Future development of global regulations of Chinese herbal products

Ethnopharmacological relevance

GP-TCM is the first EU-funded Coordination Action consortium dedicated to traditional Chinese medicine (TCM) research. One of the key deliverables of the Work Package 7 in GP-TCM was to investigate information of the existing requirements for registration of TCM products listed by global regulatory bodies. The paper aims to collate data and draw comparison of these regulations. Case studies are also presented to illustrate the problems involved in registering TCM products in different regions worldwide.

Materials and methods

A collaborative network task force was established during the early stage of the GP-TCM project and operated through exchanges, teleconferences and focused discussions at annual meetings. The task force involved coordinators, academics who are actively involved with R&;D of Chinese herbal medicines, experts on monographic standards of Chinese materia medica, representatives from regulatory agencies, experts from industries in marketing Chinese medicines/herbal medicines and natural products. The co-ordinators took turns to chair teleconferences, led discussions on specific issues at AGM discussion sessions, at joint workshops with other work-packages such as WP1 (quality issues), WP3 (toxicology issues) and WP6 (clinical trial issues). Collectively the authors were responsible for collating discussion outcomes and updating written information.

Results

A global overview of regulations on herbal registration has been compiled during the three years of the consortium. The regulatory requirements for registration of herbal products in the EU and China were compared, and this is extended to other regions/countries: Africa, Australia, Brazil, Canada, Japan, Russia, South Korea, Taiwan, and the United States. A wide variation of the regulations for the categories of herbal products exists: food (functional food, novel foods, dietary food for special medical purpose, foods for particular nutritional use, food supplement); cosmetic, traditional herbal medicine products; herbal medicines for human use and veterinary use.

Conclusion

The regulatory issues for registration of herbal products are complicated among the countries and regions worldwide. The information summarised in the text is for reference only. Some regulations which are presented in this review are still in legislation process and may change in due course. Before taking any regulatory action, readers are advised to consult current official legislation and guidance and/or to seek appropriate professional advice. The lessons learnt from global regulation of TCM will provide valuable insights for regulation of other traditional medicine such as Ayurveda and Unani medicine, as well as other forms of indigenous medicine. The WHO is well placed to co-ordinate a consultation process with the aim of putting forward suggestions for harmonisation to key regulatory agencies.     

Good practice in reviewing and publishing studies on herbal medicine, with special emphasis on traditional Chinese medicine and Chinese materia medica

Ethnopharmacological relevance

Studies on traditional Chinese medicine (TCM), like those of other systems of traditional medicine (TM), are very variable in their quality, content and focus, resulting in issues around their acceptability to the global scientific community. In an attempt to address these issues, an European Union funded FP7 consortium, composed of both Chinese and European scientists and named “Good practice in traditional Chinese medicine” (GP-TCM), has devised a series of guidelines and technical notes to facilitate good practice in collecting, assessing and publishing TCM literature as well as highlighting the scope of information that should be in future publications on TMs. This paper summarises these guidelines, together with what has been learned through GP-TCM collaborations, focusing on some common problems and proposing solutions. The recommendations also provide a template for the evaluation of other types of traditional medicine such as Ayurveda, Kampo and Unani.

Materials and methods

GP-TCM provided a means by which experts in different areas relating to TCM were able to collaborate in forming a literature review good practice panel which operated through e-mail exchanges, teleconferences and focused discussions at annual meetings. The panel involved coordinators and representatives of each GP-TCM work package (WP) with the latter managing the testing and refining of such guidelines within the context of their respective WPs and providing feedback.

Results

A Good Practice Handbook for Scientific Publications on TCM was drafted during the three years of the consortium, showing the value of such networks. A “deliverable – central questions – labour division” model had been established to guide the literature evaluation studies of each WP. The model investigated various scoring systems and their ability to provide consistent and reliable semi-quantitative assessments of the literature, notably in respect of the botanical ingredients involved and the scientific quality of the work described. This resulted in the compilation of (i) a robust scoring system and (ii) a set of minimum standards for publishing in the herbal medicines field, based on an analysis of the main problems identified in published TCM literature.

Conclusion

Good quality, peer-reviewed literature is crucial in maintaining the integrity and the reputation of the herbal scientific community and promoting good research in TCM. These guidelines provide a clear starting point for this important endeavour. They also provide a platform for adaptation, as appropriate, to other systems of traditional medicine.     

Guidelines for randomised controlled trials investigating Chinese herbal medicine

Ethnographic relevance

Clinical trials investigating Chinese herbal medicine (CHM) have been frequently criticised for their lack of scientific rigour. As part of the GP-TCM project a team of experienced clinical researchers and CHM practitioners have developed clinical trial guidelines for CHM that combine an appreciation for traditional methods of practice with detailed and practical advice on research methodology.

Materials and methods

This paper presents an executive summary of this work. It introduces the practice of CHM and the key considerations that need to be addressed whilst researching this traditional medical system.

Results

These guidelines emphasise the importance of identifying best practice, and then developing and applying appropriate and rigorous research methodologies to investigate CHM as a whole system.

Conclusions

It is hoped that this will encourage a thoughtful and meticulous process of investigation that will clarify the contribution that CHM can make to our future healthcare. Innovative new approaches are considered including the application of the new “omic” technologies and systems biology as a way of enhancing our understanding of traditional practice     

Correlation between tobacco and alcohol use and Traditional Chinese Medicine constitutions: an analysis based on a sample from general population of China

Objective

To investigate the relationship between smoking and drinking and constitution types from Traditional Chinese Medicine (TCM) theory.

Methods

The Constitution in Chinese Medicine Questionnaire (CCMQ) was used. A sample of 8448 subjects from nine provinces and municipalities was chosen from the database of the TCM constitution and health status survey. Constituent ratio and correspondence analysis were used to find the relationship between smoking and drinking and TCM constitution.

Results

There was an association between smoking and drinking and the Gentleness, phlegm-dampness, and dampness-heat type constitutions. People that did not smoke tobacco or drink alcohol tended to have Yang-deficiency, Yin-deficiency, Qi-depression, Qi-deficiency, special diathesis, or blood-stasis type constitutions.

Conclusion

There was a significant correlation between tobacco and alcohol use and TCM constitutions. To improve patient health, more attention should be paid to tobacco and alcohol control.     

Application of proteomics to determine the mechanism of action of traditional Chinese medicine remedies

Ethnopharmacological relevance

The rationale for using traditional Chinese medicine (TCM) is based on the experience that has been gained from its wide use over thousands of years. However, the mechanisms of action of many TCM are still unclear. Proteomics, which mainly characterizes protein functions, protein–protein interactions, and protein modification in tissues or animals, can be used to investigate signaling pathway perturbations in cells or the whole body. Proteomics has improved the discovery process of effective TCM compounds, and has helped to elucidate their possible mechanisms of action. Therefore, a systematic review of the application of proteomics on TCM research is of great importance and necessity. This review strives to describe the literature on the application of proteomics to elucidate the mechanism of action of TCM on various diseases, and provide the essential discussion on the further utilization of proteomics data to accelerate TCM research.

Materials and methods

Literature survey was performed via electronic search on Pubmed with keywords ‘Proteomics’ and ‘Traditional Chinese Medicine’. The papers written in English were acquired and analyzed in this review.

Results

This review mainly summarizes the application of proteomics to investigate TCM remedies for neuronal disease, cancer, cardiovascular disease, diabetes, and immunology-related disease.

Conclusions

Researchers have applied proteomics to study the mechanism of action of TCM and made substantial progresses. Further studies are required to determine the protein targets of the active compounds, analyze the mechanism of actions in patients, compare the clinical effects with western medicine.     

Mechanisms of Qi-blood circulation and Qi deficiency syndrome in view of blood and interstitial fluid circulation

Objective

Based on comparison between fundamental theories of Traditional Chinese Medicine (TCM) and Western medicine (WM) and modern scientific research on meridians, we find that “Qi” in TCM is closely related to tissue fluid. In this study, the essence of Qi is explored in the view of circulation of blood and interstitial fluid.

Methods

Because the concept of Qi is complicated, Qi-deficiency syndrome (QDS) is chosen to probe the relationship between of Qi deficiency and Qi-Xue circulation (QXC). We analyze Qi-Xue theory in terms of WM, set up a hemodynamic model to describe QXC, and review clinical research on QDS in the view of blood-interstitial fluid circulation.

Results

QDS is caused by imbalances of substance exchanges between blood and interstitial fluid, leading to an increase in the interstitial liquid volume or a decrease in nutrients and retention of metabolic wastes in interstitial fluid.

Conclusion

This study describes the essence of Qi, providing support for further research on theories of Qi and Qi-Xue circulation in TCM.     

MEDLINE-based assessment of animal studies on Chinese herbal medicine

Ethno-pharmacological relevance

The scientific proof and clinical validation of Chinese herbal medicine (CHM) require a rigorous approach that includes chemical standardization, biological assays, animal studies and clinical trials.

Aim of the study

To assess the experimental design of animal studies on the activity of CHM by selection and scrutinizing of a series of papers in some major disease areas.

Materials and methods

We have analyzed the English publications reported in MEDLINE (ISI web of knowledge).

Results

Our data showed that (i) research of CHM during the last 10 years had been highly intensified and become more accessible worldwide through increased publications in English, although still most authors had Chinese names; (ii) English journals publishing animal research of CHM were comparable to those publishing animal studies of non-Chinese phytotherapy in terms of impact factor; and (iii) published data on authentication and quality control of CHM, as well as research design of animal studies were far from sufficient to meet the criteria needed to support their reproducibility and reliability.

Conclusions and perspectives

The recent decade witnessed an increase in CHM research activities and CHM English publications. Based on common problems identified in publications on CHM animal studies, we have proposed a checklist that could help in preliminary selection of publications lacking the most common problems and thus would be useful for a quick search of reproducible CHM regimens that are likely to be effective in a given context. The second application of this checklist is to help avoid the most common problems when designing experiments.     

Clinical trials of traditional Chinese medicine in the treatment of diabetic nephropathy—A systematic review based on a subgroup analysis

Ethnopharmacological relevance

The purpose of this study is to systematically evaluate the efficacy of traditional Chinese medicine (TCM) decoctions with different ingredients in the treatment of diabetic nephropathy (DN).

Materials and methods

Papers obtained after the retrieval of randomized controlled clinical trials (RCTs) of TCM treatments of diabetic nephropathy through online database (e.g. Medline, CBM, CNKI, VIP, the online database of Chinese medicine, CDFD, CMFD, and CENTRAL FROM Cochrane Library, etc.) as well as research data in our library. They were published between January 2001 and December 2012. According to the categories of the main TCM ingredients, all the cases in the literature were divided into a liver–kidney YIN deficiency group, a QI-BLOOD YIN-and-YANG deficiency group, and a spleen–kidney YANG deficiency group. Stata 11.0 was applied for subgroup analysis.

Results

A total of 21 Chinese RCTs were included in this review. The Q values of the three groups were 13.18, 0.25 and 3.27, respectively, P>0.05, and thus, there was no clinical heterogeneity. The combined relative risk (RR) value and its 95% confidence interval were 1.48 (1.37, 1.60), 1.19 (1.06, 1.34), and 1.33 (1.19, 1.50), respectively, P<0.05.

Conclusions

Compared with the qi-blood yin-and-yang deficiency group and the spleen–kidney yang deficiency group, the liver–kidney yin deficiency group has better prospects in clinical application to ensure renal function during the treatment of DN, and this possibility is worthy of further study.     

Analysis of TCM syndrome elements and relevant factors for senile diabetes

Objective

To explore the laws governing the distribution of TCM syndrome elements (SEs) of senile diabetes (SD) and their relationship to relevant factors.

Method

An investigation of patients who met the inclusion criteria was conducted by trained doctors, using case report forms. All related data were collected, including body mass index (BMI =body weight [kg]/height² [m]), glycated hemoglobin, illness course, complications, symptoms, and tongue and pulse manifestation. The SEs of each patient were judged by three qualified associate chief physicians independently.

Result

The main SEs of SD are Yin deficiency, Qi deficiency, blood stasis, and phlegm turbidity. Yin deficiency, Qi deficiency, blood stasis, and phlegm turbidity are most commonly seen among 4-SE combinations. Yang deficiency is typically related to illness course and BMI, phlegm turbidity to hypertension and hyperlipidemia, excessive heat to diabetic microangiopathy, and blood stasis to illness course and diabetic macroangiopathy.

Conclusion

SD pathogenesis has a deficiency in origin and excess in superficiality. Deficiency syndrome mainly manifests as deficiency of both Qi and Yin, and concurrently in Yang deficiency. Excess syndrome is characterized by blood stasis and phlegm turbidity. SE analysis provides a basis for the prevention and treatment of SD with Traditional Chinese Medicine (TCM) and lays the foundation for objectively evaluating multicentric clinical research for SD in TCM.     

Compatibility art of traditional Chinese medicine: From the perspective of herb pairs

Ethnopharmacological relevance

Over the past decades, research of traditional Chinese medicine (TCM) mainly focused on developing potential candidates from Chinese medicinal herbs, while the wisdom of applying these traditional herbs has not been paid as much attention as it deserves. As is well-known, multi-herb therapy is one of the most important characteristics of TCM, but the modernization drive of this conventional wisdom has faced many obstacles due to its unimaginable complexity. Herb pairs, the most fundamental and the simplest form of multi-herb formulae, are a centralized representative of Chinese herbal compatibility. In light of their simplicity and the basic characteristics of complex formulae, herb pairs are of great importance in the studies of herb compatibility.

Materials and methods

A systematic search of herb pair related research was carried out using multiple online literature databases, books and monographs published in the past 20 years.

Results

A comprehensive introduction to the compatibility of TCM, the position of herb pairs in TCM and the progresses of several famous herb pairs were provided in this review. Furthermore, the clinical study and the future research trends of herb pairs were also discussed.

Conclusions

Herb pairs have played, and may continue to play a key role in full investigation of general herb compatibility for their indispensable position in TCM. Much more research is needed for the standardization, safety evaluation, and mechanism exploration of herb pairs.     

The effects of the Chinese herbal medicine EMF01 on salicylate-induced tinnitus in rats

Aim of the study

Traditional Chinese medicine (TCM) has been reported to successfully alleviate tinnitus, although well-controlled studies have not been conducted. In this study, we attempted to test a TCM, Er Ming Fang (EMF01) containing Rehmannia glutinosa, Cornus officinalis, Salvia mittiorrhiza, Pueraria, Schisandra chinensis, Poria cocos and Platycodon grandiflorum, on salicylate-induced tinnitus in rats, using a conditioned lick suppression paradigm.

Materials and methods

A pilot study examined the effect of 8.75 g/kg and 17.5 g/kg EMF01 (delivered by oral gavage for 20 days) and showed a slight decrease in the suppression ratio (SR) in the 8.75 g/kg group. In order to confirm the possible effect of EMF01 on tinnitus at 8.75 g/kg, a further study was carried out with a larger sample size.

Results

While there were statistically significant differences between the treatment groups, post hoc tests revealed that EMF01 did not have any significant effect on salicylate-induced tinnitus.

Conclusions

While this study does not support the efficacy of EMF01 in the treatment of salicylate-induced tinnitus, further studies should be conducted to determine if it alleviates tinnitus associated with acoustic trauma.     

Ethnomedicinal knowledge, belief and self-reported practice of local inhabitants on traditional antimalarial plants and phytotherapy

Ethnopharmacological relevance

This paper reveals the trend of knowledge and practice of traditional antimalarial plants (TAPs) to prevent/treat malaria.

Materials and methods

Stratified, systematic random sampling was adopted. The ethnomedicinal survey was conducted between January and March 2011 by involving the selected 371 household members on knowledge and practice of TAPs by administering a pre-tested questionnaire.

Results

Overall, 54.4% respondents had adequate awareness and usage custom of TAPs and 16 types of plant have been most commonly known and employed by the respondents to prevent/treat malaria. Leaves (57.2%) were most commonly used plant part to prepare traditional antimalarial phytotherapy remedies. Decoction was one of the most commonly used methods to administer TAPs. The chi-square test result revealed that a significant association is found between the usage custom of traditional antimalarial plants and gender (P-value = 0.0282), age (P-value = 0.0024), educational status (P-value = 0.0295), and monthly income (P-value = 0.0001), although not with the ethnicity (P-value = 0.7933) of the respondents.

Conclusion

TAPs usage is an integral part of the tradition and custom of the Ethiopians. However, nearly half of the respondents have had lack of awareness about TAPs and majority of them are reluctant in exercising either due to its ineffectiveness or its bitter taste. Therefore, further laboratory-based research is extremely imperative to identify their antiplasmodial activity and bioactive molecules which could pave the way to formulate the novel affordable as well as accessible potent antimalarials in the near future.     

Clinical efficacy and safety of Traditional Chinese Medicine combined with Western Medicine in patients with diabetic acute ischemic stroke

Objective

To observe the clinical efficacy and safety of Traditional Chinese Medicine (TCM) combined with Western Medicine (WM) in patients with diabetic acute ischemic stroke.

Methods

Ninety patients with diabetic acute ischemic stroke were randomly divided into a treatment group and a control group. The 45 patients in the treatment group were given standardized treatment with TCM combined with WM. They received corresponding oral Chinese decoctions three times daily, according to their TCM syndromes, along with basic western medical treatment. The 45 patients in the control group were given non-standardized treatment with TCM combined with WM. They received an oral Chinese decoction for promotion of blood circulation to inhibit hemostasis, regardless of their TCM syndromes, along with basic western medical treatment. The treatments lasted for 4 weeks. Scores were evaluated on the National Institutes of Health Stroke Scale (NIHSS) score, activity of daily life (ADL) scores, and TCM symptoms before treatment and 2 and 4 weeks after treatment.

Results

Analysis of variance for repeated measurements showed that there were significant differences in NIHSS and ADL score before and after treatment in both groups (P<0.05). There were also significant differences between the scores at 2 and 4 weeks after treatment. There were significant differences in TCM syndrome scores before and after treatment in both groups (P<0.05). There were also significant differences between the scores at 2 and 4 weeks after treatment. The χ² test showed no statistically significant difference in the incidence of adverse reactions between the two groups (P>0.05).

Conclusion

Standardized treatment was superior to non-standardized treatment for clinical efficacy of TCM combined with WM in patients with diabetic acute ischemic stroke, and the superiority was more obvious in improving neural dysfunction, ADL score, and TCM symptoms. The adverse reactions were similar in the two treatment groups.     

Therapeutic effect in patients with coronary heart disease based on information analysis from Traditional Chinese Medicine four diagnostic methods

Objective

To study information gained by Traditional Chinese Medicine (TCM) four diagnostic methods and characteristics of syndrome development before and after treatment in patients with coronary heart disease, and to probe into assessment indexes of therapeutic effects with distinctive TCM features.

Methods

Information from the four diagnostic methods before and after treatment in 100 patients with coronary heart disease was collected using the TCM interrogation scale, a pulse condition instrument, a tongue-face diagnosis instrument, and a voice diagnosis information collection system. Changes in the four diagnostic method results from before and after treatment were analyzed with frequency analysis and t-test methods.

Results

Before treatment, deficiency syndrome complicated with hyperactivity of pathogenic factors was most common. After treatment, deficiency syndrome was most common. This change from complex syndromes to single syndromes indicates disease and syndrome alleviation. Frequencies of symptoms gained by interrogation after treatment for syndrome of deficiency of heart-Qi, syndrome of deficiency of heart-Yin, and turbid phlegm syndrome were all less severe than those before treatment. Parameters of face color, color on all sub-regions of tongue, color of tongue fur, septic and greasy fur, and lip color after treatment all had significant changes. After treatment, part of the voice diagnosis parameters in the deficiency of heart-Yin and turbid phlegm syndromes had significant changes, but no significant changes were found in the deficiency of heart-Qi syndrome.

Conclusion

Use of the TCM four diagnostic methods can provide an effective basis for TCM syndrome diagnosis, observation of development of state of illness, and evaluation of clinical therapeutic effects.     

Expression of the psoriasis-associated antigen,Pso p27, is inhibited by Traditional Chinese Medicine

Aim of the study

Pso p27 is shown to be an autoantigen in psoriasis and the objective of the present study was to investigate whether Traditional Chinese Medicine (TCM) would influence the expression of Pso p27.

Materials and methods

Skin biopsies obtained from psoriatic patients before and after treatment with TCM were analyzed for the presence of Pso p27 antigen by indirect immunofluorescence using murine monoclonal antibodies against Pso p27.

Results

A significant reduction in the amount of Pso p27 in the psoriatic skin was obtained after treatment with TCM for 3 months.

Conclusions

The presence of Pso p27 in psoriatic skin is reduced when psoriatic patients are treated with TCM.     

A quantification model of Traditional Chinese Medicine syndromes in children with idiopathic precocious puberty and early puberty

Objective

To establish a quantification model of Traditional Chinese Medicine (TCM) syndromes by sampling patients undergoing idiopathic precocious puberty (IPP) and early puberty.

Methods

A questionnaire for classifying and quantifying TCM syndromes was designed and administered. All the results were analyzed; the relationship between 3 types of syndrome and 47 symptoms were summated. Meanwhile, the frequency distribution of each symptom or sign was aggregated. Fuzzy mathematics was used to develop a quantification model of TCM syndromes.

Results

We found that precocious puberty had 3 types of syndrome, including hyperactivity of fire due to Yin deficiency (Syndrome I), depressed liver Qi transforming into fire (Syndrome II), and end retention of damp heat (Syndrome III). In the IPP group, Syndrome I was the most common principal syndrome (100%). Forty-six patients (43.81%) were diagnosed with Syndrome I accompanied by Syndrome II and 11 (10.48%) were diagnosed with Syndrome I accompanied by Syndrome III. In the early puberty group, Syndrome I was also the main syndrome (98.39%). The degrees of most symptoms were mild to moderate. Reddened tongue was the most common tongue manifestation (62.86% prevalence) in the IPP group. The most common pulse manifestations were slippery pulse, thread pulse, and taut pulse. The Asymptotic Normalization Coefficient (ANC) method was used to quantify the TCM syndromes in 167 cases. Diagnostic accuracy rate reached 91%, comparable to expert diagnosis.

Conclusion

We find that there are 3 types of syndrome in the IPP group and in the early puberty group. Syndrome I (hyperactivity of fire due to Yin deficiency) is the main syndrome in the two groups. ANC may be an appropriate for quantification model of TCM syndromes.     

Curative effect of warming kidney and fortifying spleen recipe on diarrhea-predominant irritable bowel syndrome

Objective

To observe the curative effect of a recipe for warming the kidney and fortifying the spleen on diarrhea-predominant irritable bowel syndrome (IBS-D).

Methods

This multi-center, double-blind, randomized, and controlled trial included 240 patients that met the inclusion criterion and were then divided into two groups of 120. Patients in the treatment group (group A) took modified Sishen Wan orally for warming the kidney and fortifying the spleen and patients in the control group (group B) took a placebo, Chao Maiya, for 4 weeks. 28 days after withdrawal, there was a 6-month follow-up to observe patient recurrence condition. The total effective rate, curative effect, and recurrence rate were evaluated after treatment.

Results

There was statistical difference (P<0.01) between the two groups in total effective rate (92.24% in the treatment group and 49.07% in the control group), in curative effect of TCM syndrome (90.52% and 47.22%, respectively), and in the recurrence rate (15.79% and 56.86%, respectively) within 6 months after treatment.

Conclusion

Modified Sishen Wan, for warming the kidney and fortifying the spleen, can effectively treat IBS-D and better control its recurrence.     

Comparison of effectiveness and safety between granules and decoction of Chinese herbal medicine: a systematic review of randomized clinical trials

Background

The clinical use of Chinese herbal medicine granules is gradually increasing. However, there is still no systematic review comparing the effectiveness and safety of granules with the more traditional method of herbal decoctions.

Method

A literature search was conducted using China National Knowledge Infrastructure Databases (CNKI), Chinese Science and Technology Periodical Database (VIP), China Biomedical Database web (CBM), Wanfang Database, PubMed, and the Cochrane Library until March 10, 2011. Clinical controlled trials (CCTs) including randomized trials (RCTs) comparing the effectiveness and safety between Chinese herbal medicine granules and decoction were included. Two authors conducted the literature searches, and extracted data independently. The assessment of methodological quality of RCTs was based on the risk of bias from the Cochrane Handbook, and the main outcome data of trials were analyzed by using RevMan 5.0 software. Risk ratio (RR) or mean difference (MD) with a 95% confidence interval (CI) were used as effect measure.

Results

56 clinical trials (n = 9748) including 42 RCTs and 14 CCTs were included, and all trials were conducted in China and published in Chinese literature. 40 types of diseases and 15 syndromes of traditional Chinese medicine (TCM) were reported. Granules were provided by pharmaceutical companies in 13 trials. The included RCTs were of generally low methodological quality: 7 trials reported adequate randomization methods, and 2 of these reported allocation concealment. 10 trials used blinding, of which 5 trials used placebo which were delivered double blind (blinded participants and practitioners). 98.2% (55/56) of studies showed that there was no significant statistical difference between granules and decoctions of Chinese herbal medicine for their effectiveness. No severe adverse effects in either group were reported.

Conclusions

Due to the poor methodological quality of most of the included trials, it is not possible to reach a definitive conclusion whether both Chinese herbal medicine granules and decoctions have the same degree of effectiveness and safety in clinical practice, but this preliminary evidence supports the continued use of granules in clinical practice and research. Standardization of granules and further more rigorous pharmacological, toxicological and clinical studies are needed to demonstrate the equivalence with decoctions.