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
DESIGN OF A CASE-CONTROLSTUDY 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).
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 CONTROLS Who is a CONTROL Sources:1.hospital-based2.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 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.
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
WHEN A CASE-CONTROL STUDYIS WARRANTED Often the 1st step in determining whether an exposure is linked to an increased risk of ds. Rare ds.
CASE-CONTROL STUDIES BASED INA DEFINED COHORT Defined Initial Data &/or Sr.,Urine or Cohort Other specimens YEARS Develop Disease Have Not developed disease Sub-gr CASES selected as CONTROL
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 ACASE-CONTROL STUDY IN ADEFINED COHORT Recall 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 .) Interviews Questionnaires Past records of cases -hospital records -employment records etc.
ANALYSIS Exposure rates among cases & controls to suspected factor. Estimation of ds risk asso. With exposure( ODDS RATIO).
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
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= ad bc CALCULATING ‘OR’ IN A MATCHED PAIRS CASE- CONTROL STUDY: CONTROL Exposed Not exposed C Exposed p q A S Not exposed r s E OR=Ratio of discordant pairs=q/r.
BIAS Bias due to confounding. Recall bias. Selection bias. Berkesonian bias. Interviewer’s 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.
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.
EXAMPLES MATERNAL DES THERAPY & ADENOCARCINOMA OF VAGINA IN FEMALE OFFSPRINGS: CASES CONTROLS SIGNIFICANCE (8) (32) LEVELMaternal 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: CASES(Venous CONTROLS thrombosis & pul.embolism) (84) (168)% who used OCP 50 14THALIDOMIDE TRAGEDY: CASES(46) CONTROLS(300)Thalidomide exposure in 41 --early pregnancy