CASE CONTROL STUDIES..skp

CASE CONTROL STUDIES: 

CASE CONTROL STUDIES DR. Sudhira Kumar Parida .

OVERVIEW: 

Introduction. Design of a Case-Control Study. Hallmark. Selection of cases. Selection of controls. Problems in control selection. Multiple control. Matching. When warranted? Case-Control Study based in a defined cohort. Measurement of exposure. Analysis & Interpretation . Bias. Advantages & disadvantages. Examples. OVERVIEW

INTRODUCTION Epidemiological Studies: 

Observational studies A.Descriptive studies B.Analytical studies 1.Ecological/ Correlational 2.Cross-sectional/ Prevalence 3.Case-control/ Case-reference 4.Cohort/ Follow-up Experimental studies A.RCT/ Clinical trials B.Field trials/ Community intervention studies C.Community trials. INTRODUCTION Epidemiological Studies

DESIGN OF A CASE-CONTROL STUDY: 

DESIGN OF A CASE-CONTROL STUDY First Select CASES CONTROLS (with disease) (without ds ) THEN MEASURE PAST EXPOSURE Were Exposed a b Were Not exposed c d Total a+c b+d Proportions Exposed a b a+c b+d

HALLMARK: 

It begins with people with the disease(CASES) & COMPARES them to people without the ds (CONTROLS). HALLMARK

SELECTION OF CASES: 

Definition of a CASE: i )diagnostic criteria & stage of the ds ,if any. ii)eligibility criteria-preferably incident cases. Sources: 1.hospital-based 2.population-based Case verification Exclusion criteria SELECTION OF CASES

SELECTION OF CONTROLS: 

Who is a CONTROL  Sources: 1.hospital-based 2.population-based i )school rosters ii)selective service lists iii)insurance company lists iv) neighbourhood v)best friend vi)spouse/ sibling vii)dead SELECTION OF CONTROLS

USE OF MULTIPLE CONTROLS: 

Same types: -increases the power of the study(only upto 1case:4control) Different types: -for exploring alternate hypotheses -for taking account possible potential biases like recall bias. USE OF MULTIPLE CONTROLS

MATCHING: 

Def: The process of selecting the controls so that they are similar to cases in certain characteristics ,such as age,race,sex,socio -eco. status & occupation. Types: 1.Group/ Frequency 2.Individual/ Matched pairs. Problems: a)practical-difficulty in finding a control b)conceptual-cannot study that characteristic c)unplanned matching d)overmatching MATCHING

WHEN A CASE-CONTROL STUDY IS WARRANTED : 

Often the 1 st step in determining whether an exposure is linked to an increased risk of ds . Rare ds . WHEN A CASE-CONTROL STUDY IS WARRANTED 

CASE-CONTROL STUDIES BASED IN A DEFINED COHORT: 

CASE-CONTROL STUDIES BASED IN A DEFINED COHORT Defined Cohort Develop Disease Have Not developed disease CASES Sub- gr selected as CONTROL YEARS Initial Data &/or Sr.,Urine or Other specimens

Slide 12: 

Nested Case-Control Studies: -controls are a sample of individuals who are at risk for the ds at the time of each case of the ds develops. -cases & controls are matched on calendar time & length of follow-up. Case-Cohort Studies: -controls are randomly chosen. -Adv: possible to study different diseases.

ADVANTAGES OF EMBEDDING A CASE-CONTROL STUDY IN A DEFINED COHORT: 

Recall bias-eliminated. Abnormalities in biologic characteristics like lab values –risk factors. More economical. Less lab burden. Greater comparability b/w cases & controls. ADVANTAGES OF EMBEDDING A CASE-CONTROL STUDY IN A DEFINED COHORT

MEASUREMENT OF EXPOSURE: 

( IN PRECISELY THE SAME MANNER BOTH FOR CASES & CONTROLS .) Interviews Questionnaires Past records of cases -hospital records -employment records etc. MEASUREMENT OF EXPOSURE

ANALYSIS: 

Exposure rates among cases & controls to suspected factor. Estimation of ds risk asso. With exposure( ODDS RATIO). ANALYSIS

Slide 16: 

EXPOSURE RATES: Direct estimation. A Case-Control Study of Smoking &Lung cancer. Cases Controls (with Lung cancer) (without lung cancer) Smokers(<5 cigarettes/d) 33 (a) 55 (b) Non-smokers 2 (c) 27 (d) Total 35 ( a+c ) 82 ( b+d ) . Cases= a/ a+c = 33/35 =94.2% . Controls= b/ b+d =55/82 =67%. Exposure rates:

Slide 17: 

ODDS RATIO (RELATIVE ODDS/ CROSS-PRODUCTS RATIO.) A measure of the Strength of the association b/w risk factor & ds . Def: OR= = = = Odds that a case was exposed Odds that a control was exposed a/c b/d ad bc Product of 2 cells that SUPPORT the hypothesis Product of 2 cells that NEGATE the hypothesis

Slide 18: 

Interpretation: OR=1 (exposure is not related to the ds ) >1 (+ ly related) <1 (- ly related). OR is a good approximation of RR when: -cases studied are representative of those with the ds . -controls studied are representative of those without the ds . - ds being studied does not occur frequently.

Slide 19: 

CALCULATING ‘OR’ IN AN UNMATCHED CASE-CONTROL STUDY: OR= CALCULATING ‘OR’ IN A MATCHED PAIRS CASE-CONTROL STUDY: ad bc Exposed Not exposed Exposed p q Not exposed r s CONTROL CASE OR=Ratio of discordant pairs=q/r.

BIAS: 

Bias due to confounding. Recall bias. Selection bias. Berkesonian bias. Interviewer’s bias. BIAS

ADVANTAGES: 

Relatively easy. Rapid & inexpensive. Rare ds . No risk to subjects. Allows study of several different aetiological factors. Risk factors can be identified-----  rational prevention & control programme No attrition problems. Minimal ethical problem. ADVANTAGES

DISVANTAGES: 

Recall bias. Selection of appropriate control gr. –may be difficult. Cannot measure incidence. Cannot distinguish b/w causes & asso. Factors. Not suited to evaluation of Tt / Px of ds . Concern about representativeness of cases & controls. DISVANTAGES

EXAMPLES: 

MATERNAL DES THERAPY & ADENOCARCINOMA OF VAGINA IN FEMALE OFFSPRINGS: EXAMPLES CASES (8) CONTROLS (32) SIGNIFICANCE LEVEL Maternal age 26.1 29.3 n.s . Maternal smoking 7 21 n.s . Antenatal radiology 1 4 n.s . Oestrogen exposure 7 -- P< 0.00001

Slide 24: 

OCP & THROMBOEMBOLIC DISEASE: THALIDOMIDE TRAGEDY: CASES(Venous thrombosis & pul.embolism ) (84) CONTROLS (168) % who used OCP 50 14 CASES(46) CONTROLS(300) Thalidomide exposure in early pregnancy 41 --

REFERENCES: 

Leon Gordis,4 th ed. Silman , Macfarane ,2 nd ed. Park,20 th ed. REFERENCES

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THANK YOU.