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Applied Epidemiologic Analysis
Patricia Cohen, Ph.D.
Henian Chen, M.D., Ph. D.
Teaching Assistants
Julie Kranick
Chelsea Morroni
Applied Epidemiologic Analysis
Fall 2002
Sylvia Taylor
Judith Weissman
Outline Lecture 1
1) Overview of unique and common aspects of
epidemiological analysis in the larger scientific context
2) Review of the changing epidemiological research
climate
3) Review of measures of disease frequency
Applied Epidemiologic Analysis
Fall 2002
Learning Objectives
• To understand how study design and statistical
analyses are linked components in sound
epidemiologic investigations
• To appreciate the changing nature of disease
definitions and the consequent impact on design
and analysis
• To review alternative measures of disease
frequency
Applied Epidemiologic Analysis
Fall 2002
Some Themes to Review in
R&G Modern Epidemiology
• Discussion of the meaning of causality
• New understanding of the case-control study as a
special kind of cohort study
• Views on statistical hypothesis testing
Applied Epidemiologic Analysis
Fall 2002
Considerations Determining Study Design
•Classic issues
– Disease frequency
– Exposure measures
• Increasing importance
– Participation rate problems
– Concern about biased reports and recall
– Difficulty isolating risk factors
– Appreciation of multiple contributing factors
– Appreciation of potential contingent effects
– Wide availability of sophisticated statistical analytic techniques
Applied Epidemiologic Analysis
Fall 2002
Why Review Epidemiological Study
Designs?
• Measures of disease frequency depend on study
designs
• Measures of exposure effect depend on study
designs
• Appropriate statistical considerations depend on
study designs including sampling issues
Applied Epidemiologic Analysis
Fall 2002
Cohort Designs:
• Classical: sampling two or more disease-free
groups differing on exposure to a potential
disease cause (e.G. Snow study of cholera:
“sampling” of two residential areas differing on
water source)
• Current: occupational or residentially-based
cohorts
• Extended: sampling of a single cohort
heterogeneous on exposure, e.g. birth or age
cohorts, samples from selected occupational
groups or residential areas
Applied Epidemiologic Analysis
Fall 2002
Cohort Designs (Cont.)
• May be prospective, retrospective, or crosssectional (x-sec may be considered a distinct
category especially suited for “fixed” exposures)
• Prospective: usually current or recent risks
assessed at original sampling and disease assessed
at follow-up
• Retrospective: often risks assessed by means of
prior records: may also be assessed by
retrospective report of participants
Applied Epidemiologic Analysis
Fall 2002
Case-control Designs:
• Classic method for assessing risk for rare
diseases
• Ideally samples incident cases, but may sample
prevalent cases (note sampling bias associated
with disease duration)
• Notes R & G discussion of case-control designs
as a “weighted sample” kind of cohort design
Applied Epidemiologic Analysis
Fall 2002
Study Designs We Will Not Focus On:
• Ecological studies
• Proportional mortality studies
• Infectious disease studies
Applied Epidemiologic Analysis
Fall 2002
Nature of the Disease
• Major influence on study design, the disease
measure, and the statistical analysis
• Classically, especially infectious, brief onset
period and clear, often time-limited disease
• Increasingly, chronic and insidious, gradual onset
or progression
– e.g many mental illnesses, artherosclerosis, obesity,
diseases of old age
– often also a certain arbitrariness in the “cut-point’ defining
disease
Applied Epidemiologic Analysis
Fall 2002
Frequency of Both Disease
and Studied Exposures
• Increasing interest in high frequency disorders
(like many of the chronic ones discussed)
• Increasing interest in high frequency and graded
“exposures”: diet, environmental risks)
• Increasing felt need to incorporate genetic issues
Applied Epidemiologic Analysis
Fall 2002
Other Influences on Selected Study Designs
• Measures of disease frequency
– Incidence measures: what data are needed/how obtained
– Prevalence measures: limitations
– Scaled measures of prevalence
Applied Epidemiologic Analysis
Fall 2002
A review of some recent studies
We recently surveyed the types of studies and
analyses reported in three consecutive issues of
American Journal of Epidemioloy. For your first
homework assignment you will be asked to do a
similar task, although a bit more thorough.
Applied Epidemiologic Analysis
Fall 2002
Survey results
27 articles produced the following results:
Design type
Outcome variable
type
Statistical analyses
12
Cohort
17
Dichotomous
14
Logistic regression
4
Cross
sectional
10
Scaled
4
Survival analysis
8
Case-control
9
Multiple regression
1
Clinical trial
1
Conditional logistic regression
1
Poisson regression
2
ANOVA
1
Multilevel regression
1
Repeated measure analysis
Applied Epidemiologic Analysis
Fall 2002
Design and outcome determinants
The selection of both the outcome measure
(incidence; prevalence) and the study/analytic
design depends on:
The nature of the morbidity measure
The nature of the exposure(s) of interest.
Applied Epidemiologic Analysis
Fall 2002
Issues relating to exposures
• Is there a clear distinction between exposed and
unexposed?
• Is the exposure another disease?
• Is the exposure to be found in one
area/occupation/ but not in another otherwise
comparable population?
• Is the exposure a prevention or treatment
program?
Applied Epidemiologic Analysis
Fall 2002
Other current exposure measures:
• Biological markers
• Environmental measures
• Scaled measures of behavior (e.g. dietary intake,
exercise)
Applied Epidemiologic Analysis
Fall 2002
Incidence measures: When are they feasible?
Point exposures:
Industrial accidents (e.g. radiation exposure)
Natural disasters (e.g. hurricane
Unnatural disasters (e.g. 9/11)
Infection exposure
Note: must be known and considerations of sequellae
experiences complicate the question of timing of effective
exposures.
Applied Epidemiologic Analysis
Fall 2002
Period or duration of exposures prior to onset
Occupational exposures
Exposures related to own behavior (e.g. smoking, diet)
Age may be used as a proxy for duration of chronic exposures
(e.g. as in mortality studies)
Note: Considerations of level of exposure often complicate
these analyses, although in a case-control design these may
be treated separately by stratification.
Applied Epidemiologic Analysis
Fall 2002
Prevalence measures: When are they used?
• Insidious onset
• Fluctuating or recurring course
• Indistinct or somewhat arbitrary “cut-off” points
to define
Applied Epidemiologic Analysis
Fall 2002
Measures of Disease Frequency
Incidence Time: times at which new disease
occurs among population members
Incidence Rate: occurrence of new disease per unit of
person-time
Incidence Proportion: proportion of people who develop
new disease during a specified period of time
Prevalence: proportion of people who have a disease at
a specific time
Applied Epidemiologic Analysis
Fall 2002
Induction Time and Latent period
Induction time
Causal action
of a component
cause
Latent period
Disease
Occurrence
Disease
Detection
Induction time only in relation to a specific cause
Latent period - characteristic of disease, can be
influenced by screening
Applied Epidemiologic Analysis
Fall 2002
Definitions of terms in equations for measures of disease
N = number of person in sample (or population) at a given time or
at a given interval
t = a time unit,  t = the disease-free (pre-onset) time observed for
each person in sample
A = number of disease onsets
R = risk of disease onset in a specified time interval
S = survival proportion
I = incidence rate
Open population -- population size is balanced by equal entrances
and exits, at least within particular age, sex or other strata
Closed sample -- censoring needs to be taken into account
Applied Epidemiologic Analysis
Fall 2002
Incidence Rate
Numerator: count onsets among people whose event
occurred while contributing to denominator
Denominator: sum of time periods (e.g. months, years)
prior to onset across all persons at risk, defined as
those without disease
Need unit of time to interpret numerical value
Applied Epidemiologic Analysis
Fall 2002
Incidence and survival proportions
Proportion of closed
population with an
onset in a given
(constant) period
Measure of average risk (risk applies to individuals)
Range from 0 to 1, dimensionless
S = Survival proportion = 1-R
Applied Epidemiologic Analysis
Fall 2002
Relationship among measures
Incidence odds =
R
R

S
1 R
R
S  1 ,
 R
S
If R is small,
But S < 1, so
R
R
S
If R is small, population declines only slightly N  A  N
A At
R 
 It
N Nt
Applied Epidemiologic Analysis
Fall 2002
Relationship among measures (cont)
For a given interval k
Ak
Rk 
Nk
- population is closed
- no competing risks
- number of events at each time k is small
Ak
Ik 
N k tk
S k  1  Rk
 1  I k tk
S  sk  1  I k tk 
Applied Epidemiologic Analysis
Fall 2002
S  exp   I k tk 
R  1  S  1  exp  I k tk 
• Open populations:
– If open population, estimate incidence rate, use
exponential formula to get estimate of incidence
proportion
– plausible if open population subset of closed
population and loss to followup unrelated to risk
• Competing risks:
– population size not constant over subinterval
Applied Epidemiologic Analysis
Fall 2002
Prevalence
Under stationarity assumptions
D=duration of disease
1
I  N  P  t  P t
D
inflow = outflow
Prevalence proportion
- dimensionless
- range 0 to 1
- useful for health planning
- certain health outcomes
P
I D
NP
If P < .1 then
P
 I D
N
More
generally,
Applied Epidemiologic Analysis
Fall 2002
P
ID

N 1 I D
Learning Objectives
• To understand how study design and statistical
analyses are linked components in sound
epidemiologic investigations
• To appreciate the changing nature of disease
definitions and the consequent impact on design
and analysis
• To review alternative measures of disease
frequency
Applied Epidemiologic Analysis
Fall 2002