Goonetilleke A, Guiloff R J
Neuromuscular Unit, Charing Cross Hospital, London, UK.
J Neurol Neurosurg Psychiatry. 1995 Feb;58(2):201-8. doi: 10.1136/jnnp.58.2.201.
The continuous response variable controlled trial design is developed as a model for the efficient screening of candidate treatments in motor neuron disease. A TRH analogue (RX77368) and placebo were randomly allocated to 15 matched pairs of patients with motor neuron disease. With validated composite interval scores, this trial excluded a 50% or greater improvement with RX77368 at month 12 in scores of respiratory, lower limb, and activities of daily living function with greater than 90% power, and in bulbar function scores with 80% power. For upper limbs, 52% and 75% improvements were excluded at months 9 and 12 respectively with 80% power. Patients who died during the study had faster deterioration rates in bulbar and respiratory scores than their surviving pairs. The feasibility of screening drugs for significant biological effects with small sample sizes and good statistical power is shown. The difficulties of handling deaths and dropouts when using this design are discussed. Comparisons are made with sample sizes required using other scores and rating scales, as well as with those required in hazard and event rate studies. A simple clinical grading scale for motor neuron disease, with its corresponding composite interval scores, is described.
连续反应变量对照试验设计是作为一种有效筛选运动神经元疾病候选治疗方法的模型而开发的。将一种促甲状腺激素释放激素类似物（RX77368）和安慰剂随机分配给15对匹配的运动神经元疾病患者。通过经过验证的综合区间评分，该试验排除了RX77368在第12个月时呼吸、下肢和日常生活功能评分有50%或更大改善的可能性，功效大于90%，并排除了延髓功能评分有80%功效的50%或更大改善的可能性。对于上肢，在第9个月和第12个月时分别排除了功效为80%的52%和75%的改善情况。在研究期间死亡的患者，其延髓和呼吸评分的恶化速度比存活的配对患者更快。展示了使用小样本量和良好统计功效筛选具有显著生物学效应药物的可行性。讨论了使用该设计时处理死亡和失访的困难。与使用其他评分和评定量表所需的样本量以及与风险和事件率研究所需的样本量进行了比较。描述了一种用于运动神经元疾病的简单临床分级量表及其相应的综合区间评分。
