6.3 sources of controls

1. Principles
• Wacholder et al. series of articles – please read
• Principles of case-control studies
– Critical one is the study base principle

2. Principles
• Study base principle
– Members of the study base are people who would
have been identified as cases over the study period if
they had acquired disease
– Controls must be selected from the study base that
gave rise to the cases – identifying the appropriate
study base from which to select the controls is the
challenge in the case-control design

3. Principles
• “Study base principle. Cases and controls should
be ‘representative of the same base experience’.
• The base is the set of persons or person-time,
depending on the context, in which diseased
subjects become cases.
• The base can also be thought of as the
members of the underlying cohort or source
population for the cases during the time periods
when they are eligible to become cases.”
(Wacholder et al. 1992)

4. Sources of controls
• Sources of controls when study base cannot be
enumerated
– Random digit dial (RDD)
– Neighborhood
– Hospital/clinic
– Relative
– Dead
– Multiple control groups

5. Sources of controls
• Random digit dial (RDD) controls
– One way to contact population controls if population is
not enumerated
– Issues:
• Telephone coverage
• Cell phone only households increasing – have to include cell
phone sample
• Have to account for # phone lines and # persons in
household in analysis
• Low response
• Labor intensive especially if screening for particular criteria

6. Sources of controls
• Neighborhood controls
– Another way to contact population controls if
population not enumerated
• Could also use in secondary base study but have to assess
whether neighborhood controls satisfy study base principle
for particular study

7. Sources of controls
• Neighborhood controls
– Issues:
• Labor intensive to create neighborhood roster
• Have to do best to create a selection process independent of
exposure (presumably will not be random)
• Have to account for household as sampling unit in analysis
• Difficult to quantify non-response if can’t reach people
• Introduces geographic matching which could create
overmatching—a problem that we’ll cover in a later unit on
matching

8. Sources of controls
• Hospital/clinic controls
– One way to identify secondary study base controls
– If both are being seen in same medical setting it may
be reasonable that are part of same study base – but
have to assess that for particular study

9. Sources of controls
• Hospital/clinic controls
– Issues:
• Have to assess whether they are members of the study base
(e.g., hospital that provides specialized care for outcome
condition and/or control condition(s))
• Controls who have other diseases may not represent the
exposure in the study base – the exposure may be related to
the control disease diagnosis or hospitalization (Berkson’s
bias – to be discussed later)
• Best to include variety of diagnostic categories to dilute bias
• Convenient

10. Sources of controls
• Friend controls
– Another approach to identify secondary study base
controls
– Issues:
• Difficult to argue they represent the study base – especially
for any exposures related to sociability
• Can lead to overmatching

11. Sources of controls
• Relative controls
– Motivated by deconfounding (would not argue they
represent the study base) – matching on genetic
background (sibling) or environment (spouse)
– Issues:
• May introduce overmatching

12. Sources of controls
• Dead controls
– Violates study base principle in obvious way – cannot
be actual representatives of the study base that gave
rise to cases if they are dead
– Question is whether exposure in the dead controls
represents the exposure that would have been
observed in members of the study base
– Issues:
• Convenient for some studies (e.g., based on death records)

13. Sources of controls

14. Sources of controls
• Multiple control groups
– Although sometimes useful it can be difficult to know
what to say about discordant results
– Decide what group is best at design stage