Download Proactive Management of Drug Recalls in Resource Limited

Virginia Falcón
Advisor: Prof. Prashant Yadav
Arthritis drug Vioxx yanked off market
Study by the maker confirms risk of heart attack, stroke Company's study
confirms risk of heart attack, stroke
Sabin Russell, Chronicle Medical Writer
Friday, October 1, 2004
Pharmaceuticals
Big trouble for Merck
Nov 4th 2004
Merck Admits
a Datasales
Error on Vioxx
US $2.5 billions
in annual
Merck Agrees to Settle
Vioxx Suits
27.000
lawsuits Merck recalls Vioxx
for $4.85 Billion
By ALEX BERENSON
May 1999: FDA approves Vioxx
March 2000: study
reveals that Vioxx
patients are 2 times
more likely to have
cardiovascular problems
than Naproxen
April 2002: The FDA tells
Merck to add information
about cardiovascular risk
to Vioxx's label.
Aug. 25, 2004: database
analysis of 1.4 million
patients reveals that Vioxx
users are more likely to
suffer cardiac problems
than those taking
Celebrex.
Sept. 23, 2004: Merck
says it learned this day
that patients taking Vioxx
in a study were twice as
likely to suffer a heart
attack or stroke as those
on placebo.
Sept. 30, 2004: Merck
withdraws Vioxx from
the U.S. and the more
than 80 other countries
in which it was
marketed.


Defined by the WHO as “the science and
activities
relating
to
the
detection,
assessment, understanding and prevention of
adverse effects or any other possible drugrelated problems”
Adverse Drug Reactions account for around
3% of deaths in the developed world.
•
•
Pattern of disease burden and consequently drug use are different (developed
countries minimally use anti-TB, anti-malarial and anti-diarrheal drugs, for
example)
Patient genotype and phenotype are markedly distinct, with a large number of
malnourished patients and patients with concomitant diseases in developing
countries relative to developed countries
•
Social and economic conditions are different (higher rates of poverty and illiteracy
in developing countries)
•
Formulations and brands of drugs used are different
•
•
Diversity of drugs currently being launched (combination therapies) reaching
developing countries in greater numbers and more quickly because of new
funding
Faster scale up of public health programs due to availability of new funding from
major donors is exposing more patients to treatments.
Environment




Determine
proper
cohort
sizes
for
pharmacovigilance studies based on common
sampling techniques.
Devise sampling strategies to select sentinel
sites for data collection in order to reduce
biases.
Propose techniques to compensate for biases.
Apply all of the above in a case study for
Tanzania.
• Select at the site level those sites which could potentially bring to
the sample a representative mix of patients.
• Include in the design strategy the main sources of noise
(confounding factors) so we can either block its effects.
•Three approaches were explored: Cluster, Stratified and Quota
Sampling.
-Variables:
SSSSSSSSSSSSSSSSSSSSSSSSSSSSS
SSSSSSSSSSSSSSSSSSSSSSSSSSSSS
SSSSSSSSSSSSSSSSSSSSSSSSSSSSS
-Constraints:
•Minimum
S S S S S S Snumber
S S S S S S SofSpatients:
SSSSSSSSSSSSSS
SSSSSSSSSSSSSSSSSSSSSSSSSS SSS
•Include
S S S S SPrivate
S S S S S SFacilities:
SSSSSSSSSSSSSSSSSS
SSSSSSSSSSSSSSSSSSSSS SSSSSSSS
•Include hospitals
•Male/Female Ratio
•Urban/Rural Ratio
…
Pool of Sites
A AAAA
BBBBB
CCCCC
DDDDD
EEEEE
FFFFFF
GGGGG
HHHHH
KKKKK
MMMM
NNNNN
OOOOO
PPPPPP
QQQQQ
RRRRR
SSSSSS
TTTTT
UUUUU
IIIIIII
JJJJJJJ
Clustering
algorithms
Integer
Program
- Cohort size:
- Compensation for non-reporters:
- Compensation for biases:
Stratified
Sampling
Cluster
Sampling
Quota
Sampling



Controlling for confounders at the site
selection level for a CEM is both necessary
and feasible.
Sampling techniques can be used for site
selection.
The results of a study and its robustness
could be greatly enriched by the use of this
techniques.