open access publication

Article, 2022

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

In: Orphanet Journal of Rare Diseases, ISSN 1750-1172, Volume 17, 1, 10.1186/s13023-022-02189-w

Contributors (19)

Schoenmakers D.H. [1] [2] Beerepoot S. [1] [3] [4] van den Berg S. [2] Adang L. [5] Bley A. [6] Boelens J.J. (0000-0003-2232-6952) [7] Fumagalli F. [8] Goettsch W. (0000-0002-8022-7496) [9] [10] Gronborg S. (0000-0002-2113-9023) [11] Groeschel S. [12] van Hasselt P.M. [13] Hollak C.E.M. [2] Lindemans C.A. [4] [13] Mochel F. [14] [15] Mol P.G.M. [16] [17] Sevin C. [15] [18] Zerem A. [19] [20] Schols L. [21] [22] Wolf N.I. (0000-0003-1721-0728) (Corresponding author) [1]

Affiliations

  1. [1] Emma Children's Hospital
  2. [NORA names: Netherlands; Europe, EU; OECD]
  3. [2] Academic Medical Center
  4. [NORA names: Netherlands; Europe, EU; OECD]
  5. [3] University Medical Center Utrecht
  6. [NORA names: Netherlands; Europe, EU; OECD]
  7. [4] Princess Máxima Center for Pediatric Oncology
  8. [NORA names: Netherlands; Europe, EU; OECD]
  9. [5] Children's Hospital of Philadelphia
  10. [NORA names: United States; America, North; OECD]
  11. [6] University Medical Center Hamburg-Eppendorf
  12. [NORA names: Germany; Europe, EU; OECD]
  13. [7] Memorial Sloan Kettering Cancer Center
  14. [NORA names: United States; America, North; OECD]
  15. [8] IRCCS Ospedale San Raffaele
  16. [NORA names: Italy; Europe, EU; OECD]
  17. [9] National Health Care Institute (Zorginstituut Nederland)
  18. [NORA names: Netherlands; Europe, EU; OECD]
  19. [10] Utrecht University
  20. [NORA names: Netherlands; Europe, EU; OECD]
  21. [11] Rigshospitalet
  22. [NORA names: Capital Region of Denmark; Hospital; Denmark; Europe, EU; Nordic; OECD]
  23. [12] University Hospital Tübingen
  24. [NORA names: Germany; Europe, EU; OECD]
  25. [13] Wilhelmina Children's Hospital
  26. [NORA names: Netherlands; Europe, EU; OECD]
  27. [14] AP-HP
  28. [NORA names: France; Europe, EU; OECD]
  29. [15] Sorbonne Université
  30. [NORA names: France; Europe, EU; OECD]
  31. [16] Dutch Medicines Evaluation Board
  32. [NORA names: Netherlands; Europe, EU; OECD]
  33. [17] University Medical Center Groningen
  34. [NORA names: Netherlands; Europe, EU; OECD]
  35. [18] Hôpital de Bicêtre
  36. [NORA names: France; Europe, EU; OECD]
  37. [19] Tel Aviv Sourasky Medical Center
  38. [NORA names: Israel; Asia, Middle East; OECD]
  39. [20] Tel Aviv University
  40. [NORA names: Israel; Asia, Middle East; OECD]
  41. [21] German Center for Neurodegenerative Diseases (DZNE)
  42. [NORA names: Germany; Europe, EU; OECD]
  43. [22] Hertie Institute for Clinical Brain Research
  44. [NORA names: Germany; Europe, EU; OECD]

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 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.

Keywords

Delphi procedure, MLD, Metachromatic leukodystrophy, Rare disease registry, Rare diseases

Funders

  • European Reference Network for Hereditary Metabolic Disorders
  • Bundesministerium für Gesundheit
  • European Commission
  • German Ministry of Health
  • Bundesministerium für Bildung und Forschung
  • Deutsche Forschungsgemeinschaft
  • ERN-RND
  • Zorginstituut Nederland