4.2.2. confounding classical approach

Second approach: “Classical” approach based on a priori criteria

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“Bias of the estimated effect of an exposure on an outcome due to the presence of a common cause of the exposure and the outcome” – Porta 2008

● A factor is a confounder if 3 criteria are met:● a) a confounder must be causally or noncausally

associated with the exposure in the source population (study base) being studied;

● b) a confounder must be a causal risk factor (or a surrogate measure of a cause) for the disease in the unexposed cohort; and

● c) a confounder must not be an intermediate cause (in other words, a confounder must not be an intermediate step in the causal pathway between the exposure and the disease)

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Exposure

E

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Disease (outcome)D

Confounder

C

Confounding Schematic

Szklo M, Nieto JF. Epidemiology: Beyond the basics. Aspen Publishers, Inc., 2000. Gordis L. Epidemiology. Philadelphia: WB Saunders, 4th Edition.

Exposure

EConfounder

C

Intermediate cause

Disease

D

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Exposure

E

ConfounderC

General idea: a confounder could be a ‘parent’ of the exposure, but should not be be a ‘daughter’ of the

exposure

Disease

D

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Example of schematic (from Gordis)

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Birth Order

E

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Down SyndromeD

Confounding factor: Maternal Age

C

Confounding Schematic

HRT use Heart disease

Association between HRT and heart disease

Confounding factor: SES

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Are confounding criteria met?

BRCA1 gene Breast cancer

Confounding factor:Age

x

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Are confounding criteria met?Should we adjust for age, when evaluating the association between a genetic factor and risk of breast cancer?

No!

Sex with multiple partners Cervical cancer

Confounding factor: HPV


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Sex with multiple partners

HPV Cervical cancer

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What if this was the underlying causal mechanism?

Obesity Mortality


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Confounding factor: Hypertension

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Obesity Hypertension Mortality

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What if this was the underlying causal mechanism?

Direct vs indirect effects

Obesity Hypertension Mortality

ObesityIndirect effect

Hypertension Mortality

Direct effect

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Direct effect is portion of the total effect that does not act via an intermediate cause 30

Indirect effect

Hernan MA, et al. Causal knowledge as a prerequisite for confounding evaluation: an

appl3ic3ation to birth defects epidemiology. Am J Epidemiol 2002;155(2):176-84.

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Simple causal graphs

DC E

Maternal age (C) can confound the association between multivitamin use (E) and the risk of certain

birth defects (D)

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Complex causal graphs

Hernan MA, et al. Causal knowledge as a prerequisite for confounding evaluation: an application to birth defects epidemiology. Am J Epidemiol 2002;155(2):176-84.

E DC

U

History of birth defects (C) may increase the chance of periconceptional vitamin intake (E). A genetic factor (U) could have been the cause of previous birth defects in the family, and could again cause birth defects in the current pregnancy

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Smoking

A

ECalcium

DBone

fractures

CBMI

supplementation

U

Physical

Activity

B

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Source: Hertz-Picciotto

More complicated causal graphs!

The ultimate complex causal graph!

36A PowerPoint diagram meant to portray the complexity of American strategy in Afghanistan!

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Education

4.2.2. confounding classical approach