Mayo Clinic Children's Center, 200 1st St SW, Rochester, MN, 55905, USA.
Clinical Outcomes Solutions, Folkestone, Kent, UK.
Orphanet J Rare Dis. 2021 Feb 12;16(1):79. doi: 10.1186/s13023-021-01719-2.
Niemann-Pick disease type C (NPC) is an ultra-rare, progressive, genetic disease leading to impaired lysosomal function and neurodegeneration causing serious morbidity and shortened life expectancy. The Niemann-Pick type C Clinical Severity Scale (NPCCSS) is a 17 domain, disease-specific, clinician-reported outcome measure of disease severity and progression. An abbreviated 5-domain NPCCSS scale has been developed (measuring Ambulation, Swallow, Cognition, Speech, and Fine Motor Skills) and the scale reliability has been established. Additional psychometric properties and meaningful change of the scale need, however, to be assessed.
Mixed method studies were conducted to ascertain which NPCCSS domains were most important, as well as to explore meaningful change: 1) surveys in caregivers/patients (n = 49) and 2) interviews with clinicians (n = 5) as well as caregivers/patients (n = 28). Clinical trial data (n = 43) assessed construct validity and meaningful change through an anchor-based approach.
Domains identified as most important by clinicians, caregivers, and patients (independent of current age, age of onset, and disease severity) were Ambulation, Swallow, Cognition, Speech, and Fine Motor Skills, indicating content validity of the 5-domain NPCCSS. Criterion validity was shown with the 5-domain NPCCSS being highly correlated with the 17-item NPCCSS total score (excluding hearing domains), r = 0.97. Convergent validity was demonstrated against the 9 Hole Peg Test, r = 0.65 (n = 31 patients), and the Scale for Assessment and Rating of Ataxia (SARA), r = 0.86 (n = 49 patients). Any change was seen as meaningful by patients/caregivers across domains. Meaningful change using trial data and interviews with NPC experts (n = 5) and patients/caregivers (n = 28) suggested that a 1-category change on a domain is equivalent to 1-point change or greater in the 5-domain NPCCSS total score.
Qualitative and quantitative data support content and construct validity of the 5-domain NPCCSS score as a valid endpoint in NPC trials. A 1-category change on any domain is equivalent to 1-point change or greater in the 5 domain NPCCSS total score, representing a clinically meaningful transition and reflecting loss of complex function and increased disability. Trial registration NCT02612129. Registered 23 November 2015, https://clinicaltrials.gov/ct2/show/NCT02612129.
尼曼-皮克病 C 型（NPC）是一种罕见的、进行性的遗传疾病，导致溶酶体功能受损和神经退行性变，从而导致严重的发病率和缩短的预期寿命。尼曼-皮克 C 型临床严重程度评分（NPCCSS）是一种 17 个领域的、特定于疾病的、由临床医生报告的疾病严重程度和进展的结果测量工具。已经开发了一个简化的 5 领域 NPCCSS 量表（测量行走、吞咽、认知、言语和精细运动技能），并且已经确定了该量表的可靠性。然而，需要评估该量表的其他心理测量特性和有意义的变化。
采用混合方法研究来确定哪些 NPCCSS 领域最重要，并探讨有意义的变化：1）对护理人员/患者（n=49）进行调查和 2）对临床医生（n=5）以及护理人员/患者（n=28）进行访谈。临床试验数据（n=43）通过基于锚定的方法评估了结构有效性和有意义的变化。
临床医生、护理人员和患者（独立于当前年龄、发病年龄和疾病严重程度）确定的最重要的领域是行走、吞咽、认知、言语和精细运动技能，表明 5 领域 NPCCSS 具有内容有效性。5 领域 NPCCSS 与 17 项 NPCCSS 总分（不包括听力领域）高度相关，r=0.97，表明具有标准有效性。与 9 孔钉测试（r=0.65，n=31 例患者）和共济失调评估和评分量表（SARA）（r=0.86，n=49 例患者）的收敛效度。患者/护理人员在所有领域都认为任何变化都具有意义。使用试验数据和与 NPC 专家（n=5）和患者/护理人员（n=28）的访谈得出的有意义的变化表明，在任何领域中，类别变化相当于 5 领域 NPCCSS 总分中的 1 点或更大变化。
定性和定量数据支持 5 领域 NPCCSS 评分作为 NPC 试验中的有效终点的内容和结构有效性。任何领域的 1 个类别变化相当于 5 领域 NPCCSS 总分中的 1 点或更大变化，代表了临床有意义的转变，反映了复杂功能的丧失和残疾程度的增加。试验注册 NCT02612129。于 2015 年 11 月 23 日注册，https://clinicaltrials.gov/ct2/show/NCT02612129。
