Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Nov 18;16(1):482.
doi: 10.1186/s13023-021-02115-6.

International consensus on clinical severity scale use in evaluating Niemann-Pick disease Type C in paediatric and adult patients: results from a Delphi Study

William Evans  1   2 , Marc Patterson  3 , Frances Platt  4 , Christina Guldberg  5 , Toni Mathieson  6   7 , Jessica Pacey  8 ; Core Working Group for the Delphi Study
Collaborators, Affiliations

International consensus on clinical severity scale use in evaluating Niemann-Pick disease Type C in paediatric and adult patients: results from a Delphi Study

William Evans et al. Orphanet J Rare Dis. .

Abstract

Background: Several 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.

Methods: A 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.

Results: Nineteen 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.

Conclusions: In 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.

Keywords: Clinical Severity Scales; Consensus Paper; Delphi Study; Niemann–Pick disease Type C (NPC).

PubMed Disclaimer

Conflict of interest statement

MP has stock in IntraBio, has consulted for Orphazyme (with monies directed to the Mayo Clinic) and has received research support from Amicus, Glycomine, Idorsia, Orphazyme and Shire-Takeda (with funds to the Mayo Clinic). FP is cofounder and consultant to IntraBio, has stock in IntraBio, and has consulted for Actelion and Orphazyme. CG is an employee of Orphazyme A/S, which is conducting clinical research in NPC.

References

    1. Tang Y, Li H, Liu J. Niemann-Pick disease Type C: from molecule to clinic. Clin Exp Pharmacol Physiol. 2010;37(1):132–140. doi: 10.1111/j.1440-1681.2009.05235.x. - DOI - PubMed
    1. Patterson M, Vanier M, Suzuki K, Morris J, Carstea E, Neufeld E, et al. Niemann-Pick disease type C: a lipid trafficking disorder. Online Metab Mol Bases Inher Dis. 2001;8:3611–3634.
    1. Geberhiwot T, Moro A, Dardis A, Ramaswami U, Sirrs S, Marfa M et al. Consensus clinical management guidelines for Niemann-Pick disease type C. Orphanet J Rare Dis 2018;13(1). - PMC - PubMed
    1. Iturriaga C, Pineda M, Fernández-Valero E, Vanier M, Coll M. Niemann-Pick C disease in Spain: clinical spectrum and development of a disability scale. J Neurol Sci. 2006;249(1):1–6. doi: 10.1016/j.jns.2006.05.054. - DOI - PubMed
    1. Jones J, Hunter D. Qualitative research: consensus methods for medical and health services research. BMJ. 1995;311(7001):376–380. doi: 10.1136/bmj.311.7001.376. - DOI - PMC - PubMed

Publication types