Hart Robert G, Pearce Lesly A, Ravina Bernard M, Yaltho Toby C, Marler John R
Department of Neurology, University of Texas Health Science Center, San Antonio, Texas 78229-3900, USA.
Mov Disord. 2009 Apr 15;24(5):647-54. doi: 10.1002/mds.22432.
Treatments to slow the progression are a major unmet need in Parkinson's disease. Detailed assessment of randomized trials testing putative neuroprotective drugs was undertaken to inform the design, reporting, and interpretation of future studies. This study is a systematic review of trials testing neuroprotective drugs. Data were extracted independently by two coauthors. Fifteen completed, published trials involving 4,087 participants tested 13 different drugs in 18 double-blind comparisons with placebo. Seven comparisons involving 2,000 subjects assessed MAO-B inhibitors. The primary outcome was change in the Unified Parkinson's Disease Rating Scale score in eight trials and time to need for dopaminergic therapy in seven. Mean participant age was 62 years, 35% were women, the interval from diagnosis to entry averaged 11 months, and the number of participants averaged 272 (largest = 806). Follow-up averaged <16 months in all but two trials. Detailed randomization methods and success of double-blinding were reported in 20% and 13%, respectively. Based on the investigators' conclusions, six trials were interpreted as consistent with a neuroprotective effect, three as negative, and five as either confounded or not meeting criteria for futility. Neuroprotection trials have involved relatively uniform groups of participants early in the clinical disease course, with outcomes weighted heavily toward motor deterioration. Future trials should include participants with wider ranges of disease stages and assess broader neurological outcomes.
减缓帕金森病病情进展的治疗方法是一个尚未得到满足的重大需求。我们对测试假定神经保护药物的随机试验进行了详细评估，以为未来研究的设计、报告和解读提供信息。本研究是对测试神经保护药物的试验进行的系统评价。数据由两位共同作者独立提取。15项已完成并发表的试验涉及4087名参与者，在18次与安慰剂的双盲比较中测试了13种不同药物。7次涉及2000名受试者的比较评估了单胺氧化酶B抑制剂。8项试验的主要结局是统一帕金森病评定量表评分的变化，7项试验的主要结局是开始多巴胺能治疗的时间。参与者的平均年龄为62岁，35%为女性，从诊断到入组的间隔平均为11个月，参与者平均人数为272人（最多为806人）。除两项试验外，所有试验的随访时间平均<16个月。分别有20%和13%的试验报告了详细的随机化方法和双盲的成功情况。根据研究者的结论，6项试验被解释为与神经保护作用一致，3项试验结果为阴性，5项试验结果为混淆或未达到无效标准。神经保护试验纳入的参与者在临床病程早期相对统一，结局严重倾向于运动功能恶化。未来的试验应纳入疾病阶段范围更广的参与者，并评估更广泛的神经学结局。
