PPT 3- Cohort Studies

The Alameda County Study

Followed 7000 people, 30 - 69 years old for 9 years (1965-1974) The most isolated people were almost 3 times more likely to die of all causes during the study Studied factors associated with health and mortality. Involved residents of Alameda County, CA, ages 16-94 years. Data collected through mailed questionnaires; telephone interviews or home interviews of non-respondents. Follow-up with same procedures at years 9, 18, and 29.

Larger studies are _____

Harder to manage Organizational and administrative burdens are increased when there are multiple levels of data collection (such as phone interviews, mailed questionnaires, consent forms to access medical records).

Basic Study Design

In sentence format: What proportion developed disease "X" among those with the risk factor compared to the proportion who developed disease "X" among those without the risk factor.

In theory, if a harmful exposure can be eliminated from the population , we would expect the ______________ to decrease

In theory, if a harmful exposure can be eliminated from the population , we would expect the incidence rate in the exposed group to decrease by the amount of the attributable risk

How many observation points in a cohort study?

Include at least two observation points: one to determine exposure status and eligibility and a second (or more) to determine the number of incident cases.

Limitations of Cohort

Large sample size, multiple follow up points and long follow up period (expense $$ & time) Loss to follow up Exposure misclassification as exposures may change over long follow up period

Nurses' Health Study, 1976, B&Ws Boston

Mailed questionnaire to 170,000 nurses in 11 states - 122,00 responded (response rate) Original aim: long term consequences of oral contraceptives Mailed f/u mailed questionnaire q 2 years Married female R.N.s ages 30-55 years. Data collected through mailed questionnaires. http://www.channing.harvard.edu/nhs/

Advantages to Cohort Studies

Only observational study design which provides a direct estimation of risk (direct estimation of incidence rates in exposed and non-exposed groups) Permits multiple outcomes to be evaluated Permits study of rare exposures (e.g. occupational cohorts) Demonstrate temporal sequence between exposure and disease Length of incubation or latency period between exposure and disease

2 types of follow up

Passive Follow up Active Follow up

Wade Hampton Frost

Popularized cohort analysis method. Arranged tuberculosis mortality rates in a table with age on one axis and year of death on the other. One can quickly see the age-specific mortality for each of the available years on one axis and the time trend for each age group on the other.

Two types of cohorts

Population-based cohorts Special exposure based cohorts - ***(occupational exposure) or special resource groups cohorts (HMO, profession)

Advantages of Nested Case-Control Studies

Provide a degree of control over confounding factors. Reduce cost because exposure information is collected from a subset of the cohort only.

Prospective cohort study

Purely prospective in nature; characterized by determination of exposure levels at baseline (the present), and follow-up for occurrence of disease at some time in the future.

Case-control studies raise concerns that....

Raise concerns that recall of past exposures differs between cases and controls. Survival factor

Meaure of Association for Cohort Study

Relative risk Attributable risk

What does relative risk do?

Relative risk provides a direct measure of association between exposure and outcome. Relative risk is the ratio of the incidence of disease in the exposed group to the incidence in the non-exposed group.

Relative risk: Ratio Strength of the association between______ Uncovers _____ Attributable risk: Measuring a _________ How much of the outcome in the exposed is due ________ *****Large difference can indicate what?...

Relative risk: Ratio Strength of the association between exposure and disease Uncovers causative factors Attributable risk: Measuring a difference How much of the outcome in the exposed is due to the exposure Large difference can indicate what?...

Cohort studies begin with a group of subjects who lack a __________ and are at risk for ______

Start with a group of subjects who lack a positive history of the outcome of interest and are at risk for the outcome.

Honolulu Heart Program

Studied coronary heart disease and stroke in men of Japanese ancestry. Involved men of Japanese ancestry living on Oahu, HI, ages 45-65 years. Data collected through mailed questionnaires, interviews, and clinic examinations. http://www.nhlbi.nih.gov

Temporality refers to ___________ Did the information about cause and effect refer to the same point in time? Or, was the information about the cause garnered before or after the information about the effect?

Temporality refers to the timing of information about cause and effect. Did the information about cause and effect refer to the same point in time? Or, was the information about the cause garnered before or after the information about the effect?

Population Based Cohort

The cohort includes either an entire population or a representative sample of the population. Population-based cohorts have been used in studies of coronary heart disease.- Framingham study- Ongoing study of CHD initiated in 1949. Used a random sample of 6,500 from targeted age range of 30 to 59 years.

Attributable risk

The difference in risk between exposed and unexposed groups (a/a+b)-(c/c+d) ***Difference between the incidence rate of the disease in the exposed group and the incidence in the non-exposed group

Active Follow up

The investigator, through direct contact with the cohort, must obtain data on subsequent incidence of the outcome (disease, change in risk factor, change in biological marker). Accomplished through follow-up mailings, phone calls, or written invitations to return to study sites/centers.

The larger the size of the cohort, the greater the ________________________________.

The larger the size of the cohort, the greater the opportunity to obtain findings in a timely manner. Resource constraints typically influence design decisions.

There are several variations in cohort designs that depend on the timing of data collection.

This is known as... Temporal Differences THE THREE ARE... prospective cohort studies Historical (retrospective) cohort studies historical prospective cohort studies

When causality is assumed, the risk difference becomes the ____________

When causality is assumed, the risk difference becomes the attributable risk (AR): The amount of the absolute risk in the exposed group due to the exposure under study

YPLL - DALYs -

YPLL - Years of potential life lost DALYs - Disability-adjusted life years

Years of potential life lost (YPLL)

Years of potential life lost (YPLL) Computed for each individual in a population by subtracting that person's life span from the average life expectancy of the population. (US: 75 years) Premature mortality: 75 - age at death

In Population based cohorts _______is unknown until the first period of observation when exposure information is collected.

population

Cohorts can be both ___ & ____

retrospective and prospective

retrospective study design (with the benefits of _____________) and collection __________in a prospective cohort design.

retrospective study design (with the benefits of more immediate follow-up time) and collection of primary exposure data in a prospective cohort design.

cohort is defined as________

A cohort is defined as a population group, or subset thereof, that is followed over a period of time.

Survival curves

A method for portraying survival times To construct a survival curve, the following information is required: Time of entry into the study Time of death or other outcome Status of patient at time of outcome, e.g., dead or censored (patient is lost to follow-up)

In retrospective cohort studies a significant amount of follow-up may be accrued in a_____________________ The amount of exposure data collected can be quite extensive and available to the investigator at ____________

A significant amount of follow-up may be accrued in a relatively short period of time. The amount of exposure data collected can be quite extensive and available to the investigator at minimal cost.

Attributable Risk Formula...

(Incidence rate in the exposed) - (Incidence rate in the non-exposed) = Ie - Ine

Relative Risk

**provides a direct measure of association between exposure and outcome. Relative risk is the ratio of the incidence of disease in the exposed group to the incidence in the non-exposed group.

Example: Minnesota Breast Cancer Family Study Mailed survey A reminder postcard 30 days later A second survey A telephone call to non-responders Example of ____ followup

ACTIVE

Disability-adjusted life years (DALYs)

Adds the time a person has a disability to the time lost to early death.

Exposure based cohorts

An exposure-based cohort is made up of subjects with a common exposure... These studies overcome limitations of population-based cohort studies, which are not efficient for rare exposures. Certain groups, such as occupational groups, may have higher exposures than the general population to specific hazards.

Cohort studies are study design that permit examination of ___________

Cohort studies are study design that permit examination of multiple outcomes.

Cohort studies involve the comparison of disease rates between _______ and ______ groups

Cohort studies involve the comparison of disease rates between exposed and non-exposed groups. The comparison group is similar in demographics and geography to the exposed group, but lacks the exposure. In an occupational setting, several categories of exposure may exist.

Cross-sectional and case-control study designs are based _____________________ that is collected at the same time. Advantage- Disadvantage-

Cross-sectional and case-control study designs are based on exposure and disease information that is collected at the same time. Advantage: Efficient for generating hypotheses. Disadvantage: Leads to challenges regarding interpretation of results.

Cross sectional studies- Present difficulties in distingusihing the __________ from the _____ of disease

Cross-sectional studies: Present difficulties in distinguishing the exposures from the outcomes of the disease, especially if the outcome marker is a biological or physiological parameter.

Nested Case-Control Studies

Defined as a type of case-control study in which cases and controls are drawn from the population in a cohort study. The population of the cohort study comprises both exposed and non-exposed persons.

Demonstrating _________ is a difficulty of most observational studies.

Demonstrating temporality is a difficulty of most observational studies.

Retrospective Cohort Study

Despite substantial benefits of prospective cohort studies, investigators have to wait for cases to accrue. Retrospective cohort studies make use of historical data to determine exposure level at some baseline in the past.

Passive Folow up

Does not require direct contact with cohort members. Possible when databases containing the outcomes of interest are collected and maintained by organizations outside the investigative team e.g ...... Example: Used in the Iowa Women's Health Study.

Animal studies provide evidence that long term high lead exposure leads to neurological toxicity. Most of general population - not high lead exposure How can we study this in humans?

Exposure based cohort!! Lead battery workers - high lead exposure Sample in battery production factories Among sample different levels of lead exposure depending on specific job classification