Case-control study – Flashcards
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What is a case control study?
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A study in which a group of persons with a disease (cases) and a comparison group of persons without the disease (controls) are compared with respect to the history of past exposures to factors of interest
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What is a cohort study?
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A study in which a group of persons exposed to a factor of interest and a group of persons not exposed are followed and compared with respect to the incidence rate of the disease or other condition of interest.
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For a cohort study is incidence rate sufficient for determining relationship between exposure and disease?
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Cohort study Incidence rate in exposed group is not enough (Needs nonexposed comparison group)
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In a case-control study is past exposures sufficient for determining the relationship between exposure and disease?
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Case-control study Past exposures of a group of cases is not enough (Needs a control group for comparison)
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What is the fundamental difference between case-control and cohort?
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A cohort study starts with people: with and without the exposure of interest and compares their future disease A case-control study starts with people: with and without the disease of interest and compares their past exposures
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Is the fundamental difference between a case-control and cohort study the calendar time period during which exposures took place? Provide an example.
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No. ...for example, in a both a retrospective cohort study and a case-control study, the calendar time period during which exposures took place is in the past
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How doe we measure past exposures in a case-control study?
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Interview Medical records/charts Assays of biological specimens (e.g. nested case-control studies)
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what is the goal for case-control studie measurements?
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Goal is to measure exposures that occurred before the onset of disease
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Explain selection of cases in case-control study for incident.
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Incident (newly diagnosed) cases Risk factors might contribute to the development of the disease
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Explain selection of cases in case-control study for prevalent.
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Prevalent (existing) cases Cannot distinguish between risk factors for the development of the disease and risk factors for cure or survival More difficult to know which came first, the exposure or the disease Exposure measurements problematic
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what is prevalence? is it a proportion?
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Prevalence = Number of a given disease at a particular time point or during a particular time period (this is a proportion and not a rate)
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What is a source population?
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the population that gives rise to the cases
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what is a case?
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need to have definite medical criteria for who is a case of the disease
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explain case identification
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need to put a system in place for finding all cases who meet the case definition and are members of the source population
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what is the major methodological challenge in case-control studies?
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Selection of appropriate controls is the major methodological challenge in case-control studies
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what are wanting to determine in a case=control study?
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In a case-control study, we want to determine whether exposures of interest differ between the cases and the source population
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where should controls be selected from?
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Controls should be selected from the source population that gave rise to the cases
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should the controls be representative of the source population?
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The controls should be representative of the source population with respect to the exposures of interest
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Ideally, what should controls be?
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Ideally, controls should be a random sample of the source population
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Can prevalent cases of the disease be eligible as controls?
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No
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If controls are selected in such a way that they have higher level of exposure than the source population what occurs?
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Bias results and it shows that the exposure is negatively associated
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If controls are selected in such a way that they have lower level of exposure than the source population what occurs?
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Bias results and it shows that the exposure is positively associated with the disease
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If controls are selected in such a way that they have the same level of exposure than the source population what occurs?
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Produces an unbiased result
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What are three case-control studies classified by type of source population?
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Population-based case-control studies Hospital (or clinic)-based case-control studies Nested case-control studies
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In population based case control studies what is a source population?
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all residents of a defined geographic area who do not have Disease X
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In population based case control studies what are cases?
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all new cases of Disease X that occur among residents of a defined geographic area over a specified period of time
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In population base case-control studies what are controls?
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sample (ideally random) of the source population over the same period of time
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Explain the Selection of controls in population-based case-control studies
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Selection of controls in population-based case-control studies Random selection of telephone numbers (random digit dialing)
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explain hospital based case-control studies source population
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all people without Disease X who would attend Hospital A if they had Disease X
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explain hospital based case-control studies cases
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all new cases of Disease X identified in Hospital A over a specified period of time
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explain hospital based case-control studies controls
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sample of patients in Hospital A with diagnoses other than Disease X over the same period of time
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In selection of controls in hospital based case-control studies what is a source population?
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all persons who would attend the hospital if they developed the disease of interest
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Is a source population in hospital based case control studies usually identifiable?
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No
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Is a random sample of the general population in hospital based case-control studies sufficient?
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A random sample of the general population will not necessarily correspond to a random sample of the source population because it does not take into account the referral patterns of the hospital
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Explain referral pattern regarding hospital based case-control studies.
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referral pattern depends on the disease (e.g. specialty hospitals)
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what are hospital based controls?
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Hospital-based controls are patients without the disease from the same hospital
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are hospital based controls a random or nonrandom sample of the source population?
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Nonrandom, most of which are healthy
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what does nonrandom sampling of the source population do?
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introduces the possibility that the distribution of the exposure of interest among the controls is not the same as it is in the source population
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Hospital controls reflect or don't reflect the distribution of exposure in the source population?
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the may not reflect
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why would Hospital controls not reflect the distribution of exposure in the source population?
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Exposures of interest may cause or prevent the diseases for which patients in the control group were hospitalized Persons with an exposure of interest may be more or less likely than persons without the exposure to be hospitalized for their disease if they develop it (this could also be an issue for cases)
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Are hospital controls representative or unrepresentative of the exposure distribution in parkinsons disease?
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unrepresentative
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why were they unrepresentative?
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Controls: random sample of persons hospitalized for other diseases, many of whom were hospitalized for heart disease Low folic acid intake is a risk factor for heart disease This control group would have a lower proportion of persons with high folic acid intake than the source population
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in a hospital based case control study why would we want to limit the controls controls to those hospitalized for diseases?
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to reduce the suspicion of there being an association with the exposure of interest
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why would we want to increase the variety of diseases in the control group in a hospital based case-control study?
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to dilute the possible bias of including a disease that might be related to the exposure which is unknown to the investigator
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excluded diseases in a hospital based case control study should apply to what?
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the diagnosis at the current hospitalization
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what is the source population of a nested case-control study?
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the subjects in an ongoing concurrent cohort study (e.g. Nurses' Health Study) who did not have Disease X at baseline
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what are the cases of a nested case-control study?
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all new cases of Disease X that occurred in the cohort over a defined period of follow-up
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What are the controls of a nested case-control study?
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random sample of subjects in the cohort who did not develop Disease X over the defined period of follow-up
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Exposures may be measured in nested case-control studies how?
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Exposures measured by assay of stored biologic specimens collected from the subjects at baseline
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Collection of additional exposure information not collected at baseline in a nested case-control study requires?
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Collection of additional exposure information not collected at baseline requires labor-intensive data collection activities, such as abstraction from records
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What is the advantage of a nested case-control study?
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Nested case-control study has advantage of cohort studies: exposure measured at baseline before development of disease
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What are the advantages of the nested case-control of concurrent cohort study?
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Cost: suppose there were 32,000 women in the source population, 200 cases, and 200 controls. Causality: the exposure occurred before the disease Further research: preservation of precious biologic specimens - remaining specimens available for other studies
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How to account for confounders in selecting controls?
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Matching
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What is matching
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selection of controls such that they are similar to cases with respect to factors other than the exposures of interest
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what are common matching factors?
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Common matching factors: age, sex, race, socioeconomic status
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what is frequency matching?
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selection of controls such that the distributions of the matching factors (e.g., age, sex) are similar in the case and control groups
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what is individual matching?
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each control is individually matched to a case with respect to specific factors, resulting in matched case-control pairs
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In a case-control study can the assocation between matching factors and disease be studied?
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no
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How can overmatching occur?
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Overmatching can occur if a matching factor is associated with the exposure of interest, thus making the controls artifactually like the cases with respect to that exposure
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When may matching be taken into account?
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Matching must be taken into account in the analysis through special analytic techniques We will cover some of these techniques in this course
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In case control studies can we measure incidence rate in exposed and unexposed group?
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In a case-control study, we cannot measure incidence rates in the exposed and nonexposed groups, and therefore cannot calculate the relative risk directly
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In a case control study was is a good approximation of the relative risk?
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In a case-control study, the odds ratio is a good approximation of the relative risk in some circumstances ...
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In Odds what is the probability that cases were exposed?
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Probability that cases were exposed = a/(a+c)
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What is the probablity that cases were not exposed?
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Probability that cases were not exposed = c/(a+c)
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what is the odds of a case having been exposed?
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Odds of a case having been exposed = [a/(a+c)]/[c/(a+c)] = a/c
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what is the formula for odds of a control having been exposed?
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b/d
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what is odds ratio?
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The ratio of the odds that the cases were exposed to the odds that the controls were exposed = (a/c)/(b/d) = ad/bc
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How do we interpret the odds ratio?
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The odds ratio is a good approximation of the relative risk when the disease being studied occurs infrequently (which is the situation in most circumstances case-control studies are conducted)
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if an OR =1 what does this mean?
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OR = 1 Risk in exposed = risk in nonexposed No association
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if an OR > 1 what does this mean?
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OR > 1 Risk in exposed > risk in nonexposed Positive association The larger the OR, the stronger the association May or may not be causal
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if an OR is <1 what does this mean?
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OR < 1 Risk in exposed < risk in nonexposed Negative association The smaller the OR, the larger the negative association May or may not be causal If causal, indicates a protective effect
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Can the OR be misleading?
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The odds ratio may be a misleading approximation to relative risk if the event rate is high
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Since the odds ratio is difficult to interpret, why is it so widely used?
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Odds ratios can be calculated for case-control studies whilst relative risks are not available for such studies
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What is the attributable risk percent of exposed using odds ratio?
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[(OR - 1)/OR] x 100 Tells us what percent of the disease among the exposed is due to the exposure
