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      Position Statement: Sharing of Clinical Research Data in Spinal Muscular Atrophy to Accelerate Research and Improve Outcomes for Patients

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          Recent years have seen increasing clinical research activities in spinal muscular atrophy (SMA), involving patients, their families, clinicians, researchers, regulators and industry [1–3]. This has led to unprecedented advancements in understanding of genetic determinants of severity and prognosis, the natural history, outcome measures, and most importantly first marketed therapies [4–8]. However, many patients with SMA do not benefit yet from effective treatments or show limited clinical response or impact on their quality of life. A major barrier to carry out further clinical research is the relatively low incidence and prevalence of SMA [9, 10], considered a Rare Disorder (RD) covered by Orphan Drug Regulations in most jurisdictions. Many of the remaining challenges are not specific to SMA, but common across different RDs, across research domains and are linked to the unavailability of data of sufficient quality. Clinical trial in RDs considered as pivotal frequently do not cover the entire disease spectrum such as severity or age range. These gaps in knowledge lead to marketing approvals granted under the condition for stringent and comprehensive collection of post marketing, real-life outcome data. This is not only due to the scarcity of data, but also to the lack of options to reuse data that does exist. This may include options to take advantage of existing natural history data; and concerns related to the accuracy of the data collected. Therefore, international organizations involved in RD research have endorsed mechanisms and standards enabling data sharing [11–13], including the international charter of principles for sharing bio-specimens and data and the FAIR principles for data (findable, accessible, interoperable, reusable). Important issues to address are privacy protection issues, lack of infrastructure for data sharing, lack of standards and interoperability, reluctance to share unpublished data, lack of capacity to analyse large amounts of data, and challenges of linking different datasets in different places. The benefits of sharing data and samples in RDs are: overcoming the “rare disease problem” in clinical research, eg cohort size, powering trials and finding confirmatory cases, reducing costs and duplication of effort, facilitating validation of results and enabling engagement with experts and the patient community. A recent workshop with panellists from patient organizations, academia and industry discussed the challenges and benefits of data sharing in SMA clinical research at the international conference of SMA Europe in Krakow (full workshop report in the supplementary material). The discussion brought several activities to light where international collaboration, close interactions between different stakeholders and data sharing, have contributed to the recent successes in SMA clinical research, including the transnational collaboration of patient organizations in SMA Europe, multi-centric studies into natural history and outcome measures, global trial readiness through registries and biobanks (TREAT-NMD, 14), and commercially sponsored multinational trials. Moreover, new opportunities and challenges in SMA research were identified, that may benefit or have an impact on data sharing, including patient-reported outcome measures, trials without placebo groups, real-world outcome and safety of marketed products, and the changing legal environment in European data protection (GDPR, General Data Protection Regulation). The following statements were made during the workshop and were broadly agreed to by the authors: 1. SMA patients, families and patient organizations want to play a critical role in SMA research, not only through participation and dissemination, but through governance and design of studies and outcome measures, as well as access and use of research data. 2. Data capture in SMA should wherever possible follow the IRDiRC-recognized “FAIR Guiding Principles” in order to make the collected data Findable, Accessible, Interoperable and Reusable and thus maximise their utility for research. 3. Disease-specific registries are recommended by regulatory agencies, supported by all stakeholders, and favoured over product-specific registries to avoid fragmentation, save resources and to allow meaningful analysis across both treated and untreated SMA patients. 4. Real-life (post-marketing) outcome data capture is warranted due to regulatory and payer commitments in SMA, and requires a high degree of transnational collaboration and standardization (eg data items, data capture, IT, monitoring, analysis) to ensure reporting at the required detail, quality and speed. 5. Companies sponsoring clinical trials in SMA are encouraged to share their placebo arm data through an agreed mechanism allowing access to the data by other investigators both from the academic and the commercial sector, in order to limit or avoid placebo groups in future clinical trials as recommended by the recent EMA workshop [15]. 6. Data collections from natural history studies, clinical trials and patient registries in SMA are precious resources that involve extensive effort and investment from academics, pharmaceutical companies and most of all the patients themselves. Benefits derived from these collections must be shared amongst contributing stakeholders and the principles of equality of access, benefit sharing and return of results should at all times be considered. 7. The GDPR in Europe coming into effect in May 2018 does not prevent data sharing in clinical SMA research, but provides legislation that is less divergent amongst different European member states than current frameworks. Similar principles and recommendations might be applicable to other areas of SMA research, such as standards of care, biomarkers and burden of illness, but were not covered in the workshop. Similarly, data sharing in preclinical research – beyond the publication in peer-reviewed scientific journals – is very pertinent and reviewed elsewhere. DISCLAIMER This statement reflects the personal opinion of the authors, but cannot be seen as binding to the organisations the authors are affiliated with. It aims to reflect and summarize a multi-stakeholder discussion that took place at the SMA Europe conference in Krakow in January 2018. Supplementary Material Supplementary Material Click here for additional data file.

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          Most cited references 11

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          Advances in therapy for spinal muscular atrophy: promises and challenges

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            Disease impact on general well-being and therapeutic expectations of European Type II and Type III spinal muscular atrophy patients.

            Spinal muscular atrophy (SMA) is a neurodegenerative disorder showing a broad clinical spectrum and no cure to date. To design and select evaluation criteria for the potential assessment of drugs currently being developed, the patient's perspective is critical. A survey, aiming to obtain a view on the current clinical state of European Type II and Type III SMA patients, the impact of this situation on their quality of life and their expectations regarding clinical development, was carried out by SMA-Europe member organizations in July 2015. A questionnaire was set up, translated into 8 European languages and sent out directly via electronic mailing to the targeted SMA patient population by the respective European patient organizations. We were able to collect 822 valid replies in less than two weeks. The questionnaire captured the current abilities of the respondents, their perception of the disease burden which appeared very similar across Europe despite some regional variations in care. According to the great majority of the respondents, stabilization of their current clinical state would represent a therapeutic progress for a compelling majority of the respondents to the questionnaire.
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              The International Rare Diseases Research Consortium: Policies and Guidelines to maximize impact

              The International Rare Diseases Research Consortium (IRDiRC) has agreed on IRDiRC Policies and Guidelines, following extensive deliberations and discussions in 2012 and 2013, as a first step towards improving coordination of research efforts worldwide. The 25 funding members and 3 patient umbrella organizations (as of early 2013) of IRDiRC, a consortium of research funders that focuses on improving diagnosis and therapy for rare disease patients, agreed in Dublin, Ireland in April 2013 on the Policies and Guidelines that emphasize collaboration in rare disease research, the involvement of patients and their representatives in all relevant aspects of research, as well as the sharing of data and resources. The Policies and Guidelines provide guidance on ontologies, diagnostics, biomarkers, patient registries, biobanks, natural history, therapeutics, models, publication, intellectual property, and communication. Most IRDiRC members—currently nearly 50 strong—have since incorporated its policies in their funding calls and some have chosen to exceed the requirements laid out, for instance in relation to data sharing. The IRDiRC Policies and Guidelines are the first, detailed agreement of major public and private funding organizations worldwide to govern rare disease research, and may serve as a template for other areas of international research collaboration. While it is too early to assess their full impact on research productivity and patient benefit, the IRDiRC Policies and Guidelines have already contributed significantly to improving transparency and collaboration in rare disease research.

                Author and article information

                J Neuromuscul Dis
                J Neuromuscul Dis
                Journal of Neuromuscular Diseases
                IOS Press (Nieuwe Hemweg 6B, 1013 BG Amsterdam, The Netherlands )
                29 May 2018
                : 5
                : 2
                : 131-133
                [a ]Department of Neuropediatrics and Muscle Disorders, Medical Center – University ofFreiburg , Faculty of Medicine, Freiburg, Germany
                [b ]Data Science – Personalized HealthCare, F. Hoffmann-La Roche , Basel, Switzerland
                [c ]Biogen , Cambridge, MA, USA
                [d ]Department of Pediatrics, Division of Neurology, Nemours Children’s Hospital , Orlando, USA
                [e ]Department of Pediatrics and Child Neurology, University Hospitals Leuven , Leuven, Belgium
                [f ]Fundación Atrofia Muscular Espinal , FundAME, Madrid, Spain
                [g ]Children withSpinal Muscular Atropy, Charitable Foundation , Kharkiv, Ukraine
                [h ]University College LondonGreat Ormond Institute of Child Health , London, UK; and NIHR Great Ormond Street Hospital Biomedical Research Centre, London UK
                [i ]AFM-Telethon , Evry, Ile-de-France, France
                [j ]Deutsche Gesellschaft für Muskelkranke e.V. , Freiburg, Germany
                [k ]Health Connect Partners , Brussels, Belgium
                [l ]SMA Europe , Chipping Campden, UK
                Author notes
                [* ]Correspondence to: Hanns Lochmüller, MD, FAAN, Department of Neuropediatrics and Muscle Disorders, Medical Center– University of Freiburg, Mathildenstr. 1 79160 Freiburg Germany. E-mail: Hanns.Lochmuller@ 123456gmail.com .
                © 2018 – IOS Press and the authors. All rights reserved

                This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.



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