ANALYTICAL STUDIES

Prospective StudiesCOHORT

Prepared by: Dr. Sahar SabbourCommunity Medicine Department

Points discussed

• Types of analytic studies

• Aim of analytic studies

• Flow chart of the design

• Types of cohort studies

• Analysis of results

• Examples from the literature

• Advantages & disadvantages

Intended Learning Outcomes

Students should be able to:• List types of analytical studies• Define cohort, identify types of cohort studies• Describe the prospective approach• Investigate problems using the prospective

design• Draw a flow chart showing the cohort study• Compare between cohort and case control

studies• Calculate rates from cohort studies

Analytical StudiesIntroduction:

Analytical studies are either:

• Observational Case-Control

Cohort Study

• Experimental (Intervention):

Animal Experiments

Human Therapeutic trials

Preventive trials

Analytic Studies

• Analytic studies, etiologic studies, are performed to test specific hypothesis about a specific health problem.

• In general, associations observed in descriptive studies are often the basis for gathering more specific data and testing hypothesis in additional studies.

• Analytic studies involve the selection and comparison of two or more groups of persons, based on either their exposure or disease status…. WHY?

• To evaluate an association between exposure and disease.

• Analytic studies focuses on the magnitude of the association between the exposure and the health problem under the study.

Retrospective (Case-Control)

a b

dc

DISEASEpresent absentEXPOSURE

present

absent

cases

controls

Total

Total

Pro

sp

ecti

ve

(

Coh

ort

)

exposed

Not exposed

A fourfold table

Mausner, 1985

• The difference between the two types of studies lies in the way the study groups are assembled

• With either method of study, if there is a positive association between the factor and the disease:

• Those exposed will tend to develop the disease (group a),

• Those not exposed will tend not to develop it (group d).

The Prospective Approach

• The general concept of a prospective study is relatively simple.

• This type of study has been described by a variety of items: -Cohort

-Incidence

-Longitudinal

-Forward looking

-Follow-up

Prospective Cohort

“concurrent”

• COHORT

Study

Retrospective Cohort

“non-concurrent”

Historical prospective

The Prospective Approach (cont.)

• 1. It starts with a group of people (a cohort) all considered to be free of a given disease.

• Information is obtained to determine persons having a particular characteristic (certain exposure) that is suspected of being related to the development of disease being investigated.

• 2. These individuals are then followed for a period of time to observe who develops/or dies from that disease

• 3. Incidence or death rates for the disease are then calculated.

The Prospective Approach (cont.)

• 4. Rates are compared for those with the characteristic and those without it.

• 5. If the rates (of development of disease) are different, an association can be said to exist between the characteristic (exposure) and the disease.

• 6. It is important to obtain information on other characteristic of the study groups: age, sex, … to account for an influence of any factors related to the disease.

What is a cohort?

• A cohort is a group of persons who share a common experience within a defined time period.

Example:

• Birth cohort, marriage cohort, occupational cohort

Cohort Study (cont.)

Essential points:

• Exposed individuals in the study should be representative of all exposed persons.

• Unexposed persons should be representative of all unexposed persons in the population.

Cohort Study (cont.)

Selection of Cohorts: several approaches

• Accessible group (volunteers)

• Group with available records/history of exposure

• Group experiencing some particular exposure (arising during work)

Cohorts may be heterogeneous or homogenous

• Heterogeneous: with respect to some previous exposure as study of lung cancer and smoking.

• Homogenous in exposure:As study of the frequency of cancer among

asbestos workers. The comparison group is the general

population valuesDemonstrate excess in deaths among

asbestos workers.

Cohort Study (Prospective Design)

Passive smoking & respiratory infections in children

• Is passive exposure to tobacco smoke associated with increased respiratory infections in children ?

• Design:

Children exposed and not exposed tobacco smoke in their homes

Follow them in time for disease occurrence.

Children <(12 yrs)

1000

Family smoker500 childrenExposed

Family non-smoker500 childrenNot exposed

1 year

Diseased 300

Not diseased 200

Diseased 120

Not diseased 380

OutcomeStart

Rate: Incidence rate

•Incidence of Resp. Infection among exposed children: 300

500 = 60%

•Incidence of Resp. Infect. Among non exposed children: 120

500 = 24%

Cohort Study (cont.)Relative Risk: Incidence rate among exposed Risk Ratio Incidence rate in non exposed.

60 24 = 2.5

Relative Risk is a direct measure of risk (to assess the etiologic role of a factor in disease occurrence).

300 x 500 500 120

Cohort Study (cont.)Relative Risk:

Smoking

- Lung Cancer mortality: RR=18.57

- Myocardial infarction mortality: RR=1.35

It measures the strength of association

Cohort Study (cont.)Attributable Risk: The absolute

difference in Incidence rates among groups. “Risk Difference” RD

60 - 24 = 36%The extent to which the incidence of disease

can be attributed to the risk factor

Smoking-Lung cancer mortality: RD=1.23-Myocardial infarction mortality RD=1.25

Exposure Category

Annual Death Rates / 100,000 persons

Heavy smokers

Nonsmokers

Measures of Excess Risk

Relative Risk:

Attributable risk:

Lung Cancer Coronary Heart D.

166 599

7 422

166 / 7 = 23.7 599 / 422 = 1.4

166 – 7 =159 599 – 422 = 177

Doll and Hill study : Mortality of British doctors cited from Mausner, 1985

• The previous table suggests that prevention of coronary heart disease would require alteration of other factors in addition to smoking.

• The population attributable risk: relates both relative risk and frequency of the factor in the population

• i.e. a large proportion of the deaths from lung cancer in the total population are due to smoking not only because of the high RR associated with smoking, but also bec large proportion of the pop that smoke.

Examples from the literature

• Framingham Heart Study

initiated in 1948 by US Public Health Services: to study the relationship of a variety of factors to the subsequent development of heart disease

Group of persons30 – 62yrs

6,500Both sexes

20 years follow up

Information:S. cholest.levelBl.pressure , weightCig. Smoking

outcome

Occupation Based Studies to study effect of

exposures

•

•Benzene workers and Leukemia• Coke-oven workers and lung cancer•Asbestos workers and lung cancer•Radium dial painters and oral cancer

Initial Serum Cholesterol Level

Males Females

(45-54y) (45-54)

200 - < 220

220 - < 240

320 - < 340

340 - < 970

RR RR

1.35 1.3

1.48 1.43

2.85 2.57

3.25 2.89

There is an increasing risk of CHD with increasing initialSerum cholest. Levels in the 45-54 age group from a relativeRisk of 1.13-3.25 M, 1.13-2.89 F

Advantages of Cohort Study

• Correct classification of exposure before disease develops.

• Permits calculation of incidence rates thus, a direct measure of relative risk, and attributable risk.

• Many possible outcomes to the same exposure can be studied.

• No chick egg dilema• Accurate

Disadvantages of Cohort Study

• Large number of people are needed (large scale).

• Time consuming (follow up)• Losing people in follow up (Attrition)• Expensive• Status of subjects may be changed leading

to error in classification of exposure eg. Change in habit, occupation.

• Administrative problems: loss of staff, funding, high costs of the extensive record keeping

Non concurrent studies Retrospective Cohort

• The period of observation starts from some date in the past.

• They usually involve specially exposed groups or industrial populations.

• Done by using company records of past & present employees:

• Information: - date of employment - date of departure - duration, degree of

exposure - status: living/dead