RANDOM ERROR, BIAS,

CONFOUNDING

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 Errors
• There are two broad classes of
observational errors: random error
and systematic errors (bias)
 Random Errors
• Random errors are fluctuations in the
measured data due to limitations in precision
of the measuring device resulting in findings
that are too high or too low...
• It occurs because there are a large number of
parameters beyond the control of the
experimenter that may interfere with the
results of the experiments
• A random error can occur due to the measuring
instrument and the way it is affected by changes
in the surroundings.
• For example, a weighing scale may show
variations in measurement due to conditions of
loading and unloading
• Random errors are present in all experiments,
difficult to predict
• Can be reduced by increasing sample size and
taking the average of multiple measurements
 What is bias?
• any systematic error in the design, conduct or
analysis of a study that results in a mistaken
estimate of an exposure’s effect on the risk of
disease”-
• any trend in the collection, analysis,
interpretation, publication or review of data that
can lead to conclusions that are systematically
different from the truth”-
• Bias is a major issue in virtually any type of
epidemiologic study design
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• Unlike random error, systematic error cannot
be overcome by increasing the sample size.
You’ll merely end up with more precise biased
estimates!!

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 Types of bias?
• Selection Bias
– Non response bias
– Exclusion bias
– Prevalence-incidence bias/ Neyman bias
– Selective survival bias
– Follow-up/drop-out bias
– Membership bias
– Berksonian bias

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• Information Bias
– Misclassification bias
– Recall bias
– Reporting bias
– Surveillance bias/ Detection bias
 Selection Bias
• Bias in an association as a result of the manner
of selection of study subjects
• An error in selecting a study group/groups
within the study
• Participants selected for the study are not
representative of the general population

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Selection Bias – Prospective Study
• In a prospective study, SB arises when exposed
and unexposed are selected into the study in
such a way that the risk of outcome is
different, but for reasons other than those
related to the exposure itself

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 Selection Bias – Retrospective Study
• In a case-control study, SB arises when the
likelihood of being exposed is different for
cases and controls, but for reasons other than
those related to the outcome itself

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 Non response Bias
• Occurs when the response rate of potential
subjects is higher in people with the outcome
(disease) who were exposed than in people
with the disease who were not exposed, an
apparent association could be observed even if
in reality there is no association

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 Preventing Non Response Bias
• Do everything possible to obtain a high response
rate in all groups being compared (but this doesn’t
always help)
• To assess whether response bias occurred:
• Calculate the response rate
• Compare any available baseline characteristics of
responders and non-responders
• Intensify efforts to obtain information on a sub-
sample of non-responders to compare with
original responders

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 Exclusion Bias
• Results from the investigators’ applying
different eligibility criteria to the cases and to
the control

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 Prevalence-Incidence Bias
• Occurs when prevalence data do not show
the same E-O relationship that would have
been detected had incidence data been used
• e.g. if there is a change in exposure status
after a disease has been diagnosed, the
prevalence data will produce a systematically
different (i.e. biased) impression of the E-O
relationship than would have been obtained
from incidence data

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 Selective Survival Bias
• Occurs when the likelihood of an
individual remaining alive till the time of study
is different in the four cells of the 2*2 table
• e.g. if exposed persons with the disease are
more likely than unexposed persons with the
disease to die between disease onset and time
of cross-sectional study, then the prevalence
ratio will differ from the incidence ratio

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 Follow-up Bias
• Occurs when those successfully followed-up
differ in a systematic way from the source
population or from the original sample
enrolled in the study (from those not followed-
up)
• Serious potential problem in prospective
cohort studies and clinical trials

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 Membership Bias
• Occurs when controls are selected from a
group in which membership implies a risk of
disease that is different from that of the parent
population from which the cases arose (e.g.
smokers, joggers, employed people)

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 Berksonian Bias
• Study design: case-control
• Setting:can occurwhen sample is hospital-
based rather than community based
• Problem: exposed cases have a greater
likelihood of hospitalization than the other
study participants
• Result: leads to overestimation of the
association

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 Information Bias
• Bias in an association as a result of a
systematic “error” in the way the information
is collected
• Main types of IB:
• Misclassification bias
– Reporting bias
– Recall bias

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 Misclassification Bias
• Occurs when cases are misclassified as
controls or controls are misclassified as cases
• Misclassification of exposure status could also
occur
• Reasons for misclassification:
– Limited sensitivity and specificity of diagnostic
tests
– Inadequate/incomplete medical/other records

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 Forms of misclassification bias
• Differential
Rates of misclassification differ in different
study groups
• e.g. women who had malformed baby tended
to remember more mild infection that occurred
during pregnancy than did mothers of normal
infants i.e. more unexposed cases were
misclassified as exposed than unexposed
controls

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Forms of misclassification (cont’d)
• Non differential
• Occurs when diseased people are included in
control group and some non diseased in case
group
• OR/RR tends to be diluted and shifted towards
1, less likely to detect an association even if it
exists

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 Reporting Bias
• Occurs as a result of underreporting either
among the cases or controls
• A subject may be reluctant to report an
exposure he is aware of because of attitudes,
beliefs and perceptions
• Problems of self reporting

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 Recall Bias
• Occurs as a result of differential recall between
cases and controls
• A serious potential problem in case-control
studies
• Can lead to erroneous conclusions regarding
associations

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 Preventing Recall Bias
• Review available documentary sources (e.g.,
hospital records
• Use biological markers

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 Detection Bias
• Occurs when the exposure produces a greater
(or lesser) likelihood of detecting the disease
of interest
• if exposed individuals are more likely to have
the disease detected, the odds ratio will be
overestimated

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 Detection Bias Example
• Case Control study of association between
estrogen use and endometrial cancer
• Detection bias may result from more rigorous
surveillance of estrogen users (in comparison
to non-users) because estrogen use tends to
cause vaginal bleeding
• Controls should therefore be selected from
gynecological patients who are subject to
similar surveillance as estrogen users

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 Confounding and Bias
• Distortion of the estimated effect of an
exposure on an outcome, caused by the
presence of an extraneous factor associated
both with the exposure and the outcome”

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 Effects of Bias in epidemiologic
studies
• Affects internal validity of a study
• Incorrect odds ratio/ relative risks
• Non valid inferences regarding associations of
exposure and outcome

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 How to overcome bias
• Researchers can attempt to minimize bias at
different stages of the research process
• When designing a study, always consider the
validity and reliability of the measures to be
employed
• In the analysis, correction can sometimes be
made for known measurement error
• In the interpretation, estimation of possible
biases and their implication must be addressed

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 How to overcome bias (cont’d)
• Selection Bias
– Clearly define study population in time and place
– Use methods that results in high recruitment rates
– Random allocation(RCT’)
– Minimize loss to follow-up
– Review non-respondents
• Information Bias
– Use valid reliable tools
– Train staff and monitor their use of research tools
– Quality checks of research tools
– Blinding of study subjects and assessors
– Subjects in C-C study unaware of study hypothesis
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 Confounding
Distortion of an exposure-disease
association by the effect of some third
factor

3rd factor
Well /
Ill / Case Control
Exposed
Not
exposed
 CONFOUNDING
• To be a confounder, the variable of interest
must have 3 characteristics:
• 1. It must be a risk factor for the disease in
question.
• 2. It must be associated with the exposure
under study, in the population from which the
cases are derived.
• 3. A confounding variable must not be an
intermediate step in the causal pathway
between the exposure and the disease.
 Potential Effects of Confounding

• Overestimation of true association

(including simulation of an association
when none exists)
• Underestimation or masking of true
association
• Reverse direction of true association
 How to Deal with
In the study design:
Confounding
• Randomization
• Restriction
• Matching
In the analysis:
• Stratification and summarization (“controlling
for confounding”)
• Modeling (Multivariate Analysis)
 CONTROL FOR CONFOUNDING
• Randomization is applicable only in
intervention studies. A randomized controlled
trial will attempt to ensure that all confounders
are spread equally throughout all groups in the
trial. Randomization has the ability to control
for unknown confounders, but will be
successful only if the sample size is
sufficiently large.
 CONTROL FOR CONFOUNDING
• Restriction occurs when the level of a known
confounder is kept constant within all groups,
by limiting the study population to a particular
set of individuals. For example, if age and
gender are potential confounders, by restricting
a study to females aged 50 only, this
confounding will no longer be an issue. If the
criteria are not sufficiently narrow, however,
some confounding may still occur.
 CONTROL FOR CONFOUNDING
• Stratified analysis involves the measurement of
the strength of association in well-defined and
homogenous categories (strata) of the
confounding variables. For example, if gender
is a confounder, the association between
exposure to a risk factor and disease could be
measured separately in men and women.
 FURTHER READING
• Abramson JH, Abramson ZH. Making sense of data. 3rd
edn . Oxford University press 2001
• Abramson JH, Abramson ZH. Research methods in
community medicine. 6th edn. New York: Wiley 2008
• Heinonen OP, Shapiro S, Tuoominen L et al. : Reserpine use
in relation to breast cancer. Lancet 2:675-677, 1974
• Leon Gordis. Epidemiology. 5th edn. Saunders 2014
• Ronmark E, Lundqvist A, Lundback B et al.: Non
responders to a postal questionnaire on respiratory
symptoms and diseases. Eur J Epidemiol 15:292-299, 1999
• Sackett DL. Bias in analytic research. Journal of Chronic
Diseases 32: 51-63, 1979

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