Chapter 7: Observational Cohort Studies

1. Chapter 7: Observational Cohort Studies Ch 7: Cohort Studies 1

2. Ch 7 Outline 7.1 Introduction 7.2 Historical perspective 7.3 Assembling and following a cohort 7.4 Prospective, retrospective, and ambidirectional 7.5 Addressing the potential for confounding 7.6 Data analysis 7.7 Wade Hampton Frost (optional) Ch 7: Cohort Studies

3. Basic Cohort Design • Recruit study subjects • Classify individual as exposed or non-exposed • Follow individuals over time, ascertain outcomes • Compare incidences of study outcomes Exposed individuals Incidence1 Closed population RR or RD RR or RD RR or RD RR or RD non-exposed individuals Incidence0 Ch 7: Cohort Studies

4. Do not lose sight of individual experiences from the beginning to the end (William Farr) From the Latin cohors “an enclosure” a unit of the Roman army Historical notes Ramazzini studied worker health (1713) Louis studied clinical outcomes in patients (18th century) Pinel studied mental health outcomes associated with humane treatment (18th century) Doll & Hill studied British doctors and smokers (1951 - present) Americans studied the causes of heart disease in Framingham Massachusetts Historical Perspective Ch 7: Cohort Studies

5. 80% of nonsmoker survived to age 70 50% heavy smokers survived to 70 British Doctors Study Survival Curves Begun in 1951 by Doll and Hill with a mailing of a 6 question questionnaire sent to 59,600 individual addresses. Source: Doll, R., Peto, R., Wheatley, K., Gray, R., & Sutherland, I. (1994). Mortality in relation to smoking: 40 years' observations on male British doctors. British Medical Journal, 309(6959), 901-911. Ch 7: Cohort Studies

6. WHI project included both experimental and observational cohorts Observational study: 93,676 women, 50-79 @ 40 clinical centers Recruitment period 1993 - 1998 Up to 15 years of follow-up WHI Observational Cohort Ch 7: Cohort Studies

7. WHI Observational CohortBreast CA & Analgesic Use Ch 7: Cohort Studies

8. Prospective, Retrospective, Ambidirectional • Based on proximity of data collection to actual events • Prospective = data collected near time of event • Retrospective = data are from the past (“historical data”) • Ambidirectional - combination of prospective and retrospective data Ch 7: Cohort Studies

9. WHI analgesic / breast cancer study Proximity of Data Collection Initial data collection Analgesic use history Breast cancer occurrence The ascertainment of the exposure was retrospective. The ascertainment of the outcome (breast cancer) was prospective. Overall, the study was ambi-directional. Ch 7: Cohort Studies 12

10. Example 7.4 (Retrospective Cohort)Chemical workers and bladder cancer • Exposure to benzidine, β-naphthylamine, alpha-naphthylamine • Historical cohort: occupational records of 4622 men in the British chemical industry, 1900 to 1950 • Bladder cancer info from death certificates 1921 – 1950 • Data collection: 1952 • Retrospective (“historical”) cohort study Initial data collection Chemical Exposures Bladder tumors Ch 7: Cohort Studies

11. Let R0≡ rate per 1000 p-yrs in referent group Let R1≡ rate per 1000 p-yrs in NSAID users of 1-4 years Let R2≡ rate per 1000 p-yrs in NSAID users of 5+ years RR1 = R1 / R0 = 46.4 / 49.0 = 0.95 [no units] RR2 = R2 / R0 = 40.5 / 49.0 = 0.83 [no units] RD1 = R1 − R0 = 46.4 − 49.0 = −2.6 per 1000 p-yrs RD2 = R2 − R0 = 40.5 − 49.0 = −8.5 per 1000 p-yrs Multiple levels of exposureAnalgesics and Breast cancer Ch 7: Cohort Studies

12. OpenEpi.com for data analysis • “Counts” menu for incidence proportions, prevalences, and case-control data • “Person Time” menu for rate data • Descriptive and inferential (confidence intervals and P-values) statistics • Can be used as a learning tool Ch 7: Cohort Studies

13. Ch 7: Cohort Studies

14. Ch 7: Cohort Studies