07

Anwar Batiha

Aref Al-Mutairi
 The concept of confounding variable/factors:

What is confounding?

The concept basically establishes a relationship between an exposure(E) of a person

to an (event, incident, bad habit, environment, it may be anything) and a disease(D)
that is caused fully or partly by a third factor(C). An example would be the relationship
between high blood pressure and coronary artery disease. There is a relationship
between the two conditions mentioned earlier, however there is a variable that links the
two together that is a confounding variable which is hyperlipidemia.

Or A confounding factor (C) is: “a factor that is associated causally (or not causally) with
the disease and at the same time associated with the exposure of interest (E); but it
should not be caused by the exposure (E), i.e., it should not be on the causal pathway
between E and D.

Think of it like a triad or a third hidden angle that links the exposure and disease to
one another and forms a more reasonable link between the theory of HBP and CAD, so
hyperlipidemia leads to an increase in high blood pressure and causes CAD. Finally, it
should be made clear that hypertension alone if taken as a disease may be caused by
other underlying conditions which may not lead to CAD.
E= high blood pressure
D= CAD
C= hyperlipidemia/ hypercholesterolemia

Confounding is an error in interpretation not in measurement. This differentiates

confounding from bias which is a measurement error. However, sometimes
confounding is classified as “confounding bias”. It should be clear that an observed
association due to confounding is a real association, but it is interpreted, totally or
partially, as due to a third factor (a confounder).

Age and gender are frequently referred to as “the universal confounders”, since they
often confound associations. Example: Age is a potential confounder of the association
of coronary artery disease and physical exercise, because age is a risk factor of CAD
and older people are less likely to exercise. At least, part of the association between low
exercise and CAD is due to age.
A Hypothetical example of confounding:

• A case-control study reported that obesity was significantly associated with gall
bladder stones (cholelithiasis). However, gender as a potential confounder was
not controlled for in the study. This was the main criticism for the study
• The overall odds ratio (OR) for the association between obesity and cholelithiasis
was 7.4, a strong association indeed.
• After stratifying by gender (studying the association separately in males and
females), the OR declined to 1 in males and also to 1 in females. This means
that the observed overall association between obesity and cholelithiasis was
totally due to confounding by
gender. Stratifying by gender removed the effect of obesity on cholelithiasis.

• Explanation: obese subjects were more likely to be females who in turn are
more likely to have cholelithiasis. In other words, the proportion of females in the
case group was much higher than the proportion of females in the control group,
i.e., the 2 study groups were not balanced on gender.

Control of Confounding Variable/factors:

This is achieved by a few methods that may be implemented during either the design
stage or the analysis stage, this method is used to control factors that influence the
results of the association between the exposure and disease.

Methods used in control of confounding variables:

● Stratification: Stratify by the confounder (for example gender) and then assess
the association separately in males and females.

● Restriction: you restrict and limit the study to one stratum during the study: if
Gender was the confounding factor, then each gender will have the study
conducted separately i.e., males will have their own study and so will the
females. Done during the design stage.

● Matching: For each case you select one or more controls matched to the cases
on certain potential confounding variables.
● Standardization(adjustment): This is a statistical procedure to minimize or
remove confounding, usually by using a standard population (for example, the
world population as a standard). There are many ways for standardization such
as direct adjustment and indirect adjustment.

● Multivariate regression: A statistical procedure that provides the effect of a

variable after removing the effect of potential confounders

- Another example of multiple variables such as in smoking cessation

Multiple variables such as socioeconomic status, method of cessation, age,
which are multiple variables. Each of those variables is excluded one at a time
until a solid relationship is formed between one of the exposure variables and the
response variable

Conclusion
• In any study, investigators collect data on the variable of interest, and also on
many other variables envisaged as potential confounders. These potential
confounders are identified through a good review of the literature.
• Confounders can be dealt with using the methods mentioned in the previous
slides. The validity of the study results requires controlling for all potential
confounders. Otherwise, an observed association can be attributed to
confounding.

Done by Aref Al-Mutairi

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