Impact of referral bias on clinical and epidemiological studies of Alzheimer's disease

doi:10.1016/0895-4356(95)00031-3

Journal of Clinical Epidemiology

Volume 49, Issue 1, January 1996, Pages 79-83

https://doi.org/10.1016/0895-4356(95)00031-3 Get rights and content

Abstract

We used the resources of the Rochester Epidemiology Project to compare sociodemographic and clinical characteristics in three groups of Alzheimer's disease patients. The first group included incidence cases occurring among residents of Rochester, Minnesota (population-based series; n = 241). The second group was a sample of patients referred to the Mayo Clinic from the remainder of Minnesota and the four surrounding states (n = 58); the third was a sample referred from the remainder of the United States (n = 94). Patients from Rochester were more frequently women, less highly educated, less commonly white collar workers, more frequently institutionalized, less frequently married, and more often lived alone than those in the two referral groups. Patients from Rochester also had a more advanced age of onset of dementia. For occupation, education, and living arrangement, the differences across groups increased with increasing distance of referral. Clinical and epidemiological studies based on patients referred from primary to secondary or tertiary care centers may suffer from severe selection bias.

References (23)

DL Sackett
Bias in analytic research
J Chron Dis
(1979)
JM Steckelberg et al.
Influence of referral bias on the apparent clinical spectrum of infective endocarditis
Am J Med
(1990)
MA Warner et al.
Effects of referral bias on surgical outcomes: A population-based study of surgical patients 90 years of age or older
LK Bickerstaff et al.
Abdominal aortic aneurysms: The changing natural history
J Vase Surg
(1984)
J Berkson
Limitations of the application of fourfold table analysis to hospital data
Biometrics
(1946)
LJ Melton
Selection bias in the referral of patients and the natural history of surgical conditions
LT Kurland et al.
The patient record in epidemiology
Sci Am
(1981)
CM Beard et al.
Lack of association between Alzheimer's disease and education, occupation, marital status, or living arrangement
Neurology
(1992)
E Kokmen et al.
Epidemiologic studies of dementia in Rochester, Minnesota
E Kokmen et al.
Clinical risk factors for Alzheimer's disease: A population-based case-control study
Neurology
(1991)

G McKhann et al.

Clinical diagnosis of Alzheimer's disease: Report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease

Neurology

(1984)

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Phenotypes and body mass in women with polycystic ovary syndrome identified in referral versus unselected populations: systematic review and meta-analysis
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Citation Excerpt :
Berkson's bias, a form of selection bias, was first described in 1946 and questioned the validity of epidemiological studies performed in medical settings (60). Extensive evidence demonstrates that patients with Alzheimer's disease, cancer, and surgical conditions identified in clinical facilities are not necessarily representative of the same diagnoses in the general population (61–63). Cases identified in clinical settings tend to have a more severe manifestation of the disease and differ from the general population in socioeconomic variables.
To compare the prevalence of polycystic ovary syndrome (PCOS) phenotypes and obesity among patients detected in referral versus unselected populations.
Systematic review and meta-analysis.
Not applicable.
Thirteen thousand seven hundred ninety-six reproductive-age patients with PCOS, as defined by the extended Rotterdam 2003 criteria.
Review of PUBMED, EMBASE, and Cochrane Library, 2003–2016. Only observational studies were included. Data were extracted using a web-based, piloted form and combined for meta-analysis.
PCOS phenotypes were classified as follows: phenotype A, clinical and/or biochemical hyperandrogenism (HA) + oligo-/anovulation (OA) + polycystic ovarian morphology (PCOM); phenotype B, HA+OA; phenotype C, HA+PCOM; and phenotype D, OA+PCOM.
Forty-one eligible studies, reporting on 43 populations, were identified. Pooled estimates of detected PCOS phenotype prevalence were consequently documented in referral versus unselected populations, as [1] phenotype A, 50% (95% confidence interval [CI], 46%–54%) versus 19% (95% CI, 13%–27%); [2] phenotype B, 13% (95% CI, 11%–17%) versus 25% (95% CI, 15%–37%); [3] phenotype C, 14% (95% CI, 12%–16%) versus 34% (95% CI, 25–46%); and [4] phenotype D, 17% (95% CI, 13%–22%) versus 19% (95% CI, 14%–25%). Differences between referral and unselected populations were statistically significant for phenotypes A, B, and C. Referral PCOS subjects had a greater mean body mass index (BMI) than local controls, a difference that was not apparent in unselected PCOS.
The prevalence of more complete phenotypes in PCOS and mean BMI were higher in subjects identified in referral versus unselected populations, suggesting the presence of significant referral bias.
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^☆: This study was supported in part by research grants NS17750, AG06786, and AG08031 from the National Institutes of Health, Bethesda, Maryland.

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Original articleImpact of referral bias on clinical and epidemiological studies of Alzheimer's disease☆

Abstract

J Chron Dis

Am J Med

J Vase Surg

Limitations of the application of fourfold table analysis to hospital data

Biometrics

Selection bias in the referral of patients and the natural history of surgical conditions

The patient record in epidemiology

Sci Am

Lack of association between Alzheimer's disease and education, occupation, marital status, or living arrangement

Neurology

Epidemiologic studies of dementia in Rochester, Minnesota

Clinical risk factors for Alzheimer's disease: A population-based case-control study

Neurology

Clinical diagnosis of Alzheimer's disease: Report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease

Neurology

Original article
Impact of referral bias on clinical and epidemiological studies of Alzheimer's disease☆