IN THE NAME OF GOD - PowerPoint Presentation

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IN THE NAME OF GODSlide2

Advanced EpidemiologySlide3

CHAPTER 11

Cause Slide4

Clinicians are confronted frequently with information about possible causal relationships.

Example

:

Relationship between the cigarette smoking habits of obstetricians and vigor of babies

.

they deliveredSlide5

Cause

:anything

producing an effect or a result

Cause is discussed under such heading as “etiology “,” pathogenesis” ,”mechanism” , “risk factors”.

Cause is important to practicing physicians primarily because it guides their approach to three clinical tasks: prevention , diagnosis and treatment.

Belief in a causal relationship underlies every

therapeutic intervention in clinical medicine.

Concepts of causeSlide6

Koch set forth postulate for determining that infectious agent is the cause of a disease . Basic to his approach was the assumption that a particular disease has one cause and a particular cause results in one disease.

The organism must be present in every case of the disease;

it must be isolated and grown in pure culture;

it must cause a specific disease when inoculated into an animal;

it must then be recovered from the animal and identified.

Single and Multiple CausesSlide7

Usually many factors act together to cause disease in what has been called the “

web of causation.”

A causal web is well understood in conditions such as coronary artery disease, but is also

true for infectious disease, where presence of the organism is a

necessary cause

for disease to occur but not necessarily a

sufficient causeSlide8

When biomedical scientists study cause , they usually search for the underlying

pathogenetic

mechanism or final common pathway of disease.

Disease is also determined by less specific ,more remote cause, or risk factors such as peoples behavior or characteristic of their environments.

Proximity of Cause to EffectSlide9

Even when the pathogenetic

mechanism is not clear, knowledge of strong risk factors may still lead to effective treatment and preventions.

For many diseases , both

pathogenetic

mechanism and nonspecific risk factors have been important in the spread and control of the disease.Slide10
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In fact, social and economic improvements influencing host susceptibility ,such as less crowded living space and better nutrition may have played a more prominent role in the decline in TB rates in developed countries than treatments created through the biomedical

pathogenentic

research model.Slide12
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When more than one cause acts together, the resulting risk may be greater or less than would be expected by simply combining the effects of the effects of the separate causes . this is called

interaction

.

Clinicians call this phenomenon

synergism

when the joint effect is greater than the sum of the effects of the individual causes and

antagonism

when it is less. Sometimes, the

term biologic interaction is used to distinguish it from

statistical interaction

.

Interaction of Multiple CauseSlide15
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Interaction is often expressed as

effect modification

when the strength of the relationship between two variables is different according to the level of some third variable , called an

effect modifier

.

Effect ModificationSlide17
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It is only possible to increase ones conviction of a cause-and-effect relationship by means of empiric evidence to the point at which for all intents and purposes , cause is established

A postulated cause-and-effect relationship should be examined in as many different ways as possible

Establishing CauseSlide19

Two factors _ the suspected cause and the effect- obviously must be associated if they are to be considered as causally related however , not all association are causal.

Selection and measurement biases and chance can give rise to apparent associations that do not exist in nature.

Association and CauseSlide20
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When considering a possible causal relationship , the strength of the research design used to

establish the relationship is an important piece of evidence.

The best evidence for a cause-and –effect relationship come from well conducted randomized controlled trials , with adequate numbers of patients , blinding of therapists ,patients and researchers ;limited or no loss to

follow_up

; and carefully standardized methods of measurement and analysis.

Hierarchy of Research DesignsSlide22

Clinicians ordinarily rely on RCTs to provide evidence about causal relationship for treatments and prevention.

In

general,the

further one departs from randomized

trials,the

less the research design protects against possible biases and the weaker the evidence is for a cause-and-effect relationship.

Well-conducted cohort studies are the next best design.

Weakest of all studies are case series.Slide23

Studies in which exposure to a risk factor is characterized by the average exposure of the group to which individuals belong are called

aggregate risk studies

(ecological studies ).

Example:relationship

between wine consumption and cardiac mortality in developed countries.

Ecological StudiesSlide24
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Aggregate risk studies are rarely definitive in and of themselves. The main problem is a potential bias called the

ecological fallacy

, which affected individuals in a generally exposed group may not them selves have been the ones exposed to the risk factor. Slide26

In a

time-series study

, the effect is measured at various points in time before and after the

purported cause has been introduced

If changes in the purported cause are followed by changes in the purported

effect,the

associations is less likely to be spurious.

An advantage of a

time_series analysis is that it can distinguish between changes occurring over time from the effects of the intervention.

Time-series StudiesSlide27
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In a time-series study

, the suspected cause is introduced into several different groups at different times. Measurements are then made among the groups to determine whether the effect occurred in the same sequential manner in which the suspected cause was introduced.

Multiple Time-series StudiesSlide29

In 1965 the British statistician proposed a set of features that should be sought when deciding whether a relationship between some environmental factor and a sickness is causal or just an association.

Evidence For and Against CauseSlide30
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Causes should obviously precede effects.

Sometimes,however

, the principal can be overlooked when interpreting cross-sectional and case-control

studies,in

which both the purported cause and the effect are measured at the same point in time.

Although it is absolutely necessary for a cause to precede an effect, an appropriate temporal sequence alone is weak evidence for cause.

Temporal Relationships Between Cause and EffectSlide32

A strong association between a purported cause ,as expressed by a large relative or absolute risk , is better evidence for a causal relationship than a weak association . Thus , the strength of association between smoking and lung cancer is much greater than smoking and renal cancer.

Strength of the AssociationSlide33

A dose-response relationship is present if increasing the exposure to the purported cause is followed by a larger and larger effect.

Although a dose-response curve is good evidence for a causal relationship, especially when coupled with a large relative or absolute risk, its existence does not exclude confounding factors.

Dose-response relationshipsSlide34
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A factor is more likely to be a cause of disease when ever its removal results in a decreased risk of disease.

Reversible associations are strong , but not infallible , evidence of a causal relationship . confounding could conceivably explain a reversible association.

Reversible associationsSlide36
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When several studies,conducted

at different times indifferent settings and with

diffirent

kinds of patients, all come to the same conclusion , evidence for a causal relationship is strengthened.

It is often the case that different studies produce different results. Lack of consistency does not

necessaily

mean that the results of a particular study are in valid . one good study should outweigh several poor ones.

consistencySlide38

The assertion that cause and effect is consistent with our knowledge of the mechanism of disease , as it is currently understood , is often given considerable weight when causation is being assessed.

It is important to remember , however , that what is considered biologically plausible depends on the state of medical knowledge at the time.

Biologic PlausibilitySlide39

It is more often found for acute infectious disease(such as polio myelitis

and tetanus) and for genetic disease(such as FAP ,

ochronosis

, and PKU).

The presence of specificity is strong evidence for

cause,but

the absence of specificity is weak evidence for

cause,but

the absence of specificity is weak evidence against a cause-and-effect relationship.specificitySlide40

The argument for a cause-and-effect relationship is strengthened when examples exist of well-established causes that are analogous to the one in question.

In general ,analogy is weak evidence for cause.

AnalogySlide41

When determining cause, one must consider the evidence from all available

studies.After

examining the research design and quality and the elements for and against cause ,the case for causality can be strengthened or eroded . This calls for a good deal of judgment , especially when the evidence from different studies is conflicting.

Weighing The EvidenceSlide42
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All relevant studies are reviewed according to specific criteria. This

systematic review

is then used to determine the strength of the evidence for the causal relationship.

Grading the Quality of the EvidenceSlide44

Thank you!