Cohort Study Designs Ahmed Mandil Dept of Family & Community Medicine College of Medicine King Saud...
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Transcript of Cohort Study Designs Ahmed Mandil Dept of Family & Community Medicine College of Medicine King Saud...
Cohort Study Designs
Ahmed MandilDept of Family & Community Medicine
College of MedicineKing Saud University
Headlines
Definitions Observational studies Characteristics Advantages, disadvantages,
problems Examples Analysis
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Observation Methods
Selected Units: individuals, groups Study Populations: cross-sectional,
longitudinal Data collection timing:
prospectively, retrospectively, combination
Data collection types: primary, secondary
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Study populations Cross-sectional: where only ONE set of
observations is collected for every unit in the study, at a certain point in time, disregarding the length of time of the study as a whole
Longitudinal: where TWO or MORE sets of observations are collected for every unit in the study, i.e. follow-up is involved in order to allow monitoring of a certain population (cohort) over a specified period of time. Such populations are AT RISK (disease-free) at the start of the study.
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Epidemiological Measures
Frequency measures: incidence; prevalence
Effect measures: risk ratio (relative risk); odds ratio
Impact measures: attributable fraction; prevented fraction
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Observational Designs Exploratory: used when the state of
knowledge about the phenomenon is poor: small scale; of limited duration.
Descriptive: used to formulate a certain hypothesis: small / large scale. Examples: case-studies; cross-sectional studies
Analytical: used to test hypotheses: small / large scale. Examples: case-control, cross-sectional, cohort.
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Cross-sectional Studies (I)
(a) Characteristics: A study to detect point prevalence A reference population from which a
random sample of chosen Allows for stratification Suitable for relatively frequent conditions We are looking for both the disease and
exposure status simultaneously
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Cross-sectional Studies (II)
(b) Advantages: Feasible, relatively easy to administer Less time-consuming (compared to
prospective cohort studies) Less costly Allows for studying several conditions
/exposures at the same time Useful for health planning
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Cross-sectional Studies (III)
(c) Disadvantages: Does not establish the temporal
sequence of events necessary to suggest causal inference (temporal ambiguity)
Cannot distinguish risk from prognostic factors
Insufficient for studying of rare diseases (e.g. cancers)31 Oct, 2009 9Cohort Studies
Case-control studies (I)
(a) Characteristics: Two distinct source populations We know the disease status, looking for the
exposure status Ratio of case:controls chosen by the
investigator, minimum is 1:1. Usually cannot calculate frequency measures We have to assume that the non-cases
(control) group is representative of the same source population of cases, in order to make any causal inferences.
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Case-control studies (II)
(b) Advantages: Least expensive (smaller number of
subjects involved) Least time-consuming (relatively quick
results) Suitable for study of rare diseases
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Case-control studies (III)
(c) Disadvantages: Not suitable for rare exposures Cannot calculate frequency measures Liable to selection bias (controls are
usually selected after occurrence of cases)
Liable to recall bias -> measurement error, especially with effect estimation.
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Cohort Studies (I)
(a) Characteristics: A “cohort” is a group of people, referred to as
“disease-free population” or “population at risk” A survey is first carried out to exclude prevalent
cases from the cohort A period of "follow-up“ is specified, for possible
new cases' occurrence We know the exposure status, looking for the
disease status Historical designs are preferred under
occupational settings, for less frequent effects / exposures.
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Cohort Studies (II)
Two types are recognized: Prospective (longitudinal):
forward in time follow-up study Retrospective (historical):
backward in time study (depends on records: medical / employment). This is the type preferred under occupational settings
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Cohort Studies (III)
(b) Advantages: No / little temporal ambiguity (suggests cause-
effect relationship) Calculation of incidence rates Suitable for rare exposures Factors associated with selection cannot
influence disease status and hence the results. Several outcomes can be studied, after follow-
up starts.
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Cohort Studies (IV)
( c ) Disadvantages (of prospective):
Expensive Time-consuming May be impractical Loss to follow-up may affect
sample-size
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IDEAL COHORT
An ideal cohort should be: STABLE COOPERATIVE COMMITTED WELL-INFORMED
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Examples of Study Cohorts
1. General population
2. Selected occupational groups, e.g. health professionals (physicians, nurses, lab technologists, etc), manufacturers of mercury batteries for vehicles; asbestos workers, miners, etc31 Oct, 2009 18Cohort Studies
Sources of Cohorts
Population groups Occupational settings
(employment, medical records) Hospital registers (medical
records) Death certificates
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Follow-up Techniques
1. PERIODICAL MEDICAL EXAMINATIONS AND MAILED QUESTIONNAIRES
2. DIRECT PERSONAL INTERVIEWS OR EXAMINATIONS 3. VIDEOCONFERENCE, NEIGHBORS, FRIENDS AND RELATIVES4. LOST PERSONS CAN BE TRACED THROUGH THE LETTERS, FROM
THEIR RELATIVES AND FRIENDS5. MIGRATED COHORT SUBJECTS CAN ALSO BE TRACED THROUGH
TRAVEL AND IMMIGRATION AUTHORITIES6. DEAD PERSONS - LOCAL OR REGIONAL MORTALITY REGISTERS OR DEATH CERTIFICATES
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Problems during Follow-up
FOLLOW-UP OF A LARGE GROUP LIMITED RESOURCES TIME SCARCITY PAUCITY OF TRAINED PERSONNEL ATTRITION, LOSS ON FOLLOW UP ETHICAL CONCERNS
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Attrition Reduction
OBTAINING THE INFORMED CONSENT RECORDING COMMITMENT TO CONTINUE AND
COOPERATE IN THE STUDY TRACING LOST SUBJECTS, TRYING TO INCLUDE
THEM IN THE STUDY CONSIDERING INFORMATION OF LOST PERSONS
AT THE TIME OF ANALYSIS KEEPING NON-RESPONSE AT A LOW LEVEL TO
IMPROVE THE VALIDITY
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Examples of Cohort Studies
1. POPULATION-BASED
1. CARDIOVASCULAR
2. CHILD HEALTH
3. SPECIAL EXPOSURES
2. NON-POPULATION BASED
1. OCCUPATIONAL – for convenience
2. OCCUPATIONAL – to study the occupation
3. HEALTH CARE SETTINGS
4. VETERANS
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CARDIOVASCULAR DISEASE
USA: Framingham, MA; Tecumseh, MI; Evans county, GA; Muscatine, IA; Bogalusa, LA (children)
WHO MONICA (multi-center) North Karelia, Norway
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Framingham Study (1951 – present time)
1ST Step: Selection of cohorts Initially, 5209 subjects were enrolled
into the study Currently, thousands of people are
followed up, both for cardiovascular risk factors (e.g. high serum cholesterol, smoking, hypertension, BMI, etc) and possible outcomes
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CHILD HEALTH National Birthday Trust Studies
One week of births in England and Wales in 1946, 1958, 1970, etc
Project on Premature InfantsAll births < 1,500 g or < 32 weeks in a specific nation
The National Children Study http://www.nichd.nih.gov/about/despr/despr.htm
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SPECIAL EXPOSURES Atomic Bomb Casualty Commission
(ABCC): Hiroshima and Nagasaki survivors (effects of radiation)
Dutch famine survivors (effects of starvation)
Seveso (effects of dioxin exposure)
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OCCUPATION-BASED COHORTS,
CONVENIENT FOLLOW-UP British Doctors Study
(Doll – smoking) Nurses Study
(Speizer, Willett – many issues) London civil servants
(Marmot - SES) Taiwanese civil servants
(Beasley – liver cancer)
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OCCUPATION BASED, TO STUDY EXPOSURES
Benzene-workers (leukemia) Coke-oven workers (lung
cancer) Asbestos workers (lung cancer) Radium dial painters (oral
cancer)
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SAMPLING FROM HEALTH CARE SETTINGS
National Collaborative Perinatal Project:Almost all pregnancies at 12 medical centers 1959-1966 – N about 50,000. (causes of CP)
Child Health and Development Studies:
Kaiser-Permanente births (many issues) Patients treated with radiation for
polycythemia or ankylosing spondylitis (radiation and cancer)
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VETERANS
Mustard-gas poisoning from WW I (lung disease)
Vietnam Veterans (post-traumatic stress disorder, agent orange effects)
Gulf War Veterans (Gulf war syndrome)
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2x2 Table
Disease No Disease
Exposed a = Exposed Cases
b = Exposed Non-Cases
Total exposed (a + b)
Not Exposed c = Non-Exposed Cases
d = Non-Exposed Non-Cases
Total non-exposed
(c + d)
Total Cases Total Non-Cases
n =
a + b + c + d
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INCIDENCE RATES
INCIDENCE AMONG THE EXPOSED (NEW CASES AMONG THE SMOKERS) = (A/ A+B)
INCIDENCE AMONG THE NON-EXPOSED (NEW CASES AMONG THE NON-SMOKERS) = (C/ C+D )
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Risk Calculations
Relative Risk or Risk Ratio (RR) (RR) = [A / (A+B)] / [C / C +D)] (incidence in
the exposed (smokers) / incidence in the non-exposed (non-smokers)
Attributable risk (AR = excess risk/ incidence among the exposed (AETIOLOGICAL FRACTION)
Population attributable risk (PAR) = incidence in the total population minus incidence among the non-exposed.
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RR Interpretations Unity: exposure has no effect on outcome
in the studied population (cohort) More than 1: exposed have a higher risk of
developing the outcome, compared to the unexposed
Less than 1: either no relationship, or a “protective” one exists (e.g. effect of interventions, immunization, health education, management, etc)
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Frequency & Effect Measures
Design Frequency Effect Calculation
Cross-sectional
Prevalence Odds Ratio ad / bc
Case-control Neone Odds Ratio ad / bc
Cohort Incidence Risk Ratio Ie [a / a + b] /
Iue [c /c + d]
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Choice of study design
Status of existent knowledge Occurrence of disease Duration of latent period Nature and availability of
information Available resources Time constraints
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References
1. Last JM. A dictionary of epidemiology. 5th edition. New York, Oxford, Toronto: Oxford University Press, 2008.
2. Gordis L. Epidemiology. Third edition. Philadelphia, London, New York, Sydney: W.B. Saunders, 2004.
3. Beaglehole R, Bonita R, Kjellstrom T. 2nd edition. Basic epidemiology. Geneva: WHO, 2006.
4. Friis RH, Sellers TA. Epidemiology for public health practice. Gaithersburg, MD: Aspen Publishers, 1999.
5. Kelsey JL, Thompson WD, Evans AL. Methods in observational epidemiology. New York: Oxford University Press, 1986.
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Thank you for your kind attention
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