CaseControl Studies

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Case-Control Studies
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TROHOC STUDIES

• This disparaging term was given to case-control
  studies because their logic seemed backwards
  (trohoc is ?? spelled backwards) and they seemed
  more prone to bias than other designs.
• No basis for this derogation.
• Case-control studies are a logical extension of
  cohort studies and an efficient way to learn
  about associations.

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Introduction

• Hypothesis Pesticide exposure increases the risk
  of breast cancer.
• Consider a hypothetical prospective cohort study
  of 89,949 women aged 34-59 1,439 breast cancer
  cases identified over 8 years of follow-up
• Blood drawn on all 89,949 at beginning of
  follow-up and frozen
• Exposure Level of pesticides (e.g. DDE) in blood
  characterized as high or low

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Introduction

• Results

Breast Cancer
Pesticide
Relative Risk RR (360/13,636) /
(1,079/76,313) 1.9
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Introduction

• Practical Problem Quantifying pesticide levels
  in the blood is very expensive -- it's not
  practical to analyze all 89,949 blood samples
• To be efficient, analyze blood on all cases
  (N1,439) but just take a sample of the women who
  did not get breast cancer, say two times as many
  cases (N2,878)

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Introduction
Breast Cancer
DDE
These data can be used to estimate the relative
risk.
We have just identified cases of disease from a
defined population, and then taken a sample of
that population for comparison. Exposure
histories are determined for each group. This is
an example of the case-control method of
sampling.
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General Definition of a Case-Control Study A
method of sampling a population in which cases of
disease are identified and enrolled, and a sample
of the population that produced the cases is
identified and enrolled. Exposures are
determined for individuals in each group.
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When is it desirable to conduct a case-control
study?

• When exposure data are expensive or difficult to
  obtain
• - Ex Pesticide study described earlier
• When disease has long induction and latent period
• - Ex Cancer, cardiovascular disease

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When is it desirable to conduct a case-control
study?

• When the disease is rare
• Ex Studying risk factors for birth defects
• When little is known about the disease
• Ex. Early studies of AIDS
• When underlying population is dynamic
• Ex Studying breast cancer on Cape Cod

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Cases

• Criteria for case definition should lead to
  accurate classification of disease
• Efficient and accurate sources should be used to
  identify cases existing registries, hospitals
• What do the cases give you? Think of the
  standard 2 X 2 table

Disease
Exposed
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Cases give you the numerators of the rates of
disease in exposed and unexposed groups being
compared

• Rate of disease in exposed a/?
• Rate of disease in unexposed c/?

What is missing? The denominators! If this were
a cohort study, you would have the total
population (if you were calculating cumulative
incidence) or total person-years (if you were
calculating incidence rates) for both the exposed
and non exposed groups, which would provide the
denominators for the compared rates.
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Where do you get the information for the
denominators in a case control study? THE
CONTROLS.

• A case-control study can be considered a more
  efficient form of a cohort study.
• Cases are the same as those that would be
  included in a cohort study.
• Controls provide a fast and inexpensive means of
  obtaining the exposure experience in the
  population that gave rise to the cases.

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Controls

• Definition A sample of the source population
  that gave rise to the cases.
• Purpose To estimate the exposure distribution in
  the source population that produced the cases.

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Selecting Controls

• General population controls
• Most often used when cases are selected from a
  defined geographic population
• Sources random digit dialing, residence lists,
  drivers license records
• Example Upper Cape Cancer Study

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Selecting Controls

• Advantages of general population controls
• Because of selection process, investigator is
  usually assured that they come from the same base
  population as the cases.

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Selecting Controls

• Disadvantages of general population controls
• Time consuming, expensive, hard to contact and
  get cooperation may remember exposures
  differently than cases

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Selecting Controls

• Hospital controls
• Used most often when cases are selected from a
  hospital population

Example Study of cigarette smoking and
myocardial infarction among women. Cases
identified from admissions to hospital coronary
care units. Controls drawn from surgical,
orthopedic, and medical unit of same hospital.
Controls included patients with musculoskeletal
and abdominal disease, trauma, and other
noncoronary conditions.
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• Advantages of hospital controls
• Same selection factors that led cases to hospital
  led controls to hospital
• Easily identifiable and accessible (so less
  expensive than population-based controls)
• Accuracy of exposure recall comparable to that of
  cases since controls are also sick
• More willing to participate than population-based
  controls

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• Disadvantages of hospital controls
• Since hospital based controls are ill, they may
  not accurately represent the exposure history in
  the population that produced the cases
• Hospital catchment areas may be different for
  different diseases

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• What illnesses make good hospital controls?
• Those illnesses that have no relation to the
  risk factor(s) under study
• Example Should respiratory diseases be used as
  controls for a study of smoking and myocardial
  infarction? Do they represent the distribution of
  smoking in the entire population that gave rise
  to the cases of MI?

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Selecting Controls

• Special control groups like friends, spouses,
  siblings, and deceased individuals.
• These special controls are rarely used.
• Some cases are not able to nominate controls
  because they have few appropriate friends, are
  widowed, or are only or adopted children.
• Dead controls are tricky to use because they are
  more likely than living controls to smoke and
  drink.

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Sampling a cohort population for controls nested
case-control study

• 1. Sample the population at risk at the start of
  the observation period
• -------------------------------------------------
  ------------------------
• Start FU
  End FU

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Sampling a cohort population for controls nested
case-control study

• 2. Sample population at risk as cases develop
• -------------------------------------------------
  ------------------------
• Start FU
  End FU
• 
  

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Sampling a cohort population for controls nested
case-control study

• 3. Sample survivors at the end of the observation
  period
• -------------------------------------------------
  -----------------------
• Start FU
  End FU
• 
  

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Recall nested case-control study on pesticides
and breast cancer

• Hypothetical cohort study of 89,949 women 1,439
  breast cancer cases identified over 8 years of
  follow-up
• Blood drawn on all 89,949 at beginning of
  follow-up and frozen
• Exposure Level of pesticides (e.g. DDE) in blood
  characterized as high or low

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Recall nested case-control study on pesticides
and breast cancer
Breast Cancer
DDE
To be efficient, we analyzed blood on all cases
(N1,439) and took take a sample of the women who
did not get breast cancers (N2,878). What type
of control sampling is this? Anyone of the three
sampling methods could have been used to select
the controls.
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Important consideration for selecting controls
the would criterion

• Review Controls are a sample of the source
  population that gave rise to the cases. Purpose
  is to provide information on the exposure
  distribution in the source population.
• When selecting a control group consider the
  WOULD CRITERION If a member of the control
  group actually had the disease under study WOULD
  he/she end up as a case in your study? Answer
  should be YES.
• Example Spontaneous abortion study

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Analysis of case-control studies
Exposed
Because controls are a sample of the population
that produced the cases, size of the total
population is often unknown. Thus, you cant get
a cumulative incidence or incidence rate of
disease or calculate the measures of association
using the methods that we have learned. Instead
you get a number called an odds which will
function as a rate.
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Analysis of case-control studies

• Definition of odds the ratio of the
  probability of an event occurring to that of it
  not occurring
• Example Probability of getting a heads on one
  coin toss ½ .50. Probability of NOT getting
  a heads on one coin toss ½ .50. Odds of
  getting a heads on a coin toss .5/.5 11

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Analysis of case-control studies

• Two possible outcomes for an exposed person case
  or not
• Oddsa/b
• Two possible outcomes for an unexposed person
  case or not Oddsc/d
• Odds ratio odds of an exposed person being a
  case a/b ad/bc
• odds of unexposed person being a case c/d
• Just like the incidence rate ratio and cumulative
  incidence ratio, the odds ratio is a ratio
  measure of association.

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Analysis of case-control studies

• EXAMPLE Case control study of spontaneous
  abortion and prior induced abortion (OUTCOME
  spontaneous abortion EXPOSURE prior induced
  abortion)

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Analysis of case-control studies

• Odds of being a case among the exposed
• 42/247 (a/b)
• Odds of being a case among the unexposed
  107/825 (c/d)
• Odds ratio (a/b) / (c/d)
• (42/247) / (107/825)
  1.3
• Women with a history of induced abortion had a
  30 increased risk of having a spontaneous
  abortion compared to women who never had an
  induced abortion.

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Strengths of case-control studies

• Efficient for rare diseases and diseases with
  long induction and latent period.
• Can evaluate many risk factors for the same
  disease. So, good for diseases about which little
  is known.

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Weaknesses of case-control studies

• Inefficient for rare exposures
• Vulnerable to bias because of retrospective
  nature of study
• May have poor information on exposure because
  retrospective
• Difficult to infer temporal relationship between
  exposure and disease
• How do these strengths and weaknesses
  compare to cohort studies?