This document discusses risk and how estimates of risk are obtained through observational studies. It defines risk as the probability that exposed people will develop a disease more often than unexposed people. Risk factors are factors associated with an increased risk of disease. Observational studies like cohort studies are often used to study risk since experiments are not always ethical or possible. Cohort studies involve assembling groups of people and observing them over time to see who develops diseases and compare exposure status.

1. RISK
Research Methods
Dent 313
1

2. 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
2

3. 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
3

4. 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
4

5. 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
5

6. Amount of exposure
Relevant questions
– Ever been exposed
– Current dose
– Largest dose taken
– Total cumulative dose
– Years of exposure
– Years since first exposure
6

7. 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
7

8. Choice of appropriate measures
Based on
– Clinical and biological effects
– Pathophysiology of the disease
– Previous epidemiological studies
8

9. 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
9

10. 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
10

11. 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
11

12. 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
12

13. 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
13

14. 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
14

15. 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
15

16. 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
16

17. Uses of risk
Prediction of the occurrence of disease
Search for cause
Diagnosis
Screening
Prevention
17

18. 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
18

19. 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
19

20. 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
20

21. 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
21

22. 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
22

23. 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
23

24. 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
24

25. 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
25

26. 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
26

27. 27

28. 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
28

29. Cohort study
Disease outcome
YES
Exposed to risk factor
NO
People
at risk
TIME
YES
Not exposed to risk factor
No
29

30. Types of cohort studies
Concurrent (prospective)
Historical (retrospective)
30

31. 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
31

32. 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
32

33. Cohort studies
PAST
Cases assembled
PRESENT
FUTURE
been followed-up
HISTORICAL COHORT STUDY
Cases assembled
To be followed-up
CONCURENT COHORT STUDY
33

34. 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
34

35. 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
35

36. 36