Post on 07-May-2015
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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