y Greetings from Uppsala

y New Publication

y Verona Communications Workshop

y The Uppsala Team in San Diego

y News from WHO Collaborating Centres

y What happens to SIGNALS issued by the Centre?

y Product News

y News from around the world

y Training Course

y Annual meeting of national ADR centres in Lisbon

y European Medicinal Product Identification Standard

We were delighted with the warm and positive response to the first edition of Uppsala Reports. Please do keep your reactions and contributions coming in!

With this edition you'll find a simple form on which you are warmly invited to record your opinion - or to send us news and views for possible inclusion in the next edition.

Do fax or mail or e-mail a few words to us.

One of our concerns is that health professionals still rely heavily on publications with only lists of adverse reactions. We believe that the communication of risk (and benefit) information should be developed much more imaginatively.

This concern underlies the joint workshop described below, which we hope will contribute to pushing this issue forward in research and practice.

With our Annual International meeting coming up in Lisbon, Portugal, just a few weeks away, we're looking forward to renewing old friendships - and making new ones - and addressing the many important issues in drug safety which have emerged since Bangkok 1995. From all member countries we hope to have some representation - even if it is only a written communication of your interests and preoccupations. But we look forward to seeing many of you in person!

I and the team here wish you all the very best - and hope, as always, that you'll contact us if we can be of any service to you.

Ralph Edwards.

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New Publication

Directory of National Pharmacovigilance Centres

Within the next few months we will be publishing a directory of the 45 national pharmacovigilance centres from all over the world participating in the WHO programme. Each centre is described in detail in a "country profile" providing facts about sources of information, methods of case follow­up, recording, assessment, decision making, contact names and communications details.

In part II of the directory there is an international overview of procedures used at National Centres, which demonstrates how widely approaches to pharmacovigilance differ. An appendix displays the various data elements requested in national ADR reporting forms.

The information is based on responses to a comprehensive questionnaire sent out by us. Data was verified by national centre staff during 1995.

It will be in a loose-leaf format, so it can be quickly updated. We shall need lots of help from our friends around the world to ensure that the information is as contemporary as possible.

If you are interested in this publication and wish to receive an offer at the time of its release, please let us know. For national pharmacovigilance centres the publication will be free of charge.

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Communications in Pharmacovigilance Verona Study Group

The University of Verona, The Uppsala Monitoring Centre and CIOMS are sponsoring an exploratory study group to look at all aspects of communications in pharmacovigilance this autumn.

The group will bring together clinicians, pharmacists, regulators, lawyers, journalists, consumer interests and industry to examine current problems, dilemmas and opportunities for improved understanding and practice.

It is intended that the proceedings of the meeting should be published and that they should pave the way for a major international symposium next year.

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The Uppsala Team in San Diego

Presenting our latest work

The annual meeting of the Drug Information Association (DIA) was held in San Diego, California, USA, 9 ­ 13 June, 1996. At the meeting the Centre was given the opportunity to present many of our current development activities:

1. A new data model for storage of ADR case information based on the proposal of the CIOMS 1A working group

2. A new data model of the extended WHO Drug Dictionary including the proposals of the CEN working group for identification of pharmaceutical products (see below)

3. A data model intended to collect detailed pathophysiological and clinical data from cases with severe ADRs or intoxication (TOXICASE) has been developed under the auspices of IPCS (International Program on Chemical Safety).

4. Recording of adverse reaction diagnoses with the aid of a controlled vocabulary approach as an alternative to hierarchical terminologies. This topic was presented by Dr Harley Quilliam from University of Guildford, UK.

5. The use of artificial neural networks in the analysis of large adverse reaction databases for the identification of new adverse reaction signals. Mr Roland Orre from the Royal Institute of Technology, Stockholm, made the presentation.

6. The ADR Signal Analysis Project, ASAP, combining adverse reaction reporting data from the WHO database with drug utilization statistics from IMS and official demographical statistics. Dr Norman Taylor of IMS contributed in the presentation of this issue.

7. The development of a classification system for herbal remedies compatible with the ATC­system. The project is designed in collaboration with the Royal Botanic Gardens in Kew, (UK), Exeter University, (UK), and the Royal Dutch Association for the Advancement of Pharmacy, (The Netherlands). Obviously input from experts from all parts of the world, representing different therapeutic traditions, will be indispensable in carrying out this project.

In addition to presenting the above projects the Centre had all its current products and services on display in the exhibition area of the DIA conference. We have also reached an agreement with DIA that our home­page on Internet will have a link from theirs.

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News from WHO Collaborating Centres

Norway

The WHO Collaborating Centre for Drug Statistics Methodology in Oslo, responsible for management of the ATC­system for classification of pharmaceuticals and for establishment of DDDs (Defined Daily Doses) recently came under the aegis of Division of Drug Management and Policy at WHO headquarters, Geneva, through an agreement between WHO and Norway.
Previously the Oslo centre was connected to the WHO Regional Centre for Europe.

South Africa

The Department of Clinical Pharmacology of the University of Cape Town Medical School was recently designated a WHO Collaborating Centre for Drug Policy and Safety Monitoring. Director of the Centre is Professor Peter Folb. The address is: Observatory 7925, South Africa, fax: +27­21­4486181

Spain

Last year the Catalan Institute of Pharmacology at the Autonomous University of Barcelona was designated a WHO Collaborating Centre for Research and Education in Pharmacoepidemiology. Professor Joan­Ramon Laporte of the Centre may be contacted at the following address: Ciutat Sanitaria Vall d'Hebron, 08035 Barcelona; fax: +34­3­4285112

Sweden

A WHO Collaborating Centre for Drug Utilization Studies has been established at the Department of Clinical Pharmacology, Karolinska Institute, Huddinge Hospital, 141 86 Huddinge, Sweden. Director of the Centre is Professor Folke Sjöqvist. Fax number is +46­8­7468821.

New Face in Uppsala

Mats Persson joined the staff of the Uppsala Monitoring Centre in July. He has a degree in Business Management and Marketing and has long experience in working with different sales and marketing activities for the Swedish pharmaceutical industry. At the Centre he will be in charge of sales and promotion of WHO dictionaries and other publications to users in commercial companies.

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What happens to SIGNALS issued by the Centre?

The Centre here uses a panel of experts to assist us in assessing early indications from the database of new drug­reaction associations, not previously described or insufficiently documented. Short summaries prepared by the experts are compiled in a document with a bright yellow cover called SIGNAL, which is made available to National Centres at regular intervals, normally six to eight times a year.

As this scheme has been in operation since 1990 we decided to contact the member countries of the WHO Drug Monitoring Program to find out if the information in the SIGNAL document has had any impact in the various countries and to get their thoughts and opinions about the material.

New Alerts

Another question closely related to this matter was if the produced signals are genuine new alerts, later substantiated by other findings. To investigate this we made a thorough literature search comparing the signals found over the past five years with the medical world literature. This research resulted in a paper presented at the DIA Annual Meeting in Florida last June. It was also recently published in the Drug Information Journal (H.Fucik.,I.R. Edwards; Impact and Credibility of the WHO Adverse Reaction Signals 1996;30:461­464).

A questionnaire was sent to National Centres in member countries and associate member countries, - a total of the 60 centres. The response rate was 60%. Of those who responded 11% thought the SIGNAL material was always useful and 50% found it often useful.

Action

When asked about what actions had been taken in response to the 44 signals sent out from the WHO Centre in 1994, 24 National Centres stated that associations were recorded for follow­up at a national level, 8 centres initiated a total of 38 further investigations (from 1 to 15 per centre) and considered 10 associations as being supported. Nine National Centres stated that they distribute the information to people concerned within their country. If those stating that they publish the signals in their National Drug Bulletin are included (19 centres) this figure is considerably higher. Labelling changes were reported by 9 centres in up to 5 cases per centre. Approaching manufacturers was mentioned by 8 centres to have occurred in 10 cases.

Impact

As shown above the impact of SIGNAL varies considerably across member countries ­ from little or none, suggested by the remark that 'the information in SIGNAL is too tentative to take action upon' ­ through to substantial, for example, in taking specific regulatory action such as labelling changes. The tentative nature of an early signal should not normally lead to decisive regulatory action, but neither should it lead to no activity at all! It seems that more discussion on how to use a signal is warranted and we welcome your thoughts and suggestions.

A Five - year Perspective

To compare the signals from the past five years with the world literature we used Reactions Weekly (by Adis press), Medline and our own literature reference follow­up. The 248 signals compared were serious (based on the WHO Critical Terms List) or of interest to an expert clinical panel. We found that 30 of the signals have been reported in articles in internationally acknowledged journals. Many of them were picked up as new signals through the WHO database 2­3 years before they were found in other literature.

Industry

A final issue was that few authorities approached pharmaceutical manufacturers with the material from SIGNAL. This must relate, at least in part, to a view about the tentative nature of the signals. It does however appear that many drug safety professionals working in industry would like to have access to the material in SIGNAL to compare with their own information and ensure that they can fulfil their own responsibilities optimally. The Uppsala Centre has a prime responsibility to provide information for member states; it is each of those regulatory agencies which becomes the distribution focus for SIGNAL and other WHO information. This is a second area where discussion may be needed.

Conclusion

Our conclusion is that the WHO Programme for International Drug Monitoring is successful in its mission in finding new drug-ADR associations at an early stage and in providing useful information to National Centres. It needs to be emphasised that the purpose is to increase the safety of drug products by keeping an open dialogue with all parties involved. The ultimate concern is to optimise drug use and drug safety worldwide.

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Product News