Chance, Bias,

Confounding,
Principles of
Causality
HSC 3102

Ms. Sasha
Walrond
August,
2015

Outline
Define chance
2 Define Sampling Error
3 Define Bias and types of bias
4 Use the principles of causality to interpret estimates
of association
1

Chance
Chance is a random error appearing to cause an
association between an exposure and an outcome.
2 A principal assumption in epidemiology is that we can
draw inference about the experience of the entire
population based on the evaluation of a sample of the
population.
3 However a problem with drawing such an inference is
that the play of chance may affect the results of an
epidemiological study because the effects of random
variation from sample to sample.
1

Sampling Error
Because of chance, different samples will produce
different results and therefore must be taken into
account when using a sample to make inferences
about a population.
2 This difference is referred to as the sampling error and
the variability is measures by the standard error.
3 Sampling error may result in:
1

1
2
4

Type 1 error- Rejecting the null hypothesis when it is true

Type 2 error- Accepting the null hypothesis when it is false

Reducing sampling error: (Cannot be eliminated but can

be reduced):
1

An appropriate study design

Use of an appropriate sample size

Bias
Bias is any systematic error in the design, conduct or
analysis of a study that results in a mistaken estimate
of an exposures effect on the risk of disease.
2 Types of biases in epidemiologic studies:
1

1
2

Selection Bias
Information Bias

Selection Bias
Selection bias is an error in selecting a study group or groups
within the study and can have a major impact on the internal
validity of the study and the legitimacy of the conclusion.
2 If the way in which case and controls, or exposed and nonexposed individuals were selected is such that an apparent
association is observed-even if , in reality, exposure and
disease are not associated- the apparent association is the
result of selection bias.
3 Response bias is a type of selection bias. Example, if we are
studying the possible relationship of an exposure and a disease
and the response rate of potential subjects is higher in people
with the disease who were exposed than in people who were
not exposed, an apparent association could be observed even if
in reality there is no association.
Another example, those who agree to be in a study may be in
some way different from those who refuse to participate.
Volunteers may be different from those who are enlisted.
1

Information Bias
1

Information bias can occur when the means for obtaining

information about the subjects in the study are inadequate so that
as a result some of the information gathered regarding exposures
and/or disease outcomes is incorrect.

Types of information bias:

1

3
4

5
6

Recall Bias: In a case-control study, data on exposure are collected

retrospectively. The quality of data is determined to a large extent by the
patients ability to accurately recall past exposure(s). Those persons with a
particular outcome or exposure may remember events more clearly or amplify
their recollections.

Interviewer Bias: An interviewers knowledge may influence the

structure of the questions and the manner of presentation, which may
influence responses
Observer Bias: observers may have preconceived expectations of what
they should find in an examination.
Loss to follow up- Those that are lost to follow up or who withdraw from
the study may be different from those who are followed for the entire
study.
Surveillance bias: The group with the known exposure or outcome may
be followed more closely or longer than the comparison group
Misclassification Bias: errors are made in classifying either disease or
exposure status

Association to Causation
1

Once an association is established by an

epidemiological study (Relative Risk (RR) or Odds Ratio
(OR) not equal to 1) the next step is to determine
whether the observed association is causal.

Approaches for studying disease

etiology
In animal studies:
Advantages: allows the control of the exposure dose and environmental
conditions and genetic factors precisely; minimise loss to follow up
Disadvantages: require extrapolation of findings across species, from
animals to human populations. Certain diseases seen in humans have
neither occurred been produced in animals. It is also difficult to extrapolate
animal doses to human doses, and species differ in their responses.

In vitro systems ( cell or organ culture)

Disadvantage: Difficulty in extrapolating from artificial systems
to whole human organism.
conclusion as to whether a
substance causes disease in
human beings, we need to
If we want to be able to draw a

make observations in human

populations.

Approaches for studying disease

etiology in human populations
1

We cannot ethically randomise humans to most

common exposures

Epidemiology takes advantage of natural

experiments e.g. by comparing people who have been
exposed for non- study reasons to people who are not
exposed.
3 A common sequence is followed in conducting human
studies:
2

Types of association
1

There are 2 types of association:

1
2

Real: (Is it a true (real) association)

False (Spurious): (Is it a false or spurious association)

A spurious association may be observed because of

chance or issues with the study design that lead to bias.

Examples of well-known real associations:

1
2
3

Smoking and lung cancer

Hypertension and stroke
Obesity and type ii diabetes

Interpreting Real Associations

If an association is real, is it causal?
Not if it is accounted for a third factor associated with
both exposure and outcome (confounding).

Confounding
A confounder accounts, totally or in part, for the
observed association between exposure and outcome.
2 The
confounder is associated with both the
exposure and the outcome.
1

Confoundi
ng

Confoundi
ng
1.

Smoking is
a
known
risk factor
for
pancreatic
cancer

Smoking is
associated
with
coffee
drinking, but
is
not
a
result
of
2.

coff ee drinking.

Causal pathways
1

Direct or indirect

In direct causation, a factor directly causes a

disease without any intermediate step.
3 In indirect causation, a factor causes a disease, but
only through an intermediate step or steps.
4 In human biology, intermediate steps are virtually always
present in an causal process. Example, smoking inhalation
of carcinogens various metabolic changes cellular
abnormalities tissue abnormalities lung cancer
2

What is a cause?
1

In epidemiology, the cause of disease may be

defined as:
1
2
3

..An event, condition or characteristics

. That preceded the disease
and without which the disease event would not
have occurred
at all or until some later time
Rothmon and Greenland, 1998

There are four types of causal relationships that

are possible:
1

Necessary and sufficient

2
3
4

Necessary, but not sufficient

Sufficient, but not necessary
Neither sufficient nor necessary

Types of causal relationships

1- Necessary and sufficient cause:
1

3
4

Without the factor, the disease never develops (the factor is

necessary)
In the presence of the factor , the disease always develops ( the
factor is sufficient)
This situation rarely ever occurs
Example, lead poisoning.

2- Necessary, But not sufficient cause:

1 Without the factor the disease never develops, but
2 The presence of the factor does not inevitable lead to
disease
3

Example: tuberculosis (Tubercle bacillus is a necessary

factor, even though its presence may not be sufficient to

produce the disease in every infected individual.)

Types of causal relationships

3- Sufficient, but not necessary cause:
1 The presence of the factor invariably leads to disease,
but
2 The disease can occur even when the factor is absent
3 Also uncommon because very few causes are sufficient
on their own
4 Example,

Types of causal relationships

4- Neither sufficient nor necessary cause:
1 Disease can occur even if the factor is absent
2 Factor usually needs to work in combination with some
other factor
Most likely model of causality for most diseases,
especially chronic diseases
4 These
are known as contributory causes and the
disease are called multifactorial diseases
3

Causality in epidemiology:
important note
In epidemiology, causation is determined by what
occurs in groups of people or populations as opposed
to what occurs in any particular individual
2 From the group data, we can make predictions about
individuals, but we cannot expect that the predictions
will always be correct.
3 For example, everyone seems to know someone who
smoked four packs of cigarettes a day, had high
blood pressure and drank like a fish, but lived until
103.
1

However, health care policy decisions must be based

on the majority and not the exceptions.

Evidence for a causal relationship

Historically, major diseases were infectious.
2 Evidence
for causality related to proving that a
particular organism was responsible for a particular
disease.
3 Kochs postulates for causation:
1.
The organism is always found with the disease
2.
The organism is not found with any other disease
3.
The organism, when isolated from one who has the
disease, and cultured through several generations,
produces the disease (in experimental animals)
4.
Even without transmission, the regular and
exclusive presence of the organism supports
causality.
1

Evidence for a causal relationship

1

Kochs postulates apply to infectious diseases

What about non-communicable (chronic) diseases
where there is no infectious agent involved?
th

Mid- 20 century, guidelines for judging whether a

relationship is causal were developed by an expert
committee reviewing evidence about tobacco
smoking and lung cancer.

Guidelines for judging whether an

observed association is causal
1.

2.

3.

4.

5.

Temporal relationship: If a factor is believed to be the

cause of a disease, exposure to the factor must have
occurred before the disease.
Strength of the association: Is measured by the RR or OR.
The stronger the association, the more likely it is that the
relationship is causal
Dose- Response relationship: A s the dose of exposure
increases, the risk of disease also increases.
Replication of the findings: If the relationship is causal, we
would expect to find it consistently in different studies and
in different populations.
Biologic Plausibility: Coherence of theory/ finding with
existing biological knowledge. Epidemiologic evidence

sometimes precedes biologic knowledge. Criterion should

be applied with caution.

Guidelines for judging whether an

observed association is causal
Consideration of alternate explanations : In judging
whether a reported association is causal, the extent to
which the investigators have taken other possible
explanations into account and the extent to which they have
ruled out such explanations are important considerations.
7. Cessation of exposure: If a factor is a cause of a disease,
we would expect the risk of the disease to decline when
exposure to the factor is reduced or eliminated.
8. Consistency with other knowledge: If the relationship is
causal, we would expect the findings to be consistent with
other data.
9. Specificity of the association: An association is specific
when a certain exposure is associated with only one
disease, this is the weakest of all the guidelines and should
probably be deleted from the list.
6.

References
th

Gordis L. (2014) .Epidemiology (5

edition).
Philadelphia. Elsevier Saunders. (Chapter 14 and 15)
2 Lecture notes from Dr. Reeta Gobin, November 2014
and January, 2015
1