1 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

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

3 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

4 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

5 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 = patients needed) long-term toxicity cost assessment

6 Why PV (3) Impact of ADRs The cost factor 588 million $ / year in Germany (1997), > $ billion in the US in 2000, $847m / year in the UK (2006, BMJ) Humanitarian reasons: 4-6 th 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

7 Why PV (4) Newer reasons Access driven (HIV AIDS, Malaria, TB) If access to medicines is a human right, then preventing avoidable 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

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

9 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

10 WHO Programme for International Drug Monitoring

11 WHO Programme for International Drug Monitoring WHOHQWHOCollaborating Centre, Uppsala NationalCentres

12 History 16 th WHA (1963) Pilot project of 10 countries (Australia, Canada, Denmark, Germany, Ireland, Netherlands, New Zealand, Sweden, United Kingdom, USA) 23 rd WHA (1970) 1978 WHO-Swedish agreement

13 Pharmacovigilance in HQ 1. Exchange of Information 2. Policies, guidelines, normative activities 3. Country support 4. Collaborations

14 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)

15 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)

16 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)

17 4. Collaborations & Partnerships within WHO Malaria HIV/AIDS Patient Safety Leprosy Lymphatic Filariasis and Helminths Poisons and Chemicals Safety Traditional Medicines

18 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

19 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)

20 Software for National Centres Vigibase on-line Dr RC NC Vigibase E2B Search Analysis

21 Signal Detection & Follow-up Combinations.db (reported quarterly) Triage (filter) Quarterly analysis BCPNN Vigibas e Review panel SIGNAL YesNo National Centres Pharma Company Follow-up

22 Examples of WHO signals generated by data mining Topiramate and glaucoma Spring 2001 Antipsychotics and myocarditis Spring 2001 Olanzapine and granulocytopenia Spring 1998

23 Vigisearch adverse reaction profiles

24 Countries in the Programme

25

26 Performance indicator (2005) Frequency of reporting At least 4 submissions/12 months – performing well

27 Western Pacific Region Performing well Australia (+) New Zealand (+)

28 South East Asian Region Performing well Malaysia Singapore (+) Thailand

29 Eastern Mediterranean Region Performing well Iran Jordan (+) Morocco Oman

30 African Region Performing well South Africa Ghana

31 European Region Performing well Moldova Russia Sweden Switzerland Turkey United Kingdom

32 American Region Performing well Argentina (+) Brazil (+) Canada (+) USA (+) Venezuela

33 Equal partnership for effective pharmacovigilance WHOHQWHOCollaborating Centre, Uppsala NationalCentres