Case Control Study - 2009

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In the early 1940s, Alton Ochsner, a surgeon inNew Orleans, observed that virtually all of thepatients 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 thatOchsner made his observation.He hypothesized that cigarette smoking was linkedto lung cancer . Based only on his observations incases of lung cancer,

was this conclusion valid ?


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Again in the 1940s, Sir Norman Gregg, an Australianophthalmologist, observed a number of infants and youngchildren in his ophthalmology practice who presented withan 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 betweenprenatal rubella exposure and the development of theunusual cataracts.Keep in mind that at that time there was no knowledge thata virus could be teratogenic. Thus, he proposed hishypothesis solely on the basis of observational data, theequivalent of data from ambulatory or bedside practice

today.


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Disease

No Disease

Exposed

NotExposed

Exposed

NotExposed

Design of a case-control study


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CASES(with disease)

aa + c

CONTROLS(without disease)

bb + d

Were exposed a b

Were not exposed c d

TOTAL a + c b + d

Proportionsexposed

First, select :

Then, measurepast exposure :


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CHD CONTROLS

Smoke cigarettes 112 176

Do not smoke cigarettes 88 224

Total 200 400

% Smoking cigarettes 56.0 44.0

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


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artificialsweetener use CASES CONTROLS

Ever 1,293 2,455

Never 1,707 3,321

Total 3,000 7,776

Leon Gordis, p.126

History of use of artificial sweetenersin bladder cancer, cases and controls


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Average daily

cigarettesCASES CONTROLS

01-45-1415-24

25-4950+

Total

755

489475

29338

1,357

61129570431

15412

1,357

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

Distribution of 1,357 male lung cancer patients and a male controlgroup according to average number of cigarettes smoked daily overthe 10 years preceeding onset of the present illness


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Selection of cases

Sources :- hospital patients

- physicians practice patients

- clinic patients- registries of patients with certain diseases

in the community


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Selection of controls

Sources :

- Non-hospitalized persons living in thecommunity

- Hospitalized patients


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2. Hospitalized patients

- advantages* Captive population

* more economical to carry out a study- disadvantages

they represent a sample of an ill-health defineddiffer from people in the community

- from the same hospital?- all other patients admitted?

(other than those with the cases diagnosis)


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Population-based CCS Hospital-based CCS

Source population is better defined

Easier to make certain that casesand controls derive from the samesource population

Exposure histories of controls morelikely to reflect those of personswithout the disease of interest

Subjects are more accessible

Subjects tend to be more cooperative

Background characteristics of cases andcontrols may be balanced

Easier to collect exposure informationfrom medical records and biologicalspecimens

Relative strength of population-based and hospital-based

case-control study

Greenberg, p. 132


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Without disease

With disease

Source population

CASES

Study sample

Sampling

CONTROLS

Sampling

exposed

unexposed

THE ORIGIN OF SELECTION BIAS

Greenberg, p.132


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Is the process of selecting the controls so that they aresimilar to the cases in certain characteristics, such as age,race, sex, socioeconomic status, and occupation.

2 TYPES OF MATCHING

1. GROUP MATCHING2. INDIVIDUAL MACHING


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MATCHING1. GROUP MATCHING

(FREQUENCY MATCHING)

Selecting the controls in such a manner that the proportionof controls with a certain characteristic is identical to theproportion of cases with the same characteristic

e.g. :

If 25 % of the cases 25% of the controlsare married are married

ALL OF THE CASES BE SELECTED FIRST !!!


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2. INDIVIDUAL MATCHING(MATCHED PAIRS)

For each case selected for the study, a control isselected who is similar to the case in terms of thespecific variable or variables concern

using hospital controls


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THE PROBLEMS WITH MATCHING

PRACTICAL PROBLEMS

TOO MANY CHARACTERISTICS TO BE MATCHEDDIFFICULT OR IMPOSSIBLE TO IDENTIFY

AN APPROPRIATE CONTROL

CONCEPTUAL PROBLEMSONCE WE HAVE MATCHED CONTROLS TO CASES ACCORDINGTO A GIVEN CHARACTERISTIC, WE CANNOT STUDY THATCHARACTERISTIC


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ADVANTAGES DISADVANTAGES

May increase the precision of case-control comparisons and thus allowa smaller study

The sampling process is easy to

understand and explain

May be time-consuming and expensiveto perform

Some potential cases and controls maybe excluded because matches cannot

be made

The matched variables cannot beevaluated as risk factors in the studypopulation

Greenberg R.S, p 133


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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


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1. CONTROLS OF DIFFERENT TYPES

2. CONTROLS OF THE SAME TYPE


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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 CASESAVAILABLE FOR STUDY


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2. MULTIPLE CONTROLS OF DIFFERENT TYPES

e.g.

Brain tumor CASES

Other cancer CONTROLS

NormalCONTROLS

Prenatal history of radiation exposure

No history

CHILDREN


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CASE CONTROL STUDY

CASES CONTROLS Total

Exposed A B A + B

Unexposed C D C + D

Total A + C B + D A+B+C+D


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Exposed cases ACase exposure probability = =

All cases A + B

Odds of Exposed cases Unexposed casescase exposure =

All cases All cases

A C= A + C A + C

= A

C

Odds of Bcontrol exposure = D


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A B A x DODDS RATIO = =

C D B x C


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Case Control Study - 2009

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