WHO Collaborating Centre for International Drug Monitoring

The WHO Programme for

International Drug Monitoring

The Uppsala Monitoring Centre

Monica Plöen

WHO Collaborating Centrethe 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

Commercial sector activities

Funding

WHO Drug Dictionaries

UMC organizationDirector

Marie Lindquist

Finance and Core servicesBirgitta Toreheim

6 people

External AffairsSten Olsson

5 people

Safety Support and ServicesMonica Plöen

22 people

MarketingAnnika Wallström

11 people

ResearchNiklas Norén

7 people

Production, Development and QualityJohanna Eriksson

17 people

WHO Drug Monitoring ProgrammeFounding Members 1968

WHO Drug MonitoringProgramme

WHO Drug MonitoringProgrammeFounding membersFounding members

1968

Member countries 1968-2009

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Cumulative number of correct reports processed per year

Country Distribution in VigibaseOctober 2009

WHO-ART WHO Drug Dictionary

National Centre

E2b

National Centre

Intdis

Home-built tools

Eudra-vigilance

VigiFlow

Win ADR(simple entry tool)

Home-built tools

MedDRA

VigiSearch/ VigiMine

Custom Searches

WHO database

VigiBase

VigiFlow – a software for management of ADR case data

• SwissMedic 2001

• Web based

• E2B format

• Less report delay

• Free text possible

• Mandatory fields

• Error checks

• National database

UMC Function 1Signal detection

• Primary UMC task

• Identification of previously unknown drug reactions

Signal

• 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.

WHO definition

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

SSRI Neonatal convulsions or neonatal withdrawal syndrome

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Signal Detection & Follow-upCombinations.db

(reported quarterly)

Quarterly analysisBCPNN

Vigibase

National Centres

Triage (filter)

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-upCombinations.db

(reported quarterly)

Triage (filter)

Quarterly analysisBCPNN

Vigibase

Review panel

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 reviewB RCT showing increased riskC 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 (Anatomical-Therapeutic-Chemical) classification system

• Ingredient names according to INN

WHO herbal ADR databaseValid 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

Common name Botanical name Chemical relation

Chinese, Asian Ginseng Panax ginseng Meyer StandardAmerican Ginseng Panax quinquefolius L. SimilarTienchi Ginseng Panax pseudoginseng Wall. SimilarSiberian Ginseng Eletherococcus senticosus Maxim. DifferentRussian Ginseng Acanthopanax senticosus Harms. Different Brazilian Ginseng Rumex hymenosepalus Torr. DifferentWild red Am. Ginseng Pfaffia paniculata (Mart.) Kunze. DifferentAlaskan Ginseng Echinopanax horridum (Sm.) Decne. DifferentWild Ginseng Aralia nudicaulis L. DifferentAyurvedic Ginseng Withania somnifera (L.) Dunal DifferentGinseng of the Andes’ Lepidium meyenii Walpers Different

The common name problem

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

Ministry of Health

National Centre

the UMC

WHO-HQGeneva

1

2

3

4

52. Ministry of Health sends

formal application to WHO-HQ, Geneva

3. National Centre sends sample reports to the UMC

4. UMC notifies WHO-HQ that reports are compatible

5. WHO-HQ advises Ministry of Health of admittance to the Programme