2Epidemiologic Studies Identify new diseasesIdentify populations at risk for a diseaseIdentify possible causative agents of diseaseIdentify factors or behaviors that increase risk of a disease
3Study DesignsMeans 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.
4Types of Study Designs Analytic Studies (to test hypotheses) Experimental studiesRandomized clinical trialsObservational studiesCross-sectional studiesCohort studies (prospective study)Case-control studies
5What is Cohort?Cohort is an ancient Roman military unit of menA group of soldiers marching forward in battle
6Cohort studies starts with people free of disease longitudinalProspective studiesForward looking studyIncidence studystarts with people free of diseaseassesses exposure at “baseline”assesses disease status at “follow-up”
7Cohort Studies Study Population Exposure isself selectedNon-exposedExposedFollow throughtimeDiseaseNo DiseaseDiseaseNo Disease
8Cohort Study ExamplesStudy to determine if smokers have a higher risk of lung cancerStudy to determine if children who receive influenza vaccination miss fewer days of schoolStudy to determine if the Russian Salad was the cause of a foodborne illness outbreak
92 x 2 TableUsed to summarize counts of disease and exposure in order to do calculations of associationOutcome/DiseaseExposureYesNoTotalaba + bcdc + da + cb + da + b + c + d
102 x 2 Tables a b c d a + b = total number who are exposed a = number who are exposed and have the outcomeb = number who are exposed and do not have the outcomec = number who are not exposed and have the outcomed = number who are not exposed and do not have the outcome*****************************************************a + b = total number who are exposedc + d = total number who are not exposeda + c = total number who have the outcomeb + d = total number who do not have the outcomea + b + c + d = total study populationOutcomeYes NoYesExposureNoabcd
11Incidence among exposed Relative Risk (RR)It is the “ratio of incidence of disease among exposed to incidence of disease among non- exposed”Incidence among exposedRelative Risk = Incidence among not exposed
12Relative RiskThe relative risk is the risk of disease in the exposed group divided by the risk of disease in the non-exposed groupRR is the measure used with cohort studiesOutcomeYes No Totalaa + bRR =cc + dRisk amongthe exposedYesExposureNoabcda + bc + dRisk amongthe unexposed
13Relative Risk Example Food Poisoning a / (a + b) 23 / 33 RR = = = 6.67 Russian SaladYesNoTotal231033760673070100a / (a + b) / 33RR = = = 6.67c / (c + d) / 67
14Advantages of Cohort Studies Temporality: Exposure precedes outcome because the cohort is disease free at baselineEfficient for studying rare exposuresMay be used to study multiple outcomesAllows for calculation of incidence of diseases in exposed and unexposed individualsMinimizes recall bias
15Disadvantages of Cohort Studies Tend to be expensive (large sample size) and time consuming (long follow-up period)Loss to follow-upWhen multiple outcomes or specific disease incidence is the outcome of interest, bias can be a serious problemInefficient to study rare diseases
16Framingham Study Design Framingham, Massachusetts population was 28,000Study started in 1948Study design called for a random sample of 6,500Enrollment questionnaire from targeted age range yearsNo clinical evidence of atherosclerotic cardiovascular diseaseCohort re-examined every two years
17The Framingham Study Exposures included: Smoking Alcohol use Obesity Elevated blood pressureElevated cholesterol levelsLow levels of physical activity, etc.
18The Framingham Study Hypotheses: Persons with hypertension develop CHD at a greater rate than those who are normotensiveElevated blood cholesterol levels are associated with an increased risk of CHDTobacco smoking and habitual use of alcohol are associated with an increased incidence of CHDIncreased physical activity is associated with a decrease in development of CHDAn increase in body weight predisposes a person to CHD
19Types 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 populationsThe only difference is calendar time.
20Concurrent 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)ExpensiveAge of investigator
21Retrospective Cohort Study The cohort is defined from historical data and followed up for disease up to the present timeCan telescope the frame of calendar time for the study and obtain results soonerDisadvantage:Quality depends on the historical data that are available – both to define exposure and to identify the outcome.
22Assessment 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
23ExerciseHow would you design a cohort study of the association between preterm delivery and cigarette smoking?
24ResultsAn 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.
25Exercise : The RRA 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 dataUse the formula to calculate the RRCheck your result with mineInterpret the result.
26Exercise 2: 2 x 2 table Yes No Yes 120 2380 2500 2450 No 50 2500 170 CADYesNoYes12023802500HyperCholesterolemia2450No50250017048305000
27Exercise 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 becomesIe / Iu = a / (a + b)c / (c + d)The Answer is120 / 250050 / or120 / 50 =2.4The 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
29To ReviewThe 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.