Association and Causation

Kriengkrai Srithanaviboonchai MD, MPH

27 November 2013
Introduction to Community Medicine II

vs

vs

Epidemiological studies
Observational
studies
Descriptive studies

Cross-sectional studies

Experimental
studies

Analytical studies

Case-control studies

Cohort studies

 (Descriptive studies)

(person), (place)
(time)

(control group)
(association)

prevalence, incidence,
mortality rate, (surveillance), case
series

 (Analytical studies)

Analytical study

()

Cross-sectional analytic,
Case-control, Cohort

Risk factor

Disease

Prognostic studies

Prognostic factor

Outcome

Experimental

Intervention

Clinical endpoint


1.
2.
3.

Disease/Outcome exposed

Disease/Outcome

exposed

= (measure of association)

Measures of association

Relative measures
(Multiplicative)

Scale -
expose
outcome

Additive measures
(Health impact)

Scale -
expose
outcome

Contingency (2 by 2) Table
Disease

No
disease

Exposed

a+b

Non
exposed

c+d

a+c

b+d

a+b+c+d

Relative Risk (RR)

Relative measure of association (multiplicative scale)

Exposed Risk factor Exposed Risk

factor

Incidence in exposed
RR =
Incidence in unexposed

RR in cohort study of Cumulative Incidence (CI)

Disease

No
disease

Exposed

a+b

Unexposed

c+d

a+c

b+d

a+b+c+d

CIR = RR =
=

Risk of having disease in exposed

Risk of having disease in un-exposed
a / (a + b)
c / (c + d)


Cohort study of risk

Yes
No
Total

Yes

Total

No
27
31
58

455
1,831
2,286

482
1,862
2,344

RR = CI in exposed / CI in un-exposed
= a /(a + b) c / (c + d) = (27/482) (31/1,862)
= 0.056 / 0.017 = 3.3

RR for cohort study of person-time

Disease

No
disease

Exposed

PY1

Unexposed

PY0

a+c

PY1 + PY2

IR in exposed
IRR = RR = IR in un-exposed
a / PY1
=
c / PY2


Cohort study of
person-time

Yes
No
Total

Yes

Person-year

No
27
31
58

RR = IR in exposed / IR in un-exposed
= (27/1,230) (31/4,765)
= 0.022 / 0.0065 = 3.38

1,230
4,765
5,995

RR in cross-sectional analytic study

Disease

No
disease

Exposed

a+b

Unexposed

c+d

a+c

b+d

a+b+c+d

PRR = RR =
=

Prevalence of having disease in exposed

Prevalence of having disease in un-exposed
a / (a + b)
c / (c + d)


Cross-sectional study

Yes
No
Total

Yes

Total

No
27
31
58

455
1,831
2,286

482
1,862
2,344

PRR = Prevalence in exposed / Prevalence in un-exposed

= a /(a + b) c / (c + d) = (27/482) (31/1,862)
= 0.056 / 0.017 = 3.3

Odds Ratio (OR)

Case-control study
Prevalence Incidence RR

OR RR

Cross-sectional, Cohort Clinical trial

OR
Odds of exposed in a case
OR =
Odds of exposed in a control

Probability vs Odds

Probabilities and Odds

Probabilities:

Odds:

:
Probability 1 = 1 / 6
Odds 1 = (1 / 6) (5 / 6)
=1/5

Probabilities and odds

Pr obability
Odds
;
1 Pr obability
Odds
0.001
0.010
0.020
0.053
0.111
0.250
0.333
1.00
4.00
9.00
49.00
99.00

1.6
1.4
1.2
1

Odds

Probability
0.001
0.01
0.02
0.05
0.10
0.20
0.25
0.50
0.80
0.90
0.98
0.99

Odds
Pr obability
1 Odds

0.8
0.6
0.4
0.2
0
0

0.1

0.2

0.3

Probability

0.4

0.5

Odds Ratio (OR)

Case

Control

Exposed

a+b

Unexposed

c+d

a+c

b+d

a+b+c+d

Odds of exposed in a case

OR =
Odds of exposed in a control
= (a/a+c) (c/a+c)
(b/b+d) (d/b+d)

Cross product

a/c b/d = (a)(d)

(b)(c)


Case-control study

Yes
No
Total

Yes

No
27
31
58

OR =

Total

a/c b/d = (a)(d)

(b)(c)

= (27)(51) / (7)(31)
= 1377 / 217

= 6.35

7
51
58

34
82
116

OR RR

outcome
(rare)
OR
Cross-sectional,
Cohort, Intervention
RR

Case

Control

Exposed

a+b

Unexposed

c+d

a+c

b+d

a+b+c+
d

a/(a+b) a/b ad
RR =
=
= OR

c/(c+d)
c/d bc

RR and OR

0 to

1 = No association
> 1 = Positive association (Risk factor)
< 1 = Inverse association (Protective factor)

outcome

Measures of association

Relative measures
(Multiplicative)

Additive measures
(Health impact)

Attributable risk (ARexp)

: Excess risk

Additive measure of association

exposed
risk factor
ARexp = Incidence in exposed Incidence in un-exposed
In cohort study of person-time, ARexp = IRe IRo
In cohort study of risk,

ARexp = CIe CIo

Yes
No
Total

Yes

Total

No
27
31
58

455
1,831
2,286

482
1,862
2,344

AR = Incidence in exposed - Incidence in un-exposed

= a / (a + b) c / (c + d) = (27/482) - (31/1,862)
= 0.056 0.017 = 0.039

Attributable risk percent (%ARexp)

: Attributable rate percent, Attributable proportion,

Etiologic fraction

Exposed Risk
factor Exposed

Exposed
Risk factor

ARexp
%ARexp =
Incidence in exposed

X 100

Yes
No

Yes
No
Total

27
31
58

Total

455
1,831
2,286

AR
%AR =
X 100
Incidence in exposed
=

0.039
0.056

= 69.64%

482
1,862
2,344

Population attributable risk (PAR)

Exposed Risk
factor

Risk factor

PAR = Incidence in population Incidence in unexposed

or
= (AR) * (proportion of exposed in the population)

Yes
No
Total

Yes

Total

No
27
31
58

455
1,831
2,286

482
1,862
2,344

PAR =Incidence in population - Incidence in un-exposed

= a + c / (a+b+c+d) c / (c + d) = (58/2,344) - (31/1,862)
= 0.025 0.017 = 0.008

%PAR

exposed
risk factor

risk factor

PAR
X 100
%PAR =
Incidence of disease in population
=

{Pe(RR-1)}
X 100
{Pe(RR-1)} + 1
Pe=proportion of exposure in population

Yes
Yes
No
Total

No
27
31
58

455
1,831
2,286

PAR
%PAR =
Incidence in population
=

0.008
0.025

Total

= 32%

482
1,862
2,344

X 100

 AR, %AR, PAR, %PAR

5.6

6
5

PAR
= 0.8/2.5
= 32%
%

4
3
2

2.5

AR
3.9%
PAR = 0.8%

1.7

1
0
un-exposed

population

exposed

AR
= 3.9/5.6
= 69.6%
%

Additive measure of association (Health impact)

AR, %AR, PAR, %PAR

Causation

 vs

Analytical studies

()

 vs

Yes
/

No

Yes

No
Yes

No

Sir Austin
Bradford Hill

Hills Criteria of Causality

1. (Strength of association)
RR OR

2. (Consistency)

Weight gain in smoker after quitting cigarette (Aubin HJ, et al. 2012)

Hills Criteria of Causality

3. (Specificity)

4. (Temporality)

Hills Criteria of Causality

5. (Dose
response relationship)

Hills Criteria of Causality

5. (Dose
response relationship)

6. (Biologic plausibility)

Hills Criteria of Causality

7. (Coherence)

8. (Experimental evidence)

9. (Analogy)

1. Case-control study Odds

Ratio 1 exposed Independent variable
A.
B.
C.
D.
E.

2.


Thalidomide
Hills criteria of causation
A. Biologic plausibility
B. Temporal relationship
C. Analogy
D. Coherence
E. Consistency

3. Cohort study HIV

1.6 4.8 / person-year relative risk

A. 3
B. 3.2
C. 33%
D. 32%
E. 0.33

5. 3,000 2,000

A.
B.
C.
D.
E.

6. Cochrane Collaboration Hill's criteria of

causation
A. Analogy
B. Coherence
C. Consistency
D. Experimental evidence
E. Strength of association

Question!!!
ksrithanaviboonchai@gmail.com
ksrithan@med.cmu.ac.th