Case control studies Dr/ Mirella Youssef
Case control study= retrospective study=case referent study • Purpose: 1- study the association between disease and one or more exposure factors 2- confirmation of new hypothesis
:Design • Two groups are compared 1- the group of cases, defined according to the presence of the disease 2- the group of controls defined according to the absence of the disease
:Cases • Defined as having the disease( the working definition of the disease should be set) • Selected to represent all the population of cases in the community (inclusion of mild cases or severe cases only is not representative of the whole spectrum of the disease
:Cases • Should have some reasonable probability of having had their diseases induced by the exposure under study. Ex: In studying the association between oral contraceptive (OC) and deep venous thrombosis (DVT), cases with post-operative DVT should not be included
:Cases • Should have been at potential risk of exposure to the factor under study: ex.: unmarried , hyterectomized, or women with contraindications for OC are not eligible for the above study
:Cases • Should better be newly diagnosed (incident cases): -To avoid to be missed in the selection as in
short course diseases and diseases with high fatality - To avoid recall bias - Ambiguity of temporal relationship
:Cases • Should have a reasonable probability of homogeneity of etiology: Ex.: in studying lung cancer and smoking, squamous cell type (RR=3040) is not homogenous with adenocarcinoma (RR=3-4)
:Cases • Source may be -the hospital -Disease registries -Records -Community survey
:Controls • Similar to cases in everything except the disease under the study • Must have a similar chance of exposure compared to cases • Source may be :general population, neighbors, friends of cases
:Controls
• Number of control per case - 1/1 when cases are easy to find at no extra cost - >1/1 when the number of cases is limited up to 4/1 • Number of control groups - Usually one group - If the control group is suspected to have a specific bias a second group might be used to increase validity
:Controls • Matching may be used to ensure equal distribution in the two groups of factors that might affect the studied relationship • Assessment of exposure is done in both groups (case and control) using the same maneuver
+ E
+ Cases (D)
E retrospective assessment of exposure + E E
(Controls (D
:Analysis of case control studies exposed Cases (D +) Control (D -) total
A 80 C 30 A+C 110
Nonexposed B 20 D 70 B+D 90
total A+B 100 C+D 100 A+C+ B+D 200
(Odds ratio (OR 1- The probability that a case was exposed previously is estimated by The case exposure probability= exposed cases all cases = A/A+B = 80/100 2-The probability that a case was not exposed previously is estimated by cases not exposed all cases =B/A+B= 20/100
(Odds ratio (OR • The odds of exposure of cases = cases not exposed all cases =
A/A+B B/A+B
exposed cases all cases
=A/B= 80/20=4
• The odds of exposure of controls =C/D= 30/70=0.4
(Odds ratio (OR • The odds ratio is the odds of exposure for cases divided by the odds of exposure for controls= A/B = AD/BC= 70x80/20x30=56/6=9.3 C/D This represents the degree of association between the disease and exposure under investigation
Advantages of case- control studies • Feasibility: short time and costs • Confirms a new hypothesis • Most suitable for the studying of rare diseases • High statistical efficiency due to equal groups
:Problems • Misclassification: this is the placement of a study subject in an improper cell in the 2x2 table • - misclassification of disease ex. Classify case as disease or the reverse will lead to underestimate the OR • Classification of exposure
:Problems
• Selection bias: this may be encountered in either cases or controls: - Selection of cases from the hospital may lead to: 1- missing all cases that didn’t need hospital care (mild cases) 2- missing all cases that are not able to reach the hospital( died – lack of money…) 3- lack of representation of cases referred from wide areas to a specialized center - Selection of controls from the hospital lead to lack of representation because the hospital population is different from the general population (higher exposure to many risk factors)
:Problems • Difficult in selection of proper control group • Recall bias • Uncertainty of temporal relationship between exposure and outcome specially in chronic diseases of insiduous onset