analytic epidemiological designs
DESCRIPTION
Basic Question in Analytic Epidemiology Exposure DiseaseTRANSCRIPT
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Analytic Epidemiological
Designs
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Basic Question in Analytic Epidemiology
Exposure Disease
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Cohort Study
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Cohort is an ancient Roman military unit of 300 – 600 men.
A group of soldiers
marching forward in
battle
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In epidemiology, cohort is a group of
people who share a common characteristic
or experience within a defined period (e.g.,
are born, are exposed to a drug or a
vaccine, etc.).
Thus a group of people who were born
on a day or in a particular period, say 1980,
form a birth cohort.
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A study design that follows over time one or more
populations (called cohorts) to determine which
patient characteristics (risk factors) are
associated with the development of a disease or
outcome.
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Key Point:
Presence or absence of risk factor
is determined before outcome
occurs.
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General consideration while selection of cohorts
Both the cohorts are free of the disease.
Both the groups should equally susceptible to disease
Both the groups should be comparable
Diagnostic and eligibility criteria for the disease should be defined well in advance.
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timeStudy begins here
Studypopulation
free ofdisease
Factorpresent
Factorabsent
disease
no disease
disease
no disease
presentfuture
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ANALYSIS
• Calculation of incidence rates among exposed and non exposed groups
• Estimation of risk
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Incidence rates of outcome
N
dc
ba
Yes No
Disease Status
Yes
No
Exposure Status
a+b
c+d
b+d a+c
Total
Exposed
Non Exposed
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Relative Risk• General interpretation of relative risk (RR)
• If RR > 1 Positive association between disease and risk factor = 1 No association
< 1 Negative association • The “reference group” is in the denominator• Reference group generally chosen as the “unexposed” group• RR estimates the magnitude (strength ) of association between
exposure & disease
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Risk estimation
AR: Attributable RiskExcess risk attributed to exposure
AR%: Attributable Risk percentExpress the gain or the benefit if
the exposure removed
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Incidence
I. among
exposed
A R% A R
Base-line risk
I. among non
exposed
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Smoking Lung cancer Total
YES NO
YES 70 6930 7000
NO 3 2997 3000
73 9927 10000
Find out RR and AR for above data
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• Incidence of lung cancer among smokers70/7000 = 10 per 1000
• Incidence of lung cancer among non-smokers3/3000 = 1 per thousand
RR = 10 / 1 = 10(lung cancer is 10 times more common among smokers than non smokers)
AR = 10 – 1 / 10 X 100= 90 %
(90% of the cases of lung cancer among smokers are attributed to their habit of smoking)
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Timeframe of Studies• Prospective Study - Outcomes have not yet occurred as
study begins. looks forward, looks to the future, examines future events, follows a condition, concern or disease into the future
time
Study begins here
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Timeframe of Studies• Retrospective Study - Outcomes have already occurred as
the study begins. “to look back”, looks back in time to study events that have already occurred
time
Study begins here
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Strengths
• We can find out incidence rate and risk• More than one disease related to single
exposure • can establish cause - effect• good when exposure is rare• minimizes selection and information bias
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Weaknesses
• losses to follow-up• often requires large sample• Ineffective for rare diseases• long time to complete• Expensive• Ethical issues
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...… several famous large cohort
studies continue to provide important
information..…
Framingham Heart Study
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Case Control study
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Why case-control study?• In a cohort study, you need a large number of the
subjects to obtain a sufficient number of case, especially if you are interested in a rare disease.
• Gastric cancer incidence in Japanese male: 128.5 / 100,000 person year
• A case-control study is more efficient in terms of study operation, time, and cost.
Case Control
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Definition….• The case-control study is an analytic epidemiologic research design in
which the study population consists of 2 groups who either have (cases) or do not have a particular health problem or outcome (controls).
• The investigator looks back in time to measure exposure of the study subjects. The exposure is then compared among cases and controls to determine if the exposure could account for the health condition of the cases.
Case Control
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Case-Control Studies
Cases: DiseaseControls: No disease
Case Control
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Case-control study - Sequence of determining exposure and outcome status
• Step1: Determine and select cases of your research interest
• Step2: Selection of appropriate controls
• Step3: Determine exposure status in both cases and controls
Case Control
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Design of Case Control Studycases with the disease
Should have clear case definition i.e. clear criteria for defining the disease of interest
May be taken from clinics, hospitals, disease registries
Preferred newly diagnosed
Case Control
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Design of Case Control StudyAppropriate controls without the disease
Should comes from the same study base or population as cases
Can come from geographical sample, medical inistitution, neighbors, friends,….
Can have multiple control groupsMay be matched
Case Control
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1) a population-based case-control studyBoth cases and controls are recruited from the
population.
2) a case-control study nested in a cohortBoth case and controls are members of the cohort.
3) a hospital-based case-control studyBoth case and controls are patients who are
hospitalized or outpatients.Controls with diseases associated with the exposure
of interest should be avoided.
Types of case-control studies
Case Control
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Case
-Con
trol D
esig
nStudy
population
Cases(disease)
Controls(no disease)
factor present
factor absent
factor present
factor absentpresent
past
time
Study begins here Case Control
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Disease
+ -
Exp + a b
Exp - c d
d 1 d 0
Case-control Study – DesignSelect subjects on the basis of disease status
ORa /cb /d
adbc
Case Control
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Interpretation of (OR) odds ratio> 1 means the exposure is a risk factor.
= 1 means the exposure is not associated with the disease.
< 1 means the exposure is protective
Case Control
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Lung cancer Controlscases
N=100N=100Smokers (NOT recently started)
↓ ↓ 70 40
An example of unmatched case-control study
Cases Controlssmoker 70 40
Non-smoker 30 60
Odds ratio=Case Control
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Advantages
1. Simple, not time consuming (quick) and inexpensive.2. Suitable for rare diseases. 3. Can examine multiple exposures for a single disease.4. Support, but not provide causal association.5. Suitable for diseases of long latency period6. Dose response relationship can be assessed7. Small sample size8. No ethical problem
Case Control
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Disadvantages1. Recall bias 2. Selection bias3. Different diagnostic tools so “case groups” may be not
homogenous.4. The chosen cases are selective survivors (the history of
died cases may be different) thus the cases does not represent a universe of cases.
5. The time sequence between the exposure and the disease is not clear.
6. Control of confounding factors7. Not suitable for rare exposure8. Only one outcome
Case Control
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Controlling extraneous variables (confounding)• Exposure of interest may be confounded by a factor that is associated
with the exposure and the disease i.e., is an independent risk factor for the disease
A B
CCase Control
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How to control for confounding• At the design phase
• Randomization• Restriction• Matching
• At the analysis phase• Age-adjustment• Stratification• Multivariable adjustment (logistic regression modeling, Cox
regression modeling)
Case Control
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MatchingSelection of controls to match specific characteristics of cases
a) Frequency matchingSelect controls to get same distribution of variable as cases (e.g. age group)
b) Individual matchingSelect a specific control per case by matching variable (e.g. date of birth)
Case Control
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Intervention or Experimental studies
Therapeutic• Study population
• Patients with disease
• Objectives• Cure patients• Diminish symptoms• Prevent recurrence of disease/risk of
death
Preventive• Study Population
• Population at risk
• Objectives• Reduce the risk of developing disease
Clinical trials are the most well known experimental design Such designs are differentiated from observational designs by the fact that there is manipulation of the study factor (exposure), and randomization (random allocation) of subjects to treatment (exposure) groups.
RCT
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Why Performed ?
1. Provide stronger evidence of the effect (outcome) compared to observational designs, with maximum confidence and assurance
2. Yield more valid results, as variation is minimized and bias controlled
3. Determine whether experimental treatments are safe and effective under “controlled environments” (as opposed to “natural settings” in observational designs), especiallywhen the margin of expected benefit is doubtful / narrow (10 - 30%)
RCT
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Experimental Studies• A study in which a population is selected for a planned trial of a regimen,
whose effects (consequences of some treatment on some outcome) are measured by comparing the outcome of the regimen between 2 groups.
• The subjects in the study who actually receive the treatment of interest are called the treatment group.
• The subjects in the study who receive no treatment or a different treatment are called the comparison group.
RCT
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Expe
rimen
tal
Desig
n
timeStudy begins here (baseline point)
Studypopulation
Intervention
Control
outcome
no outcome
outcome
no outcome
baselinefuture
RANDOMIZATION
RCT
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Types of trials
B lind ed N o t b lind ed
R a nd o m ised N o t ran d om ised
C o n tro lled N o t co n tro lled
T ria l
RCT
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Design - conductDifferent phases
• Enrollment (selection of study population)
• Allocation of study regimes
• Follow-up• Maintainence and assessment of adherence• High and uniform rates of ascertainment
• Analysis and interpretation
RCT
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Population hierarchy for intervention study
Reference population
Experimental populationExclusion criteriaInformed consent
ExcludedRefused
Study population
Intervention group Control group
Outcome
Losses to follow-up Losses to follow-up
Random allocation
RCT
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RCT Advantages (I)
• the “gold standard” of research designs. They thus provide the most convincing evidence of relationship between exposure and effect. Example:
• trials of hormone replacement therapy in menopausal women found no protection for heart disease, contradicting findings of prior observational studies
RCT
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RCT Advantages (II)
• Best evidence study design• No inclusion bias (using blinding)• Controlling for possible confounders• Comparable Groups (using randomization)
RCT
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Disadvantages
• Large trials (may affect statistical power)• Long term follow-up (possible losses)• Compliance• Expensive• Public health perspective ?• Possible ethical questions
RCT
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• Blinding
• Hiding information about the allocated study regimes from key participants in a trialDepending on
outcome of interestEthics, feasibility, compromise
By Using Placebo which is Inert medication, i.e No effect, intended to give the patient the perception they are receiving treatment
Types:1. Single – blind :Observer or subject are kept ignorant about allocated study regime2. Double blind :Both observer and the subject are kept ignorant about allocated study
regime
RCT
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