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 Adv & disadv. Examples

INTRODUCTION Epidemiological StudiesObservational

studiesA.Descriptive studiesB.Analytical studies 1.Ecological/

Correlational 2.Cross-sectional/

Prevalence 3.Case-control/ Case-

reference 4.Cohort/ Follow-up

Experimental studies

A.RCT/ Clinical trialsB.Field trials/

Community intervention studies

C.Community trials.

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

HALLMARKIt begins with people with the

disease(CASES) & COMPARES them to people without the ds(CONTROLS).

SELECTION OF CASESDefinition of a CASE: i)diagnostic criteria & stage of the ds ,if any. ii)eligibility criteria-preferably incident cases.Sources: 1.hospital-based 2.population-basedCase verificationExclusion criteria

SELECTION OF CONTROLSWho 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

USE OF MULTIPLE CONTROLSSame 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.

MATCHINGDef: 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

WHEN A CASE-CONTROL STUDY IS WARRANTED Often the 1st step in determining whether an

exposure is linked to an increased risk of ds.Rare ds.

CASE-CONTROL STUDIES BASED IN A DEFINED COHORT

Defined Cohort

Develop Disease

Have Not developed

disease

CASESSub-gr

selected as CONTROL

YEARS

Initial Data &/or Sr.,Urine or Other specimens

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 COHORTRecall bias-eliminated.Abnormalities in biologic characteristics like

lab values –risk factors.More economical.Less lab burden.Greater comparability b/w cases & controls.

MEASUREMENT OF EXPOSURE ( IN PRICESLY THE SAME MANNER BOTH

FOR CASES & CONTROLS .)InterviewsQuestionnairesPast records of cases -hospital records -employment records etc.

ANALYSISExposure rates among cases & controls to

suspected factor.Estimation of ds risk asso. With

exposure( ODDS RATIO).

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:

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/dadbc

Product of 2 cells that SUPPORT the hypothesis

Product of 2 cells that NEGATE the hypothesis

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.

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.

BIASBias due to confounding.Recall bias.Selection bias.Berkesonian bias.Interviewer’s bias.

ADVANTAGESRelatively easy.Rapid & inexpensive.Rare ds.No risk to subjects.Allows study of several different aetiological

factors.Risk factors can be identified----- rational prevention & control programmeNo attrition problems.Minimal ethical problem.

DISVANTAGESRecall 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.

EXAMPLES MATERNAL DES THERAPY &

ADENOCARCINOMA OF VAGINA IN FEMALE OFFSPRINGS:

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

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 --

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

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