Choosing a reference group

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Choosing a reference group

• James Stuart
• EPIET, Mahon
• September 2006

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Objectives

• Define source population
• Understand importance of representativeness
• Describe advantages and disadvantages of
  selecting different types of controls
• Apply public health principles to choice of
  reference groups in case-control studies

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Making comparisons

• Incidence in exposed and unexposed
• Exposure in cases and controls
• Incidence over time

fundamental to epidemiology
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Field epidemiology

• Can be difficult to select reference group
• Especially in case control studies
• Constraints of time and resource

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Case control study

• Outbreak
• 24 cases of Salmonella Typhimurium
• Cornwall (population 500,000)
• South West England
• not far from Wales
• long way from Scotland
• onset through May 2004
• age range 16 56 years
• 9 male, 6 female
• no recent travel abroad

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Who are the right controls?
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Controls

• Controls should be representative
• of population from which cases arise
• (source population)

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Control characteristics

• If controls represent source population
• be representative of exposures in source
  population
• be identified as cases if they had disease under
  study
• have same exclusion and restriction criteria as
  cases

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Source population
Cases
Exposed
Sample
Unexposed
Controls Sample of the denominator
Representative with regard to exposure
Controls
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Who is source population?

• Start with your case definition

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Case definition

• Resident of Cornwall aged above 15 years with
  isolate of Salmonella Typhimurium in faecal
  sample during May 2004
• Exclusion Travel abroad in week before illness
• What is source population?

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Source population

• Residents of Cornwall aged above 15 years
• during May 2004
• who have not recently travelled abroad
• Controls should then be
• representative of this population

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Q2. How to select controls?

• Aim for random sample of source population
• Not always feasible

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Selecting controls (examples)

• Population
• random from register/list/directory
• stratified (age/sex/general practice)
• Friends
• Neighbourhood
• Hospital

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Population controls

• Is there a list or register of source population?
  
• Such a list should
• be complete
• contain all cases
• be readily accessible
• identify specified characteristics e.g. age
• Take random sample

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or... random digit dialling

• using residential directories or mobile numbers
  (e.g. add 5 to case number)
• quick and easy
• but may be bias in selection
• telephone ownership
• availability
• geographical area
• participation

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or stratification

• Stratification in study design matching
• e.g. same age, same sex, same doctor
• Matching useful if
• do not have full list of source population
• do not want to measure effect of matching
  variables
• Presentation next week

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Friend controls

• Advantages
• good matching for social factors
• can be quick and efficient
• validity in food poisoning investigations

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Friends controls

• Disadvantages
• Co-operation may be limited (concern about giving
  out names)
• if exposure same as in cases, may not detect
  causal association
• Overmatching

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Neighbourhood controls

• Advantages
• no need for population register
• similar socio- economic status
• Disadvantages
• low co-operation
• may be time consuming and expensive
• might be too similar to cases

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Hospital controls

• Advantages
• useful if all cases identified from hospital
  register
• easily identified
• cost and time efficient
• Disadvantages
• different catchments for different diseases
• overmatching on exposures for other diseases

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Sample size

• Often limited by number of cases available
• Unusual to select more than 2-3 controls/case
• Little extra power beyond this number

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Controls may not be easy to find
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Source population

• Residents of Cornwall aged above 15 years
• during May 2004
• who have not recently travelled abroad

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Which reference group ?

• You are in charge of the case control study
• What is your control definition?
• How would you select them?
• No population register or list is available
• Please discuss with your neighbourhood control

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Some common questions

• Non-cases as controls
• Asymptomatic cases
• Immune populations
• 100 exposure

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Non-cases as controls

• If attack rate high
• high risk that non-cases do not represent
  exposures in source population
• If attack rate low
• low risk that non-cases do not represent
  exposures in source population
• can use as controls

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Non-cases as controls
start
end
High attack rate
Cases
Sourcepopn
Non- cases
Low attack rate
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Asymptomatic cases

• Does it matter if we fail to identify mild cases?
  
• Analogous to non-response
• Example 40 cases, 40 controls

OR 20.30/20.10 3.0
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Asymptomatic cases

• If we only identify half the cases and exposure
  is the same

OR 30.10/10.10 3.0 No bias
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Immune subjects

• Not eligible as cases
• So not in source population
• Difficult to identify
• May have been cases in past
• May have similar level of exposure to risk factor
  as current cases in study
• Bias in OR towards 1 (null value)

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100 exposure

• What if close to 100 of population exposed?
• e.g. foodborne disease outbreaks where little
  choice in menu
• Try to measure dose response
• Reference group lowest level of exposure (case
  study to come)

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Key points in choosing controls

• Define source population
• Aim for representative sample
• Review pros and cons of available options
• Plan to minimise bias, taking account of
  resources and urgency

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Be prepared to defend your choice
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and

• do the study!

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References

• Rothmann KJ, Greenland S. Modern epidemiology.
  Lippincott-Raven 1998.
• Hennekens CH, Epidemiology in Medicine.
  Lippincott-Williams and Wilkins 1987.
• Gregg MB. Field epidemiology. Oxford University
  Press 1996.
• Wacholder S, McLaughlin JK, Silverman DT, Mandel
  JS. Selection of controls in case control studies
  I-III. Am J Epidemiol 1992 135 1019-50.

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Volvo factory, Sweden 3000 employees 200 cases
of gastroenteritis
Although preferable to do a cohort study, you
are short of staff to do the investigation and
you decide to do a case control study using 200
controls from the same factory How would you
select the 200 controls?