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Are Nested Case-Control Studies Biased?
Open accessAbstract
It has been recently asserted that the nested case-control study design, in which case-control sets are sampled from cohort risk sets, can introduce bias ("study design bias") when there are lagged exposures. The bases for this claim include a theoretical and an "empirical evaluation" argument. We examined both of these arguments and found them to be incorrect. We describe an appropriate empirical evaluation method to explore the performance of nested case-control study designs and analysis methods from an existing cohort. This empirical evaluation approach relies on simulating case-control outcomes from risk sets in the cohort from which the case-control study is to be performed. Because it is based on the underlying cohort structure, the empirical evaluation can provide an assessment that is tailored to the specific characteristics of the study under consideration. The methods are illustrated using samples from the Colorado Plateau uranium miners cohort.
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The nested case control design provides unbiased estimates of effects when compared with the equivalent cohort study.
“With respect to study design, our estimates generalise to those surviving at least four years after their initial anticholinergic exposure, and the nested case control design provides unbiased estimates of effects when compared with the equivalent cohort study.35”
From Anticholinergic drugs and risk of dementia: case-control study (2018) · cites this paper as [35]
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Anticholinergic drugs and risk of dementia: case-control study
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Metadata
- Authors
- Langholz, B., & Richardson, D.
- Affiliations
- University of Southern California (US)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Langholz, Bryan
- ORCID
- Langholz, Bryan
- Venue
- Epidemiology
- Published
- 2009-05
- Volume
- 20
- Issue
- 3
- Pages
- 321-329
- ISSN
- 1044-3983 (ISSN-L)
- PMC
- PMC4194079
- OpenAlex
- W2076430538
- Cited by
- 29
- References
- 0
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2022: 2 · 2021: 1 · 2020: 1 · 2018: 3 · 2016: 1 · 2013: 2 · 2012: 4
- FWCI
- 3.05
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Epidemiology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- National Cancer Institute (R01CA042949)
- National Institute of Environmental Health Sciences (P30ES007048)
- Topics
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Epidemiology
- Health Sciences › Medicine › Oncology › Global Cancer Incidence and Screening
- Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Meta-analysis and systematic reviews
- Keywords
- nested case-control study, study design bias, lagged exposure, cohort structure, Colorado Plateau
- MeSH terms
- Adult, Aged, Aged, 80 and over, Humans, Middle Aged, Mining, Uranium, Epidemiologic Research Design, Bias, Proportional Hazards Models, Case-Control Studies, Occupational Exposure, Risk Assessment
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