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Data Analysis: Confounders, Mediators, and Moderators

Data Analysis: Confounders, Mediators, and Moderators

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A Evans<br />

<strong>Data</strong> <strong>Analysis</strong>: <strong>Confounders</strong>, <strong>Mediators</strong>, <strong>and</strong> <strong>Moderators</strong><br />

Example 1:<br />

Q: Is one type of procedure for treating kidney stones more effective than another?<br />

<strong>Data</strong>: Procedure Success rate<br />

Adjust for size of stone:<br />

Conclusions<br />

Open 78% (273/350)<br />

Percutaneous 83% (289/350)<br />

Small stones Open 93%<br />

Percutaneous 83%<br />

Large stones Open 73%<br />

Percutaneous 69%<br />

F<br />

A ? B<br />

Procedure<br />

Stone size<br />

?<br />

Success<br />

1. The association between procedure <strong>and</strong> success rate is confounded (mixed up<br />

<strong>and</strong> confused) with stone size.<br />

2. After adjusting for stone size, open procedure appears to be more effective.<br />

A Evans, March 2006 <strong>Confounders</strong>, <strong>Mediators</strong>, <strong>Moderators</strong> 1


Example 2:<br />

Q: Does smoking affect quality of life?<br />

<strong>Data</strong>: Smoking mean QOL score<br />

Adjust for lung disease:<br />

Yes 75<br />

No 85<br />

No COPD Yes 90<br />

No 90<br />

COPD Yes 71<br />

Confounder? Moderator? Mediator?<br />

F<br />

A ? B<br />

No 71<br />

?<br />

Smoking<br />

Lung<br />

disease<br />

?<br />

QOL<br />

A Evans, March 2006 <strong>Confounders</strong>, <strong>Mediators</strong>, <strong>Moderators</strong> 2


Example 3:<br />

Q: Does hypertension cause strokes?<br />

<strong>Data</strong>: Risk of stroke by hypertension <strong>and</strong> smoking:<br />

Smoking No smoking<br />

Hypertension 33 1.1<br />

No hypertension 3 0.1<br />

Questions:<br />

1. Is smoking a potential confounder?<br />

2. Does smoking modify the relationship between hypertension <strong>and</strong> disease?<br />

3. In a logistic regression model, would the interaction term be significant?<br />

Confounder? Moderator? Mediator?<br />

A<br />

F<br />

?<br />

smoking<br />

Hypertension Stroke<br />

B<br />

hypertension*smoking<br />

+ smoking<br />

Hypertension<br />

Stroke<br />

– smoking<br />

A Evans, March 2006 <strong>Confounders</strong>, <strong>Mediators</strong>, <strong>Moderators</strong> 3


Summary<br />

Confounding is a bias you hope to prevent or control.<br />

Effect modification (interaction) is a more detailed<br />

description of the effect itself.<br />

Confounding is something to avoid.<br />

Effect modification is something to identify <strong>and</strong> report.<br />

<strong>Mediators</strong> clarify the causal pathway.<br />

Don’t control for a factor that is caused by the exposure<br />

of interest.<br />

Don’t control for a factor that is caused by the outcome<br />

of interest.<br />

Draw a conceptual model before analyzing data.<br />

References<br />

Weinberg. Toward a clearer definition of confounding. Am J Epidemiol 1993;137:1-8.<br />

Greenl<strong>and</strong>, Pearl, Robins. Causal diagrams for epidemiologic research. Epidemiology<br />

1999;10:37-48.<br />

Kaufman, Cooper. Commentary: Considerations for use of racial/ethnic classification in<br />

etiologic research. Am J Epidemiol 201;154:291-8.<br />

A Evans, March 2006 <strong>Confounders</strong>, <strong>Mediators</strong>, <strong>Moderators</strong> 4


Questions<br />

1. Are there disparities across ethnic groups in the burden<br />

of suffering from asthma?<br />

Do you control for SES?<br />

2. Is the disparity in asthma morbidity across ethnic groups<br />

mediated by SES?<br />

Do you control for depression score or local air pollution?<br />

3. Is the effect of ethnicity on asthma morbidity modified<br />

by socioeconomic factors?<br />

Equivalent null hypotheses:<br />

The difference in asthm morbidity between blacks <strong>and</strong> non-blacks is the<br />

same for each level of each socioeconomic factor.<br />

The interaction term between ethnic group <strong>and</strong> each socioeconomic<br />

factor will have a coefficient of zero.<br />

4. Which of the following are examples of confounding,<br />

interaction, both, or neither?<br />

Example Crude OR Stratum 1 Stratum 2 Adj OR<br />

1 2.36 2.43 2.32 2.37<br />

2 2.36 3.48 3.52 3.51<br />

3 2.36 1.03 1.18 1.06<br />

4 2.36 1.03 5.46 2.34<br />

5 2.36 2.43 5.46 4.02<br />

6 2.36 0.54 0.63 0.59<br />

7 2.36 0.54 3.52 1.98<br />

A Evans, March 2006 <strong>Confounders</strong>, <strong>Mediators</strong>, <strong>Moderators</strong> 5


5. Consider the two graphs below. Is there an interaction<br />

between exposure <strong>and</strong> age? Incidence of disease is plotted<br />

on the vertical axis <strong>and</strong> age (a potential confounder) is<br />

plotted on the horizontal axis. Separate lines are drawn the<br />

exposed (E+) <strong>and</strong> unexposed groups (E-).<br />

AGE<br />

E+<br />

E–<br />

AGE<br />

A Evans, March 2006 <strong>Confounders</strong>, <strong>Mediators</strong>, <strong>Moderators</strong> 6<br />

E+<br />

E–


6. You perform a case control study to evaluate alcohol as<br />

a cause of lung cancer. You (properly) select 150 cases <strong>and</strong><br />

150 controls. The results are below.<br />

CA No CA<br />

Alcohol 107 78<br />

No 43 72<br />

Total 150 150<br />

OR = 2.3 (P

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