Professional Documents
Culture Documents
Goals of Research
Evaluate new therapies and diagnostics Evaluate screening procedures Determine cause effect relationships Describe a disease, prevalence and natural history Determine a prognosis Medical Review
Fixed Cohort
Loss to follow-up Deaths
Open Cohort
Out -
Migrations
In Time
Migrations
Retrospective
Direction of inquiry moves back in time
1990
2010
Study Population
Define Population at Risk using inclusion criteria Individuals with outcome of interest at time of screening and enrollment are not eligible for study Sub-clinical presentation of diseases may be present challenges in defining the cohort
Study Populations
Examples
Framingham study of cardiovascular disease
Individuals 30 62 years old in community at risk for disease Framingham, MA, 1948 to present
Framingham Study
Cohort Assembly
No. Men 3,074 2,024 No. Total Women 3,433 6,507 2,445 4,469
Volunteers
Respondents free of CHD
312
1975
428
2,418
740
4,393
307
2,282
427
2,845
734
5,127
Study Populations
MACS
Multi-Centered AIDS Cohort Study
Goal to elucidate the natural history of HIV/AIDS 5000 gay men, volunteers 5 cities in US 1984 1999 Extensive evaluations
Questionnaire Physical examination Laboratory testing Repository
Cohort Types
Representative cohort
May have low level of exposure
Enriched cohort
Enrich cohort with exposed individuals
Occupational cohort
MD Health study, RN health study, businessmen
Administrative cohorts, e.g., HMOs, PPOs Infectious disease outbreaks Institutional cohorts Etc.
Measuring Exposure
Content - Nature of the exposure; biologic mechanisms Quality
Continuous - e.g., serum cholesterol Periodic - e.g., cigarettes, sexual contacts Singular - e.g., nuclear exposure
Quantity
Continuous and periodic exposures must be quantified Dose-response relationship
Measuring Exposure
Measurements
Chart review Interview Blood tests or other specimens
Biomarkers
Measuring Exposure
Measuring exposure is one of the fundamental activities of a cohort study Exposure measurement must be comparable for all members of the cohort Carefully defined in advance of study Specific attention should be given to the accuracy and precision of proposed measurements
Pilot studies often needed
Outcome Definition
Primary outcome - the main event that will be related to the exposure
Failure-time outcomes
Death Disease occurrence
Repeated measures
Secondary outcomes - other events that are of interest and may corroborate the findings of the main outcome
Follow-up
Completeness and non-participation
90% rule of thumb
All subjects must have an equal likelihood for detecting the outcome Disease ascertainment must be comparable between the exposed and unexposed subjects
Number of visits Reasons for additional evaluations
Follow-up mechanisms
Active Passive
Follow-up
Passive Surveillance
Hospitals Disease Registries Clinics or physician offices Surveillance systems, e.g., National Death Index, CDC reportable conditions
Active surveillance
Systematic evaluations for outcome of interest Regular time intervals In all study subjects
Regardless of active or passive surveillance, the persons evaluating subjects must be blinded to exposure status
Information bias
The quality of information is different between exposed and unexposed subjects
Relative Risk
Disease Exposed A No Disease B A+B
Unexposed
C
A+C
D
B+D
C+D
N
Incidenceexp= A/A + B
Incidenceunexp = C/C + D
Relative Risk
a Incidence exposed a b RR c Incidence unexposed cd
Risk Difference
RD Incidence Incidence unexposed exposed
c a c d a b
Analytic Methods
Life-table methods Failure-time methods
Cox proportional hazards
Confounding
A variable related to both the exposure and the outcome may interfere with the interpretation of the relative risk
Weaknesses
Inefficient for rare diseases Expensive Requires excellent followup Losses to follow-up can invalidate the study