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Disclaimer / Caveat
The views expressed
are those of the presenter.
Pharmacovigilance
Ass
essm
ent
Und
erst
andi
ng
Det
ecti
on
Pre
vent
ion
Assessment of the effectiveness of these interventions
Size and severity of the problem
25 studies 1970-95
Hospital admissions due to ADRs4.2 - 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
MEDUNSA
NPC
NADEMC
OTHER PV CENTRES
Pharmacovigilance Whose Responsibility?
Responsibility is shared betweenManufacturer, 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 problemsquantifying risksdetection of increases in frequencyidentification of risk factorsassessing risk-benefitpreventing 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
%100
50
0
Activity in an adult individual (100 %)
Birth
Most cytochromesP450s
Cytochrome P450 3A7
Conjugation withglucuronic acid
Conjugation with sulphate
A Rane Sep 03
Paracetamol metabolism
sulfate PARACETAMOL glucuronide
oxidised metabolite
glutathione conjugate
sulfate PARACETAMOL glucuronide
oxidised metabolite
glutathione conjugate
in fetal and
neona-tal
period
in adult
life
35
7
Bailey et al. Br J Clin Pharmacol; 1998; 46: 101-110
WATER
GRAPEFRUIT JUICE
This is your medicine. Tell me if you will
have any adverse
reactions and I’ll give you another
drug.
Sorry doc, but…. could you please give me the other drug just now?
Major Pharmacovigilance Methods in SA
Individual Case Reports (Spontaneous reports)
Clinical TrialsObservational 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 reportingPrimary method --- reasons
large population all medicines hospital and out-patient care long perspective patient analyses possible non-interventional low cost
Spontaneous ADR reportingdisadvantages
under-reporting difficult to detect
delayed reactionsreactions 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 AfricaMay 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 post-marketing 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, co-morbidity, 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 reportsLack of efficacy reports – with details of event
not givenNo 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: 700,000Accidental deaths caused by physicians per year: 120,000Accidental deaths per physician: 0.171(U.S. Dept.of Health & Human Services)
Number of gun owners in the US: 80,000,000Number of accidental gun deaths per year (all age groups): 1,500Accidental 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."
Reports in VigiBase 1968 - 2008
0
1
2
3
4
5
1968
1970
1972
1974
1976
1978
1980
1982
1984
1986
1988
1990
1992
1994
1996
1998
2000
2002
2004
2006
2008
Million r
eport
s cu
mula
tive
South Africa is part of an international PV system
Country Distribution in VigiBaseOctober 2008
Spain2%
United States50%
United Kingdom11%
Other Countries11%
Netherlands2%
Thailand2%
Germany6%
France5%
Canada5%
Australia4%
Sweden2%
0
100
200
300
400
500
600
700
800
900
1000
Average ADR-reports /1 million Inhabitants2003 - 2007
Reporting Rates for South Africa
(< 100 reports/million inhabitants)
Thank you for your attention!
The future