Uppsala Reports
Issue 4
May 1997

For everyone concerned with the issues of pharmacovigilance and toxicovigilance

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    A New Image!
    Reporting Adverse Drug Reactions
    ADR Signal Analysis Programme - ASAP
    National Pharmacovigilance Systems
    News from Around the World




    Greetings from Uppsala


    A Message from Ralph Edwards, Director

    We very much hope that you enjoy reading this ?new look? edition of Uppsala Reports.

    As always, we want to make it as useful and interesting as possible for all of our readers - so if you have any suggestions or queries, we would be delighted to hear from you.

    Some time ago, over twenty countries requested that we support the handling of
    CIOMS I reports from industry, and produce summarised information from the reports at intervals. The response to enquiries from industry was lukewarm because of two main drawbacks: that the limitations of our current database meant that they might need to answer frequent requests for additional data, and that inputs, outputs, changes and accesses must all be logged.

    We decided to wait for the development of our new database to fully answer the challenges posed. Our new database for ADRs is now under trial. It is based on the CIOMS Ia and ICH E2B proposals with some additions. Certainly there is a comprehensive set of fields and the workflow software provides adequate audit, thus answering the objections above.

    We will be very interested to hear from national centres and industry who feel their workload may benefit from using a service for CIOMS I, industry and case reports (which will be annotated as direct from industry in the new data base). It is clear that there will be some duplication between these reports and the industry reports forwarded through national centres. Such duplication occurs with the current situation, and it is hoped that the use of the same database will facilitate checking between the two sets of data.

    Please let us know if you wish to join a trial of our new database. We need at least one national centre and one international company to do this - so do get in touch!



    the Uppsala Monitoring Centre

    A Simpler Form of Address

    ?The WHO Collaborating Centre for International Drug Monitoring? has always been a bit of a mouthful for everyday use. Now we?ve shortened and simplified it to ?The Uppsala Monitoring Centre? and adopted a new logo to reflect the change.

    We still hold full responsibility for all activities and services associated with the WHO Programme on International Drug Monitoring and for providing general and technical support to member countries. On the other hand, the abbreviated title is not only more convenient, but it also recognises that we have activities in addition to those of the WHO Programme.

    We hope you will associate this new image with our vision for the future of quality in service and our expanding range of activities, products and services.

    ADR Signal Analysis Project - ?ASAP? This research project which combines the features of the database of the WHO drug monitoring programme with drug utilization statistics from IMS International and official demographic statistics, got a two-year research grant from the Biomed fund of the European Union. The final report of the research project was presented to EU in January 1997.

    RESULTS
    The main purpose of the project was to examine the use of the WHO ADR database, the IMS drug utilisation database and international demographics for the investigation of drug safety signals. Although no definitive algorithms could be applied to every analysis, a number of standard tabulations were developed, together with methods to bring together the data and recalculate sales and prescription figures into internationally comparable measurements.

    The analyses made showed that the methodology can be used for a wide range of drug safety problems. Both the technological and scientific findings made will add to existing international pharmacovigilance practices. Some of the analyses have led to publications in reputable journals, and the ASAP team suggests a way to develop the strategy as a new pharmacovigilance service, which should benefit administrations, prescribers, manufacturers, and, above all, patients.


    Major Scientific Breakthroughs And/or Industrial Applications
    The comparison of adverse reaction reporting rates, as compared with raw numbers of reports, across countries and over time has never been achieved before, and could only be achieved in this way, with the cooperation of the participating experts and the two international databases.

    There are direct drug safety benefits of the project: the results show that the methodology is a cheap and quick way of analysing international ADR signals, and that it can provide information that adds to existing knowledge.



    Reporting adverse drug reactions - why do (some) doctors actually take the time to do it?

    The Uppsala Monitoring Centre has made a pilot study to find out why some physicians and pharmacists take the time to report adverse reactions. Previous studies have tended to concentrate on why they do not report. The National Drug Monitoring Centres in the WHO programme were asked to send a letter to 20 reporters, with a copy of one of their own reports, to ask why they had chosen to report that particular reaction. They were also asked to give comments about adverse reaction reporting in general, and their own habits in particular.

    Twelve countries replied and gave information about the habits and views of the reporters of 177 cases. Since this was an explorative pilot study the letter to reporters had only an open question about reasons for reporting.

    The responses were categorised at the WHO Collaborating Centre into 14 groups, with the great majority in the top six:

      * motivation to contribute to medical knowledge
      * reaction previously unknown to reporter
      * reaction to new drug
      * reporter reports all significant reactions
      * known association between drug and reaction
      * severity of reaction
    

    From the responses some useful - if obvious! - recommendations can be made. The proposals are based on comments from doctors who have reported, but who represent only a small proportion of professionals who are keener and more aware than the majority.

      actively promote the professional and public health benefits of ADR reporting
      consider the needs of particular professional groups in promotional activities
      focus attention on new drugs, observed possible ADRs, and on the most important categories 
     of reactions ( severe reactions rather than serious)
      develop simple, accessible forms and systems for reporting and follow-up
      give personal encouragement, recognition and feed-back for those who submit reports
      give evidence of the usefulness of submitted reports in publications, bulletins, notified 
     regulatory decisions etc.
    
    Cecilia Biriell, Ralph Edwards: Reasons for Reporting Adverse Drug Reactions - Some Thoughts Based on an International Review, Pharmacology and Drug Safety 6: 21-26 (1997)

    Please contact the Uppsala Monitoring Centre for a full copy of the publication



    News from the Uppsala Monitoring Centre

    Since mid March Jonathan Edwards has been a member of our team. His main task is to be in charge of maintenance of our computer hardware and software. Jonathan will also be responsible for the development of new software to support us and our clients.

    Mr Andrew Bate has been working with us as a research assistant since January this year. In addition to his collaborative work on artificial neural networks with the Royal Institute of Technology, Stockholm, he helps take care of incoming adverse reaction reports.

    From September this year we will not have the capability to receive or produce any magnetic tapes. The computer with a tape station is now old-fashioned and expensive to maintain, and we shall not be replacing it. If you have submitted adverse reaction reports to us on magnetic tape or have got any of our computerised registers on that medium, please consider using diskettes or direct file transfer instead. If this causes you problems, please call us to discuss possible alternatives.

    During the summer, tentatively in August this year, we expect to move to new premises in central Uppsala. This is the result of the expansion of our tasks and our staff which has taken place over the last few years. Up to now our landlord, the Medical Products Agency, has managed to provide us with the office space we need but now we have reached the limit of what the present premises can accommodate. On In April our Board decided that we can move to new premises located at Stora Torget 3. The new office, overlooking the Central Square, provides excellent working conditions and very good communications for visitors. For everyone working at the Centre this is a very positive development. We will let you know as soon as we have details of our new postal address and telephone number - and hope to welcome some of you to our new home.

    Last year Ralph Edwards and Sten Olsson from the Centre gave lectures to audiences in Melbourne and in Sydney, Australia, though a video-conference connection. Unfortunately the studio used in Uppsala was closed down shortly afterwards with the effect that this service could not be offered to others. However, we have now got access to another video-conferencing facility in Uppsala. Consequently we can now offer this facility as a cheaper alternative to our travelling to course venues around the world. The technology allows for discussions and simultaneous display of illustrations to all parties.

    We recently established a list of e-mail addresses called ?Vigimed? that includes pharmacovigilance professionals associated with the WHO Programme. The list is meant to provide a forum for rapid exchange of information on drug safety issues to a limited number of concerned individuals. An e-mail message sent to ?Vigimed? will automatically be distributed to everyone included on the list. If you are collaborating with the WHO Drug Monitoring Programme, have an e- mail address and are still not on the Vigimed mailing list, please contact Sten Olsson at sten.olsson@who-umc.org



    National Pharmacovigilance Systems now available

    This attractive and comprehensive publication offers the first detailed overview of national pharmacovigilance systems throughout the world. It can be used in a variety of different ways:
     * To gain an insight into how the national pharmacovigilance system is set up
       and operated in a particular country
     * To get a global overview of how systems resemble each other or differ, including 
          variations in national adverse reaction reporting forms
    * To understand how national centres collaborate and interact globally under the auspices of the World Health Organization
    The publication will benefit health care practitioners, professionals working within the pharmaceutical industry, drug regulators and all those interested in pharmacovigilance. It covers details of 45 national systems over 235 pages. It also provides a comprehensive directory of names, addresses and communication details, which should contribute towards intensifying world-wide communications on issues of drug safety and pharmacovigilance practices.

    Annual up-dates will be provided, so that the dynamic and changing systems outlined in the directory can be kept as up to the minute as possible.

    For further details, please contact Sten Olsson at the Uppsala Monitoring Centre



    Product News

    The Drug Dictionary
    The development of the structure of the new Drug Dictionary proceeds as planned. To get continuous information about progress, please look at our homepage (see below for details) where you will find current information. We will, of course, also give you up-to-date information at the next Users? group meeting.

    The printed version of the Drug Dictionary (the former WHO Drug Reference List) will be produced and available during May/June this year. It will contain information up to and including the first quarter of 1997. As the new ATC codes are not available until the beginning of the year and as we find it important to have them added to the new edition we decided to postpone the production by a few months. We hope the delay in availability will not be of any inconvenience for you.

    The Adverse Reaction Terminology
    The new printed versions of the Adverse Reaction Terminology (English, French, Spanish and Portuguese) are at the printers and are now available for distribution.

    Jonathan Edwards has recently started the development of a Adverse Reaction Terminology product containing software with search facilities like the DD Access product provides for the Drug Dictionary. The new product is likely to be available for sale in September/October this year.

    The current computerized versions of the Dictionaries contain information up to and including the fourth quarter of 1996. The next versions, containing information as per the first quarter of 1997, will be ready for distribution during May/June.

    The new updated DD and ART information leaflets are now also available in French.

    For current information on our products and activities we would like to remind you of our homepage (see address below) which is updated regularly, and also to contact us as soon as you have any queries at all regarding our products and/or services.

    http://www.who-umc.org

    WHO Dictionaries Users? Group Meetings
    The next Users? group meeting will be held at the annual DIA meeting in Montreal on Monday June 22. The Centre's representatives at the meeting will be Marie Lindquist, Research and Development Manager, and Liza Storm, Marketing Manager.

    Unfortunately there was no Users? group meeting at the Philadelphia DIA meeting in March. However, those of you who have not received the minutes from the London meeting, held in November last year, please contact us and we will send you a copy.

    Once again we would like to remind you of the fact that a new chairperson/convener for the Users? Group has not yet been elected. We think it is very important to have an active users? group, so if you have any suggestions for a suitable person, please let us or the DIA know.

    FTP
    As we have mentioned earlier, we plan to introduce the capability of delivering the Dictionaries files by direct file transfer(FTP). This option will be available from September/October this year. Those of you who are interested in receiving the files by FTP, please contact us.



    News from Around the World

    EU
    Mr Philippe Meyer who was the principal administrator at the Commission of the European Union, Brussels, in charge of pharmacovigilance affairs, has moved on to the external relations department within the Commission.

    Iran
    The national pharmacovigilance centre in Iran has been moved from the quality control laboratory to National Drug Information Centre (NDIC). Dr Mahlegha Mahmoodi is director of NDIC while Dr Mohammad Shafzadeh is in charge of the pharmacovigilance unit. The contact address is: Iranian Drug Information Center, ADR Unit, Under Secretary for Curative and Drug Affairs, Buildin No 3, Fakhre Razi, Englabe Ave, Tehran 13145. Fax: +98-21-675868.

    Japan
    The new head of the Japanese national pharmacovigilance centre is Mr Koichi Ishii who has succeeded Mr Tatsuo Kurokawa, now the director of the food chemistry division within the Ministry of Health and Welfare.

    Portugal
    Dr António Faria Vaz has been appointed head of the national pharmacovigilance centre at INFARMED, the Portuguese drug control authority, replacing Dr Ana Maria Corrêa Nunes.

    Dr Faria Vaz and colleagues paid a short visit to Uppsala in early April.

    Venezuela
    The present head of the national pharmacovigilance centre is Dr Carmen Lozada Aranguren. She has replaced Dr Evelyn Uzcátegui. The contact address is Instituto Nacional de Higiene ?Rafael Rangel?, Sección de Farmacología Sanitaria, Apartado Postal 60.412-Oficina del Este, Caracas, tel +58-2-662 4797, fax +58-2-6625074
    The Philippines
    The second National ADR Training Workshop is being held in Manila 13-14 May 1997.



    Pharmacovigilance Meetings

    The 9th Annual Euromeeting of the Drug Information Association (DIA) will be held in Düsseldorf, Germany, May 26 - 28, 1997. The pharmacovigilance track will have three main themes: 1) Maturation of pharmacovigilance in an international environment moving towards harmonization 2) Practical issues facing the pharmaceutical industry 3) Risk management in a global regulatory environment. More information may be obtained from DIA European office, fax +41-61 3829050, e- mail diaeurope@stepnet.de

    Management Forum will arrange a basic training course on Pharmacovigilance for Those Working on Drug Safety Monitoring in the EU in London, UK, June 4 - 6, 1997. Please fax +44-1483 536424 for additional information

    The Drug Information Association will have its 33rd Annual Meeting in Montreal, Canada, June 22 - 26, 1997. One of the main tracks concerns drug safety. The session topics are as follows: 1) Black box warnings 2) The challenges of managing the serious adverse event database from IND to NDA 3) CIOMS update and benefit risk analysis 4) Working methods of national adverse drug reaction centres 5) ICH M1 medical terminology 6) EU safety update 7) Electronic transfer and management of safety data 8) Pre- and post-marketing adverse event handling-the daily challenge 9)US FDA safety update 10)ICH update 11) Communicating safety information effectively 12)Signal identification and follow up. More information may be obtained from DIA, fax +1-215 641 1229, e-mail dia@diahome.org

    Instituto Nacional de Higiene ?Rafael Rangel?, Caracas, Venezuela, will organize an international workshop on pharmacovigilance 10 - 11 July, 1997. Please fax Dr Carmen Lozada +58- 2-6934967 for further information.

    ISPE, the International Society for Pharmacoepidemiology, will have its 13th International Conference at Walt Disney World Dolphin Hotel, Orlando, Florida, USA on August 24 - 27, 1997. More information about the conference may be obtained from Professor Stanley Edlavitch, fax +1-913- 588-2791, e-mail: ispe@kumc.edu, website: http://www.kumc.edu/ISPE/

    European Society on Pharmacovigilance (ESOP) will hold its fifth annual meeting in Berlin, Germany, September 15 - 16, 1997. Topics will include 1) Would we prevent the thalidomide disaster today? 2) Delayed allergy-like reactions to x-ray contrast media 3) Allergy, toxicity and resistance - the problems with anti-bacterials 4) Risks of long-term suppression of HCl-secretion 5) Pro-arrhythmic effects of drugs 6) Contribution of drug-utilization studies to pharmacovigilance. For more information contact Dr Jürgen Beckmann, Federal Institute for Drugs and Medical Devices, fax +49-30 45483515

    The 2nd Congress of the European Association for Clinical Pharmacology and Therapeutics will also be held in Berlin, September 17 - 20, 1997. One symposium will be on adverse drug reactions with the following themes: 1) Mechanisms of ?idiosyncratic? drug toxicity 2) Hepatotoxicity 3) Assessment of oral contraceptives 4) Pharmacoepidemiology in pharmacovigilance. For more information contact FGU Berlin, fax +49-30 21295420

    SOBRAVIME (Sociedade Brasileira de Vigilância de Medicamentos) will organize its IV Brazilian Congress on Pharmacovigilance in Curitiba, Brazil, 23 - 26 September, 1997. Further information and a draft programme may be obtained from the SOBRAVIME secretariate, fax +55-11- 2584241, e-mail: sobravim@eu.ansp.br



    The Uppsala Team

    Director: Professor Ralph Edwards
    General Manager: Sten Olsson
    Research and Development Manager: Marie Lindquist
    Science and Quality Assurance Manager: Cecilia Biriell
    Marketing Manager: Liza Storm
    Sales and Promotions Manager: Mats Persson
    Expert, Herbals Project: Mohamed H. Farah
    Pharmaceutical Officers: 
     Helena Fucik
     Anna-Karin Karlsson
     Monica Pettersson
     Malin Zaar
    Software Development Coordinator: Jonathon Edwards
    Research Assistant: Andrew Bate
    Executive Secretary: Anna Lindquist
    Sales and Services Assistant: Maria Bergström
    Communications information:
    
    Uppsala Reports © The Uppsala Monitoring Centre 1997
    
    Postal Address:
    The Uppsala Monitoring Centre
    Box 26, S-751 03 Uppsala, Sweden
    
    Telephone:
    +46 (18) 17 48 50
    
    Fax:
    +46 (18) 50 78 40
    
    E-mail:
    info@who-umc.org
    Personal e-mail messages may be sent to members of the team by substituting the name of the 
    addressee (e.g. ralph.edwards or liza.storm for info)
    
    Internet:
    http://www.who-umc.org