Table 3 Responses to statement included in Round 2 (16 respondents)

1. A single, standardised NPC clinical severity scale that can be used in routine clinical practice as well as clinical research on a global scale is desirable

81% (13)

19% (3)

2. A single, standardised NPC clinical severity scale that can be used in routine clinical practice as well as clinical research on a global scale is achievable within the scope of existing scales

75% (10)

25% (6)

3. A clinical consensus paper recommending which NPC clinical severity scale to use per different clinical setting (comprising routine practice and trial research) would be valuable to the international clinical and patient community

100% (16)

0% (0)

4. Assessment across the following 5-domains, provides an accurate clinical understanding of NPC severity: Ambulation, Cognition, Fine motor, Speech, Swallowing

87% (14)

13% (2)

5. If only one existing NPC severity scale was to be used for the evaluation of disease in normal clinical practice internationally, I would recommend the 5-domain NPCCSS scale

81% (13)

19% (3)

6. It is essential to measure all 17-domains in the NPCCSS during a clinical trial to capture all potential treatment benefits for people living with NPC

69% (9)

31% (7)

7. It is sufficient to measure the 5-domains in the 2018 NPCCSS during a clinical trial to capture relevant potential treatment benefits for people living with NPC

75% (10)

25% (6)

8. I believe the 5-domain NPCCSS scale satisfies requirements for use in all clinical settings, to standardise assessments on a global scale

69% (9)

31% (3)

9. I believe it is feasible and there is a need to develop a new NPC clinical severity scale that satisfies requirements for use in all clinical settings, to standardise assessments on a global scale

31% (7)

69% (9)

10. If a new universal NPC clinical severity scale were to be developed, the most important way that it would differ from existing scales would be…

Summary of key insights:

To balance breadth with brevity and usability

To focus on domains where change can be expected with disease progression or therapy

To evaluate cognition at different ages

To include quality of life measures

To determine the impact of epilepsy

To incorporate video of the performance of patients during the 9HPT and 8-min walk test

To include age/subtypes-dependant items (e.g. epilepsy and cataplexy in late infantile-juvenile, psychiatry in adolescent-adult…)

Based on the largest possible source data from natural history cohorts as well as clinical trials and take into account that NPC manifests and progresses differently across age groups and patient populations

Used across regions, languages and cultures

11. What would be your recommendations to implement a more uniform approach to the use of NPC clinical severity scales?

Summary of key insights:

To publish a systematic review of the current scales and consensus

To publish an expert consensus on which scale is preferred for clinical routine practice and which for trials

To develop detailed SOPs and training on the use of severity scales

To select a simple scale that can be used in different setting and is sensitive enough to capture the impact of the disease in the NPC patient

To add QoL measures to 5-domain NPCCSS

To gain insights from the community on what matters to patients and carers

To provide patients with score sheets, a booklet or app, to complete regularly and which they present to their doctors at every appointment

To include clinical scale biochemical markers and neuroimaging

To evolve clinical scales with available data and distinct uses (e.g. in a specific NPC sub-population, or to track changes in a specific subject), particularly as personalised medicine is a goal of this decade

To capture real-world results of scales systematically (e.g. INPDR) so that pre/post treatment effect are comparable