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MEASURES OF ASSOCIATION Presenter: P. Ganeshkumar Moderator: Dr. Pragati Chhabra
Overview of the presentation ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
ASSOCIATION 24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
Types of association ,[object Object],[object Object],[object Object],24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
Types of association….contd. ,[object Object],[object Object],24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
Types of association……contd. ,[object Object],[object Object],24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
Types of association……contd. ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
Types of association……contd. ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
Association-types ,[object Object],[object Object],[object Object],[object Object],24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI. ,[object Object],[object Object],[object Object],Population Incidence(%) A B In exposed 40 90 In non-exposed 10  60 Difference in incidence rates(%) 30 30 Ratio of incidence rates 4.0 1.5
[object Object],[object Object],24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
Absolute differences ( Syn: Difference measures ) ,[object Object],[object Object],[object Object],24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
Relative differences  (Syn:Ratio measures) ,[object Object],[object Object],24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
Types of measures of association used in analytic epidemiologic studies. 24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI. Type Example Usual application Absolute difference AR (Attributable Risk) Primary prevention impact: search for causes. PAR(Population Attributable risk) Primary prevention impact Efficacy Impact of intervention on recurrences, case fatality etc.  Mean differences (continuous outcome) Search for determinants Relative difference Relative risk/rate Search for causes Relative odds (ODDS ratio) Search for causes
Relative risk ,[object Object],[object Object],[object Object],[object Object],[object Object],24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
Relative risk of developing the disease is expressed as the ratio of the risk(incidence) in exposed individuals  (q+)  to that in unexposed individual (q-) Total  exposed = a+b Total unexposed  = c+d 24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI. Diseased Nondiseased Exposed a b Unexposed c d
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI. Diseased Nondiseased Exposed a b Unexposed c d
Hypothetical cohort study of the one year incidence rate of acute MI. Relative risk = IE/IU Incidence among exposed = 180/10000  = 0.0180 Incidence among unexposed = 30/10000=0.0030 RR = 0.0180/0.0030 = 6.00 ar 24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI. OR/RR Myocardial infarction Blood pressure Present Absent Total Severe hypertension 180(a) 9820(b) 10000 Normal 30(c) 9970(d) 10000
Interpreting Relative risk of a disease. 24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI. RR = 1 No association RR > 1 Positive association  (possibly causal) RR < 1 Negative association (possibly protective)
Framingham study during first 12 years 24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI. Serum cholesterol Men Women 30-49 yr 50-62 30-49 50-62 Incidence rates (per 1000) <190 38.2 105.7 11.1 155.2 190-219 44.1 187.5 9.1 88.9 220-249 95.0 201.1 24.3 96.3 250+ 157.5 267.8 50.4 121.5 Relative risks <190 1.0 2.8 0.3 4.1 190-219 1.2 4.9 0.2 2.3 220-249 2.5 5.3 0.6 2.5 250+ 4.1 7.0 1.3 3.2
Statistical test for RR ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
[object Object],[object Object],24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
RR-STATISTICAL TEST ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],9820 180(10000)  9970 30(10000) = 0.197 6.0 0.197 6.0 0.197 = 4.08 = 8.83 24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
Odd’s ratio(Relative odds) ,[object Object],[object Object],[object Object],24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
[object Object],[object Object],[object Object],[object Object],24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
Odds ratio in a cohort study ,[object Object],[object Object],[object Object],[object Object],[object Object],What are the odds that the disease will develop in an exposed person? 24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI. Develop disease Do not develop disease Exposed a b Unexposed c d
Odds ratio in a case-control study What are the odds that a case was exposed? ,[object Object],[object Object],[object Object],[object Object],24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI. Cases(with disease) Controls (without disease) H/O of expos a b No H/O expos c d
[object Object],product of the two cells that support the hypothesis of an association product of the two cells that negate the hypothesis of an association : ad bc : 24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI. Cases(with disease) Controls (without disease) H/O of expos a b No H/O expos c d
Odds ratio in a matched case control study ,[object Object],[object Object],24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
Calculation of the odds ratio is based on discordant pairs. Odds ratio (matched pairs) =  b/c 24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI. Concordant pairs Pairs in which both the case and controls were  exposed. (a) Pairs in which neither the case nor the control were unexposed  (d) Discordant pairs Pairs in which the case was exposed but the control was not (b) Pairs in which the control was exposed and the case was not. (c) CASE- CONTROL PAIRS CONTROL Exposed Unexposed CASE Expsoed a b Unexposed c d
Birth weight of index child: matched pairs comparison of cases and normal controls(>8 lb vs. <8 lb). Risk factors for brain tumors in children. Am. J Epidemiol 109 ,[object Object],24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI. CASE- CONTROL PAIRS Normal controls 8+ lb < 8 lb Cases 8+ lb  8 18 < 8 lb 7 38
Relationship between OR and RR ,[object Object],[object Object],[object Object],24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
Mathematical relationship between the OR and RR ,[object Object],[object Object],[object Object],[object Object],RR BIAS 24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
[object Object],[object Object],[object Object],[object Object],[object Object],24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
Hypertension/myocardial infarction example ,[object Object],[object Object],[object Object],[object Object],24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
Incidence of local reactions in the vaccinated and placebo groups, influenza vaccination trial. Seltser et al 24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI. Local reaction Group Present Absent Total Probability Probability odds Vaccine 650 1920 2570 650/2570= 0.2529 650/(2570-650) =650/1920  = 0.3385 Placebo 170 2240 2410 170/2410=0.0705 170/(2410-170) = 170/2240 = 0.0759
[object Object],Hence when the condition has a high incidence and when prospective data are available , there will be considerable bias when using OR to estimate RR. 24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
Example.  Vaccine : local reaction  ,[object Object],[object Object],24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
Example.  Vaccine : local reaction  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
Relationship between RR and OR by the incidence of the outcome. 24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
ATTRIBUTABLE RISK (AR) ,[object Object],[object Object],[object Object],[object Object],24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
Terms ,[object Object],[object Object],[object Object],24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
AR in exposed individuals ,[object Object],[object Object],[object Object],[object Object],[object Object],24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
Example: MI and HT   ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
%AR in case-control studies This formula can be used in case-control studies , in which the incidence data are unavailable, but the odds ratio can be used as an estimate of the relative risk if the disease is relatively rare. 24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
EFFICACY ,[object Object],[object Object],[object Object],24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
AR exp BACKGROUND RISK 24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
POPULATION  ATTRIBUTABLE  RISK ,[object Object],[object Object],[object Object],[object Object],p e    prevalence of exposure in total population. 1- p e     prevalence of non-exposure. 24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
Smoking and heart disease: Hypothetical cohort study of 3000 cigarette smokers and 5000 non-smokers Assuming the proportion of smokers in the pop.   P e  : 44% Therefore the proportion of non-smokers (1-  p e  ): 56% 21.3% of the incidence of CHD in the total population can be attributed to smoking. If an effective prevention program eliminated smoking, the best that we could hope to achieve would be reduction of 21.3% in the incidence of CHD in the total population consisting of both smokers and  non-smokers. 24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI. CHD develops CHD does not develop Total Incidence per 1000 per year Smoke  84 2916 3000 ( q+ )28 Do not smoke 87 4913 5000 (q-)17.4
24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
AR and RR From Doll R,Peto R: Mortality in relation to smoking:20 yrs observation on male British doctors. Br Med J 2:1525-1536,1976 24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI. ,[object Object],[object Object],[object Object],[object Object],Age adjusted death rates per 100000 Smokers Non smokers RR AR %AR Lung cancer 140 10 14.0 130 92.9% CHD 669 413 1.6 256 38.3%
CAUSATION ,[object Object],[object Object],[object Object],[object Object],[object Object],24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
[object Object],[object Object],24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
Bradford Hill’s  criteria ,[object Object],views 24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
STRENGTH ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
CONSISTENCY ,[object Object],[object Object],[object Object],[object Object],[object Object],24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
SPECIFICITY ,[object Object],[object Object],[object Object],24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
TEMPORALITY ,[object Object],[object Object],24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
BIOLOGICAL GRADIENT ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
PLAUSIBILITY ,[object Object],[object Object],[object Object],24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
COHERENCE ,[object Object],[object Object],24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
EXPERIMENTAL EVIDENCE ,[object Object],[object Object],[object Object],[object Object],24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
ANALOGY ,[object Object],24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
REFERENCES 24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI. 3.Measures of Association and Hypothesis Testing by Deborah Rosenberg, PhD and Arden Handler, DrPH 4.Causation and Causal Inference in Epidemiology Kenneth J.Rothman, DrPH, Sander  Greenland, MA, MS, DrPH, C Stat
Hypothesis testing  for RR 24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.

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Measures Of Association

  • 1. MEASURES OF ASSOCIATION Presenter: P. Ganeshkumar Moderator: Dr. Pragati Chhabra
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  • 3. ASSOCIATION 24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
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  • 10. 24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
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  • 15. Types of measures of association used in analytic epidemiologic studies. 24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI. Type Example Usual application Absolute difference AR (Attributable Risk) Primary prevention impact: search for causes. PAR(Population Attributable risk) Primary prevention impact Efficacy Impact of intervention on recurrences, case fatality etc. Mean differences (continuous outcome) Search for determinants Relative difference Relative risk/rate Search for causes Relative odds (ODDS ratio) Search for causes
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  • 17. Relative risk of developing the disease is expressed as the ratio of the risk(incidence) in exposed individuals (q+) to that in unexposed individual (q-) Total exposed = a+b Total unexposed = c+d 24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI. Diseased Nondiseased Exposed a b Unexposed c d
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  • 19. Hypothetical cohort study of the one year incidence rate of acute MI. Relative risk = IE/IU Incidence among exposed = 180/10000 = 0.0180 Incidence among unexposed = 30/10000=0.0030 RR = 0.0180/0.0030 = 6.00 ar 24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI. OR/RR Myocardial infarction Blood pressure Present Absent Total Severe hypertension 180(a) 9820(b) 10000 Normal 30(c) 9970(d) 10000
  • 20. Interpreting Relative risk of a disease. 24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI. RR = 1 No association RR > 1 Positive association (possibly causal) RR < 1 Negative association (possibly protective)
  • 21. Framingham study during first 12 years 24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI. Serum cholesterol Men Women 30-49 yr 50-62 30-49 50-62 Incidence rates (per 1000) <190 38.2 105.7 11.1 155.2 190-219 44.1 187.5 9.1 88.9 220-249 95.0 201.1 24.3 96.3 250+ 157.5 267.8 50.4 121.5 Relative risks <190 1.0 2.8 0.3 4.1 190-219 1.2 4.9 0.2 2.3 220-249 2.5 5.3 0.6 2.5 250+ 4.1 7.0 1.3 3.2
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  • 31. Calculation of the odds ratio is based on discordant pairs. Odds ratio (matched pairs) = b/c 24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI. Concordant pairs Pairs in which both the case and controls were exposed. (a) Pairs in which neither the case nor the control were unexposed (d) Discordant pairs Pairs in which the case was exposed but the control was not (b) Pairs in which the control was exposed and the case was not. (c) CASE- CONTROL PAIRS CONTROL Exposed Unexposed CASE Expsoed a b Unexposed c d
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  • 37. Incidence of local reactions in the vaccinated and placebo groups, influenza vaccination trial. Seltser et al 24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI. Local reaction Group Present Absent Total Probability Probability odds Vaccine 650 1920 2570 650/2570= 0.2529 650/(2570-650) =650/1920 = 0.3385 Placebo 170 2240 2410 170/2410=0.0705 170/(2410-170) = 170/2240 = 0.0759
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  • 41. Relationship between RR and OR by the incidence of the outcome. 24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
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  • 47. %AR in case-control studies This formula can be used in case-control studies , in which the incidence data are unavailable, but the odds ratio can be used as an estimate of the relative risk if the disease is relatively rare. 24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
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  • 49. AR exp BACKGROUND RISK 24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
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  • 51. Smoking and heart disease: Hypothetical cohort study of 3000 cigarette smokers and 5000 non-smokers Assuming the proportion of smokers in the pop. P e : 44% Therefore the proportion of non-smokers (1- p e ): 56% 21.3% of the incidence of CHD in the total population can be attributed to smoking. If an effective prevention program eliminated smoking, the best that we could hope to achieve would be reduction of 21.3% in the incidence of CHD in the total population consisting of both smokers and non-smokers. 24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI. CHD develops CHD does not develop Total Incidence per 1000 per year Smoke 84 2916 3000 ( q+ )28 Do not smoke 87 4913 5000 (q-)17.4
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  • 57. 24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.
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  • 67. REFERENCES 24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI. 3.Measures of Association and Hypothesis Testing by Deborah Rosenberg, PhD and Arden Handler, DrPH 4.Causation and Causal Inference in Epidemiology Kenneth J.Rothman, DrPH, Sander Greenland, MA, MS, DrPH, C Stat
  • 68. Hypothesis testing for RR 24-Dec-08 DEPT. OF COMMUNITY MEDICINE, UCMS&GTBH DELHI.