EPID 600; Class 8

Bias

University of Michigan School of Public Health

1
 Bias

Systematic error in the design, conduct or analysis of a

study that results in a mistaken estimate of an exposure’s
effect on disease

2
 Bias

Systematic error in the design, conduct or analysis of a

study that results in a mistaken estimate of an exposure’s
effect on disease

Wrong study design!

Wrong sampling strategy!

3
 Bias

Systematic error in the design, conduct or analysis of a

study that results in a mistaken estimate of an exposure’s
effect on disease

Problems in enrollment of cases, of controls!

Loss to follow-up!
Poor collection of data!

4
 Bias

Systematic error in the design, conduct or analysis of a

study that results in a mistaken estimate of an exposure’s
effect on disease

Wrong modeling assumptions!

Miscategorization of variables!

5
Rothman KJ. Epidemiology: An Introduction. Oxford, 2002. 6
 Evaluating bias

1.  Why did it occur?

2.  What effect does it have on the observed association?
3.  What can be done to control for bias in this study and to
prevent it in future studies?

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 Types of (important) bias

1.  Selection bias

Error in selection of study participants
2.  Information bias
Errors in procedures for gathering relevant information

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 1. Selection bias

Systematic error in selecting subjects into one or more of

the study groups, such as cases and controls, or exposed
and unexposed

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 Study question

Does coffee drinking cause pancreatic cancer?

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 Selection Bias: in a case-control study

Cases: patients hospitalized with a diagnosis of

pancreatic cancer

Controls: patients hospitalized for other reasons by the

same gastroenterologist who had hospitalized the case

Results: found a strong relationship between coffee

drinking and pancreatic cancer

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 What happened?

POPULATION
Persons who do not drink
Cancer
coffee are more likely to be
Yes No
controls
Coffee

Yes
No

Cancer
Yes No
Coffee

Yes

No
STUDY SAMPLE
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 Study question

Is there a relation between occupational exposure to

asbestos and lung cancer?

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 Selection Bias: in a cohort study

Exposed: workers who handle asbestos (100%

participation)

Unexposed: workers in other areas of the factory who

agree to participate
(50% participation)

Results: found NO relationship between asbestos and

lung cancer

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 What happened?

UNEXPOSED workers who

POPULATION
participate are those at high risk
Cancer for lung cancer, so unexposed
Yes No with disease are over-
represented
Asbestos

Yes
No

Cancer
Yes No
Asbestos

Yes

No
STUDY SAMPLE
15
 2. Information Bias

Systematic error in obtaining information regarding

subjects in the study

Examples: bias in recall, in collecting data, in interview,

in reporting

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 Study question

Is perinatal infection associated with a risk of congenital

malformation?

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 Information Bias in a case-control study:
Example 1
Cases: newborns with congenital malformations

Controls: healthy newborns

Results: found a strong relationship between mother’s

recall of infection during pregnancy and malformation

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 What happened?

Recall bias

Parents of children with congenital malformations were

more likely to report infection during pregnancy than
parents of children without congenital malformations

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 What happened?

POPULATION
Congenital
Malformation
Yes No
pregnancy
Infection

Yes
during

No
Congenital
Malformation
Yes No
pregnancy
Infection

Yes
during

No
STUDY SAMPLE
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 What happened?

POPULATION Misclassification of unexposed as

Congenital exposed is more common in cases
Malformation
than in controls  DIFFERENTIAL
Yes No
MISCLASSIFICATION
pregnancy
Infection

Yes
during

No
Congenital
Malformation
Yes No
pregnancy
Infection

Yes
during

No
STUDY SAMPLE
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 What happened?

POPULATION
Misclassification of unexposed as
Congenital exposed is more common in cases
Malformation
Yes No than in controls  DIFFERENTIAL
MISCLASSIFICATION
pregnancy
Infection

Yes
during

No
Congenital
Malformation
Yes No
pregnancy
Infection

Yes
during

No
STUDY SAMPLE 22
 What if there is misclassification and it
is similar in both cases and controls ?

Case Non-Case
Yes
Infection

No

Non-differential misclassification

Usually biases estimate of association towards 1 (the null)

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 “Toward the null”

2
”the null”

0.5

0
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 Study question

Is smoking associated with an increased risk of myocardial

infarction (MI) ?

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 Information Bias in a case-control study:
Example 2
Cases: hospitalized cases of MI in elderly adults

Controls: elderly adults, randomly selected from the

community, who have never been hospitalized for MI

Results: found a weak relationship between smoking and

MI

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 What happened?

Many true cases of MI are misclassified as non-cases, and

are included in the controls (they were not hospitalized and
had no symptoms)

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 What happened?

POPULATION
Misclassification of cases as controls
Myocardial is similar in smokers and non-
Infarction
smokers  NON-DIFFERENTIAL
Yes No
MISCLASSIFICATION
Smoke

Yes
No
Myocardial
Infarction
Yes No
Smoke

Yes
No
STUDY SAMPLE 28
 What happened?

POPULATION
Misclassification of cases as
Myocardial controls is similar in smokers and
Infarction
non-smokers  NON-
Yes No
DIFFERENTIAL
Smoke

Yes MISCLASSIFICATION
No
Myocardial
Infarction
Yes No
Smoke

Yes
No
STUDY SAMPLE 29
 What happened?

POPULATION
Misclassification of cases as
Myocardial
controls is similar in smokers and
Infarction
Yes No non-smokers  NON-
DIFFERENTIAL
Smoke

Yes MISCLASSIFICATION
No
Myocardial
Infarction
Yes No
Smoke

Yes
No
STUDY SAMPLE 30
 Study question

Is use of oral contraceptives (OC) associated with an

increased risk of venous thrombophlebitis (blood clots)?

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 Information Bias: in a cohort study

Exposed: women who use OC

Unexposed: women who do not use OC

Results: found a strong relationship between OC use

and thrombophlebitis

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 What happened?

Detection bias (also called surveillance bias)

Women who are on oral contraceptives are more likely to

receive a diagnosis of thrombophlebitis

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 What happened?

POPULATION
Thrombophlebitis
Yes No
OC Use

Yes
No
Thrombophlebitis
Yes No
OC Use

Yes
No
STUDY SAMPLE 34
 What happened?

Misclassification of non-disease as
POPULATION disease is different in exposed
Thrombophlebitis and unexposed persons 
Yes No DIFFERENTIAL
MISCLASSIFICATION
OC Use

Yes
No
Thrombophlebitis
Yes No
OC Use

Yes
No
STUDY SAMPLE 35
 What happened?

Misclassification of non-disease as
POPULATION disease is different in exposed
Thrombophlebitis and unexposed persons 
Yes No DIFFERENTIAL
MISCLASSIFICATION
OC Use

Yes
No
Thrombophlebitis
Yes No
OC Use

Yes
No
STUDY SAMPLE 36
 Putting numbers to the differential vs. non-
differential examples, 1

POPULATION Misclassification of non-disease as

Thrombophlebitis disease is different in exposed
Yes No and unexposed persons 
DIFFERENTIAL MISCLASSIFICATION
OC Use

Yes 50 25
RESULTING IN BIAS AWAY FROM
No 50 100 THE NULL
Thrombophlebitis
REAL OR = Yes No BIASED OR =
OC Use

(100*50)/ Yes 70 5 (100*70)/

(50*25)=4 No 50 100
(50*5)=28
STUDY SAMPLE 37
 Putting numbers to the differential vs. non-
differential examples, 2
Misclassification of unexposed as
POPULATION exposed is more common in cases
Congenital than in controls  DIFFERENTIAL
Malformation MISCLASSIFICATION RESULTING
Yes No
IN BIAS AWAY FROM THE NULL
pregnancy
Infection

Yes50 25
during

No 50 100
Congenital
Malformation
Yes No BIASED OR =
REAL OR =
pregnancy
Infection

Yes75 25 (100*75)/
during

(100*50)/
No 25 100
(25*25)=12
(50*25)=4
STUDY SAMPLE 38
Putting numbers to the differential vs. non-
differential examples, 3

POPULATION Misclassification of exposed as

unexposed is more common in cases
Disease
than in controls  DIFFERENTIAL
Yes No MISCLASSIFICATION RESULTING IN
Exposure

Yes50 25 BIAS TOWARDS THE NULL

No 50 100
Disease
Yes No BIASED OR =
REAL OR =
Exposure

Yes 25 25 (100*25)/
(100*50)/
No 75 100
(25*75)=1.3
(50*25)=4
STUDY SAMPLE 39
 Putting numbers to the differential vs. non-
differential examples, 4
Misclassification of cases as
controls is similar in smokers and
POPULATION non-smokers  NON-
Myocardial DIFFERENTIAL
Infarction MISCLASSIFICATION RESULTING
Yes No IN BIAS TOWARDS THE NULL
50 25
Smoke

Yes
No 50 100
Myocardial
Infarction
REAL OR = Yes No BIASED OR =
(100*50)/ 25 50
Smoke

Yes (125*25)/
(50*25)=4 No 25 125
(25*50)=2.5
STUDY SAMPLE 40
 Accuracy of weight/height reports
Obesity is acknowledged as a critical health problem
internationally
Studies often use reported (as opposed to measured) data to
estimate the prevalence of overweight and obesity at the
population level
There have been investigations regarding the “truth” of these
reported values in adults and adolescents; the validity of
parent-reported weight and height was studied by a team in
Canada.

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Dubois and Girad. Accuracy of maternal reports of pre-schoolers’ weights and heights as estimates of BMI values. Int J Epid. 2007; 36: 132-138.
 Height/weight reports

3) Investigators
examined the
prevalence of
obesity based on
reported values
versus
2) Within 3 months, prevalence of
1) Mothers asked to
children’s weight obesity based on
report on height and
and height were measured values
weight of children
aged 4 directly measured

42
Dubois and Girad. Accuracy of maternal reports of pre-schoolers’ weights and heights as estimates of BMI values. Int J Epid. 2007; 36: 132-138.
 Height/weight reports

The cohort: 4-year old children in 2002, who were part of a regional
stratified sample of children born in Quebec in 1998
Height/Weight report: One care-giver, usually the mother, reported height
and weight to an interviewer; the caregiver was not told that subsequent
measurement would be taken.
Interviewers made sure that mothers recalled these values rather than
measuring them on the spot
Height and weight measurement: Within three months of the interview,
nutritionists followed a standardized protocol and measured height and
weight of children

43
Dubois and Girad. Accuracy of maternal reports of pre-schoolers’ weights and heights as estimates of BMI values. Int J Epid. 2007; 36: 132-138.
 Height/weight report: is it the same for
all?

Is any group of people

consistently over-
reporting BMI of children?

Odds ratios among boys:

BMI>95th Percentile

SES Reported Measured

Highest 1 1
Middle 1.8 1.7
Lowest 2.2 1.9

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Dubois and Girad. Accuracy of maternal reports of pre-schoolers’ weights and heights as estimates of BMI values. Int J Epid. 2007; 36: 132-138.
 Height/weight reports
In this figure, the measured
weight is 17 kg for a 51-
month-old child who is 1.03m
tall. This child ranks at the
71st percentile if the child is a
girl and at the 65th percentile if
the child is a boy.

If the mother reports the

weight as being 2 kg less than
the actual value, the child
would be classified as being
below the 15th percentile.

45
Dubois and Girad. Accuracy of maternal reports of pre-schoolers’ weights and heights as estimates of BMI values. Int J Epid. 2007; 36: 132-138.
 Height/weight report: findings

Heights were reported more accurately than weights (there was no

difference in the means of reported vs. measured heights)
A greater proportion of mothers overestimated boys weights; a
greater proportion of lower SES mothers misreport
12% of the children were classified as overweight based on the
reported data; 9% were classified as overweight using measured
data  3% overestimation of overweight in this population

46
Dubois and Girad. Accuracy of maternal reports of pre-schoolers’ weights and heights as estimates of BMI values. Int J Epid. 2007; 36: 132-138.
 Special biases

Non-respondent bias

Persons who do not participate in a particular study may be

different than those who do

e.g., in telephone surveys, women are more likely to

answer surveys than are men; if the exposure of interest is
differentially distributed between women and men and if
gender is associated with the outcome of interest bias will
result

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 Other special biases

Unmasking (detection signal) bias

Membership bias
Diagnostic suspicion bias
Exposure suspicion bias
Recall bias
Family information bias
Neyman bias
Berkson bias
etc

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 Evaluating Bias

1.  Why did it occur?

2.  What effect does it have on the observed association?
3.  What can be done to control for bias in this study, and
to prevent it in future studies?

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 Preventing Bias

Careful attention to sampling

Minimize non-response
Standardization of measurements
Training and quality control
Blinding

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