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

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.

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

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

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.

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

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

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

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

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

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

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)

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)

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

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

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

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

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

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

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.)

Number of members of the WHO International Drug Monitoring Programme The increase of new member countries 1968-2009. There was a turning-point in 1990. After that the trend is a steady increase.

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

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

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)

Challenges to Pharmacovigilanc

Type of assistance needed

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

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

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

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

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

Members of PV Consultants Network for Africa

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

Thank you for your attention www.who.int info@who-umc.org www.who-umc.org