case control study

(1)

Case-control study

(2)

Introduction for case-control study

• Patients with a disease (case) are compared

with controls who do not have the disease.

– 以‘有病’及‘無病’做為主要分組

– 估計‘暴露因子 (exposure)’ 或‘ suspected fa

ctors’ 的相對危險性 (relative risk) 。

• 優點： cheaper than cohort study

• 限制： difficult in the choice of appropriate

controls

(3)

An efficient method of retrospective

sampling within a cohort study.

• By definition, exposure (dietary intakes) must be

established retrospectively

– 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.

– The best control should mimic the control from the cohort study

(4)

Study population and selection of case

• Formulating the research questions.

• Then select the best population to address the qu

estions.

– The study population must be large enough and have a high enough incidence of disease

– To provide a sufficient numbers of case over the cour se of the investigation.

– In practice, the choice of a study population is often c onstrained by operational requirements.

– e.q. The investigator may only have resources to con duct the study in the area where he/she normally wor ks.

(5)

4. Research questions of interest

• Occasionally the study population is the

starting point of an investigation

– 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.

(6)

Case ascertainment and selection

• To ensure that cases were ascertained by uniform crit

eria.

• Another consideration in the selection cases is the sp

ecificity of the diagnosis.

• E.g. 研究 vitamin E 與肺癌的關係

– 肺癌有幾種 subtypes

– 選其中一種 subtype 做研究，較能得到顯著的結果

– Vitamin E 只對患有 squamous carcinoma 有保護效果

• E.g. Chilli pepper

– Effect being stronger in relating to intestinal-type gastric c ancer than to diffuse-type gastric cancer.

(7)

Ascertainment of exposure factors

• Exposure factors must be measured

– Risk factors of interest (dietary or nutritional)

• 可選擇與特定營養素含量豐富的食物為 exposure factors

• E.g.: 研究鈣質攝取量與大腿骨折發生率的關係：選擇富

含鈣質的食物做研究 ---- milk, cheese, cake, biscuits, pud dings

– Confounding factors

• Associated with both causal agent and resulting event

• E.g. 研究 dietary factors and lung cancer confounding fact ors ： smoking habits, air pollution.

(8)

3. Factors affecting exposure assessment

• If the disease has a long pre-clinical phase, the rel

evant exposure may have occurred many years be

fore diagnosis, and in nutrition studies this can po

se particular difficulty

– E.g. liver cancer and unfresh peanut consumption.

• Exposure recall may be affected by the disease sta

tus

– Changing dietary pattern due to pre-clinical disease – Recall bias

• e.q. 對於腎結石患者 --- 較無法真正得知其發病前真正的飲水量，所以較不易探討「發病前的飲水量」和「腎結石」之關係

• 解決方式

– 以 pre-clinical phase 的病人為病例 – 以 Blinding 的方式做資料的取得

(9)

Bias encountered in the case-control study

• 常見 case-control study 的偏差

– Selection bias: sampling the case and control

groups

• 解決方式：

– 訂出一套標準的 inclusion and exclusion criteria

– e.q. 選取 case and control groups 時，除了疾病條件不同外，其他條件儘量相同

– Information bias: observation bias and recall

bias

– Confounding factors

(10)

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.

(11)

病例組及對照組

人數或資料特性分布可能不同時

• 解決方式

– 事前

• 限制 Restriction

• 配對 Matching

– 事後

• 分層 Stratification

• 標準化 Standardization

• 校正 adjustment

(12)

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 populati on (or from the same catchment area)

– Where possible, the method used to ascertain exposur e should be similar for cases and controls.

– If information is to be obtained at interview or by phy sical examination, this should, where possible, be carr ied out blind to the case/control status of the subjects.

(13)

Controls from hospital

• 若從醫院選擇某一疾病為 cases

• 則一般 controls 會選擇醫院其他疾病

的患者。

– 優點：方便取得 controls

– 需注意事項：

• 實驗組的疾病是否會和對照組中的疾病分享共

致因

• 例如，研究造成動脈硬化的飲食危險因子，若

對照組選擇糖尿病的病人是不適合的，因為動脈硬化和糖尿病 share 許多共同因子。

(14)

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