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RISK

Research Methods

Dent 313

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Risk

Risk is the probability of some untoward event

Definition

– The probability that people who are exposed to certain risk factors will subsequently develop the disease more often than similar unexposed people

Risk factors

– factors associated with an increased risk of becoming diseased

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This lecture

The lecture describes how estimates of

risk are obtained by observing the

relationship between exposure to possible

risk and the subsequent development of

the disease

– Looking forwards

– Looking backwards

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Risk Factors

Physical environment factors

– Toxin, infectious agents, gas, pollutants

Social environment factors

– Emotional illness, stress, loss of family members,

culture

Behavioral factors

– Smoking, driving without seat belts, inactivity

Inherited factors

– Diabetes, cholesterol, triglyceride

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Exposure to risk factors

The exposed person

– Has come in contact with risk factor

– Or has manifested the factor in question

– Before becoming ill

Duration of exposure

– At a single point in time Example: nuclear bomb in Hiroshima

– Over a period of time Example: smoking

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Amount of exposure Relevant questions

– Ever been exposed

– Current dose

– Largest dose taken

– Total cumulative dose

– Years of exposure

– Years since first exposure

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Measures of risk factor-disease

relationship

Exposure dose-disease relationship may not

exist with all risk factors

– Relationship: cumulative doses of sun exposure &

non-melanoma skin cancer

– No relationship: episodes of severe sunburn &

melanoma

Thus, correct measure has to be chosen to

confirm the association between risk factor and

disease

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Choice of appropriate measures

Based on

– Clinical and biological effects

– Pathophysiology of the disease

– Previous epidemiological studies

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Recognizing risk

It is easy to recognize the association of

acute disease and risk factors clinically

– Examples: radiation, sunburn, acute

poisoning

It is more difficult to establish association

between risk factors and chronic

conditions clinically

– WHY

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Information about risk

Because

– Long latency period between exposure and

disease

– Frequent exposure to risk factors

– Low incidence of disease

– Small risk from exposure

– Common disease

– Multiple causes of a disease

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Long latency period between

exposure and disease

Chronic diseases have long latency period

between the exposure and the 1st

manifestation of the disease

It might be years later

– E.g., Hypertension & heart disease

The original exposure might be forgotten

The link between the disease and the risk

factors is not readily clear

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Common exposure to risk factors

Common risk factors – Smoking, cholesterol in Heart disease

Comparing patterns of disease between – Those with the risk factors

– Those without the risk factors (certain population subgroups)

E.g., All Mormons (no smoking)

E.g., Vegetarians (no fat diet)

Comparisons through cross-sectional studies

Investigating subgroups with low exposure to risk factors gives more information about the true risk-disease association

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Low incidence of disease

The incidence of diseases is very low

(even with common diseases)

– Lung cancer in heavy smokers is 2/1000

– Doctors might witness some rare disease

once or few times in their practice

It is difficult to draw a conclusion about

infrequent events

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Small risk

Chronic disease caused by several risk factors

acting together

The risk of a single factor alone is very small

If the risk is small, then large number of cases is

needed to demonstrate the association of

disease and risk factors

– Example: coffee and heart diseases

If the risk is high you can establish conclusion

easily

– Hepatitis B and hepatoma

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Common disease

If the disease is ordinary or commonly

occurring and its risk factor is already

known

– There is no incentive to find new risk factors

– Examples: heart disease, cancer, stroke

If the disease is rare, careful investigation

about risk factors are carried out

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Multiple causes and effects

There is no one-to-one relationship between a risk factor and a disease – E.g., Hypertension & CHD

– Some people with HT develop CHD while others don’t

– Some people without HT develop CHD

Multiple risk factors for each particular disease

Dental caries is a multifactorial disease – Bacterial

– Carbohydrate

– Host factor

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Uses of risk

Prediction of the occurrence of disease

Search for cause

Diagnosis

Screening

Prevention

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Prediction of the occurrence of disease

The quality of prediction depends on similarity of an individual patient with – A large number of patients

– Who have past experience of the condition

– With similar risk factors

On an individual level, presence of a strong risk factor does not mean that the person is very likely to get the disease

Prediction is expressed as a probability

No better way than to use probability to guide clinical decision making at the individual level

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Search for cause

Search for risk factor is search for cause

Causes

– Immediate. E.g., virus – infection

– Distant. E.g., maternal education – low birth wt

A risk factor predicting disease is not necessarily a

causal factor

Marker: non-causal risk factor

– Risk factor may mark the disease outcome indirectly

– It is called marker because it marks the increase

probability of the disease

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Diagnosis

The presence of a risk factor increase the

probability that a disease is present

– Therefore, knowledge of risk factor can be

used in the diagnosis process

The absence of risk factor helps to rule out

a disease

– Absence of high fluoride intake rules out

fluorosis and strengthens other possibilities

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Screening

Knowledge of risk factors improves the

efficiency of screening programs

– By selecting subgroups at high risk

– E.g., Risk of breast cancer is high among

women with affected young women relatives

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Prevention

Removal of risk factor can prevent the

disease regardless whether or not the

mechanism of action of the risk factor in

known

– Stopping drinking of certain water (risk factor)

prevents cholera infection in people

– Stopping water with F > 1 ppm prevents

fluorosis

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Studies of risk

Conducting an experiment helps to

determine whether exposure to a potential

risk develops disease

People without disease divided into 2

groups

– One subjected to risk factor

– The other group is not

– Otherwise the 2 groups are treated the same

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When aren’t experiments possible

Unethical to impose hazardous risk factors

on healthy people for the purpose of a

scientific research

People hate to have their behavior

modified by others for long period of time

Experiments can be expensive to run

Therefore, the choice goes in these

situations towards observational studies

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Observational studies

Are clinical studies in which the researcher gathers data by simply observing events as they happened

Have more potential for bias than experimental studies

Most studies of risk factor

Types

– Cohort studies

– Case-control studies

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Cohort studies

Cohort: a group of people with something in common in assembly who are observed for a period of time to see what happens to them

Two condition to conduct cohort study They do not have the disease at the time they are

assembled

They should be observed for a meaningful period of time in the nature history of the disease in question Enough time for the risk to be expressed

All member of the cohort should be observed over the full period of time

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Cohort study

People assembled has not experienced the

outcome but have equal susceptibility to develop

the outcome

People are then observed over a period of time

Examine which people experience the outcome

Other synonyms

– Incidence studies

– Longitudinal studies

– Prospective studies

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Cohort study

People

at risk

Exposed to risk factor

Not exposed to risk factor

YES

YES

NO

No

TIME

Disease outcome

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Types of cohort studies

Concurrent (prospective)

Historical (retrospective)

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Concurrent cohort

The group of people (cohort) are

assembled in the present and followed in

the future

The data are collected for the purpose of

the study with full anticipation of what is

needed

– Bias can be avoided

– Accuracy can be increased

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Historical cohort studies

Cases are assembled in the past and

followed forward to the present

The data are collected from available past

records of patients

Data may not be of sufficient quality for

rigorous research

Example: study cohort using dental records

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Cohort studies

PAST PRESENT FUTURE

Cases assembled been followed-up

To be followed-up Cases assembled

HISTORICAL COHORT STUDY

CONCURENT COHORT STUDY

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Advantages of Cohort studies

The only way of establishing incidence directly

Can assess the relationship between exposure

and many diseases

Best substitutes for true experimental studies

when not possible

Follow the same logic as a clinical trial

Allow measurement of exposure to a risk factor

Avoid bias because the “unknown” but “expected”

outcome develops after exposure to risk factor not vice

versa

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Disadvantages of cohort studies

– Need large number of people at risk

– The people must remain under the study for a long period of time

– Can not be used for rare diseases

– Expensive to run – Subjects are “free living” and not under control as in

experimental studies

– Expensive to keep track of them

– Need resources employed for a long time

– Usually limited to life-threatening diseases to justify the big budget

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