Transcript Technical Briefing Seminar 22

The need for
Pharmacovigilance
Mary R Couper and Shanthi Pal
Quality Assurance and Safety of Medicines
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Technical Briefing Seminar 22- 26 September 2008
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Technical Briefing Seminar 22- 26 September 2008
Medicine Safety
 To undergo treatment you
have to be very healthy,
because apart from your
sickness you have to
withstand the medicine.
Molière
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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
drug-related problem.
This applies throughout the life cycle of a medicine equally to
the pre-approval stage as to the post-approval.
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Technical Briefing Seminar 22- 26 September 2008
Pharmaco - Vigilance
 Pharmaco = medicine
 Vigilare = to watch
– 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
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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
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Technical Briefing Seminar 22- 26 September 2008
Why do we need pharmacovigilance?
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Technical Briefing Seminar 22- 26 September 2008

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1959 / 61– Epidemia de focomelia por Talidomida (4.000 – 10.000 casos no
mundo, com 15% de mortos)
Technical Briefing Seminar 22- 26 September 2008
Why do we need pharmacovigilance?
Reason 1:
 Humanitarian concern –
– Insufficient evidence of safety from clinical trials
– Animal experiments
– Phase 1 – 3 studies prior to marketing authorization
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Technical Briefing Seminar 22- 26 September 2008
Drug Development
Clinical development of medicines
Phase I
20 – 50 healthy volunteers
to gather preliminary data
250 – 4000 more varied
patient groups – to
determine short-term safety
and efficacy
Phase II
Phase IV
150 – 350 subjects with
disease - to determine
safety and dosage
recommendations
Post-approval studies to
determine specific safety issues
Phase I
Phase II
Development
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Technical Briefing Seminar 22- 26 September 2008
Phase III
Regi
Preclinical
Animal
Experiments
strat
ion
Animal experiments for
acute toxicity, organ
damage, dose dependence,
metabolism, kinetics,
carcinogenicity,
mutagenicity/teratogenicity
Phase III
Phase IV
Spontaneous
Post-approval
Reporting
Post Registration
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
 Examples of serious and unexpected
adverse events leading to withdrawal
of medicine
 Medicine
Year
 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
 Veralipride
2007
 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
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Technical Briefing Seminar 22- 26 September 2008
 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
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Technical Briefing Seminar 22- 26 September 2008
 125 Patients
 24 Patients experienced ADRs (19%)
(59%) were avoidable
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Technical Briefing Seminar 22- 26 September 2008
Why do we need pharmacovigilance?
Reason 3: ADRs are expensive !!
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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
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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
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Technical Briefing Seminar 22- 26 September 2008
Prescription
Dr A. Who
31 December 2000
Re: Mr Joseph Bloggs
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abacavir + lamivudine + zidovudine 1 BD
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atenolol 100 mg/d
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acetylsalicylic acid 150mg/d
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cerivastatin 10 mg/d
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gemfibrozil 200 mg/d
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metformin 500 mg/d
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fluoxetine 50 mg/d
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Sildenafil
Technical Briefing Seminar 22- 26 September 2008
Italian
Cohort
I
C O
N A
Main reasons of discontinuation
of first HAART regimen within
1st year: ICONA
Naive
Antiretroviral
Toxicity
Failure
Non-adherence
Other
Continued
Monforte et al. AIDS 1999
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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
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Technical Briefing Seminar 22- 26 September 2008
ALLEGATION:
Known about SSRI
prescribing at
unsafe doses for a
decade
Guardian Weekly
March 18-24 2004
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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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Technical Briefing Seminar 22- 26 September 2008
Safety concerns now high on the agenda of ALL
countries
 Developed countries
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 Developing countries
Need for Pharmacovigilance
Freetown, Sierra Leone 19th Aug.th2008
Technical Briefing Seminar 22- 26 September
2008
PV in Emerging
Countries, CPT2008 29 July 2008
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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
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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
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Technical Briefing Seminar 22- 26 September 2008