Brief CommunicationPooling of Confounders Did Not Induce Residual Confounding in Influenza Vaccination Studies
Introduction
In observational studies on influenza vaccine effectiveness, several confounding variables are often pooled into a single dichotomous confounder 1, 2, 3. For example, several diagnoses of chronic diseases are combined into a single variable, indicating the presence of at least one of the included diagnoses. However, concerns have been raised recently that such pooling of confounders may result in residual confounding (4). Nevertheless, empirical studies quantifying this potential bias are scarce. We set out to study the effects of combining several confounders into classes of co-morbidity in a study on the association between influenza vaccination and mortality risk among community-dwelling elderly.
An important reason to combine several confounders is the limited number of cases in a dataset; hence, precision may be at stake when the number of covariates adjusted for in multivariable models is too large 5, 6. We used a large dataset from a retrospective cohort study with enough cases to include all confounders as separate covariates in a multivariable model according to the rule of thumb (10 cases per variable) 5, 6. Effect estimates derived from the dataset using different confounding variable approaches could, therefore, be adequately compared.
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Methods
We used data from the computerized medical database of the University Medical Center Utrecht General Practitioner Research Network. This database complies with Dutch guidelines on the use of medical data for research purposes and has shown to be valid in influenza vaccine effectiveness studies (2). Diagnoses are coded according to the International Classification of Primary Care (ICPC) coding system. Information on all elderly (age ≥65 years) from seven influenza epidemic periods (1995/1996,
Results
The prevalence of different types of cardiovascular co-morbidity ranged from 0.3% (chronic ischemic heart disease) to 3.3% (congestive heart failure). The prevalence of pulmonary co-morbidity ranged from 0.2% (lung cancer) to 4.4% (COPD). The prevalence of different types of cancer ranged from 0.04% (Hodgkin's disease) to 0.8% (skin cancer). In total, 379 persons died during 44,418 influenza epidemic periods of observation. During 32,388 periods of observation (72.9%) subjects received
Discussion
Estimates of the effect of influenza vaccination on mortality obtained after adjustment for all individual diagnoses and after adjustment for three pooled co-morbidity variables were similar.
Effects of influenza vaccination on serious, infrequent outcomes such as mortality have only been studied in observational studies 1, 9. Obviously, such study designs are prone to confounding bias and which variables are important confounders in these studies has been fiercely debated 4, 9, 10, 11. These
References (16)
- et al.
Efficacy and effectiveness of influenza vaccines in elderly people: A systematic review
Lancet
(2005) - et al.
A simulation study of the number of events per variable in logistic regression analysis
J Clin Epidemiol
(1996) - et al.
Design of the Dutch prevention of influenza, surveillance and management (PRISMA) study
Vaccine
(2003) - et al.
Mortality benefits of influenza vaccination in elderly people: an ongoing controversy
Lancet Infect Dis
(2007) - et al.
Clinical effectiveness of influenza vaccination in persons younger than 65 years with high-risk medical conditions: the PRISMA study
Arch Intern Med
(2005) - et al.
Effectiveness of influenza vaccine in the community-dwelling elderly
N Engl J Med
(2007) - et al.
Functional status is a confounder of the association of influenza vaccine and risk of all cause mortality in seniors
Int J Epidemiol
(2006) - et al.
Relaxing the rule of ten events per variable in logistic and Cox regression
Am J Epidemiol
(2007)
Cited by (0)
This study is part of a personal grant of Dr. E. Hak to study confounding in observational intervention studies by the Netherlands Scientific Organization (VENI no. 916.56.109). There are no conflicts of interest.