Département de Pharmacologie Clinique, Hôpital de la Pitié-Salpêtrière, APHP, UPMC Pharmacologie, Paris 6, UMR 7211, Paris, France.
PLoS One. 2011;6(8):e22293. doi: 10.1371/journal.pone.0022293. Epub 2011 Aug 4.
The Natural History and Neuroprotection in Parkinson Plus Syndromes (NNIPPS) study was a large phase III randomized placebo-controlled trial of riluzole in Progressive Supranuclear Palsy (PSP, n = 362) and Multiple System Atrophy (MSA, n = 398). To assess disease severity and progression, we constructed and validated a new clinical rating scale as an ancillary study.
Patients were assessed at entry and 6-montly for up to 3 years. Evaluation of the scale's psychometric properties included reliability (n = 116), validity (n = 760), and responsiveness (n = 642). Among the 85 items of the initial scale, factor analysis revealed 83 items contributing to 15 clinically relevant dimensions, including Activity of daily Living/Mobility, Axial bradykinesia, Limb bradykinesia, Rigidity, Oculomotor, Cerebellar, Bulbar/Pseudo-bulbar, Mental, Orthostatic, Urinary, Limb dystonia, Axial dystonia, Pyramidal, Myoclonus and Tremor. All but the Pyramidal dimension demonstrated good internal consistency (Cronbach α ≥ 0.70). Inter-rater reliability was high for the total score (Intra-class coefficient = 0.94) and 9 dimensions (Intra-class coefficient = 0.80-0.93), and moderate (Intra-class coefficient = 0.54-0.77) for 6. Correlations of the total score with other clinical measures of severity were good (rho ≥ 0.70). The total score was significantly and linearly related to survival (p<0.0001). Responsiveness expressed as the Standardized Response Mean was high for the total score slope of change (SRM = 1.10), though higher in PSP (SRM = 1.25) than in MSA (SRM = 1.0), indicating a more rapid progression of PSP. The slope of change was constant with increasing disease severity demonstrating good linearity of the scale throughout disease stages. Although MSA and PSP differed quantitatively on the total score at entry and on rate of progression, the relative contribution of clinical dimensions to overall severity and progression was similar.
The NNIPPS-PPS has suitable validity, is reliable and sensitive, and therefore is appropriate for use in clinical studies with PSP or MSA.
ClinicalTrials.gov NCT00211224.
自然病史和神经保护在帕金森加综合征（NNIPPS）研究是一项大型的 III 期随机安慰剂对照试验的利鲁唑在进行性核上性麻痹（PSP，n = 362）和多系统萎缩（MSA，n = 398）。为了评估疾病的严重程度和进展，我们构建并验证了一个新的临床评分量表作为辅助研究。
患者在进入研究时和 6 个月时进行评估，最长可达 3 年。评估量表的心理测量特性包括可靠性（n = 116）、有效性（n = 760）和反应性（n = 642）。在初始量表的 85 个项目中，因子分析显示 83 个项目对 15 个临床相关维度有贡献，包括日常生活/移动活动、轴性运动迟缓、肢体运动迟缓、僵硬、眼球运动、小脑、延髓/假性延髓、精神、直立、尿、肢体张力障碍、轴性张力障碍、锥体束、肌阵挛和震颤。除了锥体束维度外，其他所有维度的内部一致性都很好（Cronbach α≥0.70）。总评分的观察者间信度很高（组内相关系数=0.94），9 个维度的观察者间信度也很高（组内相关系数=0.80-0.93），6 个维度的观察者间信度中等（组内相关系数=0.54-0.77）。总评分与其他严重程度的临床测量之间的相关性很好（rho≥0.70）。总评分与生存率呈显著线性关系（p<0.0001）。以标准化反应均值表示的总评分变化斜率的反应性较高（SRM = 1.10），尽管 PSP 中的反应性（SRM = 1.25）高于 MSA（SRM = 1.0），表明 PSP 的进展更快。随着疾病严重程度的增加，变化斜率保持不变，表明该量表在整个疾病阶段具有良好的线性。尽管 MSA 和 PSP 在总评分、进展率上存在差异，但临床维度对整体严重程度和进展的相对贡献是相似的。
NNIPPS-PPS 具有适当的有效性，可靠且敏感，因此适用于 PSP 或 MSA 的临床试验。
ClinicalTrials.gov NCT00211224。
