title: Biomarker time out.
abstract: The advancement of knowledge relies on scientific investigations. The timing between asking a question and data collection defines if a study is prospective or retrospective. Prospective studies look forward from a point in time, are less prone to bias and are considered superior to retrospective studies. This conceptual framework conflicts with the nature of biomarker research. New candidate biomarkers are discovered in a retrospective manner. There are neither resources nor time for prospective testing in all cases. Relevant sources for bias are not covered. Ethical questions arise through the time penalty of an overly dogmatic concept. The timing of sample collection can be separated from testing biomarkers. Therefore the moment of formulating a hypothesis may be after sample collection was completed. A conceptual framework permissive to asking research questions without the obligation to bow to the human concept of calendar time would simplify biomarker research, but will require new safeguards against bias.
authors.affiliation: Department of Molecular Neuroscience, UCL, ION, The Wolfson Center for Neurodegeneration, London, UK a.petzold@ucl.ac.uk.
authors.forename: Axel
authors.initials: A
authors.lastname: Petzold
authors.affiliation: Gregory W Fulton ALS and Neuromuscular Research Center, Divisions of Neurology and Neurobiology, Barrow Neurological Institute St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Bowser
authors.affiliation: Clinica Neurologica, Università di Perugia Ospedale S. Maria della Misericordia, Andrea delle Fratte Perugia, Italy and IRCCS Fondazione S Lucia Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Calabresi
authors.affiliation: Department of Molecular Neuroscience, UCL, ION, The Wolfson Center for Neurodegeneration, London, UK Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Department of Neurology, MS Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Bernard M J
authors.initials: BM
authors.lastname: Uitdehaag
mesh_terms: D000818:Animals; D015415:Biomarkers; D042241:Early Diagnosis; D006801:Humans; D009103:Multiple Sclerosis / Q000175:diagnosis*; D011446:Prospective Studies; D012189:Retrospective Studies; D013997:Time Factors
chemical_list: D015415:Biomarkers
keywords: Alzheimer disease; Amyotrophic lateral sclerosis; Biomarker study design; Parkinson syndrome; bias; multiple sclerosis; traumatic brain injury