CLINICAL TRIAL METHODOLOGY IN SCHIZOPHRENIA

我们提出的研究计划涉及到 临床试验方法学，包括新的试验设计和 抗精神病药物研究的统计分析方法 治疗精神分裂症的药物：(1)虽然 “灵活剂量”或“医生选择”设计镜面临床 练习并适应患者的个体差异 受到了严厉的批评。我们将发展统计生物检测 在估计相对效力的同时考虑到 安慰剂应答者和耐受性。患者以及剂量 信息。(2)当一项测试相对于标准的相对效力 对我们所有的行为和副作用变量来说并不相同 将开发允许识别子组的方法 关于相对效力的变量 常量。(3)一般情况下，评级中项目的类别 标度具有通过任意赋值来量化隐式排名顺序 将等间距整数值添加到类别中。我们将发展 根据剂量进行标量赋值的方法 来自试验本身的回应数据。(4)符合以下条件的交叉设计 有效且可分析的，无论结转效应是否 将开发出相对较小的样本量 将有足够的力量进行对比治疗。(5)模型到 分析多变量观测以评估 同时分析两种处理的生物等效性 所有患者的血清药物和/或代谢物水平 将制定观测时间点。(六)我们要发展 评估组合优点的统计方法 治疗。零假设的性质导致了 在分析组合研究中存在相当大的混乱 心理治疗。这些通常涉及Ho形式的假设： 不比A好的组合或不比B好的组合。 (七)协商中出现的其他统计问题和 将考虑与临床研究人员合作。

The research program we propose concerns the development of clinical trial methodology, including new experimental designs and methods of statistical analysis, for the study of antipsychotic drugs used in the treatment of schizophrenia: (1) Although "flexible dose" or "doctor's choice" designs mirror clinical practice and accommodate individual patient variations they have been seriously criticized. We will develop statistical bioassay models that estimate relative potency while taking into account placebo responders and refractory.patients as well as the dosage information. (2) When the relative potency of a test to a standard is not the same for all behavioral and side effect variables we will develop methods that permit the identification of subgroups of the variables with respect to which relative potency is constant. (3) Generally, the categories within items in a rating scale have implicit rank order quantified by arbitrarily assigning equispaced integer values to the categories. We will develop methods whereby scalar assignments are made on the basis of dose response data from the trial itself. (4) Crossover designs that are efficient and are analyzable whether or not carryover effects are present will be developed so that a relatively small sample size will have adequate power to contrast therapies. (5) Models to analyze multivariate observations for evaluation of the bioequivalence of two treatments through the simultaneous analysis of serum levels of drug and/or metabolites at all of the observation time points will be developed. (6) We shall develop statistical methodology for assessing the merits of combination therapies. The nature of the null hypothesis has led to considerable confusion in the analysis of studies of combination therapy. These usually involve hypotheses of the form HO: combinations not better than A or combination: not better than B. (7) Other statistical problems that arise in consultation and collaborating with clinical researchers will be considered.