THE UNIVERSITY OF THE SOUTHERN CARIBBEAN

PRESENTER: Tara S Bisnath

GROUP: JUNIORS (3RD YEAR NURSING STUDENTS)

SEMESTER: 1ST : SEPTEMBER 2o15-2016

COURSE CREDITS: TWO (2)

FOCUS: Clinical Epidemiology: The Essentials

Chapter 11
Cause
Objectives
At the end of the session the students should be able to
discuss the following:
1. Concepts of Cause
2. Establishing cause
3. Evidence for and against Cause
Quote
“In what circumstances can we pass from [an]
observed association to a verdict of causation?
Upon what basis should we proceed to do so?”

-- Sir Austin Bradford Hill, 1965

 Cause
 When clinicians encounter a disease condition, their major
concern is about the cause of the disease.
 Clinical issues such as abnormality, diagnosis, studies of risk,
prognosis, treatment and chance, have all examined various
aspects of cause.
 Cause, according to Webster’s Dictionary, is “anything
producing an effect or a result.” In medical texts, it is
discussed as etiology, pathogenesis, mechanisms or risk
factors.
 The knowledge of cause helps clinicians to deal with three
basic tasks:
1. Prevention
2. Diagnosis
3. treatment
 Concepts of Cause
 The knowledge of the relationship between cause and its
effect can therefore lead to successful prevention strategies
or treatment modalities.

 For example, a clinician checks a patient’s blood pressure

because he is aware that:
1. High blood pressure (cause) has an effect on the patient’s
health in terms of morbidity and mortality.
2. Treatment of high blood pressure (cause), prevents strokes,
myocardial infarction and congestive heart failure (effects).

 Many factors act together to cause disease.

 People’s behavior or characteristics of their environment
are examples of less specific factors that cause disease.
Concepts of Cause
Consideration is given to four concepts of cause:
1. Single and Multiple Causes
2. Proximity of Cause to Effect
3. Interaction of Multiple Causes
4. Effect Modification
 Concepts of Cause
1. Single and Multiple Causes
The single cause theory: An infectious agent as a cause for a
disease implying a one cause-one disease relationship.
This theory stipulates that:
 the organism must be present in every case of the disease
 The organism must be isolated and grown in pure culture
 The organism must cause a specific disease when
inoculated into an animal
 The organism must then be recovered from the animal and
identified
Concepts of Cause
Single and Multiple Causes
The multiple causes theory: “Web of causation” or
“Causal Web” – Many factors act together to cause
disease.
 Coronary artery disease for instance, has multiple causes
including: cigarette smoking, hypertension, diabetes,
hypercholesterolemia, inflammation and heredity (189).
 Note: While the presence of the organism is a necessary cause
for disease to occur, it may not be necessarily a sufficient cause
(e.g. AIDS cannot occur without exposure to HIV, but exposure to HIV
does not necessarily result in AIDS)
 Example explained: when a person sustains a needle stick injury
from a HIV infected patient, there is rarely sero-conversion to
HIV, because the virus is not as infectious as hepatitis B virus
which cause infection on a single needle stick.
 Concepts of Cause
2.Proximity of Cause to Effect
When study of cause is generally done, it involves a search for the
underlying pathogenetic mechanism of disease.
 The cause can either be specific and closely related to the
disease (e.g. germ-cell genetic changes associated with some
cancers) or less specific, more remote causes, or risk factors (e.g.
people’s behaviour or characteristics of their environment)
 Remote risk factors are sometimes more important causes of
disease than pathogenetic mechanisms.
 Even when the pathogenetic mechanism is not clear, knowledge
of strong risk factors may still lead to effective treatments and
preventions.
 Both pathogenetic mechanisms and nonspecific risk factors
have been important in the spread and control of diseases.
Concepts of Cause
Proximity of Cause to Effect
There are very important components of cause of disease:
 Susceptibility of host ( eg. For TB or AIDS)
 Level of exposure
 Genetic changes in the infectious agent
Susceptibility of host - Social factors such as living space
- Economic factors such as nutrition
- Health of the immune system
Level of contact - proximity to infectious agent
Genetic changes - noncompliance with treatment can results
in multidrug resistance strains of bacilli due to genetic
changes in the mycobacterium (e.g. tuberculosis)
 Concepts of Cause
3. Interaction of Multiple Causes
 The interplay of environment, behaviour and sub-cellular
biology may be very complex when thinking about cause.
 Interaction : when more than one cause acts together,
the resulting risk for developing the disease may be either
greater than expected or even less than is expected when
the effects of each separate cause are combined.
 Synergism : when the joint effect is greater than the sum
of the effects of the individual cause.
 Antagonism : when the joint effect is less than the sum
of the effects of the individual cause.
 It is more difficult to explain cause when many factors
play a part than when a single factor is predominant.
 When multiple causative factors interact together,
changing one or more of them can impact health
Concepts of Cause
Effect Modification
Effect Modification relates to interaction among
causative factors when the strength of the relationship
between two variables changes if a third variable is
introduced.
Effect Modifier refers to the level of the third variable
and its modifying effect on the effects of the causative
factors. (See example on p. 191 – the relationship between alcohol
consumption and breast cancer [two variables] and the modifying effect
of folate [third variable and effect modifier] on breast cancer risk.
Establishing Cause
 In clinical medicine it is not possible to prove causal
relationships beyond any doubt. Understanding and
proving causal relationships cannot be accomplished
beyond a shadow of a doubt.
 Empirical evidence must be used to establish one’s
conviction of cause –and-effect relationships.
 Equally, evidence can be mounted against a cause to the
point of making a cause-and-effect relationship unlikely.
 It is important to note that several studies must be done in
order to build empirical evidence for or against cause.
 Two ways of establishing cause:
 Association and Cause
 Hierarchy of Research Design
 Establishing Cause
1. Association and Cause
 Cause and Effect must be associated if they are to be
considered as causally related.
 All associations are not causal, therefore, association
does not prove cause. One must ask whether the claim
of an apparent association between a cause and an
effect is real or whether it was manufactured through
bias or chance.
 Selection bias, measurement bias and chance can result
in apparent associations that are not present in nature.
 If these biases and chance are unlikely in the situation
then a true association exists.
 Confounding bias and extraneous variables can also
warp results of causal relationships and must therefore
be controlled for as well.
Establishing Cause
 The strength of the research design used to establish
possible causal relationship is very important.
 The validity of the study is dependent on the manner
in which the study is performed.
 The best evidence for a cause-and-effect relationship
can be achieved by a well-conducted randomized
controlled trial with the following characteristics:
 Adequate numbers of patients
 Blinding of therapists, patients and researchers
 Limited or no loss to follow-up
 Carefully standardized methods of measurement
 Carefully standardized methods of analysis
Evidence for and Against Effect
 In studies of cause, and especially when randomized
controlled trials are not available, a number of features
assist in deciding whether a relationship between a risk
factor and a disease is causal or just an association:
 Temporal relationships between cause and effect
 Strength of association
 Dose-response relationships
 Reversible associations
 Consistency
 Biological plausibility
 Specificity
 Analogy
Evidence For and Against Effect
1. Temporal relationships between cause and effect
Cause must absolutely precede an effect, therefore
deviation from this is evidence against cause. However,
temporal sequence alone is weak evidence for cause,
because some things may precede the event that has
nothing to do with the event.
2. Strength of Association
A strong association between a suspected cause and an
effect, expressed a large relative or absolute risk, is
better evidence for a causal relationship. Small relative
risks could be as a result of unrecognized bias.
(p.g, 197)
 Evidence For and Against Effect
3. Dose response Relationships
A dose-response relationship is present when increasing the
exposure to the suspected cause is directly linked to larger rates of
the disease.( linking lung cancer deaths to the amount of
cigarettes some one smokes)
4. Reversible Associations
A factor is more likely to be a cause of disease when ever removal
of the factor results in a decreased risk of disease. (E.g. when
smokers give up smoking they decrease their likelihood of getting lung
cancer).
5.Consistency
Evidence for a causal relationship is strengthened when several
studies, conducted at different times, in different settings,
with different kinds of patients, using different research
designs, all come to the same conclusion. Lack of consistency
does not mean that results are invalid.
 Evidence For and Against Effect
6. Biological Plausibility
What is considered as biologically plausible when causation is being
assessed, depends on answers that are consistent with the medical
knowledge of the mechanism of disease at the time. However, lack
of plausibility may indicate the limitations of medical knowledge,
rather than lack of a causal relationship.( pg 198)
7. Specificity
The notion of one cause leading to one effect is strong evidence for
cause, while at the same time, absence of specificity is a weak
argument against cause (pg 199)
8. Analogy
The argument for a cause-and-effect relationship is strengthened when
examples exist of well-established causes that are similar to the one
in question. However, analogy (similarity) is weak evidence for
cause.(pg,199)
 Conclusion
Weighing the Evidence
 When determining cause, one must consider the evidence
from all available studies. After examining the research design
and quality of studies and the elements for and against cause,
the case for causality can be strengthened or eroded. Good
judgment must be used especially when the evidence from
different studies is conflicting, clinicians must decide where
the weight of the evidence lies.
Grading the quality of evidence
 Systematic Review is used to determine the strength of
evidence for the causal relationship which entails:
 Undertaking a literature review
 Reviewing all relevant studies according to specific criteria
(i.e. research design and methodology)
Questions Please?