Transcript Choosing a reference group - European Centre for Disease

Epidemio l o gy
Choosing a reference group
James Stuart
EPIET, Mahon
September 2006
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
Making comparisons
• Incidence in exposed and unexposed
• Exposure in cases and controls
• Incidence over time
fundamental to epidemiology
Field epidemiology
• Can be difficult to select reference group
• Especially in case control studies
• Constraints of time and resource
Case control study
Outbreak
• 24 cases of Salmonella Typhimurium
• Cornwall (population 500,000)
South West England
not far from Wales
long way from Scotland
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•
•
•
onset through May 2004
age range 16 – 56 years
9 male, 6 female
no recent travel abroad
Who are the right controls?
Controls
Controls should be representative
of population from which cases arise
(source population)
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
Source population
Exposed
Sample
Cases
Unexposed
Controls:
Sample of the denominator
Representative with
regard to exposure
Controls
Who is source population?
Start with your case definition
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?
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
Q2. How to select controls?
• Aim for random sample of source population
• Not always feasible
Selecting controls (examples)
• Population
random from register/list/directory
stratified (age/sex/general practice)
• Friends
• Neighbourhood
• Hospital
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
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
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
Friend controls
Advantages
• good matching for social factors
• can be quick and efficient
• validity in food poisoning investigations
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
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
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
Sample size
• Often limited by number of cases available
• Unusual to select more than 2-3 controls/case
• Little extra power beyond this number
Controls may not be easy to find
Source population
Residents of Cornwall aged above 15 years
during May 2004
who have not recently travelled abroad
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
Some common questions
• Non-cases as controls
• Asymptomatic cases
• Immune populations
• 100% exposure
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
Non-cases as controls
start
end
Cases
Source
popn
High attack rate
Noncases
Low attack rate
Asymptomatic cases
• Does it matter if we fail to identify mild cases?
• Analogous to non-response
• Example: 40 cases, 40 controls
Cases
Controls
Exposed
20
10
Not exposed
20
30
OR = 20.30/20.10 = 3.0
Asymptomatic cases
• If we only identify half the cases and %
exposure is the same
Cases
Controls
Exposed
10
10
Not exposed
10
30
OR = 30.10/10.10= 3.0
No bias
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)
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)
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
Be prepared to defend your choice…
…and
do the study!
References
• Rothmann KJ, Greenland S. Modern epidemiology.
Lippincott-Raven 1998.
• Hennekens CH, Epidemiology in Medicine. LippincottWilliams 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.
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?