Abstract
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.
Highlights
Metachromatic leukodystrophy (MLD, Online Mendelian Inheritance in Man (OMIM) 250,100 and 249,900) is an autosomal recessively inherited lysosomal storage disorder with an estimated birth prevalence of 1 in 40.000 [1]
Schoenmakers et al Orphanet Journal of Rare Diseases (2022) 17:48 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
We provide an overview of the modified Delphi procedure used for this goal and the resulting list of data elements
Summary
Metachromatic leukodystrophy (MLD, OMIM 250,100 and 249,900) is an autosomal recessively inherited lysosomal storage disorder with an estimated birth prevalence of 1 in 40.000 [1]. Myelin sheaths of the central and peripheral nervous system are especially affected, resulting in progressive demyelination. This causes neurological deterioration and, if untreated, eventually leads to death [4]. Symptom-onset at a younger age is generally associated with a faster disease progression and shorter life expectancy, as shown in Fig. 1 [2, 5, 6]. Metachromatic Leukodystrophy (MLD) is a rare lysosomal disorder. 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 technol‐ ogy assessments (HTA). 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
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