Lecture 6Objective 16.Describe the elements of design of observational studies: (current) cohort studies (longitudinal studies). Discuss the advantages and disadvantages of this study design.

Prospective Cohort Studies

• select groups of exposed and unexposed individuals

• begin in current time and follow them forward to ascertain the outcomes of interest (e.g. death, disease incidence).

• strong studies that provide estimates of risk.

Coronary Disease Associated with Oral Contraceptive use

Major Coronary DiseaseDuration ofOC Use(mos) No. of

CasesRR 95% CI

None 339 1.0 -1-11 45 1.0 0.7-1.4

12-35 32 1.0 0.7-1.436-59 20 1.0 0.6-1.7

60-119 25 0.8 0.5-1.2>= 120 10 0.7 0.4-1.2

Selection of Subjects

• from population at risk based on exposure status

Assignment of Exposure

• exposure determined by genetics, environment or behavior of subject

Temporal Relationship of Exposure

• Exposure precedes investigator , outcome follows investigator observation

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Measurement of Risk and Association

• Risk: Incidence rates (IR) can be cumulative incidence (CI) or incidence density (ID)

• Association: Risk Ratio (RR) or Risk Difference (RD)

Validity

• Confounding Bias: eliminate effect of known confounders through matching, restriction

• Information Bias: eliminate with "blinding"; reduce possibility with objective diagnostic criteria

• Selection Bias: very unlikely to occur

Advantages• can estimate risk using incidence

rate• good design for interpreting

causality because exposure occurs prior to disease

• usually less expensive than experimental studies

• can be used to study associations between existing traits and disease occurrence

• good for studying rare exposures

Limitations• difficult to study rare outcomes• expensive to study outcomes

with long latent periods• potential loss of subjects to

follow‑up• cannot use random assignment

of exposure to reduce the possibility of confounding

Guide for Evaluation a Cohort Study

• Was exposure status clearly defined and did the study subjects fulfill this criteria?

• Were all subjects free of the outcome of interest at study entry?

• Were exposed and non‑exposed study subjects comparable?

Guide for Evaluation a Cohort Study

• What was the loss to follow‑up?• Were the investigators who

determined the outcome blinded?• Was the outcome clearly defined

and did the subjects fulfill these criteria?

• Was the study size sufficiently large to justify the authors conclusions?

Retrospective Cohort Studies

Objective 17.Describe the elements of design of observational studies: retrospective cohort studies. Discuss the advantages and disadvantages of this study design

Retrospective Cohort Studies

• select groups of exposed and unexposed individuals

• begin followup at some time in the past and follow them forward to ascertain the outcomes of interest (e.g. death, disease incidence).

Retrospective Cohort Studies

• Less strong than prospective studies because of the retrospective nature of the ascertainment of data

• provides estimates of risk and is commonly used in occupational studies.

• Control for potentially confounding variables is important.

DES exposure and the Incidence of Breast Ca

Exposure

Cases Woman-Years

IDper1000

RR(95% CI)

DES 118 88,912 1.33 1.4(1.1- 1.9)

NoDES

80 86,912 0.92

Total 198 175,824 1.13

Selection of Subjects

• from population at risk based on exposure status

• identified at some time in the past

Assignment of Exposure

• exposure determined by genetics, environment or behavior of subject

Temporal Relationship of Exposure

• Exposure and outcomes precede investigator observations

O1 O2

| | E ____________________ t I

Measurement of Risk and Association

• Risk: Incidence rates (IR) can be cumulative incidence (CI) or incidence density (ID)

• Association: Risk Ratio (RR) or Risk Difference (RD)

Validity

• Confounding Bias: may be difficult to get information on potential confounders because of retrospective nature of exposure; prevent confounding through matching or restrict

Validity• Information Bias: eliminate through

blinding; although it may be difficult if all information is present in the same record; reduce possibility with objective diagnostic criteria

• Selection Bias: as outcome has occurred prior to selection the potential exists knowledge of outcome status to influence subject selection

Advantages• can estimate risk using

incidence rates• no difficulty in studying diseases

with long latent periods• less expensive than prospective

studies and quickly done• good for studying rare

exposures

Limitations

• difficult to study rare disease• need good records on prior

exposure and disease occurrence

• problems of validity shared with those of retrospective studies