ACTIVITY 6: COHORT STUDIES

OBSERVATIONAL STUDIES

• Attempt to

establish an association between a characteristic (or exposure) and an outcome

OBSERVATIONAL STUDIES

• Group of individuals are

observed and evaluated over time in a natural setting

OBSERVATIONAL STUDIES

• Investigators

• are not attempting to influence the individuals or their environment by applying an intervention

  • Cause and effect cannot be determined

OBSERVATIONAL STUDIES

examples

cohort & case control study

Experimental Trials

Have a specific intervention within a defined patient sample

Observational Study

Used to determine associations between variables often involving a larger population

OBSERVATIONAL STUDY DESIGN

• Used in specific situations such as

• when large populations of patients must be followed over extended periods of time

OBSERVATIONAL STUDY DESIGN

timeline 

Can be

• prospective,

• retrospective,

• single snapshot (or slice) in time

OBSERVATIONAL STUDY DESIGN

• Interpretation of results from these types of trials

only allows associations to be formed, rather than true cause-and-effect relationships

OBSERVATIONAL STUDY DESIGN

• Types:

• Cohort Studies

• Case-control Studies

• Cross-sectional Studies

CROSS-SECTIONAL

• Outcomes and exposures both occur only at one point in time

• Also known as single snapshot

CASE-CONTROL

• Outcomes are known (today)

• Researchers use databases to go back in time to look at exposures

RETROSPECTIVE COHORT

• Exposures occurred sometime in the past

• Through database manipulation and/or chart review, patients are followed over time to determine the outcome of the exposure

PROSPECTIVE COHORT

• Exposures are known today within a particular cohort

• The cohort is followed over time (i.e., in the future) to determine the outcome of the exposure

COHORT STUDY

• Consists of subjects at risk for a disease(s) whose exposure status (e.g. aspirin use) is assessed at baseline and who are followed-up over time to detect incident (new cases of disease), such as cardiovascular disease (outcome)

The term “exposure” or “exposure status” is typically used to _

describe an innate trait, or contact, experience, or consumption, etc. with a potential risk or protective factor whose effect on the outcome is being examined in the study

COHORT STUDY

types

• Cohort Studies

• Prospective Cohort

• Retrospective Cohort

• Ambidirectional

COHORT STUDY

is interested in _

• what happens to patients (i.e. the outcome) after an exposure to a drug or risk factor

COHORT STUDY

• evaluate the _

relative risk of something occurring within a population over time (i.e., incidence rates)

RETROSPECTIVE COHORT STUDY

aka

noncurrent or historical cohort study

RETROSPECTIVE COHORT STUDY

• Studies that

go back in time via chart reviews with the help of large databases/electronic medical records and “follow” or observe patients having a particular exposure or risk factor of interest over time

RETROSPECTIVE COHORT STUDY

• Nature of the cohort is that

• it has already been created or exists in a database

  • Researchers in the present can go back and utilize that data for whatever purpose they decide to study

RETROSPECTIVE COHORT STUDY

• Able to make associations between

characteristics and an outcome and can establish incidence of an outcome 

RETROSPECTIVE COHORT STUDY

• identify a _ 

population of interest and measure characteristics that could be predictive of an outcome

• All aspects of the study have already occurred;

• The cohort has already been assembled (in some fashion)

• And outcomes and measurements have already occurred (or occur in the present)

RETROSPECTIVE COHORT STUDY

• Time frame begins in the

• past, observing a cohort over time with completion in the present

RETROSPECTIVE COHORT STUDY

disadvantage 

information may be incomplete, inaccurate, and/or measured inappropriately

RETROSPECTIVE COHORT STUDY

• Rates of outcomes in individuals with or exposed to the characteristic of interest are compared to those not exposed in order to determine if any association can be made between the characteristic and an outcome 

RETROSPECTIVE COHORT STUDY

sample study

P	16,320 patients who were admitted to the Mayo Clinic in 2010 and who had orders for zolpidem
I	Zolpidem
O	Increase risk for falls

RETROSPECTIVE COHORT STUDY

sample study

P	People who have baseline QT prolongation on ECG
I	Azithromycin
O	Cardiovascular death

RETROSPECTIVE COHORT STUDIES IN EVIDENCE-BASED MEDICINE (EBM)

• Efficient and inexpensive designs to answer a research question 

• Rely on outcomes that have already occurred and data that have already been recorded

• Large databases serve as reservoirs of information 

• Still able to identify associations that have implications for clinical practice

MATCHING

• In the process of creating two or more groups of patients in observational studies, investigators may use a process

• Subjects that are in different treatment assignments can be paired or matched based on certain baseline characteristics (e.g., sex, age, race)

MATCHED CONTROLS

• Predisposition to the disease of interest should be similar in both groups

(1) Patients who received no antibiotic but were matched based on a  cardiovascular risk score 

(2) Patients taking other antibiotics who had an established cardiovascular risk

PROSPECTIVE COHORT STUDY

• Subjects are followed from

• baseline or  “now” (today) until a time/point in the future

PROSPECTIVE COHORT STUDY

• Investigators first identify a

• population of interest (the cohort) and measure characteristics that could be predictive of an outcome before the outcome occurs

PROSPECTIVE COHORT STUDY
Determine the

incidence of an outcome or event within a population and investigate potential causes or protective factors

PROSPECTIVE COHORT STUDY
Time frame is

the present with measurements of predictive characteristics and confounders taken at baseline and periodically in the future

PROSPECTIVE COHORT STUDY
Individuals are followed over a specified period of time while

outcomes are measured

PROSPECTIVE COHORT STUDY

• At study completion,

• rates of individuals who experienced the outcome and who had the characteristic of interest are compared to those who experienced the outcome but did not have the characteristic of interest

  • These associations are measured through relative risk

PROSPECTIVE COHORT STUDY

P	American Population
I	Intake of coffee or tea
O	Oropharyngeal Cancer mortality

PROSPECTIVE COHORT STUDIES IN EVIDENCE-BASED MEDICINE (EBM)

Framingham Study (1948)
P	5,209 American men and women
I	Risk factors (high blood pressure, high cholesterol, unhealthy eating patterns, smoking, physical inactivity, or unhealthy weight, patient’s sex or race
O	Development of cardiovascular disease

AMBIDIRECTIONAL COHORT STUDY

• Looking both forward and backward in time

• Involves both prospective and retrospective components

AMBIDIRECTIONAL COHORT STUDY

EXAMPLE 

Air Force Health Study looking at pilots involved in aerial spraying of herbicides including Agent Orange during the Vietnam War

Air Force Health Study looking at pilots involved in aerial spraying of herbicides including Agent Orange during the Vietnam War

RETROSPECTIVE 

• observed the incidence of cancer and mortality from time of exposure in the war through the 1980s

Air Force Health Study looking at pilots involved in aerial spraying of herbicides including Agent Orange during the Vietnam War

PROSPECTIVE 

observing these men well into the future

 OPEN / DYNAMIC

• Participants may enter or leave based on changing characteristics, such as smoking, alcohol consumption, occupation, specific geographical location

FIXED

• Identified by an unchangeable event such as having undergone a surgical procedure or been exposed to a potential toxin like Agent Orange at a specific time. 

  • Exposures do not change or are considered fixed

CLOSED

Involves an unchangeable event that has a specific starting and ending point and involves follow-up

COHORT STUDY

• Used to investigate the

• cause of a disease or the benefits and safety risks of both medication and procedures 

• Simplest approach for studying disease incidence

COHORT STUDY

disadv 

expense and time consumption

RELATIVE RISK

- Attempts to establish a relationship between an exposure or risk factor and a subsequent outcome.

• Risk of developing a disease or adverse event in those participants exposed to a specific variable compared to those not exposed to that variable

COHORT STUDY

will not perform a 

randomization process that occurs to ensure that each participant has an equal opportunity to be in either the exposed or non-exposed group

• It is intended to group together from the start individuals who were exposed to the variable of interest. 

Cohort study has no assurance of: 

• Similar demographics for exposed and non-exposed groups

• Similar exposure levels to the variables

TWO CONCERNS DUE TO THE LACK OF RANDOMIZATION

• selection bias

• cofounder 

SELECTION BIAS

• Is a potential whenever the investigator is allowed to decide who is brought into the study and who is not selected to participate 

  • An investigator either knowingly or unknowingly selects from the general population only the healthiest individuals to be assigned to the non-exposure group while at the same time a mixture of healthy and unhealthy participants are selected for the exposure group

COFOUNDER

• Is a variable related to one or more variables defined in the study; it is common since they are the product of not using a randomization schedule 

OTHER CONCERNS

• surveillance bias

• information bias 

SURVEILLANCE BIAS

Is a potential problem when one group, generally the exposed group is more intensely monitored for changes in the outcome measure than the comparison group

Blinding

useful for surveillance bias

INFORMATION BIAS

• Can occur if the same efforts to measure outcomes are not made for both the exposed and non-exposed groups 

RELATIVE RISK (RR)

• Also called the true risk and is used for prospective cohort studies

RR > 1

• Risk among exposed persons exceeds that among unexposed persons ; 

• Exposure appears to increase risk or hazardto those involved.

RR < 1

• Risk among exposed persons is less than that among unexposed person ; 

• Exposure appears to lower risk and therefore is protective for those involved mean a protective effect from exposure (i.e., less likely of an association between the risk factor/exposure and outcome

RR = 1

• Means no association 

• Risk is identical for exposed and unexposed persons – exposure has no effect on the outcome, no association between exposure and outcome

RATE RATIO

• One can use a contrast of incidence rates (or mortality rates) for this purpose

Rate ratio < 1

An exposure associated with a lowered rate of the outcome

Rate ratio > 1

An exposure associated with an increased rate of the outcome

Rate ratio = 1

When the exposure has no association with the outcome

CONCLUSION

• Cohort studies are useful for the study of rare exposures because sampling can be based on the selective inclusion of exposed persons.

  • Very large study populations may be required for researchers to observe a sufficient number of outcome events.

• Relative risk is important in the interpretation of data for cohort studies.