Download WHO Collaborating Centre for International Drug Monitoring The

WHO Collaborating Centre for International
Drug Monitoring
The WHO Programme for
International Drug Monitoring
The Uppsala Monitoring Centre
Monica Plöen
WHO Collaborating Centre
the Uppsala Monitoring Centre
• Established as a foundation 1978
• Based on agreement Sweden - WHO
• International administrative board
• WHO Headquarters responsible for policy
• Self financing
UMC activities
WHO Programme
Funding
Commercial sector
activities
WHO Drug Dictionaries
UMC organization
Director
Marie Lindquist
Finance and Core services
Birgitta Toreheim
6 people
Marketing
Annika Wallström
11 people
Safety Support and Services
Monica Plöen
22 people
External Affairs
Sten Olsson
5 people
Research
Niklas Norén
7 people
Production, Development and Quality
Johanna Eriksson
17 people
WHO Drug Monitoring Programme
Founding Members 1968
19
68
19
70
19
72
19
74
19
76
19
78
19
80
19
82
19
84
19
86
19
88
19
90
19
92
19
94
19
96
19
98
20
00
20
02
20
04
20
06
20
08
Member countries 1968-2009
100
90
80
70
60
50
40
30
20
10
0
Cumulative number of correct
reports processed per year
Country Distribution in Vigibase
October 2009
VigiSearch/
VigiMine
WHO-ART
Custom Searches
WHO database
VigiBase
WHO Drug
Dictionary
MedDRA
E2b
Intdis
Eudravigilance
Home-built
tools
Home-built
tools
Win ADR
National Centre
VigiFlow
National Centre
(simple entry tool)
VigiFlow – a software for
management of ADR case data
• SwissMedic 2001
• Free text possible
• Web based
• Mandatory fields
• E2B format
• Error checks
• Less report delay
• National database
UMC Function 1
Signal detection
• Primary UMC task
• Identification of previously
unknown drug reactions
Signal
WHO definition
•
•
Reported information on a possible causal relationship between an adverse
event and a drug, the relationship being unknown or incompletely
documented previously.
Note:
– A signal is an evaluated association which is considered important to investigate
further.
– A signal may refer to new information on an already known association.
– Usually more than a single report is required to generate a signal, depending
upon the seriousness of the event and the quality of the information.
Advantages of computerized
signal detection
• Necessary for huge databases
• Automatic, no time loss
• Objective, unbiased
• Reproducible
• Flexible (adjustable)
Method developed by the UMC
• BCPNN
– Bayesian Confidence Propagation Neural Network
• Select combinations ”standing out”,
for clinical review
– Represented by a high value of Information
Component (IC)
IC interpretation
• IC = 0 : Combination reported as often as
expected relative to the background
• IC > 0 : Combination reported more frequently
than expected
• IC025 > 0 : Also the lower value of the 97,5%
confidence interval is higher than expected from
the background
"1988:1"
"1989:1"
"1990:1"
"1991:1"
"1992:1"
"1993:1"
"1994:1"
"1995:1"
"1996:1"
"1997:1"
"1998:1"
"1999:1"
"2000:1"
"2001:1"
"2002:1"
"2003:1"
SSRI Neonatal convulsions or neonatal
withdrawal syndrome
All SSRI
6
4
2
0
-2
-4
-6
Signal Detection & Follow-up
Combinations.db
(reported quarterly)
Triage (filter)
Quarterly analysis
BCPNN
Vigibas
e
National Centres
Triage filter - selection of associations
• IC025 > 0; two or more countries
• Quarterly IC increase of 1 or more
• New drugs and serious ADRs irrespective of IC value
• (Target reaction terms (e.g. SJS), two or more reports,
irrespective of IC value)
 Literature check
Signal Detection & Follow-up
Combinations.db
(reported quarterly)
Triage (filter)
Quarterly analysis
BCPNN
Review
panel
Vigibas
e
National Centres
Signal review panel
• 40 experts from around the world
• Evaluate signals, together with UMC staff
and National Centres
• Select associations for follow-up
• Write signals in the SIGNAL document
The SIGNAL document
• Sent to all National Centres
• Individualized section
available to industry
• All recipients encouraged
to comment on topics
presented
Or published in WHO
Pharmaceutical Newsletter
Some WHO Signals detected
with data mining
Drug Safety Issue
Quantitatively highlighted
WHO Signal
Accepted as drug related
Topiramate -glaucoma
2nd quarter 2000
April 2001
October 2001c
Infliximab – pericardial effusion
4th quarter 2001
Dec 2002
August 2004c
Infliximab- vasculitis
2nd quarter 2000
Sept 2002
August 2004c
SSRIs – neonatal convulsions
4th quarter 1999
Dec 2001
May 2005a
Abacavir – MI
2nd quarter 2004
May 2005
April 2008b
A Confirmatory literature review
B RCT showing increased risk
C Labelling change
UMC functions 2
• Signal strengthening
– Web-based search programme
(Vigisearch/Vigimine)
– Search requests
Data available to non-members
• By request to WHO Collaborating Centre
• To degree health professionals
• Caveat document
UMC functions 3
• Comparing national experiences
International Differences
(Quantitative and Qualitative)
•
•
•
•
•
•
•
•
•
Disease prevalence
Genetic
Social
Cultural
Healthcare systems
Health professional practices
Indication for, and use of medicines
Pharmaceutical formulations
Drug monitoring practices
UMC functions 4
• Identification of risk factors
Potential Risk Factors
•
•
•
•
•
•
•
•
Other drugs
Sex/gender
Age
Genetic constitution
Dosage
Duration of treatment
Route of administration
Indication
WHO Drug Dictionary
• A source of international drug names
• Includes all drugs reported to VigiBase
• Information on MAH, form, strength, source etc.
• Drugs classified according to the ATC (AnatomicalTherapeutic-Chemical) classification system
• Ingredient names according to INN
WHO herbal ADR database
Valid scientific botanical names
• No internationally standardized and accepted
classification of all botanical names of medicinal
herbs exist
• the UMC has created a list of preferred botanical
names and their synonyms
The common name problem
Common name
Botanical name
Chemical relation
Chinese, Asian Ginseng
American Ginseng
Tienchi Ginseng
Siberian Ginseng
Russian Ginseng
Brazilian Ginseng
Wild red Am. Ginseng
Alaskan Ginseng
Wild Ginseng
Ayurvedic Ginseng
Ginseng of the Andes’
Panax ginseng Meyer
Panax quinquefolius L.
Panax pseudoginseng Wall.
Eletherococcus senticosus Maxim.
Acanthopanax senticosus Harms.
Rumex hymenosepalus Torr.
Pfaffia paniculata (Mart.) Kunze.
Echinopanax horridum (Sm.) Decne.
Aralia nudicaulis L.
Withania somnifera (L.) Dunal
Lepidium meyenii Walpers
Standard
Similar
Similar
Different
Different
Different
Different
Different
Different
Different
Different
Technical support to the WHO
Programme
• Guidelines
– Why and how to set up PV centres
• Terminologies
– WHO Adverse Reaction Terminology
– WHO Drug Dictionary
• Software development
–
–
–
–
–
Vigiflow
Paniflow
CEM-flow
Vigisearch/Vigimine
DD Browser
UMC involvement in local activities
2005-2009
• 2005
– India, Germany, Moldova, Turkey, Italy, Poland, Argentina
• 2006
– Uzbekistan, Brazil, Barbados
• 2007
– India, Nepal, South Africa, Ghana, China, UAE
• 2008
– Namibia, Philippines, India, Botswana
• 2009
– Uganda, Saudi Arabia, India, Tanzania, Nigeria, Mozambique
UMC - a communication centre
• WHO Pharmaceuticals Newsletter
• Uppsala Reports
• Internet home page
http://www.who-umc.org
• Vigimed e-mail discussion
group
Thank you for your attention!
Process for joining WHO Programme
1.
Ministry of Health (or
equivalent) designates
National Centre
2. Ministry of Health sends
formal application to WHOHQ, Geneva
Ministry of Health
2
5
5. WHO-HQ advises Ministry of
Health of admittance to the
Programme
National
Centre
3
3. National Centre sends
sample reports to the UMC
4. UMC notifies WHO-HQ
that reports are compatible
1
the UMC
WHO-HQ
Geneva
4