what do case-control studies estimate? research meeting ispm – july 16th 2007 mirjam j. knol, jan...
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What do case-control studies estimate?
Research meeting ISPM – July 16th 2007
Mirjam J. Knol, Jan P. Vandenbroucke, Pippa Scott, Matthias Egger
A survey of 150 published studies
Introduction
Case-control design
• 1 of 3 main epidemiological designs
• First use 1926
• Widely used about 348,000 in Medline
• Efficient design if:
- Outcome is rare
- Exposure is expensive to measure
- Results are quickly needed
Introduction
Definition case-control study
• Study of persons with the disease (or other outcome variable) of
interest (cases) and a suitable control group of persons without
the disease (controls), where the history of exposure to a
suspected risk or preventive factor is compared between cases
and controls
Introduction
Interpretation of estimated odds ratio depends on:
• Nature of cases
- Prevalent cases
- Incident cases
• Type of source population
- Fixed cohort
- Dynamic population (stable population)
• Sampling design for controls
- From population at risk end of study period
- From population at risk beginning of study period
- From person-time at risk
Introduction
Fixed cohort
• A cohort in which no additional membership is allowed and in
which immigration cannot occur, i.e. it is fixed by being present at
some defining event
Introduction
Fixed cohort
• A cohort in which no additional membership is allowed and in
which immigration cannot occur, i.e. it is fixed by being present at
some defining event
Dynamic population
• A population that gains and loses members, i.e. a population in
which emigration and immigration may occur over the risk period
Introduction
Fixed cohort
• A cohort in which no additional membership is allowed and in
which immigration cannot occur, i.e. it is fixed by being present at
some defining event
Dynamic population
• A population that gains and loses members, i.e. a population in
which emigration and immigration may occur over the risk period
Stable population
• A population in which the distributions of all variables of interest
including exposures are not changing over time
Introduction
End of study period (exclusive / traditional) – fixed cohort
• Controls are sampled from the population still at risk at the end of
the study period.
Introduction
End of study period (exclusive / traditional) – fixed cohort
• Controls are sampled from the population still at risk at the end of
the study period.
Beginning of study period (inclusive) – fixed cohort
• Controls are sampled from all individuals in the study population
at risk at the beginning of the study period.
Introduction
End of study period (exclusive/traditional) – fixed cohort
• Controls are sampled from the population still at risk at the end of the
study period.
Beginning of study period (inclusive) – fixed cohort
• Controls are sampled from all individuals in the study population at risk
at the beginning of the study period.
Person-time
• Concurrent / matched on time – fixed and dynamic cohort
- Controls are sampled from those at risk at the time each case is
diagnosed.
• Not matched on time – dynamic cohort
- Controls are sampled from those at risk at a certain point in time
Introduction
Fixed cohort
End of study period
Assumption:Rare disease
Risk ratio
Beginning of study period
Assumption:Censoring
unrelated to exposure
Risk ratio
Concurrent
Rate ratio
Dynamic population
Matched on time
Not matched on time
Assumption:Stable population
Rate ratio
Rate ratio
Incident cases
Prevalent cases
Prevalence odds ratio
Objective
To conduct a survey of published case-control studies to examine
what was estimated by the odds ratio
Methods
Literature search
• Combining journal names and Mesh term ‘Case-control studies’
• From March 2007 backwards in time
• Total of 150 articles
Methods
Literature search
• Combining journal names and Mesh term ‘Case-control studies’
• From March 2007 backwards in time
• Total of 150 articles
Selected journals
• 5 general medicine journals 10 articles each- Annals of internal medicine, BMJ, JAMA, Lancet, NEJM
• 5 general epidemiology journals 10 articles each- AJE, Epidemiology, IJE, JCE, JECH
• 10 clinical specialist journals 5 articles each- AJRCCM, AGP, Arthritis and rheumatism, Blood, Circulation, CID, Diabetes Care,
JAGS, JNCI, Pediatrics
Methods
Data extraction
• Standardized form
- General items: sample size, exposure, outcome
- Specific items: type of source population and sampling design
• Two reviewers (MK and PS)
Methods
Data extraction
• Standardized form
- General items: sample size, exposure, outcome
- Specific items: type of source population and sampling design
• Two reviewers (MK and PS)
Data-analysis
• Frequencies of general and specific items
• Fisher‘s Exact test
• Use of flow chart
Results
General medicine articles (n=50)
General epidemiologyarticles (n=50)
Clinical specialistarticles (n=50)
Number of cases 494 (26-13,556) 611 (42-22,225) 282 (18-21,169)
Number of controls 846 (27-135,386) 1204 (85-180,220) 585 (20-423,128)
Source of cases
Population based 31 31 26
Hospital based 12 15 21
Both 1 1 0
Unclear 6 3 3
Source of controls
Population based 36 36 29
Hospital based 8 8 10
Both 2 2 2
Unclear 4 4 9
Results
General medicine articles (n=50)
General epidemiologyarticles (n=50)
Clinical specialistarticles (n=50)
Number of cases 494 (26-13,556) 611 (42-22,225) 282 (18-21,169)
Number of controls 846 (27-135,386) 1204 (85-180,220) 585 (20-423,128)
Source of cases
Population based 31 31 26
Hospital based 12 15 21
Both 1 1 0
Unclear 6 3 3
Source of controls
Population based 36 36 29
Hospital based 8 8 10
Both 2 2 2
Unclear 4 4 9
Results
General medicine articles (n=50)
General epidemiologyarticles (n=50)
Clinical specialistarticles (n=50)
Number of cases 494 (26-13,556) 611 (42-22,225) 282 (18-21,169)
Number of controls 846 (27-135,386) 1204 (85-180,220) 585 (20-423,128)
Source of cases
Population based 31 31 26
Hospital based 12 15 21
Both 1 1 0
Unclear 6 3 3
Source of controls
Population based 36 36 29
Hospital based 8 8 10
Both 2 2 2
Unclear 4 4 9
Results
General medicine articles(n=50)
General epidemiologyarticles(n=50)
Clinical specialistarticles(n=50)
Incident cases 46 45 34
Fixed cohort 10 3 11
End 4 1 6
Beginning 0 0 1
Concurrent 3 1 2
Unclear 3 1 2
Dynamic population 34 41 20
Matched on time 9 8 3
Not matched on time 7 4 3
Unclear 18 28 14
Unclear 2 1 3
Prevalent cases 2 2 6
Unclear 2 3 10
Results
General medicine articles(n=50)
General epidemiologyarticles(n=50)
Clinical specialistarticles(n=50)
Incident cases 46 45 34
Fixed cohort 10 3 11
End 4 1 6
Beginning 0 0 1
Concurrent 3 1 2
Unclear 3 1 2
Dynamic population 34 41 20
Matched on time 9 8 3
Not matched on time 7 4 3
Unclear 18 28 14
Unclear 2 1 3
Prevalent cases 2 2 6
Unclear 2 3 10
Results
General medicine articles(n=50)
General epidemiologyarticles(n=50)
Clinical specialistarticles(n=50)
Incident cases 46 45 34
Fixed cohort 10 3 11
End 4 1 6
Beginning 0 0 1
Concurrent 3 1 2
Unclear 3 1 2
Dynamic population 34 41 20
Matched on time 9 8 3
Not matched on time 7 4 3
Unclear 18 28 14
Unclear 2 1 3
Prevalent cases 2 2 6
Unclear 2 3 10
Results
General medicine articles(n=50)
General epidemiologyarticles(n=50)
Clinical specialistarticles(n=50)
Incident cases 46 45 34
Fixed cohort 10 3 11
End 4 1 6
Beginning 0 0 1
Concurrent 3 1 2
Unclear 3 1 2
Dynamic population 34 41 20
Matched on time 9 8 3
Not matched on time 7 4 3
Unclear 18 28 14
Unclear 2 1 3
Prevalent cases 2 2 6
Unclear 2 3 10
Results
General medicine articles(n=50)
General epidemiologyarticles(n=50)
Clinical specialistarticles(n=50)
Incident cases 46 45 34
Fixed cohort 10 3 11
End 4 1 6
Beginning 0 0 1
Concurrent 3 1 2
Unclear 3 1 2
Dynamic population 34 41 20
Matched on time 9 8 3
Not matched on time 7 5 3
Unclear 18 28 14
Unclear 2 1 3
Prevalent cases 2 2 6
Unclear 2 3 10
Results
What does the odds ratio estimate?
• Risk ratio if rare disease 11 (4/1/6)
• Risk ratio if exposure unrelated to censoring 1 (0/0/1)
• Rate ratio 26 (12/9/5)
• Rate ratio if stable population 75 (25/33/17)
• Prevalence odds ratio 10 (2/2/6)
• Unclear 27 (7/5/15)
Total 150 (50/50/50)
Significant difference between type of journal
Conclusions
• Majority of studies uses dynamic population (63%)
• Many studies do not explicitly say when controls were sampled
• Most studies (50%) estimate rate ratio if stable population
• Authors do not discuss stability of exposure
• Rare disease assumption only needed in few studies (7%)
• Teaching should focus more on assumption of stability of exposure
• Authors do not report what odds ratio estimates are they aware
what their odds ratio estimates?
• Better reporting is needed STROBE
Thank you all
for the nice time!