Jacobs L D, Cookfair D L, Rudick R A, Herndon R M, Richert J R, Salazar A M, Fischer J S, Goodkin D E, Granger C V, Simon J H
William C. Baird Multiple Sclerosis Research Center, Millard Fillmore Health System, Buffalo, NY 14209, USA.
Mult Scler. 1995 Jun;1(2):118-35. doi: 10.1177/135245859500100210.
The design and conduct of a randomized, double-blinded, placebo-controlled, multicenter, phase III study of recombinant interferon beta-1a (IFN-beta-1a) as treatment for exacerbating-remitting MS are described, as are baseline characteristics of the study population. The purpose of the study was to determine if 6.0 x 10(6) IU (30 micrograms) of IFN-beta-1a, administered by weekly intramuscular (i.m.) injections, was effective in delaying the onset of sustained disability. The primary outcome measure was time to onset of treatment failure, defined as a worsening on the Kurtzke Expanded Disability Status Scale (EDSS) of greater than or equal to 1.0 point compared with baseline, persisting for at least 6 months. An intent-to-treat design was used. The primary outcome measure was analyzed using the Mantel-Cox log-rank statistic and Kaplan-Meier survival curves. Secondary outcomes included quantitative measures of upper and lower extremity function, neuropsychological test performance, functional and quality of life assessments and several measures derived from annual brain MRI studies. Entry criteria included prestudy exacerbation rates of at least 0.67 per year and EDSS scores of 1.0-3.5. A total of 301 MS patients were randomly assigned to receive weekly i.m. injections of IFN-beta-1a or placebo. The average age of the study population at entry was 37 years; 92% were Caucasian and 73% were women. The mean prestudy disease duration was 6.5 years, mean prestudy exacerbation rate was 1.2 per year and the mean EDSS score was 2.3. The randomization yielded well-balanced treatment arms. Various aspects of the study are discussed, including: (1) the decision to focus study design on sustained disability; (2) the rationale for the treatment regimen; (3) measures taken to assure the reliability of the primary outcome measure; and (4) a description of the secondary outcome measures.
本文描述了一项关于重组干扰素β-1a（IFN-β-1a）治疗复发缓解型多发性硬化症（MS）的随机、双盲、安慰剂对照、多中心III期研究的设计与实施过程，以及研究人群的基线特征。该研究旨在确定每周一次肌肉注射6.0×10(6)IU（30微克）的IFN-β-1a是否能有效延缓持续性残疾的发生。主要结局指标为治疗失败的发生时间，定义为与基线相比，库尔特克扩展残疾状态量表（EDSS）评分恶化大于或等于1.0分，并持续至少6个月。采用意向性分析设计。主要结局指标采用Mantel-Cox对数秩统计量和Kaplan-Meier生存曲线进行分析。次要结局指标包括上下肢功能的定量测量、神经心理学测试表现、功能和生活质量评估以及每年脑部MRI研究得出的多项测量指标。纳入标准包括每年至少0.67次的研究前病情加重率和1.0 - 3.5的EDSS评分。共有301例MS患者被随机分配接受每周一次的肌肉注射IFN-β-1a或安慰剂。研究人群入组时的平均年龄为37岁；92%为白种人，73%为女性。研究前的平均病程为6.5年，研究前的平均病情加重率为每年1.2次，平均EDSS评分为2.3。随机分组使各治疗组达到良好的平衡。本文还讨论了该研究的各个方面，包括：（1）将研究设计重点放在持续性残疾上的决定；（2）治疗方案的基本原理；（3）为确保主要结局指标的可靠性所采取的措施；以及（4）次要结局指标的描述。
