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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 ?
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.
Exposed
Disease
Not Exposed
Exposed
No Disease
Not Exposed
First, select :
CASES
Then, measure past exposure : (with disease)
CONTROLS
(without disease)
a c a+c a a+c
b d b+d b b+d
Hypothetical example of a Case-Control Study of Coronary Heart Disease (CHD) and cigarette smoking
CHD
CONTROLS
CASES
CONTROLS
Ever
Never Total
1,293
1,707 3,000
2,455
3,321 7,776
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
CASES
CONTROLS
Selection of controls Sources : - Non-hospitalized persons living in the community - Hospitalized patients
Selection of Controls
1. Non-hospitalized persons living in the community neighborhood control - random digit dialing - best friend control - spouse or sibling control
-
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)
Hospital-based CCS
Subjects are more accessible Subjects tend to be more cooperative Background characteristics of cases and controls may be balanced Easier to collect exposure information from medical records and biological specimens
Source population
Study sample
Sampling
With disease
exposed
CASES
Sampling
CONTROLS
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
1. GROUP MATCHING
(FREQUENCY MATCHING)
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 are married 25% of the controls are married
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
CONCEPTUAL PROBLEMS
ONCE WE HAVE MATCHED CONTROLS TO CASES ACCORDING TO A GIVEN CHARACTERISTIC, WE CANNOT STUDY THAT CHARACTERISTIC
DISADVANTAGES
May be time-consuming and expensive to perform Some potential cases and controls may be excluded because matches cannot be made
The matched variables cannot be evaluated as risk factors in the study population
Greenberg R.S, p 133
PROBLEMS OF RECALL
Limitations of recall Recall bias
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
Normal CONTROLS
ANALYSIS
CASE CONTROL STUDY
CASES Exposed A
CONTROLS B
Total A+B
Unexposed
C+D
Total
A+C
B+D
A+B+C+D
All cases
Odds of case exposure Exposed cases = All cases A A+C A C B D
A+B
Unexposed cases All cases C A+C
A ODDS RATIO =
B =
AxD
BxC