title: Who is healthy? Aspects to consider when including healthy volunteers in QST--based studies-a consensus statement by the EUROPAIN and NEUROPAIN consortia.
abstract: Clinical and human experimental pain studies often include so-called "healthy" controls in investigations of sensory abnormalities, using quantitative sensory testing (QST) as an outcome measure. However, the criteria for what is considered "healthy" vary among the different studies and between study centers and investigators, partly explaining the high variability of the results. Therefore, several aspects should be considered during inclusion of healthy volunteers in QST-based trials to have homogenous groups of healthy controls with less variability between human experimental studies, so that results are less likely to be false negative or false positive because of subject-related factors. The EUROPAIN and NEUROPAIN consortia aimed to define factors influencing the variability in selection of healthy subjects in QST-based studies before the start of both projects and to give recommendations how to minimize it based on the current literature and expertise of the participants. The present suggestions for inclusion criteria of healthy volunteers into QST-based trials describe a 2-level approach including standardized questionnaires enabling the collection of relevant information on sociodemographic data, medical history, current health status, coping strategies in dealing with pain, and the motivation of the volunteer to participate in the study. These suggestions are believed to help researchers interpret their results in comparison with others and improve the quality of clinical studies including healthy volunteers as controls or in human experimental pain studies. They aim to reduce any confounding factors. Furthermore, the acquired information will allow post hoc analyses of variance for different potential influencing factors.
authors.affiliation: Division of Neurological Pain Research and Therapy, Department of Neurology, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Germany Department of Neurology, BG University Hospital Bergmannsheil GmbH, Ruhr-University Bochum, Bochum, Germany Department of Pain Medicine, BG University Hospital Bergmannsheil GmbH, Ruhr-University Bochum, Bochum, Germany INSERM U-987, Centre d'Evaluation et de Traitement de la Douleur, CHU Ambroise Paré, Boulogne-Billancourt, France Université Versailles-Saint-Quentin, Versailles, France Department Neurology and Psychiatry, Sapienza University, Roma, Italy Department of Neurology and Danish Pain Research Center, Aarhus University Hospital, Aarhus, Denmark Department of Neurosurgery, Helsinki University Central Hospital, Helsinki, Finland Etera Mutual Pension Insurance Company, Helsinki, Finland Department of Pain Management and Research, Oslo University Hospital, Oslo, Norway Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden Department of Anaesthesiology, Critical Care Medicine, Pain Therapy & Palliative Care, Pain Center Lake Starnberg, Benedictus Hospital, Tutzing, Germany Neuroscience Discovery Research, Eli Lilly and Company, Indianapolis, IN, USA Pain Research, Department of Surgery and Cancer, Imperial College, London, United Kingdom H. Lundbeck A/S, Copenhagen, Denmark Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden Department of Neurology, Odense University Hospital, Odense, Denmark Neuroscience Technologies, Barcelona, Spain Department of Neurology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany Chair of Neurophysiology, Center of Biomedicine and Medical Technology Mannheim CBTM, Medical Faculty Mannheim, Heidelberg University, Germany (T. Mainka is now with the Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany).
authors.forename: Janne
authors.initials: J
authors.lastname: Gierthmühlen
authors.forename: Elena K
authors.initials: EK
authors.lastname: Enax-Krumova
authors.forename: Nadine
authors.initials: N
authors.lastname: Attal
authors.forename: Didier
authors.initials: D
authors.lastname: Bouhassira
authors.forename: Giorgio
authors.initials: G
authors.lastname: Cruccu
authors.forename: Nanna B
authors.initials: NB
authors.lastname: Finnerup
authors.forename: Maija
authors.initials: M
authors.lastname: Haanpää
authors.forename: Per
authors.initials: P
authors.lastname: Hansson
authors.forename: Troels S
authors.initials: TS
authors.lastname: Jensen
authors.forename: Rainer
authors.initials: R
authors.lastname: Freynhagen
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Kennedy
authors.forename: Tina
authors.initials: T
authors.lastname: Mainka
authors.forename: Andrew S C
authors.initials: ASC
authors.lastname: Rice
authors.forename: Märta
authors.initials: M
authors.lastname: Segerdahl
authors.forename: Søren H
authors.initials: SH
authors.lastname: Sindrup
authors.forename: Jordi
authors.initials: J
authors.lastname: Serra
authors.forename: Thomas
authors.initials: T
authors.lastname: Tölle
authors.forename: Rolf-Detlef
authors.initials: RD
authors.lastname: Treede
authors.forename: Ralf
authors.initials: R
authors.lastname: Baron
authors.forename: Christoph
authors.initials: C
authors.lastname: Maier
mesh_terms: D035843:Biomedical Research / Q000592:standards*; D032921:Consensus; D064368:Healthy Volunteers; D006801:Humans; D019964:Mood Disorders / Q000175:diagnosis / Q000209:etiology; D010146:Pain / Q000150:complications / Q000175:diagnosis*; D010147:Pain Measurement / Q000379:methods / Q000592:standards; D017288:Pain Threshold / Q000502:physiology; D012955:Societies, Medical; D011795:Surveys and Questionnaires / Q000592:standards*