Presentation on theme: "Dr K N Prasad MD., DNB Community Medicine"— Presentation transcript:
1 Dr K N Prasad MD., DNB Community Medicine Cohort studyDr K N Prasad MD., DNBCommunity Medicine
2 Aim of Epidemiological studies To determine distribution of diseaseTo examine determinants of a diseaseTo judge whether a given exposure causes or prevents disease
3 Epidemiological study designs Descriptive studiesPopulationsCorrelated studiesIndividualsE.g. case-series, case reports, cross-sectional surveysAnalytical studiesObservational studiesCase-control studiesCohort studiesExperimental studiesIntervention studies after randomise exposureClinical trialsbut before I go into details about the cohort and case-control studies I would like to place these kind of studies in relation to other types of epidemiological studies.(klik)We have descriptive and analytical studies and the analytical studies can be divided into observational and intervention studies.Cohort and case-control studies falls into the category of analytical, observational studies.In observational studies, the investigator simply observes the natural course of events noting who is exposed and nonexposed and who has and who has not developed the outcome of interest (Hennekens and Burring pp.22).(klik)…and as you see, there are two basic types of observational analytical investigation:the case-controland the cohort studies.In practice each design offers certain unique advantages and disadvantages, and very briefly you can say that case-control studies are well-suited for investigation of rare diseases, whereas cohort studies are well-suited for relatively common diseases.but in general these study designs require an appropriate comparison group (control group).
4 Case-control study Exposed Cases Non-exposed Study Population Exposed
5 Cohort study / Follow-up study Study populationExposedNon-exposedDisease +Disease -A cohort study is a study where a group of individuals are followed. The study population is defined on basis on the presence or absence of exposure to a suspected risk factor for a disease.The cohort studies is either classified as a prospective or a retrospective study.The definition is based on the time of occurrence of the disease according to the initiation of the study.In the prospective studies the disease of interest is never occurred at initiation, the exposure are either presence at the beginning of the study or it can occur later. The prospective cohort you have to follow over time.In the retrospective cohort study, all the relevant events disease and exposure have occurred before the initiation of the study.outcomefollow- upretrospective/prospectiveProtocol: study objectives, design choices, performance goals, monitoring and analysis proceduresManual of procedures/log bookCentralised training of key personnel
6 General considerations A cohort :A group of persons, identified at one point in time, who march off together into the future under the watchful eye of an investigator.A cohort study:A group of persons is defined, certain characteristics about each individual are recorded, and they are then followed up in such a way that new events (such as disease and death) or other changes in their characteristics are detected.
7 Cohort Study Longitudinal study, Follow-up study, prospective study Definition: An analytical epidemiological study in which two or more groups of people according to the extent of exposure (e.g. exposed and unexposed) are compared with respect to outcome or disease incidenceMost reliable for showing an association between a suspected risk factor and subsequent disease
8 Features of cohort study Cohorts must be free from the disease under studyBoth the groups should be equally susceptible to disease under studyDiagnostic and eligibility criteria of the disease must be defined beforehand
9 Cohort studyExposed and non exposed individuals are followed over time to determine whether they experience the outcome of interest.Examples of exposure :Medication use, Environmental factors, condition, ProcedureExamples of outcome:Disease. Death, etc.
10 Cohort studies Retrospective Prospective Ambidirectional Exposure DiseaseYes ?No ?ProspectiveExposure DiseaseYes ?No ?AmbidirectionalA cohort study follows-up two or more groups from exposure to outcome. In its simplest form, a cohort study compares the experience of a group exposed to some factor with another group not exposed to the factor.For all cohort studies, the subjects are selected according to whether they are exposed or unexposed to the factor under investigation, and their subsequent disease status is ascertained after some time. The follow-up period are usually several years. – Example: The Nurses Health StudyGenerally, at the time exposure status is defiend, all potential subjects must be free from the disease under investigation, and eligible participants are then followed over a period of time to assess the occurrence of that outcome.Researchers doing this kind of study must, therefore, (klik) go forward in time from the present (prospective) or (klik) go back in time to choose their cohorts (retrospective).…………..The feature that distinguishes a prospective from a retrospective cohort is simply and solely whether the outcome of interest has occurred at the time the investigator initiates the study.In a retrospective cohort study, the investigation is initiated at a point i time after both the exposure and disease have already occured.At the beginning of a prospective cohort study, the groups of exposed and unexposed subjects have been assembled, but the disease has not yet occured, so that the investigator must conduct follow-up during an appropriate interval to ascertain the outcome of interest.Can you give me an – hypothetical – example of a prospective study?- Example: The Frammingham Heart Study, Nurses Health StudyA third design obtion is the ambidirectional study: This mean that data are collected both retrospectively and prospectively on the same cohort.
11 Timing of cohort studies Retrospective: both exposure and disease have occurred at start of studyExposure Disease*Study starts
12 Timing of cohort studies Prospective: exposure has (probably) occurred, disease has not occurredExposure Disease*Study startsAmbi-directional: elements of both
13 Elements of cohort study Selection of study subjects( cohorts)Selection of comparison groupObtaining data on exposureFollow upAnalysis
14 Selection of the Exposed Population Sample of the general population:Geographically area, special age groups, birth cohorts (Framingham Study)A group that is easy to identify:Nurses health studySpecial population (often occupational epidemiology):Rare and special exposurePermits the evaluation of rare outcomes
15 Selection of the Comparison Population Internal Control GroupExposed and non-exposed in the same Study population (Framingham study, Nurses health study)Minimise the differences between exposed and non-exposedExternal Control GroupChosen in another group, another cohort (Occupational epidemiology: Asbestosis vs. cotton workers)The General Population
16 Selection of comparison group Internal comparison group: according to the degrees or levels of exposureSmokers, BP, Alcohol, diet etc.External comparisonSimilar in all respects without any exposureComparison with general population ratesOutcomes are compared with the similar outcome rates in the general population
17 Sources of exposure information: Pre-existing records - inexpensive, data recorded before disease occurrence but level of detail may be inadequate.Records may be missing, / usually don't contain information on confounders
18 Sources of exposure information: Questionnaires, interviews:good for information not routinely recorded but have potential for recall biasDirect physical exams, tests, environmental monitoring may be needed to ascertain certain exposures.
19 Follow up Regular follow up of all participants Periodic medical examination of each memberReviewing physician and hospital recordsRoutine surveillance of death recordsMailed questionnaires, telephone call, periodic home visits
20 Sources of outcome information: Death certificatesPhysician, hospital, health plan recordsQuestionnaires (verify by records)Medical examinations
21 Analysis in cohort study Incidence of disease among exposed and non exposedRelative risk estimationAttributable risk estimation
22 Table for analysis cohort study Disease presentDisease absentTotalExposurePresent ( cohort)aba + bExposure absent (comparison)cdc + da + cb + da+b+c+dIncidence of disease among exposed = a / a+bIncidence of disease among non exposed = c / c+dP value should be <0.05
23 Relative risk Relative risk is calculated as Incidence of disease among exposedIncidence of disease among non exposed
24 Relative risk (Risk ratio) Quantifies magnitude of the association between exposure and diseaseVaries from 0 to infinityRR<1: exposure decreases the risk for diseaseRR=1: no associationRR>1: exposure is a risk factor for disease; increases risk for diseaseExample:RR=2.0 can be interpreted as two fold increase in risk
25 Attributable risks Also known as risk difference It is the difference in incidence rates of disease between exposed group and non exposed group.It suggests the amount of disease that might be eliminated if the risk factor could eliminated or controlled.Incidence of disease among exposed - incidence of disease among non exposedx 100Incidence of disease among non exposedex. AR is 90%. Interpretation-
26 Bias in Cohort studySelection bias - less of a problem than case control studiesInformation bias/misclassificationDegree of accuracy of classification of exposure, confounders and disease statusLoss to follow-up (affects validity)Non response (limits generalisability, not validity)Confounding
27 Cohort study Limitations Strengths Loss to follow-up Misclassification of diseaseor exposure status logistically challenging – especially for prospective design Hard to study rare diseases Changes over time in staff/methods Little control over natureand quality of data inretrospective designsStrengths Can establish time order Can obtain incidence rates Can study more than onedisease or outcome Minimizes bias inascertainment of exposurestatus and covariates –especially if collecting dataprospectively Efficient for rare exposures No controls, so no bias incontrol selection
28 Case-control study Cohort study Rare exposure Quick, inexpensive Examine multiple effects of a single exposureMinimizes bias in the in exposure determinationDirect measurements of incidence of the diseaseValidity can be affected by losses to follow-upCase-control studyQuick, inexpensiveWell-suited to the evaluation of diseases with long latency periodRare diseasesExamine multiple etiologic factors for a single diseaseSelection Bias and recall bias
29 Key points in Cohort study Presence or absence of risk factor is determined before outcome occursIdentify cohort (s).Measure exposure and outcome variablesFollow for development of outcomesEstimate incidence rates, RR and AR, if possible population AR.
30 Motivation is what gets you started. Habit is what keeps you going. Thought for the dayMotivation is what gets you started.Habit is what keeps you going.-Jim Ryun
34 Strengths of Cohort Studies Efficient for rare exposures, diseases with long induction and latent periodCan evaluate multiple effects of an exposureIf prospective, good information on exposures, less vulnerable to bias, and clear temporal relationship between exposure and disease
35 Weaknesses of Cohort Studies Inefficient for rare outcomesIf retrospective, poor information on exposure and other key variables, more vulnerable to biasIf prospective, expensive and time consuming, inefficient for diseases with long induction and latent periodKeep these strengths and weaknesses in mind for comparison with case-control studies
36 Cohort study Example of cohort studies The association between statin use and prostate cancer risk All men 45+ years enrolled in GHC for at least 2 years during Exposure is statin use, which may change over 14 years Follow 14 years until develop prostate cancer, die, or disenroll from GHC Each subject will contribute person-time to follow-up Survival analysis to account for time varying exposure, adjust for other risk factors, & accountfor censoringProstate cancerNo cancerStatin userNonuser14 years
37 Prospective vs. retrospective Cohort Studies Prospective Cohort StudiesTime consuming, expensiveMore valid information on exposureMeasurements on potential confoundersRetrospective Cohort StudiesQuick, cheapAppropriate to examine outcome with long latency periodsAdmission to exposure dataDifficult to obtain information of exposureRisk of confoundingThe prospective study is time consuming and therefore expensive on the other hand it is possible to have valid information on exposure, because it isn.t
38 Analysis in Cohort study Exposed and non-exposed individuals arefollowed over time to determine whether theyexperience the outcome of interest Examples of exposure:Environmental factor, condition, procedure Examples of outcome:Disease, death, costs