Transcript The need for Pharmacovigilance

Pharmacovigilance
WHO definition
The science and activities relating to
the detection, assessment,
understanding and prevention of
adverse effects or any other drugrelated problem
Why pharmacovigilance?
• Humanitarian concerns
– Hippocrates’ admonition
“at least do not harm”
• Economical concerns
Why pharmacovigilance?
• Drug monitoring
• Drug surveillance
• Pharmacovigilance
– check if drugs on the market fulfil their
intended role in society i.e. if resources
spent on drugs produce optimal results in
terms of
• alleviating human suffering
• reduce disease related economical loss
How knowledge about safety
problems is created
• animal experiments
• clinical trials
• epidemiological
methods
– spontaneous
reporting
• case reports
• case series
– Post-Marketing
Surveillance (PMS)
– prescription event
monitoring
– cohort studies
• intensive hospital
monitoring
– case - control
studies
– record - linkage
• meta-analysis
Animal Tests
• acute toxicity
• organ damage
• dose
dependence
• metabolism
• kinetics
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carcinogenicity
mutagenicity
teratogenicity
species specificity
Statistical considerations
Incidence of
ADR to be
detected
Spontaneous
background
incidence
360
520
730
2 000
1 in 1 000
0
1 in 10 000
1 in 1 000
1 in 100
1 in 500 0
1 800
1 in 10 000 3 200
1 in 1 000
6 700
1 in 100
35 900
1 in 5 000
0
18 200
1 in 10 000
67 400
1 in 1 000
363 000
1 in 100
3 255 000
Incidence of Spontaneous
ADR to be background
detected
incidence
1 in 100 0
1 in 10 000
1 in 1 000
1 in 100
Minimum number
of patients to be
exposed
Minimum number
of patients to be
exposed
3 600
7 300
20 300
136 400
Limitations of clinical trials
• limited size
• narrow population
• narrow indications
• short duration
Topics to be studied after approval
• fine tuning of dosage
recommendations
• reappraisal of indications
– extension or restriction
Topics to be studied after approval
- continued
• assessment of side effects
– detection of unexpected adverse effects
and interactions
• identification of risk factors
• quantitative measurement of (un)safety
– long term safety/toxicity
– study of potential risk groups
(children/elderly, pregnant women etc)
– detection of unexpected beneficial effects
Topics to be studied after approval
continued
• characteristics of drug use and
drug users
• inappropriate drug use
– e.g. addiction, non-compliance,
medication error, intoxication
• quality of life and utility
assessment
• cost assessment
Topics to be studied after approval
continued
• pharmaceutical defects and
counterfeiting
• further kinetic, pharmacological and
mechanistic studies
• assessment of long-term efficacy
– e.g. when surrogate endpoints used for
approval
Need for information
Health authority to monitor:
1. Medicines of adequate quality
2. Medicines suitable for intended
purpose
benefit/risk balance
3. Medicines used rationally
science and experience
Need for information (2)
Health practitioner
– Each patient a therapeutic challenge
1. Knowledge
2. Therapeutic tools
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diet
surgery
medicines
etc
3. Knowledge and tools changing
– need for up-dating
Rational
therapy
Patient
Experience
report
Drug
Information
Health professional
Drug
experience
report
Drug
Information
Drug info/ADR reporting
Centre
Drug Authority
Spontaneous ADR reporting
Principle
The alert health professional connects
an undesirable medical event with drug
exposure
SUSPICION
Reports suspicion to information
collecting centre
International differences
Quantitative and Qualitative
• Disease prevalence
• Genetic
• Social
• Cultural
• Health care systems
• Health practices
• Indication for and use of medicines
• Pharmaceutical formulations
• Drug monitoring practices
Size and severity of the ADR problem
Meta-analysis
• 39 prospective studies from US
hospitals
• Overall incidence of serious ADRs =
6.7%
• Overall incidence of fatal ADRs =
0.32%
(106 000 individuals)
• 4th - 6th leading cause of death
Lazarou et al JAMA 1998;279: 1200 - 1205
ADRs in hospital patiens
Wiffen P et al. Bandolier Extra 2002; June: 1 - 16
Size and severity of the problem
25 studies 1970-75
• Hospital admissions due to ADRs
– 4.2 - 6.0% with a median of 5.8%
Pharmacoepidem & Drug Safety 6; suppl 3: s71-s77 (1997)
US estimate for 2000
• Cost of drug-related morbidity and
mortality
>177.4 billion US$
Ref. Ernst & Grizzle J Am Pharm Assoc. 41: 192(2001)
Direct costs of ADRs
13 studies 1980-95
• Median length of stay in hospital = 8.7 days
• Total estimated cost of ADRs in Germany =
588 million $/year
• 30.7% of admissions estimated to be
preventable
Pharmacoepidemiol & Drug Safety 6; suppl 3: S79-S90 (1997)
Burden of ADRs
England
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6.5% of hospital admissions
4% of hospital bed capacity
0.15% fatality
70% avoidable
Cost to NHS £466 million/year
• Pirmohamed M. et al. Br Med J 329:15-19 (2004)
Ethics in pharmacovigilance
• To know of something that is harmful
to another person, who does not
know, and not telling, is unethical
Modifiers
– knowledge - suspicion
– if other person should have known
– seriousness
– distance
Consequence
• Not reporting a serious unknown
reaction is unethical
valid for everyone
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patient
health professional
manufacturer
authorities
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