We thank patients and their families, investigators, and staff from all the participating sites. We thank Rama Mylapuram, Pharm D, Novartis Healthcare Pvt. Ltd. for providing medical editorial assistance with this manuscript.
Authors’ contributions
JCK was responsible for designing the study, patient accrual, clinical care, data interpretation, drafting, revising, final review, and approval of the manuscript. GBd’A was responsible for designing the study, data interpretation, drafting, revising, final review, and approval of the manuscript. ElB was responsible for designing the study, patient accrual, clinical care, data interpretation, drafting, revising, final review, and approval of the manuscript. JCF was responsible for designing the study, patient accrual, clinical care, data interpretation, drafting, revising, final review, and approval of the manuscript. TC was responsible for designing the study, data interpretation, drafting, revising, final review, and approval of the manuscript. RC was responsible for designing the study, patient accrual, trial management, data collection, trial statistician, data analysis, data interpretation, drafting, revising, final review, and approval of the manuscript. VC was responsible for designing the study, data interpretation, drafting, revising, final review, and approval of the manuscript. PC was responsible for designing the study, patient accrual, clinical care, data interpretation, drafting, revising, final review, and approval of the manuscript. MD was responsible for designing the study, patient accrual, clinical care, data interpretation, drafting, revising, final review, and approval of the manuscript. PJdeV was responsible for designing the study, data interpretation, drafting, revising, final review, and approval of the manuscript. MF was responsible for designing the study, patient accrual, clinical care, data interpretation, drafting, revising, final review, and approval of the manuscript. CF was responsible for designing the study, data interpretation, drafting, revising, final review, and approval of the manuscript. GG was responsible for designing the study, patient accrual, trial management, data collection, trial statistician, data analysis, data interpretation, drafting, revising, final review, and approval of the manuscript. CH was responsible for designing the study, patient accrual, clinical care, data interpretation, drafting, revising, final review, and approval of the manuscript. SJ was responsible for designing the study, patient accrual, clinical care, data interpretation, drafting, revising, final review, and approval of the manuscript. JAL was responsible for designing the study, patient accrual, clinical care, data interpretation, drafting, revising, final review, and approval of the manuscript. AM was responsible for designing the study, patient accrual, clinical care, data interpretation, drafting, revising, final review, and approval of the manuscript. RN was responsible for designing the study, patient accrual, clinical care, data interpretation, drafting, revising, final review, and approval of the manuscript. FO’C was responsible for designing the study, data interpretation, drafting, revising, final review, and approval of the manuscript. MPB was responsible for designing the study, patient accrual, clinical care, data interpretation, drafting, revising, final review, and approval of the manuscript. JQ was responsible for designing the study, data interpretation, drafting, revising, final review, and approval of the manuscript. RM was responsible for designing the study, patient accrual, trial management, data collection, trial statistician, data analysis, data interpretation, drafting, revising, final review, and approval of the manuscript. VS was responsible for designing the study, patient accrual, clinical care, data interpretation, drafting, revising, final review, and approval of the manuscript. MS was responsible for designing the study, patient accrual, clinical care, data interpretation, drafting, revising, final review, and approval of the manuscript. YT was responsible for designing the study, data interpretation, drafting, revising, final review, and approval of the manuscript. RT was responsible for designing the study, patient accrual, clinical care, data interpretation, drafting, revising, final review, and approval of the manuscript. SY was responsible for designing the study, data interpretation, drafting, revising, final review, and approval of the manuscript. BZ was responsible for designing the study, patient accrual, clinical care, data interpretation, drafting, revising, final review, and approval of the manuscript. ACJ was responsible for designing the study, patient accrual, clinical care, data interpretation, drafting, revising, final review, and approval of the manuscript.
Ethics approval and consent to participate
All patients (or their legal representatives) provided written informed consent before enrolling in the TOSCA disease registry. The study was designed, implemented, and reported in accordance with the principles of Good Clinical Practice, Good Pharmacoepidemiology Practices of the International Society for Pharmacoepidemiology (ISPE 2008), the STROBE (Strengthening and Reporting of Observational Studies in Epidemiology) guidelines, and the ethical principles laid down in the Declaration of Helsinki, and all local regulations. The study protocol and all amendments were reviewed and approved by independent ethics committee/institutional review board for each center (National Hospital Organization Central Ethics Committee; Gazi University Clinical Research Ethics Committee; Independent Multidisciplinary Committee on Ethical Review of Clinical Trials; Peking Union Medical College Hospital; Commissie Medische Ethiek UZ Brussel; CNIL (Commission National de l’Informatique et des Libertés), CCTIRS (Comité Consultatif sur le traitement de l’information en matière de recherche dans le domaine de la santé); Comité Etico Investigación Clínica de Euskadi (CEIC-E); Consejeria de Salud y Bienestar Social, Dirección General de Calidad, Investigación, Desarrollo e Innovación, Comité Coordinador de Ética de la Investigación Biomédica de Andalucía; Research Ethics Committee of the University of Tartu (UT REC); National Bioethics Committee of Medicine and of Medical Devices; Ethikkommission der Medizinischen Universität Graz; North Wales REC – West; Regionala Etikprövningsnämnden i Göteborg; REK – Regionale komiteer for medisinsk og helsefaglig forskningsetikk; Komisja Bioetyczna przy Instytucie “Pomnik Centrum Zdrowia Dziecka”; Ethikkommission bei der, Ludwig-Maximilians-Universitat Monchen; Hokkaido University Hospital Independent clinical research Institutional Ethics Committee; Medical Juntendo University Institutional Ethics Committee; Nationak Center for Chile Health and Deveropment of IRB; Osaka University Hospital of IRB; Ethics Committee at Moscow Institute of Pediatrics and Pediatric Surgery; Peking University First Hospital; Chinese PLA general hospetal; Sanbo Brain Hospital Capital Medical University; Tianjin Children’s Hospital; Childrens Hospital Of Fudan University; Zhongshan Hospital Fudan University; Fudan University Shanghai Cancer Center; The Second Affiliated Hospital of Guangzhou Medical University; The First Affiliated Hospital, Sun Yan-Sen University; The First Affiliated Hospital Of Guangzhou Medical University; Shenzhen Children’s Hospital; West China Hospital, Sichuan University; Xijing Hospital; Children’s Hospital of Chongqing Medical University; Wuhan Children’s Hospital; The second affiliated hospital of Xi’an jiaotong university; Guangdong 999 brain hospital; Seoul National University Hospital Institutional Review Board; National Taiwan University Hospital (NTUH) Research Ethics Committee (REC); Institutional Review Board of the Taichung Veterans General Hospital; Institutional Review Board of Chung Shan Medical University Hospital; Institutional Review Board, Tungs’ Taichung MetroHarbor Hospital; Institutional Review Board of National Cheng Kung University Hospital; Metro South Human Research Ethics Committee; Sydney Children’s Hospital Network Human Research Ethics Committee; St Vincents Hospital Human Research Ethics Committee; Royal Melbourne Hospital Human Research Ethics Committee; Siriraj Institutional Review Board; Institutional Review board; The committee on Human Rights Related to Research Involving Human Subjects; The Institutional Review Board; Research Ethics Committee; Research and Development; Human Research Ethics Committee; Shaare Zedek Meidcla center Helsinki comittee; Sheba Medical center Helsinki comittee; Tel Aviv Sourasly Medical center Helsinki comittee; General University Hospital of Patras Ethics Committee; Pendeli Children’s Hospital Ethics Committee; General University Hospital of Athens’G. Gennimatas Ethics Committee; Evaggelismos General Hospital Ethics Committee; General University Hospital of Thessaloniki “AHEPA” Ethics Committee; General University Hospital of Ionnina Ethics Committee; METC UMC Utrecht; Comité Ético de Investigación Clínica Hospital Infantil Universitario Niño Jesús, Dirección General de Ordenación e Inspección, Consejería de Sanidad Comunidad de Madrid, Servicios de Control Farmacéutico y Productos Sanitarios; Comité Ético de Investigación Clínica Fundació Sant Joan de Déu, Generalitat de Catalunya. Departament de Salut, Direcció General de Regulació, Planificació i Recursos Sanitaris; Comité Ético de Investigación Clínica del Hospital Universitario Vall d´Hebron de Barcelona, Generalitat de Catalunya. Departament de Salut, Direcció General de Regulació, Planificació i Recursos Sanitaris; Comité Ético de Investigación Clínica Hospital Universitario La Paz, Dirección General de Ordenación e Inspección, Consejería de Sanidad Comunidad de Madrid, Servicios de Control Farmacéutico y Productos Sanitarios; Comité Etico Investigación Clínica del Hospital Universitario y Politécnico de La Fe, Dirección General de Farmàcia i Productes Sanitaris, Generalitat de Valencia; Comité de Ética de la Investigación de Centro de Granada, Consejeria de Salud y Bienestar Social, Dirección General de Calidad, Investigación, Desarrollo e Innovación, Comité Coordinador de Ética de la Investigación Biomédica de Andalucía; Instituto Aragonés de Ciencias de la Salud (IACS), Comité Ético Investigación Clínica de Galicia; Comité Etico Investigación Clínica Regional del Principado de Asturias, Dirección General de Asistencia Sanitaria, Consejería de Sanidad, Gobierno del Principado de Asturias; Comité Etico Investigación Clínica Hospital 12 de Octubre, Dirección General de Ordenación e Inspección, Consejeria de Sanidad Comunidad de Madrid, Servicios de Control Farmacéutico y Productos Sanitarios; Comité Etico Investigación Clínica Hospital Universitario Virgen de la Arrixaca, Dirección General de Planificación, Ordenación Sanitaria y Farmacéutica e Investigación, Consejeria de Sanidad y Política Social Región de Murcia; Sección de Ordenación e Inspección Farmacéutica Departamento de Salud; Comité Ético de Investigación Clínica del Hospital Universitario del Río Hortega de Valladolid, Consejería de Sanidad, Dirección General de Salus Pública, Junta de Castilla León; Comissão de Ética para a Saúde (CES), Centro Hospitalar de Lisboa Ocidental, EPE; Comissão de Ética para a Saúde (CES), Centro Hospitalar do Porto, E.P.E.; Comissão de Ética para a Saúde (CES), Centro Hospitalar Lisboa Central, EPE; Comissão de Ética para a Saúde (CES), Hospital Garcia de Orta, EPE; Comissão de Ética para a Saúde (CES), Centro Hospitalar de São João, EPE; Comissão de Ética para a Saúde (CES), Hospital Professor Doutor Fernando Fonseca, EPE; Comissão de Ética para a Saúde (CES), Centro Hospitalar do Algarve, EPE (Unidade de Faro); LUHS Kaunas Regional Biomedical Research Ethics Committee; Paula Stradiņa klīniskās universitātes slimnīcas, Attīstības biedrības Klīniskās izpētes Ētikas komiteja, Ethics Committee for Clinical Research; Komisija Republike Slovenije za medicinsko etiko; Comitato Etico Indipendente Presso La Fondazione Ptv Policlinico Tor Vergata Di Roma; Comitato Etico Interaziendale Milano Area A c/o O Azienda Ospedaliera Ospedale Luigi Sacco; Comitato Etico Regione Calabria Sezione Centro c/o A.O.U. Mater Domini Di Catanzaro; Comitato Etico Azienda Ospedaliera Universitaria Di Cagliari; Comitato Etico Cardarelli-Santobono c/o Ao Cardarelli; Comitato Etico Per La Sperimentazione Clinica Delle Province Di Verona E Rovigo, Presso Aoui Verona; Eticka Komise Fn Brno; Eticka Komisia Dfnsp Bratislava; Eticka Komisia Pri Dfn Kosice; Eticka Komisia Bratislavskeho Samospravneho Kraja).