist were evaluated to capture a more comprehensive picture of the study reports. These were clinical trial registration, the availability of full protocol, source of funding, authors’ affiliations, ethics approval, acknowledgement, and disclosure of conflict of interest. Data were summarised using descriptive statistics with Excel version 2010.
We also compared the differences between ASEAN and Plus Six Countries to reveal information on the number of RCTs conducted, and the overall quality of reporting between the two Groups of Countries. Chi-Square tests were performed using SPSS Software (SPSS Inc. Released 2008. SPSS Statistics for Windows, Version 17.0. Chicago: SPSS Inc.). Fisher’s Exact values were read when more than 20% of cells had expected values of less than 5.
The report of the present systematic review, where applicable, adhered to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions [25].
Results
The electronic searches identified a total of 1,785 records. The screening of titles and abstracts excluded 1,696 records due to duplication, studies were non-randomised controlled trials, they were not herbal interventions of interest or were of countries of interest, or they were not published in English. Eighty-nine articles were selected for full text review, subsequently a further 18 studies were excluded because they were not of herbal interventions of interest, non-RCTs, unclear randomisation, the herbs were not being used as interventions or were published in non-English language. A total of 71 articles [26]–[96] were included (Figure 1).
General characteristics
The general characteristics of the 71 included RCT articles are presented in Table 1. The overall picture revealed that 30 (42.25%) RCTs were from ASEAN Countries, in contrast more than half (57.75%) were of the Plus Six origin. Thailand published the most RCTs of herbal interventions among the ASEAN Plus Six Countries (26 articles, 36.62%), which was followed by India (17 articles, 23.94%), and China (11 articles, 15.49%). Few studies were from Japan (5 articles, 7.04%) and South Korea (6 articles, 8.45%), while Philippines and Malaysia published the least having reported one article (1.41%) each.
From the scope of our interventions from 20 herbal species of interest, there were 12 species of herbs that were studied within the ASEAN Plus Six Countries. Zingiber officinale was the most frequently investigated herb (36 articles, 50.70%), and approximately one-tenth of the reported RCTs were of Curcuma longa L. (9 articles, 12.68%). The least investigated herbs were Clinacanthus nutans, Derris scandens Benth., Musa paradisiaca L., and Orthosiphon grandiflorus (1 article, 1.41% each).
The most common types of herbal preparations were capsule (38 articles, 53.52%), powder (6 articles, 8.45%), plaster (6 articles, 8.45%), and tablet (5 articles, 7.04%). Other types of preparations were decoction, granule, cream, tea, stick, gel, and juice. Seventeen RCTs studied commercial and marketed herbal products, and three RCTs examined non-marketed proprietary preparations, whereas 51 RCTs (71.83%) investigated herbal preparations with no commercial status reported.
With regard to the training or qualifications of first-authors, a total of 18 studies (25.35%) were from authors with Doctor of Medicine (MD) qualification, of which 4 had Doctor of Philosophy (PhD). Other studies were from a specialist in anaesthesiology (1.41%), a postgraduate resident (1.41%), and a nurse with a Bachelor of Science in Nursing (1.41%), etc. However, 46 studies (64.79%) did not clearly report the training or qualifications of first-authors, but they were affiliated with Medical College/Medical University/Hospital (39.44%), Traditional Chinese Medical College/Hospital (5.63%), University (7.04%), or Research Centre/Institute (8.45%).
Most of the studies were published between 2001 and 2013 (94.37%), and only a few studies were published in the 1990s (5.63%). The highest publication records were seen in 2006 (16.90%) and 2011 (12.68%).
It was found that nausea and vomiting during pregnancy (7 articles, 9.86%), osteoarthritis of the knees (7 articles, 9.86%), and post-operative nausea and vomiting (6 articles, 8.45%) were the most studied clinical conditions. Other commonly studied conditions were type 2 diabetes mellitus, post-surgical pain, nausea and vomiting in cancer patients, and physical performance and cognitive function in the elderly (3 articles, 4.23% per each condition).
Quality of reporting
Overall CONSORT checklist items.
The findings of the quality of reporting are represented in Table 2. Adherence to the recommended CONSORT checklist items for reporting of randomised controlled trials of herbal interventions among ASEAN Plus Six Countries ranged from 0% to 97.18%.
Fifteen CONSORT checklist items were reported, under the recommended sections, by most of the RCTs (more than 80%), including: how participants were allocated to interventions, under the abstract section (e.g., “random allocation”, “randomised”, or “randomly assigned”), statement of reasons for the trial with reference to the specific herbal medicinal product being used, the type of product used [e.g. raw (fresh or dry), extract], statistical methods used to compare groups for primary outcome(s), and discussion of the trial results in relation to trials of other available products.
Less than half of the RCTs reported the methods used to generate the random sequence allocation (item 8, 47.89%), and implement random allocation sequence (item 9 allocation concealment, 29.58%). Only one RCT completely reported the implementation of randomisation (item 10, 1.41%). In terms of blinding, approximately 31% RCTs clearly reported that they were double-blind studies with descriptions of who were blinded to group assignments (item 11). Around 27% RCTs reported diagrams of flow of participants through each stage (item 13). Albeit, 54.93% RCTs included drop-out reporting.
CONSORT checklist item 4.
Under the CONSORT checklist item 4, where the report of precise details of the interventions intended for each group were recommended, more than half of the RCTs reported the part(s) of plant used to produce the product or extract (item 4B: characteristics of the herbal product, 53.52%), the type of product used (item 4B: characteristics of the herbal product, 81.69%), the content of all quantified herbal product constituents per dosage unit form (item 4C: dosage regimen and quantitative description, 80.28%), and the rationale for the type of control or placebo used (item 4E: placebo/control group, 95.77%).
However, only few studies presented the complete report of the method of authentication of raw material (item 4B: characteristics of the herbal product, 2.82%), the product’s chemical fingerprinting and methods used (item 4D: qualitative testing, 4.23%), and the description of any special testing/purity testing (item 4D: qualitative testing, 5.63%). Less than a quarter of the RCTs (18.31%) reported information on standardisation of the herbal products (item 4D: qualitative testing).
ASEAN versus Plus Six Countries
Thirty RCTs (42.25%) were from ASEAN Countries, in contrast more than half (57.75%) were of the Plus Six Group. It can be clearly observed that studies from the Plus Six Group contributed larger proportions of the overall quality of reporting compared to studies from the ASEAN Countries, which could be directly related to the higher number of RCTs (41 studies versus 30 studies, respectively). This includes the method of authentication of raw material (item 4B) and product’s chemical fingerprint and methods used (item 4D).
Results of Chi-Square Tests (Table 2) showed that for most of the Elaborated CONSORT statement checklist items, there were no statistically significant differences between the quality of reporting of ASEAN and Plus Six Countries (P values>0.05). The checklist items that revealed statistically significant differences were 1) item 1 herbal medicinal product’s Latin binomial (P = 0.010); 2) item 4A name of the manufacturer of the product (P = 0.006); and 3) Proprietary product name (brand name) or the exact name (P = 0.049).
It was noted that the checklist item 1 herbal medicinal product’s Latin binomial was the only item that was reported more frequently in the RCTs of ASEAN Countries versus Plus Six Countries (P = 0.010).
Additional items
The results of the assessment of additional items are presented in Table 3. In general, ethics approval was reported by 74.65% of the RCTs, where almost all of the RCTs from ASEAN Countries (27 of 30 studies) provided ethics approval information, in comparison with the RCTs from Plus Six Countries, only 26 of 41 studies provided such information (P = 0.011). Reports on clinical trial registration and disclosure of conflict of interest were not common (7.04% and 23.94%, respectively). National and University/Institute were the most common sources of funding reported (14.08% for both sources), which was followed by funding from the industry (9.86%). Most of the authors (85.92%) were affiliated to universities or national institutes. Less than half of the studies (45.07%) acknowledged contributors other than the authors. No RCTs reported any information on the availability of full clinical trial protocol.
Discussion
Our study is the first to assess the reporting quality of RCTs of herbal interventions in ASEAN Plus Six Countries using the Elaborated CONSORT Statement. The study identified 71 RCTs of herbal interventions of interest, from the 20 herbal species listed in the NLEM (Thailand), which were conducted in the ASEAN Plus Six Countries. These RCTs were published since 1990. We generally found that none of the RCTs reported all of the CONSORT checklist items under the recommended sections. From the pool of herbal interventions of interest, more RCTs from Plus Six Countries were identified as opposed to those from ASEAN Countries. Thus explained why reports of RCTs from the Plus Six Group contributed larger proportions to the general quality of reporting. Few studies were from Australia, Japan and South Korea. This may be driven by the scope of the herbal species within the present study, which were limited to those from the list of Thailand’s NLEM.
Importantly, we highlighted that the reporting quality was poor under the checklist items 4B (characteristics of the herbal product), 4D (qualitative testing), and 4F (descriptions of practitioners). Previous study of quality of reporting of RCTs of herbal medicine interventions by Gagnier who assessed 206 reports of RCTs [5] also commented that specific characteristics of the herbal intervention were not adequately reported. However, the result of our study on diagram of flow of participants through each stage (item 13) was different from that of Gagnier [5], where we found 19% of RCTs from ASEAN Plus Six Countries reported such item versus 75.2% from Gagnier. Furthermore, all important adverse events or side effects in each intervention group (item 19) were reported in 47% of RCTs in our study compared to 64.1% of Gagnier. Another point to note is that the interpretation of the results, taking into account study hypotheses, sources of potential bias or imprecision, and the dangers associated with multiplicity of analyses and outcomes, these items were assessed as one item in Gagnier study (reported by 68.5% of RCTs). In contrast, our study assessed these items separately and the results showed that 39% reported interpretation of the results in light of the product and dosage regimen used (item 20); and 32% reported sources of potential bias or imprecision. Moreover, our study assessed the reporting of item 21 that is where possible, discuss how the herbal product and dosage regimen used related to what is used in self-care and/or practice, which was reported by 50% of RCTs from ASEAN Plus Six Countries.
In the light of ASEAN integration where a single market is aimed for 2015, harmonisation of evaluation of traditional medicines and health supplements is the main focus of interest. Special attention should be directed to ensure safety, efficacy and quality of the herbal products. Specifically, the type of extraction solvent used where applicable (in the case of the product is an extract) in addition to the plant to plant extract ratio. This is of great value as it provides the readers with information on how much of the starting plant material was required to produce a specific amount of the finished extract [8]. Furthermore, RCTs should report method of authentication of raw material, product’s constituents in terms of chemical profiling, especially special testing or purity testing as herbal medicines are often contaminated [97]. Moreover, standardisation of active chemical component(s) per dosage unit form should be reported, where applicable, to enable the audience to determine a specific effect in a clinical situation [5].
On the issue of randomisation and blinding, less than half of RCTs adequately reported information on method used to generate the random allocation sequence (47.89%), method for the implementation of random allocation sequence (29.58%), and blinding (30.99%). Other studies also found inadequate reporting of RCTs of herbal interventions [5], Traditional Chinese Medicine [98], and complementary and alternative medicine [4]. Such information is essential for readers to make judgment whether the results of the trials were subjected to bias.
Readers should be aware of the limitations within the present study. Only RCTs reported in the English language were included in the assessment. Hence, it may be considered as a language bias. In such manner, our findings can only be considered applicable to RCTs of herbal interventions reported in English. Although the selection of our databases may be considered as comprehensive, but this cannot be reciprocated for the selection or scope of our interventions of interest. Our selection was limited to those 20 herbal species listed in the NLEM of Thailand. Consequently, it may not represent the overall evidence base for ASEAN Plus Six Countries. This was clearly seen where there were more RCTs conducted in Thailand using those 20 herbal species compared to other countries within the Communities. Other countries in the ASEAN Plus Six Group may have conducted RCTs of other herbal species. Consequently, were not included in the present study as they were not part of the inclusion criteria. This may also have affected the number of the included studies, and the overall picture of the reporting quality. Nevertheless, our study represents a starting point for the assessment of RCT reporting quality of herbal interventions from ASEAN Plus Six Group.
Conclusion
Traditional Medicine is of great importance and plays an integrative role in the ASEAN Communities. The present study highlights the need to improve reporting quality of RCTs of herbal interventions across ASEAN Plus Six Group. Efforts to support research associated with the products of herbal origins should aim to improve the quality of RCTs, including the complete and adequate reporting thereof.
Supporting Information
Checklist S1.
PRISMA 2009 Checklist for systematic review.
https://doi.org/10.1371/journal.pone.0108681.s001
(DOC)
Table S1.
Herbal search terms used in the present study.
https://doi.org/10.1371/journal.pone.0108681.s002
(DOCX)
Table S2.
An electronic search strategy used in the EMBASE database.
https://doi.org/10.1371/journal.pone.0108681.s003
(DOCX)
Author Contributions
Conceived and designed the experiments: CP RS PD NC. Performed the experiments: CP RS PD. Analyzed the data: CP RS PD. Contributed reagents/materials/analysis tools: CP RS PD NC. Wrote the paper: CP RS PD NC.
References
- 1.
ASEAN Secretariat (2009) ASEAN Socio-Cultural Community Blueprint. ASEAN Secretariat. Available: http://www.asean.org/archive/5187-19.pdf. Accessed 9 December 2013.
- 2.
Urata S (2008) An ASEAN+6 Economic Partnership: Significance and Tasks. Asia Research Report 2007. Japan Center for Economic Research. Available: http://www.jcer.or.jp/eng/pdf/asia07.pdf. Accessed 10 December 2013.
- 3. Linde K, Jonas WB, Melchart D, Willich S (2001) The methodological quality of randomized controlled trials of homeopathy, herbal medicines and acupuncture. International journal of epidemiology 30(3): 526–531.
- 4. Moher D, Soeken K, Sampson M, Ben-Porat L, Berman B (2002) Assessing the quality of reports of systematic reviews in pediatric complementary and alternative medicine. BMC pediatrics 2: 3.
- 5.
Gagnier JJ, DeMelo J, Boon H, Rochon P, Bombardier C (2006) Quality of reporting of randomized controlled trials of herbal medicine interventions. The American journal of medicine 119(9): 800 e1–11.
- 6. Wolsko PM, Solondz DK, Phillips RS, Schachter SC, Eisenberg DM (2005) Lack of herbal supplement characterization in published randomized controlled trials. The American journal of medicine 118(10): 1087–1093.
- 7. Gagnier JJ, Boon H, Rochon P, Moher D, Barnes J, et al. (2006) Reporting randomized, controlled trials of herbal interventions: an elaborated CONSORT statement. Annals of internal medicine 144(5): 364–367.
- 8. Gagnier JJ, Boon H, Rochon P, Moher D, Barnes J, et al. (2006) Recommendations for reporting randomized controlled trials of herbal interventions: Explanation and elaboration. Journal of clinical epidemiology 59(11): 1134–1149.
- 9.
Department of Health, Australian Government (2013) Schedule of Pharmaceutical Benefits. Commonwealth of Australia. Available: http://www.pbs.gov.au/browse/publications. Accessed 18 December 2013.
- 10.
Ministry of Health (2012) National Essential Drugs List 2012 Edition. Ministry of Health, China. Available: http://www.moh.gov.cn/mohywzc/s3580/201303/f01fcc9623284509953620abc2ab189e.shtml. Accessed 19 December 2013.
- 11.
Ministry of Health and Family Welfare (2011) National List of Essential Medicines of India 2011. The Government of India. Available: http://cdsco.nic.in/writereaddata/National%20List%20of%20Essential%20Medicine-%20final%20copy.pdf. Accessed 18 December 2013.
- 12.
Ministry of Health, Labour and Welfare (2012) National Health Insurance Drug List. Ministry of Health, Labour and Welfare, Japan. Available: http://apps.who.int/medicinedocs/en/m/abstract/Js19548ja/. Accessed 18 December 2013.
- 13.
Pharmaceutical Management Agency (2012) New Zealand Pharmaceutical Schedule: August 2012. New Zealand Government. Available: http://apps.who.int/medicinedocs/en/m/abstract/Js19465en/. Accessed 18 December 2013.
- 14. Chun CB, Kim SY, Lee JY, Lee SY (2009) Republic of Korea: Health system review. Health Systems in Transition 11(7): 1–184.
- 15.
Ministry of Health (1998). Scheme of charges for the Ministry of Health. Negara Brunei Darussalam. Available: http://www.moh.gov.bn/generalinformation/medicalcharges.htm. Accessed 18 December 2013.
- 16.
The Committee for Establishing the National Essential Medicines List (2010) The Cambodian Essential Medicines List 2009, 6th revision. Department of Drugs and Food, Ministry of Health, Cambodia. Available: http://www.ddfcambodia.com/bureau/essential-drug-bureau.html. Accessed 18 December 2013.
- 17.
Ministry of Health of the Republic of Indonesia (2008) National List of Essential Medicines 2008. Ministry of Health, Republic of Indosia. Available: http://apps.who.int/medicinedocs/en/m/abstract/Js18011en/. Accessed 18 December 2013.
- 18.
World Health Organization and Ministry of Health, Lao PDR (2012) Health Service Delivery Profile: Lao PDR, 2012. World Health Organization and Ministry of Health, Lao PDR. Available: http://www.wpro.who.int/health_services/service_delivery_profile_laopdr.pdf. Accessed 18 December 2013.
- 19.
Pharmaceutical Services Divisions (2012) National Essential Drug List (NEDL), 3rd Edition, 2012. Ministry of Health Malaysia. Available: http://www.pharmacy.gov.my/v2/en/documents/national-essential-medicine-list-neml.html. Accessed 18 December 2013.
- 20.
Ministry of Health (2010) Essential and Complementary Medicines and Vaccines for Myanmar, 2010. Government of the Union of Myanmar. Available: http://www.moh.gov.mm/file/NLEM.pdf. Accessed 18 December 2013.
- 21.
The National Formulary Committee (2008) Philippine National Drug Formulary. Essential Medicines List Volume I, 7th Edition, 2008. Department of Health, Philippines. Available: http://apps.who.int/medicinedocs/en/d/Js19477en/. Accessed 18 December 2013.
- 22.
Ministry of Health (2013) National List of Drugs. Ministry of health, Singapore Available from: http://www.moh.gov.sg/content/moh_web/home/costs_and_financing/schemes_subsidies/drug_subsidies.html. Accessed 18 December 2013.
- 23.
National Drug Committee (2011) National List of Essential Medicines, 2011. Ministry of Public Health, Thailand. Available from: http://drug.fda.moph.go.th:81/nlem.in.th/. Accessed 18 December 2013.
- 24.
Ministry of Health (2008) National List of Essential Medicines, 2008. Ministry of Health, Vietnam. Available from: http://www.who.int/selection_medicines/country_lists/vnm/en/. Accessed 18 December 2013.
- 25. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, et al. (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Journal of clinical epidemiology 62(10): e1–34.
- 26. Agarwal KA, Tripathi CD, Agarwal BB, Saluja S (2011) Efficacy of turmeric (curcumin) in pain and postoperative fatigue after laparoscopic cholecystectomy: a double-blind, randomized placebo-controlled study. Surg Endosc 25(12): 3805–3810.
- 27. Apariman S, Ratchanon S, Wiriyasirivej B (2006) Effectiveness of ginger for prevention of nausea and vomiting after gynecological laparoscopy. J Med Assoc Thai 89(12): 2003–2009.
- 28. Banerjee P, Maity S, Das T, Mazumder S (2011) A double-blind randomized placebo-controlled clinical study to evaluate the efficacy and safety of a polyherbal formulation in geriatric age group: a phase IV clinical report. J Ethnopharmacol 134(2): 429–433.
- 29. Biswas SC, Dey R, Kamliya GS, Bal R, Hazra A, et al. (2011) A Single-masked, Randomized, Controlled Trial of Ginger Extract in the Treatment of Nausea and Vomiting of Pregnancy. International Medical Sciences Academy 24(4): 167–169.
- 30. Bo P, Chen QM, Zhu HH, Zhang XD, Xu HR, et al. (2010) Clinical observations on 46 cases of globus hystericus treated with modified Banxia Houpu decoction. J Tradit Chin Med 30(2): 103–107.
- 31. Cao B, Den W (2012) Clinical observation of treatment with Yiqi Jianpi decoction combined with FOLFOX4 for the postoperation patients of colorectal cancer. Chinese-German Journal of Clinical Oncology 11(10): 605–608.
- 32. Xuemei C, Jiaping T, Ling W (2006) Treatment of cholelithiasis by acupuncture and oral decoction. J Tradit Chin Med 26(3): 167–169.
- 33. Charuwichitratana S, Wongrattanapasson N, Timpatanapong P, Bunjob M (1996) Herpes zoster: treatment with Clinacanthus nutans cream. Int J Dermatol 35(9): 665–666.
- 34. Chittumma P, Kaewkiattikun K, Wiriyasiriwach B (2007) Comparison of the effectiveness of ginger and vitamin B6 for treatment of nausea and vomiting in early pregnancy: a randomized double-blind controlled trial. J Med Assoc Thai 90(1): 15–20.
- 35. Chopra A, Saluja M, Tillu G, Venugopalan A, Sarmukaddam S, et al. (2011) A Randomized Controlled Exploratory Evaluation of Standardized Ayurvedic Formulations in Symptomatic Osteoarthritis Knees: A Government of India NMITLI Project. Evid Based Complement Alternat Med 2011: 724291.
- 36. Chopra A, Saluja M, Tillu G, Venugopalan A, Narsimulu G, et al. (2012) Comparable efficacy of standardized Ayurveda formulation and hydroxychloroquine sulfate (HCQS) in the treatment of rheumatoid arthritis (RA): a randomized investigator-blind controlled study. Clin Rheumatol 31(2): 259–269.
- 37. Chopra A, Saluja M, Tillu G, Venugopalan A, Narsimulu G, et al. (2012) Evaluating higher doses of Shunthi - Guduchi formulations for safety in treatment of osteoarthritis knees: A Government of India NMITLI arthritis project. J Ayurveda Integr Med 3(1): 38–44.
- 38. Chopra A, Saluja M, Tillu G, Sarmukkaddam S, Venugopalan A, et al. (2013) Ayurvedic medicine offers a good alternative to glucosamine and celecoxib in the treatment of symptomatic knee osteoarthritis: a randomized, double-blind, controlled equivalence drug trial. Rheumatology (Oxford) 52(8): 1408–1417.
- 39. Dans AM, Villarruz MV, Jimeno CA, Javelosa MA, Chua J, et al. (2007) The effect of Momordica charantia capsule preparation on glycemic control in type 2 diabetes mellitus needs further studies. Journal of clinical epidemiology 60(6): 554–559.
- 40. Fuangchan A, Sonthisombat P, Seubnukarn T, Chanouan R, Chotchaisuwat P, et al. (2011) Hypoglycemic effect of bitter melon compared with metformin in newly diagnosed type 2 diabetes patients. J Ethnopharmacol 134(2): 422–428.
- 41. Guo H, Huang Y, Xi Z, Song Y, Guo Y, et al. (2006) Is bowel preparation before excretory urography necessary? A prospective, randomized, controlled trial. J Urol 175(2): 665–669.
- 42. Hanai H, Iida T, Takeuchi K, Watanabe F, Maruyama Y, et al. (2006) Curcumin maintenance therapy for ulcerative colitis: randomized, multicenter, double-blind, placebo-controlled trial. Clin Gastroenterol Hepatol 4(12): 1502–1506.
- 43. He C, Chen P, Wang X, Ding M, Lan Q, et al. (2006) The clinical effect of herbal magnetic corsets on lumbar disc herniation. Clin Rehabil 20(12): 1058–1065.
- 44. Hu L, Hu X, Yang M, Xie H, Xiang Y (2008) Clinical effects of the method for warming the middle-jiao and strengthening the spleen on gastric mucosa repair in chronic gastritis patients. J Tradit Chin Med 28(3): 189–192.
- 45. Kim KS, Kim DW, Yu YK (2006) The effect of capsicum plaster in pain after inguinal hernia repair in children. Paediatr Anaesth 16(10): 1036–1041.
- 46. Kim KS, Kim KN, Hwang KG, Park CJ (2009) Capsicum plaster at the Hegu point reduces postoperative analgesic requirement after orthognathic surgery. Anesth Analg 108(3): 992–996.
- 47. Kim KS, Koo MS, Jeon JW, Park HS, Seung IS (2002) Capsicum plaster at the korean hand acupuncture point reduces postoperative nausea and vomiting after abdominal hysterectomy. Anesth Analg 95(4): 1103–1107.
- 48. Kim KS, Nam YM (2006) The analgesic effects of capsicum plaster at the Zusanli point after abdominal hysterectomy. Anesth Analg 103(3): 709–713.
- 49. Kim SW, Ha KC, Choi EK, Jung SY, Kim MG, et al. (2013) The effectiveness of fermented turmeric powder in subjects with elevated alanine transaminase levels: a randomised controlled study. BMC Complement Altern Med 13: 58.
- 50. Koosirirat C, Linpisarn S, Changsom D, Chawansuntati K, Wipasa J (2010) Investigation of the anti-inflammatory effect of Curcuma longa in Helicobacter pylori-infected patients. Int Immunopharmacol 10(7): 815–818.
- 51. Kositchaiwat S, Suwanthanmma W, Suvikapakornkul R, Tiewthanom V, Rerkpatanakit P, et al. (2006) Comparative study of two bowel preparation regimens for colonoscopy: senna tablets vs sodium phosphate solution. World J Gastroenterol 12(34): 5536–5539.
- 52. Kumar A, Garai AK (2012) A clinical study on Pandu Roga, iron deficiency anemia, with Trikatrayadi Lauha suspension in children. J Ayurveda Integr Med 3(4): 215–222.
- 53. Kuptniratsaikul V, Pinthong T, Bunjob M, Thanakhumtorn S, Chinswangwatanakul P, et al. (2011) Efficacy and safety of Derris scandens Benth extracts in patients with knee osteoarthritis. J Altern Complement Med 17(2): 147–153.
- 54. Kuptniratsaikul V, Thanakhumtorn S, Chinswangwatanakul P, Wattanamongkonsil L, Thamlikitkul V (2009) Efficacy and safety of Curcuma domestica extracts in patients with knee osteoarthritis. J Altern Complement Med 15(8): 891–897.
- 55. Leelarasamee A, Trakulsomboon S, Sittisomwong N (1990) Undetectable anti-bacterial activity of Andrographis paniculata (Burma) wall. ex ness. J Med Assoc Thai 73(6): 299–304.
- 56. Maenthaisong R, Chaiyakunapruk N, Tiyaboonchai W, Tawatsin A, Rojanawiwat A, et al. (2014) Efficacy and safety of topical Trikatu preparation in relieving mosquito bite reactions: A randomized controlled trial. Complement Ther Med 22(1): 34–39.
- 57. Manusirivithaya S, Sripramote M, Tangjitgamol S, Sheanakul C, Leelahakorn S, et al. (2004) Antiemetic effect of ginger in gynecologic oncology patients receiving cisplatin. Int J Gynecol Cancer 14(6): 1063–1069.
- 58. Mato L, Wattanathorn J, Muchimapura S, Tongun T, Piyawatkul N, et al. (2011) Centella asiatica Improves Physical Performance and Health-Related Quality of Life in Healthy Elderly Volunteer. Evid Based Complement Alternat Med 2011: 579467.
- 59. Misra MN, Pullani AJ, Mohamed ZU (2005) Prevention of PONV by acustimulation with capsicum plaster is comparable to ondansetron after middle ear surgery. Can J Anaesth 52(5): 485–489.
- 60. Nale R, Bhave S, Divekar DS (2007) A Comparative Study of Ginger and Other Routinely Used Antiemetics for Prevention of Post Operative Nausea and Vomiting. J Anesth Clin Pharmacology 23(4): 405–410.
- 61. Nanthakomon T, Pongrojpaw D (2006) The efficacy of ginger in prevention of postoperative nausea and vomiting after major gynecologic surgery. J Med Assoc Thai 89 Suppl 4: S130–S136.
- 62. Niempoog S, Pawa KK, Amatyakul C (2012) The efficacy of powdered ginger in osteoarthritis of the knee. J Med Assoc Thai 95 Suppl 1: S59–S64.
- 63. Nik Hazlina NH, Pazudin IM, Nor Aliza AG, Mohsin Sahil JS (2005) Clinical study to compare the efficacy and adverse effects of Nona Roguy Herbal Formulation and gonadotrophin releasing hormone agonist (GnRH) in the treatment of uterine fibroids. International Medical Journal 12(4): 295–302.
- 64. Paocharoen V (2010) The efficacy and side effects of oral Centella asiatica extract for wound healing promotion in diabetic wound patients. J Med Assoc Thai 93 Suppl 7: S166–S170.
- 65. Paramdeep G (2013) Efficacy and tolerability of ginger (Zingiber Officinale) in patients of osteoarthritis of knee. Indian J Physiol Pharmacol 57(2): 177–183.
- 66. Park HS, Kim KS, Min HK, Kim DW (2004) Prevention of postoperative sore throat using capsicum plaster applied at the Korean hand acupuncture point. Anaesthesia 59(7): 647–651.
- 67. Patankar S, Dobhada S, Bhansali M, Khaladkar S, Modi J (2008) A prospective, randomized, controlled study to evaluate the efficacy and tolerability of Ayurvedic formulation “varuna and banana stem” in the management of urinary stones. J Altern Complement Med 14(10): 1287–1290.
- 68. Pillai AK, Sharma KK, Gupta YK, Bakhshi S (2011) Anti-emetic effect of ginger powder versus placebo as an add-on therapy in children and young adults receiving high emetogenic chemotherapy. Pediatr Blood Cancer 56(2): 234–238.
- 69. Pongrojpaw D, Chiamchanya C (2003) The efficacy of ginger in prevention of post-operative nausea and vomiting after outpatient gynecological laparoscopy. J Med Assoc Thai 86(3): 244–250.
- 70. Pongrojpaw D, Somprasit C, Chanthasenanont A (2007) A randomized comparison of ginger and dimenhydrinate in the treatment of nausea and vomiting in pregnancy. J Med Assoc Thai 90(9): 1703–1709.
- 71. Premgamone A, Sriboonlue P, Disatapornjaroen W, Maskasem S, Sinsupan N, et al. (2001) A long-term study on the efficacy of a herbal plant, Orthosiphon grandiflorus, and sodium potassium citrate in renal calculi treatment. Southeast Asian J Trop Med Public Health 32(3): 654–660.
- 72. Rassameemasmaung S, Sirikulsathean A, Amornchat C, Maungmingsook P, Rojanapanthu P, et al. (2008) Topical application of Garcinia mangostana L. pericarp gel as an adjunct to periodontal treatment. Complement Ther Med 16(5): 262–267.
- 73. Rassameemasmaung S, Sirikulsathean A, Amornchat C, Hirunrat K, Rojanapanthu P, et al. (2007) Effects of herbal mouthwash containing the pericarp extract of Garcinia mangostana L on halitosis, plaque and papillary bleeding index. J Int Acad Periodontol 9(1): 19–25.
- 74. Saenghong N, Wattanathorn J, Muchimapura S, Tongun T, Piyavhatkul N, et al. (2012) Zingiber officinale Improves Cognitive Function of the Middle-Aged Healthy Women. Evid Based Complement Alternat Med 2012: 383062.
- 75. Saxena RC, Singh R, Kumar P, Yadav SC, Negi MP, et al. (2010) A randomized double blind placebo controlled clinical evaluation of extract of Andrographis paniculata (KalmCold) in patients with uncomplicated upper respiratory tract infection. Phytomedicine 17(3–4): 178–185.
- 76. Singla V, Pratap Mouli V, Garg SK, Rai T, Choudhury BN, et al. (2014) Induction with NCB-02 (curcumin) enema for mild-to-moderate distal ulcerative colitis - A randomized, placebo-controlled, pilot study. J Crohns Colitis 8(3): 208–214.
- 77. Sontakke S, Thawani V, Naik MS (2003) Ginger as an antiemetic in nausea and vomiting induced by chemotherapy: A randomized, cross-over, double blind study. Indian J Pharmacol 35: 32–36.
- 78. Sripramote M, Lekhyananda N (2003) A randomized comparison of ginger and vitamin B6 in the treatment of nausea and vomiting of pregnancy. J Med Assoc Thai 86(9): 846–853.
- 79. Sukandar EY, Permana H, Adnyana IK, Sigit JI, Ilyas RA, et al. (2010) Clinical study of turmeric (Curcuma longa L.) and garlic (Allium sativum L.) extracts as antihyperglycemic and antihyperlipidemic agent in type-2 diabetes-dyslipidemia patients. International Journal of Pharmacology 6(4): 438–445.
- 80. Sukandar EY, Sudjana P, Sigit JI, Leliqia NPE, Lestari F (2013) Safety of garlic (Allium Sativum) and turmeric (Curcuma domestica) extract in comparison with simvastatin on improving lipid profile in dyslipidemia patients. J Med Sci 13(1): 10–18.
- 81. Tang T, Targan SR, Li ZS, Xu C, Byers VS, et al. (2011) Randomised clinical trial: herbal extract HMPL-004 in active ulcerative colitis - a double-blind comparison with sustained release mesalazine. Aliment Pharmacol Ther 33(2): 194–202.
- 82. Tang YP, Li PG, Kondo M, Ji HP, Kou Y, et al. (2009) Effect of a mangosteen dietary supplement on human immune function: a randomized, double-blind, placebo-controlled trial. J Med Food 12(4): 755–763.
- 83. Thamlikitkul V, Dechatiwongse T, Theerapong S, Chantrakul C, Boonroj P, et al. (1991) Efficacy of Andrographis paniculata, Nees for pharyngotonsillitis in adults. J Med Assoc Thai 74(10): 437–442.
- 84. Ushiroyama T, Hosotani T, Mori K, Yamashita Y, Ikeda A, et al. (2006) Effects of switching to wen-jing-tang (unkei-to) from preceding herbal preparations selected by eight-principle pattern identification on endocrinological status and ovulatory induction in women with polycystic ovary syndrome. Am J Chin Med 34(2): 177–187.
- 85. Ushiroyama T, Sakuma K, Nosaka S (2006) Comparison of effects of vitamin E and wen-jing-tang (unkei-to), an herbal medicine, on peripheral blood flow in post-menopausal women with chilly sensation in the lower extremities: a randomized prospective study. Am J Chin Med 34(6): 969–979.
- 86. Ushiroyama T, Sakuma K, Souen H, Nakai G, Morishima S, et al. (2007) Xiong-gui-tiao-xue-yin (Kyuki-chouketsu-in), a traditional herbal medicine, stimulates lactation with increase in secretion of prolactin but not oxytocin in the postpartum period. Am J Chin Med 35(2): 195–202.
- 87. Ushiroyama T, Sakuma K, Ueki M (2005) Efficacy of the kampo medicine xiong-gui-tiao-xue-yin (kyuki-chouketsu-in), a traditional herbal medicine, in the treatment of maternity blues syndrome in the postpartum period. Am J Chin Med 33(1): 117–126.
- 88. Visalyaputra S, Petchpaisit N, Somcharoen K, Choavaratana R (1998) The efficacy of ginger root in the prevention of postoperative nausea and vomiting after outpatient gynaecological laparoscopy. Anaesthesia 53(5): 506–510.
- 89. Vutyavanich T, Kraisarin T, Ruangsri R (2001) Ginger for nausea and vomiting in pregnancy: randomized, double-masked, placebo-controlled trial. Obstet Gynecol 97(4): 577–582.
- 90. Vyjayanthi G, Subhashchandra S, Saxena VS, Prathibha DN, Venkateshwarlu K, et al. (2003) Randomized, double-blind, placebo-controlled trial of Aller-7 in patients with allergic rhinitis. Emerging Drugs - Vol II IV–15–IV-24.
- 91. Wattanathorn J, Mator L, Muchimapura S, Tongun T, Pasuriwong O, et al. (2008) Positive modulation of cognition and mood in the healthy elderly volunteer following the administration of Centella asiatica. J Ethnopharmacol 116(2): 325–332.
- 92. Xiaoxiang Z (2006) Jinger moxibustion for treatment of cervical vertigo –a report of 40 cases. J Tradit Chin Med 26(1): 17–18.
- 93. Yang Y, Li H, Zhang S, Li Q, Yang X, et al. (2005) TCM treatment for 63 cases of senile dyssomnia. J Tradit Chin Med 25(1): 45–49.
- 94. Yip YB, Tam AC (2008) An experimental study on the effectiveness of massage with aromatic ginger and orange essential oil for moderate-to-severe knee pain among the elderly in Hong Kong. Complement Ther Med 16(3): 131–138.
- 95. Willetts KE, Ekangaki A, Eden JA (2003) Effect of a ginger extract on pregnancy-induced nausea: a randomised controlled trial. Aust N Z J Obstet Gynaecol 43(2): 139–144.
- 96. Smith C, Crowther C, Willson K, Hotham N, McMillian V (2004) A randomized controlled trial of ginger to treat nausea and vomiting in pregnancy. Obstet Gynecol 103(4): 639–645.
- 97. Chan K (2003) Some aspects of toxic contaminants in herbal medicines. Chemosphere 52(9): 1361–1371.
- 98. Wang G, Mao B, Xiong ZY, Fan T, Chen XD, et al. (2007) The quality of reporting of randomized controlled trials of traditional Chinese medicine: a survey of 13 randomly selected journals from mainland China. Clinical therapeutics 29(7): 1456–1467.