Goetz Christopher G, Wuu Joanne, McDermott Michael P, Adler Charles H, Fahn Stanley, Freed Curt R, Hauser Robert A, Olanow Warren C, Shoulson Ira, Tandon P K, Leurgans Sue
Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois 60612, USA.
Mov Disord. 2008 Apr 15;23(5):690-9. doi: 10.1002/mds.21894.
Placebo-associated improvements have been previously documented in small series of Parkinson's disease (PD) patients. Using a strict definition of placebo-associated improvement, we examined rates and timing of placebo responses to identify patient- and study-based characteristics, predicting positive placebo response in several PD clinical trials. We collected individual patient data from the placebo groups of 11 medical and surgical treatment trials involving PD patients with differing PD severities and placebo-assignment likelihoods. We defined a positive placebo response as > or = 50% improvement in total Unified Parkinson's Disease Rating Scale motor (UPDRSm) score or a decrease by > or = 2 points on at least two UPDRSm items compared to baseline. We calculated positive placebo response rates at early (3-7 weeks), mid (8-18 weeks), and late (23-35 weeks) stages of follow-up. Odds ratios for patient- and study-based characteristics were obtained from a model fitted using generalized estimating equations. There were 858 patients on placebo who met inclusion criteria for analysis. Three studies involved patients without need of symptomatic treatment, two involved patients without motor fluctuations needing symptomatic treatment, and six (three medical and three surgical) involved patients with motor fluctuations. The overall placebo response rate was 16% (range: 0-55%). Patients with higher baseline UPDRSm scores and studies that focused on PD with motor fluctuations, surgical interventions, or those with a higher probability of placebo assignment showed increased odds of positive placebo response. Placebo responses were temporally distributed similarly during early, mid, and late phases of follow-up. Placebo-related improvements occur in most PD clinical trials and are similarly distributed across all 6 months of follow-up. Recognition of factors that impact placebo response rates should be incorporated into individual study designs for PD clinical trials.
安慰剂相关的改善此前已在一小部分帕金森病（PD）患者中得到记录。我们使用对安慰剂相关改善的严格定义，检查了安慰剂反应的发生率和时间，以确定基于患者和研究的特征，从而预测在多项PD临床试验中的阳性安慰剂反应。我们从11项药物和手术治疗试验的安慰剂组中收集了个体患者数据，这些试验涉及不同PD严重程度和安慰剂分配可能性的PD患者。我们将阳性安慰剂反应定义为与基线相比，帕金森病统一评分量表运动部分（UPDRSm）总分改善≥50%，或至少两项UPDRSm项目得分降低≥2分。我们计算了随访早期（3 - 7周）、中期（8 - 18周）和晚期（23 - 35周）的阳性安慰剂反应率。基于患者和研究的特征的优势比是通过使用广义估计方程拟合的模型获得的。有858名接受安慰剂治疗的患者符合纳入分析标准。三项研究涉及无需对症治疗的患者，两项研究涉及无运动波动但需要对症治疗的患者，六项研究（三项药物研究和三项手术研究）涉及有运动波动的患者。总体安慰剂反应率为16%（范围：0 - 55%）。基线UPDRSm评分较高的患者以及专注于有运动波动的PD、手术干预或安慰剂分配可能性较高的研究显示出阳性安慰剂反应的几率增加。安慰剂反应在随访的早期、中期和晚期阶段的时间分布相似。安慰剂相关的改善在大多数PD临床试验中都会出现，并且在整个6个月的随访中分布相似。对影响安慰剂反应率的因素的认识应纳入PD临床试验的个体研究设计中。
