Download Uppsala Monitoring Centre - World Health Organization

WHO Collaborating Centre for
International Drug Monitoring
the Uppsala Monitoring Centre
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WHO Drug Monitoring Programme
Founding Members 1968
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WHO Collaborating Centre
the Uppsala Monitoring Centre
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established as a foundation 1978
based on agreement Sweden - WHO
international administrative board
WHO Headquarters responsible for policy
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Flow of information
MEDICAL
PRACTICE
NATIONAL
CENTRES
MANUFACTURERS
WHO
COLLABORATING
CENTRE
WHO HQ
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WHO Database 2002.07.27
Number of Reports by Year
250000
Number of Reports
200000
150000
100000
50000
0
1968
1972
1976
1980
1984
1988
Year (Based on Onset Date)
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1992
1996
2000
Submitting ADR Reports
to WHO
• diskette requiring pc only
• diskette produced by national computer
system
• computer network (FTP/e-mail)
• Vigibase on-line
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Submitting ADR Reports
to WHO
• ICH - E2b format
• WHO agreed format
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Staff
– Medical Director
– 3 senior pharmacists
– 1 administrative manager
– 11pharmaceutical officers
– 3 R&D scientists
– 4 IT specialists
– 3 project coordinators
– 3 sales and marketing
– 2 assistants
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Functions 1
• Signal detection
– Identification of previously unknown drug
reactions
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New Signalling Procedure
What should be achieved?
• Signals should not be missed
• Signals should be found early
• ‘False’ signals should be kept to a
minimum
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Why use a Bayesian neural
network?
• An automated procedure with a power
to consider all combinations
– drug - ADR
– drug - indication - age - ADR
• All combinations are considered in an
unbiased manner
• Strong associations are highlighted for
clinical assessment
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Signal detection using a neural
network approach
• If the Posterior probability > Prior
probability
– The drug ADR combination is present more
often than expected
– This is represented by a high value of
Information Component (IC)
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Information Component (IC)
• Definition
– IC=log2 (Posterior Probability/ Prior
Probability)
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Captopril - Coughing
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0
-1
IC
-2
79:1 81:1 83:1 85:1 87:1 89:1 91:1 93:1 95:1
Time(year)
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Practolol, ATC C07AB - Peritonitis
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6
4
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-2
-4
Practolol
ATC C07AB
-6
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74
77
80
83
86
year
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89
92
95
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Procedure for signal analysis
Quantitative
threshold
Associations
Clinical
evaluation
Signals
Combinations
Quantitative information
Statistical measurements
Signal
document
Drug safety data
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Panel of signal reviewers
• 38 clinical and ADR experts
• voluntary consultants recruited globally
– assess associations in specialist area for
clinical significance
– write assessment report for SIGNAL
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Functions 2
• Signal strengthening
– Annual Type-A document
– Search requests
– Web-based search programme
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Functions 3
• adverse reaction profiles
IBUPROFEN - ADR profile
System Organ Class
Vision
Skin
Repro
Neoplasms
Liver-bil
Foetal
Cardiovasc
Appl site
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1000
2000
3000
4000 5000
No of reports
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6000
7000
8000
Functions 4
• Comparing national experiences
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International Differences
• Examples
– metamizole
– nitrofurantoin
– mianserin
– flucloxacillin
blood cells
respiratory neurological
blood cells
liver
Apparent or Real?
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International Differences
(Quantitative and Qualitative)
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disease prevalence
genetic
social
cultural
healthcare systems
health professional practices
indication for, and use of medicines
pharmaceutical formulations
drug monitoring practices
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Functions 5
• identification of risk factors
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Potential Risk Factors
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other drugs
sex / gender
age
genetic constitution
dosage
duration of treatment
route of administration
indication
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Functions 6
• Combining ADR figures with other data
– drug utilization statistics
– population statistics
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UMC - a communication centre
• WHO Pharmaceuticals Newsletter
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UMC - a communication centre
• WHO Pharmaceuticals Newsletter
• Uppsala Reports
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UMC - a communication centre
• WHO Pharmaceuticals Newsletter
• Uppsala Reports
• Internet home page
http://www.who-umc.org
• Vigimed e-mail discussion group
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Pharmacovigilance Training
• Training course
– Uppsala, Canberra
– 2 weeks
– 25 participants
– 8th course May 2003
• Internet-based training
• Regional and local activities
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UMC involvement in local
activities 1998 - 2002
• 1998
– Norway, China, Portugal, Malaysia, Morocco, India
• 1999
– Philippines, Venezuela, Mexico, South Africa
• 2000
– India, China, Kuwait, Romania, Uruguay
• 2001
– Oman, Russia, Ghana, Fiji, Singapore, Vietnam
• 2002
– Cuba, Chile, Morocco, Malaysia, Cyprus
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Technical support
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documentation of established
systems
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Technical support
• literature coverage
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Technical support
• literature coverage
• guidelines
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Technical support
• literature coverage
• guidelines
• terminologies
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Terminologies
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WHO Adverse Reaction Terminology
WHO Drug Dictionary
ATC Classification
ICD Classification
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Technical support
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literature coverage
guidelines
terminologies
software development
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Software for National Centres
Vigibase on-line
Search
Analysis
E2B
Dr
RC
NC
Vigibase
E2B
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UMC Functions
• Harmonisation
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Definitions established
within the WHO Programme
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Adverse reaction
Adverse event
Side effect
Signal
Serious reaction
Causality:
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certain
probable/likely
possible
unlikely
conditional/unclassifiable
unassessable
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Worldwide network of
knowledge and competence
• Annual meeting of representatives of
National Centres
• Working relations with relevant
organizations
– CIOMS, ISoP, ISPE, DIA, IPCS, HAI, IFPMA, etc
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Research and development
• Methods for signal identification and analysis
– data-mining approach to signal analysis
• Improved monitoring of traditional medicines
– collaboration with Royal Botanical Gardens, Kew,
UK
• Good communications practice in
pharmacovigilance; collaboration with:
– University of Verona
– EQUUS
– CIOMS
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Ideas in Planning Phase
• Single international database for
industry reports
• Phenotype/genotype testing of affected
subjects
• Chemical structure/clinical safety
relationship
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Data available to non-members
• by request to WHO Collaborating Centre
• summary figures from all countries
• case reports by consent (automatic
from 50 countries)
• Caveat document
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Requirements for joining the
WHO Programme
• programme for collection of
spontaneous ADR reports established
• a National Centre designated by
Ministry of Health
• technical competence to fulfil WHO
reporting requirements
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Process for joining WHO Programme
1. Ministry of Health (or
equivalent) designates
National Centre
2. Ministry of Health sends
formal application to WHOHQ, Geneva
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Ministry of Health
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National
Centre
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3. National Centre sends
sample reports to the UMC
the UMC
4. UMC notifies WHO-HQ
that reports are compatible
WHO-HQ
Geneva
5. WHO-HQ advises Ministry of
Health of admittance to the
Programme
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Thank you for your attention!
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