Final Report Summary - GP-TCM (Good Practice in Traditional Chinese Medicine research in the post-genomic era)
Executive summary:
4.1.1 Executive summary:
traditional Chinese medicine (TCM), especially Chinese herbal medicine (CHM) and acupuncture, is the ancient medical system used by the people in China and some other Asian countries for thousands of years to maintain the health of one of the largest populations in the world [1,2]. In recent years, TCM has been used by an increasing number of people in Europe and has attracted intense research interests from European scientists [3,4,5].
as an emerging area in Europe, TCM research requires collaboration and coordination. Good Practice in Traditional Chinese Medicine Research in the Post-genomic Era, also known as GP-TCM, was the 1st EU-funded Seventh Framework Programme (FP7) Coordination Action dedicated to informing the best practice and harmonising TCM research through interdisciplinary exchanges among TCM experts and scientists [3].
project Context and Objectives:
4.1.2 Summary description of project context and objectives:
in recent years, TCM has been increasingly used in Europe [3,4,5]. However, in contrast to the reductionist approach of Western medicine that is based on anatomy, physiology, pharmacology, cell and molecular biology, TCM is based on thousands of years of recorded clinical experience, guided by Chinese philosophy, e.g. the Yin-Yang theory emphasising the balance of functional systems. TCM uses a theoretical system with a personalised and holistic approach to describe health and disease [2]. Speaking in metaphors, while Western medicine tends to see trees but not the wood, TCM, on the other hand, often sees the wood but not the trees. Therefore, both systems can learn from each other.
project Results:
4.1.3 Description of the main S&T (Science and Technology) results/foregrounds:
by 31st October 2012, through 3.5 years of team building, the GP-TCM consortium had grown into a large collaborative network involving approximately 200 scientists from 24 countries and 110 institutions.
1.3.1 WP1 - Quality Control of CHM
objectives: The main objectives of WP1 were to design a standard system to review the literature on papers associated with plants used in CHM and use the information gained from this review to develop a system for the quality control of CHM in the EU. The system will take into account what is known about the complexity of CHM such as the nomenclature, the need to ensure plants had been identified correctly and that researchers were aware of the complexity of the different names that could be used to describe a species.
description of work: A group of specialists in different aspects of the quality control of TCM plants from the EU and China was brought together in a series of one-to-one meetings and telephone meetings. Because the aims of WP1 were closely aligned with those of WP2 and WP4, joint meeting took place between the groups during the three years of the projects. WP1 was initially going to review the literature on the top 100 plants entering the EU and then narrow the range of species to 20-40 as outlined in the project proposal. However, it was decided at the first Annual Conference at Henley to concentrate on gathering data about the plants as used in CHM formula.
priority areas:
- The production of a database that brings together the Latin accepted scientific binomial names of the plants, synonyms, pharmaceutical and Chinese names;
- Research that further our understanding of the chemical profile of a quality plant based on a better understanding of the pharmacology of the extracts tested;
- Improved understanding of the agricultural practices needed to produce good quality place;
- Better understanding of the supply chain of the plant used in TCM to ensure that there are plentiful supplies of quality plants obtained from sustainably harvested sources;
- Development of molecular methods (DNA and chemical) that can be used to identify species and enable the identification of substitutes and adulterants.
1.3.2 WP2 - Extraction and Component Analysis of CHM
objectives: The objectives of WP2 were situated around the extraction and component analysis of CHMs. In general, the currently employed traditional extraction technologies had to be evaluated with regard to special phytochemical characteristics of CHM. Problems and gaps of knowledge that need to be addressed for a reasonable modernisation of the traditional preparations towards more convenient application forms had to be identified.
description of work: Due to the close relation between WP1 and WP2 that had been figured out early in the project, WP2 started its activities with a joint workshop with WP1 in London. On that occasion the joint compilation of plant-species-related literature data was identified as a field of mutual collaboration between the WPs. This collaboration continued in the organisation of further joint face-to-face meetings and telecommunication events throughout the project's lifetime.
outcomes: Traditional CHM preparations, mainly elaborative decoctions of complex herbal mixtures with water, are more and more replaced by modernised and more convenient products like granules that are just to be suspended in water before application. However, there is lack of evidence that such preparations are comparable with their traditional prototypes in terms of activity and chemical composition.
the outcomes are represented by the WP2 deliverables, including dissemination (Review paper published in Journal of Ethnopharmacology and presentation of results on an International conference).
priority areas:
- Comparative studies on the activity and chemical composition of traditional and modernised extracts of CHM;
- Elucidation of the impact of traditional post-harvest processing techniques (drying, wet-cutting, paozhi, soaking in cold water, co-extraction) on the product's chemical profile using metabolomic techniques;
- Identification of quality determining chemical components from traditionally prepared CHM taking advantage of the rich traditional variability of TCM drugs for the application of activity-guided metabolomic techniques;
- Simplification of complex traditional preparations by (i) identification and removal of dispensable herbal ingredients and (ii) identification and deletion of dispensable methods of processing (please refer to deliverable D2.12 report for more details).
1.3.3 WP3 - Functional Genomics in Toxicology Study of CHM
objectives: The research protocols, standards and methods for the evaluation of the safety and efficacy of TCM, including CHM, are more complex than those for conventional medicines. Indeed, TCM presents a unique set of pharmaceutical theories that include particular methods for processing, combining and decocting CHM, which probably contribute to reduce their eventual toxicity and enhance their efficacy. The evaluation of CHM safety is complicated by multiple factors, such as the geographical origin of plant material, different processing techniques, dosage, route of administration and compatibility with other medicines.
description of work:
- To achieve its intended goals, the WP3 group has established a network of experts in the field, which has been strengthened all along the project duration. WP3 has developed a series of literature searches;
- The WP3 kick-off meeting, "Functional genomics and toxicological studies applied to TCM", was held on 24th and 25th October 2009 in Brussels La Hulpe, bringing together 8 WP3 groups from both China and Europe (out of a total of 13 groups), the Coordinator of WP5 and 3 guests from Belgium and D. R. Congo; Xinmin Liu has organised 5 mini-workshops for Chinese participants in Beijing to draft WP3 plans;
- A series of e-mail contacts circulated lists of plants and composed preparations, thanks to Dr. You-Ping Zhu (China-Netherlands Medical and Pharmaceutical Centre, NEDICHIN BV, The Netherlands), Prof. Benny Mei of ACUMED, London UK, Kelvin Chan, Xinmin Liu, Yanjiang Qiao, Elizabeth Williamson and Debbie Shaw: Best selling herbs in Europe, top 15 PCM in Europe, PCM substitutable by aristolochic acids containing herbs, herbs associated with unpredictable hepatotoxicity, herbs from the "973 programme";
- Three web-based meetings were organised and frequent exchanges of e-mails between all WP3 members allowed to discuss the finalisation of deliverables, to prepare the final WP3 reports, to prepare the Henley (1st AGM), Braga (2nd AGM) and final conferences, to obtain feedback on the drafts for the SOP literature panel, to move on the different reviewing topics, to assign tasks to WP3 members and to define the organisation of the work for "systematic literature review and translation";
- A survey on the perception of safety by stakeholders was designed, launched and analysed by Prof. Pierre Duez and his team for deliverable D3.6 with support from number of WP3 members;
- Hani El-Nezami, Joëlle Nortier, Pierre Duez, Jue Zhou, Fan Qu and Caroline Stévigny have coordinated literature reviewing on some toxicities by PhD and master students;
- A joint workshop was organised with WP1, WP3, and WP7 members and experts of the EDQM European Pharmacopoeia TCM workgroup (Strasbourg, France, 29th September 2011). Prof. Duez presented a short talk: "GP-TCM Introduction and brief progress of WP3";
- A workshop was organised (September 2011) by Prof. Xinmin Liu in Luzhou Medical College, Sichuan Province, China, for discussing review manuscripts on toxicity of CHMs;
- Prof. Xinmin Liu introduced GP-TCM to Mr Yu Wenming, Deputy General-Director of SATCM, Ms. Xiaopin Wang, Director of Department of International Cooperation of SATCM, Dr. Jijun Xing, Deputy Director of China Science and Technology Exchange Centre, MOST and Dr. Philippe Vialatte, the representative from Science and Technology Section, EU Delegation in China;
- Prof. Duez organised a 3-months writing session for WP3 reviews, jointly with M. Ouédraogo, C. Stévigny, J. Nortier and T. Baudoux;
- Prof. Xinmin Liu helped the Hunan University of TCM in Changsha, Hunan, China, to set up "Sino-EU Contact Office (Traditional Medicine), with strong support from Dr. Jijun Xing, the Deputy Director of China Science and Technology Exchange Centre, MOST, China.
outcomes:
WP3 has defined the meaning of "toxicity" with regard to its activities as follows: "Possible harmful reaction to the body which is not related to therapeutic effect. Toxicity can then be classified into (i) side effects (covered by pharmacodynamics and often predictable), (ii) reactions occurring as a result of overdose, over-duration, tolerance, dependence-addiction (covered either by pharmacodynamics and pharmacovigilance), (iii) hypersensitivity, allergic and idiosyncratic reaction (covered by pharmacovigilance), (iv) mid-term and long-term toxic effects (liver, renal, genotoxicity, teratogenecity, neurotoxicity, cardiotoxicity, )". It has been agreed that point (iv) is the most important field for 'omics' predictive toxicology.
priority areas:
- Development and validation of screening methods to rapidly identify herbs that may raise safety concerns, focusing on medium- and long-term toxicities;
- Development of research methodology and protocols for evaluating toxicity and safety of Chinese herbal medicine, taking into account TCM characteristics such as combination of herbs and processing;
- Reinforcement of pharmacovigilance for herbals, including all marketing status (drugs, food supplements, etc);
- Training scientists to meet the challenges of toxicological evaluation of herbals.
1.3.4 WP4 - Functional Genomics of CHM Research in Vitro
objectives: The aim was to define and propose standardisation of in-vitro systems and their use in functional genomics studies (all the so-called 'omic' techniques) of CHM. The aim was accomplished by developing a general strategy and then identifying and defining quality criteria and procedures. Particular attention was paid to establishing best practice criteria for research methods and reporting. This enabled a further objective of evaluation of existing publications. This approach was to be used similarly to evaluate the quality of existing databases and in-silico tools, and to establish guidelines for good practice in in-silico research in CHM research.
description of work: The main activities performed by WP4 were concerned with establishing a multidisciplinary network of experts in the field of in-vitro CHM research, to propose good practice and guidelines in the field. This was achieved by holding a number of face-to-face meetings together with e-contacts and conference calls. In particular, the kick-off meetings were useful for networking and to establish a formal organisation and agenda, though the main outputs of the meetings were focused on contents and output strategies, resulting in proposed criteria for literature evaluation.
outcomes:
the WP4 outcomes are innovative insights in the field of "omics" applied to CHM research and their dissemination in the scientific community with reports, articles, on line resources and meetings (all the eighteen WP4 deliverables are available in the website), including 3 reports, 3 handbooks, a questionnaire survey, a dedicated webpage on WP4, a searchable database of critically reviewed and quality scored articles, a presentation at the 2012 meeting in Leiden, a review article (Omic techniques in systems biology approaches to traditional Chinese medicine research), and a review article (In-silico studies in Chinese herbal medicines' research: Evaluation of in-silico methodologies and phytochemical data sources), and a review of research to date.
priority areas:
- Application of omics to CHM research;
- Encourage by all means possible the utilisation of the guidelines established in the WP work as standard for publication;
- TCM and pro-active approaches for prevention in the era of Personalised Medicine.
1.3.5 WP5 - Functional Genomics Studies of CHM in Vivo
objectives: The aim of WP5 was to establish best practice for animal studies of CHM in the EU. This was achieved by examining the biomedical literature on CHM in general and assessing the studies in animal models of selected diseases. Particular attention was paid to identify the most relevant methodological problems in these studies and to propose solutions, as well as to give directions for the application of functional genomics.
description of work: To achieve the WP5 objectives, the group leadership built an expert network in CHM in animal models of disease. The WP5 kick-off meeting was held in Alcala de Henares University the days 2nd 3rd June 2009 bringing together eleven WP5 members which discussed the 3-year plan of the WP and assigned jobs related to deliverables.
outcomes: The main WP5 outcomes are as follows:
- Identification of the main features and trends of the studies of CHM recorded in MEDLINE, which special focus on the last decade and on studies in animal models of disease;
- Identification of the main problems in the experimental design of animal studies of CHM;
- Assessment of the scientific proof of the efficacy of CHM provided by animal studies;
- Provision of a checklist for i) the quick assessment of the quality of any animal study of CHM and ii) helping in the experimental design of new studies in animals through avoiding the most common methodological problems found in these studies;
- A presentation at the GP-TCM Congress held in Leiden (April 2012);
- 2 poster presentations in the 11th Congress of the International Society of Ethnopharmacology (Albacete, Spain, 2010: Animal Models for Cancer Research in TCM and Scientific Publications on Animal Studies of CHM and 1 poster presentation in the TCM Symposium (Braga, Portugal, 2011: State of the art in animal studies of CHM);
- One review article on: Omic techniques in systems biology approaches to traditional Chinese medicine research; http://dx.doi.org/10.1016/j.jep.2012.01.055
- One review article on: Medline-based assessment of animal studies on Chinese herbal medicine. Http://dx.doi.org/10.1016/j.jep.2012.02.008
priority areas:
- Standardisation of the whole procedure of preparation of CHM formulations to be used in animal studies;
- Identification of key CHM for the treatment of selected diseases by getting proof of efficacy of selected CHM in comparable and reproducible animal studies;
- Application of omics to CHM research in animals.
1.3.6 WP6 - Functional Genomics in Clinical Studies of CHM
objectives: The overall objectives for WP6 were to focus on reviewing current practice of CHM research, identifying problems and proposing solutions and to ensure that an unbiased view of current research in functional genomics of CHM was produced. This was to be achieved by initially establishing a European-Chinese partnership to in order to develop a clinical trial network in CHM. This expert group was to provide a platform to develop expert guidelines for clinical research and propose standard protocols on methodology for CHM trials.
outcomes:
- Established an international expert network with expertise in clinical trials and CHM to facilitate future clinical research collaborations and research planning.
- Two surveys were conducted. The first focused on good practice guidelines to ascertain their attitudes towards the integration of complementary and alternative medicines (CAM) and Western healthcare in a representative county in the UK. It also identified the availability of CAM including herbal medicines and acupuncture in primary care.
- Provided clinical trial guidelines for the conduct of CHM trials for use by CHM researchers, in order to provide guidance and recommendations for good practice in CHM clinical trials.
- Reviewed the most recent evidence supporting CHM in some of the key selected conditions of interest to the WP6 members.
- Appraisal of literature on functional genomics. There was a lack of good quality studies in this area, and studies reviewed highlighted the general scope that such new approaches could offer. It was also recognised that the following were key issues to be addressed:
- Authenticity and quality of plant material
- Analysis of the mode of action of single plants and multi-component mixtures
- Assessment of the toxicity of CHM
- Drug metabolisation (individual drug responses)
- Ascertained topics areas for the future focus of CHM trials by engaging with TCM practitioners on defining priority areas.
priority areas:
- Safety of CHM Further research on adverse effects of CHM is required given a much lower reporting rate by Chinese practitioners;
- Key areas identified by CHM practitioners where more evidence is required suggested future areas where research should focus (obstetric/gynaecological complaints, dermatology and cancer);
- Conduct research on multi-herb formulae as used in clinical practice in conjunction with syndrome differentiation;
- Carry out further comparisons of different CHM preparations and methods of CHM delivery e.g. decoction, standardised formulae and semi standardised formulae using clinical trial methodology;
- Improve quality and reporting of clinical trials by the publication of trial protocols and ensuring voucher identification of CHM specimens.
1.3.7 WP7 - Functional Genomics in Research and Development(R&D) of CHM
objectives: The overall objective for WP7 was to establish a collaborative network towards formulating an easy-to-follow statement on the various regulatory frameworks, with emphasising the synergies and highlighting the differences with the aim of helping to establish a universal harmonised regulatory framework for botanicals.
A further key objective was to focus on searching literature beyond herbal products and summarise what has been reported on the application of "omics" and functional genomics in R & D and regulation of any drugs and then discuss its implications on R & D and regulation of CHM and other complex herbal products (CHP).
description of work: In order to achieve the objectives of WP7, a WP7 face-to-face kick off meeting was held in 2 phases: Phase 1 held at Brunel Institute of Bioengineering, Brunel University, London (31st August to 1st September 2009), and Phase 2 held at King's College London (25th-26th July 2010). During interim teleconferences and annual meetings specific checkpoints were inspected, status of deliverables was surveyed and tasks were checked, defined and further focused, if needed. Changes in WP7 membership necessitated quite crucial reorganizations and delineations of objectives and tasks.
outcomes:
the task to collect, organise, compare and summarize data on the regulation of herbal medicinal products, including TCM, in different parts of the world was focused on writing a reader-friendly document highlighting the complexity of the regulatory issues for registration of herbal products worldwide. The lessons learnt from global regulation of TCM provide valuable insights for regulation of other traditional medicine such as Ayurveda and Unani medicine, as well as other forms of indigenous medicine.
as the key deliverables of WP7, two major papers were published in the GP-TCM theme issue in Journal of Ethnopharmacology. The first one is a comprehensive summary of different herbal regulations worldwide titled Future development of global regulations of Chinese herbal products, which provides an updated information to researchers, regulatory authorities as well as industry worldwide.
other outcomes: WP7 Co-Coordinator Tai-Ping Fan announced that as a legacy for GP-TCM, he has been invited by American Association for the Advancement of Science magazine Science to edit a special sponsored issue on TCM in July 2013. He has assembled an executive editorial board with Prof. Peter Hylands of KCL and Prof. Jan van der Greef of University of Leiden. Prof. Kelvin Chan and Prof. Pierre Duez led the GP-TCM SOP team to produce a review Good practice in reviewing and publishing studies on herbal medicine, with special emphasis on traditional Chinese medicine and Chinese materia medica in Journal of Ethnopharmacology.
priority areas:
- Advance and emphasise global harmonization of regulation of complex herbal products in general and CHM in particular;
- Strengthen research agenda to employ functional genomic approach with all omics tools in connection with network systems pharmacology/toxicology;
- Engage the British Pharmacopoeia, the European Pharmacopoeia and the Chinese Pharmacopoeia in mutual recognition of a selection of medicinal herbs;
- Initiate dialogue with The WHO with respect to its place to co-ordinate a consultation process with the aim of putting forward suggestions for harmonisation to key regulatory agencies.
1.3.8 WP8 - Functional Genomics in Studies of Acupuncture-Moxibustion and Meridians
objectives: The overall objective of WP8 was to optimise and standardise acupuncture protocols and discuss the application of the functional genomics approach and to examine the efficacy of acupuncture and moxibustion for the treatment of common diseases in the EU countries. The specific objective was to first establish a communication and collaboration platform to evaluate the current status of acupuncture research and practice in both China and EU. And then, define and prioritise research areas or topic in acupuncture that would be appropriate for conducting functional genomic studies. Another objective was to obtain general agreement on the common standards for acupuncture protocols. The most important objective was focusing on future research strategies within appropriate areas for functional genomics.
outcomes:
the expert panel of WP8 has changed and expanded over the project period, but WP8 has maintained a close relationship among all WP members and with WP10. Several considerations were planned and carefully balanced during the entire team assembly processes, such as stability/dynamism, specialty/collaboration, broad coverage/representative subjects, and experienced seniors/young enthusiasts, etc. Based on the international collaborations and coordination, an extensive collaborative panel clinical and basic research in acupuncture was established both in China and EU. Activities such as a WP kick-off meeting, some other face-to-face meetings, literature studies, a number of teleconferences and many email communications were carried out in order to meet the WP objectives and milestones. The current status of clinical and basic research on acupuncture was highlighted to foster research collaboration both within and between China and the EU.
priority areas:
- The results from the online survey identified differences in practice and training between acupuncturists in China and the EU and between EU member states. It is suggested that creation of collaborative networks is crucial in overcoming these differences to facilitate international, multi-centre clinical trials.
- WP8 has created a review of existing literature and suggested a preferred strategy for future acupuncture/moxibustion research. Focused on several diseases or symptoms with evidence of effectiveness by acupuncture treatment, the approach of combination Omic technologies with functional molecular imaging will be a preferred strategy for future acupuncture research.
- WP8 also defined the status of current Chinese clinical-related acupuncture basic research in order to highlight future inter-collaborative research between and within China and EU.
1.3.9 WP9 - Final Conference
objectives: The task for WP9 was to organise and host the final conferences. This task was split up in two parts. One was the Final Conference, which was for project members to finalise the conclusions of their WPs; the other was for results to be presented in an international forum open to the public, i.e. the GP-TCM Congress. The deliverable D9.2 reports the full details of the organisation and results of both meetings.
description of work: From the very beginning of the project, the local organizers in Leiden have been exploring various sites for the Final Conference. They visited several facilities and eventually have chosen for the congress centre in Rolduc, an old monastery which can easily be reached by train from both Germany and the Netherlands. The Rolduc meeting attracted 80 participants. It was also decided with the management committee that besides the internal symposium for the beneficiary and non-beneficiary members of the project, WP9 also should organise a second meeting to disseminate the results to the scientific community.
priority areas:
- Networking will be a key aspect of further integration of the research;
- To have a COST project on TCM research;
- GP-TCM Research Association should organise postdoctoral courses on systems approaches to TCM research;
- EU and China should come to a mutual agreement to support studies on the integration of Chinese and European medicine;
- Dissemination of results to the general public.
1.3.10 WP10 - Management: Sustainable development and coordination of TCM research in the EU
objectives: As the overall management team of the consortium, WP10 aimed to coordinate WP leadership, membership and collaboration, to steer research direction, to organise quality assurance, collation and integration of data, as well as dissemination of results.
description of work: In 3.5 years, WP10 organised more than 50 major teleconferences covering management, science and good practice issues, 3 face-to-face consortium-wide meetings with relevant stakeholders' involvement, and numerous other face-to-face meetings to facilitate effective and efficient communication platforms and discussion for a moving the project forward.
outcomes:
- Ever-strengthening interdisciplinary, intersectoral and interregional collaborative network: By the 3rd year of the project, the consortium membership profile was increased from "28 beneficiary and 24 non-beneficiary partners across 12 countries" to "29 beneficiary and 82 non-beneficiary partners across 24 countries" giving access to further expertise and resources while strengthening the delivery of project objectives.
- Consortium-wide conclusions on grand Issues in TCM research: WP10 broke barriers among WPs and between GP-TCM and the other related communities and organised the GP-TCM "Grand Issues in Traditional Chinese Medicine Research Survey" open to all consortium members and non-members. The outcomes of the survey established high-quality research on efficacy/effectiveness and mechanisms of action of CHM and acupuncture and identification of priority disease areas where TCM could achieve better outcomes as grand priorities. TCM contribution to the management of one of EU's top healthcare challenges, i.e. long-term conditions and chronic diseases was regarded as the top opportunity.
results of the poll were made freely available through the following web links:
http://project.GP-TCM.org/2011/08/"grand-priorities-challenges-and-opportunities"-survey/
http://www.sciencedirect.com/science/article/pii/S0378874112001110
- The open-access GP-TCM Journal of Ethnopharmaology special issue: WP10 played a key role in disseminating the project findings. To summarise the research outcomes and recommendations from all GP-TCM WPs in a way convenient for future reference, the consortium prepared a series of publications derived from the GP-TCM consortium to be collated into a special issue of the Journal of Ethnopharmacology. The special issue was published in April 2012 and comprised 20 articles, with contributions from all WPs as well as independent papers complementary to the work of GP-TCM. The consortium made all articles open-access, allowing all interested parties to download the articles free of charge
http://www.sciencedirect.com/science/journal/03788741/140
- The GP-TCM Research Association: GP-TCM good practice guidelines need dissemination, validation and further development through continued interregional, interdisciplinary and intersectoral collaborations. Hence to promote this, WP10 led the process of establishing a new international association, known as "the GP-TCM Research Association", which was founded in April 2012 and has fully succeeded the 3.5-year fixed-term FP7 GP-TCM consortium since November 2012 (see http://www.GP-TCM.org/ online).
- Members' answers to the question "What have I learnt through the GP-TCM project?": To mention a few, Prof. PC Leung (Chinese University of Hong Kong, China) said: "GP-TCM has demonstrated the potential of collaboration in the vast field of TCM; GP-TCM should be continued." Prof. Olavi Pelkonen (University of Oulu, Finland) acclaimed: "Networking of scientists with variable backgrounds is powerful!" Prof. Rob Verpoorte (Leiden University, The Netherlands) conlcuded: "GP-TCM has lowered barriers between scientists from the EU and China, the GP-TCM Research Association will be instrumental in further lowering these barriers."
- Dissemination of findings to academia, industry, regulators and funders and the public: As detailed in Part 2 of this report (4.2A2) and the Deliverable D10.9 report.
difficulties and solutions:
- As part of the financial difficulties of UMINHO, Portugal, some attendees of the 2nd GP-TCM AGM could not be reimbursed of their travel costs by the host institution UMINHO. KCL made the use of its budget for unforeseeable costs and had all the outstanding claims sorted to ensure that the reputations of the EU and the FP7 GP-TCM consortium were un-affected.
- All 10 WPs underwent significant membership changes and 6 WPs had significant WP leadership changes. These membership and leadership changes might cause temporary difficulties in coordination, but they served very well to ensure that each WP had all the needed human resources, expertise and vigorous leadership and eventually a success.
- Language barriers and lack of reliable and sustainable databases and literature resources in English remain key barriers for European scientists to get access to TCM literature. This was partially solved through recruiting scientists who are competent in both Chinese and English.
overall conclusions and recommendations:
due to its personalised and function-oriented features and its holistic and pre-emptive approaches, TCM is highly complementary to the current model of Western medicine and thus represents an important field for future research. Looking forward, prospects for the whole area largely depend on how experts in different disciplines and stakeholders in different regions and sectors collaborate and how much funding is invested into this field.
priorities:
- Sustainable governmental and non-governmental funding in this promising area, e.g. supporting EU-China joint initiatives on TCM research and development, supporting training programmes on good practices in TCM research, etc;
- Interregional, intersectoral and interdisciplinary collaborations in quality control, pharmacovigilance, toxicology and pharmacology of CHMs and high-quality clinical trials;
- Special focus on research of TCM interventions, including prevention and treatment, for chronic diseases.
potential Impact:
4.1.4 The potential impact and the main dissemination activities and exploitation of results:
GP-TCM played a keen role to have a durable impact on European focused TCM research. All its major activities including development of sustainable expert networks, generation of guidelines, reviews, recommendations and priorities, as well as development of online resources and establishment of the new TCM research association were designed to have maximum impact on development of European agenda for future research and funding, as well as policy making.
1.4.1 Impact through Developing a Large Interactive and Collaborative Expert Network:
GP-TCM was characterised as an open-start and open-ending consortium. With the launch of the consortium in May 2009, scientists in Europe and China, who had been working on TCM research independently, were gathered under the project's banner and their efforts were unified to reach consensus on good practice guidelines, state-of-the-art functional genomics, as well as grand priorities, challenges and opportunities in studies of TCM.
1.4.2 Impact through Novel Literature Research Findings and Recommendations of 10 WPs:
during the lifetime of the project, the consortium reviewed existing TCM literature and other data to assess the state-of-the art omic technologies and their use in evidencing safety, efficacy and mechanisms of action of TCM. These reviews and peer discussions allowed our scientists to identify knowledge gaps and provide standardised methodologies and good practice guidelines in relevant TCM research fields. Their studies especially focused on challenging areas, which will have impact on health of EU citizens.
the findings and conclusions of the consortium WPs have been presented in the forms of reports, guidelines, handbooks, peer-reviewed scientific articles, web posts, newsletters, posters, talks, etc. The material produced by the consortium has been tailored to serve the needs of the public as well as the expert community (science, policy making and funders).
contributions by each WP to advance TCM research in Europe are summarised below:
WP1 (Quality Control):
- Compiling a "priority list of species" of particular importance for the EU;
- Report showing the different scientific names that can be assigned to the species used in a classical CHM formula Liu Wei Di Huang Wan.
- Information about the methods used to prepare the species used in Liu Wei Di Huang Wan as well as information about institutes that contain verified vouchers for these species.
- Review article: Good practice guidelines in reviewing and publishing studies on herbal medicine, with special emphasis on Traditional Chinese Medicine and Chinese Materia Medica. J Ethnopharmacol. 2012; 140: 469-475.
- Review article: The formation of Daodi Chinese materia medica. J Ethnopharmacol. 2012; 140: 476-481.
WP2 (Extraction and Component Analysis):
- Report summarising techniques and standards employed for the analysis of simple and complex herbal extracts;
- Report summarising techniques and standards employed for the preparation of extracts used in TCM;
- Report on best practice in information analysis for fingerprinting and component analysis;
- Report on the methodology used in the analysis of 'priority list preparations';
- Report on identified gaps of information and non-standard areas;
- Recommendations for future research agenda;
- Review article: The potential of metabolic fingerprinting as a tool for the modernisation of TCM preparations. J Ethnopharmacol; 2012; 140: 482-491.
WP3 (Toxicology):
- Establishing the definition to "toxicity" as "possible harmful reaction to the body which is not related to therapeutic effect;
- Classification of "toxicity" into four major groups: (i) side effects (covered by pharmacodynamics and often predictable), (ii) reactions occurirng as a result of overdose, overduration, tolerance, dependence-addiction (covered either by pharmacodynamics and pharmacovigilance), (iii) hypersensitivity, allergic and idiosyncratic reaction (covered by pharmacovigilance), (iv) mid-term and long-term toxic effects (liver, renal, genotoxicity, teratogenecity, neurotoxicity, cardiotoxicity, etc);
- Consensus on (iv) mid-term and long-term toxic effects as the most important field for omics predictive toxicology;
- Review article: Review of current and omics methods for assessing the toxicity (genotoxicity, teratogenicity and nephrotoxicity) of herbal medicines and mushrooms. J Ethnopharmacol; 2012; 140:492512.
- Review article: Pharmacovigilance practice and risk control of TCM in China. J Ethnopharmacol; 2012; 140: 519525.
- Review article: Pharmacovigilance of herbal medicines. J Ethnopharmacol; 2012; 140: 513518.
- GP-TCM collaboration led to new projects entitled "Neuro-biological mechanism of KXS on memory enhancement" and "Research of effective components from Polygala tenuifolia on improving learning and memory in vivo", which have been funded by MOST, China.
WP4 (In-vitro and In-silico Pharmacology):
- Evaluation criteria for scoring scientific articles on CHM research articles, which can be used to evaluate the quality of the scientific reporting; freely available to the scientific community for scoring scientific papers in the field;
- An online repository of literature encompassing in-vitro research and functional genomic applications of CHM, which is available to the scientific community and can be used to understand the weighed quality of papers on specific CHM subjects;
- Report of the discussion group on biological target oriented database, which is available to the public on the GP-TCM project website and can stimulate scientific debate;
- Report on quality criteria and scoring of the CHM database, which is available to the public on the GP-TCM project website and can stimulate scientific debate;
- Report on existing databases and software for in-silico studies of phytocomplexes, which is available to the public on the GP-TCM project website and can stimulate scientific debate;
- Handbook on good practice in the reporting of CHM experimental work, which is available to the scientific community on the GP-TCM project website and suggests good practices for scientific reporting in in-vitro CHM research;
- Handbook of guidelines for using in-silico tools in CHM research, which is available to the scientific community on the GP-TCM project website and suggests good practices for using databases and software in in-silico CHM research;
- Handbook for using functional genomics techniques in in-vitro CHM research, which is available to the scientific community on the GP-TCM project website;
- A questionnaire survey on scientists' views regarding the value of the application of omic and in-silico methods in TCM research, which is available to the scientific community on the GP-TCM project website and can be shared by the scientific community to repeat the analytical test in different contexts;
- A searchable online repository of critically reviewed and quality scored articles, which is available to the scientific community on the GP-TCM project website and can be used for reviewing purposes by the scientific community;
- Review article: Omic techniques in systems biology approaches to traditional Chinese medicine research: Present and future. J Ethnopharmacol. 2012; 140: 535-544;
- Review article: In-silico studies in Chinese herbal medicines' research: Evaluation of in-silico methodologies and phytochemical data sources, and a review of research to date. J Ethnopharmacol. 2012; 140: 526-534.
WP5 (In-vivo Pharmacology):
- Review article: MEDLINE-based assessment of animal studies on Chinese herbal medicine. J Ethnopharmacol. 2012; 140: 545-549.
- This review on CHM literature involving animal models resulting in the identification of the main problems in the experimental design of animal studies of CHM and the assessment of the scientific proof of the efficacy of CHM provided by animal studies. This can be used for the scientific community;
- Provision of a checklist that could help in the preliminary selection of publications lacking the most common problems of animal studies of CHM and thus would be useful for a quick search of reproducible CHM treatments 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. Therefore the checklist provides guidelines for the good practice in the conduct of CHM studies in animals and it is recommended for use by researchers. This will ensure a solid evidence base for the efficacy of CHM and for the use of more holistic approaches based upon the application of omic technologies.
- Review article: Omic techniques in systems biology approaches to traditional Chinese medicine research: Present and future. J Ethnopharmacol. 2012; 140: 535-544.
- This WP4 and WP5 joint review highlighted the application of omics and systems biology technologies in both in-vitro and in-vivo studies of TCM and can be used as a state-of-the-art report on this important issue;
WP6 (Clinical Studies):
- Provision of clinical research good practice guidelines for CHM trials. These will be recommended for use by researchers and the academic community. This will in the future ensure the provision of a solid evidence base for policy and clinical CHM use.
- Report on clinical use of CHM, specifically comparing the clinical use of different kinds of preparations of CHM. This and future research in this area will impact on good clinical practice and improve patient care.
- Report on the role of Omic technologies for CHM highlighting the general scope where future research may prove useful. This underpins the need for good practice and highlighted the importance of defining quality standards for CHM products, toxicity, differentiating the actions of single and multi-component CHM mixtures and drug responses. This is of key importance to clinicians, researchers, the pharmaceutical industry and policy makers.
- Identification of areas of clinical importance to and evidence gaps in clinical practice by engaging with TCM practitioners and Western conventional practitioners. This may have impact on integration of TCM and conventional medicine.
- Review article: Comparison of effectiveness and safety between granules and decoction of Chinese herbal medicine: A systematic review of randomized clinical trials. J Ethnopharmacol. 2012; 140: 555-567.
- Review article: Guidelines for randomised controlled trials investigating Chinese herbal medicine. J Ethnopharmacol. 2012; 140: 550-554.
WP7 (Commercial R&D and Regulatory Issues):
- A comprehensive paper providing comparisons of the different regulatory pathways for CHM products and other traditional herbal medicines including tabular comparisons and flow diagrams;
- A comprehensive analysis of omic technology being used for R&D of pharmaceuticals and how this can be applied to the future R&D of CHMs;
- An extensive collaborative international network of experts in CHM R&D and in particular, the applicable regulations and omic technology. Experts representing a good cross section of the life sciences i.e. academia, industry, government;
- Dialogue with key regulatory agencies and inclusion of Agency staff in WP7 membership.
- Review article: Future development of global regulations of Chinese herbal products. J Ethnopharmacol. 2012; 140: 568-586.
- Review article: Omics and its potential impact on R&D and regulation of complex herbal products. J Ethnopharmacol. 2012; 140: 587-593.
WP8 (Acupuncture and Moxibustion Studies):
- An effective collaborative international network of experts in acupuncture research has been identified for future clinical trial research;
- WP8 and WP6 launched an acupuncture and TCM practitioner survey across Europe and China. The survey (WP8 part) explored the acupuncture practitioners to identify the most common conditions treated by acupuncturists and compare the different conditions treated by acupuncture practitioners in China and EU. Their views on effectiveness were ascertained in order to identify areas where clinical trials on acupuncture should focus. This is of use to clinicians, government, researchers and academics in defining the topics for future clinical trials and the current evidence gaps;
- Literature reviews suggested that disease-oriented studies using the approach of multi-indexed high-throughput technologies and systems biology analyses could be a preferred strategy for future acupuncture/moxibustion research. This will be of use to all stakeholders in acupuncture research.
- Review article: A review of Omics research in acupuncture: The relevance and future prospects for understanding the nature of meridians and acupoints. J Ethnopharmacol. 2012; 140: 594-603.
- Review article: Exploring practice characteristics and research priorities of practitioners of traditional acupuncture in China and the EU-A survey. J Ethnopharmacol. 2012; 140: 604-613.
WP9 (Final Conferences):
- Through advertising the Leiden meeting we reached many colleagues in the field, resulting in new members of the network.
- The GP-TCM Journal of Ethnopharmacology Special Issue [2012; 140(3)] was freely distributed and promoted at the two WP9 meetings; it will sets standards for research on traditional medicines for a number of years to come.
- The GP-TCM Association was initiated at one of the two meetings organised by WP9.
- Identification of future stakeholders that expressed their interests in the Association through the survey spread to all participants.
- Dissemination of results to a large scientific community.
- Review article: Good Practices: The basis for evidence-based medicines. J Ethnopharmacol. 2012; 140: 455-457.
WP10 (Management):
- Identified a future research agenda for Europe and beyond through the GP-TCM survey entitled "Grand Issues in TCM Research", focusing on grand priorities, challenges and opportunities". This document will serve as a major guideline to help shape the future research focus and funding opportunities by funders, policy makers and TCM scientists'.
- Organised the publication of an open-access GP-TCM Journal of Ethnopharmacology Special Issue to provide all-in-one reference document summarising project's focus areas, literature reviews, findings and recommendations.
- The GP-TCM Research Association was founded to sustain coordination of good practice in TCM research in the EU and a stronger alliance with the other parts of the world.
- Review article: Establishing an EU-China consortium on traditional Chinese medicine research. Chin Med. 2010; 5: 42.
- Review article: Traditional Chinese medicine research in the post-genomic era: Good practice, priorities, challenges and opportunities. J Ethnopharmacol. 2012; 140: 458-468.
- Review article: Good practice in reviewing and publishing studies on herbal medicine, with special emphasis on traditional Chinese medicine and Chinese materia medica. J Ethnopharmacol. 2012; 140: 469-475.
- Review article: Network pharmacology and TCM. In: Alternative Medicine. Sakagami H, ed. Intech, ISBN 978-953-51-0903-7. This is an in-press Intech open-access book chapter, which introduced the concept of network pharmacology, TCM network pharmacology and their applications in TCM research.
- Review article: "The role of the GP-TCM Research Association to modernization and globalization of Traditional Chinese Medicine" in the book "Antitumor Potential and other Emerging Medicinal Properties of Natural Compounds" to be published by Springer.
- Review article: The quest for modernisation of TCM. Submitted to an open-access journal BMC Medicine. This manuscript reviewed the concept and practice of the "modernisation of TCM" in an international, historic and scientific perspective, leading to the three "I" principles below.
1.4.3 Impact through Developing the Three "I" Principle:
the consortium has recommended three "I"s to guide future development of TCM research, i.e. integrity, integration and innovation, which are interpreted as follows.
- Integrity
- Holism. As a holistic medicine, TCM considers the human body as a whole, emphasises the importance of functions and emotions and considers patients as part of a system interacting with its environmental factors, such as diet, climate and life style. This is embodied in TCM diagnosis, prescriptions and life style interventions.
- Ethics. Since the era of Sun Simiao (581-682) ethics has become an integral part of TCM. In ancient China, practitioners' ethics were at the centre of the TCM profession. Now, modern TCM ethics should apply to not only TCM practitioners, but also the agricultural, industrial and scientific communities, and all stakeholders. Conflict of interests should be avoided, stated and properly regulated.
- Good practice. As defined by the FP7 GP-TCM project and the GP-TCM Research Association, TCM requires continuous development, refinement and dissemination of good practice guidelines in all its multiple aspects. In such epic efforts, collaboration and sharing must be encouraged and we must strive for consensus while respecting differences. Good practice is especially required in authentication, quality control, safety assessments and sustainable use of TCM drugs and materials; agricultural and manufacturing practices; commercial and clinical practices; clinical and basic research of TCM; application of routine and emerging technologies; as well as differentiation between valuable knowledge and superstitious, erroneous and misleading anecdotes.
- Integration
- Education, clinical practice and research. Integration of these three important aspects was one of the most important achievements in modernisation of TCM.
- Cultural, philosophical and scientific perspectives. TCM is an important part of Chinese culture and is guided by Chinese philosophy. Thus, researchers of the scientific, cultural and philosophical values of TCM should collaborate with and learn from each other.
- TCM, Western medicine and modern science. In China and some other countries, TCM and Western medicine are both in mainstream healthcare and intend to complement each other. In the international context, dialogue between TCM and Western medicine needs to be promoted; China's experiences and lessons should be studied in light of modern science so that both medical traditions may contribute to forging tomorrow's medicine. Bringing evidence-based medicine to recognise the value of TCM will have to integrate a thorough rethinking of both Western and TCM practices to generate scientifically and statistically convincing evidence of the TCM-based approaches.
- Interregional, intersectoral and interdisciplinary collaborations. Due to the complexity and the vast range of TCM, collaborations between different regions, different business sectors, as well as different areas of knowledge must be encouraged in order to share resources and expertise and join forces to meet the challenges together. For example, the various distribution channels encountered in different countries must be connected in order to develop harmonised pharmacovigilance procedures suitable to rapidly and globally detect and assess warning signals for adverse events.
- Holistic, relationist and analytical, reductionist approaches. TCM emphasises holistic and relationist approaches of thinking, while Western medicine is largely based on analytical and reductionist approaches. To see both the trees and the wood, these approaches must be integrated.
- Quality, toxicology and pharmacology. These three most important aspects of TCM are so much interrelated that future training and research must further integrate these crucial elements to better ensure safety and efficacy.
- Innovation
- Modernisation of TCM is more than Westernisation. Although some achievements have already arisen through studying TCM using a Western approach, e.g. isolating pure compounds, real innovations should include both TCM-inspired changes in mode of thinking and practice in Western medicine and TCM refinements inspired by modern science.
- TCM diagnosis. Among all aspects of TCM, holistic TCM diagnosis has probably the most complementary elements to modern medical practice, including its function-oriented description of organ systems and diagnostic approach (leading to syndrome differentiation), its emphasis on modulation of functional balance, its comprehensive categorisation and interpretation of tongue and pulse patterns, its characteristic categorisation of the nature of diseases and drugs, etc. These could be important sources for developing and validating innovative mind-set, methods, tools and strategies that could complement biology-based diagnosis.
- Preventive and comprehensive interventions. TCM is characterised by both pre-emptive approaches and interventions with multiple components. It emphasises intervention before disease arises and often combines dietary advice, physical exercises such as Taijiquan (Tai Chi Chuan), meditation, herbal medicines, massage, acupuncture and moxibustion, etc. The values of these individualised and integrated approaches are important directions for future public health.
- Innovative, more robust methodology. The complexity of TCM demands novel and more robust ways of thinking, approaches, tools and methods. For example, the individualised and holistic nature of TCM requires tools for complexity research, research of the science of individuality and personalised medicine, as well as novel statistics. It also awaits the maturation of omics, systems biology and other systems-based technologies.
- Prioritisation and focus. In view of the vast areas of TCM yet to be explored and the limited resources available for such an emerging area of research in the global context, prioritisation and focus become the key to achieving real innovation. In this regard, a Steve Jobs approach for innovation is to "say no to 1,000 things" and to focus only on those that could make real differences becomes all the more compelling.
1.4.4 Impact through Developing Online Resources:
the consortium developed numerous reports, peer-reviewed articles, guidelines, databases and newsletters to support best practice, exchange of experience and strengthen EU focussed international collaboration in TCM research. These resources were made available online through various sources open to members or to the public. It is envisaged that these online resources will continue to support and enhance Pan-European studies of TCM research while being used as references by policy makers and funders.
- The GP-TCM project (archived) and the GP-TCM Research Association websites: The project website will be kept online for at least three years after completion of the project's funded lifetime to allow continuous access to our outcomes by the public.
http://project.GP-TCM.org; http://www.GP-TCM.org/
- The GP-TCM public deliverable reports ranging from technical reports, databases, guidelines to meeting proceedings open access (74 documents)
http://project.GP-TCM.org/about/deliverables/
- The GP-TCM internal deliverable reports members only (100 documents)
- The GP-TCM Special Issue open access (20 review articles)
http://www.sciencedirect.com/science/journal/03788741/140
- The GP-TCM Newsletters open access (54 issues published between October 2007 and October 2012): http://www.GP-TCM.org/news/
- GP-TCM Guidelines for randomised controlled trials investigating CHM
http://www.GP-TCM.org/2012/12/GP-TCM-guidelines-for-randomized-controlled-trials-investigating-chinese-herbal-medicine-chm-2/
1.4.5. Impact through Founding a New Association:
with the exception of the GP-TCM consortium, there was no pan-European organisation to coordinate TCM research in Europe. Hence, the consortium established a new organisation to carry on coordinating TCM research after completion of the project and ensure a sustainable development of TCM research in Europe and worldwide. The GP-TCM Research Association was officially at a dissemination event organised by WP9 of the GP-TCM project, i.e. the GP-TCM Congress held in Leiden, the Netherlands, 16th 18th April 2012.
the Association is a non-for-profit organisation, which is currently in the process to be registered as a charity in the UK. It will be dedicated to promoting high-quality evidence-based research of TCM through developing, disseminating and implementing good practice. The objectives for which the Association was established are:
- Perpetuate the interactive network established by the FP7 GP-TCM consortium;
- Promote discussion and implementation of good practice in TCM research and development, including the use of sustainably sourced materials;
- Advocate high-quality evidence-based research and development on TCM as well as on its integration with conventional medicine;
- Organise and co-organise scientific meetings and specialist courses;
- Nurture young TCM researchers at different levels in an interdisciplinary approach, including BSc, MSc, PhD and post-doctoral programmes;
- Facilitate collaborations and sharing of resources, expertise and good practice among members, industry and regulatory agencies;
- Encourage collaborations with existing relevant societies, consortia and organisations;
- Strengthen interdisciplinary, interregional, and intersectoral collaborations in TCM research and development;
- Perpetuate good practice in publishing TCM research outcomes;
- Disseminate scientific research outcomes and latest developments in regulatory sciences to stakeholders, industry, professional groups and the public.
1.4.6. Impact through Dissemination Activities:
GP-TCM was keen to disseminate findings on good practice issues and other important findings on the safety, efficacy and mechanisms of CHM and acupuncture to stakeholders and the public. Through agreed best practice, guidance and dissemination, the consortium aimed to harmonise activity to adhere to highest principles of scientific rigor within this complex field.
to achieve the consortium's dissemination goals, the following main activities were undertaken to inform the findings of the network to the widest possible audience including scientific community, industry, policy makers and the public:
- GP-TCM website and monthly newsletters;
- Consortium publications such as deliverable reports (public), periodic reports, a journal special issue and many other papers in scientific journals and books;
- Seminars, talks, workshops, demonstrations, interview reports by radio, TV, newspaper, specialist magazines and websites aimed at spreading the accruing research and review results to large communities;
- The Sino-EU GP-TCM Workshop (The GP-TCM Kick-off meeting, Beijing, China, 2009), Annual Meetings (Henley, UK, 2010; Braga, Portugal, 2011), the Final Conference and the GP-TCM Congress (Kerkrade and Leiden, the Netherlands, 2012); the 2012 Shanghai International Conference on TCM and Natural Medicine and the GP-TCM Research Association First Annual Meeting (Shanghai, China, 2012); and the International Symposium on Standardisation and Cooperation of TCM (Beijing, China, 2012);
- Establishment of the GP-TCM Research Association to sustain coordinated TCM research in Europe. Since its official launching in April 2012, the Association has joined forces with the GP-TCM project in dissemination efforts.
1.4.7 Impact through Exploitation of Results and Resources Assembled by the Project:
- Made the best use of the ever-expanding FP7 GP-TCM network collaborating on good practice of TCM to establish an international Association, the GP-TCM Research Association.
- Made the best use of the communication and dissemination tools such as GP-TCM project website, newsletters and Essential Manual to build the GP-TCM Research Association website and newsletters;
- Informing the outcomes of the GP-TCM "Grand Issues in TCM Research" survey to stakeholders in the EU and China to serve forging an EU agenda for future TCM research and to guide future funding;
- Made the best use of GP-TCM agreements on state of the art, definition of good practice, guidelines and principles, priorities, challenges and opportunities to develop scientific publications;
- One PhD thesis on CHM was completed as part of WP5 literature studies;
- Three rounds of bidding for Seventh Framework Programme (FP7) Marie Curie Initial Training Network funding were launched in 2009, 2010 and 2011, respectively, with the expertise pool of the GP-TCM project;
- GP-TCM partnership between University of Vienna and Chinese Academy of Sciences led to successful seventh Framework Programme (FP7) in 2012;
- GP-TCM partnership between Chinese Academy of Medical Sciences and European partners led to successful funding from the Chinese government in 2012;
- Collaborations in the GP-TCM project and the GP-TCM Research Association led to closer collaborations and partnerships between many members. To mention a few, (i) the sister centre relationship between Shanghai Research Centre for TCM Modernization, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (China) and the Institute of Pharmaceutical Sciences, Department of Pharmacognosy, Karl-Franzens-University Graz (Austria) was established in 2012; (ii) a memorandum of understanding was signed between King's College London (UK) and Chengdu University of TCM (China) to jointly support research and teaching of integrative Chinese medicine; and (iii) a new partnership between China Academy of Chinese Medical Sciences (China) and The Norwegian University of Science and Technology (Norway).
list of Websites:
http://project.GP-TCM.org
4.1.1 Executive summary:
traditional Chinese medicine (TCM), especially Chinese herbal medicine (CHM) and acupuncture, is the ancient medical system used by the people in China and some other Asian countries for thousands of years to maintain the health of one of the largest populations in the world [1,2]. In recent years, TCM has been used by an increasing number of people in Europe and has attracted intense research interests from European scientists [3,4,5].
as an emerging area in Europe, TCM research requires collaboration and coordination. Good Practice in Traditional Chinese Medicine Research in the Post-genomic Era, also known as GP-TCM, was the 1st EU-funded Seventh Framework Programme (FP7) Coordination Action dedicated to informing the best practice and harmonising TCM research through interdisciplinary exchanges among TCM experts and scientists [3].
project Context and Objectives:
4.1.2 Summary description of project context and objectives:
in recent years, TCM has been increasingly used in Europe [3,4,5]. However, in contrast to the reductionist approach of Western medicine that is based on anatomy, physiology, pharmacology, cell and molecular biology, TCM is based on thousands of years of recorded clinical experience, guided by Chinese philosophy, e.g. the Yin-Yang theory emphasising the balance of functional systems. TCM uses a theoretical system with a personalised and holistic approach to describe health and disease [2]. Speaking in metaphors, while Western medicine tends to see trees but not the wood, TCM, on the other hand, often sees the wood but not the trees. Therefore, both systems can learn from each other.
project Results:
4.1.3 Description of the main S&T (Science and Technology) results/foregrounds:
by 31st October 2012, through 3.5 years of team building, the GP-TCM consortium had grown into a large collaborative network involving approximately 200 scientists from 24 countries and 110 institutions.
1.3.1 WP1 - Quality Control of CHM
objectives: The main objectives of WP1 were to design a standard system to review the literature on papers associated with plants used in CHM and use the information gained from this review to develop a system for the quality control of CHM in the EU. The system will take into account what is known about the complexity of CHM such as the nomenclature, the need to ensure plants had been identified correctly and that researchers were aware of the complexity of the different names that could be used to describe a species.
description of work: A group of specialists in different aspects of the quality control of TCM plants from the EU and China was brought together in a series of one-to-one meetings and telephone meetings. Because the aims of WP1 were closely aligned with those of WP2 and WP4, joint meeting took place between the groups during the three years of the projects. WP1 was initially going to review the literature on the top 100 plants entering the EU and then narrow the range of species to 20-40 as outlined in the project proposal. However, it was decided at the first Annual Conference at Henley to concentrate on gathering data about the plants as used in CHM formula.
priority areas:
- The production of a database that brings together the Latin accepted scientific binomial names of the plants, synonyms, pharmaceutical and Chinese names;
- Research that further our understanding of the chemical profile of a quality plant based on a better understanding of the pharmacology of the extracts tested;
- Improved understanding of the agricultural practices needed to produce good quality place;
- Better understanding of the supply chain of the plant used in TCM to ensure that there are plentiful supplies of quality plants obtained from sustainably harvested sources;
- Development of molecular methods (DNA and chemical) that can be used to identify species and enable the identification of substitutes and adulterants.
1.3.2 WP2 - Extraction and Component Analysis of CHM
objectives: The objectives of WP2 were situated around the extraction and component analysis of CHMs. In general, the currently employed traditional extraction technologies had to be evaluated with regard to special phytochemical characteristics of CHM. Problems and gaps of knowledge that need to be addressed for a reasonable modernisation of the traditional preparations towards more convenient application forms had to be identified.
description of work: Due to the close relation between WP1 and WP2 that had been figured out early in the project, WP2 started its activities with a joint workshop with WP1 in London. On that occasion the joint compilation of plant-species-related literature data was identified as a field of mutual collaboration between the WPs. This collaboration continued in the organisation of further joint face-to-face meetings and telecommunication events throughout the project's lifetime.
outcomes: Traditional CHM preparations, mainly elaborative decoctions of complex herbal mixtures with water, are more and more replaced by modernised and more convenient products like granules that are just to be suspended in water before application. However, there is lack of evidence that such preparations are comparable with their traditional prototypes in terms of activity and chemical composition.
the outcomes are represented by the WP2 deliverables, including dissemination (Review paper published in Journal of Ethnopharmacology and presentation of results on an International conference).
priority areas:
- Comparative studies on the activity and chemical composition of traditional and modernised extracts of CHM;
- Elucidation of the impact of traditional post-harvest processing techniques (drying, wet-cutting, paozhi, soaking in cold water, co-extraction) on the product's chemical profile using metabolomic techniques;
- Identification of quality determining chemical components from traditionally prepared CHM taking advantage of the rich traditional variability of TCM drugs for the application of activity-guided metabolomic techniques;
- Simplification of complex traditional preparations by (i) identification and removal of dispensable herbal ingredients and (ii) identification and deletion of dispensable methods of processing (please refer to deliverable D2.12 report for more details).
1.3.3 WP3 - Functional Genomics in Toxicology Study of CHM
objectives: The research protocols, standards and methods for the evaluation of the safety and efficacy of TCM, including CHM, are more complex than those for conventional medicines. Indeed, TCM presents a unique set of pharmaceutical theories that include particular methods for processing, combining and decocting CHM, which probably contribute to reduce their eventual toxicity and enhance their efficacy. The evaluation of CHM safety is complicated by multiple factors, such as the geographical origin of plant material, different processing techniques, dosage, route of administration and compatibility with other medicines.
description of work:
- To achieve its intended goals, the WP3 group has established a network of experts in the field, which has been strengthened all along the project duration. WP3 has developed a series of literature searches;
- The WP3 kick-off meeting, "Functional genomics and toxicological studies applied to TCM", was held on 24th and 25th October 2009 in Brussels La Hulpe, bringing together 8 WP3 groups from both China and Europe (out of a total of 13 groups), the Coordinator of WP5 and 3 guests from Belgium and D. R. Congo; Xinmin Liu has organised 5 mini-workshops for Chinese participants in Beijing to draft WP3 plans;
- A series of e-mail contacts circulated lists of plants and composed preparations, thanks to Dr. You-Ping Zhu (China-Netherlands Medical and Pharmaceutical Centre, NEDICHIN BV, The Netherlands), Prof. Benny Mei of ACUMED, London UK, Kelvin Chan, Xinmin Liu, Yanjiang Qiao, Elizabeth Williamson and Debbie Shaw: Best selling herbs in Europe, top 15 PCM in Europe, PCM substitutable by aristolochic acids containing herbs, herbs associated with unpredictable hepatotoxicity, herbs from the "973 programme";
- Three web-based meetings were organised and frequent exchanges of e-mails between all WP3 members allowed to discuss the finalisation of deliverables, to prepare the final WP3 reports, to prepare the Henley (1st AGM), Braga (2nd AGM) and final conferences, to obtain feedback on the drafts for the SOP literature panel, to move on the different reviewing topics, to assign tasks to WP3 members and to define the organisation of the work for "systematic literature review and translation";
- A survey on the perception of safety by stakeholders was designed, launched and analysed by Prof. Pierre Duez and his team for deliverable D3.6 with support from number of WP3 members;
- Hani El-Nezami, Joëlle Nortier, Pierre Duez, Jue Zhou, Fan Qu and Caroline Stévigny have coordinated literature reviewing on some toxicities by PhD and master students;
- A joint workshop was organised with WP1, WP3, and WP7 members and experts of the EDQM European Pharmacopoeia TCM workgroup (Strasbourg, France, 29th September 2011). Prof. Duez presented a short talk: "GP-TCM Introduction and brief progress of WP3";
- A workshop was organised (September 2011) by Prof. Xinmin Liu in Luzhou Medical College, Sichuan Province, China, for discussing review manuscripts on toxicity of CHMs;
- Prof. Xinmin Liu introduced GP-TCM to Mr Yu Wenming, Deputy General-Director of SATCM, Ms. Xiaopin Wang, Director of Department of International Cooperation of SATCM, Dr. Jijun Xing, Deputy Director of China Science and Technology Exchange Centre, MOST and Dr. Philippe Vialatte, the representative from Science and Technology Section, EU Delegation in China;
- Prof. Duez organised a 3-months writing session for WP3 reviews, jointly with M. Ouédraogo, C. Stévigny, J. Nortier and T. Baudoux;
- Prof. Xinmin Liu helped the Hunan University of TCM in Changsha, Hunan, China, to set up "Sino-EU Contact Office (Traditional Medicine), with strong support from Dr. Jijun Xing, the Deputy Director of China Science and Technology Exchange Centre, MOST, China.
outcomes:
WP3 has defined the meaning of "toxicity" with regard to its activities as follows: "Possible harmful reaction to the body which is not related to therapeutic effect. Toxicity can then be classified into (i) side effects (covered by pharmacodynamics and often predictable), (ii) reactions occurring as a result of overdose, over-duration, tolerance, dependence-addiction (covered either by pharmacodynamics and pharmacovigilance), (iii) hypersensitivity, allergic and idiosyncratic reaction (covered by pharmacovigilance), (iv) mid-term and long-term toxic effects (liver, renal, genotoxicity, teratogenecity, neurotoxicity, cardiotoxicity, )". It has been agreed that point (iv) is the most important field for 'omics' predictive toxicology.
priority areas:
- Development and validation of screening methods to rapidly identify herbs that may raise safety concerns, focusing on medium- and long-term toxicities;
- Development of research methodology and protocols for evaluating toxicity and safety of Chinese herbal medicine, taking into account TCM characteristics such as combination of herbs and processing;
- Reinforcement of pharmacovigilance for herbals, including all marketing status (drugs, food supplements, etc);
- Training scientists to meet the challenges of toxicological evaluation of herbals.
1.3.4 WP4 - Functional Genomics of CHM Research in Vitro
objectives: The aim was to define and propose standardisation of in-vitro systems and their use in functional genomics studies (all the so-called 'omic' techniques) of CHM. The aim was accomplished by developing a general strategy and then identifying and defining quality criteria and procedures. Particular attention was paid to establishing best practice criteria for research methods and reporting. This enabled a further objective of evaluation of existing publications. This approach was to be used similarly to evaluate the quality of existing databases and in-silico tools, and to establish guidelines for good practice in in-silico research in CHM research.
description of work: The main activities performed by WP4 were concerned with establishing a multidisciplinary network of experts in the field of in-vitro CHM research, to propose good practice and guidelines in the field. This was achieved by holding a number of face-to-face meetings together with e-contacts and conference calls. In particular, the kick-off meetings were useful for networking and to establish a formal organisation and agenda, though the main outputs of the meetings were focused on contents and output strategies, resulting in proposed criteria for literature evaluation.
outcomes:
the WP4 outcomes are innovative insights in the field of "omics" applied to CHM research and their dissemination in the scientific community with reports, articles, on line resources and meetings (all the eighteen WP4 deliverables are available in the website), including 3 reports, 3 handbooks, a questionnaire survey, a dedicated webpage on WP4, a searchable database of critically reviewed and quality scored articles, a presentation at the 2012 meeting in Leiden, a review article (Omic techniques in systems biology approaches to traditional Chinese medicine research), and a review article (In-silico studies in Chinese herbal medicines' research: Evaluation of in-silico methodologies and phytochemical data sources), and a review of research to date.
priority areas:
- Application of omics to CHM research;
- Encourage by all means possible the utilisation of the guidelines established in the WP work as standard for publication;
- TCM and pro-active approaches for prevention in the era of Personalised Medicine.
1.3.5 WP5 - Functional Genomics Studies of CHM in Vivo
objectives: The aim of WP5 was to establish best practice for animal studies of CHM in the EU. This was achieved by examining the biomedical literature on CHM in general and assessing the studies in animal models of selected diseases. Particular attention was paid to identify the most relevant methodological problems in these studies and to propose solutions, as well as to give directions for the application of functional genomics.
description of work: To achieve the WP5 objectives, the group leadership built an expert network in CHM in animal models of disease. The WP5 kick-off meeting was held in Alcala de Henares University the days 2nd 3rd June 2009 bringing together eleven WP5 members which discussed the 3-year plan of the WP and assigned jobs related to deliverables.
outcomes: The main WP5 outcomes are as follows:
- Identification of the main features and trends of the studies of CHM recorded in MEDLINE, which special focus on the last decade and on studies in animal models of disease;
- Identification of the main problems in the experimental design of animal studies of CHM;
- Assessment of the scientific proof of the efficacy of CHM provided by animal studies;
- Provision of a checklist for i) the quick assessment of the quality of any animal study of CHM and ii) helping in the experimental design of new studies in animals through avoiding the most common methodological problems found in these studies;
- A presentation at the GP-TCM Congress held in Leiden (April 2012);
- 2 poster presentations in the 11th Congress of the International Society of Ethnopharmacology (Albacete, Spain, 2010: Animal Models for Cancer Research in TCM and Scientific Publications on Animal Studies of CHM and 1 poster presentation in the TCM Symposium (Braga, Portugal, 2011: State of the art in animal studies of CHM);
- One review article on: Omic techniques in systems biology approaches to traditional Chinese medicine research; http://dx.doi.org/10.1016/j.jep.2012.01.055
- One review article on: Medline-based assessment of animal studies on Chinese herbal medicine. Http://dx.doi.org/10.1016/j.jep.2012.02.008
priority areas:
- Standardisation of the whole procedure of preparation of CHM formulations to be used in animal studies;
- Identification of key CHM for the treatment of selected diseases by getting proof of efficacy of selected CHM in comparable and reproducible animal studies;
- Application of omics to CHM research in animals.
1.3.6 WP6 - Functional Genomics in Clinical Studies of CHM
objectives: The overall objectives for WP6 were to focus on reviewing current practice of CHM research, identifying problems and proposing solutions and to ensure that an unbiased view of current research in functional genomics of CHM was produced. This was to be achieved by initially establishing a European-Chinese partnership to in order to develop a clinical trial network in CHM. This expert group was to provide a platform to develop expert guidelines for clinical research and propose standard protocols on methodology for CHM trials.
outcomes:
- Established an international expert network with expertise in clinical trials and CHM to facilitate future clinical research collaborations and research planning.
- Two surveys were conducted. The first focused on good practice guidelines to ascertain their attitudes towards the integration of complementary and alternative medicines (CAM) and Western healthcare in a representative county in the UK. It also identified the availability of CAM including herbal medicines and acupuncture in primary care.
- Provided clinical trial guidelines for the conduct of CHM trials for use by CHM researchers, in order to provide guidance and recommendations for good practice in CHM clinical trials.
- Reviewed the most recent evidence supporting CHM in some of the key selected conditions of interest to the WP6 members.
- Appraisal of literature on functional genomics. There was a lack of good quality studies in this area, and studies reviewed highlighted the general scope that such new approaches could offer. It was also recognised that the following were key issues to be addressed:
- Authenticity and quality of plant material
- Analysis of the mode of action of single plants and multi-component mixtures
- Assessment of the toxicity of CHM
- Drug metabolisation (individual drug responses)
- Ascertained topics areas for the future focus of CHM trials by engaging with TCM practitioners on defining priority areas.
priority areas:
- Safety of CHM Further research on adverse effects of CHM is required given a much lower reporting rate by Chinese practitioners;
- Key areas identified by CHM practitioners where more evidence is required suggested future areas where research should focus (obstetric/gynaecological complaints, dermatology and cancer);
- Conduct research on multi-herb formulae as used in clinical practice in conjunction with syndrome differentiation;
- Carry out further comparisons of different CHM preparations and methods of CHM delivery e.g. decoction, standardised formulae and semi standardised formulae using clinical trial methodology;
- Improve quality and reporting of clinical trials by the publication of trial protocols and ensuring voucher identification of CHM specimens.
1.3.7 WP7 - Functional Genomics in Research and Development(R&D) of CHM
objectives: The overall objective for WP7 was to establish a collaborative network towards formulating an easy-to-follow statement on the various regulatory frameworks, with emphasising the synergies and highlighting the differences with the aim of helping to establish a universal harmonised regulatory framework for botanicals.
A further key objective was to focus on searching literature beyond herbal products and summarise what has been reported on the application of "omics" and functional genomics in R & D and regulation of any drugs and then discuss its implications on R & D and regulation of CHM and other complex herbal products (CHP).
description of work: In order to achieve the objectives of WP7, a WP7 face-to-face kick off meeting was held in 2 phases: Phase 1 held at Brunel Institute of Bioengineering, Brunel University, London (31st August to 1st September 2009), and Phase 2 held at King's College London (25th-26th July 2010). During interim teleconferences and annual meetings specific checkpoints were inspected, status of deliverables was surveyed and tasks were checked, defined and further focused, if needed. Changes in WP7 membership necessitated quite crucial reorganizations and delineations of objectives and tasks.
outcomes:
the task to collect, organise, compare and summarize data on the regulation of herbal medicinal products, including TCM, in different parts of the world was focused on writing a reader-friendly document highlighting the complexity of the regulatory issues for registration of herbal products worldwide. The lessons learnt from global regulation of TCM provide valuable insights for regulation of other traditional medicine such as Ayurveda and Unani medicine, as well as other forms of indigenous medicine.
as the key deliverables of WP7, two major papers were published in the GP-TCM theme issue in Journal of Ethnopharmacology. The first one is a comprehensive summary of different herbal regulations worldwide titled Future development of global regulations of Chinese herbal products, which provides an updated information to researchers, regulatory authorities as well as industry worldwide.
other outcomes: WP7 Co-Coordinator Tai-Ping Fan announced that as a legacy for GP-TCM, he has been invited by American Association for the Advancement of Science magazine Science to edit a special sponsored issue on TCM in July 2013. He has assembled an executive editorial board with Prof. Peter Hylands of KCL and Prof. Jan van der Greef of University of Leiden. Prof. Kelvin Chan and Prof. Pierre Duez led the GP-TCM SOP team to produce a review Good practice in reviewing and publishing studies on herbal medicine, with special emphasis on traditional Chinese medicine and Chinese materia medica in Journal of Ethnopharmacology.
priority areas:
- Advance and emphasise global harmonization of regulation of complex herbal products in general and CHM in particular;
- Strengthen research agenda to employ functional genomic approach with all omics tools in connection with network systems pharmacology/toxicology;
- Engage the British Pharmacopoeia, the European Pharmacopoeia and the Chinese Pharmacopoeia in mutual recognition of a selection of medicinal herbs;
- Initiate dialogue with The WHO with respect to its place to co-ordinate a consultation process with the aim of putting forward suggestions for harmonisation to key regulatory agencies.
1.3.8 WP8 - Functional Genomics in Studies of Acupuncture-Moxibustion and Meridians
objectives: The overall objective of WP8 was to optimise and standardise acupuncture protocols and discuss the application of the functional genomics approach and to examine the efficacy of acupuncture and moxibustion for the treatment of common diseases in the EU countries. The specific objective was to first establish a communication and collaboration platform to evaluate the current status of acupuncture research and practice in both China and EU. And then, define and prioritise research areas or topic in acupuncture that would be appropriate for conducting functional genomic studies. Another objective was to obtain general agreement on the common standards for acupuncture protocols. The most important objective was focusing on future research strategies within appropriate areas for functional genomics.
outcomes:
the expert panel of WP8 has changed and expanded over the project period, but WP8 has maintained a close relationship among all WP members and with WP10. Several considerations were planned and carefully balanced during the entire team assembly processes, such as stability/dynamism, specialty/collaboration, broad coverage/representative subjects, and experienced seniors/young enthusiasts, etc. Based on the international collaborations and coordination, an extensive collaborative panel clinical and basic research in acupuncture was established both in China and EU. Activities such as a WP kick-off meeting, some other face-to-face meetings, literature studies, a number of teleconferences and many email communications were carried out in order to meet the WP objectives and milestones. The current status of clinical and basic research on acupuncture was highlighted to foster research collaboration both within and between China and the EU.
priority areas:
- The results from the online survey identified differences in practice and training between acupuncturists in China and the EU and between EU member states. It is suggested that creation of collaborative networks is crucial in overcoming these differences to facilitate international, multi-centre clinical trials.
- WP8 has created a review of existing literature and suggested a preferred strategy for future acupuncture/moxibustion research. Focused on several diseases or symptoms with evidence of effectiveness by acupuncture treatment, the approach of combination Omic technologies with functional molecular imaging will be a preferred strategy for future acupuncture research.
- WP8 also defined the status of current Chinese clinical-related acupuncture basic research in order to highlight future inter-collaborative research between and within China and EU.
1.3.9 WP9 - Final Conference
objectives: The task for WP9 was to organise and host the final conferences. This task was split up in two parts. One was the Final Conference, which was for project members to finalise the conclusions of their WPs; the other was for results to be presented in an international forum open to the public, i.e. the GP-TCM Congress. The deliverable D9.2 reports the full details of the organisation and results of both meetings.
description of work: From the very beginning of the project, the local organizers in Leiden have been exploring various sites for the Final Conference. They visited several facilities and eventually have chosen for the congress centre in Rolduc, an old monastery which can easily be reached by train from both Germany and the Netherlands. The Rolduc meeting attracted 80 participants. It was also decided with the management committee that besides the internal symposium for the beneficiary and non-beneficiary members of the project, WP9 also should organise a second meeting to disseminate the results to the scientific community.
priority areas:
- Networking will be a key aspect of further integration of the research;
- To have a COST project on TCM research;
- GP-TCM Research Association should organise postdoctoral courses on systems approaches to TCM research;
- EU and China should come to a mutual agreement to support studies on the integration of Chinese and European medicine;
- Dissemination of results to the general public.
1.3.10 WP10 - Management: Sustainable development and coordination of TCM research in the EU
objectives: As the overall management team of the consortium, WP10 aimed to coordinate WP leadership, membership and collaboration, to steer research direction, to organise quality assurance, collation and integration of data, as well as dissemination of results.
description of work: In 3.5 years, WP10 organised more than 50 major teleconferences covering management, science and good practice issues, 3 face-to-face consortium-wide meetings with relevant stakeholders' involvement, and numerous other face-to-face meetings to facilitate effective and efficient communication platforms and discussion for a moving the project forward.
outcomes:
- Ever-strengthening interdisciplinary, intersectoral and interregional collaborative network: By the 3rd year of the project, the consortium membership profile was increased from "28 beneficiary and 24 non-beneficiary partners across 12 countries" to "29 beneficiary and 82 non-beneficiary partners across 24 countries" giving access to further expertise and resources while strengthening the delivery of project objectives.
- Consortium-wide conclusions on grand Issues in TCM research: WP10 broke barriers among WPs and between GP-TCM and the other related communities and organised the GP-TCM "Grand Issues in Traditional Chinese Medicine Research Survey" open to all consortium members and non-members. The outcomes of the survey established high-quality research on efficacy/effectiveness and mechanisms of action of CHM and acupuncture and identification of priority disease areas where TCM could achieve better outcomes as grand priorities. TCM contribution to the management of one of EU's top healthcare challenges, i.e. long-term conditions and chronic diseases was regarded as the top opportunity.
results of the poll were made freely available through the following web links:
http://project.GP-TCM.org/2011/08/"grand-priorities-challenges-and-opportunities"-survey/
http://www.sciencedirect.com/science/article/pii/S0378874112001110
- The open-access GP-TCM Journal of Ethnopharmaology special issue: WP10 played a key role in disseminating the project findings. To summarise the research outcomes and recommendations from all GP-TCM WPs in a way convenient for future reference, the consortium prepared a series of publications derived from the GP-TCM consortium to be collated into a special issue of the Journal of Ethnopharmacology. The special issue was published in April 2012 and comprised 20 articles, with contributions from all WPs as well as independent papers complementary to the work of GP-TCM. The consortium made all articles open-access, allowing all interested parties to download the articles free of charge
http://www.sciencedirect.com/science/journal/03788741/140
- The GP-TCM Research Association: GP-TCM good practice guidelines need dissemination, validation and further development through continued interregional, interdisciplinary and intersectoral collaborations. Hence to promote this, WP10 led the process of establishing a new international association, known as "the GP-TCM Research Association", which was founded in April 2012 and has fully succeeded the 3.5-year fixed-term FP7 GP-TCM consortium since November 2012 (see http://www.GP-TCM.org/ online).
- Members' answers to the question "What have I learnt through the GP-TCM project?": To mention a few, Prof. PC Leung (Chinese University of Hong Kong, China) said: "GP-TCM has demonstrated the potential of collaboration in the vast field of TCM; GP-TCM should be continued." Prof. Olavi Pelkonen (University of Oulu, Finland) acclaimed: "Networking of scientists with variable backgrounds is powerful!" Prof. Rob Verpoorte (Leiden University, The Netherlands) conlcuded: "GP-TCM has lowered barriers between scientists from the EU and China, the GP-TCM Research Association will be instrumental in further lowering these barriers."
- Dissemination of findings to academia, industry, regulators and funders and the public: As detailed in Part 2 of this report (4.2A2) and the Deliverable D10.9 report.
difficulties and solutions:
- As part of the financial difficulties of UMINHO, Portugal, some attendees of the 2nd GP-TCM AGM could not be reimbursed of their travel costs by the host institution UMINHO. KCL made the use of its budget for unforeseeable costs and had all the outstanding claims sorted to ensure that the reputations of the EU and the FP7 GP-TCM consortium were un-affected.
- All 10 WPs underwent significant membership changes and 6 WPs had significant WP leadership changes. These membership and leadership changes might cause temporary difficulties in coordination, but they served very well to ensure that each WP had all the needed human resources, expertise and vigorous leadership and eventually a success.
- Language barriers and lack of reliable and sustainable databases and literature resources in English remain key barriers for European scientists to get access to TCM literature. This was partially solved through recruiting scientists who are competent in both Chinese and English.
overall conclusions and recommendations:
due to its personalised and function-oriented features and its holistic and pre-emptive approaches, TCM is highly complementary to the current model of Western medicine and thus represents an important field for future research. Looking forward, prospects for the whole area largely depend on how experts in different disciplines and stakeholders in different regions and sectors collaborate and how much funding is invested into this field.
priorities:
- Sustainable governmental and non-governmental funding in this promising area, e.g. supporting EU-China joint initiatives on TCM research and development, supporting training programmes on good practices in TCM research, etc;
- Interregional, intersectoral and interdisciplinary collaborations in quality control, pharmacovigilance, toxicology and pharmacology of CHMs and high-quality clinical trials;
- Special focus on research of TCM interventions, including prevention and treatment, for chronic diseases.
potential Impact:
4.1.4 The potential impact and the main dissemination activities and exploitation of results:
GP-TCM played a keen role to have a durable impact on European focused TCM research. All its major activities including development of sustainable expert networks, generation of guidelines, reviews, recommendations and priorities, as well as development of online resources and establishment of the new TCM research association were designed to have maximum impact on development of European agenda for future research and funding, as well as policy making.
1.4.1 Impact through Developing a Large Interactive and Collaborative Expert Network:
GP-TCM was characterised as an open-start and open-ending consortium. With the launch of the consortium in May 2009, scientists in Europe and China, who had been working on TCM research independently, were gathered under the project's banner and their efforts were unified to reach consensus on good practice guidelines, state-of-the-art functional genomics, as well as grand priorities, challenges and opportunities in studies of TCM.
1.4.2 Impact through Novel Literature Research Findings and Recommendations of 10 WPs:
during the lifetime of the project, the consortium reviewed existing TCM literature and other data to assess the state-of-the art omic technologies and their use in evidencing safety, efficacy and mechanisms of action of TCM. These reviews and peer discussions allowed our scientists to identify knowledge gaps and provide standardised methodologies and good practice guidelines in relevant TCM research fields. Their studies especially focused on challenging areas, which will have impact on health of EU citizens.
the findings and conclusions of the consortium WPs have been presented in the forms of reports, guidelines, handbooks, peer-reviewed scientific articles, web posts, newsletters, posters, talks, etc. The material produced by the consortium has been tailored to serve the needs of the public as well as the expert community (science, policy making and funders).
contributions by each WP to advance TCM research in Europe are summarised below:
WP1 (Quality Control):
- Compiling a "priority list of species" of particular importance for the EU;
- Report showing the different scientific names that can be assigned to the species used in a classical CHM formula Liu Wei Di Huang Wan.
- Information about the methods used to prepare the species used in Liu Wei Di Huang Wan as well as information about institutes that contain verified vouchers for these species.
- Review article: Good practice guidelines in reviewing and publishing studies on herbal medicine, with special emphasis on Traditional Chinese Medicine and Chinese Materia Medica. J Ethnopharmacol. 2012; 140: 469-475.
- Review article: The formation of Daodi Chinese materia medica. J Ethnopharmacol. 2012; 140: 476-481.
WP2 (Extraction and Component Analysis):
- Report summarising techniques and standards employed for the analysis of simple and complex herbal extracts;
- Report summarising techniques and standards employed for the preparation of extracts used in TCM;
- Report on best practice in information analysis for fingerprinting and component analysis;
- Report on the methodology used in the analysis of 'priority list preparations';
- Report on identified gaps of information and non-standard areas;
- Recommendations for future research agenda;
- Review article: The potential of metabolic fingerprinting as a tool for the modernisation of TCM preparations. J Ethnopharmacol; 2012; 140: 482-491.
WP3 (Toxicology):
- Establishing the definition to "toxicity" as "possible harmful reaction to the body which is not related to therapeutic effect;
- Classification of "toxicity" into four major groups: (i) side effects (covered by pharmacodynamics and often predictable), (ii) reactions occurirng as a result of overdose, overduration, tolerance, dependence-addiction (covered either by pharmacodynamics and pharmacovigilance), (iii) hypersensitivity, allergic and idiosyncratic reaction (covered by pharmacovigilance), (iv) mid-term and long-term toxic effects (liver, renal, genotoxicity, teratogenecity, neurotoxicity, cardiotoxicity, etc);
- Consensus on (iv) mid-term and long-term toxic effects as the most important field for omics predictive toxicology;
- Review article: Review of current and omics methods for assessing the toxicity (genotoxicity, teratogenicity and nephrotoxicity) of herbal medicines and mushrooms. J Ethnopharmacol; 2012; 140:492512.
- Review article: Pharmacovigilance practice and risk control of TCM in China. J Ethnopharmacol; 2012; 140: 519525.
- Review article: Pharmacovigilance of herbal medicines. J Ethnopharmacol; 2012; 140: 513518.
- GP-TCM collaboration led to new projects entitled "Neuro-biological mechanism of KXS on memory enhancement" and "Research of effective components from Polygala tenuifolia on improving learning and memory in vivo", which have been funded by MOST, China.
WP4 (In-vitro and In-silico Pharmacology):
- Evaluation criteria for scoring scientific articles on CHM research articles, which can be used to evaluate the quality of the scientific reporting; freely available to the scientific community for scoring scientific papers in the field;
- An online repository of literature encompassing in-vitro research and functional genomic applications of CHM, which is available to the scientific community and can be used to understand the weighed quality of papers on specific CHM subjects;
- Report of the discussion group on biological target oriented database, which is available to the public on the GP-TCM project website and can stimulate scientific debate;
- Report on quality criteria and scoring of the CHM database, which is available to the public on the GP-TCM project website and can stimulate scientific debate;
- Report on existing databases and software for in-silico studies of phytocomplexes, which is available to the public on the GP-TCM project website and can stimulate scientific debate;
- Handbook on good practice in the reporting of CHM experimental work, which is available to the scientific community on the GP-TCM project website and suggests good practices for scientific reporting in in-vitro CHM research;
- Handbook of guidelines for using in-silico tools in CHM research, which is available to the scientific community on the GP-TCM project website and suggests good practices for using databases and software in in-silico CHM research;
- Handbook for using functional genomics techniques in in-vitro CHM research, which is available to the scientific community on the GP-TCM project website;
- A questionnaire survey on scientists' views regarding the value of the application of omic and in-silico methods in TCM research, which is available to the scientific community on the GP-TCM project website and can be shared by the scientific community to repeat the analytical test in different contexts;
- A searchable online repository of critically reviewed and quality scored articles, which is available to the scientific community on the GP-TCM project website and can be used for reviewing purposes by the scientific community;
- Review article: Omic techniques in systems biology approaches to traditional Chinese medicine research: Present and future. J Ethnopharmacol. 2012; 140: 535-544;
- Review article: In-silico studies in Chinese herbal medicines' research: Evaluation of in-silico methodologies and phytochemical data sources, and a review of research to date. J Ethnopharmacol. 2012; 140: 526-534.
WP5 (In-vivo Pharmacology):
- Review article: MEDLINE-based assessment of animal studies on Chinese herbal medicine. J Ethnopharmacol. 2012; 140: 545-549.
- This review on CHM literature involving animal models resulting in the identification of the main problems in the experimental design of animal studies of CHM and the assessment of the scientific proof of the efficacy of CHM provided by animal studies. This can be used for the scientific community;
- Provision of a checklist that could help in the preliminary selection of publications lacking the most common problems of animal studies of CHM and thus would be useful for a quick search of reproducible CHM treatments 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. Therefore the checklist provides guidelines for the good practice in the conduct of CHM studies in animals and it is recommended for use by researchers. This will ensure a solid evidence base for the efficacy of CHM and for the use of more holistic approaches based upon the application of omic technologies.
- Review article: Omic techniques in systems biology approaches to traditional Chinese medicine research: Present and future. J Ethnopharmacol. 2012; 140: 535-544.
- This WP4 and WP5 joint review highlighted the application of omics and systems biology technologies in both in-vitro and in-vivo studies of TCM and can be used as a state-of-the-art report on this important issue;
WP6 (Clinical Studies):
- Provision of clinical research good practice guidelines for CHM trials. These will be recommended for use by researchers and the academic community. This will in the future ensure the provision of a solid evidence base for policy and clinical CHM use.
- Report on clinical use of CHM, specifically comparing the clinical use of different kinds of preparations of CHM. This and future research in this area will impact on good clinical practice and improve patient care.
- Report on the role of Omic technologies for CHM highlighting the general scope where future research may prove useful. This underpins the need for good practice and highlighted the importance of defining quality standards for CHM products, toxicity, differentiating the actions of single and multi-component CHM mixtures and drug responses. This is of key importance to clinicians, researchers, the pharmaceutical industry and policy makers.
- Identification of areas of clinical importance to and evidence gaps in clinical practice by engaging with TCM practitioners and Western conventional practitioners. This may have impact on integration of TCM and conventional medicine.
- Review article: Comparison of effectiveness and safety between granules and decoction of Chinese herbal medicine: A systematic review of randomized clinical trials. J Ethnopharmacol. 2012; 140: 555-567.
- Review article: Guidelines for randomised controlled trials investigating Chinese herbal medicine. J Ethnopharmacol. 2012; 140: 550-554.
WP7 (Commercial R&D and Regulatory Issues):
- A comprehensive paper providing comparisons of the different regulatory pathways for CHM products and other traditional herbal medicines including tabular comparisons and flow diagrams;
- A comprehensive analysis of omic technology being used for R&D of pharmaceuticals and how this can be applied to the future R&D of CHMs;
- An extensive collaborative international network of experts in CHM R&D and in particular, the applicable regulations and omic technology. Experts representing a good cross section of the life sciences i.e. academia, industry, government;
- Dialogue with key regulatory agencies and inclusion of Agency staff in WP7 membership.
- Review article: Future development of global regulations of Chinese herbal products. J Ethnopharmacol. 2012; 140: 568-586.
- Review article: Omics and its potential impact on R&D and regulation of complex herbal products. J Ethnopharmacol. 2012; 140: 587-593.
WP8 (Acupuncture and Moxibustion Studies):
- An effective collaborative international network of experts in acupuncture research has been identified for future clinical trial research;
- WP8 and WP6 launched an acupuncture and TCM practitioner survey across Europe and China. The survey (WP8 part) explored the acupuncture practitioners to identify the most common conditions treated by acupuncturists and compare the different conditions treated by acupuncture practitioners in China and EU. Their views on effectiveness were ascertained in order to identify areas where clinical trials on acupuncture should focus. This is of use to clinicians, government, researchers and academics in defining the topics for future clinical trials and the current evidence gaps;
- Literature reviews suggested that disease-oriented studies using the approach of multi-indexed high-throughput technologies and systems biology analyses could be a preferred strategy for future acupuncture/moxibustion research. This will be of use to all stakeholders in acupuncture research.
- Review article: A review of Omics research in acupuncture: The relevance and future prospects for understanding the nature of meridians and acupoints. J Ethnopharmacol. 2012; 140: 594-603.
- Review article: Exploring practice characteristics and research priorities of practitioners of traditional acupuncture in China and the EU-A survey. J Ethnopharmacol. 2012; 140: 604-613.
WP9 (Final Conferences):
- Through advertising the Leiden meeting we reached many colleagues in the field, resulting in new members of the network.
- The GP-TCM Journal of Ethnopharmacology Special Issue [2012; 140(3)] was freely distributed and promoted at the two WP9 meetings; it will sets standards for research on traditional medicines for a number of years to come.
- The GP-TCM Association was initiated at one of the two meetings organised by WP9.
- Identification of future stakeholders that expressed their interests in the Association through the survey spread to all participants.
- Dissemination of results to a large scientific community.
- Review article: Good Practices: The basis for evidence-based medicines. J Ethnopharmacol. 2012; 140: 455-457.
WP10 (Management):
- Identified a future research agenda for Europe and beyond through the GP-TCM survey entitled "Grand Issues in TCM Research", focusing on grand priorities, challenges and opportunities". This document will serve as a major guideline to help shape the future research focus and funding opportunities by funders, policy makers and TCM scientists'.
- Organised the publication of an open-access GP-TCM Journal of Ethnopharmacology Special Issue to provide all-in-one reference document summarising project's focus areas, literature reviews, findings and recommendations.
- The GP-TCM Research Association was founded to sustain coordination of good practice in TCM research in the EU and a stronger alliance with the other parts of the world.
- Review article: Establishing an EU-China consortium on traditional Chinese medicine research. Chin Med. 2010; 5: 42.
- Review article: Traditional Chinese medicine research in the post-genomic era: Good practice, priorities, challenges and opportunities. J Ethnopharmacol. 2012; 140: 458-468.
- Review article: Good practice in reviewing and publishing studies on herbal medicine, with special emphasis on traditional Chinese medicine and Chinese materia medica. J Ethnopharmacol. 2012; 140: 469-475.
- Review article: Network pharmacology and TCM. In: Alternative Medicine. Sakagami H, ed. Intech, ISBN 978-953-51-0903-7. This is an in-press Intech open-access book chapter, which introduced the concept of network pharmacology, TCM network pharmacology and their applications in TCM research.
- Review article: "The role of the GP-TCM Research Association to modernization and globalization of Traditional Chinese Medicine" in the book "Antitumor Potential and other Emerging Medicinal Properties of Natural Compounds" to be published by Springer.
- Review article: The quest for modernisation of TCM. Submitted to an open-access journal BMC Medicine. This manuscript reviewed the concept and practice of the "modernisation of TCM" in an international, historic and scientific perspective, leading to the three "I" principles below.
1.4.3 Impact through Developing the Three "I" Principle:
the consortium has recommended three "I"s to guide future development of TCM research, i.e. integrity, integration and innovation, which are interpreted as follows.
- Integrity
- Holism. As a holistic medicine, TCM considers the human body as a whole, emphasises the importance of functions and emotions and considers patients as part of a system interacting with its environmental factors, such as diet, climate and life style. This is embodied in TCM diagnosis, prescriptions and life style interventions.
- Ethics. Since the era of Sun Simiao (581-682) ethics has become an integral part of TCM. In ancient China, practitioners' ethics were at the centre of the TCM profession. Now, modern TCM ethics should apply to not only TCM practitioners, but also the agricultural, industrial and scientific communities, and all stakeholders. Conflict of interests should be avoided, stated and properly regulated.
- Good practice. As defined by the FP7 GP-TCM project and the GP-TCM Research Association, TCM requires continuous development, refinement and dissemination of good practice guidelines in all its multiple aspects. In such epic efforts, collaboration and sharing must be encouraged and we must strive for consensus while respecting differences. Good practice is especially required in authentication, quality control, safety assessments and sustainable use of TCM drugs and materials; agricultural and manufacturing practices; commercial and clinical practices; clinical and basic research of TCM; application of routine and emerging technologies; as well as differentiation between valuable knowledge and superstitious, erroneous and misleading anecdotes.
- Integration
- Education, clinical practice and research. Integration of these three important aspects was one of the most important achievements in modernisation of TCM.
- Cultural, philosophical and scientific perspectives. TCM is an important part of Chinese culture and is guided by Chinese philosophy. Thus, researchers of the scientific, cultural and philosophical values of TCM should collaborate with and learn from each other.
- TCM, Western medicine and modern science. In China and some other countries, TCM and Western medicine are both in mainstream healthcare and intend to complement each other. In the international context, dialogue between TCM and Western medicine needs to be promoted; China's experiences and lessons should be studied in light of modern science so that both medical traditions may contribute to forging tomorrow's medicine. Bringing evidence-based medicine to recognise the value of TCM will have to integrate a thorough rethinking of both Western and TCM practices to generate scientifically and statistically convincing evidence of the TCM-based approaches.
- Interregional, intersectoral and interdisciplinary collaborations. Due to the complexity and the vast range of TCM, collaborations between different regions, different business sectors, as well as different areas of knowledge must be encouraged in order to share resources and expertise and join forces to meet the challenges together. For example, the various distribution channels encountered in different countries must be connected in order to develop harmonised pharmacovigilance procedures suitable to rapidly and globally detect and assess warning signals for adverse events.
- Holistic, relationist and analytical, reductionist approaches. TCM emphasises holistic and relationist approaches of thinking, while Western medicine is largely based on analytical and reductionist approaches. To see both the trees and the wood, these approaches must be integrated.
- Quality, toxicology and pharmacology. These three most important aspects of TCM are so much interrelated that future training and research must further integrate these crucial elements to better ensure safety and efficacy.
- Innovation
- Modernisation of TCM is more than Westernisation. Although some achievements have already arisen through studying TCM using a Western approach, e.g. isolating pure compounds, real innovations should include both TCM-inspired changes in mode of thinking and practice in Western medicine and TCM refinements inspired by modern science.
- TCM diagnosis. Among all aspects of TCM, holistic TCM diagnosis has probably the most complementary elements to modern medical practice, including its function-oriented description of organ systems and diagnostic approach (leading to syndrome differentiation), its emphasis on modulation of functional balance, its comprehensive categorisation and interpretation of tongue and pulse patterns, its characteristic categorisation of the nature of diseases and drugs, etc. These could be important sources for developing and validating innovative mind-set, methods, tools and strategies that could complement biology-based diagnosis.
- Preventive and comprehensive interventions. TCM is characterised by both pre-emptive approaches and interventions with multiple components. It emphasises intervention before disease arises and often combines dietary advice, physical exercises such as Taijiquan (Tai Chi Chuan), meditation, herbal medicines, massage, acupuncture and moxibustion, etc. The values of these individualised and integrated approaches are important directions for future public health.
- Innovative, more robust methodology. The complexity of TCM demands novel and more robust ways of thinking, approaches, tools and methods. For example, the individualised and holistic nature of TCM requires tools for complexity research, research of the science of individuality and personalised medicine, as well as novel statistics. It also awaits the maturation of omics, systems biology and other systems-based technologies.
- Prioritisation and focus. In view of the vast areas of TCM yet to be explored and the limited resources available for such an emerging area of research in the global context, prioritisation and focus become the key to achieving real innovation. In this regard, a Steve Jobs approach for innovation is to "say no to 1,000 things" and to focus only on those that could make real differences becomes all the more compelling.
1.4.4 Impact through Developing Online Resources:
the consortium developed numerous reports, peer-reviewed articles, guidelines, databases and newsletters to support best practice, exchange of experience and strengthen EU focussed international collaboration in TCM research. These resources were made available online through various sources open to members or to the public. It is envisaged that these online resources will continue to support and enhance Pan-European studies of TCM research while being used as references by policy makers and funders.
- The GP-TCM project (archived) and the GP-TCM Research Association websites: The project website will be kept online for at least three years after completion of the project's funded lifetime to allow continuous access to our outcomes by the public.
http://project.GP-TCM.org; http://www.GP-TCM.org/
- The GP-TCM public deliverable reports ranging from technical reports, databases, guidelines to meeting proceedings open access (74 documents)
http://project.GP-TCM.org/about/deliverables/
- The GP-TCM internal deliverable reports members only (100 documents)
- The GP-TCM Special Issue open access (20 review articles)
http://www.sciencedirect.com/science/journal/03788741/140
- The GP-TCM Newsletters open access (54 issues published between October 2007 and October 2012): http://www.GP-TCM.org/news/
- GP-TCM Guidelines for randomised controlled trials investigating CHM
http://www.GP-TCM.org/2012/12/GP-TCM-guidelines-for-randomized-controlled-trials-investigating-chinese-herbal-medicine-chm-2/
1.4.5. Impact through Founding a New Association:
with the exception of the GP-TCM consortium, there was no pan-European organisation to coordinate TCM research in Europe. Hence, the consortium established a new organisation to carry on coordinating TCM research after completion of the project and ensure a sustainable development of TCM research in Europe and worldwide. The GP-TCM Research Association was officially at a dissemination event organised by WP9 of the GP-TCM project, i.e. the GP-TCM Congress held in Leiden, the Netherlands, 16th 18th April 2012.
the Association is a non-for-profit organisation, which is currently in the process to be registered as a charity in the UK. It will be dedicated to promoting high-quality evidence-based research of TCM through developing, disseminating and implementing good practice. The objectives for which the Association was established are:
- Perpetuate the interactive network established by the FP7 GP-TCM consortium;
- Promote discussion and implementation of good practice in TCM research and development, including the use of sustainably sourced materials;
- Advocate high-quality evidence-based research and development on TCM as well as on its integration with conventional medicine;
- Organise and co-organise scientific meetings and specialist courses;
- Nurture young TCM researchers at different levels in an interdisciplinary approach, including BSc, MSc, PhD and post-doctoral programmes;
- Facilitate collaborations and sharing of resources, expertise and good practice among members, industry and regulatory agencies;
- Encourage collaborations with existing relevant societies, consortia and organisations;
- Strengthen interdisciplinary, interregional, and intersectoral collaborations in TCM research and development;
- Perpetuate good practice in publishing TCM research outcomes;
- Disseminate scientific research outcomes and latest developments in regulatory sciences to stakeholders, industry, professional groups and the public.
1.4.6. Impact through Dissemination Activities:
GP-TCM was keen to disseminate findings on good practice issues and other important findings on the safety, efficacy and mechanisms of CHM and acupuncture to stakeholders and the public. Through agreed best practice, guidance and dissemination, the consortium aimed to harmonise activity to adhere to highest principles of scientific rigor within this complex field.
to achieve the consortium's dissemination goals, the following main activities were undertaken to inform the findings of the network to the widest possible audience including scientific community, industry, policy makers and the public:
- GP-TCM website and monthly newsletters;
- Consortium publications such as deliverable reports (public), periodic reports, a journal special issue and many other papers in scientific journals and books;
- Seminars, talks, workshops, demonstrations, interview reports by radio, TV, newspaper, specialist magazines and websites aimed at spreading the accruing research and review results to large communities;
- The Sino-EU GP-TCM Workshop (The GP-TCM Kick-off meeting, Beijing, China, 2009), Annual Meetings (Henley, UK, 2010; Braga, Portugal, 2011), the Final Conference and the GP-TCM Congress (Kerkrade and Leiden, the Netherlands, 2012); the 2012 Shanghai International Conference on TCM and Natural Medicine and the GP-TCM Research Association First Annual Meeting (Shanghai, China, 2012); and the International Symposium on Standardisation and Cooperation of TCM (Beijing, China, 2012);
- Establishment of the GP-TCM Research Association to sustain coordinated TCM research in Europe. Since its official launching in April 2012, the Association has joined forces with the GP-TCM project in dissemination efforts.
1.4.7 Impact through Exploitation of Results and Resources Assembled by the Project:
- Made the best use of the ever-expanding FP7 GP-TCM network collaborating on good practice of TCM to establish an international Association, the GP-TCM Research Association.
- Made the best use of the communication and dissemination tools such as GP-TCM project website, newsletters and Essential Manual to build the GP-TCM Research Association website and newsletters;
- Informing the outcomes of the GP-TCM "Grand Issues in TCM Research" survey to stakeholders in the EU and China to serve forging an EU agenda for future TCM research and to guide future funding;
- Made the best use of GP-TCM agreements on state of the art, definition of good practice, guidelines and principles, priorities, challenges and opportunities to develop scientific publications;
- One PhD thesis on CHM was completed as part of WP5 literature studies;
- Three rounds of bidding for Seventh Framework Programme (FP7) Marie Curie Initial Training Network funding were launched in 2009, 2010 and 2011, respectively, with the expertise pool of the GP-TCM project;
- GP-TCM partnership between University of Vienna and Chinese Academy of Sciences led to successful seventh Framework Programme (FP7) in 2012;
- GP-TCM partnership between Chinese Academy of Medical Sciences and European partners led to successful funding from the Chinese government in 2012;
- Collaborations in the GP-TCM project and the GP-TCM Research Association led to closer collaborations and partnerships between many members. To mention a few, (i) the sister centre relationship between Shanghai Research Centre for TCM Modernization, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (China) and the Institute of Pharmaceutical Sciences, Department of Pharmacognosy, Karl-Franzens-University Graz (Austria) was established in 2012; (ii) a memorandum of understanding was signed between King's College London (UK) and Chengdu University of TCM (China) to jointly support research and teaching of integrative Chinese medicine; and (iii) a new partnership between China Academy of Chinese Medical Sciences (China) and The Norwegian University of Science and Technology (Norway).
list of Websites:
http://project.GP-TCM.org
