Pharmacovigilance

Shanthi Pal, M.Pharmacy, PhD

Quality Assurance and Safety of Medicines

WHO

2

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

3

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?

5

The science and activities relating to the detection, evaluation, understanding and

prevention of adverse drug reactions or any other drug-related problems

Pharmacovigilance

6

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

7

Why Pharmacovigilance?

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

8

Why Pharmacovigilance?

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

9

Why Pharmacovigilance?

Adverse Drug Reactions are among the top ten causes of mortality

(Lazarou J. et al., 1998)

10

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)

11

Why Pharmacovigilance?

Economic impact

Drug related morbidity and mortality expenses exceeded US$ 177.4 billion in the USA in

2000

(Ernst & Grizzle, 2001)

12

WHO Programme for International Drug WHO Programme for International Drug MonitoringMonitoring

WHOWHOHQHQ

WHO WHO Collaborating Collaborating

Centre, UppsalaCentre, Uppsala

National National CentresCentres

13

WHO Programme for International Drug Monitoring (HQ)

Policy Exchange of Information Technical support to countries Advisory Committee on Safety of Medicinal

Products

14

15

Technical support to countries

Training courses on pharmacovigilance (Regional Training Courses, biennial course by UMC and HQ)

Annual Meeting of Pharmacovigilance Centres

16

WHO Collaborating Centre (Uppsala Monitoring Centre)

ADR database No of reports: more than 3.5 million Each year increase ~160,000 / year

17

WHO Collaborating Centre (Uppsala Monitoring Centre)

ADR Reports Analysis Output

Feedback to National Centres Signal documents

18

19

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

20

Public Health or community health

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

21

Public Health Programmes

Specific to each country (developed or developing)

Dependent on:

The specific burden of illness

The epidemiology of prevalent disease

22

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

23

PHP

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

24

PHP ORGANIZATION

LEVEL

INTERNATIONAL

NATIONAL

LOCAL

SPONSORSWHO

OTHERS

MALARIA

PROGRAMME MANAGERS

HEALTH WORKERS

PATIENTS

V a c c i n e sMalaria

Tuberculosis HIV/AIDSFilariasis

MALARIA

PUBLIC HEALTH

PROGRAMMES

LOCAL COORDINATOR FOR HEALTH PROGRAMMES

Others

25

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?

26

PHP guidelines (WHO, National)

Inadequate (no) reference to: ADRs Pharmacovigilance Reporting

27

New Challenges in PHPs

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

28

Eroding confidence in the malaria programme

29

Main reasons of discontinuation of first HAART regimen within 1st year: ICONA

I C ON A

ItalianCohort

NaiveAntiretroviral

Monforte et al. AIDS 1999

Toxicity

Failure

Non-adherence

Other

Continued

30

EXISTING SYSTEMS

WHOPROGRAMME

S

WHOPROGRAMME

S

V a c c i n e sMalaria

TuberculosisFilariasis

HIV / AIDS

WHO-PV(UMC)

PV CoordinatorNational PV centre

PATIENTS

NATIONAL PUBLIC HEALTH PROGRAMMES

VaccinesMalaria

Tuberculosis Filariasis

HIV/AIDS

Health workers

Health workers

PATIENTS

31

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

32

Expert Safety Review Panel

INTEGRATING P.H.P AND PVFUNCTIONAL AND STRUCTURAL RELATIONSHIP

W.H.OPROGRAMME

S

W.H.OPROGRAMME

S

V a c c i n e sM a l a r i a

T u b e r c u l o s i sF i l a r i a s i s

T r a c h o m a t i s

WHO ADVISORYCOMMITTEE

WHO-PV(UMC)

PV CoordinatorNational PV centre

Health workers

NATIONAL PUBLIC HEALTH PROGRAMMES

V a c c i n e sM a l a r i a

T u b e r c u l o s i sF i l a r i a s i s

T r a c h o m a t i s

DISTRICT INVESTIGATION

TEAM

DRUG REGULATORY AUTHORITY

PATIENTS

PATIENTS

33

Strengthen spontaneous reporting systems Establish active surveillance component in public

health programmesHIV/AIDSMalariaLymphatic filariasis

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

PV and PHP Synergy

34

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

35

Collaboration with HIV/AIDS

Workshop in Pretoria 2004 Action plan developed by ACSoMP 2005 Joint training course planned for April 2006

36

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

37

"Dying from a disease is sometimes unavoidable. But, dying from an adverse

drug reaction is unacceptable".

- Dr Vladimir Lepakhin

Geneva 2005

38

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 YouThank You

Merci beaucoup !Merci beaucoup !