Being a member of the WHO Programme - Uppsala Monitoring Centre

Being a member ofthe WHO MedicinesSafety Programme

Figure 1. World map showing the offi cial and associatemember countries as of October 2012.Offi cial MemberAssociate MemberBackgroundWhen a country becomes a member of the WHO Medicines Safety Programme, it is essentialthat national centre staff are fully aware of the benefits and obligations of membership. Thisdocument gives an overview of the services provided by WHO and UMC as well as therequirements that national centres are expected to meet.The WHO Medicines Safety Programme was set up in 1968 as a direct consequence of thethalidomide tragedy. In the 1960s it was discovered that this medicine could cause limbdeformities in babies if taken by pregnant women. This was the modern starting point ofpharmacovigilance, the science focusing on patient problems caused by the use of medicines.The intention of the WHO Programme was to ensure that early signs of previously unknownmedicine-related safety problems would be identified and information about them shared andacted upon throughout the world.The WHO Medicines Safety Programme has grown to become a global network of pharmacovigilancecentres in over 140 countries. In each participating country the Ministry of Health, orequivalent, has appointed a national centre for pharmacovigilance responsible for maintainingcontacts with WHO on issues related to medicine safety. The network of national centres iscoordinated by a WHO Collaborating Centre for International Drug Monitoring in Uppsala,Sweden, known as the Uppsala Monitoring Centre (UMC). This is a foundation created by theSwedish government on the basis of an agreement with WHO. A provision of this agreement isthat WHO headquarters is responsible for all policy issues relating to the Programme.UMC manages a database of Individual Case Safety Reports (ICSRs) received from nationalcentres in the WHO network. The database, called VigiBase, currently contains over 8million descriptions of individual cases in which medicines, including vaccines and biologicals,have been suspected of contributing to an adverse reaction in the exposed patient.2Background

Membership benefits – what you get from us· Access to VigiBase– containing worldwide medicine safety data· Early information about potential safety hazards– based on analyses of worldwide data and communications from member countries· Terminologies and software– tools for reporting, storing, structuring, searching, and analysing ICSRs· Support, training, guidelines and resources– on pharmacovigilance practice· Access to the international network– knowledge and expertise of member countriesAccess to VigiBase: Using the VigiSearch toolVigiBase is the name of the WHO global ICSR database containing more than 8 millioncase reports of suspected adverse drug reactions submitted by the increasing number of membercountries since 1968. The information in VigiBase is shared free of charge and withoutrestrictions with members and associate members of the WHO Programme. Member countrieshave different approaches to confidentiality of case information and provision of data to thirdparties. The present WHO position on confidentiality is that case information from VigiBasemay be provided to any inquirer with a health professional education, provided the rules of aCaveat statement are accepted. This statement explains the limitations of the data in VigiBaseand the implications for interpretation. Case reports in VigiBase do not contain identificationof the patient or the reporter.VigiBase is a valuable reference source for medicine safety information and for comparisonsof national experiences. A new easy-to-use web-based tool, called VigiLyze, will replaceVigiSearch in late 2012. VigiLyze will enable member countries to search, filter and analysedata in the global database more efficiently. This includes clickable graphic objects and summarydata using several standard presentation formats. More importantly, the integrated access toindividual case reports allows more in-depth analysis of drug safety issues through aninteractive, streamlined and intuitive interface. VigiLyze brings the VigiBase data set withinthe reach of member countries and will contribute further to improving patient safety.VigiLyze is provided free of charge to member and associate member countries. If the facilitiesin VigiLyze are not sufficient for users, customized searches can be performed on request, byUMC staff, free of charge to members of the WHO programme, while non-members will becharged for this service.Membership benefits 3

Information about potential safety hazards: Signal documentThe case information submitted to VigiBase is screened on a regular basis for signs of any medicineinducedproblems that have yet to be identified.Since 1998, routine data mining of VigiBase has been performed on a quarterly basis, usingstatistical methods. A triage (filter) procedure is used to find drug-ADR pairs of interest and expertclinical review is undertaken by UMC and an international panel of experts. The results of theseintensive analyses are available to national centres as a restricted memorandum called SIGNAL andthe WHO Pharmaceuticals Newsletter.The data mining tool, VigiMine, used for analysis and detection of drug–ADR pairs of interest,using several filtering and sorting functions, is available only on request. Meanwhile, VigiLyze isbeing further developed with improved analytical features.Terminologies and software: WHO Drug Dictionary, WHO-ART and VigiFlowThe WHO Drug Dictionaries and WHO Adverse Reaction Terminology (WHO-ART) aremaintained by UMC. These terminologies are built on information derived from ICSRs frommember countries and are used for coding and analysis of drugs and adverse reactions. TheWHO-DD is accessible via VigiLyze, VigiFlow (see below) and the WHO Drug DictionaryBrowser. The latest version of WHO-ART is available via VigiLyze and VigiFlow or as a filedistributed to member countries on request.National centres are requested to submit their national ICSRs to UMC in an internationalstandardized format (ICH-E2B). For member countries that lack an E2B compatible databasefor ICSR management, UMC has developed the web-based tool VigiFlow. This is designedto function as a complete case management system and national report database. No localinstallation is needed and the only requirement is an internet connection (minimum speedof 1 Mbit/s) and a web browser.WHO-ARTMedDRAWHO DrugDictionaryIntdisE2BNationalPharmacovigilanceCentreNationalDatabasee.g. VigiFlowVigiLyzeFigure 2. The National Centre sends ICSRs to VigiBase at the UMC. This information helps create WHO-ART and theWHO-DD. International safety information can be retrieved from VigiBase by the VigiLyze tool for use by national centres.4Membership benefits

The system, currently available in English, French, Spanish and Russian can be used simultaneouslyon a central and regional level, with an unlimited number of users, which facilitates the workflow and saves resources. VigiFlow is easy to handle with built-in help texts and error messages.Search and statistics can be performed on the reports entered, which are also easily forwarded toUMC to be included in VigiBase.The system provides access to the latest versions of the terminologies described above, as wellas the International Classification of Diseases (ICD-10) and MedDRA (Medical Dictionary forRegulatory Activities). Since UMC is maintaining and constantly developing VigiFlow, anannual license fee is charged for access to the complete version of the system. However, a limitedversion is available free of charge, intended for countries that are not interested in the full reportmanagement functionality but need a system for reporting ICSRs to the WHO Programme.Some specialised tools are available for patient reporting and cohort event monitoring; moreinformation is available from UMC.Support and resources: Guidelines, publications and websitesUMC offers guidance and support for the establishment and running of a pharmacovigilance centreand a national programme. Several guidelines and publications for good pharmacovigilance practicehave been developed by WHO/UMC and are available free of charge in several languages.The UMC and WHO headquarters also produce their respective newsletters: Uppsala Reportsand WHO Pharmaceuticals Newsletter. These are free publications available to a wide audience.Uppsala Reports, issued four times a year, contains information about developments in pharmacovigilancein general, at UMC and at national centres in particular. The WHO PharmaceuticalsNewsletter, issued six times a year, provides a record of regulatory decisions, warnings and labelingchanges made by countries on grounds of safety. Member countries are also offered a heavilydiscounted subscription to the secondary literature review journal Reactions Weekly, the mainjournal for scanning the medical literature on adverse drug reactions, through an agreement withthe publisher.The WHO and UMC websites have a lot of useful information about the WHO Programme,current activities, definitions and concepts in pharmacovigilance, meetings and courses aroundthe world and an FAQ section. Most of the publications mentioned are also available as pdf filesfor download from the web. Please make frequent visits to: www.who.int/medicines and www.who-umc.org.Access to the international network: Vigimed, meetings and coursesSince worldwide collaboration and information sharing is crucial in pharmacovigilance for promotionof patient safety, member countries are encouraged to communicate frequently with eachother. One forum for such communication is Vigimed, a web platform set up by UMC to stimulatediscussions and facilitate rapid exchange of information between national centres. Vigimed is a closedsite so that members may feel confident sharing preliminary findings, suspicions and opinions withother pharmacovigilance professionals, knowing that such information will not be seen by or givento other parties, the public or to media without consent of the originator.Membership benefits 5

Member countries are invited by WHO to the National Centres Annual Meeting which isusually held between October and December. These annual meetings provide good opportunitiesfor learning, networking and discussions regarding topical pharmacovigilance issues both inrelation to methodological developments and individual medicines. It is highly recommended fornational centres to be represented at these meetings, although funding and some knowledge ofEnglish are required.UMC also runs a two-week pharmacovigilance training course in Uppsala in May every year.The course is intended for healthcare professionals who have recently become engaged in theoperation of spontaneous adverse reaction reporting programmes in a hospital, regulatory orindustry setting. Theoretical and practical aspects of adverse drug reactions and pharmacovigilanceare covered.WHO supports or organizes pharmacovigilance training courses in regions of the world on anad hoc basis, depending on local needs and the availability of funds. These training courses aresometimes focused on pharmacovigilance in Public Health Programmes, e.g. for managers inmalaria or HIV/AIDS programmes.WHO also organizes Technical Briefing Seminars annually in Geneva with the objective ofadvancing collaboration between WHO and other stakeholders from governmental and nongovernmentalorganizations engaged in promoting the quality and safety of medicines in theglobal community.Membership obligations – what we expect from youTo ensure the most effective global safety monitoring by keeping VigiBase up to date withinternational patient safety data, member countries are expected to submit ICSRs to UMC atleast every quarter and preferably more frequently than once a month. If a member country, forany reason, temporarily cannot comply with this obligation, UMC must be informed. Failure tocommunicate with UMC could lead to loss of some membership privileges.Reporting format compatibility and quality of ICSRsICSRs should be submitted to UMC in the International Conference on Harmonization E2B(ICH E2B) format. This is the international standardized format for electronic transmission ofICSRs and includes all relevant data fields, which allows for a comprehensive medical analysisof the data. UMC still accepts ICSRs submitted in the old WHO format (INTDIS) from somemember countries but all countries are strongly recommended to convert to the ICH E2B format.VigiFlow is offered to all new member countries and to current members who want to convertto an ICH E2B compatible national database (see page 4).To ensure the availability of high quality data in VigiBase, member countries are expectedto submit complete ICSRs to UMC. With the exception of confidential patient and reporterdetails, no information available on the original report should be left out when transmitting anICSR; the more information on a case, the simpler and more accurate the assessment. UMCcomplies with EU data protection law, and adheres to the guidance in ICH E2B for protectingpatient and reporter confidentiality.6Membership obligations

Member countries are expected to submit all post-marketing ICSRs to VigiBase, irrespectiveof their origin, source or reporter type, causality, or seriousness. ICSRs on all types of drug-relatedproblems should be submitted , also those associated with biological medicines (including vaccines),traditional medicines, counterfeit/substandard medicines as well as medication errors. VigiBasedoes not include ICSRs on veterinary medicines, cosmetic/hygiene products or medical devices.Drug referencesTo be able to find ICSRs by searching on a drug name in VigiBase, the names and basic detailsof the drug must be included in the WHO Drug Dictionaries. To perform this task, UMC staffneed reliable reference sources for local drug information. Therefore, member countries shouldsend a printed or electronic version of their National Drug Formulary or equivalent (e.g. referenceto a website approved by the national drug authority) to UMC.Regulatory informationProduction of local and national ADR newsletters and bulletins is recommended as a good wayof sharing important information within a country. Member countries should provide UMC withinformation about their medicine safety newsletters if available. UMC needs to know the websiteaddress of the national centre, if available. This is provided for others as a link on the UMC website.Active participationMember countries are expected to actively participate in the WHO Programme; this can beachieved in various ways. National centres should maintain good communication with UMCand provide updates on reorganizations, changes of staff and other relevant information. Nationalcentres are encouraged to be active participants in Vigimed (see page 5) and contribute todiscussions and information exchange. If possible, member countries should also send at leastone delegate to the National Centres Annual Meeting (see page 5) where topics of currentinterest are addressed and important relationships are formed. Established national centresare encouraged to assist in training professionals from newly established centres to promotepharmacovigilance.Please do not hesitate to contact us if you:· need support on ICSR reporting issues and/or VigiFlow· need a VigiLyze user account to access VigiBase· need a WHO-DD Browser user account to accessWHO Drug Dictionaries· need any WHO/UMC publications,or Reactions Weekly· need a user account to access the Vigimedweb portal· want to attend our meetings and/or coursesMembership obligations 7

Uppsala Monitoring CentreWHO Collaboratoring Centre forInternational Drug MonitoringBox 1051SE-751 40 UppsalaSwedenTel: +46 (0) 18 65 60 60Fax: +46 (0) 18 65 60 88E-mail: info@who-umc.orgwww.who-umc.orgWorld Health OrganizationQuality and Safety; Medicines20 Avenue AppiaCH-1211 Geneva 27SwitzerlandTel: +41 (0) 22 791 38 34Fax: +41 (0) 22 791 47 43E-mail: empinfo@who.intwww.who.int