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1、Case-control studies,This version is made for bilingual teaching .Case-control study is an essential research design of Epidemiology, which involves identifying patients who have the outcome of interest (cases) and control patients who do not have that same outcome, and looking back to see if they h

2、ad the exposure of interest. The exposure could be some environmental factor, a behavioural factor, or exposure to a drug or other therapeutic intervention.,Select Study Design to Match the Research Goals,Case-Control Studies,Introduction Matching Investigate Example Design of Case-Control Studies D

3、ata collection and analysis Bias Strengths and Weaknesses Several important features,Introduction,Historical Perspective Definition Types of Design,Unique contribution of epidemiology to the repertoire of clinical research designs First case-control study performed in late 1950s Doll and Hills study

4、 of lung cancer and smoking behavior among physicians Jerome Cornfields classic description of “Retrospective Studies” New statistical tools were developed to analyze the study design - logistic regression,Historical Perspective,Introduction,Definition,A case-control study is a design in which indiv

5、iduals with an event or condition of interest, CASES, are identified and then compared with regard to one or more exposures to individuals without the event or condition of interest, CONTROLS. Case-control investigations typically are designed to assess the association between occurrence of disease

6、and an exposure suspected of causing (or preventing) that disease.,Introduction,a,b,c,d,Cases,Controls,Direction of inquiry,Exposed,Exposed,Unexposed,Unexposed,a/(a+c),b/(b+d),Introduction,Types,Family of epidemiological study designs Traditional case-control design Case-control studies within cohor

7、ts Nested case-control study design Case-cohort study design Case-parent study design Case-only study design,Introduction,Matching,Summarize Types Problems with Matching,Matching is defined as the process of selecting controls so that they resemble the cases with regard to certain characteristics Th

8、e goal of matching is to create similar distributions between cases and controls with regard to certain characteristics Matching can be used to Adjust for potential confounding factors Increase precision of estimate,Matching,Summarize,Individual level matching For each case in the study, one or more

9、 controls are selected with identical (similar) characteristics as the case Frequency, or group, matching Select controls so that the proportion with a certain characteristic is identical to the proportion of cases with that characteristic,Matching,Types,Difficult and expensive Cannot evaluate the e

10、ffect of controlled variables May limit the ability to control for other variables Overmatching Controls resemble cases in terms of known and unknown characteristics, some of which may be associated with the disease,Problems with Matching,Matching,Investigate Example,the association between occurren

11、ce of Eosinophilia-myalgia syndrome(EMS) and Ingestion of L-tryptophan. Background conduct results,Investigate Example,Background,EMS was first recognized in October 1989, it occurs predominantly in women and is relatively rare. when astute physicians determined that three people with unexplained my

12、algias and eosinophilia had consumed L-tryptophan. Prompt response by health departments quickly led to case-control studies,the results of which suggested that ingestion of L-tryptophan was the cause of EMS.,The Centers for Disease Control and Prevention(CDC) conducted a series of case-control stud

13、ies in 1989 and 1990. One of the studies conducted in Minnesota, Researchers selected 63 case subjects of EMS in the metropolitan area of Minneapolis-St.Paul. Researchers randomly selected 5188 control subjects in the same area. Researchers interviewed subjects and asked abort potential risk factors

14、 and about their use of L-tryptophan.,Investigate Example,Conduct,L-tryptophan was taken significantly more frequently by cases than by controls 61 of 63 case subjects (97%),but only 101 of 5188 control subjects (2%). L-Tryptophan-containing products were taken off the market in November1989,In 1990

15、,after the recall of L-tryptophan,the number of reported cases fell to near zero.,Investigate Example,Results,Selection of Cases Develop a case definition then identify new cases within a specified time period Selection of Controls The sample of controls should have the same prevalence of exposure a

16、s the source population of unaffected persons. Determination of Exposure,Design,Selection of Cases,Design,Sources of cases Species of cases Something important,Selection of Cases Sources of Cases,Sources of Cases Hospital or clinic Because risk factors may result from referral patterns to specific h

17、ospitals, multiple hospitals/clinics often chosen Referral of more ill patients to hospitals, especially tertiary care centers Population-based or community New cases reported to health departments, registries, hospital record departments, etc. Cases cannot be selected based on known or unknown asso

18、ciation with exposure of interest,Design,Selection of Cases Species of Cases,Newly diagnosed or incident cases Previously existing or prevalent cases Incident cases preferred over prevalent cases in most settings If prevalent cases chosen, then risk factors identified for disease may be those relate

19、d more to survival with disease than disease occurrence. Survivorship bias also true for incident cases, but minimized,Design,Specify the definition of a case The criteria should minimize the likelihood that an affected person (true case) is missed (i.e,the criteria must be sensitive). A nonaffected

20、 person is falsely classified as a case (i.e, the criteria must be specific).,Design,Selection of Cases Something Important,Selection of Controls,Sources of controls Multiple controls Something important,Design,Hospital control group Hospitalized patients, best if chosen from the same hospital as ca

21、ses in order to control for unknown reference population Select from all patients admitted to the hospital Select from specific diagnosis,Design,Selection of Controls Sources of Controls (1),Selection of Controls Sources of Controls (2),Community control group Probability sample best, but not often

22、practical Select from school rosters, insurance companies, etc. Neighbors of cases Random digit dialing Best friend,Design,Selection of Controls Multiple Controls,Controls of the same type May improve precision of the measure of association Precision rarely improved with more than 5 controls per cas

23、e Controls of different types Hospital controls and community controls per case,Design,Controls cannot be selected based on known or unknown association with exposure(s) or risk factors of interest,Design,Selection of Controls Something Important,Exposure Something important,Determination of Exposur

24、e,Design,Determination of Exposure Exposure,Exposure is determined in a retrospective manner, that is one must look back in time to assess exposure status before a person became a case. Each individuals prior exposure to the risk factor of interest Other exposures,Design,Determination of Exposure So

25、mething Important (1),Cases and controls must be assessed for exposure in the same way Interviews should be standardized, monitored, and conducted by trained interviewers.,Design,Exposure must be measured in a blinded manner Data collectors must be unaware of whether subject is a case or control Dat

26、a collectors should be unaware of the study hypothesis,Design,Determination of Exposure Something Important (2),Data collection and analysis,Collection of Data Analysis of Data OR Unmatched analysis Matched analysis Analytic Strategy,Collection of Data,Interviews and questionnaires Information conce

27、rning risk factors may also be obtained from medical,occupational,or other records.,Data collection and analysis,Analysis of Data,Data collection and analysis,Unexposed - c,Exposed - a,Population at Risk,Exposed - b,Cases,Controls,Unexposed - d,The power of the study design lies in the symmetry of t

28、he OR. OR is the odds of exposure given disease divided by the odds of exposure given no disease. Remember that the odds of exposure among cases compared with controls is the same as the odds of disease among exposed and unexposed.,Data collection and analysis,Odds Ratio,Unmatched analysis,Data coll

29、ection and analysis,Unmatched analysis,Data collection and analysis,Case-control pairs that share the same exposure status do not contribute to the estimate of risk.,Data collection and analysis,Matched analysis,Matched analysis,Data collection and analysis,Analytic Strategy,Assess relationship/asso

30、ciation between Exposure and independent variables Case/Control status and independent variables Calculate crude, or unadjusted, OR for exposure - case association Matched analysis required for matched studies,Data collection and analysis,Analytic Strategy,Stratified analysis Calculate stratum-speci

31、fic ORs for exposure-case relationship Determine presence of confounding and interaction Logistic regression analysis Regression technique used to adjust for confounding and interaction Special logistic model applied in matched studies,Data collection and analysis,Bias,Introduction Selection bias In

32、formation bias Confounding,Introduction,Case-control studies are subject to bias and confounding, both will distort the results of the study Bias is defined as the deviation of results, or inferences, from the truth, or processes leading to such deviation. There are about 75 different types of bias

33、now identified in published case-control studies,Bias,Selection Bias,Features Types,Bias,Features (1),Selection bias reflects systematic errors that arise from the way in which subjects are selected. If the prior exposure of the cases studied differs from that of all cases arising from the source po

34、pulation or if prior exposure of controls differs from that of persons in the source population without the disease or interest selection bias may be present.,Bias,Features (2),Preferential diagnosis of exposed cases may lead to selection bias. Low participation may lead to selection bias. Errors in

35、 sampling controls from the source population can also create selection bias.,Bias,Types,Admission rate bias Prevalence-incidence bias Detection signal bias Time effect bias,Bias,Information Bias,A distortion in measuring exposure or outcome data that results in different quality (i.e., accuracy or reliability) or frequency of information between comparison groups. Recall bias Conf

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