Pharmacovigilance Shanthi Pal, M.Pharmacy, PhD Quality Assurance and Safety of Medicines WHO

Learning objectives Participants will be aware of what pharmacovigilance is Participants will learn why safety monitoring is important Participants will learn what WHO is doing in pharmacovigilance Participants will learn what they could do in pharmacovigilance

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

Pharmacovigilance What IS this?

Pharmacovigilance The science and activities relating to the detection, evaluation, understanding and prevention of adverse drug reactions or any other drug-related problems

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

Why Pharmacovigilance? Pre-marketing safety data Animal Experiments: Relevant? Clinical Trials: Complete?

Why Pharmacovigilance? Post Marketing Topics Unexpected adverse reactions Interactions Risk factors Quality of life Long-term efficacy Cost assessment

Why Pharmacovigilance? Adverse Drug Reactions are among the top ten causes of mortality (Lazarou J. et al., 1998)

Why Pharmacovigilance? The percentage of hospital admissions due to drug related events in some countries is about or more than 10%. (Bhalla et al, 2003; Imbs et al, 1999)

Why Pharmacovigilance? Economic impact Drug related morbidity and mortality expenses exceeded US$ 177.4 billion in the USA in 2000 (Ernst & Grizzle, 2001)

WHO Programme for International Drug Monitoring HQ WHO Collaborating Centre, Uppsala National Centres

WHO Programme for International Drug Monitoring (HQ) Policy Exchange of Information Technical support to countries Advisory Committee on Safety of Medicinal Products

Technical support to countries Training courses on pharmacovigilance (Regional Training Courses, biennial course by UMC and HQ) Annual Meeting of Pharmacovigilance Centres

WHO Collaborating Centre (Uppsala Monitoring Centre) ADR database No of reports: more than 3.5 million Each year increase ~160,000 / year

WHO Collaborating Centre (Uppsala Monitoring Centre) ADR Reports Analysis Output Feedback to National Centres Signal documents

Why Pharmacovigilance for Procurement and Management Supply Plans? It is not always the product that determines drug safety but how it is used There is a high risk of misuse of drugs Disease Population Drug Health care system More than 50% of ADRs are preventable

Public Health or community health Science and art of preventing disease, prolonging life and promoting health and efficiency through organized community efforts.

Public Health Programmes Specific to each country (developed or developing) Dependent on: The specific burden of illness The epidemiology of prevalent disease

DEVELOPING COUNTRIES Endemic and/or epidemic diseases Tuberculosis, Leprosy, HIV/AIDS, STD Malaria, Schistosomiasis, Amoebiasis, Leishmaniasis, Trachoma, Lymphatic filariasis, Onchocerciasis, High morbidity and mortality rates

PHP Education Environmental modifications Nutrition intervention Lifestyle and behavioural changes Mass free distribution of drugs

LOCAL COORDINATOR FOR HEALTH PROGRAMMES PHP ORGANIZATION I NTERNATIONAL Others SPONSORS WHO OTHERS Filariasis HIV/AIDS LEVEL Tuberculosis Malaria V a c c i n e s PUBLIC HEALTH PROGRAMMES MALARIA MALARIA NATIONAL PROGRAMME MANAGERS LOCAL COORDINATOR FOR HEALTH PROGRAMMES HEALTH WORKERS LOCAL PATIENTS

What about the risk / effectiveness of drugs used? PHP monitoring Incidence and prevalence of the disease Morbidity and mortality rates Number of patients treated Number of drug units delivered What about the risk / effectiveness of drugs used?

PHP guidelines (WHO, National) Inadequate (no) reference to: ADRs Pharmacovigilance Reporting

New Challenges in PHPs Adherence Mass treatment regimens Nutritional aspects Unlabelled and off-labelled indications (pregnant or breast feeding woman, small children, elderly people) Drug resistances New drugs Co-morbidities Adherence

Eroding confidence in the malaria programme

Italian Cohort Main reasons of discontinuation of first HAART regimen within 1st year: ICONA I C O N A Naive Antiretroviral Monforte et al. AIDS 1999

NATIONAL PUBLIC HEALTH PROGRAMMES HIV / AIDS Filariasis Tuberculosis Malaria V a c c i n e s WHO-PV (UMC) WHO PROGRAMMES EXISTING SYSTEMS HIV/AIDS Filariasis Tuberculosis Malaria PV Coordinator National PV centre Vaccines NATIONAL PUBLIC HEALTH PROGRAMMES Health workers Health workers PATIENTS PATIENTS

Urgent need for synergistic collaboration PHP opportunity to implement PV activities Offer a cohort of patients under controlled conditions to be monitored for safety over a period of time PV detect, evaluate, and prevent adverse events promote rational use of drugs in mass treatment programmes Evaluate the impact of the programmes improve acceptability of the programme

WHO-PV (UMC) PATIENTS PATIENTS Health workers INTEGRATING P.H.P AND PV FUNCTIONAL AND STRUCTURAL RELATIONSHIP T r a c h o m a t i s F i l a r i a s i s T u b e r c u l o s i s M a l a r i a V a c c i n e s WHO-PV (UMC) WHO ADVISORY COMMITTEE W.H.O PROGRAMMES DRUG REGULATORY AUTHORITY Expert Safety Review Panel T r a c h o m a t i s F i l a r i a s i s T u b e r c u l o s i s M a l a r i a PV Coordinator National PV centre V a c c i n e s NATIONAL PUBLIC HEALTH PROGRAMMES DISTRICT INVESTIGATION TEAM PATIENTS PATIENTS Health workers

PV and PHP Synergy Strengthen spontaneous reporting systems Establish active surveillance component in public health programmes HIV/AIDS Malaria Lymphatic filariasis Work with the WHO Collaborating Centre for International Drug Monitoring (the Uppsala Monitoring Centre)

Malaria Collaboration Joint training course Joint reviews of specific antimalarials Artemesinin derivatives Chlorproguanil-dapsone Amodiaquine-artesunate Joint initiatives for collaboration with pharmaceutical industry – Novartis Agreement

Collaboration with HIV/AIDS Workshop in Pretoria 2004 Action plan developed by ACSoMP 2005 Joint training course planned for April 2006

Collaboration with TDR Chlorproguanil-dapsone example Joint initiatives on post-marketing surveillance studies (Phase 4 clinical trials) Joint initiatives on development of pregnancy registers for antimalarials and antrietrovirals

"Dying from a disease is sometimes unavoidable "Dying from a disease is sometimes unavoidable. But, dying from an adverse drug reaction is unacceptable". Dr Vladimir Lepakhin Geneva 2005

Procurement and Supply Management Plan 2.6 Ensuring rational use of medicines Is there a system for monitoring adverse drug reactions and drug resistance? If yes, describe briefly how the system works. If no, describe plans to establish a system.

Thank You Merci beaucoup !