Modified Delphi procedure-based expert consensus on endpoints for an international disease registry for Metachromatic Leukodystrophy: The European Metachromatic Leukodystrophy initiative (MLDi)
Schoenmakers, Daphne H; Beerepoot, Shanice; van den Berg, Sibren; Adang, Laura; Bley, Annette; Boelens, Jaap-Jan; Fumagalli, Francesca; Goettsch, Wim G; Grønborg, Sabine; Groeschel, Samuel; van Hasselt, Peter M; Hollak, Carla E M; Lindemans, Caroline; Mochel, Fanny; Mol, Peter G M; Sevin, Caroline; Zerem, Ayelet; Schöls, Ludger; Wolf, Nicole I
(2022) Orphanet Journal of Rare Diseases, volume 17, issue 1, pp. 1 - 14
(Article)
Abstract
BACKGROUND: Metachromatic Leukodystrophy (MLD) is a rare lysosomal disorder. Patients suffer from relentless neurological deterioration leading to premature death. Recently, new treatment modalities, including gene therapy and enzyme replacement therapy, have been developed. Those advances increase the need for high-quality research infrastructure to adequately compare treatments, execute post-marketing surveillance, and
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perform health technology assessments (HTA). To facilitate this, a group of MLD experts started the MLD initiative (MLDi) and initiated an academia-led European MLD registry: the MLDi. An expert-based consensus procedure, namely a modified Delphi procedure, was used to determine the data elements required to answer academic, regulatory, and HTA research questions. RESULTS: Three distinct sets of data elements were defined by the 13-member expert panel. The minimal set (n = 13) contained demographics and basic disease characteristics. The core set (n = 55) included functional status scores in terms of motor, manual, speech and eating abilities, and causal and supportive treatment characteristics. Health-related quality of life scores were included that were also deemed necessary for HTA. The optional set (n = 31) contained additional clinical aspects, such as findings at neurological examination, detailed motor function, presence of peripheral neuropathy, gall bladder involvement and micturition. CONCLUSION: Using a modified Delphi procedure with physicians from the main expert centers, consensus was reached on a core set of data that can be collected retrospectively and prospectively. With this consensus-based approach, an important step towards harmonization was made. This unique dataset will support knowledge about the disease and facilitate regulatory requirements related to the launch of new treatments.
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Keywords: Delphi procedure, MLD, Metachromatic leukodystrophy, Rare disease registry, Rare diseases, Genetics(clinical), Pharmacology (medical)
ISSN: 1750-1172
Publisher: BioMed Central
Note: Funding Information: The following authors of this publication are members of the European Reference Network for Rare Neurological Diseases (ERN-RND) – Project ID No 739510: S. Groeschel, L. Schöls, C. Sevin, N. I. Wolf. The following authors of this publication are members of the European Reference Network for Hereditary Metabolic Disorders (Metab-ERN): C.E.M. Hollak, F. Mochel, S. Grønborg. The following author of this publication are members of the European Reference Network for transplantation in Children (ERN TransplantChild): C. Lindemans. Funding Information: LA is consultant for Orchard, co-investigator for the Metachromatic leukodystrophy trial of Takeda, MEGMA. AB is coinvestigator for a trial in MLD (Shire/Takeda) but receives no personal payment related to this role. JB received honorarium for consulting / ad boards from Omeros, Avrobio, Advanced Clinical, BlueRock, Sanofi, Race Oncology and Medexus (all not related to this topic). FF is an investigator of gene therapy clinical trials for MLD sponsored by Orchard Therapeutics, the license holder of investigational medicinal product arsa-cel. FF has acted as ad hoc consultant for an Orchard Therapeutics and Takeda advisory boards. SabG is speaker honoraria from PTC Therapeutics; advisory boards for Takeda Pharma A/S, bluebird bio GmbH, PTC Therapeutics, Orchard Therapeutics; travel grants from Sanofi Genzyme A/S; Principal Investigator in CT-ORZY-NPC-002 (Orphazyme). SamG received institutional research support from Shire/Takeda. He is advisor and coinvestigator for trials in MLD (Shire/Takeda, Orchard) but receives no personal payment related to this role. Funded by DFG grant GR 4688/2-1. CH is involved in premarketing studies with Idorsia, Sanofi and Protalix, outside the scope of this manuscript. LS is consultant for VICO Therapeutics and receives funding of the German Ministry of Health (BMG grant ZMVI1-2520DAT94E) to LeukoExpert, of the German Ministry of Education and Research (BMBF grant 01GM1907A to Treat-ION and grant 01GM1905A to TreatHSP) and of the European Commission (grant 947588 to the ERN-RND registry). NW is consultant for Passage Bio, Ionis, Orchard, co-investigator for the Metachromatic leukodystrophy trial of Shire/Takeda. She receives research support from Metakids and ZonMW. She is in the scientific advisory board of European Leukodystrophy Association (ELA), Mission Massimo, Yaya foundation. She is editor of Neuropediatrics, member of the editorial boards of Neurology and European Journal of Pediatric Neurology. Funding Information: This work is part of the platform Medicine for Society, for which funding is provided by the Nationale Postcode Loterij (part of Dutch Charity Lotteries). The MLD initiative is partially supported by the National Health Care Institute (Zorginstituut Nederland) in the context of the project "Managing patient registries for expensive drugs". The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Publisher Copyright: © 2022, The Author(s).
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