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Tutorial
:Epidemiology
E id i l
and
d
Bi t ti ti for
Biostatistics
f NT
Dr. Chanon Kongkamol
Occupational Health Unit,
Community Medicine,
PSU
STEP I : 10 % = 30
1. Fundamental concepts
p of measurement
2. Fundamental concepts of study design
3. Fundamental concepts of hypothesis testing
and statistical inference
1.1 FFundamental
d
l concepts off MEASUREMENT
Scales of measurement
Distributions,
Di ib i centrall tendency,
d
variability, probability
Disease prevalence and
incidence
Disease outcomes
(eg.
Fatality rate)
2. Fundamental concepts of
st d design
study
Confidence
C fid interval
it l
Statistical significance and Type I error
Statistical power and Type II error
Part I :
Fundamental concepts of
MEASUREMENT
MEASUREMENT
1.1 FFundamental
d
l concepts off MEASUREMENT
1. Scales of measurement
2.2 Distributions,
Di t ib ti central
t l tendency,
t d
variability, probability
3. Disease prevalence and incidence
((eg.g
4. Disease outcomes
Fatality rate)
QQ.11
Ratio
A.
B.
C.
D
D.
E.
A.
B.
C.
D
D.
E.
a)
b)
c))
d)
e)
a) Ratio
b) Nominal
N i l
c)) Ordinal
O di l / NNominal
i l
d) Nominal
e) Nominal
1.1 FFundamental
d
l concepts off MEASUREMENT
1. Scales of measurement
2.2 Distributions,
Distributions central tendency
tendency,
variability, probability
3. Disease prevalence and incidence
4. Disease outcomes
(eg.
Fatality rate)
Q2.
M di = 180,
Median
180 Q1 = 150,
150 Q3=
Q3 200
Extreme
A.
B.
C.
D
D.
E.
A. 360
B. 340
C. 330
D 20
D.
E. 10
13
BOX Plot
180(150,200)
IQR = 200-150 = 50
Upper = Q3 + 1.5
1 5 IQR
= 200 +1.5*50 = 275
Lower = Q1- 1.5 IQR
= 150 - 1.5*50 = 75
Upper Outlier = Q3 + 3IQR
= 200 + 3(50) = 350
Lower Outlier = Q
Q1 - 3 IQR
Q
= 150 - 3 (50) = 0
350
275
75
0
15
Q3. Hct% 60
Gaussian distribution
A.
B
B.
C
C.
D.
E.
A .Median
B Mean
B.
M
C Median
C.
D. Mean
E. Mode
S.D.
SD
S.D.
Q1 Q3
Q1,Q3
Q1,Q3
Q1,Q3
Normal distribution
Mean + S.D.
1.1 FFundamental
d
l concepts off MEASUREMENT
1. Scales of measurement
2.2 Distributions,
Distributions central tendency
tendency,
variability, probability
(eg.
- 400,000
400 000
- 40 130,000
- 48 450 15
- 49 = 80 49
A.
B
B.
C.
D
D.
E.
80/ 400,000
80 / 130,000
130 000
450 / 130000
80 / (130000-450)
(130000 450)
80 / (130000-450-15)
(
)
Incidence = new cases / pop at risk
80 / (130000-450-15)
A. 35
1000
B.
20
1000
C. 50
1000
D
D.
35
100
E. 50
100
35 100
pop at risk
Incidence HIV
A.
AIDS
B
B.
HIV
C.
D.
AIDS
E
E.
HIV
HIV
???
60 1,000 DM 200
DM
50
incidence
A.
A
B.
C.
D.
E
E.
5%
6.25%
20%
25%
50%
Incidence = new cases / pop at risk
I = 50 / (1000 200 )
I = 6.25 %
1. 50 1000
2.
500 1000
3.3
250 1000
A.
B
B.
C.
D.
E.
> >
> >
> >
> >
> >
1.1 FFundamental
d
l concepts off MEASUREMENT
1. Scales of measurement
2.2 Distributions,
Distributions central tendency
tendency,
variability, probability
3. Disease prevalence and incidence
4. Disease outcomes
Fatality rate)
((eg
eg.g.
4.0 //
0.2
case fatality rate
A.
B
B.
C.
D.
E.
0.005 %
0 05 %
0.05
5%
0.2 %
5
Case fatality
y rate is
The proportion of individuals
contracting
t ti a disease
di
who
h di
die off
that disease.
/
0.2
4
CFR = 0.2*100 / 4 = 5%
Jap. B encephalitis
- 500 serology
- 300
- 100
- 50
- 5
fatality rate
A. 5/50
B. 5/150
C 5/155
C.
D. 5/500
Case fatality rate is
The proportion of
individuals contracting a disease who die of that disease.
5
100
100+50+5
50 5
CFR = 5/155
Mortality rate
250/1000
50/1000
5
D.
50
Indirect / SMR
ER
A.
B.
C
C.
D
D.
E.
Odds Ratio
Relative risk
M
Mortality
li rate
Prevalence
Incidence
F Strength of Association
Case Control Study
Odds Ratio
1.1 FFundamental
d
l concepts off MEASUREMENT
Scales of measurement
Distributions,
Distributions central tendency
tendency,
variability, probability
Disease prevalence and incidence
Disease outcomes
(eg.
Fatality rate)
Associations
(eg Correlation and
(eg.
covariance)
Health impact (eg. Risk differences
and ratio)
Efficacy of drug therapy (eg. Number
needed to harm))
Sensitivity, specificity, predictive
values
...
Q :
%
39
A.
B.
C
C.
D
D.
E
E.
40
Bradford-Hill criteria
Strength
Consistency
Specificity
S
ifi it
Temporality
Biological gradient
Plausibility
Coherence
Experiment
E
i
t
Analogy
The strength
g of association
Same Question Answer
Same pop factor- disease
Exposure Disease
D
Dose-response
relationship
l ti
hi
Biological knowledge
Lab and epidemiologic study
p
confirmation
Experimental
Acommonly accepted phenomenon
in one area can be applied to
another area.
Systemic review A, B
causal association
A.
B.
C
C.
D.
E.
Temporality
Reversibility
Consistency
Dose-effect
Biological plausibility
microalbuminuria
HbA1C 7
HbA1C 7
Mentel Haensel OR
Crude OR 1.39
ORMH 1.22
A.
B.
C.
D.
E.
43
Crude
C d OR = 1.39
1 39
ORMH = 1.22
1 22
= ((1.38-1.22)) *100 / 1.38 = 12%
15 %
2 model
Case-control study :
Odds Ratio
(Crude)
95% CI
(Crude)
Odds Ratio
(
(Adjusted)
)
95%
CI
(Adjusted)
j
5.62
3.79-8.33
4.48
2.88-6.98
2-4
2 94
2.94
1 92-44.51
1.92
51
1 51
1.51
0 93-22.46
0.93
46
>4
4.43
2.26-8.68
1.86
0.89-.386
A
A.
2-4
B.
2-4
2 4
C. 2-4
D. 4
E.
46
AA.
B.
C.
D.
E.
Errors
Random errors
Neyman bias
Berkson bias
Confounder
47
S l ti bi
Selection
bias
Neyman bias
Berkson bias
Exposure suspicious bias
Detection signal bias
Non respondent bias
Susceptibility bias
II IInformation/Observation
II.
f
ti /Ob
ti Bi
Bias
Recall bias
Interviewer bias
Misclassification bias
Loss to follow up bias
cuff
A.
B.
C
C.
D.
E.
Bias
Confounder
Contamination
Co-intervention
Ethics
50
1.1 FFundamental
d
l concepts off MEASUREMENT
Scales of measurement
Distributions,
Di ib i centrall tendency,
d
variability, probability
Disease prevalence and
incidence
Disease outcomes
(eg.
Fatality rate)
3
4
6
8
12
600
400
1000
400
1600
2000
1000
2000
3000
OR = (600*1600) / (400*400) = 6
Case
C control
t l study
td
Caffeine
NO
YES
YES
40
60
NO
200
100
240
160
100
300
400
OR
OR
A.
B.
C
C.
D.
E.
0.2
0.33
06
0.6
2
3
55
Case
C control
t l study
td
Caffeine
NO
YES
YES
40
60
NO
200
100
240
160
100
300
400
OR = (60*200) / (40*100) = 3
Cohort study
A 30,000
A
5
. 10,000
10 000
10
8
5 .
A.
B.
C.
D.
E.
2
2.5
3
5
7.5
RR = Ie/Io
RR = (10/10,000) / (8/20,000)
RR = 2.5
25
0.18
0
18
0.19
0 20
0.20
0.21
0.25
59
59
Method 1 : manual
OR = 23/207
D+
E+
230
E01
0.1
D-
2300-230
=2070
0.1
2300
0.2
http://www.physicsforums.com/showthread.php?t=3
9140
61
A. A 0.05
B. A 0.1
C
C.
Date
D. 5
E. 10
62
62
Strong Association
1-5
Percent Attribution Risk Percent Population
Risk
malnutrition = 25 and 10 %
1.5
1 5
B.
15
C.
25 %
D.
15%
E.
10 %
1.1 FFundamental
d
l concepts off MEASUREMENT
1. Scales of measurement
2.2 Distributions,
Distributions central tendency
tendency,
variability, probability
3. Disease prevalence and incidence
4. Disease outcomes
(eg.
Fatality rate)
8
2
A.
B.
C.
D
D.
E.
4
6
10
17
25
67
Ie = 8%
Io = 2%
AR = (8-2) /100 = 6/100
NNH = 16.67 = 17
68
Vaccine X X
Vaccine
30,000
,
350
Vacc
Vaccinee
45,000
5,000
1200
00
A.
B
B.
C.
D.
E
E.
44.75
51 00
51.00
53.75
56.25
98 83
98.83
(Io-Iv) * 100
Io
((1200/45000) (350/30000)) *100) / (1200/45000)
56.25
1,500
1,500 250
300 Number need to treat
A.
A
B
B.
C.
D.
E
E.
10
20
30
40
50
AR = 300/1500 250/1500 = 50/1500
NNT =1/AR = 1500/50 = 30
A 25
A.
B. 50
C. 75
D. 100
E. 125
NNT = 1/AR
AR = CER - EER
BUT
RR = Ie / Io
0.8 = 4 / x
X=5
AR = 4/100 5/100 =
1/100
NNT = 100/1 = 100
Vaccine
A 25
A.
B. 50
C. 75
D. 100
E. 125
RR = Ie / Io
0.5
0 5 = 0.001
0 001 / Io
I
Io = 0.002
Efficiency
Effi i
= (Io-Ie)*100
(I I )*100 / Io
I
)
/ 0.002
= ((0.002-0.001)*100
= 50 %
1.1 FFundamental
d
l concepts off MEASUREMENT
1. Scales of measurement
2.2 Distributions,
Distributions central tendency
tendency,
variability, probability
3. Disease prevalence and incidence
4. Disease outcomes
(eg.
Fatality rate)
Positive
Negative
Total
Positive
a+b
Negative
c +d
a + c
b + d
Total
Disease status
Name
True positive
(a)
Specificity
= d/ (b + d)
= a/ (a + b)
LR+ = Sn / (1
(1-Sp)
Sp)
LR- = (1 Sn) / Sp
Accuracy =
a+d
a + b+ c+ d
Bayes theorem
Bayes
PPV
NPV
sensitivity X prevalence
sensitivity
iti it X prevalence
l +( 1-specificity)X
1 ifi it )X (1
(1-prevalence)
l )
specificity X (1-prevalence)
Interpretation of Kappa
K
<0
0 - 0.19
0.20- 0.39
0.40- 0.59
0 60- 0.79
0.600 79
0.80- 1.00
Interpretation
No agreement
Poor agreement
Fair agreement
Moderate agreement
Substantial agreement
Almost perfect agreement
Landis JR
JR, Koch GG
GG. Biometrics 1977; 33:159-174.
33:159 174
0
1-3
4-6
7-9
10-12
13 15
13-15
Sensitivity
100
96
90
88
65
52
Specificity
0
50
60
80
93
97
Sensitivi Specifici LR+
LR
LR
ty
ty Sn/1-SP 1-Sn / Sp
Prev
PPV
NPV
1 00
1.00
0 00
0.00
1 00
1.00
#DIV/0!
0 30
0.30
0 30
0.30
#DIV/0!
0<=3
0.96
0.50
1.92
0.08
0.30
0.45
29.52
4<=6
0.90
0.60
2.25
0.17
0.30
0.49
14.42
7<=9
0.88
0.80
4.40
0.15
0.30
0.65
16.12
10<=12
0.65
0.93
9.29
0.38
0.30
0.80
6.85
13<=15
0.52
0.97
17.33
0.49
0.30
0.88
5.39
PPV
((Goal standard))
37
10
48
55
85
65
47
103
150
PPV =
test test
PPV = 37/85
1000
250
50
100
600
350
650
300
700
1000
Specificity
Specificity =
(600*100)
100) / 700 = 86 %
Sp = (600
cut off -
sensitivity
sensitivity Specificity
Cost effective
B
2. Fundamental concepts of
st d design
study
1.
Type
yp of Studies
2. +
3. Intervention
Case-control Study
disease
Observed
cause
Experimental Study
observed
assigned
disease
exposure
XXX YYY
incidence
YYY ZZZ
XXX
A.
B.
C.
D.
E.
Case-control studyy
Cohort study
Experimental study
Cross-sectional studyy
Descriptive study
1.
2. +
3. Intervention
Cohort study
Observational
Prospective Analytic study
Hep.
H A
A incidence Hepp A
A.
B.
C.
D
D.
E.
Cross-sectional study
y
Cohort study
Case control study
Meta analysis
Meta-analysis
Clinical trials
exposure disease
Retro cohort
1
AA.
B
B.
C.
D.
E.
clinical
li i l trials
il
Cohort study
Case series
Case control study
Cross sectional study
N
For causation Case Control
clinical trial
AA.
B.
C.
D.
E.
100%
Randomized
comparable
A
Cli i l ttrials
Clinical
i l phase
h
A.
A
B
B.
C.
D.
E
E.
Preclinical
P
li i l
Phase 0
Phase 1
Phase 2
Ph
Phase
3
100
Phase 0
:
human microdosing studies =
pharmacokinetics + pharmacodynamics
Phase I
Phase III
Phase IV
st d design
study
2. Fundamental concepts of
.
1000
100 10
10
100
A.
B.
C.
D
D.
E
E.
Cluster sampling
Simple random sampling
Systematic random sampling
St tifi d random
Stratified
d sampling
li
Purposive sampling
Systematic random sampling
120
350
A.
B.
C.
D.
E.
Cluster sampling
Accidental sampling
p g
Purposive sampling
Stratified random sampling
Systematic random sampling
Systematic random sampling
A.
B.
C.
D.
E.
Cluster sampling
Simple random sampling
Stratified sampling
Multi-stage sampling
Systemic sampling
Multi-stage sampling
st d design
study
2. Fundamental concepts of
A.
A
B.
C.
D.
E
E.
Sampling technique
Allocation
Internal Validity
S
Statistical
Analyses
Ethics
110
Internal validity
External validity
2. Fundamental concepts of
st d design
study
Level of evidence
L l off evidence
Level
id
A
consensus
L l off recommendation
Level
d ti
1
L l off recommendation
Level
d ti
1A
1B
1C
L l off recommendation
Level
d ti
0A
0B
0C
Confidence
C fid interval
it l
Statistical significance and Type I error
Statistical power and Type II error
Basic Biostatistics
Point estimation
OR = 3,
3 Diff = 10
Confidence interval
OR(95% CI) = 0.5 -10
10
Diff (95% CI) = 1 - 20
P-value = 0.08
P-value = 0.04
Point & CI
odds ratio
A.
B.
C
C.
D.
E.
0.5
1
5
100
Point
P i t estimation
ti ti
2.5
95% CI = 0.9 6.2
A.
B.
C
C.
D.
E.
A.
B.
C
C.
D.
E.
Chis square
T-test
Normal distribution
Binomial
ANOVA
Binomial
Bayer's
Bayer s law
P(B/A)
(
) = P(Bi)P(A/Bi)
( ) (
)
P(A)
84
95 % CI = 79-87
99 % CI = 78
78-88
88
10,000
78-88
A.
A
B
B.
C.
D.
E
E.
9900
9500
500
100
99
Prevalence of HBsAg
g
A.
B.
C
C.
D.
E.
Chi-square
Student t-test
Analysis of variance
Paired t-test
Linear regression
Proportion
P
ti ttestt
Chi-square
q
A.
B.
C
C.
D.
E.
Regression
Correlation
Anova
Student t-test
Chi-square
Predict Regression
= correlation
= 1.25 + 0.8()
90 3
A.
B
B.
C
C.
D.
E.
Z-test
Tt t
T-test
Anova
Chi-square
Multiple regression
Repeated ANOVA
T pe I & II Errors
Type
Type I error =
Type II error =
Type
I error =5, Type II error = 20
Ho
error
A.
B
B.
C.
D.
E.
5
10
15
20
25
Ho
..
=== Type II error
20
4/1000
P-value = 0.9
09
ppower = 93%
A.
A
B.
C.
D
D.
E
E.
Power 1- Beta
1-0.93
0.07
50
(
)
()
Type II error
A.
B.
C
C.
D.
E.
P < 0.05
0 05
P < 0.01
0 01
P < 0.05 P < 0.10
??
case control
t l
aspirin
i i
1.3)
0.3
0
3 1.3
13
0.3 - 0.7
0.5 - 0.9
0.1 - 1.1
1 3 - 2.9
1.3
29
OR = 0.7
0 7 95 % CI = 0.3
0 3 -1.3
13
sample
p size 95 % CI
95 % CI = 0.5 - 0.9
1.
2.
3.
4
4.
5
5.
143
1.
2.
3.
4.
5.
(Cholera)
12.
(Typhus)
(Plague)
13.
((Variola Smallpox)
p )
14.
(Yellow fever)
15.
((Meningococcal
g
16.
Meningitis)
17.
6. (Diphtheria)
7 (Tetanus
7.
(T t
18.
neonatorum)
8
8.
(Poliomyelitis)
9. (Influenza)
10. (Encephalitis)
11. (Rabies)
(Tuberculosis)
((Anthrax))
(Trichinosis)
((Yaws))
(Acute flaccid
paralysis)
(
p
y
Severs Acte Respiratory
Syndome)
144
24
.. 2551
1. SARS
meningitis
7
7.
2. Cholera
8. Encephalitis
p
3. Acte Severely ill or 9. -AFP
death of unknown 10.
10
etiology)
4 Cluster
4.
Cl t off diseases
di
with unknown
11
11.
etiology
12.
5 Anthrax
5.
145
6. Meningococca
1 .. 2551
1.
2 Influenza
2.
Infl en a
3.
4.
5
5.
(Hand food Mouth
Diseases)
6. Leptospirosis
6
L
i i
( y
y)
7. (Dysentery)
8. .
9
9.
146
1.
2
2.
3.
y
y
4.
5
5.
6.
7.
y
147
148
Stage 6 : Global
Epidemiology
E id i l SSurveillance
ill
Epidemiology
E id i l SSurveillance
ill
Target
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