3. case control study

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    Dr. Maher D. Fuad Fuad

    Lecturer

    Faculty of Medicine

    Department of Community Medicine

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    Definition

    Observational epidemiologic study

    Persons with the disease & a suitable control(comparison, reference) group of persons without thedisease.

    The relationship of an attribute to the disease is

    examined by comparing the diseased and non-diseased with regard to how frequently the attribute ispresent

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    Def. continue It is a retrospective or backward looking study as the

    study commences with the cases in which disease inquestion had already appeared.

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    Purpose

    Establish the cause and effect relationship (causal

    association) Testing causal hypothesis for rare diseases

    When results are expected less expensively and inshort time

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    EXPOSED

    EXPOSED

    NOT

    EXPOSED

    NOTEXPOSED

    TIME

    Direction of inquiry

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    STEPS OF CASE CONTROL STUDY Selection of cases

    Selection of controls

    Matching Enquiry and records verification for amount of

    exposure in both groups

    Comparison analysis and risk measurement

    If exposure is more in cases than in controls causalassociation suspected

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    Selection of Cases Study begins with CASES- Patients in whom the disease has already occurred- were enquired for all the details of their exposure to thesuspected cause

    Do the cases need to represent all patients with thedisease? No Restricted to a specific type or severity Usually new cases (incidence) is chosen not prevalent

    cases? Similar clinical, histological, pathological. Duration of exposureSelected independent ofexposure. (very important recap

    XS)

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    Continue.. Time of admission and duration of hospital stay

    has also to be considered while selecting thecases.

    Hospital cases will be usually of advanced stage ofdisease and this factor should be kept in mindwhile selecting the cases

    otherwise it will lead to selection bias (error).

    If possible, it is always advisable to select all cases

    from similar environmental exposure. Sources

    Hospital

    Community

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    Selection of Controls

    Carefully chosen otherwise validity of the study will be

    defective Should be obtained from same population

    Hospital-based.

    Community-based.

    Friends, relatives, Neighbors.

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    Hospital-basedADVANTAGES DISADVANTAGES

    Efficiency in obtainingsubjects.

    Can carry out Diagnostictest.

    Less recall bias

    Willingness to participate.

    Less likely to drop out.

    Cost saving

    Unknown potentialconfounders drugs.

    Exclusion criteria=case

    Without exclusion riskunderestimate

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    Community-basedADVANTAGES DISADVANTAGES

    Prevalence of exposure can beused as an estimate ofexposure

    Sampling frame Cost contacting lists of

    potential controls

    Interviewing subjects

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    Friends, Relatives, NeighborsADVANTAGES DISADVANTAGES

    Cooperation

    Predominantly healthy Can adjust confounders by

    cultural or geographical

    Over matching underestimate true effect

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    Selection ofControlscontinue..

    Number of controls taken may be

    four timesTwice

    even equal to that of cases

    the ratio depends upon the availability of suitable

    matched controls, available time and finances.

    Equal number, if they are better matched, are enoughto conduct the study.

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    MATCHING Is a comparative technique of neutralizing all other

    variables present in cases and control EXCEPT thevariable under study

    Known confounding variable eg. age, gender,occupation etc.

    Unknown confounding variable playing a role in

    causation

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    Cases are made identical with controls i.e. all theknown variables of the cases (like age, sex, occupation,social status,..etc) are (eliminated) with those ofcontrols except the factor (disease) under study.

    Cases and controls of same age, same sex, sameoccupation and living same village may be selected forbetter comparison, if feasible.

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    When selected from hospitals, it is essential to choosepatients with other diseases, not with the diseaseunder question and if possible, preferably from same

    hospital from where the cases were selectedStudy on the association between lung cancer andsmoking

    if lung cancer cases were selected as study group

    thyroid cancer patients can be taken as controls fromthe same hospital.

    This improves the efficiency of comparison and alsothe validity of the study by avoiding error

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    Both the groups were made identical in all their other

    characteristics except for the presence of lung cancer,which will be present only in cases.

    This can be done by proper selection and by matchingthe known variables in both groups.

    Then, we measure the proportion of smoking in casesand controls and compare.

    If it is significantly more in cases than in controlgroup, causal association is suspected

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    Design of case-control studiesFirst select

    Then measure pastexposure

    Cases with disease Control withoutdisease

    Exposed a b

    Not exposed c d

    a+c b+d

    Proportions Exposed P E/D+ = [a/(a+c)] P E/D- = [b/(b+d)]

    Ratio between above 2 proportions is mathematically possible but conceptuallywrong because they are not true prevalences

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    Hypothetical example of case control

    study of CHD and Cigarette SmokingCHD CONTROL

    SMOKE 112 176

    DO NOT SMOKE 88 224

    TOTAL 200 400

    OR = ??????

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    What should be always true for a

    case-control study?1. Cases and controls are randomly selected.

    2. Cases are a representative sample of all cases in thegeneral population

    3. Controls are a representative sample of the generalpopulation

    4. Cases and controls have the same population of

    origin5. Always start with some cases, then identify their

    valid controls

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    RR & AR in case-control study? Recall WHAT is Relative Risk & Attributable Risk?

    RRduration = Risk (E+)/ Risk (E-)

    ARduration= Risk (E+

    ) Risk (E-

    ) Since risk cannot be computed directly from a case-

    control study (why?), RR and AR cannot be computed.

    Answer: because we can not calculate incidence.

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    Advantages of Case-Control

    Studies1. Less expensive and simpler

    2. Require smaller sample sizes

    3. Shorter duration than prospective study4. Study multiple risk factors for 1 disease.

    5. Easily reproduced in different populations bydifferent investigators.

    6. Used for rare diseases.

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    Disadvantages of Case-Control

    Studies1. Liable for selection and recall bias.

    2. Population of origin for cases is difficult to defineprecisely.

    3. Difficult to identify appropriate control group

    4. Does not provide estimate of risks and attributablerisk.

    5. not suitable for rare exposures

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    Thank you