Virginia Falcón

Advisor: Prof. Prashant Yadav

US $2.5 billions in annual sales

27.000 lawsuits

PharmaceuticalsBig trouble for MerckNov 4th 2004

Merck Agrees to Settle Vioxx Suits for $4.85 Billion By ALEX BERENSON

Merck recalls Vioxx

Merck Admits a Data Error on Vioxx

Arthritis drug Vioxx yanked off marketStudy by the maker confirms risk of heart attack, stroke Company's study confirms risk of heart attack, strokeSabin Russell, Chronicle Medical WriterFriday, October 1, 2004

Defined by the WHO as “the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other possible drug-related 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.

S S S S S S S S S S S S S S S S S S S S S S S S S S S S S

S S S S S S S S S S S S S S S S S S S S S S S S S S S S S

S S S S S S S S S S S S S S S S S S S S S S S S S S S S S

S S S S S S S S S S S S S S S S S S S S S S S S S S S S S

S S S S S S S S S S S S S S S S S S S S S S S S S S S S S

S S S S S S S S S S S S S S S S S S S S S S S S S S S S S

S S S S S S S S S S S S S S S S S S S S S S S S S S S S S

-Variables:

-Constraints:•Minimum number of patients:

•Include Private Facilities:

•Include hospitals

•Male/Female Ratio

•Urban/Rural Ratio

…

Clustering algorithms

Integer Program

Pool of Sites

- Compensation for non-reporters:

- Cohort size:

- 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.