Abstract
Background:
Despite concerns about the representativeness of patients from ALS tertiary centers as compared to the ALS general population, the extent of referral bias in clinical studies remains largely unknown. Using data from EURALS consortium we aimed to assess nature, extent and impact of referral bias.
Methods:
Four European ALS population-based registries located in Ireland, Piedmont, Puglia, Italy, and Limousin, France, covering 50 million person-years, participated. Demographic and clinic characteristics of ALS patients diagnosed in tertiary referral centers were contrasted with the whole ALS populations enrolled in registries in the same geographical areas.
Results:
Patients referred to ALS centers were younger (with difference ranging from 1.1 years to 2.4 years), less likely to present a bulbar onset, with a higher proportion of familial antecedents and a longer survival (ranging from 11% to 15%) when compared to the entire ALS population in the same geographic area.
Conclusions:
A trend for referral bias is present in cohorts drawn from ALS referral centers. The magnitude of the possible referral bias in a particular tertiary center can be estimated through a comparison with ALS patients drawn from registry in the same geographic area. Studies based on clinical cohorts should be cautiously interpreted. The presence of a registry in the same area may improve the complete ascertainment in the referral center.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aged
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Amyotrophic Lateral Sclerosis / diagnosis
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Amyotrophic Lateral Sclerosis / epidemiology*
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Bias*
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Delayed Diagnosis
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Europe / epidemiology
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Female
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Humans
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Male
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Middle Aged
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Public Health Surveillance
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Referral and Consultation* / statistics & numerical data
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Registries
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Tertiary Care Centers
Grants and funding
James Rooney was funded by the Health Research Programme Clinical Fellowship Programme. Marwa Elamin, Alice Vajda and Mark Heverin report no disclosures and no conflicts of interest. Orla Hardiman is funded by the Health Research Board Clinician Scientist Programme. Prof. Hardiman has received speaking honoraria from Novarits, Biogen Idec, Sanofi Aventis and Merck-Serono. She has been a member of advisory panels for Biogen Idec, Allergen, Ono Pharmaceuticals, Novartis, Cytokinetics and Sanofi Aventis. She serves as Editor-in-Chief of Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. She funded by Euro-MOTOR FP7/2007-2013, grant agreement 259867 Giancarlo Logroscino, serves as associate editor for the Neuroepidemiolgy journal, Karger. He received founding from Ministry of Health, Ministry of University and Research, Regione Puglia Special program for research. He funded by Euro-MOTOR FP7/2007-2013, grant agreement 259867. Adriano Chiò has grants from the Motor Neurone Disease Association, ALS Association, National Institute for Health Research, European Commission, Medical Research Council and Economic and Social Research Council. He has grants from Italian Ministry of Health (Ricerca Finalizzata), University of Turin, and Fondazione Vialli e Mauro onlus. Ettore Beghi reports research grants from European Union [Euro-MOTOR (FP7/2007-2013, grant agreement 259867)], The American ALS Association, UCB-Pharma, the Italian Ministry of Health, the Italian Drug Agency, the Fondazione Borgonovo, and the Associazione IDIC-15, outside the submitted work. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.