Lecture 5 case control & cross-sectional spring 2013

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  • Sharon - the idea here is like the relation between oral contraceptives and thromboembolism. Because physicians were more likely to hospitalize women presenting with symptoms of thromboembolism if they currently used oral contraceptives, any case control investigation of the relationship between this exposure and disease that utilized only hospitalized cases could overestimate the true relationship since the proportion of exposed women would be artificially high among those hospitalized with thromboembolism compared with all cases of thromboembolism.
  • Sharon - the idea here is like the relation between oral contraceptives and thromboembolism. Because physicians were more likely to hospitalize women presenting with symptoms of thromboembolism if they currently used oral contraceptives, any case control investigation of the relationship between this exposure and disease that utilized only hospitalized cases could overestimate the true relationship since the proportion of exposed women would be artificially high among those hospitalized with thromboembolism compared with all cases of thromboembolism.
  • Sharon - the idea here is like the relation between oral contraceptives and thromboembolism. Because physicians were more likely to hospitalize women presenting with symptoms of thromboembolism if they currently used oral contraceptives, any case control investigation of the relationship between this exposure and disease that utilized only hospitalized cases could overestimate the true relationship since the proportion of exposed women would be artificially high among those hospitalized with thromboembolism compared with all cases of thromboembolism.
  • Sharon - the idea here is like the relation between oral contraceptives and thromboembolism. Because physicians were more likely to hospitalize women presenting with symptoms of thromboembolism if they currently used oral contraceptives, any case control investigation of the relationship between this exposure and disease that utilized only hospitalized cases could overestimate the true relationship since the proportion of exposed women would be artificially high among those hospitalized with thromboembolism compared with all cases of thromboembolism.
  • Sharon - the idea here is like the relation between oral contraceptives and thromboembolism. Because physicians were more likely to hospitalize women presenting with symptoms of thromboembolism if they currently used oral contraceptives, any case control investigation of the relationship between this exposure and disease that utilized only hospitalized cases could overestimate the true relationship since the proportion of exposed women would be artificially high among those hospitalized with thromboembolism compared with all cases of thromboembolism.
  • Sharon - the idea here is like the relation between oral contraceptives and thromboembolism. Because physicians were more likely to hospitalize women presenting with symptoms of thromboembolism if they currently used oral contraceptives, any case control investigation of the relationship between this exposure and disease that utilized only hospitalized cases could overestimate the true relationship since the proportion of exposed women would be artificially high among those hospitalized with thromboembolism compared with all cases of thromboembolism.
  • Sharon - the idea here is like the relation between oral contraceptives and thromboembolism. Because physicians were more likely to hospitalize women presenting with symptoms of thromboembolism if they currently used oral contraceptives, any case control investigation of the relationship between this exposure and disease that utilized only hospitalized cases could overestimate the true relationship since the proportion of exposed women would be artificially high among those hospitalized with thromboembolism compared with all cases of thromboembolism.
  • Lecture 5 case control & cross-sectional spring 2013

    1. 1. Study Designs Cross-sectional Case-control 1
    2. 2. Study Designs Observational ExperimentalCase-control Cross-sectional Cohort 2
    3. 3. Experimental Studies• Produce the most scientifically rigorous data• Difficulties enrolling subjects• High costs• Ethical issues 3
    4. 4. Observational Studies• “Natural experiments”• Cross-sectional• Case-control• Cohort 4
    5. 5. Cross-sectional design 5
    6. 6. Cross-sectional study• “Examines the relationship between diseases and other variables of interest as they exist in a defined population at one particular time.”• Selection is independent of exposure or disease status.• Done at a single point in time• Current disease status is examined in relation to current exposure status• Carried out for public health planning and for etiologic research 6
    7. 7. CROSS-SECTIONAL STUDIES• exposure and disease are assessed simultaneousin each INDIVIDUAL at a given point or SNAPSHOTin time... ONE SLICE IN TIME 7
    8. 8. CROSS-SECTIONAL STUDIES• Because unit of analysis is INDIVIDUALS… – Provides good estimate of Prevalence – NOT useful for rare events because in a one-time snapshot enough rare diseases or rare exposures may not be captured (in ecologic studies samples sizes are always large!) – May be subject to selection bias if certain INDIVIDUALS refuse to participate in the study for unknown reasons 8
    9. 9. Key features of cross-sectional studies• Examine association at a single point in time, and so measure exposure prevalence in relation to disease prevalence• Cannot infer temporal sequence between exposure and disease if exposure is a characteristic• Other limitations may include preponderance of prevalent cases of long duration and “healthy worker survivor effect”• Advantages include generalizability and low cost 9
    10. 10. CASE CONTROL STUDY DESIGN 10
    11. 11. CASE CONTROL STUDIES SOME KEY POINTS• Most frequently used study design• Participants selected on the basis of whether or not they are DISEASED (remember in a cohort study participants are selected based on exposure status)• Those who are diseased are called CASES• Those who are not diseased are called 11 CONTROLS
    12. 12. Study PopulationDISEASED non-DISEASED (Cases) (Controls) 12
    13. 13. Study PopulationDISEASED non-DISEASED (Cases) (Controls)exposed non-exposed exposed non- exposed 13
    14. 14. Because participants are selected on the basis of disease, exposures for ALL PARTICIPANTS are obtained RETROSPECTIVELY… PAST PRESENTExposure recall Cases & Controls Selected Example: lung cancer cases and non- 14 cancerous controls recall past exposure to
    15. 15. SELECTION OF CASES• FIRST decide on a specific case definition based on a medically diagnosed condition• Must consider what criteria will confirm the case definition – lung cancer confirmed by biopsy – osteoporosis confirmed by bone density measurements – atherosclerosis confirmed by ultrasound of carotid arteries 15
    16. 16. SELECTION OF CASES• SECOND will you use INCIDENT or PREVALENT cases?• Incident… – must wait for new cases to occur – study can specifically measure exposure relating to development of disease• Prevalent... – don’t have to wait while cases occur with time - more practical! – study will specifically measure exposure relating to survival with disease 16
    17. 17. SELECTION OF CASES• THIRD be aware of the unique qualities of certain groups – hospital admissions – nursing homes – screening participants – day care facilities• some groups may have better supporting medical records• some groups may be more homogenous and present less confounding variables 17
    18. 18. SELECTION OF CONTROLS• THE BIG PICTURE… – Controls should be representative of the referent population from which cases are selected (I.e. comparable) – They don’t have to be representative of the source (I.e. total) population – Controls should have the potential to become cases (they have to be susceptible for the disease of interest) 18
    19. 19. Total Population Reference Population Cases ControlsControls should be comparable to cases 19
    20. 20. Selection of controls• Controls (referent group) are a sample of the population that produced the cases• Controls come from the same base population as the cases• Controls must be sampled independently of exposure status 20
    21. 21. Sources of controls1. Individuals from the general populationAdvantage:Controls would be comparable to the cases w.r.t. demographic variablesDisadvantage:1. Time consuming and expensive to identify2. Interest in participation3. Recall bias 21
    22. 22. 2. Individuals attending a hospital or clinic• Illnesses of the controls should be unrelated to the exposure under study• Control’s illness should have the same referral pattern to the health care facility as the case’s illness.Advantages:1. Less expensive2. Easy to identify, good participation rates3. Have comparable characteristics to cases4. Recall of controls is similar to recall of casesDisadvantage:Difficulty in determining appropriate illnesses for inclusion 22
    23. 23. 3. Friends or relatives identified by the casesAdvantage:• Share the cases’ socioeconomic status, race , age, education etc..Disadvantage:1. Cases may be unwilling to nominate controls2. Bias results if cases and controls share a specific activity (exposure) 23
    24. 24. 4. Individuals who have died• Deceased controls are used when some or all of cases are dead.• Identified by reviewing death records of individuals who lived in the same geographic region and died during the same time period as the cases.• Used to ensure comparable data collection procedures (proxy interviews)Disadvantages:• May not be representative of the source population that produced the cases• More likely to have used alcohol, drugs, smoking 24
    25. 25. Sources of Exposure Information• Questionnaires• In-person• Telephone interviews• Self-administered questionnaires• Medical recordsAccuracy of the source especially that exposure is retrospective 25
    26. 26. MEASURING ASSOCIATION• because study participants in Case Control studies are selected based on disease status... – case control studies are ideal for the study of rare diseases – incidence can’t be calculated 26
    27. 27. MEASURING ASSOCIATION• Because incidence can’t be calculated, a relative risk can’t be calculated (RR is a ratio of INCIDENCE in exposed and non-exposed)• Instead of the RR, an ODDS RATIO is calculated in case control studies 27
    28. 28. Analysis of case-Control studies• The size of the population which produced the cases is not known• Can not calculate risk• => calculate Odds• The odds of an event is the probability that it will occur divided by the probability that it will not occur Odds among the exposed• Disease odds ratio = Odds among the non-exposed 28
    29. 29. MEASURING ASSOCIATION• Odds: NOT a proportion, but the ratio of the # ways an event CAN occur relative to the # of ways an event CAN NOT occur Odds = P(event occurs) = p / ( 1 - p) 1 - P(event occurs)• Odds Ratio: Odds of case being exposed Odds of control being exposed 29
    30. 30. Cases ControlsExposed a bUnexposed c d a/b adOdds ratio= = bc c/d 30
    31. 31. Is Use of Artificial Sweeteners associated with Bladder Cancer? Cases ControlsEver Used 1,293 2,455Never Used 1,707 3,321Total 3,000 5,776 ODDS RATIO = 1,293 * 3,321 = 1.026 2,455 * 1,707 31Hoover and Strasser (1980) Lancet 1: 837-840
    32. 32. Interpretation of the Odds Ratio…If O.R. = 1 then exposure NOT related todisease OR >1 then exposure POSITIVELY relatedto disease OR <1 then exposure NEGATIVELY related to disease Hoover and Strasser concluded what from their32
    33. 33. CASE CONTROL STUDY SUMMARY • cases and controls are representative of a referent population cases • controls have the potential to become casesReferent pop’n • selection based on disease and exposure assessedTotal population retrospectively 33
    34. 34. Twists and Turns in Case- control Studies 34
    35. 35. SELECTION OF CONTROLS• The investigator can elect to use more than one TYPE of control for each case… when there is no ONE group similar enough to cases EXAMPLE: a particular leukemia case may have both a neighborhood control (similar to case in terms of environment) and a sibling control (similar to case in terms of genetic background) 35
    36. 36. SELECTION OF CONTROLS• to avoid potential problems of confounding some studies use MATCHING – MATCHING: the process of selecting controls so that they are similar to cases on certain specific characteristics 36
    37. 37. Exposure Disease Confounder Confounders are third variables that are associated with both the disease and the exposure 37
    38. 38. SELECTION OF CONTROLS• CHARACTERISTICS THAT ARE OFTEN USED FOR MATCHING… – age – gender – body mass index (weight / height2) – smoking status – marital status 38
    39. 39. BIAS IN CASE CONTROL STUDIES BIAS: any systematic error (not random or by chance) in a study which leads to an incorrect estimate of the association between an exposure and the disease of interest• MAIN TYPES of bias in Case Control Studies… – selection bias – recall bias 39
    40. 40. BIAS IN CASE CONTROL STUDIES• SELECTION BIAS: systematic error due to differences in characteristics between those selected for a study and those not selected EXAMPLE in CC Studies: When cases are selected from a hospitalized population with unique exposures, controls often are not representative of the population that gave rise to cases 40
    41. 41. BIAS IN CASE CONTROL STUDIES• RECALL BIAS:systematic error due to differences in accuracy or completeness of recall to memory of past events or experiences EXAMPLE in CC Studies: Often cases faced with a serious illness will more closely scrutinize their past exposures and will be more accurate and complete in their recall than controls 41
    42. 42. What do you think will happen to ourestimate of the Odds ratio if cases recalltheir exposure status better than controls? D NDExposure a bNo exposure c dOdds Ratio = ( a ) d / b c 42
    43. 43. Strengths of case-control studies• Efficient for rare diseases• Efficient for diseases with long induction and latent periods• Can evaluate multiple exposures in relation to a disease• can use smaller sample sizes• cost/time effective when using previously collected (RETROSPECTIVE) exposures 43
    44. 44. Weaknesses• Inefficient for rare exposures• May have poor information on exposures because retrospective• Vulnerable to bias because retrospective• Difficult to infer temporal relationship between exposure and disease• can’t calculate incidence• selecting appropriate controls can be challenging 44
    45. 45. When is it desirable to use case- control design?• Exposure data are difficult or expensive to obtain• The disease is rare• The disease has a long latent period• Little is known about the disease• The underlying population is dynamic 45

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