• First undertakings that resembled cohort studies were at the turn of the century

History

History• In the early 1900s tuberculosis was the leading

cause of mortality in the US• What would now be recognized as cohort

studies were conducted to examine the course of disease (e.g., mortality, survival time) and effects of therapies (e.g., exposure to outdoor air and sunshine)

History

History

Y-axis 0-40 per 1000 person-years

History

Y-axis 0-600 per 100,000 person-years = 0-6 per 1000 person-years

History• Brown and Pope followed 1000 tuberculosis

patients discharged from a sanitarium• Used life-table (actuarial) methods to examine

survival of the patients• Compared patients’ survival to general

population life-table (Farr’s English Life Table no. 3)

• Considered first application of life-table method in a clinical cohort study

History• Wade Hampton Frost pioneered the non-

concurrent cohort design• Described tuberculosis rates among members of

132 black families in Tennessee• Interviewed family members to reconstruct

household membership and age of onset of TB

• Estimated person-years of “life experience” from birth until TB or death from other cause

• Estimated age-specific rates of tuberculosis

History• Landmark cohort studies established around

1950– Large studies, often considering a wide range of

exposures and outcomes, sustained follow-up over decades, rich data collected

History• Framingham – started in late 1940s to study

causes of rising cardiovascular disease• Small and cooperative community (Framingham,

MA)• Sustained support from NIH which maintained

study as intramural project• Rigorous standardized protocols for data

collection

History• Supplemental studies of other disease• Offspring of original cohort in a cohort study• Third generation in a new cohort study• Methodological advances for longitudinal

data were made of necessity to study this data

• General population study of several diseases that tests multiple hypotheses

History• “Three Generations of Dedication”

History• Atomic bomb survivors in Hiroshima and

Nagasaki• Examined consequences of ionizing radiation

exposure• Began almost immediately after bombs dropped

in 1945• Jointly funded by the US and Japan

History• Harm of radiation exposure was known but harm

had not been precisely quantified• Radiation doses were reconstructed• Principal source of evidence on harms of

radiation exposure and basis of standards throughout the world

History• Prompted methodologic work around

– Time and age dependence of radiation risks– Combined effects of radiation with other exposures– Issues of measurement error

• Location and shielding of survivors obtained by extensive interview

• Radiation air dose calculated as function of distance from bomb site and transmission factor to account for shielding

History• Discussion around systematic errors in air dose curves

and in shielding factors• Example of systematic errors in air dose:

– T65D (1965) were initial dose estimates– Revised in 1980 (LLNL, ORNL)

• Suggested reduced neutron doses in both cities, increased gamma doses in Hiroshima and slightly reduced gamma doses in Nagasaki

• Based on better estimates of the outputs of the two very different bombs

• Accounting for humidity appropriately in the two cities

History• Comparison of findings based on T65D dose and revised

LLNL dose

History• Non-concurrent cohort study in

1954 to examine whether aniline- based dyes increased risk of bladder cancer

• Roster of exposed workers in the UK reconstructed based on records from 1920 forward

• Identified bladder cancer cases and deaths

History• Established the feasibility of the non-concurrent

design when high quality records are available – design widely used for worker groups with employment records available to document exposures• Note use of records means the design can be

considered non-concurrent and prospective

History• Current era starting in the 1970s

– Large but more focused studies attempting to capture in more detail aspects of what we have learned about the risk factors for chronic disease

– Combinations of questionnaires and physical measures (e.g., lung function, genetic markers)

– Intensive follow up– Multisite designs– Data linkage (e.g., death indices, disease

registries)

History• Cardiovascular disease studies

– Atherosclerosis Risk in Communities Study– Cardiovascular Health Study– Strong Heart Study

• Multisite studies with standardized procedures, data coordinating centers

History• Est. 1976 to study risks of oral contraceptive use

– 122,000 married nurses from 11 states ages 30-55– Cooperative group familiar with research– Data collected by mail– Biological specimen collections– Dietary questions collected starting 1980

• Examined relations between use of hormones, diet, exercise, and other lifestyle practices with a wide range of chronic illnesses

History• Nurses’ Health Study II started in 1989 –

younger generation exposed to oral contraceptives from younger ages– 117,000 nurse-participants from 14 states

• Children of NHS II enrolled in Growing Up Today Study (GUTS) and GUTS II– Studies of factors associated with weight change

• NHS III starting currently

History• HIV epidemic prompted large

cohort• Multicenter AIDS Cohort Study

established 1984• 5000 homosexual men in 4

cities– Collection of clinical observations and

blood specimens– Started before HIV virus identified

• Women’s Interagency HIV study started in 1994

History• Many developments in analysis of cohort data

through collaboration between epidemiologists and biostatisticians

History

Samet & Muñoz 1998