CASE CONTROL STUDIES

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CASE CONTROL STUDIES
Dr. A. K. AVASARALA MBBS,
M.D. PROFESSOR HEAD DEPT OF COMMUNITY MEDICINE
EPIDEMIOLOGY PRATHIMA INSTITUTE OF MEDICAL
SCIENCES, KARIMNAGAR, A.P. INDIA
91505417 avasarala_at_yahoo.com
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PROMPT

• TWO TEACHERS IN EPIDEMIOLOGY FROM CHINA AND
  ARGENTINA, REQUESTED FOR MY PERMISSION TO USE MY
  FIRST EPIDEMIOLOGY LECTURES FOR THEIR TEACHING.
• THIS PROMPTED ME TO DEVELOP AN EPIDEMIOLOGY
  COURSE WHICH HAS A CHANCE OF BEING USED ALL
  OVER THE WORLD.
• THIS LECTURE IS A PART OF THAT ENDEVOUR TO
  SPREAD EPIDEMIOLOGY.

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LEARNING OBJECTIVES

• AT THE END OF THIS LECTURE LEARNER SHOULD BE
• ABLE TO KNOW THE VARIOUS ANALYTICAL STUDIES,
  THEIR TYPES, AND THEIR INDICATIONS?
• ABLE TO CHOOSE THE SUITABLE ANALYTICAL STUDY
  FOR TESTING THE HYPOTHESIS
• ABLE TO ANALYZE AND TEST THE CAUSAL HYPOTHESIS
  
• ABLE TO MEASURE THE VARIOUS RISKS IN POPULATION
  DUE TO THE SUSPECTED CAUSE?

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PERFORMANCE OBJECTIVES

1. BY KNOWING THE POPULATION RISKS, HE MUST BE ABLE
   TO SAVE THAT POPULATION BY ELIMINATING THAT
   RISK.

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DEFINITION

• CASE CONTROL STUDY IS AN ANALYTICAL AND
  COMPARATIVE METHOD OF OBSERVATIONAL NATURE TO
  TEST THE CAUSAL HYPOTHESIS.

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CASE-CONTROL STUDIES

• TWO GROUPSOF PERSONS
• CASES AND
• CONTROLS (GROUP WITHOUT THE DISEASE IN QUESTION)
• FORM THE BASIS FOR THE STUDY, HENCE THE NAME.

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PURPOSE

• THEY TRY TO
• ESTABLISH THE CAUSE AND EFFECT RELATIONSHIP
  (CAUSAL ASSOCIATION)
• THE STRENGTH OF THE CAUSAL ASSOCIATION

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INDICATIONS

• TESTING CAUSAL HYPOTHESES FOR RARE DISEASES AND
• WHEN RESULTS ARE EXPECTED
• LESS EXPENSIVELY AND IN SHORT TIME

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• CASE CONTROL DESIGN

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CASE CONTROL DESIGN

• CASE CONTROL DESIGN IS AN ANALYTICAL AND
  COMPARATIVE DESIGN OF OBSERVATIONAL NATURE.
• PREVALENCE OR PROPORTION OF THE CAUSE
  IN CASES IS COMPARED TO THAT OF CONTROLS.

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EXAMPLE SMOKING AND LUNG CANCER

• WE CHOOSE LUNG CANCER PATIENTS AS CASES AND
  COMPARE WITH NORMAL PEOPLE OR OTHER PATIENTS
  (OTHER THAN LUNG CANCER PATIENTS) AS CONTROL
  GROUP.

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PROPORTION OF SMOKING IN CASES AND CONTROLS
cases
controls
Smoking
Smoking
ARROWS SHOW THE EXTENT OF SMOKING AMONG CASES AND
CONTROLS
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2/2 TABLECASE CONTROL DESIGN
Exposure to smoking Lung cancer present (cases) Lung cancer absent (controls) Total
POSITIVE a b a b
NEGATIVE c d c d
Casesa c,
controls b d
If a/a c gt b /b d, the association may be
causal. Odds ratio ad/ bc
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• METHODOLOGY

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STEPS OF CASE CONTROL STUDY

• CASES SELECTED
• CONTROLS SELECTED
• MATCHED
• ENQUIRY AND RECORDS VERIFICATION FOR THE AMOUNT
  OF EXPOSURE IN BOTH GROUPS
• COMPARISON ANALYSIS AND RISK MEASUREMENT
• IF EXPOSURE IS MORE IN CASES THAN IN CONTROLS
  CAUSAL ASSOCIATION SUSPECTED

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• .

GENERAL POPULATION
HOSPITALS
RELATIVES
NEIGHBOURS
AVOID SELECTION BIAS, INFORMATION BIAS
MEASURMENT BIASES
CASES
CONTROLS
TO AVOID CONFOUNDING BIAS
.
MATCHING OF CASES WITH CONTROLS
FIND EXTENT OF CAUSE IN CONTROLS b / bd
FIND EXTENT OF CAUSE IN CASES
IF a / ac gt b / bd association may be causal.
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CASES SELECTION

• STUDY BEGINS WITH CASES, i.e. THE PATIENTS IN
  WHOM THE DISEASE HAS ALREADY OCCURRED.
• PATIENTS WITH THE DISEASE IN QUESTION (CASES)
  WERE ENQUIRED FOR ALL THE DETAILS OF THEIR
  EXPOSURE TO THE SUSPECTED CAUSE.

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SELECTION OF CASES - (Contd)

• USUALLY NEW CASES (INCIDENT CASES) WILL BE CHOSEN
  EITHER FROM THE GENERAL POPULATION OR FROM
  HOSPITALS.
• THE NEW CASES, WHICH ARE SIMILAR CLINICALLY,
  HISTOLOGICALLY, PATHOLOGICALLY AND IN THEIR
  DURATION OF EXPOSURE (STAGE) WILL BE CHOSEN TO
  AVOID ANY ERROR AND FOR BETTER COMPARISON.
• THUS SPECIFICITY AND SENSITIVITY OF CASES ARE
  GIVEN IMPORTANCE WHILE CHOOSING THEM, AS THEIR
  LACK MAY LEAD TO ERRORS IN COMPARISON AND
  ANALYSIS.

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SOURCES OF CASES

• CASES MAY BE CHOSEN EITHER FROM
• A SINGLE SOURCE (HOSPITAL) OR
• FROM MULTIPLE SOURCES.

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SELECTION OF CONTROLS

• CONTROL GROUP OR COMPARISON GROUP MUST BE VERY
  CAREFULLY CHOSEN OTHERWISE VALIDITY OF THE STUDY
  WILL BE DEFECTIVE.
• THE USUAL PRINCIPLE THAT IS TO BE OBSERVED WHILE
  SELECTING CONTROLS SHOULD BE THAT LIKE SHOULD BE
  COMPARED WITH THE LIKE TO AVOID ERRORS AND FOR
  BETTER COMPARISON.

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SOURCES FOR CONTROLS

• CONTROLS MAY BE OBTAINED EITHER FROM GENERAL
  POPULATION, HOSPITALS, RELATIVES (TWINS PREFERRED
  IF AVAILABLE) OR NEIGHBORS.

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MATCHING

• MATCHING IS A COMPARATIVE TECHNIQUE OF
  NEUTRALIZING ALL OTHER VARIABLES PRESENT IN CASES
  AND CONTROLS, EXCEPT THE VARIABLE (DISEASE) UNDER
  STUDY, TO ELIMINATE THE SYSTEMATIC ERRORS
  (BIASES) WHILE CONDUCTING THE STUDY.

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LIMITATION OF MATCHING

• BY MATCHING, WE CAN MATCH ONLY THE KNOWN
  CONFOUNDING VARIABLES LIKE AGE, SEX, OCCUPATION
  ETC, BUT NOT THE UNKNOWN CONFOUNDERS PLAYING A
  ROLE IN CAUSATION.

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ENQUIRY ABOUT EXPOSURE

• AFTER THE CASES AND CONTROLS WERE MATCHED TO THE
  MAXIMUM REQUIRED EXTENT.
• INFORMATION WAS OBTAINED IN BOTH GROUPS IN A
  SIMILAR MANNER.
• SEARCHING THE AVAILABLE RECORDS WITH REGARD TO
  THE EXPOSURE TO THE SUSPECTED CAUSE AND ITS
  DURATION.

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ANALYSIS FOR RISK MEASUREMENT

• THE PROPORTION OF THE CAUSE IN THE CASES (a/ac)
  AND THAT IN CONTROLS
• ( b /bd ) ARE MEASURED.

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EXPOSURE RATES

• EXPOSURE RATES ONLY CAN BE DIRECTLY CALCULATED
  FROM THE CASE CONTROL DESIGN, BUT NOT THE
  INCIDENCE RATES OR RELATIVE RISK.
• FOR CASES, EXPOSURE RATE WILL BE a/ ac AND FOR
  CONTROLS, IT IS b/ bd.

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ODDS RATIO (OR)

• ODDS RATIO (OR) OR CROSS-PRODUCT RATIO (ad/bc)
  WHICH ALSO ASSESSES THE RISK AND EQUALLY USEFUL
  AS RR CAN NOT BE DERIVED FROM THESE STUDIES.

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WHY ODDS RATIO?

• WHEN THE DISEASE IS RARE WITH LOW INCIDENCE, OR
  REFLECTS RR AND IS EQUALLY USEFUL.
• OR WHICH CAN BE CALCULATED FROM THE CASE CONTROL
  DESIGN, HENCE SUGGESTS THE STRENGTH OF THE
  ASSOCIATION.

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BIASES

• SYSTEMATIC ERRORS, OR DEVIATION OF RESULTS OR
  INFERENCES FROM THE TRUTH MAY ARISE AT ANY
  POINT IN THE COURSE OF STUDY OR THROUGHOUT DUE TO
  CHANCE.

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SELECTION BIAS

• SELECTION BIAS IS THE COMMONEST ERROR USUALLY
  COMMITTED.
• EITHER MATCHING (TO SOME EXTENT) OR RANDOMIZATION
  OR BOTH CAN MINIMIZE IT.

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CONFOUNDING BIAS

• CONFOUNDING VARIABLE OR FACTOR IS
• THE VARIABLE WHICH IS CAPABLE OF CAUSING THE
  EFFECT OR DISEASE DIRECTLY ON ITS OWN
• AND ALSO INDIRECTLY WITH THE ASSOCIATION OF
  ANOTHER FACTOR.
• ALLOWING THIS VARIABLE INTO THE STUDY IS
  CONFOUNDING BIAS
• .

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EXAMPLES FOR CONFOUNDING BIAS

• AGE IS A BEST-KNOWN CONFOUNDER, AS BY ITS OWN
  INCREASE, IT CAN DIRECTLY CAUSE THE DISEASE AND
  INDIRECTLY AND COMBINEDLY BY MINGLING WITH OTHER
  FACTORS RELATED TO AGE.
• USUALLY PRESENCE OF CONFOUNDERS LEADS TO INDIRECT
  CAUSAL ASSOCIATIONS e.g. GOITRE IS SEEN MOSTLY AT
  HIGH ALTITUDES, BUT ACTUALLY, THE IODINE
  DEFICIENCY AT HIGH ALTITUDES IS THE CAUSE OF
  GOITRE THERE.
• SIMILARLY, ALCOHOLISM IS SUSPECTED TO BE THE
  CAUSE OF LIVER CANCER BUT THE SMOKING, WHICH IS
  USUALLY ASSOCIATED WITH ALCOHOLISM MAY BE THE
  COMFOUNDING VARIABLE CAUSING THE DISEASE.

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INFORMATION BIAS

• ANY ERROR IN COLLECTING INFORMATION i.e. DATA
  ABOUT CAUSE WILL LEAD TO THE FALSE INFERENCE OR
  RESULTS.
• THIS BIAS IS VERY FREQUENTLY SEEN IN CASE CONTROL
  STUDIES, AS THE ENTIRE PROCESS INVOLVED IS MOSTLY
  SUBJECTIVE VERIFICATION.

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INFORMATION BIAS

• CASE CONTROL DESIGN IS PRINCIPALLY AN INFORMATIVE
  DESIGN, IN THE SENSE, INFORMATION REGARDING CAUSE
  IS OBTAINED AND COMPARED FROM BOTH THE CASES AND
  CONTROLS.
• ANY SUBJECTIVE INFORMATION OBTAINED FROM CASES OR
  CONTROLS IS VULNERABLE FOR BIAS AND ONE MUST BE
  VERY CAREFUL WHILE COLLECTING THE INFORMATION

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MEMORY BIAS OR RECALL BIAS

• IS THE INABILITY ON THE PART OF AN INDIVIDUAL
  (CASE OR CONTROL) TO RECOLLECT THINGS HAPPENED IN
  THE PAST ACCURATELY.
• SIMILARLY, PATIENT MAY GIVE WRONG INFORMATION OR
  EXAGGERATE TO PLEASE THE INVESTIGATOR.

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INTERVIEWING BIAS

• ERRORS CAN OCCUR WHILE COLLECTING DATA BY
  INTERVIEWING, IF THE INTERVIEWING TECHNIQUES ARE
  NOT STANDARDIZED AND APPLIED IN A SIMILAR FASHION
  AND FOR SIMILAR DURATION FOR ALL THE CASES AND
  CONTROLS.

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INVESTIGATOR BIAS

• THIS IS OCCASIONALLY ENCOUNTERED, USUALLY AN
  UNINTENTIONAL ONE.
• THE INVESTIGATOR MAY CONDUCT INTERVIEW ONE CASE
  OR A CONTROL FOR A LONGER TIME AND ANOTHER FOR A
  SHORT TIME.
• HE CAN PUT HIS IDEAS AND FEELINGS UNINTENTIONALLY
  WHILE INTERVIEWING DUE TO OVER ENTHUSIASM.

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MEASUREMENT BIAS

• ERRORS USUALLY OCCUR WHILE MEASURING THE EXPOSURE
  FACTOR OR THE SUSPECTED CAUSE.
• MEASUREMENT BIAS WILL CREEP INTO THE STUDY AND
  SPOILS IT, IF IT IS NOT MEASURED IN A SIMILAR
  MANNER USING SIMILAR TECHNIQUE OR METHOD BOTH IN
  CASES AND CONTROLS.

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ADVANTAGES

• CASE CONTROL STUDIES ARE VERY USEFUL WHEN THE
  DISEASE IS RARE AND WITH LOW INCIDENCE. IT IS
  PREFERRED EVEN TO THE COHORT AND RANDOMIZED
  TRIALS IN SUCH A CIRCUMSTANCE.
• IT IS ALSO USED WHEN RESULTS ARE EXPECTED
  QUICKLY AND LESS EXPENSIVELY.
• THERE IS NO NEED FOR FOLLOW UP AND THERE ARE NO
  ETHICAL PROBLEMS.
• IT IS BETTER THAN OTHER STUDIES IN CERTAIN
  CIRCUMSTANCES (RARE DISEASES) TO STUDY THE
  CAUSALITY.

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EXAMPLES

• DOLLS STUDY ON SMOKING AND LUNG CANCER
• THALIDOMIDE USE BY PREGNANT WOMEN AND CONGENITAL
  DEFECTS IN THE OFFSPRING STUDY
• ORAL CONTRACEPTIVES AND THROMBOEMBOLISM

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SUMMARY

• LESS EXPENSIVE AND QUICKER ANALYTICAL STUDY TO
  TEST HYPOTHESIS IMMEDIATELY
• IF DONE CAREFULLY AND WISELY BY ELIMINATING
  BIASES, IT IS REALLY A VALUABLE FOR
  INVESTIGATING RARE DISEASES.