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- 1. CASE CONTROL STUDY 15/03/20231 By Dr. Monisha Mary P Post graduate in Community Medicine
- 2. LEARNING OBJECTIVES ❖ Toknow the Study design of epidemiological studies ❖ To define a Case-Control Study ❖ To describe the Basic steps of a case-control study ❖ To learn the bias involved in the Case-Control study ❖ To learn about advantages and disadvantages 15/03/2023 2
- 3. Formulation of a clearlydefined hypothesis “Retrospective” study Works backwards Potential bias: • Recall • Selection The starting point is the outcome. Basic steps in case- control Defining case groups Defining control groups confounding factor 15/03/2023 3
- 4. EPIDEMIOLOGIC STUDIES Experimental studyObservational study Random allocation Comparison group Randomised control trial Non randomised controlled trial Analytical study Descriptive study COHORT STUDY CASE CONTROL STUDY CROSS SECTIONAL STUDY Exposure to outcome Outcome to exposure Exposure and outcome at the same time STUDY DESIGN- EPIDEMIOLOGICAL STUDIES 15/03/2023 4
- 5. DEFINITION OF CASECONTROL STUDY • The observational epidemiological study of people with the disease of interest and a suitable control group of persons without the disease. • A case-control study involves two populations – cases and controls. • Also called a “retrospective study”. 15/03/2023 5
- 6. It has threedistinct features • Both exposure and outcome occurred before the start of the study. • The study proceeds backward from effect to cause. • It uses a control or comparison group to support our inference. 15/03/2023 6
- 7. • We identifyCases and Controls. • We then determine what proportion of cases, controls were exposed and what proportion of cases and controls were not exposed. • The hallmark of a Case-Control study is that it begins with people with the disease and compares them to people without the disease 15/03/2023 7
- 8. WHEN IS ITDESIRABLE TO CONDUCT A CASE CONTROL STUDY? Exposure management is expensive Disease is rare Very little understanding of the disease Many risk factors can be found out Longer duration(NCD) Population is dynamic When Funds are less Carried out quickly. 15/03/2023 8
- 9. DESIGN OF A CASE CONTROL STUDY HAVE THE DISEASEDO NOT HAVE THE DISEASE WERE EXPOSED WERE NOT EXPOSED WERE EXPOSED WERE NOT EXPOSED CASES CONTROLS OUTCOME EXPOSURE 15/03/2023 9
- 10. BASIC STEPS INCASE CONTROL STUDY ❖SELECTION OF CASES AND CONTROLS ❖MATCHING ❖MEASUREMENT OF EXPOSURE ❖ANALYSIS AND INTERPRETATION 15/03/2023 10
- 11. Selection of cases andcontrols Matching Measurement of exposure Analysis and interpretation BASIC STEPS IN CASE CONTROL STUDY The researcher first comes up with a hypothesis 15/03/2023 11
- 12. SELECTION OF CASES& CONTROLS 15/03/2023 12
- 13. SELECTION OF CASES •It involves defining the case and determining the source of cases. • As the cause and effect have already occurred, the proper diagnosis of the disease under investigation is necessary in the selection of a case. • Once the diagnostic criteria are established, they should not be changed or altered till the end of the investigation. 15/03/2023 13
- 14. • Hospital patients,patients in physicians’ practices, or clinic patients. • Many communities also maintain registers for certain diseases like cancer. • Using incident or prevalent cases-Incident cases are preferable to prevalent cases for reducing ❖Recall bias and ❖Over-representation of cases of long duration. • Old or advanced stages of the disease should preferably not be used (prevalent cases). 15/03/2023 14 SOURCES OF CASES
- 15. SELECTION OF CONTROLS •Controls should be selected from the same population • the source population (i.e. study base). ❖ Non-hospitalized • Neighbourhood control • Best friend control • Spouse or sibling control ❖ Hospitalized control • All other patients admitted • Specific ‘another diagnosis’ 15/03/2023 15
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- 17. CASES CONTROLS TOTAL POPULATION DEFINEDPOPULATION SELECTION OF CASES AND CONTROLS 15/03/2023 17
- 18. USE OF MULTIPLECONTROLS • Matching 1:2,1:3 or 1:4 will increase the statistical power of our study. • Therefore many case-control studies will have more controls than cases. • These controls may be ❖Controls of the same type. ❖Controls of different types. 15/03/2023 18
- 19. MATCHING • An importantconsideration is to ensure comparability within the cases and controls. • Matching is defined as the process of selecting the controls so that they are similar to the cases . • In certain characteristics such as age, race,sex, socioeconomic status, and occupation. 15/03/2023 19
- 20. • If notadequately matched for comparability, it could distort or confound the results of the study. • Matching may be of two types: ❖Group matching (Frequency matching). ❖Individual matching(matched pairs). THE NEED FOR MATCHING 15/03/2023 20
- 21. GROUP MATCHING Consists ofselecting the controls in such a manner that the proportion of controls with a certain characteristic is identical to the proportion of cases with the same characteristic. INDIVIDUAL MATCHING In this approach, for each case selected, a control is selected who is similar to the case in terms of the specific variables of concern. 15/03/2023 21
- 22. UNPLANNED MATCHING Unplanned matchingmay inadvertently occur in case-control studies, for example Example: • Neighborhood controls-we are in effect matching for socioeconomic status as well as for cultural and other characteristics of a neighborhood. • Best friend controls-his or her best friend share many lifestyle characteristics, which in effect produces a match for these characteristics. 15/03/2023 22
- 23. 15/03/2023 23 EXAMPLE OFUNPLANNED MATCHING Oral contraceptive Study of cancer best-friend controls were considered study of oral contraceptive use and cancer Her best friend would also be likely to be an oral contraceptive user The result would be an unplanned matching of oral contraceptive use, so that this variable could no longer be investigated in this study
- 24. PROBLEMS WITH MATCHING Practicalproblems If matching is done for too many characteristics, difficult or impossible to find an appropriate control Conceptual problem Once matched controls to cases according to a given characteristic, we cannot study that characteristic. We do not match any variable that we may wish to explore in our study 15/03/2023 24
- 25. CONFOUNDING FACTOR • Theterm “confounding factor” is defined as one which is associated with both exposure and disease and is distributed unequally in study and control groups. • More specifically, a confounding factor is one that although associated with exposure under investigation by itself, independently of any such association, a risk factor for the disease. 15/03/2023 25
- 26. • Let ussuppose that we are interested in examining the relationship between the current use of oral contraceptives and ovarian cancer. • In this example, it is appropriate to match age, since age is associated with the exposure of interest (current oral contraceptive use) and is an independent risk factor for ovarian cancer. • In other words, age is a confounding factor. • Failure to match, or otherwise control, for age would result in a biased assessment of the effect of oral contraceptive use. 15/03/2023 26
- 27. OVERMATCHING • Unplanned matchingon a variable strongly related to the exposure being investigated in the study is called overmatching. • The most serious type of overmatching occurs when one matches on a factor that is both affected by exposure and a cause of disease. 15/03/2023 27
- 28. MEASUREMENT OF EXPOSURE •Information about the exposure should be obtained from both the cases and controls in the same manner. • This may be achieved by: ❖Interviews ❖Questionnaires ❖Studying past records like hospital or employment records etc ❖Medical records. 15/03/2023 29
- 29. ANALYSIS • This isthe final step in a case-control study, and it provides: ❖ Exposure rates among cases and controls to the suspected factor. ❖ Estimation of disease risk associated with exposure. 15/03/2023 30
- 30. EXPOSURE RATES • Acase-control study directly estimates the exposure rates to a suspected factor in disease and non-disease groups. • The significance of measuring the exposure rates lies in estimating the probability of associating the disease and the factor under study. 15/03/2023 31
- 31. • Exposure Rates:Cases = a/(a+c) =65/100 =65% Controls =b/(b+d) =40/200= 20% • The frequency of obesity is definitely higher among T2DM than those without T2DM. 15/03/2023 32 Diabetes + Diabetes - Obesity+ 65 (a) 40 (b) Obesity- 35 (c) 160 (d) Total 100 (a + c) 200 (b + d) CASE-CONTROL STUDY OF TYPE 2 DIABETES AND OBESITY
- 32. ODDS RATIO • Itis a measure of the strength of the association between risk factor and outcome. • It is closely related to relative risk. • The determination of the odds ratio is based on 3 assumptions ❖The disease to be investigated must be relatively rare or a chronic disease. ❖ The cases must be representative of those with the disease and ❖ The controls must be representative of those without the disease. 15/03/2023 33
- 33. ODDS OF ANEVENT Can be defined as the ratio of the number of ways the event can occur to the number of ways the event cannot occur. ODDS RATIO (OR) Compares the odds of exposure among those with the disease to the odds of exposure among those without the disease. 15/03/2023 34
- 34. DETERMINE ASSOCIATION CASES CONTROLS EXPOSEDa b UNEXPOSED c d • Assess whether exposure is distributed between the cases and controls, which may indicate that the exposure is a risk factor for the health outcome under study. 15/03/2023 35
- 35. ❖ Odds ofa case being exposed = a:c or a/c ❖ Odds of control being exposed = b:d or b/d ❖ Odds ratio = odds that cases were exposed /odds that controls were exposed = ad/bc. CASES CONTROLS EXPOSED a b UNEXPOSED c d TOTAL (a + c) (b + d) PROPORTIONS EXPOSED a/ (a + c) b/ (b + d) 15/03/2023 36
- 36. INTERPRETATION OF THEODDS RATIO • OR = 1: no association between outcome and exposure (same odds of exposure in cases and controls = same odds of disease in exposed vs. unexposed). • OR >1: exposure is associated with increased risk for the outcome (greater odds of exposure in cases than control Harmful Effect. • OR <1:exposure is associated with reduced risk for outcome (lower odds of exposure in cases than controls =lower odds of disease in exposed vs. unexposed) Protective Effect. 15/03/2023 37
- 37. CALCULATING ODDS RATIOIN AN UNMATCHED CASE CONTROL STUDY Odds Ratio=ad/bc CALCULATING ODDS RATIO IN MATCHED PAIRS CASE-CONTROL STUDY 15/03/2023 38 Concordant pairs Discordant pairs Pairs in which both case and control were exposed Pairs in which neither the case nor the control was exposed Pairs in which the case was exposed but the control was not Pairs in which the control was exposed but the case was not
- 38. • Calculation ofthe Odds ratio in such a matched pair study is based on the discordant pairs only (b) and (c) . • The concordant pairs are ignored as they do not contribute to our knowledge of how many cases and controls differ in regard to past history of exposure. 15/03/2023 39 Matched pairs odds ratio = b/c
- 39. 15/03/2023 40 2 4 13 Exposed Non exposed Control Exposed Not exposed Case Matched pairs Odds Ratio = b/c = 4/1 =4
- 40. 15/03/2023 41 Diabetes +Diabetes - Obesity+ 65 40 Obesity- 35 160 Total 100 200 CASE-CONTROL STUDY OF TYPE 2 DIABETES AND OBESITY Odds Ratio-ad/bc =65x160/40x35 =7.42 • How much higher is the odds of exposure in the cases as compared to controls? • In the above example, individuals with Diabetes are 7.42 times more likely to be obese as compared to those without Diabetes. • The odds ratio is a key parameter in case-control studies.
- 41. 15/03/2023 42 a b cd a b c d Develop disease Do not develop disease Exposed Non exposed CASES CONTROLS History of exposure No history of exposure OR=odds that an exposed person develops disease/odds that a nonexposed person develops the disease. =ad/bc OR=odds that a case was exposed/odds that control was exposed. =ad/bc a b c d Disease No Disease Exposed Non exposed Odds Ratio(OR) Cross product ratio ad/bc
- 42. Diabetes + Diabetes- Obesity+ 10 40 Obesity- 02 48 Odds of exposure among diseased 10/2 Odds of exposure among non diseased 40/48 Exposure Odds ratio 6.25 Odds of disease among exposed 10/40 Odds of disease among non exposed 2/48 Disease Odds ratio 6.25 15/03/2023 43
- 43. • Because epidemiologyis always concerned with identifying predictors of disease • And odds ratio of exposure is same as odds ratio of disease • Therefore even in case control studies , the Interpretation is always prospective . 15/03/2023 44
- 44. BIAS • Bias isany systematic error in the determination of the association between exposure and the disease. ❖Selection bias ❖Information bias. 15/03/2023 45
- 45. SELECTION BIAS • Itrefers to any error in selecting the study population ❖The people who are selected to participate in a study are not representatives of the reference population. ❖Controls are not representative of the population which produced the cases. 15/03/2023 46
- 46. Case-control study to examineHTN in women OCP to be used as one risk of factor of interest Women who take OCP have regular check ups Than women with who do not take OCP Women who take OCP more likely to be identified as having HTN for study EXAMPLE OF SELECTION BIAS IN THE SELECTION OF CASES 15/03/2023 47 We select as cases those women who have been diagnosed as having HTN in PHC
- 47. SELECTION OF CONTROLS We want to investigaterisk factors for liver cirrhosis Heavy alcohol use will be a major risk factor We select cases from hospital records People admitted to same hospital with trauma as controls People admitted to hospital =heavy users of alcohol So less diff in prevalence of risk factor in case and controls EXAMPLE OF SELECTION BIAS IN SELECTION OF CONTROLS 15/03/2023 48
- 48. INFORMATION BIAS RECALL BIAS •When cases and controls are asked questions about their past history, it may be more likely for the cases to recall the existence of events than the controls who are healthy people. • Cases may have a different recall of past events than controls. 15/03/2023 49
- 49. PROBLEMS OF RECALL •A major problem in case control studies is that of recall of a history of past exposure. • Recall problems are of two types ❖Limitations in recall ❖Recall bias • Recall bias is the main form of information bias in case control study. 15/03/2023 50
- 50. LIMITATIONS OF RECALL •Virtually all human beings are limited to varying degrees in their ability to recall. • Much of the information in case control involves collecting data from subjects through interviews. • People being interviewed may simply not have the information being requested. 15/03/2023 51
- 51. EXAMPLE OF RECALLBIAS A Mother who had a child The child was born with a birth defect She may have forgotten entirely Mother tries to identify some unusual effect While mother of a child without a brain defect Which occurred during her pregnancy Such mother can recall even a simple event She wants to know why it happened Ernst Wynder called Recall bias as Rumination Bias 15/03/2023 52
- 52. Defined Cohort Developed disease Havenot developed disease CASES Subgroup selected as CONTROLS Years Initial Data and/or Serum, Urine, or Other Specimens Obtained Design of a case-control study initiated within a cohort 15/03/2023 53
- 53. DEFINED COHORT DEVELOP DISEASE HAVE NOTDEVELOPED THE DISEASE TIME I YEAR 2 YEARS 3 YEARS 4 YEARS 5 YEARS CASE 1 CASE 2 CASE 3 AND 4 CONTROL 1 CONTROL 2 NESTED CASE CONTROL STUDY 15/03/2023 54
- 54. DEFINED COHORT DEVELOP DISEASE TIME I YEAR 2YEARS 3 YEARS 4 YEARS 5 YEARS CASE 1 CASE 2 CASE 3 AND 4 CASE 5 5 CASES 5 CONTROLS CASE COHORT STUDY DESIGN 15/03/2023 55
- 55. CASE-CROSSOVER DESIGN • Thecase-crossover design is used for studying the etiology of acute outcomes such as myocardial infarctions or deaths. • In this type of study, a case is identified (for example, a person who has suffered a myocardial infarction) and the level of the environmental exposure, is ascertained for a short time period preceding the event (the at-risk period). • This level is compared with the level of exposure in a control time period. 15/03/2023 56
- 56. WHEN IS ACASE CONTROL STUDY WARRANTED? • At an early stage in our search for an etiology, we may suspect any one of the several exposures, but we may not have evidence. • Using case control study we compare people with the disease(cases) and people without the disease (controls). • We can then explore the possible roles of a variety of exposures or characteristics in curing the disease. 15/03/2023 57
- 57. ADVANTAGES • Relatively easyto carry out. • Rapid and inexpensive. • Require comparatively few subjects. • Particularly suitable to investigate rare diseases. • No risk to subjects. • Allows study of different etiological factors. • Risk factors can be identified. 15/03/2023 58
- 58. DISADVANTAGES • Problems ofbias rely on memory or past records, the accuracy of which may be uncertain; validation of information obtained is difficult or sometimes impossible. • Selection of an appropriate control group may be difficult. • We cannot measure incidence, and can only estimate the relative risk. • Do not distinguish between causes and associated factors. 15/03/2023 59
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- 60. Cohort Case controlstudy Study group Exposed person Cases Comparison group Non exposed person Controls Measurement of risk Absolute risk Relative risk Odds ratio Attributable risk Odds ratio Time for study Long Short Cost of study Expensive Inexpensive Best when Exposure is rare Disease is rare Population size needed Relatively large Relatively small Potential bias Assessment of outcome Assessment of exposure 15/03/2023 61
- 61. EXPOSED NOT EXPOSED DISEASE DEVELOPS DISEASE DOESNOT DEVELOP PEOPLE WITH THE DISEASE PEOPLE WITHOUT THE DISEASE COMPARING CASE CONTROL AND COHORT STUDIES DISEASE DEVELOPS DISEASE DOES NOT DEVELOP WERE EXPOSED WERE NOT EXPOSED WERE EXPOSED WERE NOT EXPOSED Start with Then follow up for Start with CASES CONTROLS Then determine the exposure history COHORT STUDY CASE CONTROL STUDY 15/03/2023 62
- 62. Defined population Disease develop Disease does not develop Exposed Non Exposed Withdisease Without disease A B C A B C CASES CONTROLS In a case-control study that starts by identifying cases and controls, we can study multiple exposures but only one outcome. In a cohort study that starts with a defined population, we can study both multiple exposures and multiple outcomes. CASE CONTROL AND COHORT STUDY DESIGN 15/03/2023 63
- 63. CASE CONTROL OUTCOME TO EXPOSURE COHORTSTUDIES EXPOSURE TO OUTCOME Ca Lung patients and non patients Follows a cohort of smokers and non smokers without Ca Lung Clarifies if it was smokers who contributed to high Ca Lung Smokers develop Ca Lung more frequently 15/03/2023 64
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- 66. 15/03/2023 67 PROSPECTIVE ANDRETROSPECTIVE CASE CONTROL AND COHORT RETROSPECTIVE CASE CONTROL PROSPECTIVE RETROSPECTIVE PROSPECTIVE COHORT OUTCOME EXPOSURE EXPOSURE OUTCOME
- 67. REFERENCES 1. Park k. Textbook of preventive and social medicine. Principles of epidemiology and epidemiologic methods. 26th ed. Jabalpur: M/S Banarsidas bhanot publications; 2021.p.83- 88. 1. Gordis L., Celentano David D., Szklo Moyses. Gordis Epidemiology.Observational Studies. 6th edition. Elsevier Saunders; 2019.p. 178-186. 15/03/2023 68
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