Transcript Document

Mukesh Dheda
[email protected]
Byte Conference Centre 19 Jun 2009
Pharmaco igilance
Disclaimer / Caveat
The views expressed
are those of the presenter.
Prevention
Understanding
Assessment
Detection
Pharmacovigilance
Assessment of the effectiveness of these interventions
Size and severity of the problem
25 studies 1970-95
 Hospital admissions due to ADRs
4.2 - 6.0% with a median of 5.8%
Pharmacoepidem & Drug Safety 6; suppl 3: s71-s77 (1997)
Somerset Hospital Study
N=665 patients
 Hospital admissions due to ADRs (6.3%)
 Patients developed an ADR in hospital
(6.3%).
Mehta U et al. Br J Clin Pharmacol 2007; 65(3):396-406
National pharmacovigilance
NPC
NADEMC
MEDUNSA
OTHER PV CENTRES
Pharmacovigilance
Whose Responsibility?
Responsibility is shared between
Manufacturer, distributor, regulatory authority,
HCPs, media and consumers
Responsibility is retained throughout the
product life cycle even beyond the point of
use
Role and functions may differ between these
players
What is industry’s role?
Common goals of
Regulators and Industry
early detection of unknown safety problems
quantifying risks
detection of increases in frequency
identification of risk factors
assessing risk-benefit
preventing or minimising patient harm
Why South Africa needs its own
Pharmacovigilance programme?
Differences in:
 Access, distribution and use (e.g. indications, dose,
availability)
 Genetics, diet, traditions, language,
 Culture of medicine and drug use
 Pharmaceutical quality and composition (excipients) of
products
 Profile of diseases prevalent in the population
 Health care infrastructure, skilled human resources and
access to information, regulatory enforcement capacity
One Size doesn’t fit all…

A presentation on Promoting Safety of Medicines for Children by Anders Rane, National centres
meeting, Sweden, 2008.
Development of drug metabolising
enzymes in man
% Activity in an adult individual (100 %)
100
50
Most cytochromes
P450s
Conjugation with
glucuronic acid
Conjugation with sulphate
Cytochrome P450 3A7
0
 A Rane Sep 03
Birth
Paracetamol metabolism
in fetal
and
neonatal
period
sulfate
glucuronide
oxidised metabolite
glutathione conjugate
sulfate
in
adult
life
PARACETAMOL
PARACETAMOL
glucuronide
oxidised metabolite
glutathione conjugate
35
GRAPEFRUIT JUICE
7
WATER
Bailey et al. Br J Clin Pharmacol; 1998; 46: 101-110
Sorry doc, but…. could you please
give me the other drug just now?
This is your
medicine. Tell me
if you will have
any adverse
reactions and I’ll
give you another
drug.
Major Pharmacovigilance
Methods in SA
Individual Case Reports (Spontaneous reports)
Clinical Trials
Observational Cohort studies (controlled and
uncontrolled e.g. CEM)
Case control studies
Spontaneous ADR reporting
Principle
The alert health professional connects an
undesirable medical event with drug
exposure
SUSPICION
Reports suspicion to information collecting
centre
Spontaneous ADR reporting
Primary method --- reasons







large population
all medicines
hospital and out-patient care
long perspective
patient analyses possible
non-interventional
low cost
Spontaneous ADR reporting
disadvantages
 under-reporting
 difficult to detect
delayed reactions
reactions with high background
incidence
 number of exposed unknown
 bias
Safety reporting in South Africa
Post-Registration Safety
Reporting in SA
Based on Regulation 37 of Act 101 (1965)
Guidelines on Reporting Adverse Drug
Reactions in South Africa
May 2003
Good Pharmacovigilance Practice
includes…
 A culture of safety awareness among sales, regulatory and
marketing staff
 A proper data management system for ADR reports
 Procedures to ensure that appropriate and timely action can
be taken including a crisis management plan
 Compliance with local regulations and guidelines
 Compilation/co-ordination of safety reports and analyses
requested by regulatory authority
 A responsible appropriately trained person for pre- and postmarketing surveillance (if not a HCP, should have access to a
medically qualified person)
 Inform MRA of who this individual is
Do not submit a report unless it has
the following minimum information…
An identifiable source (reporter).
 This should include the name , address and
qualification.
An identifiable patient.
Name, initials or reference number.
Suspected product(s).
Suspected reaction(s).
Reports with all minimum info can still be of
poor quality!
What constitutes a good quality report?
 Patient clinical condition (i.e. underlying disease, comorbidity, gender, age, weight, renal function etc)
 Drug information (include all concurrent medication e.g.
OTC, complementary and chronic meds not suspected by
reporter)
 Event details (include baseline and subsequent lab data,
objective evidence of the event if any, response to
dechallenge and rechallenge, documented alternative
causes etc)
 Reporter qualifications, address and if patient referred,
then referring doctor to enable follow-up and further
investigation
What happens to reported ADR
 On receipt ---assign number
 Acknowledgement
 Database
 Evaluated individually and also check for similar
reports
 Recommendation made to committee/council
 Act on recommendation (draft MSA, PI changes,
request additional data from applicant, inform other
departments in DoH)
Opportunities to Improve Individual
Case Reporting
 Pregnancy exposures with no outcome reported
 Duplication of reports
 Lack of efficacy reports – with details of event not given
 No identifiable patient, reporter, ADR, or drug
 Inadequate clinical data/ summarised clinical data
submitted as ADR report instead of complete report
submitted by initial reporter
 Name of initial reporter anonymised – not in keeping with
guidelines
Opportunities to improve
communication of post-registration
safety information
Published safety studies and other regulatory decisions
– communication delayed or no communication
Changes to risk-benefit profile or where significant PI
changes are required (i.e. changes in conditions of
registration) –within 3 calendar days
Current guidelines do request that all safety data
derived from risk management activities are submitted
when regulatory action is necessary
Doctors v. Gun Owners
Number of physicians in the US: 700,000
Accidental deaths caused by physicians per year: 120,000
Accidental deaths per physician: 0.171
(U.S. Dept.of Health & Human Services)
Number of gun owners in the US: 80,000,000
Number of accidental gun deaths per year (all age groups): 1,500
Accidental deaths per gun owner: 0.0000188
Statistically, doctors are approximately 9,000 times
more dangerous than gun owners
"Not everyone has a gun, but just about everyone needs a doctor."
2008
2006
2004
2002
2000
1998
1996
1994
1992
1990
1988
1986
1984
1982
1980
1978
1976
1974
1972
1970
1968
Million reports cumulative
South Africa is part of an international PV system
Reports in VigiBase 1968 - 2008
5
4
3
2
1
0
Country Distribution in VigiBase
October 2008
Spain
2%
Sweden
2%
Thailand
2%
Australia
4%
Netherlands
2%
Canada
5%
France
5%
United States
50%
Germany
6%
United Kingdom
11%
Other Countries
11%
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Average ADR-reports /1 million Inhabitants
2003 - 2007
1000
900
800
700
600
500
400
300
200
100
0
Reporting Rates for South Africa
(< 100 reports/million inhabitants)
Thank you for your attention!
The future