Nama : Ajeng Prastiwi Suci W

Nim : 16/403174/PKU/15992
Peminatan : KESLING

Tutorial Epidemiologi 5.2

Confounding and Modification Effect

Overview
Epidemiological studies aim to identify exposures that may increase or decrease the risk of
developing a certain disease (or outcome). Unfortunately, errors in the design, conduct and
analysis can distort the results of any epidemiological study. Even if errors do not seem to be
an obvious explanation for an observed association between an exposure and an outcome, it
may or may not be causal. In this session we will discuss the potential pitfalls in epidemiological
studies.

Learning objective
a. Discuss a confounding variable provides an alternative explanation for an observed
association between an exposure and an outcome
b. Discuss the interaction in an association

Confounding and Modification effect

Confounding provides an alternative explanation for an association between an exposure and
an outcome. It occurs when an observed association between an exposure and an outcome is
distorted because the exposure of interest is correlated with another risk factor. This additional
risk factor is also associated with the outcome, but independently of the exposure of interest.
An unequal distribution of this additional risk factor between those who are exposed and
unexposed will result in confounding. This situation is illustrated in Figure 9.1. Here,
association 1 is an example of confounding where smoking is the confounding variable in a
study to assess the relationship between occupation and lung cancer. In association 2, the
variable blood cholesterol is on the causal pathway between diet and heart disease, is not
associated with the disease independently of diet, and is therefore not a confounder. In
association 3, alcohol consumption is not a confounder because it is not associated with lung
cancer at all.
A potential confounder is any factor that can have an effect on the risk of disease under study.
This includes factors that have direct causal links with the disease, and factors that are proxy
measures for other unknown causes (i.e. age and social class). In the next activity, you will look
at the effect that confounding can have on the estimates of association calculated in a study

Activity 1
In a case–control study, coffee drinking was observed to be associated with the risk of cancer
of the pancreas. The importance of this association was disputed because it was noted that
coffee drinking was correlated with cigarette smoking and cigarette smoking was also
associated with cancer of the pancreas. So, cigarette smoking may have confounded the
observed association between coffee drinking and cancer of the pancreas. The observed odds
of exposure to coffee among all cases and controls are shown in Table 4.

Exposure Cases Control Total

Coffee Drinkers 450 (a) 600 (b) 1050
Non Coffee Drinkers 300 (c) 750 (d) 1050
Total 750 1350 2100

1. What is the odds ratio of exposure to coffee in cases compared to controls?

𝒂⁄ 𝟒𝟓𝟎⁄ 𝟎,𝟕𝟓
𝑶𝑹 = 𝒄⁄
𝒃
= 𝟑𝟎𝟎 𝟔𝟎𝟎 = = 𝟏, 𝟖𝟕 ≈ 1,9
𝒅 ⁄𝟕𝟓𝟎 𝟎,𝟒
≈ The odds of exposure to coffee are 1,9 times higher in cases of cancer of the pancreas
compared to healthy controls.

Because the researchers in this study believed that coffee drinking and cigarette smoking
might be correlated, and also that cigarette smoking was associated with cancer of the
pancreas, they calculated the odds ratio of exposure among smokers and non-smokers
separately (Table 5).
Smoker Non Smoker
Exposure Cases Control Cases Control Total
Coffee Drinkers 400 300 50 300 1050
Non Coffee Drinkers 200 150 100 600 1050
Total 600 450 150 900 2100

2. What is the odds ratio of exposure to coffee compared to controls among smokers
and non-smokers?
a. The odds ratio of exposure to coffee compared to controls among smokers :
𝟒𝟎𝟎⁄ 𝟏,𝟑𝟑
𝟑𝟎𝟎
𝑶𝑹 = 𝟐𝟎𝟎⁄ = =𝟏
𝟏𝟓𝟎 𝟏,𝟑𝟑
 b. The odds ratio of exposure to coffee compared to controls among non-smokers :
𝟓𝟎⁄ 𝟎,𝟏𝟕
𝟑𝟎𝟎
𝑶𝑹 = 𝟏𝟎𝟎⁄ = =𝟏
𝟔𝟎𝟎 𝟎,𝟏𝟕
≈ Smokers who drinking coffee have risk of pancreatic cancer as well as in non-smokers
3. What is your inference regarding the association between coffee drinking and cancer
of the pancreas?

The odds ratio of coffee drinking is 1 in both smokers and non-smokers. So that, the observed
association between coffee drinking and cancer of the pancreas have been confounded by the
effects of smoking

To explore confounding further, look at the evidence of association between smoking and
coffee drinking, and between smoking and cancer of the pancreas as shown in Tables 6 and
7.

Table 6. Association between smoking and coffee drinking

Exposure Smokers Non smokers Total
Coffee Drinkers 700 350 1050
Non Coffee Drinkers 350 700 1050
Total 1050 1050 2100

Table 7. Association between smoking and cancer of the pancreas

Exposure Cases Control Total
Smokers 600 450 1050
Non Smokers 150 900 1050
Total 750 1350 2100

4. What is the odds ratio of coffee drinking among smokers compared to nonsmokers?
𝟕𝟎𝟎⁄ 𝟐
𝑶𝑹 = 𝟑𝟓𝟎 𝟑𝟓𝟎 = =𝟒
⁄𝟕𝟎𝟎 𝟎,𝟓
≈ The odds of exposure are 4 times higher in smokers compared to non-smokers.

5. What is the odds ratio of smoking in cases compared controls?

𝟔𝟎𝟎⁄ 𝟏,𝟑𝟑
𝑶𝑹 = 𝟏𝟓𝟎 𝟒𝟓𝟎 = =𝟖
⁄𝟗𝟎𝟎 𝟎,𝟏𝟕
≈ The odds of smoking are 8 times higher in cases compared to control. Both coffee drinking and
smoking are risk factor of pancreatic cancer. So that either coffee drinking or smoking could become
confounder toward the other.
Activity 2
A case-control study examined the association between chronic Helicobacter pylori infection
and coronary heart disease at young ages. In total, 1122 survivors of suspected acute myocardial
infarction at age 30-49 years were recruited. For each case, a control matched for age and sex
with no history of coronary heart disease was enrolled. Chronic infection with H pylori was
confirmed serologically. Information on other risk factors for coronary heart disease was
collected, including smoking behavior, indicators of socioeconomic status, obesity, and blood
lipid concentrations. Controls were asked about their current habits and history, whereas cases
were asked about their habits and history just before their index myocardial infarction. Blood
samples were obtained from cases within 24 hours of the onset of symptoms and from controls
after collection of the information about risk factors. Early onset myocardial infarction was
significantly associated with seropositive H pylori infection antibodies (odds ratio 2.28 (99%
confidence interval 1.8 to 2.9)). The odds ratio was reduced to 1.87 (1.42 to 2.47) after
adjustment for smoking and indicators of socioeconomic status and to 1.75 (1.29 to 2.36) after
additional adjustment for blood lipid concentrations and obesity. Therefore, a moderate
association existed between coronary heart disease and H pylori infection seropositivity that
could not be fully explained by other risk factors.

Please answer this questions based on information above,

1. What kind of variables that researchers suspected to had a confounding effect in this
research?

Types of variables that researchers suspected to had a confounding effect in this research are
myocardial infraction, smoking, socioeconomic status, blood lipid concentrations, and obesity

2. How do they overcome the confounding variables?

They overcome the confounding variables with conduct matching technique between cases and
controls (age and sex).
For other confounding variables: they are adjusted by using multiple logistic regression
>> multivariate analysis

Interaction/modification effect
Interaction is a natural occurrence that we want to describe and study further. Interaction
defined as follows (MacMahon) : “when the incidence rate of disease in the presence of two or
more risk factors differs from the incidence rate expected to result from their individual effects”.
The effect can be greater than what we would expect (positive interaction) or less than we would
expect (negative interaction).

Activity 3
A case control study conducted to examine the association between smoking habit and
myocardial
infarction (MI). The result was shown in table 8 below:
Table 8. 2x 2 table of smoking and MI

1. Calculate the crude measure of association?

𝟒𝟐⁄ 𝟎,𝟐𝟕
Crude 𝑶𝑹 = 𝟐𝟏 𝟏𝟓𝟖 = = 𝟐, 𝟐𝟐
⁄𝟏𝟕𝟓 𝟎,𝟏𝟐

The Investigators decided to look at dietary fat as a confounder/effect modifier, and the
result were shown in Table 9 and 10
Table 9. Cases control in stratum dietary fat consumption < 30% calories

Table 10. Cases control in stratum dietary fat consumption > 30% calories

2. Calculate stratum-specific measures of association

a. Table 9 (dietary fat consumption < 30% calories)
𝟏𝟐⁄ 𝟎,𝟎𝟗
𝑶𝑹 = 𝟏𝟏 𝟏𝟑𝟑 = = 𝟏, 𝟎𝟎
⁄𝟏𝟐𝟑 𝟎,𝟎𝟗

b. Tabel 10 (dietary fat consumption > 30% calories)

𝟑𝟎⁄ 𝟏,𝟐
𝑶𝑹 = 𝟏𝟎 𝟐𝟓 = = 𝟔, 𝟐𝟒
⁄𝟓𝟐 𝟎,𝟏𝟗

≈ Dietary fat consumption increases the risk for myocardial infarction

3. What are your conclusions?

a. Is there effect modification

Yes, because stratum specific OR completely different in terms of magnitude and direction

b. Is there confounding

No confounding, because dietary effect come as effect modifier in this study

c. Which measures should we report

We should report the stratum-specific OR