Celebration of the thirtieth anniversary of the WHO Programme on
International Drug Monitoring, and the twentieth of the Uppsala Monitoring
Centre
Thirty years of international drug monitoring enterprise has seen many changes and new
challenges. The evaluation of collected case material via spontaneous reports from, now, 50
countries worldwide remains the most important way of signalling new concerns about drugs.
The international partners in the work have expanded. The pharmaceutical industry, consumers
and academics have all become more involved in the signal generating process, and are certainly
in the further epidemiological and laboratory evaluation of signals, and the communication of
information to the health professions and public.
The scope of the work now also includes traditional herbal medicine safety as well as
consideration of toxicology of drugs and viewing drug safety as a continuum from development
to obsolescence. A major philosophical development has been to see drug safety much more
clearly and scientifically as a benefit-to-risk balance, even comparing between drugs. In the past
there has been a tendency to consider single risk situations, deciding on their acceptability or
otherwise.
Later this year we plan to have another international meeting to complement those which
celebrated 10 and 15 years of the existence of the Centre in Sweden and 25th anniversary of the
WHO Programme. Invitations will be sent soon, together with a programme for the meeting. The
programme will be aimed at learning from the past and projecting to the next millennium what
should be the developments in drug safety.
We look forward to sharing with you the challenges, and developments, in drug safety both in the
coming year and further into the future.
I. Ralph Edwards
UMC adapts to expanded functions
Not only did we move to new, bigger offices in August 97, we also changed the organization of
work and the management structure.
The Internal Affairs Department is responsible for updating and maintaining the WHO adverse
reaction data base, that now contains more than 1.8 million adverse reaction case reports from 50
countries, and for internal management of the Centre.
The main activities of our Research & Development Department are presently to develop UMC
services over Internet, to improve methods for monitoring of traditional medicines and to do
methodological research in ADR signal analysis, focused on using international drug utilization
data and Bayesian neural network methodology.
The External Affairs Department is divided into two sections. One is concentrating on providing
information, training and other services to WHO Programme members and other clients in the
public sector. The other is serving paying clients, mainly within the pharmaceutical industry with
pharmacovigilance tools like the WHO Drug Dictionary and the WHO Adverse Reaction
Terminology.
In early 1998 two new persons were employed. Ms Inger Forssell is our new sales assistant who
will also take care of accounting for the Centre. Ms Erica Wallette, replacing Monica Pettersson
during her extended maternity leave, will mainly be working with processing of incoming
adverse reaction reports.
News from around the world
Australia
The former head of the national pharmacovigilance centre in Australia, Dr Alain Rohan, has now
become director of pharmacovigilance at the company 3M in Saint Paul, Minesota, USA. He may
be contacted by fax (+1-612-7336068) or e-mail (arohan1@mmm.com)
European Union
At the office of the Commission of the European Union, Directorate General III, in Brussels Dr
Ana de Vasconcelos Batalha now has the responsibility for pharmacovigilance issues, in this
function succeeding Mr Philippe Meyer, who has moved to DG I. Dr Batalha paid a very short
visit to our centre in November 97.
New Zealand
The Centre for Adverse Reactions Monitoring (CARM) has got a new head after Dr Peter Pillans,
who late 1997 took up a position as Professor of Clinical Pharmacology at Princess Alexandra
Hospital, Brisbane, Australia. He is replaced by Dr David Coulter, since long head of the
Intensive Medicines Monitoring Programme.
South Africa
Dr Ushma Mehta supervised a pharmacovigilance training course held in Cape Town on 29
November. There were 14 participants including representatives from Ethiopia, Sudan, Scotland,
Moczambique, Ghana and South Africa. The principles of problem-based teaching were used.
Questions like when to report, who should report, confidentiality and the special concerns of
African countries, created a lot of discussion during this short course that might be repeated next
year.
Sudan
Commissioned by the WHO Regional Office for the Eastern Mediterranean, Dr Ronnie
Meyboom of the Netherlands spent the two first weeks of 1998 in Sudan, lecturing about
pharmacovigilance and how to set up a national centre. His report will contain a plan on how
such a centre may be established in the country.
Tanzania
Ms Rose Shija, the former head of the Tanzania Drug and Toxicology Information Service
(TADATIS) in Dar-es-Salaam, has left the centre for another post in Ministry of Health. Mr
Henry Irunde is now head of the centre which has established new headquarters within the
premises of the Pharmacy Board. The relevant address is TADATIS, Pharmacy Board, P.O.Box
77150, Dar es Salaam, Tanzania
Courses and meetings in pharmacovigilance
Courses
Instituto de Saud Publica de Chile is going to organize a training course in adverse reaction
monitoring in Santiago de Chile, 15 - 20 June, 1998. The syllabus is based on that developed by
UMC for the two-week training course run in Uppsala 1993 - 96. For more information please
contact Dr Q. F. Cecilia Morgado-Cadiz, Centro Nacional de Informatión de Medicamentyos y
Farmacovigilancia, tel +56-2-2399769, fax +56-2-2398760, e-mail cmorgado@ispch.cl
The pharmacovigilance department of ANMAT, the Argentinian Administration for Control of
Drugs, Food and Medical Devices, is setting up a pharmacovigilance training course in 9
modules to run from April to November, 1998. Information may be received from Dr Mabel
Foppiano or Ms Viviana Bologna phone/fax +54-1-3400866, e-mail snfvg@anmat.gov.ar
At the UMC we have decided to again organize an international training course in adverse
reactions and adverse reaction monitoring in Uppsala. It will be held the first two weeks of
December 1998 and be combined with an anniversary symposium to celebrate the 30 years of
existence of the WHO Programme and 20 years of the Uppsala Monitoring Centre. Invitations
will be widely distributed to our contacts throughout the world. Contact person at UMC is Sten
Olsson.
Meetings
Drug Information Association (DIA) is organizing a meeting entitled 'Monitoring Safety through
the Life-Cycle of a Pharmaceutical Product' at Hotel Copthorn Tara, London 23 - 27 February
1998. Information may be received from DIA, phone +41-61-3869393, fax +41-61-3869390, e-mail diaeurope@stepnet.de
Management Forum is organizing its 10th Annual Conference on Pharmacovigilance in London 9
- 10 March, 1998. The title is 'ADR Monitoring Across Europe and USA'. Information will be
provided on phone +44-1483 570099, fax +44-1483 536424, e-mail
management_forum@psilink.co.uk
A round table conference with the theme 'Impact of pharmacovigilance. Old Problems and New
Challenges' will be organized 16 - 17 March, 1998 in Costa Rica. For more information please
contact Dr Albin Chavez phone + 506-2221878, fax +506-2577004, e-mail:
farmaco@info.ccss.sa.cr
A CODATA/ESOP-conference with the theme' Pharmacovigilance: Information Highway Tools
for Adverse Reactions- Implications on Drug Design and Pharmacogenetics' will be held in
Chambéry, France 20 - 21 April, 1998. Information may be received from prof. René-Jean Royer,
phone +33-3-83592617, fax +33-3-83592621, e-mail: pharmaco@pharmaco-med.u-nancy.fr
IBC UK Conferences Ltd organizes a meeting on 'Regulatory Requirements for ADR's and
Adverse Events' in London, 20 - 21 April, 1998, Information may be obtained at phone +44-171-6374383, fax +44-171-6313214, e-mail caroline.elliott@ibcuk.co.uk
On 4 - 5 June 1998, Smi organizes a conference in London with the title 'Successfully Meeting
Global ADR Requirements'. Information is provided by Jane Falconer on phone +44-171-8276072, fax +44-171-8276073, e-mail 100531.3067@compuserve.com
The International Society for Pharmacoepidemiology (ISPE), organizes the 14th International
Conference on Pharmacoepidemiology at Hotel Inter-Continental, Berlin, Germany on 16-19
August , 1998. For information contact Katrina Crist, phone +1-202-4161641; fax: +1-202-8333843; E-mail: kcrist@slackinc.com. The abstract deadline is February 28, 1998.
The European Society of Pharmacovigilance (ESOP) will have its sixths annual meeting in
Budapest, Hungary, 28 - 29 September, 1998. Further information may be received from János
Borvendég or Sándor Elek, The National ADR Monitoring Centre, phone/fax +36-1-2158977
The national ADR monitoring centre in Malaysia is organizing a national conference with invited
guests from the ASEAN region the first week of November, 1998. For more information please
contact Ms Abida Haq, phonel +60-3-7573611, fax +60-3-7562924, e-mail ah@bpfk.gov.my
Pharmacovigilance development in Portugal
The national pharmacovigilance centre, under the direction of Dr António Faria Vaz, recently
investigated the situation for pharmacovigilance in Portugal by 1) interviewing former staff
members 2) interviewing opinion leaders in the pharmaceutical industry, members of the medical
and pharmaceutical professions and their respective associations 3) analysing standard operating
procedures in pharmacovigilance 4) evaluating available adverse reaction data
The following main obstacles to development of pharmacovigilance in the country were
identified:
- lack of technical and scientific resources
- lack of information about the reporting system
- excessive centralization
- lack of reporting culture
- lack of research in the area
An action plan to be carried out 1997-99 has been elaborated. The following elements are
included
1. Creation of local reference centres located in universities and/or teaching hospitals
2. Dissemination of information about the national pharmacovigilance system to all health
authorities and hospital boards. Meetings with directors of hospital and clinics will be
organized in all parts of the country
3. Creation of a pharmacovigilance bulletin to be sent to all doctors and pharmacists four
times a year
4. A national campaign to promote adverse reaction reporting will be launched through
specialized media, organized by a marketing company
5. Training courses on adverse drug reactions for hospital doctors and GPs will take place in
collaboration with university pharmacology departments and the local reference centres
6. Establishment of a research promotion fund
For further information about the project, please contact Dr António Faria Vaz, phone +351-1-7908558, fax +351-1-7959116, e-mail: infarmed@mail.telepac.pt
The 21st Annual Meeting of National Centres Participating in the WHO
Programme for International Drug Monitoring
This meeting will be organized by the Ministry of Health, Japan, 8 - 11 September, 1998.
Invitations are expected to be distributed soon from WHO headquarters, Geneva.
Recent publications from the UMC
1. I.Ralph Edwards, Who cares about pharmacovigilance? European Journal of Clinical
Pharmacology (1997) 53:83-88
2. M.M.S. Stahl, M. Lindquist, M. Pettersson, I.R. Edwards, J.H. Sanderson, N.F.A. Taylor, A.P.
Fletcher, J.S. Schou, Withdrawal reactions with selective serotonin re-uptake inhibitors as
reported to the WHO system. European Journal of Clinical Pharmacology (1997) 53:163-169
3. R.H.B. Meyboom, A.C.G. Egberts, I.R. Edwards, Y.A. Hekster, F.H.P. de Koning, W.J.
Gribnau, Principles of Signal Detection in Pharmacovigilance. Drug Safety (1997) 16:355-365
3. I.R. Edwards, B. Hugman, The Challenge of Effectively Communicating Risk-Benefit
Information, Drug Safety (1997) 17:216-227
4. R.H.B. Meyboom, Y.A. Hekster, A.C.G. Egberts, F.W.J. Gribnau, I.R. Edwards, Causal or
Casual? The Role of Causality Assessment in Pharmacovigilance. Drug Safety (1997) 17:374-389
5. A.Bate, M. Lindquist, I.R. Edwards, S. Olsson, R. Orre, A. Lansner, R.M. de Freitas, A
Bayesian neural network method for adverse drug reaction signal generation. European Journal
of Clinical Pharmacology (in press)
6. S. Olsson, Role of WHO Programme on International Drug Monitoring in Co-ordinating
Worldwide Drug Safety Efforts. Drug Safety (in press)
Favourable offer for ADR software
One of our duties is to support the development of national systems for collection of drug safety
information. The lack of adequate off-the-shelf computer software at affordable prices to support
the work of pharmacovigilance centres has been a major obstacle to the establishment and
development of such centres in less resourceful countries. To remedy the situation we have, in a
joint project with our computer service company PharmaSoft, developed a software with all
functions needed to support a small or middle sized national drug monitoring centre. The
computer programme also allows convenient reporting to the WHO data base. This software,
called PS Drug Watch, is now offered to national pharmacovigilance centres in a one-PC-version
at the favourable price of USD1500.
In connection with this offer, PharmaSoft is also presenting a stand-alone version of their
comprehensive product information system, developed to support all activities involved in the
drug registration process, for drug regulatory authorities. This product, PS Regulator-Light, is
offered at the same favourable price of USD1500.
Further information about the products may be received from Sten Olsson at UMC or Sven
G.Johansson at PharmaSoft, phone +46-18-185400, fax +46-18-109200
Obituaries
Professor emeritus Garth McQueen died in his home in Dunedin, New Zealand in June, 1997.
Garth was a great man, having scholarship, vision and integrity. He and a few others with
international vision started work in drug and chemical safety that has helped to make the world a
safer place. The linking of drug with chemical safety in general and service and research
functions has become the recommended approach of the World Health Organisation, and New
Zealand was the pioneer of this approach.
The Intensive Medicines Monitoring Programme is another unique drug safety development that
started through Garth's work, and is still admired worldwide.
Prof. Garth McQueen was one of the first clinical toxicologists, using his general medical and
clinical pharmacological knowledge to great effect. He was a person with a profound interest in
his work, and initiated what was to become the National Toxicology Group in New Zealand, and
the Intensive Medicines Monitoring Programme for prescription event monitoring.
Both other specialists and students held Garth in great regard for his clinical knowledge and
wisdom. He was a good teacher and the sometimes stern exterior was frequently enlivened by
original humour. But he did not suffer fools gladly, and was not afraid to stand against the flow
for what he thought was right.
He was very active in WHO circles and New Zealand was one of the original countries involved
in the WHO Programme for International Drug Monitoring.
The fact that he learned to ski when he was about 60 perhaps gives some impression of the
determined person he was!
Dr Franz Rosa, who served as an epidemiologist and teratologist for the FDA in United States
1979 - 1996 died from cancer on 3 October, 1997. Dr Rosa was for many years an active and
much valued signal reviewer in the teratology area for the WHO Drug Monitoring Programme. A
Franz Rosa Scholarship Fund has been established by the Organization of Teratology
Information Services in the US.
Product news
Computerized WHO Adverse Reaction Terminology (WHOART) and WHO Drug Dictionary
New updated versions containing information up to and including the fourth quarter 1997 will be
available at the end February/beginning of March.
The English version of WHOART, December 31, 1997, will be available in hard copy in
March/April.
ART Access, the computerized ART with search facilities, will be updated to include information
as per the fourth quarter 1997. It will be available during March..
The hard copy version of WHO Drug Dictionary March 31, 1998, as well as the DD Access,
standard version, will be available in June.
The Centre will attend the following meetings during the next few months and exhibit its
products:
March 30 - April 1: DIA 10th Annual EuroMeeting, Nice, France
April 22 - 24: ACRP's 22nd Annual Meeting, Anaheim (CA), USA
May 13 - 15: IIR's Adverse Drug Reaction Conference, Orlando (FL), USA
June 7 - 11: DIA 34th Annual Meeting, Boston, USA.
On May 18 - 20 UMC will have its annual planning conference which means that availability of
staff members will be limited
Monitoring of herbal medicines
Plants have been the primary source of food and medicine for people of every culture throughout
the world. However, practitioners of traditional medicine need to be more aware of the problems
of toxicity. They must learn that infrequent adverse drug reactions will not be recognized without
the existence of a formal system of reporting negative experience. Dangers of dual treatment,
mixing traditional and orthodox treatments, should be recognized by both traditional and modern
health practitioners. Physicians who have patients taking any particular medicinal plant should
try to document negative experiences, in order to gather enough scientific information about the
adverse effects of the herb. Because adverse drug reaction reports are a critical source of herbal
drug safety information, the Uppsala Monitoring Centre is seeking your help in detecting and
reporting any herbal adverse reactions. Your continued support is crucial in building a more
complete herbal drug safety profile. The UMC is grateful to all who are reporting suspected
herbal adverse reactions to a national centre.
The renewed interest in the western world for plants used in traditional medicine, and the rapidly
growing interest in developing countries to start research programs in this area have ,
unfortunately, not emphasized the great importance of taxonomic botany and documentation for
such research. There is a need to adopt the most commonly used binomial names (including their
binomial synonyms) for medicinal plants, to eliminate the confusion created by the common
names. Artemisia absinthium L. for example, contains an active narcotic derivative, which can
cause central nervous system disorders and generalized mental deterioration. This herb has at
least 11 different common names (wormwood, absinthium, absinth, absinthe, madderwort,
wermuth, mugwort, mingwort, warmot, magenkraut and herba absinthii), 7 of which bear no
resemblance to its botanical name. Because only common names are used, Heliotropium
europaeum (heliotrope), containing pyrrolidine alkaloids, potent hepatoxins, is often confused
with Valerian officinalis (garden heliotrope), containing valepotriates, which act as a sedative and
muscle relaxant in laboratory animals.
Often there is uncertainty about the identity of plants reported to cause an adverse reaction.
The exact scientific name of the plant, the plant part used and the name of the manufacturer are
very important pieces of information when writing ADR reports on herbal medicines. Solving the
existing problems requires the collaboration of botanists, phytochemists and pharmacologists.
The Uppsala Monitoring Centre has established a project with the aim of attaining global
standardization for herbal medicines. The scope is to standardize information about herbal
medicines, including their scientific names and therapeutic implications, which can vary widely
between countries. The structure of the ATC-system, developed for classification of orthodox
medicines, is employed in this work. The UMC group is collaborating with the University of
Exeter and the Royal Botanical Gardens at Kew in the UK, and with several other international
experts.
In the WHO data base there are presently 8985 case reports including a herbal preparation
suspected of causing the adverse reaction. The most commonly reported reactions are
Diarrhoea 121
Tachycardia 62
Anaphylactoid reaction 59
Hepatitis 57
Bronchospasm 49
Convulsion 39
Hallucination 39
Hypertension 39
Circulatory failure 37
Thrombocytopenia 36
Respiratory depression 33
Mohamed Farah
Scientist, Herbals Project
Dramatic expansion of the WHO Drug Monitoring Programme
In the previous issue of Uppsala Reports we described the new national centre in Russia and new
contacts established in India. Since then Russia has submitted adverse reaction case reports to
UMC and become an official member of the WHO Programme. At almost the same time Peoples
Republic of China submitted the first batch of reports and applied for membership in the
Programme. India recently did the same, now nominating a national centre. Applications for
membership were recently also received from Armenia, Georgia and Macedonia although ADR
reports have still not been received from these countries.
The implications of these new countries entering the WHO Drug Monitoring Programme are
considerable. Information will be received from drug markets that are different from those now
mainly represented in the WHO data base, with different population genetics, health care
systems, therapeutic traditions etc. adding to the value of the diversity of the WHO collection of
information. It will also mean that the WHO Drug Dictionary will be enriched with drug names
used in these countries only. The WHO data base and information shared within the WHO drug
safety network will be accessible to decision makers responsible for public health for another 2.2
billion people.
Contact information to the new national centres:
Armenia China P.R
Dr Samvel Azatyan Prof. Zhu Yonghong
Department of Pharmacovigilance & National Centre for ADR Monitoring
Rational Use of Drugs National Institute for Drug Control
Armenian Drug and Medical Temple of Heaven
Technology Agency Beijing P.R.C. 100050
15, Moskowian Street phone: +86-10-7017755
Yerevan 375001 fax: +86-10-7013755
phone: +374-2-528615 e-mail: chinaadr@public.bta.net.cn
fax: +374-2-151697
e-mail: pharmag@arm.r.am
Georgia India
Dr Zaza V. Chapichadze Prof. Suresh.K. Gupta
National Centre of Pharmacovigilance Department of Pharmacology
Drug and Pharmacy Department All India Institute of Medical Sciences
Ministry of Health Ansari Nagar
2, Gudamakari st New Delhi-110029
380092 Tbilisi phone: +91-11-6864851
phone: +995-32-607535 fax: +91-11-6862663
fax: +995-32-605373
e-mail: root@drugmonc.org.ge
Macedonia Russia
Prof. Stojmir Petrov Prof V.K. Lepakhin
National Centre for ADR Monitoring Federal Ctr for Adverse Drug Reaction Study
Institute of Preclinical and Clinical Ministry of Health of the Russian Federation
Pharmacology & Toxicology Mikluho-Maklaya str 8
50 Divizija B.B Moscow 117198
91000 Skopje phone: +7-095-4335600
phone: +389-91-235966 fax: +7-095-4340292
fax: +389-91-111828
New Reference Centre connected to the WHO Programme
In November 1997 the Institute of Pharmacology of the University of Verona, Italy, headed by
Professor Giampaolo Velo, was designated as a Reference Centre for Education and
Communication within the WHO Programme for International Drug Monitoring, by WHO
headquarters, Geneva. The department has in the past made important contributions to the
development of communications in pharmacovigilance to an important topic within the
Programme. Professor Velo was instrumental in organizing the meetings leading to the 'Verona-initiative' and the 'Erice declaration'. Recognition of this contribution by WHO facilitates
further initiatives in this area.