Critical issues in ALS case-control studies: the case of the Euro-MOTOR study

Abstract

Backround: Political and sociocultural differences between countries can affect the outcome of clinical and epidemiological studies in ALS. Cross-national studies represent the ideal process by which risk factors can be assessed using the same methodology in different geographical areas. Methods: A survey of three European countries (The Netherlands, Ireland and Italy) has been conducted in which incident ALS patients and matched controls were recruited in a population-based study based on age, gender and area of residency, under the Euro-MOTOR systems biology programme of research. Findings: We have identified strengths and limitations during the trajectory of the Euro-MOTOR study, from the research design to data analysis. We have analysed the implications of factors including cross-national differences in healthcare systems, sample size, types of matching, the definition of exposures and statistical analysis. Conclusions: Addressing critical methodological aspects of the design of the Euro-MOTOR project minimises bias and will facilitate scientific assessment of the independent role of well-defined exposures.

Keywords:

• Epidemiology
• case-control study
• risk
• criticisms
• genetics

Acknowledgements

The research leading to these results has received funding from the European Community’s Health Seventh Framework Programme (FP7/2007–2013; grant agreements no. 259867).

Disclosure statement

JPKR was funded by the Health Research Board Clinical Fellowship Programme (HPF-2014-527).

OH is funded by the Health Research Board Clinician Scientist Programme and Science Foundation Ireland. OH has received speaking honoraria from Novarits, Biogen Idec, Sanofi Aventis and Merck-Serono. OH has been a member of advisory panels for Biogen Idec, Allergen, Ono Pharmaceuticals, Novartis, Cytokinetics and Sanofi Aventis. OH serves as Editor-in-Chief of Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.

AC serves on the editorial advisory board of Amyotrophic Lateral Sclerosis; AC receives research support from the Italian Ministry of Health (Ricerca Finalizzata), Regione Piemonte (Ricerca Finalizzata), University of Turin, Fondazione Vialli e Mauro onlus, and the European Commission (Health Seventh Framework Programme); AC serves on scientific advisory boards for Biogen Idec, Cytokinetics, Italfarmaco, and Neuraltus.

EB reports grants from UCB-Pharma, grants from Shire, grants from EISAI, personal fees from Viropharma, grants from Italian Ministry of Health, grants from European Union, grants from Fondazione Borgonovo, grants from Associazione IDIC 15, outside the submitted work.

FD, AEV, RCHV, JHV, LHV, GL report no conflict of interest

Supplementary material available online.