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Confounding A mixing of the effect of the exposure-disease relationship under study with the
relationship(s) of a third (or more) factor(s) to the disease.
1.
Confounding occurs when the observed exposure-disease relationship is in part or wholly
explained by the relationship between a third factor and the disease of interest.
2.
Confounding is different from bias in the sense that an association between the exposure of
interest and the outcome is a true association; it is just that the observed association is at least in
part due not to the effects of the exposure but rather to some other (cofounding) factor(s).
3.
Three essential characteristics of a confounding factor:
a)
The confounder is associated with the exposure of interest.
b)
The confounder is an independent risk factor for (i.e. causes) the disease.
c)
The confounder is not in the proposed causal pathway leading from the exposure of
interest to the disease of interest.
Causal Association of Interest
Exposure
Outcome
Association
Causal Association
Confounder
4.
5.
Example 1: A crude RR = 2.5 (95% CI: 1.5, 4.2); the adjusted RR = 1.0 after
controlling for a number of factors. These factors confound this relationship
to the extent that they completely explain the observed (crude) exposuredisease relationship
Although some have suggested that confounding can be considered present when the crude and adjusted measures differ by at
least 10% (10% rule of thumb), this is entirely arbitrary and should be replaced by a thoughtful consideration of how much
change is important in each particular situation.
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Example 2: A crude RR = 2.5 (95% CI: 1.5, 4.2); the adjusted RR = 2.0
(95% CI: 1.1, 3.4) after controlling for a number of factors. These factors
modestly confound (partially explain) this relationship, though the adjusted
(un-confounded) exposure-disease relationship is still statistically
significant.
Example 3: A crude RR = 2.5 (95% CI: 1.5, 4.2); the adjusted RR = 3.5
(95% CI: 2.2, 5.4) after controlling for a number of factors. These factors
confound this relationship but in the opposite direction (this can occur when
either the confounding factor is a protective factor rather than a risk factor,
or when the confounding factor is negatively associated with the exposure of
interest)
Example 4: A crude RR = 0.40 (95% CI: 0.15, 0.75); the adjusted RR = 0.65
(95% CI: 0.40, 1.2) after controlling for a number of factors. These factors
confound (at least partially explain) the relationship; the remaining adjusted
relationship is no longer statistically significant.
6.
7.
8.
Evaluating Confounding
a)
What was the observed effect of confounding in the study?
b)
Did the study identify and control for all of the important known confounders, i.e. are
there confounders not accounted for?
c)
Did the study measure and model the confounders appropriately, i.e. is can you identify
any possibility of residual confounding?
d)
What is the potential that there are unknown confounders still confounding the
relationship?
B.
Mediation occurs when the measured association between the exposure and the outcome is
mediated by one or more other factors
1.
2.
C.
These factors, like confounders, are associated with the exposure and cause the outcome, but
they are, by definition, in the causal pathway
We may adjust for these factors (as for confounders) to indicate how much of the association
between exposure and outcome is related to causal mechanisms involving the mediator.
Effect Measure Modification occurs when the measured association between the exposure and the
event/disease under study varies by levels of a third factor (i.e. when the measure of the effect the
exposure has on the outcome (the effect measure) is modified by varying levels of a third factor)
1.
2.
b)
These chi-square methods test the null hypothesis that the degree of
variability in the stratum-specific estimates is consistent with random
variation (thus rejecting the null hypothesis, with p-values <0.05, suggests
that the estimates are not homogeneous and should not be combined; failing
to reject the null hypothesis suggests that the estimates are homogeneous
enough to combine into an overall adjusted measure of association).
Statistical tests do not replace the need to make judgments about the
observed variation
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