CASE CONTROL STUDY

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

Design of a case-control study

First, select :

CASES
Then, measure past exposure : (with disease)

CONTROLS
(without disease)

Were exposed Were not exposed TOTAL Proportions exposed

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

Smoke cigarettes Do not smoke cigarettes Total % Smoking cigarettes

112 88 200 56.0

176 224 400 44.0

History of use of artificial sweeteners in bladder cancer, cases and controls

artificial sweetener use

CASES

CONTROLS

Ever
Never Total

1,293
1,707 3,000

2,455
3,321 7,776

Leon Gordis, p.126

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

Average daily cigarettes

CASES

CONTROLS

0 1-4 5-14 15-24 25-49 50+ Total

7 55 489 475 293 38 1,357

61 129 570 431 154 12 1,357

From Doll R, Hill AB - Leon Gordis, p.126

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

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)

Relative strength of population-based and hospital-based case-control study

Population-based CCS
Source population is better defined Easier to make certain that cases and controls derive from the same source population Exposure histories of controls more likely to reflect those of persons without the disease of interest
Greenberg, p. 132

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

unexposed Without disease

Greenberg, p.132

THE ORIGIN OF SELECTION BIAS

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

ALL OF THE CASES BE SELECTED FIRST !!!

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

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 CASES ACCORDING TO A GIVEN CHARACTERISTIC, WE CANNOT STUDY THAT CHARACTERISTIC

Advantages and disadvantages of matching in case-control study

ADVANTAGES
May increase the precision of casecontrol comparisons and thus allow a smaller study The sampling process is easy to understand and explain

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

- 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

USE OF MULTIPLE CONTROLS

1. CONTROLS OF DIFFERENT TYPES 2. CONTROLS OF THE SAME TYPE

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

2. MULTIPLE CONTROLS OF DIFFERENT TYPES

CHILDREN e.g.
No history Prenatal history of radiation exposure

Brain tumor CASES

Other cancer CONTROLS

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

Exposed cases Case exposure probability = =

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

Odds of control exposure =

A ODDS RATIO =

B =

AxD

BxC