Interaction or Effect Modification

Faculty Development Program
Clinical Epidemiology and Clinical Research
A Evans
Interaction or Effect Modification
Clinical definition:
Relationship between exposure and disease is different among different subgroups.
Epidemiologic definition:
Change in magnitude of an effect measure according to some third variable
(after exposure and disease).
Example: (cohort study)
Total Population: Heart disease No heart disease
Exposed 30 50
Unexposed 100 500
Crude RR = 2.25; Crude OR = 3.0
Males: Heart disease No heart disease
Exposed 10 10
Unexposed 5 100
RR = 10.5; OR = 20
Females: Heart disease No heart disease
Exposed 20 40
Unexposed 95 400
RR = 1.7; OR = 2.1
Confounding vs. Interaction (Rothman)
1. Confounding is a bias that you hope to prevent or control.
2. Interaction is just a more detailed description of the effect itself
(in all its rich diversity).
3. Confounding is something to avoid.
4. Interaction is something to report.
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Interactions and Clinical Trials
• Extreme caution! Most clinical trials are analyzed with logistic regression.
• Assess for interaction by asking yourself: Is the risk reduction different for different
clinical subgroups (eg, different baseline risk)?
• Do not believe the logistic model’s assessment of interaction.
• For important clinical subgroups, if the logistic model says there is no interaction,
then you have good evidence to believe the exact opposite—that is, there is variation
in treatment effectiveness!
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