Effect ModificationInteraction Effect Modification Factor that modify the

Effect Modification/Interaction

Effect Modification • Factor that modify the effect of an exposure on the outcome. • It is also known as statistical Interaction.

Effect Modification • EM is a biological phenomenon. • Can be compared to the biological concept of synergy

Effect Modification Bookish Language: In epidemiology “effect modification” describes a situation in which two or more risk factors modify the effect of each other with regard to the occurrence or level of a given outcome.

Effect Modification Simple Language: When the incidence rate of a disease in the presence of two or more factors differs from the incidence rate expected to result from their individual effects

Effect Modification Simple Language: • Effect can be greater than what we would expect (positive interaction, synergism), or • Effect can be less than what we would expect (negative interaction, antagonism)

Effect Modification/Interaction Bookish Language If the presence of the effect modifier potentiates the effect of the exposure of interest, then this modifier and the exposure are said to be synergistic (Positive interaction).

Effect Modification/Interaction Bookish Language: If it eliminates or diminishes the effect, then the modifier and the exposure are said to be antagonistic (negative interaction).

Difference with Confounding • Confounding refers to a situation in which variable that is associated with both the exposure and outcome of interest is responsible for the entirety or part of the statistical association between the exposure and outcome. • No biological phenomenon, only spurious/false finding - Confounding

EM Confounding VS Effect Modification O E E E O O C

Confounding • The confounder is causally associated with outcome. • Causally or non- causally associated with exposure. • It is not an intermediate variable in the causal pathway between exposure and outcome.

Note: to assess interaction, a minimum of 3 variables were needed in this study: • Aspirin • Anger • Coronary Heart Disease (CHD) Interaction = “Effect modification”: The “effect” of the risk factor -- anger – on the outcome – CHD -- differs depending on the presence or absence of a third factor (effect modifier) --aspirin. The third factor (aspirin) modifies the effect of the risk factor (anger) on the outcome (CHD). Aspirin Anger CHD

When is interaction present? • Two possible models to determine what is “expected” from the individual effects of the two or more factors: - Additive (effect of one exposure is added to the effect of the second exposure) - Multiplicative (effect of one exposure multiplies the effect of the second exposure) (Choice of models should be guided by our knowledge of the biology of the disease) 13

Incidence Rates and Attributable Risks for Groups Exposed to Neither Risk Factor or to One or Two Risk Factors (an Additive Model) Factor A Factor B + - + 3. 0 9. 0 15. 0 21. 0 14

Incidence Rates and Attributable Risks for Groups Exposed to Neither Risk Factor or to One or Two Risk Factors (an Additive Model) Incidence Rates Factor A + Factor B + 3. 0 15. 0 9. 0 21. 0 Attributable Risks Factor A + + 0 6 12 15

Incidence Rates and Attributable Risks for Groups Exposed to Neither Risk Factor or to One or Two Risk Factors (an Additive Model) Incidence Rates Factor A + Factor B + 3. 0 15. 0 9. 0 21. 0 Attributable Risks Factor A + + 0 6 12 18 16

Incidence Rates and Attributable Risks for Groups Exposed to Neither Risk Factor or to One or Two Risk Factors (a Multiplicative Model) Factor A Factor B + - + 3. 0 9. 0 15. 0 45. 0 17

Incidence Rates and Attributable Risks for Groups Exposed to Neither Risk Factor or to One or Two Risk Factors (a Multiplicative Model) Incidence Rates Factor A + Factor B + 3. 0 15. 0 9. 0 45. 0 Relative Risks Factor A + + 1 3 5 18

Incidence Rates and Attributable Risks for Groups Exposed to Neither Risk Factor or to One or Two Risk Factors (a Multiplicative Model) Incidence Rates Factor A + Factor B + 3. 0 15. 0 9. 0 45. 0 Relative Risks Factor A + + 1 3 5 15 19

How to determine whether it is Confounder or Interaction 20

Confounder or Interaction Criteria I (Must Remember)

Confounder or Interaction Criteria II (optional)

Herpes Zoster and Age (EM or Con? )

Herpes Zoster and Age (EM or Con? )

Herpes Zoster and Age (EM or Con? )

Thanks