Case Control Study

Question 1

Case Control Studies

Answer 1

1. Compares cases and controls with respect to their level of exposure to a risk factor of interest
2. Calculate the Odds of disease among the exposed/unexposed
3. calculate the OR

Question 2

When is a Case Control Study Desirable?

Answer 2

1. When a disease has a long induction and latent period
2. Rare/unknown diseases

Inefficient to follow participants over time

Question 3

Cases in a Case Control Study

Answer 3

Cases = the numerators of the incidence/prevalence of disease in exposed / unexposed groups

Incidence of disease in exposed = a/?
Incidence of disease in unexposed = c/?

Question 4

Controls in a Case Control Study

Answer 4

Controls = sample of base population that gave rise to the cases
*If it were a cohort study, we would have the total population or person years for both groups

If controls are selected correctly, a similar proportion of controls would have developed the disease if they had been exposed to the same exposure as the cases (counterfactual)

Question 5

Case Control :: Cohort Study

Answer 5

A case control study is conceptually the same as a cohort study

Cases and controls are expected to a common base population in order for us to compare

Question 6

Principles of Control Selection:

Base Population Principle

Answer 6

1. Cases and controls should be representative of the SAME base population
2. Method: choose a random sample of individuals from the same source of the cases, at specified time if applicable
3. “Nested case control study” - each time a case is dx’d, controls are randomly selected from the “risk set” = subjects at risk at the time of dx

Sampling from the base population:

• Simple random sampling: controls are selected randomly from the base population. Each eligible individual has the same probability of selection
• Stratified sampling/freq. matching: base pop. is subdivided into strata (i.e. by age),
• More complex sampling schemes: two-stage + cluster sampling plans

Question 7

Principles of Control Selection:

Deconfounding Principle

Answer 7

Confounding should not be allowed to distort the estimation effect.
Confounders that are measured can be controlled in analysis.
Unknown/unmeasured confounders should have as little variability as possible.

Ex: using siblings as matched controls = less variability for genetic confounders , hopefully less cofounding

Question 8

Principles of Control Selection:

Comparable Accuracy Principle

Answer 8

1. The degree of accuracy in measuring the exposure of interest for the cases should be equivalent to the degree of accuracy for the controls
2. Doesn’t eliminate information bias
3. Rationale is to reduce differential misclassification bias from differential accuracy in case info + control info
4. Misclassification of exposure due to this principle causes non-differential error – typically biases toward lack of association/null

Question 9

Selection of Control Groups

Population Controls

Answer 9

• Most often used when cases are selected from a defined geographic population
• random digit sampling, residence lists, drivers license records

Advantage:
- PI is assured that controls come from same pop. as the cases
-the distribution of exposures in the controls can be extrapolated to base pop.
Disadvantage:
- time consuming, expensive, hard to contact and recruit, may remember exposures differently than cases (recall bias)
-incomplete case ascertainment
-less motivation - may not cooperate

Question 10

Selection of Control Groups

Hospital Controls

Answer 10

Used when cases are selected from a hospital population
Ex: Cases identified from admissions to hospital coronary care units, Controls from surgical, ortho, medical units of the same hospital–illness with NO relation to cases

Advantages:
- same selection factors that led cases to hospital led controls to hospital
-easily ID’d and accessible (less expensive)
-more willing to participant than pop. controls
Disadvantages:
-hospital controls are ill = may not accurately represent exposure history in the population that produced the cases
-Hospital catchment areas may be different for different diseases

Question 11

Friend Controls

Answer 11

Controls selected from a list of friends/associates while case is being interviewed.
-reduces biases due to social class

Question 12

Relative Controls

Answer 12

Used when genetic factors confound the effect of exposure
match on genetic background, ethnicity

Spouses could be good controls if seeking matching on environmental risk factors

Question 13

Proxy Respondents and Deceased Controls

Answer 13

Used when subjects are deceased or too sick to answer questions, or for persons with cognitive disorders

Surrogates (spouses, children) generally provide accurate responses for broad categories of exposure info

detailed info less reliable

Question 14

Strengths of Basic Case Control Studies

Answer 14

1. Less expensive, time consuming than other basic designs
2. Case-control sampling is efficient for studying rare diseases bc investigator fixes the ratio of cases to controls
3. Efficient for studying diseases with long latent periods, since exposure history can be measured retrospectively

Question 15

Population-Based Case Control Studies

case control studies with a defined cohort

Answer 15

1. Special type of case control study that has certain features of a cohort design
2. A base population is followed for a given period for detection of all incident cases
3. Noncases are randomly sampled to compare the cases to
4. In this case base population is sampled directly by the investigator to obtain controls
5. Exposure info is obtained from all subjects after cases and controls are identified

Question 16

Population-Based Case Control Studies

Answer 16

Case Group = consists of all/representative sample of incident cases that occur in the defined cohort over a specified follow-up period.

Control Group = selected either from individuals at risk at the time each case occurs, OR from base population

Question 17

Nested Case Control Studies

Density Sampling of controls

Answer 17

1. Controls are selected longitudinally throughout f/u period, typically matched to cases at the time of dx/identification
2. Cases are compared with a subset of the “risk set” = subjects at risk at the time of dx
3. Controls may become cases during the study period–in analysis they would be treated as both cases + controls

Question 18

Density Sampling vs Cumulative Sampling

Answer 18

Density Sampling: the equivalent of matching cases and controls on duration of f/u; permits the use of straightforward statistical analysis

Cumulative Sampling: all controls are selected at the end of the observation period during which cases are id’d

• Density sampling preferred when observation period is long, esp. if the frequency of exposure changes over time.
• w/ cumulative sampling, if exposure frequency changes, cases + controls might differ in distribution even if exposure isn’t a real risk factor

Question 19

Case-Cohort / Case-Base Sampling

Answer 19

1. Controls are selected as a random sample of the base population at baseline
2. Controls may subsequently become cases during the study period; these subject would then be treated as both cases and controls in analysis
3. Prevalent cases should be excluded from the control group
4. A sample of the base pop. at baseline can serve as control group for different sets of cases occurring in the same cohort
5. If the baseline cohort sample is representative of the base pop., risk factor distributions and prevalence needed for population attributable risk estimate can be obtained.

Question 20

Strengths of Population-Based Case-Control Studies

Answer 20

Relative to cohort studies:

• more efficient for studying rare diseases, since exposure data are collected on a fraction of noncases
• sample control group can be used to assess effects of different diseases

Relative to basic case-control studies:

• we can estimate the frequency of disease in the base pop. .
• we are more confident that controls are representative of the base population
• less susceptible to selection bias - controls are selected from the same pop. = exposure status less likely to affect it

Question 21

Limitation of Case-Control Study within a defined cohort

Answer 21

Relative to cohort studies:

• Exposure information obtained after disease occurrence = more vulnerable to measurement error, esp. if collected retrospectively
• leads to bias in effect estimation

Relative to basic case-control:

• It tends to be more expensive or impractical because of the system needed to id all new cases in the reference pop.
• sometimes impossible