COHORT STUDIES

EPID 503Luisa N. Borrell

Review

Prevalence• Having Disease at one point/specified period of time

Interpretation: The risk of having lung cancer for an adult in the US is 5% during 1985.

ReviewIncidence

• Developing Disease over a specified period of time in an at-risk population

Interpretation: The risk of developing lung cancer among adults in the US is 9% between 1985 and 1990.

ReviewRandomized Clinical Trial

Investigator

Randomization

Exposure No Exposure

Cohort Studies

• Two or more groups of individuals that are free of disease and that are defined on the basis of presence or absence of exposure to a suspected or potential cause of the disease of interest are followed over time to assess the occurrence of the disease.

Types of Cohort Studies

Depending on the temporal relationship between the initiation of the study and the occurrence of the disease, cohort studies can be classified as:•Prospective •Retrospective

Prospective Cohort Studies

The exposures may or may not have occurred at the time of study begun, but the outcome have certainly not yet occurred. Thus, after the selection of the cohort, participants must be followed on time to assess incidence of disease.

Prospective Cohort Study

Exposed Not Exposed Time

DevelopDisease

Do not Develop Disease

Develop Disease

Do not Develop Disease

1999 Population

2000

2005

Retrospective Cohort Studies

The exposures and the outcomes have already occurred when the study is initiated.

Retrospective Cohort Study

Exposed Not Exposed Time

DevelopDisease

Do not Develop Disease

Develop Disease

Do not Develop Disease

1985 Population

1987

1992

Strengths of Cohort Studies

• Maintain temporal sequence Exposure -time- Disease• Well suited for assessing rare

exposures and rapidly fatal disease• Allows study of multiple potential

outcomes of a given exposure

Strengths of Cohort Studies• Allows for calculation of incidence of

diseases in exposed and unexposed individuals

• Provides a complete description of experience subsequent to exposure, including the rate of progression, staging and natural history of the disease

Strengths of Cohort Studies• Allows for thorough quality control in

measurement of study variables• Minimizes bias in the ascertainment of

the exposure

Weakness of Cohort Studies• Expensive• Inefficient to study rare diseases• Potentially long duration for follow-up• Must make sure to measure

confounders, but almost must second guess at the study initiation

• Must anticipate secular trends in technology, behaviors, etc…

Retrospective vs Prospective

• Less expensive• Less time consuming• Efficient for study of diseases with

long latency periodsBut• More sensitive to confounding and bias

Validity Issues in Cohort Studies

• Bias • Selection Bias• Information Bias

• Confounding

Measure of Disease Frequencies

• Incidence• Cumulative Incidence• Incidence Rate

• Prevalence• Point Prevalence• Period Prevalence

Measure of Association• Relative Risk Estimates the magnitude of an

association between exposure and disease and indicates the likelihood of developing the disease in the exposed group relative to those who are not exposed

Measure of Association• Relative Risk •Risk Ratio: Ratio of the Cumulative

Incidence among exposed compared with those not exposed.

•Rate Ratio: Ratio of the Incidence Rate in those exposed to that among those unexposed.

Disease_____ Yes No Exposure Total

Yes a b a+b No c d c+d

Total a+c b+d T

Relative Risk

• Risk Ratio (AKA Relative Risk)

RR= a/a+b / c/c+d = CIe / CIu

Disease_____ Yes No Exposure Total

Yes a - PYe

No c - PYu

Total a+c - PYT

Relative Risk

• Rate Ratio

RR= a/PYe / c/ PYu= IRe / IRu

Disease X_____ Yes No Exposure Z Total

Yes 230 400 730 No 110 369 479

Total 440 769 1209

Relative Risk

• Risk Ratio (AKA Relative Risk)

RR= CIe / Ciu = 230/730 / 110/479 =

RR= 0.3151/ 0.2296 = 1.37

Relative Risk

• Interpretation: RR = 1.37 •The risk of developing Disease X was

1.37 times higher in exposed to Z compared to those unexposed to Z between 1995 and 1999

Measure of Effect

• AKA: Risk Difference• Attributable Risk AR = Ie - Iu

Group of Interest: Exposed

Attributable Risk

•Interpretation: AR= 0.3151 - 0.2296 =0.0855 •9 out 100 cases of disease X cases

among those exposed to Z were due to Z during 1995 and 1999

Measure of Effect

• Attributable Risk Percent AR % = Ie - Iu / Ie * 100

AR % = RR-1 / RR * 100

Group of Interest: Exposed Cases

Attributable Risk Percent•Interpretation: AR= 0.3151 - 0.2296 / 0.3151= AR= 0.2731* 100= 27% AR= 1.37 -1/ 1.37 *100= 27% •27% of disease X cases among those

exposed to Z were due to Z during 1995 and 1999

Measure of Effect

• Population Attributable Risk PAR = I T - I u

Group of Interest: Total Population

Population Attributable Risk

•Interpretation: PAR= 0.3639 - 0.2296 = 0.1343 •13 out 100 of disease X cases among

the total population were due to Z during 1995 and 1999

Measure of Effect

• Population Attributable Risk Percent PAR = I T - I U / I T * 100

Group of Interest: Total Cases

Population Attributable Risk Percent

•Interpretation: PAR% = 0.3639 - 0.2296 / 0.3639= PAR%= 0.3691* 100= 36.91% •37% of all disease X cases were due

to Z during 1995 and 1999

Framingham Heart Study• The Framingham Study is one of the

best-known cohort studies of heart disease. – Since 1948, samples of residents of

Framingham, Massachusetts, have been subjects of investigations of risk factors in relation to the occurrence of heart disease and other outcomes.

– 5209 men and women aged 30 to 62 years during the first examination period (1948 - 1952) have been examined biennially

– Hundreds of studies have reported results based on the extensive measurements taken on this cohort

3,074 men3,433 women2,024 men2,445 women

Respondents

Random sample of Framingham city

312 men428 women

Volunteers54 men with CHD28 women with CHDremoved from studyTotal free of CHD = Framingham Study Population

2,282 men + 2,845 women = 5,127 individuals

Framingham Heart Study - Hypotheses

• Incidence of CHD increases with age. • Incidence of CHD higher in males, and

occurs at an earlier age.

cholesterol risk of CHD

• Other risk factors for CHD:– tobacco use– alcohol use – increased body weight – diabetes mellitus

Lifetime risk of developing coronary heart disease.

Lloyd-Jones et al, Lancet 1999;353:89-92.

• Used data from 7733 participants in the Framingham Heart Study

• Participants had been examined at least once at age 40-94 years between 1971 and 1975 and found to be free of coronary heart disease and then followed up by the investigators using later records

• What kind of study is this?

Calculating a lifetime relative risk for coronary heart

disease•Overall, 7733 subjects were followed up for a total of 109,948 person years•1157 patients developed coronary heart disease•1312 died from non-coronary heart disease causes•Lifetime risk calculated at age 40 years to be 48.6% for men and 31.7% for women

In the Framingham study, subjects were chosen on the basis of geographic location. This made the study participants readily available for follow up.

What kind of effect would loss to follow up have in a cohort study?

Measure of Association and Effect in a Cohort Study of

CHD and smokingCHD no CHD Total

Smoke cigarettes 84 29163000Did not smoke 87 4913 5000Incidence in smokers: 84/3000 = 28.0 per 1000Incidence in non-smokers = 87/5000 = 17.4 per 1000Relative risk = 28.0/17.4 = 1.609Attributable Risk = 28.0 - 17.4 = 10.6 per 1000 cases of CHD among smokers attributable to smoking

But, some lost to follow up….20% lost to follow up in the smokers, 10% lost in the nonsmokers (no data available for the disease status):

CHD no CHD TotalSmoke cigarettes 84 2316 2400Did not smoke 87 4413 4500

Incidence in smokers = 84/2400 = 35.0 per 1000Incidence in nonsmokers = 87/4500 = 19.3 per 1000

Relative Risk = 35.0/19.3 = 1.813

End result….• Different loss to follow up in the two

groups biased the true relative risk • What if the follow up was not different

in the two groups?

Equal loss to follow up….20% lost to follow up in each group:

CHD no CHD TotalSmoke cigarettes 84 2316 2400Did not smoke 87 3913 4000

Incidence in smokers = 84/2400 = 35.0 per 1000Incidence in nonsmokers = 87/4000 = 21.8 per 1000

Relative Risk = 35.0/21.8 = 1.61

End result….• When the loss to follow up is the same

in both groups, the relative risk goes towards the null value of one

• Loss to follow up can distort the true relationship between disease and exposure

• The strength of large-scale cohort studies such as the Framingham Heart Study is the closely monitored study population, where there is little loss to follow up