Mr.

Renjulal Yesodharan

Meaning
Cohort studies are a particular kind of trend

study in which specific subpopulations are

examined over time.

COMPONENTS OF THE COHORT STUDY DESIGN

A generic cohort study design has three

major components.
(1) A defined population
(2) Exposure status (3) Outcomes.

Components

 All cohort studies begin with a defined

cohort.
A cohort may be most generally defined as a

band or a group
Rothman and Greenland observe that In

epidemiology, the word cohort is often used

to designate a group of people who share a

common experience or condition.

 This group may comprise all of the defined

population or simply a sample from that

defined population.

Cohort
Those people within a geographically or

otherwise

delineated

population

who

experienced the same significant life event

within a given period of time

 A cohort may be defined as the aggregate

of individuals who experienced the same

event within the same interval 5
Group of subjects selected according to

one or more common characteristic(s) and

followed over time in order to identify,

describe or quantify an event

Exposure or non-exposure
Health sciences cohort designs normally

focus upon a single exposure or intervention

that researchers suspect causes an outcome.

 In the health sciences, these exposures or

non-exposures

can

span

range

of

conditions.
An

exposure

can

include

personal

characteristics such as the presence of a psychiatric condition.

 An exposure can be either an uncontrolled

event or a conscious decision to make a

medical intervention. Or, an exposure

actually can include people's behavior.

Cohort studies can measure exposures in

different

ways:

intensity,

duration,

regularity, or even variability.

Outcomes
In a cohort study, not all hypothesized

outcomes actually occur. Sometimes the hypotheses, null hypotheses, or alternative hypotheses fail to predict what turns out to be a completely unexpected outcome.

 One cohort study produced the unexpected

finding that moderate amounts of alcohol might have beneficial health effects. Another cohort study on the risk of developing Parkinson disease noted the possible preventive effect of caffeine. In other instances, cohort studies yield no observed outcomes.

CHARACTERISTICS OF COHORT STUDY

It starts with a group of subjects who lack a

positive history of the outcome of interest

and are at risk for the outcome.
Cohort studies can be thought of as going

from cause to effect.

 The exposure (s) of

interest is (are)

determined for each member of the cohort

at baseline or time of study; then the group

is followed through time to document the

incidence of an outcome among the exposed

and non-exposed members.

 Possible outcome measures include the

incidence

of

disease

(cohort

studies

measure
mortality,

disease
health

incidence
status, and

directly),
certain

biological parameters, which are examined

for changes that occur as a result of exposure

to a risk factor.

 Cohort

studies

include
one

at
to

least

two

observation

points:

determine

exposure status and eligibility and a second

(or more) to determine the number of

incident cases that developed during followup.

 Two or more observation points permits the

calculation of disease rates, which cannot be obtained with only a single time point of observation.
In cohort studies, the individual forms the unit of

observation and the unit of analysis,

Cohort studies almost always involve the collection

of primary data, although secondary data sources are used sometimes for both exposure and disease assessment.

SAMPLING STRATEGIES OF COHORT STUDIES

Population based Cohort Studies.

Exposure-Based Cohort Studies

SAMPLING STRATEGIES OF COHORT STUDIES

1. Population Based Cohort Studies

It includes either an entire population or a

representative sample of the population.

It starts with N; the total of exposed (A + B)

and non-exposed (C + D) subjects is determined as part of the research process.

Example -1
A cohort study of CHD was initiated in 1948 in

Framingham, Massachusetts.
When the study commenced, the town had a

population of 28,000; the study design called for a random sample of 6,500 from the targeted age

range

of

30

to

59

years.

This

sample,

representative of the population, was followed subsequently for changes in risk factors and incidence of disease.

 In a population-based cohort study the

proportion of the population exposed can be

determined either directly (entire) or

indirectly(fraction).
In a population-based cohort, exposures are

unknown until the first period of observation when exposure information is collected.

 After

administration of biologic

of

questionnaires, samples, clinical

collection

examinations, or physiologic testing, the cohort can be divided into two or more exposure

categories as a result of what is learned from the

subjects. (i.e., exposed versus non-exposed).
The non-exposed subjects become an internal

comparison group.

 Sometimes, exposure may be categorized

along a continuum, called a continuous

variable, which is a type of variable that has

an infinite set of possible values within a

specified range.

Exposure-Based Cohort Studies

Exposure

based

studies

has

benefits

regarding generalizability of results and the

measures of effect that can be estimated.

However, population-based cohort designs

are not efficient for rare exposures.

Example 1 The experiments with animals provided evidence that exposure to lead causes long-term neurologic toxicity. The amounts of lead used were much greater than those found in most human exposures. Certain occupational groups, however, such as those involved in battery production, might have sufficient occupational exposure to incur significant health risks. Although one could consider using a case-control study, because the proportion of the population employed in the battery manufacturing industry is low, there would likely be few cases or controls with exposure in the study sample. An alternative approach might be to assemble an exposure-based cohort of employees in battery production factories, quantify levels of exposure using job titles and assignments, and determine incidence rates of neurotoxicity.

OUTCOME MEASURES IN COHORT STUDIES

Three categories of outcomes: discrete

events, levels of disease markers, and

changes in disease markers can be assessed

along with the incidence of disease

(principal outcome measure).

TYPES OF OUTCOMES FOR COHORT STUDIES

Discrete events Single events -Mortality -First occurrence of a disease or healthrelated outcome -Incidence (density) -Cumulative incidence (risk) -Ratios (incidence density and cumulative incidence)

Multiple occurrences:
Of disease outcome

Of transitions between states of

health/disease
Of transitions between functional states

Level of a marker for disease or state of health Change in functional/physiologic/biochemical/ anatomical marker for disease or health
Rate of change -Patterns of growth and/or decline -"Tracking" of markers of disease/health Change in level with time (age)
(Tager Ib. Outcomes in cohort studies Epidemiologic review: 1998. 20. P16)

COHORT DESIGNS
The basic feature of all cohort studies is

measurement of exposure and follow-up for disease.

The

variations

are

prospective

and

retrospective cohort studies (fig: 3).

Prospective Cohort Studies:

A

prospective

cohort

study

is

purely

prospective in nature and is characterized by determination of exposure levels at baseline (the present) and follow-up for occurrence of disease at some time in the future. The sampling strategy may be population-based or defined by a special exposure of interest.

Advantages to prospective studies are:

Prospective cohort studies enable the investigator to

collect data on exposures.

The collection of exposure information at baseline

may result in the most direct and specific test of the

study hypothesis

 (e.g.

Assessment of diet, physical activity,

alcohol use, occupation, coping skills, and quality of life, each of which can be assessed with a few specific items or a comprehensive battery of items).

 The size of the cohort to be recruited is under greater

control by the investigators than is the size of a retrospective cohort (Cohort studies that rely on historical records are sometimes fixed in size).
Biological and physiological assays can be performed with

decreased concern that the outcome will be affected by the underlying disease process. (Examples include

measures of serum factors or nutrient levels, and medical

examinations (e.g., specific functional tests, antibody titers, or cholesterol levels).

 Direct measures of the environment (e.g.,

indoor radon levels, electromagnetic field radiation, cigarette smoke concentration, or chlorination byproducts in the water

supply) can be made in order to define exposures precisely.

Retrospective Cohort Study

Despite the substantial benefits of prospective

cohort studies, investigators must wait for cases to accrue while conducting such a study. Depending upon the size of the cohort and the prevalence of a disease in the population, several years could elapse before meaningful analyses are feasible.

 Retrospective cohort study makes use of

historical data to determine exposure level

at some baseline in the past; "follow-up" for

subsequent occurrences of disease between

baseline and the present is performed.

Example.1:
Sellers and colleagues performed a follow-up beginning in the year 1991 of a cohort of 426 families originally ascertained

between 1944 and 1952 at the Dight Institute of Genetics, at the

University of Minnesota. Three-generation pedigrees were constructed at baseline with data collected from mothers, aunts,

sisters, and daughters of breast cancer patients. Records of

breastfeeding, reproductive history, and validated occurrences of cancer were stored. Thus, when the family members were re-

contacted and interviewed regarding subsequent occurrences of

cancer, almost 50 years of follow-up was completed during a fiveyear period of funding

Example2:
Hartmann and colleagues18 at the Mayo Clinic, using an

index of surgical procedures, were able to construct a cohort of women who received prophylactic mastectomy between 1963 and 1986. Details were available in the medical record on type of surgery, age at surgery, family history of cancer, and complications following surgery. Follow-up through 1997 was performed to identify subsequent occurrences of breast cancer. Analyses based on a median 14 years of follow-up were possible, even though the actual study took less than five years to complete.

Advantages to retrospective cohort studies are:

In a relatively short period of time, a significant

amount of follow-up data may be accrued.

The amount of exposure data collected can be quite

extensive and can be available to the investigator at minimal cost.

Ambispective cohort study

A

design

that
(to

makes

use

of

both

retrospective

determine

baseline

exposure) and prospective (to determine

disease incidence in the future) features is

the historical prospective cohort study (also

known as an ambispective cohort study).

MEASURES OF INTERPRETATIONSANALYSIS OF COHORT STUDIES

 Observed frequencies are showed in the table: 1, where

a is the number of persons who are exposed to factors and have the disease, b is the number of persons who are not exposed to the factors and not have the disease, c is the number of persons who are exposed

to the factors and not have disease and d is the

number of persons who are not exposed and not have the disease.

 In the simplest case of two levels of exposure

(yes/no), two incidence rates are calculate.

The relative risk is defined as the ratio of the

risk of disease or death among the exposed,

to the risk among the unexposed.

 The risk of disease in the individuals exposed and unexposed to the factor of interest in the population can be estimated in the same way.

 A relative risk of 1.0 implies that the risk

(rate) of disease among the exposed is no different from the risk of disease among

the non-exposed. A relative risk of 2.0

implies that risk is twice as high, whereas a

relative risk of 0.5 indicates that the

exposure or interest is associated with half the risk of disease.

PRACTICAL CONSIDERATIONS, ISSUES AND CHALLENGES

Availability of Exposure Data
In most situations, investigators will find

themselves trying to weigh the trade-offs

between a retrospective study design versus the

value of collecting the primary' exposure data

in the most ideal manner in a prospective

cohort design.

Size and Cost of the Cohort

There is a direct relationship between size and cost,

and resource constraints typically influence design

decisions. One approach to design cohorts with the greatest future value is to focus initial development on the collection of risk factor data and biological samples, with subsequent (future) or parallel (nested

studies) grants to obtain funding for analyses of the

samples.

Data Collection and Data Management An axiom of epidemiologic research design is that larger studies necessarily are more demanding than smaller ones with regard to challenges in data collection and data management. Coordination of activities in the field is especially complex when multiple sites are necessary for recruitment. Additional challenges may arise from data entry, especially if individual sites enter their own data for transmittal to the coordinating center. In these situations, explicit protocols for quality control (e.g., double entry of data, and scannable forms) should be considered in the design and implementation stage.

 The organizational and administrative burdens

are increased even further when there are

multiple levels of data collection (such as

telephone interviews, mail-out questionnaires, consent forms to access medical records, and collection of biological samples) at multiple time periods (especially when active follow-up is needed).

 Cohort study research protocols may require

elaborate

data-management

systems

to

monitor the status of the various components

of data collection.

 Management of data from cohort studies

can be incredibly challenging and should be considered when staffing needs are being defined. Challenges arise from data

collected from multiple sources, merging of files, and "cleaning" of data files.

Follow-up Issues
The value of cohort studies can be realized only

if an effective system can be implemented to

follow the cohort for subsequent occurrence of

disease or other outcomes. Active follow-up is

becoming increasingly labor intensive and

oftentimes frustrating, especially in our mobile

society where addresses change often.

 Passive follow-up is possible when databases

containing the outcomes of interest arc

collected and maintained by organizations

outside the investigative team. Passive

follow-up is clearly not an option for many

diseases.

Sufficiency of Scientific Justification There should be considerable scientific rationale for a cohort study. This rationale should be grounded on prior research from various perspectives: study designs other than cohort studies; several different investigators; and several different study populations. Additional justification for cohort studies may come from laboratory experiments or animal studies.

ADVANTAGES AND DISADVANTAGES OF COHORT STUDY

Advantages of cohort studies
The time sequence of events can assess

They can provide information on a wide range

of outcome
It is possible to measure the incidence/risk of

disease directly.

 It

is possible to collect very detailed information on exposure to a wide range of factors. It is possible to study exposure to factors that are rare Exposure can be measured at a number of time points so that changes in exposure over time can be studied. There is reduced recall and selection bias compared with Case-control studies

Disadvantages of cohort studies In general, cohort studies follow individuals for long periods of time, and are therefore costly to perform. Where the outcome of interest is rare, a very large sample size is needed. As follow-up increases, there is often increased loss of patient as they migrate or leave the study, leading to biased results

 As a consequence of the long time-scale, it is

often difficult to maintain consistency of

measurements and outcomes over time

Furthermore, individuals may modify their

behaviour after an initial interview
It is possible that disease outcomes and their

probabilities, or the etiology of disease itself, may change over time

 REFERENCES Glenn ND. Cohort analysis. Beverly Hills, CA: Sage Publications,

1977:8 Ryder, N.B. (1965). The cohort as a concept in the study of social change. American Sociological Review 30(6): 843-861 Bgaud BB. in Dictionary of Pharmacoepidemiology, John Wiley & Sons, Ltd, Chichester, UK. 2000: 36. Friis R, Sellers T. Epidemiology for Public Health Practice. Gaithersburg, MD: Aspen Publishers, Inc. Melnyk B M, Fineout, Overholt E. Evidence-Based Practice in Nursing & Healthcare: A Guide to Best Practice (2nd edition). Philadelphia: 2011. Petrie A Sabin C. Medical statistics at a glance, 2nd ed, Blackwell Science, 2005. Riegelman R K. Studying a study and testing a test- how to read the medical evidence. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC128954/