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Observational Insights: Case-Control Studies in Early 20th Century Medical Research

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odysseus-emerson
27 diapositives · 413 Views · Nov 11, 2014

In the 1940s, two key observations laid the groundwork for case-control studies. Surgeon Alton Ochsner noted a striking correlation between cigarette smoking and lung cancer, suggesting a potential causal link despite the absence of comprehensive data. Meanwhile, ophthalmologist Sir Norman Gregg linked prenatal exposure to rubella with certain cataracts in children, showcasing another observational hypothesis. This study highlights the design, selection, and challenges of case-control studies, emphasizing the importance of observational data in medical research, especially in understanding disease exposure and outcomes.

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Observational Insights: Case-Control Studies in Early 20th Century Medical Research
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  1. CASE CONTROL STUDY

  2. In the early 1940s, Alton Ochsner, a surgeon in New Orleans, observed that virtually all of the patients on whom he was operating for lung cancer gave a history of cigarette smoking. Although this relationship is accepted and well recognized today, it was new and controversial at the time that Ochsner made his observation. He hypothesized that cigarette smoking was linked to lung cancer. Based only on his observations in cases of lung cancer, was this conclusion valid ?

  3. Again in the 1940s, Sir Norman Gregg, an Australian ophthalmologist, observed a number of infants and young children in his ophthalmology practice who presented with an unusual form of cataracts.Gregg noted that these children had been in utero during the time of a rubella (German measles) outbreak. He suggested that there was an association between prenatal rubella exposure and the development of the unusual cataracts. Keep in mind that at that time there was no knowledge that a virus could be teratogenic. Thus, he proposed his hypothesis solely on the basis of observational data, the equivalent of data from ambulatory or bedside practice today.

  4. Exposed Disease Not Exposed Exposed No Disease Not Exposed Design of a case-control study

  5. First, select : CONTROLS (without disease) b b + d CASES (with disease) a a + c Then, measure past exposure : Were exposeda b Were not exposedc d TOTALa + c b + d Proportions exposed

  6. Hypothetical example of a Case-Control Study of Coronary Heart Disease (CHD) and cigarette smoking

  7. History of use of artificial sweeteners in bladder cancer, cases and controls Leon Gordis, p.126

  8. Distribution of 1,357 male lung cancer patients and a male control group according to average number of cigarettes smoked daily over the 10 years preceeding onset of the present illness From Doll R, Hill AB - Leon Gordis, p.126

  9. SELECTION OF CASES AND CONTROLS Selection of cases Sources : - hospital patients - physicians’ practice patients - clinic patients - registries of patients with certain diseases in the community

  10. Selection of controls Sources : - Non-hospitalized persons living in the community - Hospitalized patients

  11. Selection of Controls 1.Non-hospitalized persons living in the community - neighborhood control - random digit dialing - best friend control -spouse or sibling control

  12. 2. Hospitalized patients - advantages * “Captive population” * more economical to carry out a study - disadvantages they represent a sample of an ill-health defined differ from people in the community - from the same hospital? - all other patients admitted? (other than those with the cases’ diagnosis)

  13. Relative strength of population-based and hospital-based case-control study Greenberg, p. 132

  14. Source population Study sample Sampling exposed With disease CASES Sampling unexposed Without disease THE ORIGIN OF SELECTION BIAS CONTROLS Greenberg, p.132

  15. MATCHING Is the process of selecting the controls so that they are similar to the cases in certain characteristics, such as age, race, sex, socioeconomic status, and occupation. 2 TYPES OF MATCHING 1. GROUP MATCHING 2. INDIVIDUAL MACHING

  16. MATCHING 1. GROUP MATCHING (FREQUENCY MATCHING) Selecting the controls in such a manner that the proportion of controls with a certain characteristic is identical to the proportion of cases with the same characteristic e.g. : If 25 % of the cases 25% of the controls are married are married ALL OF THE CASES BE SELECTED FIRST !!!

  17. 2.INDIVIDUAL MATCHING (MATCHED PAIRS) For each case selected for the study, a control is selected who is similar to the case in terms of the specific variable or variables concern using hospital controls

  18. THE PROBLEMS WITH MATCHING PRACTICAL PROBLEMS TOO MANY CHARACTERISTICS TO BE MATCHED DIFFICULT OR IMPOSSIBLE TO IDENTIFY AN APPROPRIATE CONTROL CONCEPTUAL PROBLEMS ONCE WE HAVE MATCHED CONTROLS TO CASESACCORDING TO A GIVEN CHARACTERISTIC, WE CANNOT STUDY THAT CHARACTERISTIC

  19. Advantages and disadvantages of matching in case-control study Greenberg R.S, p 133

  20. PROBLEMS OF RECALL Limitations of recallRecall bias - Collecting data from subjects by interviews - Human beings are limited to varying degrees in their ability to recall information A more serious potential problem in case-control studies

  21. USE OF MULTIPLE CONTROLS 1. CONTROLS OF DIFFERENT TYPES 2. CONTROLS OF THE SAME TYPE

  22. USE OF MULTIPLE CONTROLS 1. CONTROLS OF THE SAME TYPE 2 OR 3 CONTROLS FOR EACH CASE ARE USED TO INCREASE THE POWER OF THE STUDY UP TO A RATIO OF ABOUT 1 CASE TO 4 CONTROLS Why not keep the ratio of controls to cases at 1 : 1, and just increase the number of cases ? FOR MANY OF THE RELATIVELY INFREQUENT DISEASES, THERE MAY BE A LIMIT TO THE NUMBER OF POTENTIAL CASES AVAILABLE FOR STUDY

  23. 2. MULTIPLE CONTROLS OF DIFFERENT TYPES e.g. CHILDREN No history Prenatal history of radiation exposure Brain tumor CASES Other cancer CONTROLS Normal CONTROLS

  24. ANALYSIS CASE CONTROL STUDY

  25. Exposed cases A Case exposure probability = = All cases A + B Odds of Exposed cases Unexposed cases case exposure= All cases All cases A C = A + C A + C =A C Odds of B control exposure=D

  26. A B A x D ODDS RATIO = = C D B x C

  27. Thank you...