Casecontrol study

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Case-control study
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Introduction for case-control study

• Patients with a disease (case) are compared with
  controls who do not have the disease.
• ????????????
• ??????(exposure)?suspected factors??????
  (relative risk)?
• ??cheaper than cohort study
• ??difficult in the choice of appropriate
  controls

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An efficient method of retrospective sampling
within a cohort study.

• By definition, exposure (dietary intakes) must be
  established retrospectively, and this poses
  problems in nutritional studies, especially when
  a disease has a long pre-clinical phase and the
  effects of diet only manifest after a
  corresponding latent interval.
• Controls should be similar to case subjects in
  all ways other than their exposure to the risk
  factors under investigation.

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Study population and selection of case

• Formulating the research questions.
• Then select the best population to address the
  questions.
• The study population must be large enough and
  have a high enough incidence of disease
• To provide a sufficient numbers of case over the
  course of the investigation.
• In practice, the choice of a study population is
  often constrained by operational requirements.
• e.q. The investigator may only have resources to
  conduct the study in the area where he/she
  normally works.

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Research questions of interest
4.

• Occasionally the study population is the starting
  point of an investigation, and the choice of risk
  factors for examination is decided secondarily.
• The trigger to such an investigation might be an
  unexplained focus of disease.
• E.g. The observation of high rate of stomach
  cancer in South Louisiana prompted a case-control
  study to look for a possible dietary explanation.
  

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Case ascertainment and selection

• To ensure that cases were ascertained by uniform
  criteria.
• Another consideration in the selection cases is
  the specificity of the diagnosis.
• E.g. ??vitamin E ??????
• ?????subtypes
• ????? subtype ???,?????????
• Vitamin E ????squamous carcinoma ????
• E.g. Chilli pepper
• Being stronger related to intestinal-type gastric
  cancer than diffuse-type gastric cancer.

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Ascertainment of exposure factors

• Exposure factors must be measured
• risk factors of interest (dietary or nutritional)
• ????????????????? exposure factors
• E.g.?????????????????????????????? ---- milk,
  cheese, cake, biscuits, puddings
• Confounding factors
• Associated with both causal agent and resulting
  event
• E.g. ?? dietary factors and lung cancer
  confounding factorssmoking habits, air
  pollution.

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Factors affecting exposure assessment
3.

• If the disease has a long pre-clinical phase, the
  relevant exposure may have occurred many years
  before diagnosis, and in nutrition studies this
  can pose particular difficulty
• E.g. liver cancer and unfresh peanut consumption.
• Exposure recall may be affected by the disease
  status
• Changing dietary pattern due to pre-clinical
  disease
• Recall bias
• e.q. ??????? --- ?????????????????,???????????????
  ??????????
• ????
• ?pre-clinical phase??????
• ? Blinding ?????????

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Bias encountered in the case-control study

• ??case-control study ???
• Selection bias sampling the case and control
  groups
• ????
• ??????? inclusion and exclusion criteria
• e.q. ?? case and control groups
  ?,?????????,????????
• Information bias observation bias and recall
  bias
• Confounding factors

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Selection of controls

• The aim
• From controls, one should get reliable estimate
  of exposure to risk factors and confounders among
  members of defined or theoretical study
  population who are at risk of becoming cases
  during the period of study.
• The objects leads to two requirements
• The exposure of controls should be representative
  of that in members of study population who are at
  risk of become cases.
• The exposure of controls should be ascertainable
  with the same accuracy as for cases.

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?????????????????????

• ????
• ??
• ?? Restriction
• ?? Matching
• ??
• ?? Stratification
• ??? Standardization
• ?? adjustment

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Control subjects selected from the general
population

• Usually there is no perfect control group, and
  the choice of controls must be a compromise.
• Three general rules are worth bearing mind
• Controls should always come from the study
  population (or from the same catchment area)
• Where possible, the method used to ascertain
  exposure should be similar for cases and
  controls.
• If information is to be obtained at interview or
  by physical examination, this should, where
  possible, be carried out blind to the
  case/control status of the subjects.

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Controls from hospital

• ??????????? cases
• ??? controls ?????????????
• ?????? controls
• ?????
• ??????????????????????
• ??,???????????????,?????????????????,??????????sha
  re???????

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Matching

• Matching is used in case-control studies
• To permit allowance for confounders
• which are complex or difficult to define.
• statistically more efficient efficient analysis
  requires that there be a similar ratio of cases
  to controls at each level of exposure to the
  confounding variable.
• To reduce biases in the ascertainment of
  exposure.
• Unlike in a cohort study, matching in a
  case-control study does not in itself eliminate
  the effects of a confounders.

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Nested case-control studies

• ??Cohort ?case-control study ????
• The case-control approach
• An efficient sampling within a theoretical cohort
  study
• It can be nested within real cohort studies.
• ??
• ??colon cancer ?vitamin D ??
• ???????????
• ????????????
• ???????colon cancer??
• ?????????controls
• ??????????????? vitamin D ???
• ???colon cancer ?vitamin D ??
• ?????????

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Study size and statistical power Sample size ??
page 82 Case control ratio ?11 14
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Analysis and interpretation

• The main measure of association commonly derived
  from case-control studies is the odds ratio (OR).
• The OR approximates closely to the relative risk.

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Unmatched analysis
OR ad / bc 95 CI OR
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Matched analysis
OR s / t 95 CI OR
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Interpreting an association as causal relationship
Assessment of whether of an observes association
is likely to be directly causal and not the
result of unrecognized confounding depends upon
several consideration
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