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Design and Analysis Techniques for Case-Control Studies

Design and Analysis Techniques for Case-Control Studies. Instructor: 李奕慧 yihwei@mail.tcu.edu.tw. Lecture Overview. Case-Control Study Example: ”Risk factors associated with lung cancer in Hong Kong” OR for multiple exposure levels Confounding factors

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Design and Analysis Techniques for Case-Control Studies

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  1. Design and Analysis Techniques for Case-Control Studies Instructor: 李奕慧 yihwei@mail.tcu.edu.tw

  2. Lecture Overview • Case-Control Study • Example: ”Risk factors associated with lung cancer in Hong Kong” • OR for multiple exposure levels • Confounding factors • Methods of Controlling (adjusting for) confounders

  3. Epidemiologic Study Design • Analytical studies • Intervention studies • Clinical trials • Observational studies • Cohort studies • Case-control studies

  4. Case-control study Exposed Cases Non-exposed Study Population Exposed Controls Non-exposed

  5. Selection of cases • Establish a strict diagnostic criteria for the disease: Examples: • Type 1 diabetes in children: severe symptoms, very high BG, marked glycosuria, and ketonuria. • Type 2 diabetes: few if any symptoms, Slightly elevated BG, diagnosis “complicated”.

  6. Selection of cases • Population-based cases: include all subjects or a random sample of all subjects with the disease at a single point or during a given period of time in the defined population: • Danish childhood diabetes register • Hospital-based cases: All patients in a hospital department at a given time

  7. Selection of Controls Principles of Control Selection: • Study base: • Controls can be used to characterise the distribution of exposure • Comparable-accuracy • Equal reliability in the information obtained from cases and controls  no systematic misclassification • Overcome confounding • Elimination of confounding through control selection matching or stratified sampling

  8. Selection of Controls • General population controls: • registries, households, telephone sampling • costly and time consuming • recall bias • eventually high non-response rate • Hospitalised controls: • Patients at the same hospital as the cases • Easy to identify • Less recall bias • Higher response rate

  9. Ascertainment of Disease and exposure status • External sources: • Death certificates, disease registries, Hospital and physicians records etc. • Internal sources: • Questionnaires and interviews, information from a surrogate (spouses or mother of children), biological sampling( e.g. antibody)

  10. Bias in Case-Control studies • Selection bias • Non-response • Detection bias • cases and controls are identified not independently of the exposure • Observation bias • Recall Bias: Cases are more likely to remember exposure than controls

  11. Quick, inexpensive Well-suited to the evaluation of diseases with long latency period Rare diseases Examine multiple etiologic factors for a single disease Strengths in Case-control

  12. Case-control study Not rare exposure Incidence rates cannot be estimated unless the study is population based Selection Bias and recall bias Limitations in Case-control

  13. Risk factors associated with lung cancer in Hong Kong Lung Cancer 40 (2003) 131-140

  14. Exposure level Cases Controls OR A1 B1 OR1 High A2 OR2 B2 Medium A3 B3 OR3 Low Reference C D Not exposed Multiple Exposure Levels

  15. Multiple Exposure Levels A significant (P<0.05) increasing trend in the OR was found between nonsmokers, ex- and current smokers; and increasing amount of smoking among the ever smokers. Lung cancer.sav Lung Cancer 40 (2003) 131/140

  16. 抽煙與罹患肺癌有關， Case中抽煙者佔較高的比例(43% vs 13.7%)

  17. Data > Select cases >

  18. 只選smoking=2, 3的資料進行分析 Exsmoker 罹患肺癌是nonsmoker的1.4倍, 95%CI (0.9, 2.3) Exsmoker與nonsmoker罹癌機率沒有顯著差異

  19. Confounding factors (干擾因素） Confounder: Variable is associated with both the disease and the exposure variable.

  20. Method for control for confounders • Study design: restriction/ matching/ randomization • Statistical adjustment: • Standardization; e.g. age standardized (where age is a confounder) • Stratified by confounder (Mantel-Haenszel test) • Incorporate the confounder into a regression analysis as a covariate. (logistic regression approach)

  21. Restriction • Example 研究主旨：二手煙(ETS, exposure)與罹患肺癌(disease)的關係 confounder: 研究對象本身是否抽煙 為了避免干擾只分析ETS對nonsmoker的影響

  22. Stratified Analysis

  23. 將性別當作分層(stratum)的因子 Lung cancer2.sav

  24. Sex-Specific OR for smoking 可以將男士的OR與女士的OR合併嗎？ 怎麼併？ Lung cancer2.sav

  25. Thank you!

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