Examining the environmental risk factors of progressive-onset and relapsing-onset multiple sclerosis: recruitment challenges, potential bias, and statistical strategies.

"Declarations Conflicts of interestFrancesco Patti received personal compensation for serving on advisory board by Almirall, Alexion, Biogen, Bristol, Berck, Novartis and Roche, and further received research grant by Biogen, Merck and Roche and by FISM, Reload Association (Onlus), Italian Health Minister, University of Catania. Sara Eichau received speaker honoraria and consultant fees from Biogen Idec, Novartis, Merck, Bayer, Sanofi Genzyme, Roche and Teva. Dana Horakova received compensation for travel, speaker honoraria and consultant fees from Biogen, Novartis, Merck Healthcare KGaA (Darmstadt, Germany), Bayer, Sanofi, Roche, and Teva, as well as support for research activities from Biogen. She was also supported by the Charles University: Cooperatio Program in neuroscience. Eva Kubala Havrdova received honoraria/research support from Biogen, Merck Serono, Novars, Roche, and Teva; has been member of advisory boards for Actelion, Biogen, Celgene, Merck Serono, Novars, and Sanofi Genzyme. Francois Grand'Maison received honoraria or research funding from Biogen, Genzyme, Novartis, Teva Neurosciences, and ATARA Pharmaceuticals. Raed Alroughani received honoraria as a speaker and for serving on scientific advisory boards from Bayer, Biogen, GSK, Merck, Novartis, Roche and Sanofi-Genzyme. Maria Pia Amato received honoraria as consultant on scientific advisory boards by Biogen, Bayer-Schering, Merck, Teva and Sanofi-Aventis; has received research grants by Biogen, Bayer-Schering, Merck, Teva and Novartis. Ayse Altintas received speaker honoraria from Merck, Alexion; received travel and registration grants from Merck. Pierre Duquette served on editorial boards and has been supported to attend meetings by EMD, Biogen, Novartis, Genzyme, and TEVA Neuroscience. He holds grants from the CIHR and the MS Society of Canada and has received funding for investigator-initiated trials from Biogen, Novartis, and Genzyme. Yolanda Blanco received speaker honoraira from Merck, Biogen, Brystol, Novartis and Sanofi. Cristina Ramo-Tello received research funding, compensation for travel or speaker honoraria from Biogen, Novartis, Bristol, Janssen, Sanofi, Merck and Almirall. Guy Laureys received travel and/or consultancy compensation from Sanofi-Genzyme, Roche, Teva, Merck, Novartis, Celgene, Biogen. Tomas Kalincik served on scientific advisory boards for MS International Federation and World Health Organization, BMS, Roche, Janssen, Sanofi Genzyme, Novartis, Merck and Biogen, steering committee for Brain Atrophy Initiative by Sanofi Genzyme, received conference travel support and/or speaker honoraria from WebMD Global, Eisai, Novartis, Biogen, Roche, Sanofi-Genzyme, Teva, BioCSL and Merck and received research or educational event support from Biogen, Novartis, Genzyme, Roche, Celgene and Merck. Samia J. Khoury received compensation for scientific advisory board activity from Merck and Roche. Bhim Singhal received consultancy honoraria and compensation for travel from Biogen and Merck. Saloua Mrabet has received a MENACTRIMS clinical fellowship grant (2020). Nevin John NAJ is a local principal investigator on commercial studies funded by Novartis, Biogen, Amicus and Sanofi. Stella Hughes has received unrestricted educational grants or speaking honoraria from Biogen, Merck Serono, Novartis, Roche and Sanofi Genzyme. Pamela McCombe received honoraria and consulting fees from Novartis, Bayer Schering and Sanofi and travel grants from Novartis, Biogen and Bayer Schering. Received speakers fees and travel grants from Novartis, Biogen, T’évalua, Sanofi. Radek Ampapa received conference travel support from Novartis, Teva, Biogen, Bayer and Merck and has participated in a clinical trials by Biogen, Novartis, Teva and Actelion. Anneke van der Walt served on advisory boards and receives unrestricted research grants from Novartis, Biogen, Merck and Roche She has received speaker’s honoraria and travel support from Novartis, Roche, and Merck. She receives grant support from the National Health and Medical Research Council of Australia and MS Research Australia. Helmut Butzkueven received institutional (Monash University) funding from Biogen, F. Hoffmann-La Roche Ltd, Merck, Alexion, CSL, and Novartis; has carried out contracted research for Novartis, Merck, F. Hoffmann-La Roche Ltd and Biogen; has taken part in speakers’ bureaus for Biogen, Genzyme, UCB, Novartis, F. Hoffmann-La Roche Ltd and Merck; has received personal compensation from Oxford Health Policy Forum for the Brain Health Steering Committee. Koen de Gans served on scientific advisory boards for Roche, Janssen, Sanofi-Genzyme, Novartis and Merck, received conference fee and travel support from Novartis, Biogen, Sanofi-Genzyme, Teva, Abbvie and Merck and received educational event support from Novartis. Chris McGuigan received honoraria/research funding from Biogen, BMS, Jannsen, Merck, Novartis & Roche. Celia Oreja-Guevara received honoraria as consultant on scientific advisory boards from Biogen, Celgene, Merck, Novartis, Roche, Sanofi-Genzyme and TEVA. Maria Jose Sa received consulting fees, speaker honoraria, and/or travel expenses for scientific meetings from Alexion, Bayer Healthcare, Biogen, Bristol Myers Squibb, Celgene, Janssen, Merck-Serono, Novartis, Roche, Sanofi and Teva. Thor Petersen received funding from Biogen, Merck, Novartis, Sanofi-Aventis, Roche, and Genzyme. Angel Perez sempere received honoraria as consultant on scientific advisory boards from Biogen, Merck, Novartis, Roche and TEVA. Bart Van Wijmeersch received research and travel grants, honoraria for MS-Expert advisor and Speaker fees from Almirall, Biogen, BMS, Imcyse, Janssen, Sanofi, Merck, Novartis, Roche and Teva. Nikolaos Grigoriadis travel support and/or honoraria and/or research grants and/or lecture fees and/or advisory services and/or consulting fees from Novartis, Bayer, Merck, Genesis, Sanofi, Specifar, Roche, Biogen, Teva, Mylan, Merck Serono, Sanofi Genzyme, Celgene, and ELPEN. Julie Prevost accepted travel compensation from Novartis, Biogen, Genzyme, Teva, and speaking honoraria from Biogen, Novartis, Genzyme and Teva. Orla Gray received honoraria as consultant on scientific advisory boards for Genzyme, Biogen, Merck, Roche, and Novartis; has received travel grants from Biogen, Merck, Roche, and Novartis; has participated in clinical trials by Biogen and Merck. She has received research grant support from Biogen. Tamara Castillo Triviño received speaking/consulting fees and/or travel funding from Almirall, Biogen, Bristol Myers Squibb, Janssen, Merck, Novartis, Roche and Sanofi-Genzyme. Richard Macdonell served on scientific advisory boards for Roche, Biogen, Novartis, Teva and Genzyme and has received conference travel support from Biogen and Novartis. His institution has received research support from Biogen, Merck and Novartis. Alessandra Lugaresi has served as a Biogen, Bristol Myers Squibb, Merck Serono, Novartis, Roche, Sanofi/Genzyme Advisory Board Member. She received congress and travel/accommodation expense compensations or speaker honoraria from Alexion, Biogen, Merck Serono, Novartis, Roche (2020), Sanofi/Genzyme, and Fondazione Italiana Sclerosi Multipla (FISM). Her institutions received research grants from Novartis and Sanofi/Genzyme. Ethical standard statementThe AusImmune Study was approved by the Human Research Ethics Committee of the Australian National University. All 204 ROMS and 558 controls signed informed consent before participation. The PPMS Study was approved by Human Research Ethics Committee in Tasmania (H0014794) in 2015 and all 140 POMS participants provided signed consent forms. Waiver of consent by the AusImmune controls for the PPMS Study was approved by Human Research Ethics Committee of The Australian National University. Conflicts of interest Francesco Patti received personal compensation for serving on advisory board by Almirall, Alexion, Biogen, Bristol, Berck, Novartis and Roche, and further received research grant by Biogen, Merck and Roche and by FISM, Reload Association (Onlus), Italian Health Minister, University of Catania. Sara Eichau received speaker honoraria and consultant fees from Biogen Idec, Novartis, Merck, Bayer, Sanofi Genzyme, Roche and Teva. Dana Horakova received compensation for travel, speaker honoraria and consultant fees from Biogen, Novartis, Merck Healthcare KGaA (Darmstadt, Germany), Bayer, Sanofi, Roche, and Teva, as well as support for research activities from Biogen. She was also supported by the Charles University: Cooperatio Program in neuroscience. Eva Kubala Havrdova received honoraria/research support from Biogen, Merck Serono, Novars, Roche, and Teva; has been member of advisory boards for Actelion, Biogen, Celgene, Merck Serono, Novars, and Sanofi Genzyme. Francois Grand'Maison received honoraria or research funding from Biogen, Genzyme, Novartis, Teva Neurosciences, and ATARA Pharmaceuticals. Raed Alroughani received honoraria as a speaker and for serving on scientific advisory boards from Bayer, Biogen, GSK, Merck, Novartis, Roche and Sanofi-Genzyme. Maria Pia Amato received honoraria as consultant on scientific advisory boards by Biogen, Bayer-Schering, Merck, Teva and Sanofi-Aventis; has received research grants by Biogen, Bayer-Schering, Merck, Teva and Novartis. Ayse Altintas received speaker honoraria from Merck, Alexion; received travel and registration grants from Merck. Pierre Duquette served on editorial boards and has been supported to attend meetings by EMD, Biogen, Novartis, Genzyme, and TEVA Neuroscience. He holds grants from the CIHR and the MS Society of Canada and has received funding for investigator-initiated trials from Biogen, Novartis, and Genzyme. Yolanda Blanco received speaker honoraira from Merck, Biogen, Brystol, Novartis and Sanofi. Cristina Ramo-Tello received research funding, compensation for travel or speaker honoraria from Biogen, Novartis, Bristol, Janssen, Sanofi, Merck and Almira"

"Funding Open Access funding enabled and organized by CAUL and its Member Institutions. The AusImmune Study was supported by the National Multiple Sclerosis Society of the United States of America (Award RG3364A1/2), the National Health and Medical Research Council of Australia (No. 316901) with additional support from Multiple Sclerosis Research Australia and the Multiple Sclerosis Societies of Australia. The PPMS Study was supported by Multiple Sclerosis Research Australia Project Grant (14–031) in 2014."