Penelitian

Farmakoepidemiologi
Penentuan Besar Sampel
Pengatasan Bias
Sample Size Considerations for
Pharmacoepidemiology Studies
Epidemiologic study design
Information needed to calculate a study’s sample size
Information needed to calculate a study’s sample size
Key Points
Key Points
Bias and Confounding in
Pharmacoepidemiology
Selection Bias
Is a distortion of the measurement of an estimate of
effect, which is due to selection into the study of
groups of subjects, who have an unsual and unequal
relationship between drug exposure and outcome.

= sample distortion bias

Selection bias must be prevented at the design stage.
The objective is to prevent over the people who have a special
drug exposure-outcome relationship.

- Random sampling of the cases and controls to be included in

the study from the entire population
- Adopting a well codified accrual procedure
- Minimizing the number of subject lost to follow up in cohort
studies
- Selecting only incident cases of the condition
- Implementing a tracking procedures for those who drop out of
the study (in order to know the reason and to measure their
health status)
Biases in Pharmacoepidemiology
- Referral bias
- Recall bias
- Nondifferential or differential follow up bias
- Protopathic bias
- Prevalence study bias

For the purpose of coherence these classify in three groups

1. Selection bias (recruitment of study subjects or losses to
follow up)
2. Information bias (the accuracy of the information that is
collected on exposure & health status)
3. Confounding (pathophysiologic mechanisms of diseases
development)
Referral Bias
Occur if the reasons for refering a px may be related to
the drug exposure status.

- NSAID & abdominal pain (gastric ulcer)

- deep venous thrombosis (leg pain) & women using
OCs

If one can focus the question on more serious illness,

then this is no longer a problem
Information Bias
-Misclassification bias : exposure & disease status (the
reverse, i.e. unexposed people considered exposed &
sick people may be considered normal)

a. Nondifferential misclassification
- when the degree of misclassification is similar for all px
- independent of both exposure and health status condition -
occurs randomly
e.g.
Hazard function
Anaphylactic reactions occur rapidly
after drug exposure,
average risk the risk is thus very high during a
short period of time and null
after this period
basal risk
Anaphylaxis

hazard function Chronic long term users of

the same anti inflamatory
average risk drug are likely to be at a
lower risk of gi bleeding
than new users
basal risk

Gastric ulcer and anti inflamatory drugs

The average risk for the total period of follow up doesn’t represent the real risk
faced by the px. This measurement is likely to decrease the strength of the
association between drug exposure and adverse event.
b. Differential misclassification
When the degree of error in measuring disease
influenced by knowledge of the outcome status

- Differential recall (retrospective studies)

i.e. case control studies cases and controls may have a
different memory of their past exposures

- Differential detection
i.e. case control studies – procedures for exposure
assessment aren’t similar in cases and control
cohort studies – the follow up procedures for detecting
adverse event differ according to the exposure status
of the participant.
The problem of information bias must be revolved at
the design stage – affects the study validity.

- Blinding
- Standardization of the measurement process for both
cases and controls
- The choices of the criteria for defining drug exposure
and disease outcome
Confounding
- when the estimate of a measure of association between drug
exposure and health status is distorted by the effect of one or
several other variables which are also risk factors for the
outcome of interest.
- When the distribution of these risk factors is unbalanced
across the different levels of the drug exposure.

Confounders in pharmacoepidemiology :
- Confounding by indication for prescription
- Confounding by co-medication and other co-factor
- Effect modification by dose and drug potency
i.e.
a cohort study of drug use and risk of death (hypothetical)
a cohort study of drug use and allergy risk (hypothetical)
• Confounding occurs when the estimate of a measure of association
between drug exposure and health status is distorted by the effect of
one or several extraneous variables that are also risk factors for the
outcome of interest.
Factor influencing drug exposure
To control the effect of confounding at both the design
and the analysis level.

The design level :

- Randomization
- Matching
- Restriction

The Analysis level :

- Standardization
- Stratification
TERIMA KASIH
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