1. ANALYTICAL STUDIES Prospective Studies COHORT Prepared by: Dr. Sahar Sabbour Community Medicine Department

2. 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

3. 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

4. Analytical Studies Introduction: Analytical studies are either: Observational Case-Control Cohort Study Experimental (Intervention): Animal Experiments Human Therapeutic trials Preventive trials

5. 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.

6. 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.

8. Retrospective (Case-Control) a b d c DISEASE present absent EXPOSUREEXPOSURE present absent casescontrols Total Prospective (Cohort) exposed Not exposed A fourfold table Mausner, 1985

9. 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).

10. 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

11. Prospective Cohort “concurrent” COHORT Study Retrospective Cohort “non-concurrent” Historical prospective

12. 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.

13. 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.

14. 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

15. 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.

16. 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

17. 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 values Demonstrate excess in deaths among asbestos workers.

18. 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.

19. Children (<12 yrs) 1000 Family smoker 500 children Exposed Family non-smoker 500 children Not exposed 1 year Diseased 300 Not diseased 200 Diseased 120 Not diseased 380 OutcomeStart

20. Rate: Incidence rate Incidence of Resp. Infection among exposed children: 300 500 = 60% Incidence of Resp. Infect. Among non exposed children: 120 500 = 24%

21. 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

22. Cohort Study (cont.) Relative Risk : Smoking -Lung Cancer mortality: RR=18.57 -Myocardial infarction mortality: RR=1.35 It measures the strength of association

23. 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

24. Annual Death Rates / 100,000 personsExposure Category Lung Cancer Coronary Heart D. 166 599 7 422 166 / 7 = 23.7 599 / 422 = 1.4 166 – 7 =159 599 – 422 = 177 Heavy smokers Nonsmokers Measures of Excess Risk Relative Risk: Attributable risk: Doll and Hill study : Mortality of British doctors cited from Mausner, 1985

25. 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.

28. 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 persons 30 – 62yrs 6,500 Both sexes 20 years follow up Information: S. cholest.level Bl.pressure, weight Cig. Smoking outcome

29. 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

30. Males Females (45-54y) (45-54) Initial Serum Cholesterol Level RR 1.35 1.3 1.48 1.43 2.85 2.57 3.25 2.89 200 - < 220 220 - < 240 320 - < 340 340 - < 970 There is an increasing risk of CHD with increasing initial Serum cholest. Levels in the 45-54 age group from a relative Risk of 1.13-3.25 M, 1.13-2.89 F

31. 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

32. 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

33. Non concurrent studies Retrospective Cohort The period of observation starts from some date in the past.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