Cohort Studies

Epidemiologic Studies Identify new diseases Identify populations at risk for a disease Identify possible causative agents of disease Identify factors or behaviors that increase risk of a disease

Study Designs Means to assess possible causes by gathering and analyzing evidence. The key to any epidemiologic study is in the definition of what constitutes a case and what constitutes an exposure.

Types of Study Designs Analytic Studies (to test hypotheses) Experimental studies Randomized clinical trials Observational studies Cross-sectional studies Cohort studies (prospective study) Case-control studies

What is Cohort? Cohort is an ancient Roman military unit of 300-600 men A group of soldiers marching forward in battle

Cohort studies starts with people free of disease longitudinal Prospective studies Forward looking study Incidence study starts with people free of disease assesses exposure at “baseline” assesses disease status at “follow-up”

Cohort Studies Study Population Exposure is self selected Non-exposed Exposed Follow through time Disease No Disease Disease No Disease

Cohort Study Examples Study to determine if smokers have a higher risk of lung cancer Study to determine if children who receive influenza vaccination miss fewer days of school Study to determine if the Russian Salad was the cause of a foodborne illness outbreak

2 x 2 Table Used to summarize counts of disease and exposure in order to do calculations of association Outcome/Disease Exposure Yes No Total a b a + b c d c + d a + c b + d a + b + c + d

2 x 2 Tables a b c d a + b = total number who are exposed a = number who are exposed and have the outcome b = number who are exposed and do not have the outcome c = number who are not exposed and have the outcome d = number who are not exposed and do not have the outcome ***************************************************** a + b = total number who are exposed c + d = total number who are not exposed a + c = total number who have the outcome b + d = total number who do not have the outcome a + b + c + d = total study population Outcome Yes No Yes Exposure No a b c d

Incidence among exposed Relative Risk (RR) It is the “ratio of incidence of disease among exposed to incidence of disease among non- exposed” Incidence among exposed Relative Risk = ---------------------------------- Incidence among not exposed

Relative Risk The relative risk is the risk of disease in the exposed group divided by the risk of disease in the non-exposed group RR is the measure used with cohort studies Outcome Yes No Total a a + b RR = c c + d Risk among the exposed Yes Exposure No a b c d a + b c + d Risk among the unexposed

Relative Risk Example Food Poisoning a / (a + b) 23 / 33 RR = = = 6.67 Russian Salad Yes No Total 23 10 33 7 60 67 30 70 100 a / (a + b) 23 / 33 RR = = = 6.67 c / (c + d) 7 / 67

Advantages of Cohort Studies Temporality: Exposure precedes outcome because the cohort is disease free at baseline Efficient for studying rare exposures May be used to study multiple outcomes Allows for calculation of incidence of diseases in exposed and unexposed individuals Minimizes recall bias

Disadvantages of Cohort Studies Tend to be expensive (large sample size) and time consuming (long follow-up period) Loss to follow-up When multiple outcomes or specific disease incidence is the outcome of interest, bias can be a serious problem Inefficient to study rare diseases

Framingham Study Design Framingham, Massachusetts population was 28,000 Study started in 1948 Study design called for a random sample of 6,500 Enrollment questionnaire from targeted age range 30-59 years No clinical evidence of atherosclerotic cardiovascular disease Cohort re-examined every two years

The Framingham Study Exposures included: Smoking Alcohol use Obesity Elevated blood pressure Elevated cholesterol levels Low levels of physical activity, etc.

The Framingham Study Hypotheses: Persons with hypertension develop CHD at a greater rate than those who are normotensive Elevated blood cholesterol levels are associated with an increased risk of CHD Tobacco smoking and habitual use of alcohol are associated with an increased incidence of CHD Increased physical activity is associated with a decrease in development of CHD An increase in body weight predisposes a person to CHD

Types of Cohort Studies Concurrent Cohort Study (prospective or longitudinal) Retrospective Cohort Study (historical cohort or non-concurrent prospective study) Both designs are identical…comparing exposed and non-exposed populations The only difference is calendar time.

Concurrent Cohort Study Investigator identifies original study population at the beginning of the study. The individuals are followed prospectively through time until disease develops or does not develop. Disadvantages: Requires long follow-up time (years) Expensive Age of investigator

Retrospective Cohort Study The cohort is defined from historical data and followed up for disease up to the present time Can telescope the frame of calendar time for the study and obtain results sooner Disadvantage: Quality depends on the historical data that are available – both to define exposure and to identify the outcome.

Assessment of Exposure Techniques used to measure exposure include questionnaires (age, smoking habits), laboratory tests (cholesterol, hemoglobin), physical measurements (height, weight, blood pressure) and various special procedures (EKG, x-rays) Quantifying exposures includes information such as date of onset, frequency of exposure and duration and intensity of exposure

Exercise How would you design a cohort study of the association between preterm delivery and cigarette smoking?

Results An exposed and a non-exposed group would first be identified e.g.) women presenting to a local county health department for prenatal care would be classified by smoking status – smokers and non-smokers. These women would be followed to determine whether or not preterm delivery occurred. The rates of the preterm delivery would be compared among the smokers and non-smokers.

Exercise : The RR A cohort study was performed to study the association between hypercholesterolemia and CAD. There were 5000 people in the study, out of which 50% had the risk factor. Of these, 120 developed the disease after one year of follow-up. Only 2% of the non-exposed population developed the disease during the same time period. Calculate the RR. STEPS: Construct a 2 x 2 table and fill in data Use the formula to calculate the RR Check your result with mine Interpret the result.

Exercise 2: 2 x 2 table Yes No Yes 120 2380 2500 2450 No 50 2500 170 CAD Yes No Yes 120 2380 2500 Hyper Cholesterolemia 2450 No 50 2500 170 4830 5000

Exercise 2: Formula & Answer The formula for calculating the RR is: Incidence in exposed(Ie) = a / (a + b) Incidence in unexposed (Iu) = c / (c + d) Thus formula becomes Ie / Iu = a / (a + b) c / (c + d) The Answer is 120 / 2500 50 / 2500 or 120 / 50 = 2.4 The answer of 2.4 means there is a 2.4 times greater risk of getting CAD in the hypercholesterol-emic group as compared to the group without hypercholesterolemia

To Review The objective of the cohort study is to test a hypothesis regarding the causation of disease. The group of persons to be studied (cohort) are defined in terms of characteristics manifest prior to appearance of the disease being investigated. The defined study groups are observed over a period of time to determine and compare the frequency of disease among them.