Bias in observational study of the effectiveness of nasal corticosteroids in asthma
Open accessAbstract
Background A recent observational study suggests that intranasal corticosteroids used to treat allergic rhinitis are effective at preventing asthma outcomes, such as emergency visits. The approach to data analysis may have led to biased results because of misclassification of immortal time.Objective To illustrate the bias in the cohort approach and to present the proper time-dependent analysis by replicating the recent study using data from another source.Methods From an existing cohort of 30,569 patients with asthma age 5 to 44 years and identified from the Saskatchewan Health databases (1975-1997), we formed the cohort of all subjects who were in the source population between January 1, 1989, and December 31, 1991. Subjects were followed to the first asthma hospitalization. All prescriptions dispensed during follow-up were identified. We replicated the time-fixed approach to data analysis used in the recent study and compared it with time-dependent approaches.Results The cohort included 20,173 subjects, of whom 1849 were hospitalized for asthma between January 1, 1989, and December 31, 1991. The time-fixed approach misclassified more than 5000 person-years of follow-up, corresponding to 44% of the exposed person-time. As a result, the rate ratio of asthma hospitalization after any use of nasal corticosteroids (NCSs) was 0.57 by the biased time-fixed approach compared with 1.13 by the proper time-dependent approach. The time-fixed approach produced a paradoxical protective effect of NCS with 1 or less canisters dispensed per year (odds ratio, 0.47), which was further exaggerated when the cohort was extended to 5 years (odds ratio, 0.33). Adjusted time-dependent analyses found no protective effect, even when NCSs were dispensed regularly (rate ratio, 1.10; 95% CI, 0.54-2.21).Conclusion The time-fixed approach to the analysis of the effectiveness of NCSs on asthma outcomes leads, by its inherent misclassification of immortal time, to a considerable exaggeration of the protective effect of these medications in preventing severe asthma exacerbations.
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The studies reviewed in this section were limited to prospective randomized trials to minimize biases and weaknesses of retrospective studies.
“The studies reviewed in this section are limited to prospective randomized trials to minimize inherent biases and weaknesses of retrospective studies.1794”
From International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (2018) · cites this paper as [1794]
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- Authors
- Suissa, S., & Ernst, P.
- Affiliations
- McGill University Health Centre (CA)
- Corresponding author
- Suissa, Samy
- Venue
- Journal of Allergy and Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2005-04
- Volume
- 115
- Issue
- 4
- Pages
- 714-719
- ISSN
- 0091-6749 (ISSN-L)
- OpenAlex
- W2019885409
- Cited by
- 39
- References
- 34
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 2 · 2019: 1 · 2018: 2 · 2017: 1 · 2016: 1 · 2015: 1 · 2014: 1 · 2013: 1 · 2012: 2
- FWCI
- 4.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Allergy and Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Epidemiology
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Physical Sciences › Mathematics › Statistics and Probability › Advanced Causal Inference Techniques
- Keywords
- intranasal corticosteroids, asthma, immortal time bias, time-dependent analysis, asthma hospitalization, allergic rhinitis, bias in observational studies, asthma exacerbations
- MeSH terms
- Administration, Inhalation, Administration, Intranasal, Adolescent, Adrenal Cortex Hormones, Adult, Asthma, Child, Child, Preschool, Hospitalization, Humans, Research Design, Rhinitis, Statistics as Topic, Time, Bias, Observation
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