1. World Health Organization
28 March 2017
Challenges for the WHO Programme for International Drug Monitoring
Shanthi Pal Quality Assurance and Safety of Medicines
Cecilia Biriell
Reports, Analysis and Country Support

3. Risk
No medicinal product is entirely or absolutely safe for all people, in all places, at all times.
We must always live with some measure of uncertainty.

4. What is Pharmacovigilance?
World Health Organization
What is Pharmacovigilance?
28 March 2017
WHO definition:
The science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem.
This applies throughout the life-cycle of a medicine equally to the pre-approval stage as to the post-approval.
ADR monitoring – Medicines safety – Drug Monitoring

5. What is the scope of pharmacovigilance?
improve patient care and safety in relation to the use of medicines, and all medical and paramedical interventions,
improve public health and safety in relation to the use of medicines,
contribute to the assessment of benefit, harm, effectiveness and risk of medicines, encouraging their safe, rational and more effective (including cost-effective) use, and
promote understanding, education and clinical training in pharmacovigilance and its effective communication to the public

6. Why pharmacovigilance?
Humanitarian concerns
Hippocrates admonition
at least do not harm
Economical concerns
PV is needed to: 1. prevent unnecessary suffering 2. save money for other important things
A child with Stevens-Johnson syndrome (SJS) from an antiviral drug. SJS is a life-threatening condition affecting the skin in which cell death causes the epidermis to separate from the dermis. The syndrome is thought to be a hypersensitivity complex affecting the skin and the mucous membranes. Although the majority of cases are idiopathic, the main class of known causes is medications, followed by infections and (rarely) cancers. Important for doctors to be able to recognize it in order to immediately stop the drug.

7. Examples of product recalls due to toxicity
Medicine
Year
Examples of serious and unexpected adverse events leading to withdrawal
Thalidomide
1965
Phocomelia
Practolol
1975
Sclerosing peritonitis
Clioquinol
1970
Subacute nephropathy
Benoxaprofen
1982
Nephrotoxicity, cholestatic jaundice
Terfenadine
1997
Torsade de pointes
Rofecoxib
2004
Cardiovascular effects
Sibutramine
2010
Anxiety, depression, movement disorders

8. Studies of ADR related deaths
UK:
It has been suggested that ADRs may cause 5700 deaths per year in UK
Pirmohamed et al, 2004
US:
ADRs were 4th-6th commonest cause of death in the US in 1994
Lazarou et al, 1998
Sweden:
ADRs were 7th commonest cause of death in Sweden in 2001
Jönsson et al, 2010

9. World Health Organization
28 March 2017
125 Patients
24 Patients experienced ADRs (19%)
59% were avoidable
Intro 2

10. Cost of ADRs in the US?
Cost of drug related morbidity and mortality exceeded $177.4 billion in 2000
Ernst FR & Grizzle AJ, 2001: J American Pharm. Assoc
ADR related cost to the country exceeds the cost of the medications themselves

11. Pharmacovigilance in WHO HQ
Exchange of Information
Policies, guidelines, normative activities
Country support
Collaborations
Fund raising

12. WHO HQ Pharmacovigilance staff
Dr Shanthi Pal, Acting Manager
Medicines Saftey, QSM
+ 3 support staff

13. 1. Exchange of Information
National Information Officers
Publications
(WHO Pharm Newsletter, Restricted Pharm List, Drug Alerts, WHO Drug Information)
International Conference of Drug Regulatory Authorities (ICDRA)

14. 2. Policies, Guidelines and Normative Activities
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)

15. 3. Country support
Training courses on pharmacovigilance (Regional Training Courses, biennial course by UMC and HQ)
Address specific / stated needs: kava, ARVs, antimalarials….
Annual Meeting of Pharmacovigilance Centres

16. 4. Collaborations & Partnerships within WHO
Over a 100 million people targeted for either diethylcarbamazine citrate (DEC) plus albendazole or ivermectin plus albendazole.
Malaria
HIV/AIDS
Leprosy
Lymphatic Filariasis
Leishmaniasis
Chagas
Patient Safety
Poisons and Chemicals Safety
Traditional Medicines
Vaccines

17. 5. Resource Mobilisation
Gates foundation
European Commission
Global Fund
Others
Human resources:
WHO Consultants Network for Pharmacovigilance (PV) in Africa (PvSF – Pharmacovigilance Sans Frontières)

18. WHO International Pharmcovigilance Programme Full and Associate Members
At the moment there are 94 full member countries and 28 associate member countries. To become an associate member country, the government of a country needs to send an official application to the WHO HQ in Geneva. To become a full member the country also needs to send at least 20 ADR reports in a correct format. Less member countries in Africa but a major increase recently.
November 2010, 102 member countries

19. Uppsala Monitoring Centre (UMC) WHO Collaborating Centre for International Drug Monitoring
the operational centre of the WHO PV Programme
established as a foundation 1978
based on agreement Sweden - WHO
international administrative board
WHO Headquarters responsible for policy
self financed

20. UMC main tasks - summary
Collect and analyse ICSRs worldwide
Communicate potential drug safety issues
Actively support and provide training
Develop the science of pharmacovigilance

21. WHO Programme for International Drug Monitoring
UMC-A WHO-CC
Accra
UMC
WHO-CC
Uppsala
WHO-HQ
Geneva
National
Centres
Medical
practices
Pharma
companies
(Make doctors understand how their activity is connected to the WHO and that their contribution is critical. We are unable to do anything if they don’t produce any ADR reports in the first place.)

22. Number of members of the WHO International Drug Monitoring Programme
The increase of new member countries There was a turning-point in After that the trend is a steady increase.

23. Strengths Weaknesses Global PV network
National Centres Meetings
Only available global database of ADRs
Over 40 years track record in medicine safety
Public health approach
No hidden agendas
Weaknesses
Inadequate representation in Africa
Only Spontaneous reporting
no denominator data
poor quality reports
Little or no budget
PHPs: Vertical approach

24. Duplication of efforts Opportunities Threats Donor interest in PV
New partners
Malaria, HIV AIDS, neglected diseases
urgent PV needs
investing in new methods
Threats
Lucrative business
Lack of harmonization
Duplication of
efforts

25. Challenges to Pharmacovigilance
An analysis of pharmacovigilance activities in 55 low- and middle-income countries
Sten Olssona, Shanthi Palb, Andy Stergachisc, Mary Coupera
Drug Safety 2009/2010
(a: WHO CC, Uppsala; b: WHO QSM; c: UWa)

26. Challenges to Pharmacovigilanc

27. Type of assistance needed

28. WHO - UMC relationships
HIV/AIDS
WHO
Classifi-
cations
Vaccine
safety
Other
Tropical
Diseases
Malaria
Patient
Safety
Alliance
Medicines
Policy and
Standards
UMC

29. 3 tiers-approach for WHO
Maintain as the cheapest, easiest, most sustainable method
As before
Spontaneous reporting
Regional trainings – WHO and UMC
Country support – WHO, UMC and UMC-A
More than before
- Active surveillance
Tools - CEMFlow for Cohort Event Monitoring
Handbooks
Nigeria, Tanzania, Ghana – Cohort Event Monitoring in Public Health Programmes

30. Support, guidelines & technical resources
Expecting the Worst - Crisis Management                                                                                         
Support, guidelines & technical resources
Why do pharmacovigilance and how to do it. A critical examination of the strengths and weaknesses of present systems of safety monitoring, in order to increase their impact, and an overview of the challenges facing pharmacovigilance in the future. Guidelines for setting up (establishing) and running a Pharmacovigilance Centre.
Readings for the TBS:
The importance of pharmacovigilance
Safety of Medicines
The Safety of Medicines in public health programmes
Promoting Safety of Medicines for Children
Expecting the worst

31. 3 tiers-approach for WHO
As never before
Indicators
Minimum requirements for a Functional National PV System
Fundraising
EuropeAid; UNITAID, GFATM, PEPFAR; FP7 etc
Centres of excellence
Ghana – WHO Collaborating Centre for Advocacy and training in PV
Morocco – training for francophone countries
Developing networks
PV Consultants Network for Africa
Global Network for ADR reporting in prequalified vaccines
National Centres meeting in Ghana

32. Activities the last few months
Ghana, May
PV conference arranged by West African Health Organization
Morocco, June
Training course for francophone countries
Togo, October
PV Consultants Network for Africa
Ghana, November
Stakeholders meeting, Donors and WHO
Activities in other parts of the world:
Training course in Singapore for Asian countries
UMC country visits in eastern European countries
Restart of PV in India
Coming – training course in Mexico

33. Members of PV Consultants Network for Africa

34. Challenges for the future
To make PV systems sustainable through:
stable financing
trained and dedicated staff
Create a culture of reporting
from health professionals
the public

35. Thank you for your attention