Transcript An International AER System

The World Health Organization
(WHO) Program for International Drug
Monitoring and Its Database
Pippa Antonio, B.Sc.
Life Sciences Research Office,
Bethesda, MD 20814
Rationale behind its development
 Need for collaboration on an international scale
 To identify rare adverse reactions not previously
seen through clinical trials


Length of study
Participant selection


Co-morbid conditions
Concomitant medications
Historical Development of the WHO
Drug Monitoring Program (1)
 1968– Pilot Drug Monitoring Program began by WHO
 1970– Pilot project evaluated and methods accepted
 1978–Cooperative agreement between WHO and the
Swedish government.


Policy making decisions retained by WHO at HQ in Geneva
Database maintenance and operation moves to Uppsala
Historical Development of the WHO
Drug Monitoring Program (2)
 1978-83–Reports now filed by date of adverse event
and not by date report made
 1982– Adverse Reaction Newsletter
This is a yearly review of signals
(From the beginning of 2000 it was incorporated into the WHO
Pharmaceuticals Newsletter)
 1985– New Critical Terms list developed
Historical Development of the WHO
Drug Monitoring Program (3)
 1985-1990-- Developed a procedure for release of
data to 3rd parties
 1990– Medical Director added to the UMC
 1993 1st International Training Course, Uppsala
(5 courses 1993-1999)
Historical Development of the WHO
Drug Monitoring Program (4)
 1995– Start of Herbals monitoring project
Pilot study using data mining technique
 1996– Uppsala Reports
 1998– Vigimed email server
 1999– Pilot study from 1995 was accepted
and fully implemented.
Countries participating in the WHO International Drug
Monitoring Program to Date
Official Member Countries
Associate Member Countries
www.who-umc.org/whoprog.html
Top 10 Reporting Countries in WHO Database
(Period 1968-1997)
Country
Germany
France
USA
UK
Australia
Spain
Canada
Sweden
Netherlands
Denmark
Japan
Ireland
Year of Entry
1968
1986
1968
1968
1968
1984
1968
1968
1968
1968
1972
1968
Edwards, et al., 2002
% of Total Reports
20.0
16.5
11.9
11.1
9.0
6.6
6.2
4.5
1.6
1.4
1.4
1.4
Farah, et al., 2000
(Applies only to herbals)
WHO Definitions
 ADVERSE REACTION

WHO Technical Report No 498 (1972); 'A response to a drug
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.'
 SIGNAL

Reported information on a possible causal relationship
between an adverse event and a drug, the relationship
being unknown or incompletely documented previously.
Usually more than a single report is required to generate a
signal, depending upon the seriousness of the event and
the quality of the information.
http://www.who-umc.org/
Information Flow Towards a “Signal” Output
Patient
Patient
Health
Care
Provider
Patient
Health
Care
Provider
70 National
Pharmacovigilance
Centers
SIGNAL report
Patient
Health
Care
Provider
Patient
Patient
Health
Care
Provider
70 National
Pharmacovigilance
Centers
Health
Care
Provider
70 National
Pharmacovigilance
Centers
WHO Collaborating Center for
International Drug Monitoring
(Uppsala Monitoring Center)
Quarterly generation of
signals sent to independent
experts for evaluation
Patient
Temporary (24 month)
signal follow up list
Permanent Log
(history) file
Monitoring of Herbals
In the WHO database there are presently 11,716 suspected herbal case reports.
The most commonly reported critical terms and reported reactions are:
10.0%
9.0%
9.0%
8.0%
7.0%
8.0%
7.0%
6.0%
6.0%
5.0%
5.0%
4.0%
4.0%
3.0%
3.0%
2.0%
1.0%
2.0%
1.0%
0.0%
0.0%
Top 10 Reported Reactions
R
ea titis ma enia ion ain ions ura ath titis
em pa ede op ens st P uls rp De a
d
m
u
e o t t e v
er
e E H ngi ocy per Ch on P
D
c
C
A mb H y
Fa
o
Top 10 Critical Terms
r
Th
www.who-umc.org/projects.ht
Pr
u
U
as
rt ritis
h
ic
a
Er
yt R ria
he a
m sh
at
N ous
V aus
om ea
D itin
ia g
A
rr
bd
om F hea
in ev
al er
D Pai
yp n
sn
ea
10.0%
Bayesian Confidence Propagation Neural
Network (BCPNN)
P
IC  log
PP
xy
2
x
y
Where:
Px
= The probability of a specific drug being listed on a case report
Py = The probability of a specific adverse event being listed on a case report
Pxy = The probability that a specific drug-adverse reaction combination is
listed on a case report
Thus the Information Component (IC) value is based on:
•
•
•
•
The number of case reports with drug C (Cx)
The number of case reports with ADR Y (Cy)
The number of reports with the specific combination (Cxy)
The total number of reports
Lindquist, et. al. 2000
Signal Output
 Examples of signals highlighted by BCPNN,
identified by the panel and then circulated in the
4th quarter of 1997:
 FINESTERIDE
Breast Neoplasm
 RIFABUTIN
Corneal Ulceration
 FENFLURAMINE
Abortion
http://www.netcompetence.se/seminarier/umc/
What’s New?
 Data Management:
 New Vigibase on-line software management tool for
pharmacovigilance centers
 Publications:
 “Expecting the Worst - Crisis Management”
 “Dialogue in Pharmacovigilance” - more effective communications
 Online Tools:
 Ground-breaking Collaboration in Drug Safety Data
 Standardized Terminologies:
 Web enabled multi-dictionary browsing and encoding tool
 ICD- WHO ART Project – bringing together terminologies
References








Bate, A., et al., Eur J Clin Pharmacol (1998) 54:315-21
Bate, A., Eur J Clin Pharmacol (2002) 58: 483-490
Bate, A., et al., Drug Safety. 2002; 25(6); 393-397
Edwards, I.R., et al., Pharmacovigilance. (2002) 169182, 291-300
Farah, M., et al., Pharmacoepidemiology & Drug Safety
(2000) 9:105-112
Linquist, M., et al. Drug Safety. 2000 Dec 23 (6);533-542
Linquist, M., et al., J Rheu 2001;28-5;1180-1187
Olsson, S., Drug Safety 1998 Jul;19(1);1-10