Lecture 7

Question 1

Cohort Studies

Answer 1

Involve the formation of a cohort, which is a group of individuals followed over
time.

Question 2

4 Points to Cohort Studies

Answer 2

1. Those who enter the cohort should be outcome free. The exposure is determined before the outcome happens.
2. Selecting exposed and comparison groups
3. Following up participant
4. Determining outcome status

Question 3

What bias does cohort study design protect against? The benefits to cohort studies:

Answer 3

➢ Better exposure and confounder data
➢ Less vulnerable to information bias

Question 4

The downsides of cohort studies:

Answer 4

> more expensive
Not efficient for diseases with long latent periods

Question 5

What kind of study is this?
Purpose: To examine the relationship between working night shifts and breast cancer.
Participants: 78,562 female nurses aged 30-55 years with no history of cancer.
Exposure: Outcome: Years of night shift working obtained by questionnaire in 1988.
Incident cases of breast cancer between 1988 and 1998. Non-fatal cases were
identified using medical records. Fatal cases were identified in the National Death Index and by
contacting next of kin. Also death due to other reasons.

Answer 5

Cohort study

Question 6

If you are doing a cohort study of the relationship between multi morbidity and depression you must start with people who:

Answer 6

Do not have depression

Question 7

Prospective vs Retrospective cohort studies

Answer 7

> In prospective cohort studies, researchers follow a group over time, starting before any outcomes (like diseases) occur, collecting data on exposures and observing who develops the outcome. These studies are accurate for showing causality but take more time and money. > In retrospective cohort studies, researchers look back at existing records to study past exposures and outcomes. They are quicker and cheaper but may have less reliable data, making it harder to determine causation.
- Good retrospective studies are very rare. Because the data needs to be there, be specific and be accessible.

Question 8

The pros and cons of retrospective studies:

Answer 8

Pros:
- cheap
-efficient with diseases with long latent period
Cons:
- more vulnerable to bias
- exposure and confounder data may be inadequate
-simply don’t have access to the reports

Question 9

Established recording systems

Answer 9

military, occupational, birth cohorts

Question 10

Relative Risk in Cohort Studies is measured using the

Answer 10

Incidence (rate) Ratio
(a/(a+b))/ (c/(c+d))

Question 11

Different design of cohort studies

Answer 11

> Common Baseline Time Point. Common Outcome Assessment Time
Common Baseline Time Point.
Outcome Measured Throughout Follow-Up.
Rolling Entry Point (variable baseline) Outcome Measured Throughout Follow-Up.
Concept of person-time: people are in the study for varied durations
➢ Different times under exposure
➢ Contribute differentially to the study

Question 12

What is the PTU# in cohort study

Answer 12

Person-Time Units
measure represents the cumulative amount of time each person in the study contributes while they are at risk of developing the outcome of interest.

Question 13

Cohort Study Advantages

Answer 13

➢ Valuable when exposure is rare
➢ Can examine multiple effects of a single
exposure
➢ Easier to determine the temporal relationship
between exposure and outcome
➢ Allows measurement of incidence

Question 14

Cohort Study Disadvantages

Answer 14

➢ Validity affected by losses to follow-up (selection bias)
➢ Other factors may not be distributed evenly between exposure groups (confounding)
➢ Inefficient for evaluation of rare diseases
➢ Can be expensive and time-consuming (need for large numbers and long follow-up)
➢ If retrospective they require good records

Question 15

Recall Cohort Study Limitations

Answer 15

➢ May need large numbers of subjects to be followed for long periods of time so logistically
difficult, time consuming, expensive (especially prospective cohort studies)
➢ Loss-to-follow has potential to undermine validity
➢ Not good for rare diseases or those with long latency
➢ Not good when exposure data are expensive to obtain

Question 16

The design of a Case Control study

Answer 16

• Define population from source population
• Cases and controls are sampled without regard to their exposure status
• Classify participants according to their outcome status.
  > Cases (+disease)
  > Controls (-disease)
• Then compare prior exposure

Question 17

What to do in a situation where you can’t do a recall cohort study?

Answer 17

Case control study

Question 18

The problem with case control studies

Answer 18

the denominator has no meaning. Because the size of the control was chosen.
However the ODDS RATIO has much value!!!

➢ Cannot calculate measures of occurrence: risks and rates; why
➢ No longer have entire denominator of population at risk (because controls represent a selected SAMPLE of the total
population with an arbitrary size)
➢ 20/32 is NOT the prevalence of disease in exposed, we decided to select 20% (36 controls)
➢ No idea what the real prevalence is in exposed and unexposed, hence no information on risk
➢ Not a defect, good feature: efficiency
➢ Can only calculate the odds of exposure in cases and controls;
➢ Therefore, the only ODDS RATIO is the proper measure of association

Question 19

Only ‘Odds’ can be estimated from case-control studies. OR of Exposure is:

Answer 19

(A/C)/(B/B) = (A/B)/(C/D) = OR of outcome

Question 20

In cohort studies Odds Ratio of Exposure is equal to

Answer 20

Odds Ratio of Outcome

Question 21

Case control studies are good for

Answer 21

rare diseases

Question 22

Relative risk is

Answer 22

Prevalence Ratio
OR
Incidence Ratio
Depending on what kind of study you are conducting

Question 23

Why can you not calculate measures of occurrence: risks and rates in a case control study

Answer 23

In a case-control study, you cannot calculate measures of occurrence like risks and rates because this design lacks a true measure of person-time or population at risk over time. Here’s why:

Sampling Based on Outcome: Case-control studies start by selecting participants based on whether they have the outcome (cases) or not (controls). Unlike cohort studies, you’re not observing the entire population over time to see who develops the outcome. Instead, you’re retrospectively examining exposures in those who already have the outcome versus those who don’t.
No Follow-Up Period: Since case-control studies don’t follow participants over time, they lack the temporal dimension needed to calculate incidence rates or risks. You need to know how many people were at risk of the outcome over a period to calculate these measures accurately.
Unknown Denominator: Risks and rates require a known denominator (the total population or the person-time at risk). In a case-control study, you only have cases and controls, not a full at-risk population, making it impossible to establish the true occurrence rate.
However, case-control studies are useful for estimating the odds ratio, which approximates the risk ratio when the outcome is rare. This is often used to infer associations between exposures and outcomes indirectly.

Question 24

Selection of cases in case control study

Answer 24

➢Very clear case definition required
➢who exactly are the cases of disease in your study?
➢Ideally, case selection will involve direct sampling of cases within a source
population
➢All people in the source population who develop the disease of interest will be
included as cases
➢random sample if large number of cases, or logistical constraints
➢If someone in the source population developed the disease of interest, would
they (meet the case definition and) be included as a case in the study?

Question 25

Controls in a case control study

Answer 25

Definition = A sample of the source population that produced the cases
Purpose = To estimate the exposure distribution in source population that produced the
cases

Question 26

Selection of Controls for case control studies

Answer 26

Trickiest bit of case–control studies!
Two Necessary Requirements (This is really, really important.)
1. Controls must come from the same source population as the cases.
➢Random selection is necessary to obtain a representative sample of source population.
➢Representativeness is a very important consideration.
2. Controls must be selected independently of exposure.
➢This means that their exposure status does not influence their selection.

Question 27

Where to Find Controls

Answer 27

1.Population-based controls (preferably random selection)
2.Nested controls from a cohort population/study
3.Hospital- or clinic-based controls
4.Family or friend control

Question 28

Population-Based Controls

Answer 28

Definition: Controls selected from the general population, most suitable when cases are from well-defined
geographic area
Sources: Random digit dialing, cell-phone or Internet subscribers, residence lists, tax lists, voter registration
lists, drivers license holders
Example: Case-control study of vitamin A and lung cancer. Cases come from Massachusetts Cancer Registry,
and controls come from the roster of registered voters in Massachusetts. (Is this a good control group?)
Good News: Controls often come from well-defined source population.
Bad News: VERY time consuming, harder to inspire participation, may not recall past exposures as well as
cases

Question 29

Nested Controls

Answer 29

Definition: Controls selected from an existing cohort population. Controls represent a sub-set of the full source population.
Example: Studying pesticide exposure and risk of breast cancer in Nurses Health Study Cohort
Good News: Controls come from clearly defined source population; already enrolled → willing participants
Bad News: Restricted to members of existing cohort; may limit hypothesis that can be studied

Question 30

Most common place for case control studies

Answer 30

Though they are the worst
Hospitals are the most common place.

Question 31

Hospital- or Clinic-Based Controls

Answer 31

Definition: Controls selected from among patients at a hospital or clinic
➢ Choose control patients with diseases (often more than one) other than the case’s disease
➢ Typically used when cases are identified from a hospital
Requirements:
Same source population as cases: must consider the “would criterion” and the referral pattern Illness should be unrelated to, that is, independent of the exposure under study
(1) Illnesses that have the same catchment area as the cases.
➢ This is what we mean when we say that controls should come from the same source population as cases.
(2) Illnesses that have no known relation to the risk factor(s) under study.
➢ This is what we mean when we say selection of controls should be independent of exposure.