Cohort Study Designs

Ahmed MandilDept of Family & Community Medicine

College of MedicineKing Saud University

Headlines

Definitions Observational studies Characteristics Advantages, disadvantages,

problems Examples Analysis

31 Oct, 2009 2Cohort Studies

31 Oct, 2009

Observation Methods

Selected Units: individuals, groups Study Populations: cross-sectional,

longitudinal Data collection timing:

prospectively, retrospectively, combination

Data collection types: primary, secondary

3Cohort Studies

31 Oct, 2009

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.

4Cohort Studies

31 Oct, 2009

Epidemiological Measures

Frequency measures: incidence; prevalence

Effect measures: risk ratio (relative risk); odds ratio

Impact measures: attributable fraction; prevented fraction

5Cohort Studies

31 Oct, 2009

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.

6Cohort Studies

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

31 Oct, 2009 7Cohort Studies

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

31 Oct, 2009 8Cohort Studies

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.

31 Oct, 2009 10Cohort Studies

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

31 Oct, 2009 11Cohort Studies

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.

31 Oct, 2009 12Cohort Studies

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.

31 Oct, 2009 13Cohort Studies

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

31 Oct, 2009 14Cohort Studies

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.

31 Oct, 2009 15Cohort Studies

Cohort Studies (IV)

( c ) Disadvantages (of prospective):

Expensive Time-consuming May be impractical Loss to follow-up may affect

sample-size

31 Oct, 2009 16Cohort Studies

IDEAL COHORT

An ideal cohort should be: STABLE COOPERATIVE COMMITTED WELL-INFORMED

31 Oct, 2009 17Cohort Studies

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

31 Oct, 2009 19Cohort Studies

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

31 Oct, 2009 20Cohort Studies

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

31 Oct, 2009 21Cohort Studies

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

31 Oct, 2009 22Cohort Studies

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

31 Oct, 2009 23Cohort Studies

CARDIOVASCULAR DISEASE

USA: Framingham, MA; Tecumseh, MI; Evans county, GA; Muscatine, IA; Bogalusa, LA (children)

WHO MONICA (multi-center) North Karelia, Norway

31 Oct, 2009 24Cohort Studies

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

31 Oct, 2009 25Cohort Studies

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

31 Oct, 2009 26Cohort Studies

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)

31 Oct, 2009 27Cohort Studies

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)

31 Oct, 2009 28Cohort Studies

OCCUPATION BASED, TO STUDY EXPOSURES

  Benzene-workers (leukemia) Coke-oven workers (lung

cancer) Asbestos workers (lung cancer) Radium dial painters (oral

cancer)

31 Oct, 2009 29Cohort Studies

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)

31 Oct, 2009 30Cohort Studies

VETERANS

Mustard-gas poisoning from WW I (lung disease)

Vietnam Veterans (post-traumatic stress disorder, agent orange effects)

Gulf War Veterans (Gulf war syndrome)

31 Oct, 2009 31Cohort Studies

31 Oct, 2009

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

32Cohort Studies

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 )

31 Oct, 2009 33Cohort Studies

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.

31 Oct, 2009 34Cohort Studies

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)

31 Oct, 2009 35Cohort Studies

31 Oct, 2009

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]

36Cohort Studies

31 Oct, 2009

Choice of study design

Status of existent knowledge Occurrence of disease Duration of latent period Nature and availability of

information Available resources Time constraints

37Cohort Studies

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.

31 Oct, 2009 38Cohort Studies

Thank you for your kind attention

31 Oct, 2009 39Cohort Studies