6. Prevalence Versus Incidence
• Prevalence can be viewed
as describing a pool of
disease in a population.
• Incidence describes the
input flow of new cases
into the pool.
• Deaths and cures reflects
the output flow from the
pool.
7. Prevalence Versus Incidence
Prevalence at time t1 = 2/10 = 20%
Source: Silva 1999
Prevalence at time t2 = 3/8 = 38%
Incidence between t1 and t2: 4/8 = 50%
10. Analytic Studies
• To effectively practice medicine, we need
evidence/knowledge on 3 fundamental types
of professional knowing “gnosis”:
Dia-gnosis Etio-gnosis Pro-gnosis
11. • Most fundamental application of clinical
research: to identify causal associations
between exposure(s) and outcome(s)
Exposure Outcome
?
Analytic Studies
16. Causal Vs. Non-causal Association
A B
A is not causally associated with B
C e.g. Smoking
e.g. Lung cancere.g. Coffee
17. A Research Scenario
• Study question: Does eating affect student
intellectual ability.
• 100 students underwent an exam after eating
lunch.
• 50% failed the exam.
• You conclude that eating worsen students
intellectual ability.
18. Compared to what?
• In an old movie, comedian
Groucho Marx is asked:
“Groucho, how’s your wife?”
• Groucho quips: “Compared
to what?”
http://en.wikipedia.org
19. Outcome
Outcome
Counterfactual, unexposed cohort
Exposed cohort
Ideal counterfactual comparison to determine
causal effects
Maldonado & Greenland, Int J Epi 2002;31:422-29
“Initial conditions” are identical in
the exposed and unexposed groups
– because they are the same
population!
20. Outcome
Outcome
Counterfactual, unexposed cohort
Exposed cohort
Substitute, unexposed cohort
Outcome
What happens in reality?
counterfactual state
is not observed
(latent)
A substitute will usually be a population other than the target population
during the etiologic time period - INITIAL CONDITIONS MAY BE
DIFFERENT
25. How PAR is dependent on prevalence of
exposure
Szklo & Nieto. Epidemiology: Beyond the basics. 2nd Edition, 2007
26. Randomization helps to make the groups “comparable” (i.e. similar
initial conditions)
Eligible patients
Treatment
Randomization
Placebo
Outcomes
Outcomes
Randomized-controlled trials
Incidence
Incidence
Difference: “RR” or “RD”
34. Source: Rothman 2002
Association between maternal age and Down syndrome, stratified by
birth order
Data from Stark and Mantel (1966)
35. Criteria to define confounder
• A factor is a confounder if 3 criteria are met:
– a) a confounder must be causally or noncausally associated
with the exposure in the source population;
– b) a confounder must be a causal risk factor (or a surrogate
measure of a cause) for the disease;
– c) a confounder must not be an intermediate cause (in other
words, a confounder must not be an intermediate step in the
causal pathway between the exposure and the disease)
36. Exposure Disease (outcome)
Confounder
Confounding Schematic
E D
C
Szklo M, Nieto JF. Epidemiology: Beyond the basics. Aspen Publishers, Inc., 2000.
Gordis L. Epidemiology. Philadelphia: WB Saunders, 4th Edition.
38. Birth Order Down Syndrome
Confounding factor:
Maternal Age
Confounding Schematic
E D
C
39. HRT use Heart disease
Confounding factor:
SES
Are confounding criteria met?
Association between HRT and heart disease
40. Control of confounding: Outline
• Control at the design stage
– Randomization
– Restriction
– Matching
• Control at the analysis stage
– Conventional approaches
• Stratified analyses
• Multivariate analyses
– Newer approaches
• Propensity scores
41. Observational Study on Vit E and Coronary Heart
Disease
Fitzmaurice, 2004
Crude OR = (50)(384)/(501)(65) = 0.59
Are there potential confounders that can explain this crude OR?
42. Vitamin E CHD
Confounding factor:
Smoking
Stratify on the
confounding
variable
Could reduced smoking among Vit E users partly
explain the observed protective effect?
45. •Diagnostic 2 X 2 table*:
Disease + Disease -
Test + True
Positive
False
Positive
Test - False
Negative
True
Negative
*When test results are not dichotomous, then can use ROC curves [see later]
Diagnostic Studies
52. Continuous results:
Receiver operating characteristic (ROC)curve
Blood sugar level
(2-hour after
food) in
mg/100 ml
Sensitivity
(%)
Specificity
(100%)
70
80
90
100
110
120
130
140
150
160
170
180
190
200
98.6
97.1
94.3
88.6
85.7
71.4
64.3
57.1
50.0
47.1
42.9
38.6
34.3
27.1
8.8
25.5
47.6
69.8
84.1
92.5
96.9
99.4
99.6
99.8
100
100
100
100
Area under the curve (AUC) can range from 0.5 (random
chance, or no predictive ability; refers to the 45 degree line
in the ROC plot) to 1 (perfect discrimination/accuracy).
The closer the curve follows the left-hand border and then the
top-border of the ROC space, the more accurate the test. The
closer the curve comes to the 45-degree diagonal of the ROC
space, the less accurate the test.
57. Continuous Variables
• Two Variable
– Student t test
– Paired t test (matched
pairs)
– Univariate Linear
Regression
• More than two
variables
– ANOVA
– Multivariate Linear
Regression
Comparative analysis
58. Categorical Variables
• Descriptive analysis
– Proportion and 95% CI
• Comparative analysis
– Chi Square test
– Fisher's exact test
– Logistic Regression
59. Incidence Risk Vs. Incidence Rate
Hypothetical cohort of 12 initially disease-free subjects followed
over a 5-year period from 1990 to 1995.
Incidence risk = 5/12 = 42/100 persons
Incidence rate = 5/25 = 20/100 person-year
Kleinbaum et al. ActivEpi
65. Example
Hypothetical cohort of 12 initially disease-free subjects followed
over a 5-year period from 1990 to 1995.
Kleinbaum et al. ActivEpi
Incidence risk = 5/12 = 0.42 (42 per 100 persons)
Incidence rate = 5/25 = 0.2 per person year
67. Hypothesis Testing (P-value)
• Null hypothesis No difference.
• P-value < 0.05 Reject the null hypothesis
(there is difference).
68. Problems with P-values
• Does not measure the magnitude of the
difference.
• Depends on the sample size.
– Very small difference can become significant by
increasing the sample size.
• Multiple testing will increase the chance of
having positive (significant difference) result
due to random error.
69. Biggest problem!
• We know that the null hypothesis (difference
= zero) is not true.
• We just need enough power (sample size) to
reject the null hypothesis (and make our study
“POSITIVE”).
• Example: 5-years mortality
Group 1 Group 2
0.0021633098649999 0.0021633098649999