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WHO Programme for International Drug Monitoring : ensuring the safety of medicines

Dr Mary Couper & Dr Shanthi Pal

Quality Assurance and Safety: Medicines

Department of Medicines Policy and Standards

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Medicine Safety

To undergo treatment you have to be very healthy, because, apart from your sickness you have to withstand the medicine

Molière

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Pharmacovigilance (PV)

WHO definition

The science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem

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Why PV (1)

How pre-marketing knowledge about safety problems is created

Animal experiments (Incomplete picture) (ED50, LD50, kinetics, carcinogenicity, teratogenicity…)

Clinical trials (Incomplete information)

limited size

narrow population

narrow indications

short duration

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Why PV (2)

Topics to be studied after approval

reappraisal of indications extension or restriction

characteristics of users (risk factors, elderly/children)

inappropriate use e.g. addiction, off-label

rare adverse effects (ADR 1 in 1000 = 18 200 patients needed)

long-term toxicity

cost assessment

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Why PV (3)

Impact of ADRs

The cost factor

588 million $ / year in Germany (1997), > $ 177.4 billion in the US in 2000,

$847m / year in the UK (2006, BMJ)

Humanitarian reasons:

4-6th leading cause of death (Lazarou et al, JAMA; 1998)

Upto 19 % of in-patients will have an ADR (Davies et al, J Clin

Pharm & Ther; 2006);

up to 70 % ADRs are preventable (Pirmohamed et al, BMJ; 2006

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Why PV (4)

Newer reasons

Access driven (HIV AIDS, Malaria, TB)If access to medicines is a human right, then preventingavoidable harm from medicines is a professional and a moral obligation (Couper et al. BMJ ; 2006).

Public health approach to HIV-AIDS treatment (Gilks et al. Lancet ; 2006)

Fast track medicines in resource poor settings

Counterfeit medicines

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Why PV (5) : To be on top of things

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Pharmacovigilance : Major Aims

early detection of unknown safety problems detection of increases in frequency identification of risk factors quantifying risks preventing patients from being affected unnecessarily

Rational and Safe use of Medicines

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WHO Programme for WHO Programme for International Drug International Drug

MonitoringMonitoring

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WHO Programme for International WHO Programme for International

Drug MonitoringDrug Monitoring

WHOWHOHQHQ

WHO WHO Collaborating Collaborating

Centre, UppsalaCentre, Uppsala

National National CentresCentres

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History

16th WHA (1963) Pilot project of 10 countries (Australia, Canada,

Denmark, Germany, Ireland, Netherlands, New Zealand, Sweden, United Kingdom, USA)

23rd WHA (1970) 1978 WHO-Swedish agreement

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Pharmacovigilance in HQ

1. Exchange of Information

2. Policies, guidelines, normative activities

3. Country support

4. Collaborations

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1. Exchange of Information National Information Officers

(WHO Liaison Officers)

Publications (WHO Pharm Newsletter, Restricted Pharm List, Drug Alerts, WHO Drug Information)

International Conference of Drug Regulatory Authorities (ICDRA)

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2. Policies, Guidelines and Normative Activities Guidelines

The Importance of Pharmacovigilance (2002)

Safety Reporting - A guide to detecting and reporting adverse drug reactions (2002)

Policy perspectives on medicines (Pharmacovigilance) 2004

Safety monitoring of herbal medicines (2004)

Pharmacovigilance in Public Health Advisory Committee for the Safe Use of Medicinal Products (ACSoMP)

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3. Country Support

Strengthen spontaneous reporting systems

Establish active surveillance component in public health programmes

Work with the WHO Collaborating Centre for International Drug Monitoring (the Uppsala Monitoring Centre)

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4. Collaborations & Partnerships within WHO

Malaria HIV/AIDS Patient Safety Leprosy Lymphatic Filariasis and Helminths Poisons and Chemicals Safety Traditional Medicines

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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

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WHO CC Functions

ADR data base & management Identification of previously unknown drug reactions (Signal detection) Data management and signal detection tools (WHO-ART, WHO Drug

dictionary, ATC/DDD, Vigiflow-online, Vigisearch) ADR queries/searches PV training and country support Publications (Uppsala Reports, View Point, Signals document…) Net working (Vigimed)

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Examples of WHO signals generated by data mining

Topiramate and glaucoma Spring 2001

Antipsychotics and myocarditis Spring 2001

Olanzapine and granulocytopenia Spring 1998

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Vigisearch

adverse reaction profiles

IBUPROFEN - ADR profile

0 1000 2000 3000 4000 5000 6000 7000 8000

Appl site

Cardiovasc

Foetal

Liver-bil

Neoplasms

Repro

Skin

Vision

Sys

tem

Org

an C

lass

No of reports

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Countries in the Programme

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No of Countries

Members of WHO Drug Monitoring Programme

020406080

100

1969 1979 1989 1999

Year

No

of c

ount

ries

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Performance indicator (2005)

Frequency of reporting At least 4 submissions/12 months –

performing well

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Western Pacific Region

Performing well Australia (+) New Zealand (+)

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South East Asian Region

Performing well Malaysia Singapore (+) Thailand

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Eastern Mediterranean Region

Performing well Iran Jordan (+) Morocco Oman

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African Region

Performing well South Africa Ghana

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European Region

Performing well Moldova Russia Sweden Switzerland Turkey United Kingdom

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American Region

Performing well Argentina (+) Brazil (+) Canada (+) USA (+) Venezuela

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Equal partnership for effective Equal partnership for effective

pharmacovigilancepharmacovigilance

WHOWHOHQHQ

WHO WHO Collaborating Collaborating

Centre, UppsalaCentre, Uppsala

National National CentresCentres