c

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

2. 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)

3. History

4. History
Y-axis 0-40 per 1000 person-years

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

6. 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

7. 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

8. 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

9. 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

10. 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

11. History
• “Three Generations of Dedication”

12. 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

13. 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

14. 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

15. 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

16. History
• Comparison of findings based on T65D dose and revised
LLNL dose

17. 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

18. 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

19. 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)

20. History
• Cardiovascular disease studies
– Atherosclerosis Risk in Communities Study
– Cardiovascular Health Study
– Strong Heart Study
• Multisite studies with standardized procedures,
data coordinating centers

21. 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

22. 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

23. 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

24. History
• Many developments in analysis of cohort data
through collaboration between epidemiologists
and biostatisticians

25. History
Samet & Muñoz 1998