Modified Delphi procedure-based expert consensus on endpoints for an international disease registry for Metachromatic Leukodystrophy: The European Metachromatic Leukodystrophy initiative (MLDi)

Orphanet Journal of Rare Diseases

Nicole I. Wolf¹  Shanice Beerepoot²  Daphne H. Schoenmakers³  Sabine Grønborg⁴  Peter G. M. Mol⁵  Carla E. M. Hollak⁶  Sibren van den Berg⁶  Ludger Schöls⁷  Samuel Groeschel⁸  Peter M. van Hasselt⁹  Laura Adang^1,10  Fanny Mochel^1,11  Caroline Sevin^1,12  Caroline Lindemans^1,13  Ayelet Zerem^1,14  Francesca Fumagalli^1,15  Jaap-Jan Boelens^1,16  Annette Bley^1,17  Wim G. Goettsch^1,18 

[1] Amsterdam Leukodystrophy Center, Department of Child Neurology, Emma Children’s Hospital, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam, The Netherlands;Amsterdam Leukodystrophy Center, Department of Child Neurology, Emma Children’s Hospital, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam, The Netherlands;Center for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands;Nierkens and Lindemans group, Princess Máxima Center for pediatric oncology, Utrecht, The Netherlands;Amsterdam Leukodystrophy Center, Department of Child Neurology, Emma Children’s Hospital, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam, The Netherlands;Department of Endocrinology and Metabolism, Amsterdam University Medical Centers, Amsterdam, The Netherlands;Medicine for Society, Platform at Amsterdam University Medical Centers, Amsterdam, The Netherlands;Centre for Inherited Metabolic Diseases, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark;Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands;Dutch Medicines Evaluation Board, Utrecht, The Netherlands;Department of Endocrinology and Metabolism, Amsterdam University Medical Centers, Amsterdam, The Netherlands;Medicine for Society, Platform at Amsterdam University Medical Centers, Amsterdam, The Netherlands;Department of Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen, 72076, Tübingen, Germany;German Center of Neurodegenerative Diseases, 72076, Tübingen, Germany;Department of Paediatric Neurology and Developmental Medicine, University Children’s Hospital, Tübingen, Germany;Department of Pediatric Metabolic Diseases, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands;Division of Neurology, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA;INSERM U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau Et de La Moelle Épinière, ICM, 75013, Paris, France;Department of Genetics, Center for Neurometabolic Diseases, AP-HP, La Pitié-Salpêtrière University Hospital, 47 Boulevard de l’Hôpital, 75013, Paris, France;NeuroGenCell, Institut du Cerveau et de la Moelle Épinière, ICM, Inserm U 1127, CNRS UMR 7225, Sorbonne Université, Paris, France;Bicêtre Hospital, Neuropediatrics Unit, Le Kremlin Bicêtre, Paris, France;Nierkens and Lindemans group, Princess Máxima Center for pediatric oncology, Utrecht, The Netherlands;Department of Pediatrics, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands;Pediatric Neurology Institute, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel;Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel;San Raffaele Telethon Institute for Gene Therapy (SR-Tiget); IRCCS, San Raffaele Scientific Institute, Milan, Italy;Stem Cell Transplantation and Cellular Therapies Program, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, 10065, New York, NY, USA;University Children’s Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany;Zorginstituut Nederland (Dutch Health Care Institute), Diemen, The Netherlands;Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht, The Netherlands;

关键词: Rare disease registry;    Rare diseases;    Metachromatic leukodystrophy;    MLD;    Delphi procedure;   

DOI  :  10.1186/s13023-022-02189-w

来源: Springer

【 摘 要 】

BackgroundMetachromatic 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 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.ResultsThree 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.ConclusionUsing 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.

【 授权许可】

CC BY