Report from the WHO Collaborating Centre for International Drug Monitoring

Transcription

1 Report from the WHO Collaborating Centre for International Drug Monitoring Activities July 2010 June 2011

2 1. Introduction and Administration The activities of the WHO Collaborating Centre for International Drug Monitoring (also called the Uppsala Monitoring Centre, UMC) are based on an agreement dating from 1978, updated in December 2001, between the World Health Organization and the Swedish Government. The Centre is a foundation headed by a board of six members with personal deputies, three appointed by the Swedish government, three appointed by WHO. The Chairman of the board is Mr Anders Milton. Director of the Centre is Marie Lindquist. The organization is managed on a day-to-day basis by an Executive Committee consisting of the Director and the departmental Managers. At the end of the period the UMC had around 75 employees, of whom several were on parental or study leave. Funds for operation of the Centre, in the order of 110 million Swedish Kronor, were raised through the provision of products and services to paying clients. Supply of the WHO Drug Dictionary to the pharmaceutical industry accounted for approximately 95% of these receipts. Other income sources are training, other database services, and consultancies to paying customers. During the period of this report, the UMC received project grants in respect of involvement in the European Commission FP7 Monitoring Medicines and PROTECT projects, and funds were provided by WHO for the post of Vaccine Safety Specialist. 2. WHO Programme countries During the period July 2010 to June 2011 the following countries became full members of the WHO Programme for International Drug Monitoring: Slovenia (September 2010), Côte d Ivoire, Iraq (October 2010), Burkina Faso and Cameroon (November 2010), making a total of 104 members at the end of the period. In addition a number of other countries applied for membership and thus became associate members of the Programme: (in date order) Burundi, Albania, Maldives, Liberia, Mauritius, Gambia, Cape Verde and Niger. 3. Adverse reaction reporting VigiFlow 4.2 was released in December 2010, with features for copy functions of fields to speed up data entry, and the submission manager contained some new features such as allowing use of both pdf and E2B as formats in a submission. A first phase of implementing Automatic E2B transmission (gateway functionality) has been developed with a dash-board for monitoring progress. This last development was made in collaboration with Swissmedic, and is available on request to other VigiFlow users. The VigiFlow interface has also been translated to Russian. There was also a minor release of VigiFlow in March 2011, mostly containing bug fixes. The CemFlow tool will be used to support data collection in CEM programmes. The first pilot countries are now collecting cohort data for malaria in the system. During the year further developments have taken place to adapt CemFlow to fit collection of data with ARV treatment; Version 3.0 of CemFlow was released for some users in June 2011 with many new features, such as the possibility to partly work off-line if internet access is not reliable. 4. Feedback of information to National Centres 4.1 Output from Vigibase VigiSearch/VigiMine is a free web-based service for national centres for retrieving information from VigiBase. An updated version (3.3) was put into operation in February The improvements in this release were for increased availability of ICSRs. Previously some reports were withheld due to inconsistency of the ICSRs. This change has made it possible to have an additional 400,000 ICSRs available for searches in VigiSearch and VigiMine. In the import process some drug names do not match entries in the WHO Drug Reference List. These lines have not previously been included in the pdf of the reports, due to a bug. From now on they are

3 listed in the drug section under assessment, and the reported drug names are also included. An additional release was made in May 2011 version The improvement in this release was for increased transparency of reported adverse reaction on the ICSRs (the release notes for VigiFlow and VigiSearch have more information). 4.2 Newsletters and publications The 2010 edition of Viewpoint was distributed widely at meetings and by post, alongside downloadable copies from the UMC website. Uppsala Reports, UMC s quarterly review of the WHO Programme, the work of UMC and of pharmacovigilance developments throughout the world, continued to be published in print and pdf form four times per year, and distributed worldwide. The UMC contributed background information for the WHO Pharmaceuticals Newsletter produced by the Quality Assurance and Safety of Medicines (QSM) section at WHO Headquarters, and also contributed to Reactions Weekly with summary information from VigiBase on drug adverse reactions referenced in Reactions Weekly that are published in literature for the first time Services provided via digital media The UMC website is a major source of information about UMC, WHO and the work of its Programme for International Drug Monitoring. External web monitoring tools suggest a weekly visiting rate of 800 during the period, excluding visits to the Products and Services section. In early 2011 the UMC homepage was completely revised and extended. The communication tool Vigimed had been available for exchange of information and views between national pharmacovigilance centres in the WHO Programme since The original technology used was simple but had serious limitations. After an assessment of new software, a platform for interactive web-based collaboration groups, with the possibility of moderated discussion groups, was implemented and taken into use in early The increased complexity of the new system caused an initial reduction in the frequency of communications shared between network members. Efforts will be made to support and train participants to utilize the features offered by the new Vigimed system. UMC and WHO supported the establishment of an electronic network for pharmacovigilance specialists in Africa, PV Sans Frontières. The Products and Services department of UMC continued to maintain its website aimed at customers of UMC s commercial products and services ( Ad hoc retrievals for National Centres Requests for database investigations are directed to the UMC from investigators in industry, academia and consumer organizations. Centre staff responded to 64 requests for database retrievals from external sources during the period. The inquirers were provided with the results together with the agreed Caveat Document. In addition UMC has supported National Centres in their searches on 57 occasions. 4.5 Detection and analysis of adverse reaction signals The UMC research team has collaborated with the signal team on streamlining the signalling process and in developing a policy and processes for defining and dealing with priority signal areas. In order to reduce the number of known adverse reactions signalled in the automated detection process, a method for identification of free text extraction using fuzzy text matching from Martindale Extra Pharmacopoeia has been implemented, whereby reactions listed in this standard information source are filtered out. To get more complete information on known adverse reactions, the data extraction method has also been extended to run on EU SPC texts for 414 centrally-registered products.

4 Work started on the development of phase II of the documentation grading tool a relevance scoring of reports based on the clinical usefulness of the data for case analysis and causality assessment. A pilot implementation has been undertaken integrating electronic patient records in the routine signal analysis process. The Signal document was published in September 2010 (4 signals, 1 new drug overview), December 2010 (3 signals, 2 new drug overviews), February 2011 (3 signals, 2 overviews) and May 2011 (4 signals, 1 overview). A policy for publishing signals has been agreed by ACSoMP. 5. Collaboration with WHO headquarters, Geneva 5.1 WHO Public Health Programmes With financial support from WHO the UMC employs a Vaccine Safety Specialist who works closely with other UMC staff, WHO HQ and countries in the Global Network for Postmarketing Surveillance of Newly Pre-qualified Vaccines. A meeting of the PMS Network was held in Dakar, Senegal, in October During the year China joined the Network and the UMC vaccine expert therefore visited China for the baseline country assessment. UMC signed an agreement with the WHO department of Immunization Vaccines and Biologicals (IVB) to provide the PaniFlow tool for management of AEFIs associated with donated A/H1N1 vaccines distributed to selected countries by WHO. This agreement ended in September UMC has been a reference partner to IVB in the development of the so-called Blueprint project, which aims at improving vaccine pharmacovigilance globally in a sustainable manner. Pharmacovigilance methods that complement regular spontaneous reporting systems are being implemented in public health programmes. Cohort Event Monitoring (CEM) of medicines in tuberculosis, malaria and HIV will help address gaps in existing knowledge on adverse events with newly-introduced medicines. By introducing adverse reaction monitoring as a standard of care in cohorts of patients, using normal ADR reporting forms for recording suspected reactions (Targeted Spontaneous Reporting, TSR), the sustainability of routine safety monitoring in public health programmes in resource limited settings will be tested. The UMC is a technical partner to the WHO departments of HIV/AIDS and QSM in the implementation of a pharmacovigilance project funded by the Bill and Melinda Gates Foundation. The project involved the development of a new version of CemFlow, the data management tool supporting Cohort Event Monitoring (CEM). Site visits were made to Kenya and Tanzania to prepare for the setting up of a CEM programme and a TSR system for antiretroviral medicines. A training course was organized in Mombasa, Kenya, in June 2011 focusing on CEM for anti-malaria medicines and TSR for anti-retrovirals. Six African countries participated in the training, which was sponsored by the European Commission through the Monitoring Medicines project. Collaboration between WHO and the Global Fund to fight AIDS, Tuberculosis and Malaria (GFATM) led to the development of a joint pharmacovigilance strategy for country implementation in HIV, TB and malaria programmes. The UMC was represented in a stakeholders meeting in Accra, Ghana, in November 2010 at which the strategy was discussed. One result of this collaboration was a Pharmacovigilance Toolkit that is maintained by the WHO Collaborating Centre for Advocacy and Training in Pharmacovigilance in close collaboration with UMC and WHO-HQ. 5.2 WHO Advisory Committee on Safety of Medicinal Products WHO-QSM, Geneva has established an Advisory Committee on Safety of Medicinal Products (ACSoMP). ACSoMP had its eighth meeting in April 2011, with Sten Olsson, Marie Lindquist Ralph Edwards and Jerry Labadie representing the UMC. Summaries of results of the

5 deliberations were published in WHO Pharmaceuticals Newsletter (No 3, 2011) and in Uppsala Reports 54 (July 2011). The issue of data access policy relating to the wider openness of the WHO database of adverse drug reaction reports has been reviewed by ACSoMP, and a recommendation made that there should be a stepwise implementation of wider public access to data, starting with publication in WHO Pharmaceuticals Newsletter of the Signal document. The data access policy will be implemented with due consideration of the resources involved in the likely ensuing demands from users, as well as ethical considerations around the use of sensitive data. The UMC is involved in on-going work led by WHO HQ and ACSoMP to agree on a set of pharmacovigilance indicators which would permit analysis of the success of systems of medicines and patient safety. 5.3 Patient Safety In partnership with WHO-QSM the UMC is working on several projects funded by the European Commission Research Directorate, some of which have finished, and others are progressing well. The work packages are: 1. Supporting and strengthening consumer reporting of medicine-related problems A draft guideline for setting up a consumer reporting system is available (and will be printed later in 2011). This guideline is expected to prepare and align pharmacovigilance centres within and outside the EU region towards a more inclusive pharmacovigilance, and usher in the public as important stakeholders. The management tools to support public reporting will be formally launched in tandem with the EU legislation on consumer reporting. 2. Understanding medication errors A tool has been developed (the 'P' method), to interrogate pharmacovigilance datasets, to identify preventable ADRs within these databases. The 'P' method has been shared with ten countries for peer review, and will be validated with their national pharmacovigilance data. 3. Better use of existing global pharmacovigilance data Seeking to maximize the use of national and global data, a knowledge discovery tool has been developed that can detect patterns indicating dependence potential from ADR data. This research clearly demonstrates the potential for an earlier detection of dependence-producing properties of medicines from accruing ADR data. A comprehensive method has also been developed with the capacity of identifying instances where unexpected lack of therapeutic effect may be related to substandard or counterfeit medicines or antibiotic resistance. 6. Support to development of National Centres and UMC visits User group meetings were held for VigiFlow and VigiSearch at the National Centres meeting in Accra, Ghana in November 2010, where feedback was sought for the two systems. The UMC-Africa office in Accra, Ghana continued to lead training and resource development in Africa, while strongly linked with UMC for technical purposes, and as a WHO Collaborating Centre. The pharmacovigilance programme in China has expanded rapidly in the last few years resulting in the creation of a major national database with several million records. This database is stored in Chinese characters and is not available to the international community through VigiBase. In 2008 the UMC initiated a collaboration project with the Chinese national adverse reaction monitoring centre. This project intensified during the year leading to the signing of a collaboration agreement with the following components: Upgrade of the Chinese version of WHO-Adverse Reaction Terminology Improvement of the Drug Dictionary specifically for China

6 Establishment of a data exchange platform allowing Chinese ICSRs to be available through Vigibase Chinese-English translation standards Establishment of signal detection and data-mining systems for Chinese national database The two parties formally signed the collaboration agreement met in Beijing in July The Government of India set up a new national system for pharmacovigilance (PvPI) in July 2010 under the leadership of the Drugs Controller General of India. Since it was decided to use VigiFlow, developed and maintained by UMC, as the national system for case management, UMC became heavily involved in training of technical associates in charge of data management in local centres. By the end of the period approximately 40 local centres had received VigiFlow access. UMC participated in planning meetings for the PvPI in New Delhi in November 2010 and February 2011 (training session). Coordination of the PvPI was transferred to the Indian Pharmacopeia Commission in early Training in pharmacovigilance UMC continued to provide support and data management facilities for CEM programmes for anti-malaria medicines in Nigeria, Tanzania and Zimbabwe. An analysis of ICSRs in VigiBase related to anti-malaria medicines was carried out in collaboration with academic partners and published in Malaria Journal in early UMC also contributed to the development of a section applicable to malaria treatment of the WHO Pharmacovigilance Toolkit. In May 2011, the 13th International Pharmacovigilance Course was organized by UMC in Uppsala. The two-week course was attended by participants (depending on module) from all over the world. The group consisted of staff from regulatory authorities, the pharmaceutical industry and other institutions. The majority of lectures during the course were recorded (and are now publicly available as web-based training). UMC representatives contributed to a regional pharmacovigilance training organized by WHO- HQ in New Delhi, India in February UMC was also involved in a medication errors course organized by the Moroccan pharmacovigilance centre in March 2011 and a course on CEM and targeted spontaneous reporting, organized by the Kenyan pharmacovigilance centre in June 2011 (both activities sponsored by the Monitoring Medicines project). WHO-QSM organized an advanced training course for African pharmacovigilance consultants in Lome, Togo in September 2010 with contributions from experts from UMC. The 33 rd Annual Meeting of representatives of National Centres participating in the WHO Programme held in Accra, Ghana included a pre-meeting for beginners with an introduction to the WHO Programme and basic pharmacovigilance, as well as VigiFlow and VigiSearch/VigiMine user groups, both for new and experienced users. On-line training is provided for the WHO Drug Dictionary and VigiFlow. The collaboration between the UMC and the Department of Toxicology, University of Uppsala, in providing a 5-week undergraduate course on drug safety and pharmacovigilance to pharmacy students continued in November 2010 and February Release of adverse reaction information to external inquirers Since the WHO 10th International Conference of Drugs Regulatory Authorities (ICDRA) meeting in Hong Kong, 2002 recommended: Opening access to the WHO database to all stakeholders with a genuine public health interest and ability to evaluate such case information, case information from all countries participating in the WHO Programme is released to any inquirer fulfilling these criteria. Centre staff responded to 64 requests for database retrievals during the period. The inquirers were provided with the results together with the agreed Caveat Document. In addition UMC has supported national centres in their searches on 57 occasions.

7 9. Development of computer support systems The production and development team of computer support systems continued to further improve the production environment for all VigiBase operations; from the processing of received ICSRs and entering of drug information into the database, through to extraction of data into the WHO Drug Dictionary Enhanced and VigiBase Export. VigiFlow release 4.2 was enhanced to capture AEFI-specific data by addition of new data entry fields to accommodate the needs of the Global Network for Post-marketing Surveillance of Newly Prequalified Vaccines (PMS Network). These fields will be tested by PMS Network countries before they are made available for general use. One of the results of the 2010 annual meeting of the PMS Network in Senegal was an increase in real-time AEFI reports submission, from a total of 370 reports by 2 countries (24 June 2010) to 2,024 reports by 5 countries (23 June 2011). The Vaccine Dictionary first version has been completed and contains data on 166 WHO prequalified vaccines. The content will be updated with new vaccines as they are pre-qualified by WHO. The ultimate goal is to list all available vaccines in the Vaccine Dictionary. From 27 to 30 September 2010 and 13 to 18 December 2010 UMC s Vaccine Safety Specialist was a member of the team that conducted the WHO assessment of the Chinese vaccine regulatory system in Beijing. During the period China joined the PMS Network. A pilot project with CDC/VAERS (USA s Vaccine Adverse Event Reporting System) has been started in which the VAERS database and the AEFI reports in Vigibase will be compared and experiences and competence on AEFI-specific data-mining and analysis strategies exchanged. WHO-DD Browser is available to all National Centres; after signing an agreement, they can access information about medicinal products and herbals from around the world. 10. Terminologies 10.1 WHO Drug Dictionary As of September 1, 2011 WHO Drug Dictionary Enhanced contained: 239,491 unique names 1,841,271 different medicinal products and trade names, including, for example, form and strength information 11,520 different ingredients mentioned in these products The entries are from 120 countries Adverse Reaction Terminology The WHO-Adverse Reaction Terminology (WHO-ART) is maintained by the UMC and developed in English. WHO-ART files are distributed annually to national centres, except to ICH countries or national centres using VigiFlow. MedDRA was introduced into the WHO ICSR database in March 2008, and is used alongside WHO-ART. MedDRA is used in a majority of ICSRs sent to the UMC, and searches in VigiBase can be made using either WHO-ART or MedDRA. Since July 2010, 29 new terms have been included in the WHO-ART hierarchy, 7 of these being preferred terms. The WHO-ART MedDRA bridge linking WHO-ART Preferred terms to MedDRA terms is updated annually and was distributed to all WHO-ART customers with the March release of WHO-ART. A number of national centres in the Programme, companies and other institutions outside the WHO Programme continue to use WHO-ART in their drug safety work.

8 11. Research and development Since September 2009, Uppsala Monitoring Centre co-leads Work package 3: Methods for signal detection, within the Pharmacoepidemiological Research on Outcomes of Therapeutics (PROTECT) collaborative European project. This public-private partnership brings together groups at regulatory agencies, academic institutions and pharmaceutical industry to work towards the common goal of improved methods and processes for pharmacovigilance. As part of the PROTECT project, a major effort is being undertaken to develop and refine methods for signal detection and refinement in electronic patient records. Within the PROTECT project UMC has also contributed to several of the sub-projects concerning various aspects of signal detection. As part of the FP7 Monitoring Medicines project a pilot project has been completed aimed at identifying drug dependence indicators for medicines in the WHO global individual case safety report (ICSR) database. Results from the study were published as a letter in the European Journal of Clinical Pharmacology in December The pilot project for development of tools to identify reports indicating substandard medicines was completed (also part of FP7 Monitoring Medicines). One finding from this project was selected for oral presentation at 10th Congress of the European Association for Clinical Pharmacology and Therapeutics (EACPT) in Budapest, Hungary in June The UMC has continued to develop methods for extraction of adverse drug reaction terms from free text in standard reference sources of drug safety information. The purpose is to allow a (semi-)automated process for filtering out already known adverse drug reactions from a dataset of potential safety issues meriting in-depth clinical review. This is anticipated to free up substantial resources for more productive clinical assessment. The UMC has done research within paediatric pharmacovigilance developing methods and processes to detect previously unknown ADRs in the child population and to characterize ADRs in children. During the last year two peer-reviewed articles and one editorial on the subject were published with UMC staff as first authors. The UMC continued its research on ADRs caused by drug-drug interactions, which during the last year resulted in two published articles studying characteristics and potential identifiers of drug-drug interactions. There were three PhD projects underway, concerning aspects of drug safety in paediatrics, drug interactions, and benefit-risk assessment. It is likely that these will be concluded within the next calendar year, and will considerably add to the general development of services offered by the UMC and the WHO Programme. The UMC continued to develop its analytical tools in order to bring the latest developments into the routine work of signal detection and analysis. A key move forward has been a contract with the UK-based organisation THIN (The Health Improvement Network) which allows access to around 6 million anonymised health care records, which will add a rich source of data with the particular value of being able to examine the context and chronology of patient safety concerns. The usefulness of this data will be examined by its contribution to UMC signal detection. Early indications are that even access to 9 million patient histories are limiting for the detection of rare but important drug signals, however there is huge potential in signal strengthening and understanding that goes beyond the recognition of a possible causal relationship between a drug and an ADR. We will be able to answer more of the questions: Why did it happen? Who has the problem? What happened? What does one do if one has this ADR? The data mining method UMC uses to analyse observational data has been evaluated as part of in the Observational Medical Outcomes Partnership led by the US FDA, FNIH, and PhRMA (representatives of the US pharmaceutical industry). The purpose of the project is to evaluate different proposed methods, and different possible sources of longitudinal healthcare

9 information for early discovery of patient safety or public health issues. Overall the UMC data mining method was among the best methods, which was a very encouraging result and had the consequence of expressions of interest from a number of healthcare organisations in using the UMC approach. Overall, the research work of the UMC is committed to the completion of EU FP7 and PROTECT projects together with the novel work included in the PhD projects. The acquisition of more detailed case data as a result of patient safety projects and patient reporting will lead to the further development of the UMC pilot work in text analysis, which has been a necessary aspect of some of the previous work. The broad range of articles and commentaries by UMC staff in various media continued. During the year approximately fifteen articles by UMC staff appeared, in Drug Safety, International Journal of Risk & Safety in Medicine, European Journal of Clinical Pharmacology, Pediatric Drugs, Malaria Journal and Statistical Analysis and Data Mining. UMC s Medical Advisor had a regular commentary column in Drug Safety Impact of pharmacovigilance UMC is working together with ACSoMP to produce a set of indicators for impact assessment. Candidate outcome/impact indicators have been classified as core, complementary and optional following consultations with national centres, UMC-Africa and ACSoMP members. Candidate indicators possess certain properties, such as being easy to measure and interpret, help obtain data inexpensively, do not require a high level of expertise to use, are reproducible, sensitive enough to allow the detection of pharmacovigilance problems but sufficiently robust to serve as efficient monitoring tool. With this set of indicators, robust performance evaluation, comparison of level of maturity and self-improvement of centres will be possible. UMC is contributing to the development of a WHO global strategy for best practice in pharmacovigilance. A pharmacovigilance toolkit has been produced in collaboration with UMC-Africa. Regular surveys were made of the needs and levels of satisfaction with services provided to national pharmacovigilance centres, and for proposals for improved services. 12. Co-operation with other organizations 12.1 WHO and its Collaborating Centres UMC s Vaccine Safety Expert was in the global expert group that revised the WHO Advanced Course on AEFI Monitoring and Causality Assessment. The UMC was represented at the meetings of the Global Advisory Committee on Vaccine Safety (GACVS). The UMC s very close collaboration with WHO-QSM, manifested in regular exchange of e- mails or telephone calls on a daily basis, continued. Representatives of UMC and QSM management ran planned monthly teleconferences. Representatives of WHO-QSM are members of the UMC Board of Directors and participated in all its meetings. The UMC was represented at the annual meeting of the Advisory Committee on Safety of Medicinal Products (ACSoMP). Training courses and Technical Briefing Seminars organized by WHO-QSM included tutors from the UMC. The Manager of the WHO Programme contributed to UMC training activities. The Monitoring Medicines project, funded by the European Commission, is managed in close collaboration between WHO-QSM and UMC. WHO-EURO was continuously kept informed about progress in this project. WHO disease programmes, particularly those for malaria, HIV/AIDS and TB have become more active in pursuing pharmacovigilance activities and have involved the UMC in the technical implementation. Interactions between UMC and WHO-IVB on vaccine safety monitoring also increased dramatically.

10 UMC and WHO-ICD have interacted for several years concerning nomenclature and classification issues. A new component of classification of traditional medicines has recently been added to this collaboration. UMC has in several instances provided services to the different WHO departments on the basis of formal contracts or Agreements on Performance of Work. The UMC has one representative in the WHO Working Group for Drug Statistics Methodology under the aegis of the WHO Collaboration Centre for Drug Statistics Methodology in Oslo. Within this group the UMC has an observer role, attending all meetings (two per year: one faceto-face meeting and one video/telephone conference). The UMC actively takes part in the discussions held at the meetings. At the two meetings in 2010 and 2011 the UMC representative especially focused on the discussions regarding how to cope with the ATC classification of vaccines. The UMC representative was Malin Jakobsson. A very close and important relationship has developed between the UMC and the WHO Collaborating Centre for Advocacy and Training in Pharmacovigilance in Accra, Ghana. Activities are based on an annual action plan developed jointly between the two centres. A communication platform has been set up to facilitate exchange of information and documents and sharing of joint resources International Conference on Harmonization (ICH) Since 2006, co-operation has been in place with ISO to develop ICH-proposed standards into fully international ISO standards. ICH M5 (standards and data elements for drug dictionaries), and E2B (electronic transfer of Individual Case Safety Reports (ICSRs)) have been referred to ISO for development, including the definition of the technical formats for data exchange. In 2010 ISO decided not to take on the appointment of a maintenance organization for the content deliverables (the controlled vocabularies), a reversal of a previous decision. ICH participants have been well represented in the ISO task force teams, and the UMC activities relating to ICH M5 and E2B have been focused mainly on monitoring ISO progress. In 2010, work started in the ICH working groups on the development of implementation guides for the coming ISO standards. This work is now in its final stages. Since the ISO decision not to continue work on appointment of a maintenance body, ICH have taken on this task. UMC has throughout this process defended the existing WHO standards in this area, and maintained the view that UMC and WHO must have a key role in the maintenance of standard controlled vocabularies which are used for international exchange of medicines safety data. UMC is now negotiating with key stakeholders with the aim of coming up with a concrete proposal that will satisfy the needs of ICH, but at the same time maintain the viability of the WHO Drug Dictionaries European Union (EU) / European Medicines Agency UMC has intensified its working relationship with the European Medicines Agency (EMA) in the area of scientific methodology for identification and analysis of safety problems. In 2009, funding from the European Commission was granted for an Innovative Medicines Initiative (IMI) project, PROTECT, with EMA as lead and UMC as one of the partners. The European Commission also funded the Monitoring Medicines project, which is managed by the UMC in close collaboration with WHO QSM. UMC has for several years sought to improve the efficiency of reporting from European Union countries to the WHO global individual case safety report database, VigiBase, through a collaborative effort with EMA whereby the Eudravigilance gateway for report exchange would be made available for transfer of reports also to VigiBase. However, the EMA stance remained that a collaborative solution could not be instituted until new EU pharmacovigilance legislation had been implemented in 2012, due to lack of resources to extend the gateway capacity. A discussion has been started with EMA colleagues on how EMA can fulfil their obligations as set out in the new legislation to provide data from Eudravigilance promptly to VigiBase.

11 12.4 International Organization for Standardization (ISO) The standardisation process, which started in 2003 with UMC/WHO proposing to ICH that the WHO Drug Dictionary should be used to facilitate coding of medicinal products for international exchange of ICSRs (ADR reports), has since 2006 been taken over by ISO, on request by ICH. Two ISO task forces have been set up specifically for the purpose of developing new standards based on ICH draft guidelines; M5 and E2B(R). In the ISO forum, the work items are referred to as Identification of Medicinal Products (IDMP) and Individual Case Safety Reports (ICSR). 13. Meeting of representatives of National Centres The 33 rd Annual Meeting of representatives of National Centres participating in the WHO Programme was held in Accra, Ghana, hosted by the Foods and Drugs Board of Ghana, and attracted nearly 150 representatives from 50 countries. A restricted report of the meeting was distributed by WHO HQ in January Other presentations and meetings UMC personnel continued to attend a wide range of international technical and professional meetings, making presentations and displaying posters of UMC s work and research. In , some of the major events included: the ISPE annual meeting in Brighton, UK, X Annual Pharmacovigilance Journey in Valladolid, Spain, ISoP annual scientific meeting in Accra, the annual Mexican Association of Pharmacovigilance in Léon, the Middle East Regulatory Affairs Conference in Amman, Jordan, ISoP training courses in Minsk, Belarus, among others. 15. Visitors to the UMC Visitors during the period included: Mr Mohammed Solayman of the Clinical Pharmacy Department, Ain Shams University, Cairo, Egypt in July, Linda Härmark and Florence van Hunsel from Lareb foundation, the Netherlands in August, Mr Timo A Tanninen, Councillor for Social Affairs and Health, Finland in October, post graduate diploma course students of the Empower School of Health, New Delhi, in November, Dr Rida Al-Tubuly, head of registration department of the medicines regulatory authority of Libya in November, Five Country Safety Leads for the Nordic countries from Pfizer Tina Perborn (Sweden), Marianne Svith Hansen (Denmark/Iceland), Ewa Ahnemark (Sweden), Tor Seim (Norway) and Timo Ovaska (Finland) in November, and Chris Duncombe, Bill and Melinda Gates Foundation (BMGF) Programme Co-ordinator for HIV/AIDS at WHO, and Dr Geraldine Hill, CEM Consultant at WHO, in December The international secretariat of ReAct, Andreas Heddini, executive director, Otto Cars, chairman of the international secretariat and Cecilia Stålsby-Lundborg, scientific adviser in January; Mr Heddini returning with Dr Niyada Kiatying-Angsulee from Chulalongkorn University, Thailand in March, Bob Allkin of Royal Botanic Gardens, Kew in February, David Healy, Professor of Psychiatry, University of Cardiff in Bangor, Wales in March, Luisa Helena Valdivieso of the Pharmacovigilance Centre at the Faculty of Pharmacy of the Universidad Central de Venezuela in Caracas in May, researcher and campaigner Ulf Jonasson in May, and Sujith Chandy, Department of Clinical Pharmacology and Head of Pharmacy at Christian Medical College, Vellore in May 2011, also visited.

12 16. Publications during 2010/2011 Tengstrand M, Star K, van Puijenbroek EP, Hill, R. Alopecia in Association with Lamotrigine Use: An Analysis of Individual Case Safety Reports in a Global Database. Drug Safety 2010; 33 (8): Caster O, Norén GN, Madigan D and Bate A. Large-scale regression-based pattern discovery: the example of screening the WHO global drug safety database. Statistical Analysis and Data Mining (2010), 3: doi: /sam Olsson S, Pal SN, Stergachis A, Couper M. Pharmacovigilance Activities in 55 Low- and Middle-Income Countries: A Questionnaire-Based Analysis. Drug Safety, 33 (8), 1 August 2010, Kshirsagar NA, Olsson S, Ferner RE. Consideration of the desirable features and possible forms of practical indicators of the performance of pharmacovigilance centres. International Journal of Risk & Safety in Medicine; 22 (2010), Edwards IR, Lindquist M. First, Catch Your Signal! Drug Safety 2010; 33 (4): Edwards IR, Graedon J, Graedon T. Placebo Harm. Drug Safety 2010; 33 (6): Hauben M, Norén GN. A Decade of Data Mining and Still Counting. Drug Safety 2010; 33 (7): Edwards IR, Graedon T. What do stakeholders think about pharmacovigilance? Drug Safety 2010; 33 (8): Caster O and Edwards IR. Reflections on Attribution and Decisions in Pharmacovigilance. Drug Safety 2010; 33 (10): Edwards, IR. African Heat. Drug Safety, Volume 33, Number 12, 1 December 2010, (5). Caster O, Edwards IR, Norén GN, Lindquist M. Earlier discovery of pregabalin s dependence potential might have been possible (Letter to the Editors). Eur J Clin Pharmacol. DOI /s Strandell J, Caster O, Bate A, Norén GN, Edwards IR. Reporting patterns indicative of adverse drug interactions a systematic evaluation in VigiBase. Drug Safety, 2011; 34(3): Strandell J, Wahlin S. Pharmacodynamic and pharmacokinetic drug interactions reported to VigiBase, the WHO Global Individual Case Safety Report Database. Eur J Clin Pharmacol Jan 21. Star K. Detecting Unexpected Adverse Drug Reactions in Children. Pediatric Drugs. 2011; 13(2): Star K, Caster O, Bate A, Edwards IR. Dose Variations Associated with Formulations of NSAID Prescriptions for Children: A Descriptive Analysis of Electronic Health Records in the UK. Drug Safety. 2011;34(4): Star K, Norén GN, Nordin K and Edwards IR. Suspected Adverse Drug Reactions Reported For Children Worldwide: An Exploratory Study Using VigiBase. Drug Safety, 2011; 34(5): Kuemmerle A, Dodoo ANO, Olsson S, Van Erps J, Burri C, Lalvani PS. Assessment of global reporting of adverse drug reactions for anti-malarials, including artemisinin based combination therapy, to the WHO Programme for International Drug Monitoring. Malaria Journal, 2011, 10:57 Edwards IR, Isah, A. Pharmacovigilance and the Null Hypothesis: Do We do Much for Public Health? Drug Safety. 34(2):93-96, February 1, Edwards IR, Lindquist, M. Social Media and Networks in Pharmacovigilance: Boon or Bane? Drug Safety. 34(4): , April 1, Edwards IR. Fraudulent and Substandard Medicines: Getting Away with Murder? Drug Safety. 34(6): , June 1, 2011.