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1
Epidemiologic Measures
of Association
Lt Col Ayon Gupta
Assistant Professor
Dept of Community Medicine , AFMC
2
Epidemiologic Measures of Association
•Session Objectives
By the end of session students should be able to:
•Compute & Interpret Relative risk (RR)
& Odds ratio (OR) as a measure of
association between exposure and
Disease
• Understand when OR approximates
RR
3
Definitions
Association
• A statistical relationship between two or
more variables
Risk
• Probability conditional or unconditional of
the occurrence of some event in time
• Probability of an individual developing a
disease or change in health status over a fixed
time interval, conditional on the individual
not dying during the same time period
Absolute risk
4
Association between exposure &
Disease
• Question:
Is there an excess risk associated with a
given exposure?
• Objective:
To determine whether certain exposure is
associated with a given disease
• Methodology:
Use one of the epidemiologic study designs
Cohort
Case-control
5
Cohort Study
• Assess the cumulative incidence (CIE+) of
disease in an exposed group (absolute Risk)
Assess the cumulative incidence (CIE-) of disease
in unexposed group (absolute Risk)
e.g. Coronary Heart Disease (CHD) Risk among Smokers
1-year risk of CHD among smokers (CIE+)*
CHD
Yes No Total
Smokers 84 2916 3000
CIE+ = 84/3000 = 28/1000/yr (1-risk of CHD among smokers)
Cont.
6
CHD Risk among non-smokers
• 1-year risk of CHD among non-smokers (CIE-
)
CHD
Yes No
• Non-smokers 87 4913 5000
CIE-= 87/5000=17.4/1000/yr (1-yr risk of
CHD among non-smokers) Cont.
7
Assessment of Excess Risk (Two methods)
a. Ratio
RR (Ratio of two risks; Risk Ratio; Relative Risk)
CIE+ / CIE- = 28/17.4 = 1.6
Interpretation of RR
Smokers were 1.6 times as likely to develop CHD as were
non-smokers
b. Difference
Difference of two risks (Risk Difference)*
CIE+- CIE- = 28.0 – 17.4 = 10.6
8
OR (Odds Ratio, Relative Odds)
• In case-control study (CCS), we cannot calculate
the CI or IR,
therefore, cannot calculate the RR “directly”
• OR as a measure of association between
exposure & disease is
used when data are collected in case-control
study
• OR can be obtained however, from a cohort as
well as a
case-control study and can be used instead of
RR.
9
OR in case-control and
cohort studies
• Cohort study
Ratio of the proportion of exposed subjects who
developed the disease to the proportion of non-
exposed subjects who developed the disease
• Case-control study
Ratio of the proportion of cases who were
exposed to the proportion of controls who were
non-exposed
10
Odds Ratio
• Odds are ratio of two probabilities
i.e. Probability that event occurs / 1-Probability
that event does not occur
• Odds refer to single entity
• If an event has the probability P,
then the odds of the same event are
P/1-P
11
Derivation of OR in Cohort study
P D
+|E
+ = (exposed developed the disease) = a/(a+b)
P D
-|E
+ = (exposed did not develop the disease) = b/(a+b)
Odds of developing disease among exposed =
D+|E+/1-P D-|E+ = a/(a+b)
b/(a+b) = a/b
P D
+|E
- = (non-exposed developed the disease) = c/(c + d)
P D
-|E
- = (non-exposed did not develop the disease)= d/(c + d)
Odds of developing disease among non-exposed =
= PD+|E
-/1-P D+|E
- = c/(c+d)
d/(c + d) = c/d
Odds ratio a/b : c/d = ad/bc
12
OR in case-control study
 In case-control study RR cannot be
calculated directly to determine the
association between exposure and disease.
 Don’t know the risk of disease among
exposed and un-exposed since we start
recruiting cases and controls.
 Can use OR as measure of association
between exposure and disease in a case
control study.
13
OR in case-control Study
Probability of case being exposed = Pcase
Probability of case being non-exposed =1-Pcase
Odds of case being exposed = Pcase/1- Pcase
Probability of control being exposed = Pcontrol
Probability of case being non-exposed =1-Pcontrol
Odds of control being exposed = Pcontrol/ 1-Pcontrol
14
Derivation of OR in case-control Study
Probability of being exposed among cases = a /(a + c)
Probability of being non-exposed among cases) = c /(a + c)
Odds of being exposed among cases = a/c
Probability of being exposed among controls = b/(b + d)
Probability of being unexposed among controls = d/(b + d)
Odds of being exposed among controls = b/d
OR = ad/bc
15
• Past surgery HCV status
HCV+ HCV-
• Yes 59 168
• No 54 48
» 113 216
Example
OR in case-control Study
16
Odds of Past surgery among HCV+
P1 (Surgery among HCV+) = 59/113
1-P1 (No surgery among HCV+) = 54/113
Odds of surgery among HCV+ ) = 59/54 = 1.09
Odds of Past surgery among HCV-
P2 (Surgery among HCV-) = 168/216
1-P2 (No surgery among HCV-) = 48/216
Odds of surgery among HCV- = 168/48 = 3.5
OR = 3.50/1.09 = 3.21
17
When is the OR a good estimate of RR?
 In CCS, only OR can be calculated as measure of
association
 In Cohort study, either RR or OR is a valid measure of
association
 When a RR can be calculated from case control study?
*When exposure prevalence among studied cases
in similar and nearly similar to that of disease
subjects in the population from which cases are
taken.
*Prevalence of exposure among studied controls
is similar to that of non-diseased population from
cases were drawn.
*Rare disease (CI < 0.1)
18
Matched case-control study
 Matching: In a matched case-control
study each case is matched to a control
according to variables that are known to
be related to disease risk i.e. age, sex, race
 Data are analyzed in terms of case-
control pairs rather than for individual
subjects
 Four types of case-control
combinations are possible in regard to
exposure history.
19
 Concordant pairs are ignored since they
don’t contribute in calculation of effect
estimate (i.e. OR)
 Disconcordant pairs of cases and controls
are used to calculate the matched OR.
 Matched OR = Ratio of discordant pairs
= b /c
i.e. # of pairs in which cases exposed / # of
pairs in which controls were exposed
20
Example:
Risk factors for brain tumors in children.
Hypothesis = children with higher birth
weights are at increased risk for certain
childhood cancers.
Cases = Children with brain tumors
Controls = Normal children
Exposure = Birth weight > 8 lbs.
21
8 18
7 38
8 + 1b
Cases <8 1b
Total
26
45
15 56 71
8+ 1b <8 1b
Total
Normal Controls
Odds Ratio 18/7 = 2.57
χ2 = 4.00; P = 0.046
Interpretation the is same as before
Example

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measures of association.pptx

  • 1. 1 Epidemiologic Measures of Association Lt Col Ayon Gupta Assistant Professor Dept of Community Medicine , AFMC
  • 2. 2 Epidemiologic Measures of Association •Session Objectives By the end of session students should be able to: •Compute & Interpret Relative risk (RR) & Odds ratio (OR) as a measure of association between exposure and Disease • Understand when OR approximates RR
  • 3. 3 Definitions Association • A statistical relationship between two or more variables Risk • Probability conditional or unconditional of the occurrence of some event in time • Probability of an individual developing a disease or change in health status over a fixed time interval, conditional on the individual not dying during the same time period Absolute risk
  • 4. 4 Association between exposure & Disease • Question: Is there an excess risk associated with a given exposure? • Objective: To determine whether certain exposure is associated with a given disease • Methodology: Use one of the epidemiologic study designs Cohort Case-control
  • 5. 5 Cohort Study • Assess the cumulative incidence (CIE+) of disease in an exposed group (absolute Risk) Assess the cumulative incidence (CIE-) of disease in unexposed group (absolute Risk) e.g. Coronary Heart Disease (CHD) Risk among Smokers 1-year risk of CHD among smokers (CIE+)* CHD Yes No Total Smokers 84 2916 3000 CIE+ = 84/3000 = 28/1000/yr (1-risk of CHD among smokers) Cont.
  • 6. 6 CHD Risk among non-smokers • 1-year risk of CHD among non-smokers (CIE- ) CHD Yes No • Non-smokers 87 4913 5000 CIE-= 87/5000=17.4/1000/yr (1-yr risk of CHD among non-smokers) Cont.
  • 7. 7 Assessment of Excess Risk (Two methods) a. Ratio RR (Ratio of two risks; Risk Ratio; Relative Risk) CIE+ / CIE- = 28/17.4 = 1.6 Interpretation of RR Smokers were 1.6 times as likely to develop CHD as were non-smokers b. Difference Difference of two risks (Risk Difference)* CIE+- CIE- = 28.0 – 17.4 = 10.6
  • 8. 8 OR (Odds Ratio, Relative Odds) • In case-control study (CCS), we cannot calculate the CI or IR, therefore, cannot calculate the RR “directly” • OR as a measure of association between exposure & disease is used when data are collected in case-control study • OR can be obtained however, from a cohort as well as a case-control study and can be used instead of RR.
  • 9. 9 OR in case-control and cohort studies • Cohort study Ratio of the proportion of exposed subjects who developed the disease to the proportion of non- exposed subjects who developed the disease • Case-control study Ratio of the proportion of cases who were exposed to the proportion of controls who were non-exposed
  • 10. 10 Odds Ratio • Odds are ratio of two probabilities i.e. Probability that event occurs / 1-Probability that event does not occur • Odds refer to single entity • If an event has the probability P, then the odds of the same event are P/1-P
  • 11. 11 Derivation of OR in Cohort study P D +|E + = (exposed developed the disease) = a/(a+b) P D -|E + = (exposed did not develop the disease) = b/(a+b) Odds of developing disease among exposed = D+|E+/1-P D-|E+ = a/(a+b) b/(a+b) = a/b P D +|E - = (non-exposed developed the disease) = c/(c + d) P D -|E - = (non-exposed did not develop the disease)= d/(c + d) Odds of developing disease among non-exposed = = PD+|E -/1-P D+|E - = c/(c+d) d/(c + d) = c/d Odds ratio a/b : c/d = ad/bc
  • 12. 12 OR in case-control study  In case-control study RR cannot be calculated directly to determine the association between exposure and disease.  Don’t know the risk of disease among exposed and un-exposed since we start recruiting cases and controls.  Can use OR as measure of association between exposure and disease in a case control study.
  • 13. 13 OR in case-control Study Probability of case being exposed = Pcase Probability of case being non-exposed =1-Pcase Odds of case being exposed = Pcase/1- Pcase Probability of control being exposed = Pcontrol Probability of case being non-exposed =1-Pcontrol Odds of control being exposed = Pcontrol/ 1-Pcontrol
  • 14. 14 Derivation of OR in case-control Study Probability of being exposed among cases = a /(a + c) Probability of being non-exposed among cases) = c /(a + c) Odds of being exposed among cases = a/c Probability of being exposed among controls = b/(b + d) Probability of being unexposed among controls = d/(b + d) Odds of being exposed among controls = b/d OR = ad/bc
  • 15. 15 • Past surgery HCV status HCV+ HCV- • Yes 59 168 • No 54 48 » 113 216 Example OR in case-control Study
  • 16. 16 Odds of Past surgery among HCV+ P1 (Surgery among HCV+) = 59/113 1-P1 (No surgery among HCV+) = 54/113 Odds of surgery among HCV+ ) = 59/54 = 1.09 Odds of Past surgery among HCV- P2 (Surgery among HCV-) = 168/216 1-P2 (No surgery among HCV-) = 48/216 Odds of surgery among HCV- = 168/48 = 3.5 OR = 3.50/1.09 = 3.21
  • 17. 17 When is the OR a good estimate of RR?  In CCS, only OR can be calculated as measure of association  In Cohort study, either RR or OR is a valid measure of association  When a RR can be calculated from case control study? *When exposure prevalence among studied cases in similar and nearly similar to that of disease subjects in the population from which cases are taken. *Prevalence of exposure among studied controls is similar to that of non-diseased population from cases were drawn. *Rare disease (CI < 0.1)
  • 18. 18 Matched case-control study  Matching: In a matched case-control study each case is matched to a control according to variables that are known to be related to disease risk i.e. age, sex, race  Data are analyzed in terms of case- control pairs rather than for individual subjects  Four types of case-control combinations are possible in regard to exposure history.
  • 19. 19  Concordant pairs are ignored since they don’t contribute in calculation of effect estimate (i.e. OR)  Disconcordant pairs of cases and controls are used to calculate the matched OR.  Matched OR = Ratio of discordant pairs = b /c i.e. # of pairs in which cases exposed / # of pairs in which controls were exposed
  • 20. 20 Example: Risk factors for brain tumors in children. Hypothesis = children with higher birth weights are at increased risk for certain childhood cancers. Cases = Children with brain tumors Controls = Normal children Exposure = Birth weight > 8 lbs.
  • 21. 21 8 18 7 38 8 + 1b Cases <8 1b Total 26 45 15 56 71 8+ 1b <8 1b Total Normal Controls Odds Ratio 18/7 = 2.57 χ2 = 4.00; P = 0.046 Interpretation the is same as before Example