Tutorial

Epidemiologi 3.1
Bias

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
Discuss the different types of bias that can distort the results of epidemiological studies

A. Bias
In previous chapters we have mentioned some of the ways in which bias can occur in study design and
measurement of an association. Here, we give an overview of bias in the study designs you have met.
Bias can be categorized into two classes:
selection bias
information bias (or measurement bias)

Selection bias

Selection bias occurs when systematic errors are introduced by the selection of study participants or
allocation of individuals to different study groups. These errors can compromise the (internal) validity of
results of a study. This can occur if the participants selected for the study are not representative of the
general population to which the study will ultimately apply, or if the comparison groups are not
comparable (casecontrol or intervention studies).
For example, if subjects are allowed to choose between a new drug that is being tested and an
established drug, the more adventurous or health conscious individuals might like to try the new drug,
whereas the less adventurous or less well-informed individuals may opt for the established drug.
Differences in the effects of the two drugs observed in such a study design may be partly or entirely due
to the differences in the underlying characteristics of the study participants rather than in the effects of
the drugs. For these reasons it is preferable to randomly assign participants to the study drug or control
in intervention studies. In casecontrol studies, selection bias can occur in the selection of cases if they
are not representative of all cases within the population, or in the selection of controls if they are not
representative of the population that produced the cases.
In cohort studies, selection bias may occur if the exposed and unexposed groups are not truly
comparable. This might happen if the unexposed group is not correctly selected, and differs from the
exposed groups in other, unrelated, factors in addition to the exposure of interest. An example of this
would be comparing an occupational cohort with the general population. Any association with the
exposure and disease might be lost due to the healthy worker effect. Bias may also occur if there
are differences in follow-up between the comparison groups.

Information bias

Information (or measurement) bias occurs if an inaccurate measurement or classification of an outcome

or exposure is made. This could mean that individuals are assigned to the wrong exposure or outcome
category, and will then result in an incorrect estimation of the association between exposure and
outcome. Errors in measurement are also known as misclassifications, and might be introduced by the
observer (observer bias), by the study participants (recall bias), or by the measurement tools such as
weighing scales or questionnaires. The size and direction of the distortion of an observed association
between an exposure and an outcome depends on the type of misclassification, of which there
are two types:
differential misclassification
Non-differential (random) misclassification.
Only differential misclassification leads to information bias, although we will discuss both types of
misclassification here for completeness.


Differential misclassification
Differential misclassification occurs when one group of participants is more likely to be misclassified
than the other. In a cohort study differential misclassification can occur if exposure makes the
individuals more or less likely to be classified as having the disease. In a casecontrol study, differential
misclassification can occur if cases are more or less likely to be classified as being exposed than controls.
Differential misclassification can therefore lead to an over- or underestimation of an association
between exposure and outcome.

Activity 1
In a casecontrol study designed to investigate the association between the use of oral contraceptives
and ovarian cancer, the exposure to oral contraceptives was determined from the history given by the
study participants. Cases are women diagnosed with ovarian cancer and controls are those who do not
have ovarian cancer.
The investigators assume that women with ovarian cancer are more likely to recall the use
of oral contraceptives than those who do not have the cancer.

1. Do you think differential misclassification is likely to occur?
2. If so, how do you think it would affect the observed effect of use of contraceptives on ovarian
cancer?

Table 1 shows the odds of exposure to contraceptives in cases and controls in the study.

Table 1 Odds of exposure to oral contraceptives in cases and control
cases
control
Exposure
n=400
n=400
oral contraceptive user
40
50
oral contraceptive non users
60
50
Total
100
100

3. What is the actual odds ratio of exposure to contraceptives in cases compared to controls?

Table 2 Observed odds of exposure in scenario 1

cases
n=400
40
60
100

control
n=400
30
70
100

Exposure
oral contraceptive user
oral contraceptive non users
Total

Suppose that the cases recalled the use of oral contraceptives accurately, but the controls did not
(scenario 1). This could lead to the results shown in Table 2 above.

4. What is the observed odds ratio of exposure to contraceptives in cases compared to controls in
scenario 1?

Non-differential misclassification
Non-differential misclassification occurs when both groups (cases or controls, exposed or unexposed)
are equally likely to be misclassified. This form of misclassification is therefore independent of exposure
status or outcome status. Non differential misclassification usually leads to underestimation of an
association between exposure and outcome, and will therefore reduce the observed strength of the
association. Suppose that, in the casecontrol study discussed above, the exposure to oral
contraceptives was determined from the records of family planning clinics. It is likely that the records of
some women might not be traceable. However, the loss of records would probably be distributed
equally among the cases and the controls, since record-keeping in family planning clinics is independent
of the risk of women developing cancer. If the investigators decided to classify all women who did not
have a record in the family planning clinics as unexposed to contraceptives, then the odds of exposure
to contraceptives would be underestimated in both cases and controls. Although the odds of exposure
to contraceptives would be underestimated equally among cases and controls, it would lead to
underestimation of the effect of contraceptives on ovarian cancer.

Activity 2
Continuing with the study considered in activity 1, suppose now that the records of 40% of both the
cases and the controls who had used oral contraceptives were not traced and these subjects were
misclassified as non-users (scenario 2). The observed odds of exposure in scenario 2 are shown in Table
3.
What is the observed odds ratio of exposure to contraceptives in cases compared to
controls in scenario 2?
Table 3 Observed odds of exposure in scenario 2
cases control
Exposure
oral contraceptive user
oral contraceptive non users
Total

n=100
24
76
100

n=100
30
70
100

ACTIVITY 3
Please determine what kind of bias or misclassification occured on each of the following statement :
1. You and your colleagues would like to conduct a study to see the prevalence of substance abuse
among high school students living in Riyadh. You randomly chose your sample from a number of
schools in Riyadh and distributed your questionnaires.
2. You were conducting a study on the association between duration of breastfeeding and
malnutrition. You randomly select a group of mothers attending the MMR immunization clinic and
ask them about the pattern and duration of breastfeeding they had for their children.

For question 3-7 we will using figure 1 above.
3. What type of study if this?
4. From the information given in the methods, comment on the factors that may have reduced bias
and could been a source of bias in the selection of cases and controls
5. The result sections tells us that :
Overall response rates were 52% for patients with glioma and 44% for controls, representing the
proportion of all eligible cases and controls from the study area who were interviewed in the study
Do you think this could affect the study? If so, how?

6. What could the investigator have done to see if the response rate had resulted in biassed result?
7. Interviews can be susceptible to observer bias. Can you explain how that could happen? And how
this may be overcome?