Abstract
BackgroundSeveral scales have been developed in the past two decades to evaluate Niemann–Pick disease Type C (NPC) severity in clinical practice and trials. However, a lack of clarity concerning which scale to use in each setting is preventing the use of standardised assessments across the world, resulting in incomparable data sets and clinical trial outcome measures. This study aimed to establish agreed approaches for the use of NPC severity scales in clinical practice and research.MethodsA Delphi method of consensus development was used, comprising three survey rounds. In Round 1, participants were asked nine multiple-choice and open-ended questions to gather opinions on the six severity scales and domains. In Rounds 2 and 3, questions aimed to gain consensus on the opinions revealed in Round 1 using a typical Likert scale.ResultsNineteen experts, active in NPC paediatric and adult research and treatment, participated in this study. Of these, 16/19 completed Rounds 1 and 2 and 19/19 completed Round 3. Consensus (defined as ≥ 70% agreement or neutrality, given the study aim to identify the severity scales that the clinical community would accept for international consistency) was achieved for 66.7% of the multiple-choice questions in Round 2 and 83% of the multiple-choice questions in Round 3. Consensus was almost reached (68%) on the use of the 5-domain NPCCSS scale as the first choice in clinical practice. Consensus was reached (74%) for the 17-domain NPCCSS scale as the first choice in clinical trial settings, but the domains measured in the 5-domain scale should be prioritised as the primary endpoints. Experts called for educational and training materials on how to apply the NPCCSS (17- and 5-domains) for clinicians working in NPC.ConclusionsIn achieving a consensus on the use of the 17-domain NPCCSS scale as the first choice for assessing clinical severity of NPC in clinical trial settings but prioritising the domains in the 5-domain NPCCSS scale for routine clinical practice, this study can help to inform future discussion around the use of the existing NPC clinical severity scales. For routine clinical practice, the study helps provide clarity on which scale is favoured by a significant proportion of a representative body of experts, in this case, the 5-domain NPCCSS scale.
Highlights
Niemann–Pick disease Type C (NPC) is a devastating, rare neurodegenerative disease characterised by a defect that severely impedes cellular lipid trafficking [1]
Participants Each survey round of this Delphi study comprised a representative panel of clinical experts treating both paediatric and adult NPC patients, from seven different countries: United States of America (n = 6), United Kingdom (n = 5), Germany (n = 3), Spain (n = 2), Brazil (n = 1), France (n = 1) and Australia (n = 1)
Round 1 In Round 1, consensus was reached amongst the 16 international experts on the five most important domains to be measured to assess NPC clinical severity in the context of all three clinical settings
Summary
Niemann–Pick disease Type C (NPC) is a devastating, rare neurodegenerative disease characterised by a defect that severely impedes cellular lipid trafficking [1]. Cholesterol and sphingolipids accumulate within the endosomal/lysosomal system, degrading the central nervous system (CNS) and causing a diverse number of neurological symptoms depending on the patient’s age at onset. These symptoms may include cerebellar ataxia, dysarthria, dysphagia, cataplexy, seizures, dystonia, vertical gaze palsy, progressive dementia and death by 8–25 years of age [2]. The severe disabilities caused by NPC, during the later stages of the disease, affect a patient’s entire family and optimal disease management requires highly specialised healthcare within a multidisciplinary care setting. Several scales have been developed in the past two decades to evaluate Niemann–Pick disease Type C (NPC) severity in clinical practice and trials. This study aimed to establish agreed approaches for the use of NPC severity scales in clinical practice and research
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have