Technical Briefing Seminar 22- 26 September 2008

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.
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Technical Briefing Seminar 22- 26 September 2008

What is Pharmacovigilance? WHO definition:

The science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drugrelated problem.
This applies throughout the life cycle of a medicine equally to the pre-approval stage as to the postapproval.
Technical Briefing Seminar 22- 26 September 2008

Pharmaco - Vigilance

Pharmaco = medicine Vigilare = to watch

o

alert watchfulness

forbearance of sleep; wakefulness watchfulness in respect of danger; care; caution; circumspection the process of paying close and continuous attention
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Technical Briefing Seminar 22- 26 September 2008

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
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Technical Briefing Seminar 22- 26 September 2008

Adverse event/experience WHO definition Any untoward medical occurrence that may present during treatment with a pharmaceutical product but which does not necessarily have a causal relationship with this treatment
Technical Briefing Seminar 22- 26 September 2008

Adverse Reaction to a medicine (ADR) WHO Definition A reaction which is noxious and unintended, and which occurs at doses normally used in man for the prophylaxis, diagnosis or therapy of disease, or for the modification of physiological function
Technical Briefing Seminar 22- 26 September 2008

Why do we need pharmacovigilance?

Technical Briefing Seminar 22- 26 September 2008

1959 / 61 Epidemia de focomelia por Talidomida (4.000 10.000 casos no mundo, com 15% de mortos)
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Technical Briefing Seminar 22- 26 September 2008

Why do we need pharmacovigilance?

Reason 1:

Humanitarian concern o Insufficient evidence of safety from clinical trials

o

Animal experiments

Phase 1 3 studies prior to marketing authorization

Technical Briefing Seminar 22- 26 September 2008

Drug Development
Technical Briefing Seminar 22- 26 September 2008

Limitations of phase 1 -3 clinical trials

limited size: no more than 5000 and often as little as 500 volunteers narrow population: age and sex specific

narrow indications: only the specific disease studied short duration: often no longer than a few weeks
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Technical Briefing Seminar 22- 26 September 2008

Examples of product recalls due to toxicity

Medicine Year Thalidomide 1965 Practolol 1975 Clioquinol 1970 Benoxaprofen 1982 Terfenadine 1997

Rofecoxib 2004 Veralipride 2007 Examples of serious and unexpected adverse events leading to withdrawal of medicine Phocomelia Sclerosing peritonitis Subacute nephropathy Nephrotoxicity, cholestatic jaundice Torsade de pointes Cardiovascular effects Anxiety, depression, movement disorders
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Technical Briefing Seminar 22- 26 September 2008

Why do we need pharmacovigilance?

Reason 2

Medicines are supposed to save lives

Dying from a disease is sometimes unavoidable; dying from a medicine is unacceptable. Lepakhin V. Geneva 2005
Technical Briefing Seminar 22- 26 September 2008

UK: US:

ADRs were 4th-6th commonest cause of death in the US in 1994 Lazarou et al, 1998 It has been suggested that ADRs may cause 5700 deaths per year in UK. Pirmohamed et al, 2004

Technical Briefing Seminar 22- 26 September 2008

125 Patients 24 Patients experienced ADRs (19%)

(59%) were avoidable

Technical Briefing Seminar 22- 26 September 2008

Why do we need pharmacovigilance? Reason 3: ADRs are expensive !!

Technical Briefing Seminar 22- 26 September 2008

6.5% of admissions are due to ADRs Seven 800-bed hospitals are occupied by ADR patients

Cost 446 million per annum

Technical Briefing Seminar 22- 26 September 2008

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
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Technical Briefing Seminar 22- 26 September 2008

Why do we need pharmacovigilance? Reason 4: Promoting rational use of medicines and adherence
Technical Briefing Seminar 22- 26 September 2008

Prescription Dr A. Who 31 December 2000 Re: Mr Joseph Bloggs 1) abacavir + lamivudine + zidovudine 1 BD 2) 3) 4) atenolol 100 mg/d acetylsalicylic acid 150mg/d cerivastatin 10 mg/d

5)

gemfibrozil 200 mg/d

6) metformin 500 mg/d 7) fluoxetine 50 mg/d

Sildenafil

HIV Clinic 2005

Technical Briefing Seminar 22- 26 September 2008

Main reasons of discontinuation of first HAART regimen within 1st year: ICONA
I C O N A

Italian Cohort Naive Antiretroviral

Monforte et al. AIDS 1999

Technical Briefing Seminar 22- 26 September 2008

Why do we need pharmacovigilance? Reason 5: Ensuring public confidence If something can go wrong, it will Murphy's law
Technical Briefing Seminar 22- 26 September 2008

Guardian Weekly March 18-24 2004

disaster!!
ALLEGATION: Known about SSRI prescribing at unsafe doses for a decade
Technical Briefing Seminar 22- 26 September 2008

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Technical Briefing Seminar 22- 26 September 2008

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Technical Briefing Seminar 22- 26 September 2008

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Need for Pharmacovigilance
Freetown, Sierra Leone 19th Aug. 2008

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PV in Emerging Countries, CPT2008 29th July 2008

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Safety concerns now high on the agenda of ALL countries

Developed countries Developing countries

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Technical Briefing Seminar 22- 26 September 2008

Why do we need pharmacovigilance?

Reason 6: Ethics To know of something that is harmful to another person who does not know, and not telling, is unethical
Technical Briefing Seminar 22- 26 September 2008

Consequence

Not reporting a serious unknown reaction is unethical valid for everyone

patient health professional manufacturer authorities

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Technical Briefing Seminar 22- 26 September 2008

Pharmacovigilance is Essential