The Norwegian Multiple Sclerosis Registry and Biobank

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1 Acta Neurol Scand 2015: 132 (Suppl. 199): DOI: /ane John Wiley & Sons A/S. Published by John Wiley & Sons Ltd ACTA NEUROLOGICA SCANDINAVICA Review Article The Norwegian Multiple Sclerosis Registry and Biobank Myhr K-M, Grytten N, Torkildsen Ø, Wergeland S, Bø L, Aarseth JH. The Norwegian Multiple Sclerosis Registry and Biobank. Acta Neurol Scand 2015: 132 (Suppl. 199): John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system with unknown cause and various benefits from disease modifying therapies. Systematic recording of data into national MS registries is therefore needed to optimize treatment and define the pathogenesis of the disease. The Norwegian MS Registry and Biobank was established for systematic collection of clinical and epidemiological data, as well as biological samples. Data collection is based on informed consent from the individual patients and recordings by treating neurologists. All researchers have, by application, access to data and biological samples from the Norwegian Multiple Sclerosis Registry and Biobank. By this combined effort from both patients and healthcare personnel, the Registry and Biobank aims to facilitate research for improved understanding of disease mechanisms and improved health care in MS. K.-M. Myhr 1,2, N. Grytten 2,3, Ø. Torkildsen 2,3, S. Wergeland 2,3, L. Bø 2,3, J. H. Aarseth 1,2 1 Norwegian Multiple Sclerosis Registry and Biobank, Department of Neurology, Haukeland University Hospital, Bergen, Norway; 2 KG Jebsen MS Research Centre, Department of Clinical Medicine, University of Bergen, Bergen, Norway; 3 Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital, Bergen, Norway Key words: multiple sclerosis; registry; biobank K.-M. Myhr, Norwegian Multiple Sclerosis Registry and Biobank, Department of Neurology, Haukeland University Hospital, 5021 Bergen, Norway Tel.: / Fax: [email protected] Accepted for publication January 4, 2015 Introduction Multiple sclerosis (MS) is one of the major causes of neurological disability in young people, reduces life expectancy by 8 10 years (1, 2), and generates high costs to society (3). The disease is caused by a complex interplay between genetic and environmental risk factors (4), and the diagnosis is based on disease history, clinical examination, magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) analyses (5). Although no curable treatment is available, disease modifying therapies reduce disease activity, but the efficacy of available therapies varies between patients with apparently similar demographic and clinical characteristics (6). Thus, biomarkers to predict disease prognosis and treatment response are needed for personalized treatment strategies to improve health care in MS. Biomarkers may also help researchers to define the pathogenesis of the disease and contribute to the development of new treatment strategies. The Norwegian MS Registry and Biobank was therefore established to improve health care for patients with MS, by optimizing treatment, and to facilitate research aiming at defining the cause of the disease (7). The Norwegian Multiple Sclerosis Registry and Biobank The Norwegian MS Registry was approved by the Regional Committee for Research Ethics and granted license from the Norwegian Data Protection Authority in Enrollment, based on written informed consent from the individual patient, was initiated in The registration was performed by the local neurologist responsible for diagnosis and treatment of the patients and included from the beginning three different register paper forms; one for basic information on diagnosis and demographic factors, and two forms for treatment initiation and follow-up. During 2007, the registry was expanded to include a biobank of blood samples (DNA and serum) and cerebrospinal fluid collected during the diagnostic procedure, and brain tissue obtained at autopsy. Its name was accordingly changed to the Norwegian MS Registry and Biobank (8). The registry has been included in the Norwegian program for Medical Quality Registries ( and was recently adapted for web-based online registration at Norwegian Health Network (Norsk Helsenett; The 24

2 The Norwegian Multiple Sclerosis Registry and Biobank registry is located at the Norwegian MS Competence Centre at Haukeland University Hospital in Bergen (9). The CSF and tissue biobank samples are stored at Haukeland University Hospital, and the DNA and serum samples are stored at the Norwegian Institute of Public Health in Oslo. The aims of the registry are to provide quality control of diagnosis and treatment of patients with MS and also to supply data and biological samples for MS research. All researchers have, by application, access to data and biological samples. Applications are evaluated by the registry s board of representatives from the four Regional Health Authorities, The Norwegian Institute of Public Health, and the Norwegian MS Society. The registry is funded by the Norwegian health authorities, through The Western Norway Regional Health Authority. The Norwegian Research Council, by the NevroNor research program, funded the initial phase for the biobank collection ( ). Registry variables The registry collects individual data on demography and results from diagnostic procedures, as well as risk factors and treatment. Data on clinical and magnetic resonance imaging (MRI) disease activity are registered at least once yearly (10 16). Information related to possible risk factors in addition to comorbidity and concomitant treatments are also included (Table 1). Separate modules for patient-reported outcome (PRO) and patient-reported evaluation (PRE) of the healthcare service are currently being developed. Registry data in MS research Several epidemiological research projects have benefited from the data recorded at the registry. A linkage study of the MS registry and the Medical Birth Registry of Norway showed a significantly lower mean birthweight in term births by women with established MS compared to those with pregnancy before MS onset and diagnosis (17). Grytten et al. (1) reported a median survival from onset of 41 years compared to 49 years in the corresponding population, and standardized mortality ratio (SMR) analyses showed a 2.7-fold increased risk of death among patients MS from Hordaland County, Western Norway. Analysis of relative mortality ratio (RMR) among patients with MS showed that women had higher relative mortality than men. Data from the MS registry were also included in a study on offshore workers in the Norwegian upstream petroleum industry, Table 1 Variables included in the Norwegian Multiple Sclerosis Registry and Biobank Demographics and diagnostic evaluation Person identification/demographics Name and identification number Year of birth Gender Informed consent Diagnosis Year of onset Year of diagnosis Disease course Onset symptoms Number of relapses or progressive symptoms at diagnosis Number of signs of neurological dysfunction at diagnosis Magnetic resonance imaging (MRI) at diagnosis Evoked potentials at diagnosis Cerebrospinal fluid (CSF)-analyses at diagnosis Disease modifying treatment and follow-up Ongoing treatment Any previous medication and reason for changes Any reason for no treatment Any side effects Neutralizing antibody analysis during interferon beta and natalizumab treatment JC-virus screening and JCV-index during natalizumab treatment Disease activity and clinical scoring Any relapse and any relapse treatment is recorded MRI examination, total lesion load (categorized) and diagnosis, and appearance of new lesions Expanded Disability Status Scale [EDSS, (10)] Multiple Sclerosis Functional Composite [MSFC, (11)] Symbol Digit Modalities Test [SDMT, (12)] Symptom checklist, including the presence of symptoms and any treatment of those Patient-reported outcome measures Fatigue Severity Scale [FSS, (13)] Multiple Sclerosis Impact Scale [MSIS-29, (14,15)] Health-related quality of life assessment by EuroQol-5D [EQ-5D, (16)] Other variables Comorbidity Concomitant medication Family members with MS Previous Epstein-Barr virus infection and/or infectious mononucleosis Serum vitamin D levels Smoking habits Vital signs which showed no increased risk of MS compared with the general working population in Norway after adjustment for education (18). Education 25

3 Myhr et al. analysis, however, showed a marked and linear inverse relationship between level of education and the risk of MS in the total study population (18). Registry data have been included in analyses of month of birth and gender differences in MS incidence (19 22). The registry activity has also inspired several Norwegian researchers to conduct local and regional projects on epidemiological studies of MS prevalence and incidence (23, 24). The Norwegian contribution to the large international case control study on environmental risk factors in MS (EnvIMS) was based on the Norwegian MS registry (25). Results from this study have shown that obesity from childhood until young adulthood increases the risk, while exposure to sunlight and the use of cod-liver oil especially during adolescence may reduce the risk of developing MS (26 28). The EnvIMS study has also provided evidence for an association between infectious mononucleosis and an increased risk of MS, independent of season, and therefore also probably independent of serum levels of vitamin D (29). DNA samples obtained from the registry biobank have contributed to numerous studies of genetic risk factors in MS (30 44). Current status and future perspectives The registry has currently included close to 6000 patients. Most data are from prevalent cases, but longitudinal data on treatment and clinical and MRI disease activity will grow rapidly with increasing use of web-based online registration. The biobank includes about 2200 samples of patient DNA, 700 family member control samples, about 300 CSF samples, and tissue samples from about 80 MS brains. The web-based MS registry aims to be a userfriendly tool in the neurologist s everyday clinical practice. The registry provides an intuitive and yet comprehensive graphic interface of all relevant variables in a typical MS consultation. It generates a report of essential information that can be included in the electronic patient record. The web-based MS registry also provides information on all patients with MS on an institutional, department or treating physician level. In the future, we also aim to include modules for online recording of patient-reported outcome measures. A future prospect for the new web-based system is to generate close to complete follow-up data sets of patients that can be used for quality control of individual diagnosis and treatment. Hence, the registry would improve utilization of healthcare services and increase access to medical treatment to all patients fulfilling the criteria for disease modifying treatment (45). The registry would, by the symptom checklist, also promote optimal evaluation and initiation of symptomatic treatment. A systematic recording of treatment effects and possible adverse events would also significantly contribute to safety evaluation of new medications. The Norwegian MS Registry and Biobank will actively seek participation in collaborative initiatives, such as the European MS Registry (EUReMS) (46), and hopefully also with the other Scandinavian MS registries in Sweden and Denmark (47, 48). Acknowledgments and source of funding The Norwegian Multiple Sclerosis Registry and Biobank receive funding from The Western Norway Regional Health Authority and have received funding from the Norwegian Research Council (NevroNor) for biobank sample collection. Conflict of interest KMM has received honoraria for lecturing, participation in advisory boards or pharmaceutical company sponsored clinical trials, and travel support from Allergan, Almirall, Bayer Schering, Biogen Idec, Genzyme/Sanofi Aventis, Merck-Serono, Novartis, and/or TEVA. NG reports no conflict of interests. 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