Struthers Parkinson's Center, Golden Valley, Minnesota.
Division of Biostatistics, University of Texas at Houston.
JAMA Neurol. 2014 Jun;71(6):710-6. doi: 10.1001/jamaneurol.2014.391.
Optimizing assessments of rate of progression in Parkinson disease (PD) is important in designing clinical trials, especially of potential disease-modifying agents.
To examine the value of measures of impairment, disability, and quality of life in assessing progression in early PD.
DESIGN, SETTING, AND PARTICIPANTS: Inception cohort analysis of data from 413 patients with early, untreated PD who were enrolled in 2 multicenter, randomized, double-blind clinical trials.
Participants were randomly assigned to 1 of 5 treatments (67 received creatine, 66 received minocycline, 71 received coenzyme Q10, 71 received GPI-1485, and 138 received placebo). We assessed the association between the rates of change in measures of impairment, disability, and quality of life and time to initiation of symptomatic treatment.
Time between baseline assessment and need for the initiation of symptomatic pharmaceutical treatment for PD was the primary indicator of disease progression.
After adjusting for baseline confounding variables with regard to the Unified Parkinson's Disease Rating Scale (UPDRS) Part II score, the UPDRS Part III score, the modified Rankin Scale score, level of education, and treatment group, we assessed the rate of change for the following measurements: the UPDRS Part II score; the UPDRS Part III score; the Schwab and England Independence Scale score (which measures activities of daily living); the Total Functional Capacity scale; the 39-item Parkinson's Disease Questionnaire, summary index, and activities of daily living subscale; and version 2 of the 12-item Short Form Health Survey Physical Summary and Mental Summary. Variables reaching the statistical threshold in univariate analysis were entered into a multivariable Cox proportional hazards model using time to symptomatic treatment as the dependent variable. More rapid change (ie, worsening) in the UPDRS Part II score (hazard ratio, 1.15 [95% CI, 1.08-1.22] for 1 scale unit change per 6 months), the UPDRS Part III score (hazard ratio, 1.09 [95% CI, 1.06-1.13] for 1 scale unit change per 6 months), and the Schwab and England Independence Scale score (hazard ratio, 1.29 [95% CI, 1.12-1.48] for 5 percentage point change per 6 months) was associated with earlier need for symptomatic therapy.
AND RELEVANCE In early PD, the UPDRS Part II score and Part III score and the Schwab and England Independence Scale score can be used to measure disease progression, whereas the 39-item Parkinson's Disease Questionnaire and summary index, Total Functional Capacity scale, and the 12-item Short Form Health Survey Physical Summary and Mental Summary are not sensitive to change.
clinicaltrials.gov Identifiers: NCT00063193 and NCT00076492.
优化帕金森病（PD）进展率的评估对于临床试验的设计很重要，特别是对于潜在的疾病修饰剂。
研究在早期 PD 中，评估损伤、残疾和生活质量的措施在评估进展方面的价值。
设计、地点和参与者：413 名未经治疗的早期 PD 患者的队列分析，这些患者参与了 2 项多中心、随机、双盲临床试验。
参与者被随机分配到 5 种治疗方法之一（67 人接受肌酸治疗，66 人接受米诺环素治疗，71 人接受辅酶 Q10 治疗，71 人接受 GPI-1485 治疗，138 人接受安慰剂治疗）。我们评估了损伤、残疾和生活质量测量值的变化率与开始进行有症状药物治疗之间的关系。
从基线评估到需要开始进行有症状的 PD 药物治疗之间的时间是疾病进展的主要指标。
在调整了统一帕金森病评定量表（UPDRS）第二部分评分、UPDRS 第三部分评分、改良 Rankin 量表评分、教育程度和治疗组的基线混杂变量后，我们评估了以下测量值的变化率：UPDRS 第二部分评分；UPDRS 第三部分评分；施瓦布和英格兰独立量表评分（用于评估日常生活活动能力）；总功能能力量表；39 项帕金森病问卷、综合指数和日常生活活动子量表；以及 12 项简短健康调查问卷物理综合和心理综合的第 2 版。在单变量分析中达到统计学阈值的变量被输入到多变量 Cox 比例风险模型中，以有症状治疗的时间作为因变量。UPDRS 第二部分评分（每 6 个月变化 1 个单位，风险比为 1.15 [95%CI，1.08-1.22]）、UPDRS 第三部分评分（每 6 个月变化 1 个单位，风险比为 1.09 [95%CI，1.06-1.13]）和施瓦布和英格兰独立量表评分（每 6 个月变化 5 个百分点，风险比为 1.29 [95%CI，1.12-1.48]）的变化更快与更早需要进行有症状的治疗相关。
在早期 PD 中，UPDRS 第二部分评分和第三部分评分以及施瓦布和英格兰独立量表评分可用于测量疾病进展，而 39 项帕金森病问卷和综合指数、总功能能力量表以及 12 项简短健康调查问卷物理综合和心理综合对变化不敏感。
clinicaltrials.gov 标识符：NCT00063193 和 NCT00076492。
