Transcript 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 [email protected].

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
[email protected]
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.
LEARNING OBJECTIVES
AT THE END OF THIS LECTURE LEARNER SHOULD BE
1.
ABLE TO KNOW THE VARIOUS ANALYTICAL
STUDIES, THEIR TYPES, AND THEIR INDICATIONS?
2.
ABLE TO CHOOSE THE SUITABLE ANALYTICAL
STUDY FOR TESTING THE HYPOTHESIS
3.
ABLE TO ANALYZE AND TEST THE CAUSAL
HYPOTHESIS
4.
ABLE TO MEASURE THE VARIOUS RISKS IN
POPULATION DUE TO THE SUSPECTED CAUSE?
PERFORMANCE OBJECTIVES
1. BY KNOWING THE POPULATION
RISKS, HE MUST BE ABLE TO
SAVE THAT POPULATION BY
ELIMINATING THAT RISK.
DEFINITION
• CASE CONTROL STUDY IS AN
ANALYTICAL AND COMPARATIVE
METHOD OF OBSERVATIONAL
NATURE TO TEST THE CAUSAL
HYPOTHESIS.
CASE-CONTROL STUDIES
TWO GROUPSOF PERSONS
• CASES AND
• CONTROLS (GROUP WITHOUT
THE DISEASE IN QUESTION)
FORM THE BASIS FOR THE
STUDY, HENCE THE NAME.
•
PURPOSE
THEY TRY TO
1. ESTABLISH THE CAUSE AND
EFFECT RELATIONSHIP
(CAUSAL ASSOCIATION)
2. THE STRENGTH OF THE CAUSAL
ASSOCIATION
INDICATIONS
• TESTING CAUSAL HYPOTHESES FOR
RARE DISEASES AND
• WHEN RESULTS ARE EXPECTED
LESS EXPENSIVELY AND IN SHORT
TIME
• CASE CONTROL DESIGN
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.
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.
PROPORTION OF SMOKING IN
CASES AND CONTROLS
cases
controls
Smoking
Smoking
ARROWS SHOW THE EXTENT OF SMOKING
AMONG CASES AND CONTROLS
2/2 TABLE
CASE CONTROL DESIGN
Exposure Lung
to smoking cancer
present
(cases)
Lung
cancer
absent
(controls)
Total
POSITIVE
a
b
a+b
NEGATIVE
c
d
c+d
Cases=a +c,
controls = b +d
If a/a +c > b /b +d, the association may
be causal.
Odd’s ratio = ad/ bc
• METHODOLOGY
STEPS OF CASE CONTROL STUDY
1.
2.
3.
4.
CASES SELECTED
CONTROLS SELECTED
MATCHED
ENQUIRY AND RECORDS’ VERIFICATION
FOR THE AMOUNT OF EXPOSURE IN BOTH
GROUPS
5. COMPARISON ANALYSIS AND RISK
MEASUREMENT
6. IF EXPOSURE IS MORE IN CASES THAN IN
CONTROLS CAUSAL ASSOCIATION
SUSPECTED
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 CASES
FIND EXTENT OF CAUSE
IN CONTROLS b / b+d
IF a / a+c > b / b+d association may be causal.
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.
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.
SOURCES OF CASES
• CASES MAY BE CHOSEN EITHER
FROM
• A SINGLE SOURCE (HOSPITAL)
OR
• FROM MULTIPLE SOURCES.
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.
SOURCES FOR CONTROLS
• CONTROLS MAY BE OBTAINED
EITHER FROM GENERAL
POPULATION, HOSPITALS,
RELATIVES (TWINS PREFERRED
IF AVAILABLE) OR NEIGHBORS.
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.
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.
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.
ANALYSIS FOR RISK
MEASUREMENT
• THE PROPORTION OF THE
CAUSE IN THE CASES (a/a+c)
AND THAT IN CONTROLS
• ( b /b+d ) ARE MEASURED.
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/ a+c AND FOR
CONTROLS, IT IS b/ b+d.
ODD’S RATIO (OR)
• ODD’S RATIO (OR) OR CROSSPRODUCT RATIO (ad/bc)
WHICH ALSO ASSESSES THE
RISK AND EQUALLY USEFUL
AS RR CAN NOT BE DERIVED
FROM THESE STUDIES.
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.
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.
SELECTION BIAS
• SELECTION BIAS IS THE
COMMONEST ERROR USUALLY
COMMITTED.
• EITHER MATCHING (TO SOME
EXTENT) OR RANDOMIZATION OR
BOTH CAN MINIMIZE IT.
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
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.
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.
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
•
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.
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.
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.
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.
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.
EXAMPLES
• DOLL’S STUDY ON SMOKING AND
LUNG CANCER
• THALIDOMIDE USE BY PREGNANT
WOMEN AND CONGENITAL DEFECTS
IN THE OFFSPRING STUDY
• ORAL CONTRACEPTIVES AND
THROMBOEMBOLISM
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.