Marshall Randall D, Collins Abigail, Escolar Maria L, Jinnah H A, Klopstock Thomas, Kruer Michael C, Videnovic Aleksandar, Robichaux-Viehoever Amy, Swett Laura, Revicki Dennis A, Bender Randall H, Lenderking William R
Formerly of Retrophin, Inc. Cambridge Massachusetts USA.
Departments of Pediatrics and Neurology University of Colorado School of Medicine Denver Colorado USA.
Mov Disord Clin Pract. 2019 Jan 22;6(2):139-149. doi: 10.1002/mdc3.12716. eCollection 2019 Feb.
Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal-recessive, neurodegenerative disorder with a mixed-motor phenotype caused by a defective PanK2 enzyme, for which there are few adequate treatment options. Clinimetrically sound measures of patient-reported outcomes are necessary to facilitate therapeutic development for this debilitating disease. This study's objective was to develop such a scale and assess its clinimetric properties.
A conceptually driven, iterative, content development process incorporating input from experts, caregivers, and patients was used. Scale items were initially adapted from the Unified Parkinson's Disease Rating Scale (UPDRS) Part II resulting in the 12-item Pantothenate Kinase-Associated Neurodegeneration Activities of Daily Living (PKAN-ADL). The PKAN-ADL scale was administered to caregivers (n = 37) and patients (n = 2) twice over 2 weeks, along with selected Quality of Life in Neurological Disorders (Neuro-QoL) measures, selected attributes of the Health Utilities Index (HUI)-2/3, and the Stroke Aphasia Depression Questionnaire (SADQ-10) to assess construct validity.
Internal consistency was 0.93, with excellent test-retest reliability (intraclass correlation coefficient = 0.99). Of the 12 items, 25% (n = 3) showed a ceiling effect >30% (range, 31-54) and 42% (n = 5) showed a floor effect >30% (range, 31-46), reflecting disease heterogeneity. Convergent validity was shown with Neuro-QoL measures (s > 0.90) and HUI-2/3 attributes (s ≥ 0.48); divergent validity was demonstrated with the SADQ-10 ( = 0.11). Participants reported a high level of comprehension (98%), and average item relevance ratings (0-10 scale) ranged from 7.0 to 9.9.
The PKAN-ADL scale demonstrated acceptable content validity, with evidence of construct validity and excellent reliability. Overall results support the use of the PKAN-ADL scale in clinical trials.
泛酸激酶相关神经变性（PKAN）是一种常染色体隐性神经退行性疾病，具有由缺陷的泛K2酶引起的混合运动表型，针对该疾病几乎没有足够的治疗选择。临床上合理的患者报告结局测量方法对于促进这种使人衰弱的疾病的治疗发展是必要的。本研究的目的是开发这样一种量表并评估其临床测量特性。
采用了一个概念驱动的、迭代的内容开发过程，纳入了专家、护理人员和患者的意见。量表项目最初改编自统一帕金森病评定量表（UPDRS）第二部分，从而产生了包含12个条目的泛酸激酶相关神经变性日常生活活动量表（PKAN-ADL）。在2周内，对护理人员（n = 37）和患者（n = 2）进行了两次PKAN-ADL量表测试，同时还进行了选定的神经疾病生活质量（Neuro-QoL）测量、健康效用指数（HUI）-2/3的选定属性以及中风失语抑郁问卷（SADQ-10），以评估结构效度。
内部一致性为0.93，重测信度极佳（组内相关系数 = 0.99）。在12个条目中，25%（n = 3）显示天花板效应>30%（范围为31 - 54），42%（n = 5）显示地板效应>30%（范围为31 - 46），反映了疾病的异质性。与Neuro-QoL测量（s > 0.90）和HUI-2/3属性（s ≥ 0.48）显示出收敛效度；与SADQ-10（ = 0.11）显示出区分效度。参与者报告理解程度很高（98%），平均项目相关性评分（0 - 10分制）范围为7.0至9.9。
PKAN-ADL量表显示出可接受的内容效度，有结构效度的证据且信度极佳。总体结果支持在临床试验中使用PKAN-ADL量表。
