Goetz Christopher G, Leurgans Sue, Raman Rema
Department of Neurological Sciences Rush University, Rush Presbyterian St. Luke's Medical Center, Chicago, Illinois 60612, USA.
Mov Disord. 2002 Mar;17(2):283-8. doi: 10.1002/mds.10024.
The Unified Parkinson's Disease Rating Scale (UPDRS) is primarily composed of an investigator-derived objective rating of motor function and a patient-derived assessment of activities of daily living (ADL). Using a stringent definition of placebo effect, we examined the frequency, temporal development, and stability of improvements during placebo treatment over 6 months in a large placebo-controlled trial of deprenyl and tocopherol in early Parkinson's disease (DATATOP). One hundred ninety-nine subjects received placebo treatment in the randomized, multicenter, placebo-controlled DATATOP study. We compared the baseline UPDRS motor section scores with follow-up scores at 4, 13, and 26 weeks. Placebo-associated improvement was defined as an improvement over baseline score in motor UPDRS of at least 50% or a change in at least two motor items at any one visit by two or more points. Seventeen percent of the 185 subjects who qualified for analysis met the placebo response criteria. The group prevalence of response was steady (7% to 10%) at any one visit without a marked predominance of an early study effect. Older subjects with more motor impairment at baseline were most likely to show a placebo-associated improvement. ADL scores were low throughout the study, and ADL improvements did not identify the subjects with objectively defined placebo-associated improvement. Prominent improvements in investigator-derived objective measures of Parkinson's disease motor impairment occur during clinical trials, including one that was not aimed at showing improved short-term efficacy. Although the notion of placebo effect often implies patient-based perceptions, we found subjective changes to be infrequent in placebo-treated patients, suggesting that either: (1) the placebo effect was rater-driven; (2) the ADL questionnaire is insensitive to transient but objectively demonstrable motor changes; or (3) that the objective changes, albeit major, are within the realm of natural variation in the UPDRS motor scale from visit to visit.
统一帕金森病评定量表（UPDRS）主要由研究者得出的运动功能客观评分以及患者得出的日常生活活动（ADL）评估组成。在一项关于早期帕金森病（DATATOP）的大剂量安慰剂对照试验中，我们采用对安慰剂效应的严格定义，研究了6个月安慰剂治疗期间改善情况的频率、时间发展过程及稳定性。199名受试者在随机、多中心、安慰剂对照的DATATOP研究中接受了安慰剂治疗。我们比较了基线UPDRS运动部分评分与4周、13周和26周时的随访评分。安慰剂相关改善被定义为运动UPDRS评分较基线至少提高50%，或在任何一次访视时至少两个运动项目的变化达到两分或更多。符合分析条件的185名受试者中，17%达到了安慰剂反应标准。在任何一次访视时，反应的组患病率稳定（7%至10%），未出现早期研究效应的明显优势。基线时运动障碍更严重的老年受试者最有可能出现安慰剂相关改善。在整个研究过程中，ADL评分较低，ADL改善情况无法识别出具有客观定义的安慰剂相关改善的受试者。在临床试验期间，帕金森病运动障碍的研究者得出的客观测量指标出现了显著改善，包括一项并非旨在显示短期疗效改善的试验。尽管安慰剂效应的概念通常意味着基于患者的认知，但我们发现接受安慰剂治疗的患者中主观变化并不常见，这表明要么：（1）安慰剂效应是由评估者驱动的；（2）ADL问卷对短暂但客观可证明的运动变化不敏感；要么（3）尽管客观变化很大，但仍在UPDRS运动量表每次访视的自然变化范围内。
