One‐ and two‐stage design proposals for a phase II trial comparing three active treatments with control using an ordered categorical endpoint

Phase II clinical trials are performed to investigate whether a novel treatment shows sufficient promise of efficacy to justify its evaluation in a subsequent definitive phase III trial, and they are often also used to select the dose to take forward. In this paper we discuss different design proposals for a phase II trial in which three active treatment doses and a placebo control are to be compared in terms of a single‐ordered categorical endpoint. The sample size requirements for one‐stage and two‐stage designs are derived, based on an approach similar to that of Dunnett. Detailed computations are prepared for an illustrative example concerning a study in stroke. Allowance for early stopping for futility is made. Simulations are used to verify that the specified type I error and power requirements are valid, despite certain approximations used in the derivation of sample size. The advantages and disadvantages of the different designs are discussed, and the scope for extending the approach to different forms of endpoint is considered. Copyright © 2008 John Wiley & Sons, Ltd.     

Measurement in clinical trials: A neglected issue for statisticians?

Biostatisticians have frequently uncritically accepted the measurements provided by their medical colleagues engaged in clinical research. Such measures often involve considerable loss of information. Particularly, unfortunate is the widespread use of the so‐called ‘responder analysis’, which may involve not only a loss of information through dichotomization, but also extravagant and unjustified causal inference regarding individual treatment effects at the patient level, and, increasingly, the use of the so‐called number needed to treat scale of measurement. Other problems involve inefficient use of baseline measurements, the use of covariates measured after the start of treatment, the interpretation of titrations and composite response measures. Many of these bad practices are becoming enshrined in the regulatory guidance to the pharmaceutical industry. We consider the losses involved in inappropriate measures and suggest that statisticians should pay more attention to this aspect of their work. Copyright © 2009 John Wiley & Sons, Ltd.     

Is the political system really related to health?

We analyze whether the political system and its stability are related to cross-country differences in health. We apply factor analysis on various national health indicators for a large sample of countries over the period 2000–2005 and use the outcomes of the factor analysis to construct two new health measures, i.e., the health of individuals and the quality of the health care sector. Using a cross-country structural equation model with various economic and demographic control variables, we examine the relationship between the type of regime and political stability on the one hand and health on the other. The political variables and the control variables are measured as averages over the period 1980–1999. Our results suggest that democracy has a positive relationship with the health of individuals, while regime instability has a negative relationship with the health of individuals. Government instability is negatively related to individual health via its link with the quality of the health care sector, while democracy is positively related with individual health through its link with income. Our main findings are confirmed by the results of a panel model and various sensitivity tests.     

间日疟原虫深圳株红内期SSUrDNA基因片段的克隆与序列分析

目的 体外扩增间日疟原虫深圳株红内期小亚单位核糖体核糖核酸编码基因(SSUrDNA)片段，研究其结构与功能。方法 设计一对特异性引物，采用聚合酶链反应(PCR)从间日疟原虫患者血样中扩增出间日疟原虫SSUrDNA片段，以PUC19质粒T载体构建重组子导入大肠杆菌JM109；阳性克隆双酶切鉴定后，双脱氧末端终止法测定序列。结果 间日疟原虫SSUrDNA扩增片段大小为341bp；阳性克隆双酶切及PCR扩增均得到预期大小的片段；序列测定插入片段为341bp，与Sal I株顺序相比，仅在第151位处缺失一个碱基C。结论 成功克隆了间日疟原虫SSUrDNA片段．该序列在间日疟原虫虫株间高度保守。     

国产促动力药物治疗功能性消化不良的成本-效果分析

目的　评价不同药物治疗功能性消化不良的经济效果。方法　运用经济学中的成本 -效果分析方法 ,对莫沙必利、伊托必利和吗丁啉治疗功能性消化不良方案进行分析。结果　莫沙必利与吗丁啉成本效果比相当 ,但所需增长的成本效果比高 ;伊托必利的成本效果比和增长的成本效果比均高于吗丁啉。结论　吗丁啉是治疗功能性消化不良的最佳用药方案     

《实用美容整形外科杂志》（1999—2003年）载文分析

目的 探讨《实用美容整形外科杂志》的载文特点。方法 利用文献计量学方法统计1999～2003年出版的30期《实用美容整形外科杂志》的多项文献计量学指标。结果 5年的总载文量为975篇，总页数为1680页。有较为固定的十几个栏目，平均发表时滞为242．6天，平均基金论文比为0．05。合著的论文占总数的84．8％，平均论文作者合作度为3．26。作者分布在全国29个省、自治区或直辖市。工作在省市医院、医药院校附属医院和部队医院的作者较多。结论 《实用美容整形外科杂志》是以省市医院、医药院校附属医院和部队医院的中级以上职称的中青年作者为主要作者群的国家级美容整形外科专业核心期刊。     

精液白细胞与不育症之间关系探讨

目的以瑞-姬染色方法,油镜精细观察,区分精液中生精细胞与白细胞,探讨精液白细胞的检出率与不育症之间关系,以提供临床参考。方法293例精液采用瑞-姬染色,油镜进行白细胞及其他细胞形态分类,并进行统计处理。结果293例不育症精液中检出白细胞阳性136例占46.4%;阴性157例占53.6%。年度精液白细胞阳性率1990年为13.8%;1993年为21.5%;1997年为34.1%;2006年为46.4%,说明有逐渐增加趋势。对2006年136例精液白细胞数量分布统计,以≤5个者最多占70.6%;6~20个占8.9%;21~40个占3.4%;>40个占1.3%。1~4个组与5~9个组、>20个组比较,有显著差异(P<0.001)。56例精液与前列腺液进行白细胞对照观察,两者均有白细胞者为48.2%(27/56)。精液中非生精细胞检出率,以前列腺上皮细胞最高为27.3%;其次是吞噬细胞为23.5%;再次是淋巴细胞为10.8%;支持细胞和间质细胞均为8.1%。结论精液白细胞有逐年增加趋势,影响精液质量造成不育症,实验室应认真检测,以油镜观察≤5个者,可考虑来源于精液;>5个者应检查前列腺,临床应注意其来源,对症治疗。     

我国艾滋病健康教育现状分析

分析我国艾滋病健康教育的现状，指出目前艾滋病健康教育方面所存在的问题和不足，并从加大艾滋病健康教育投入、实施综合干预、借鉴国外理论、建立评价指标体系等方面提出优化的方法和途径。     

北京地区高学历吸毒者的情况分析

目的:了解北京地区高学历吸毒者的情况,为采取有效防范措施提供依据。方法:自拟调查问卷对北京市安康医院戒毒中心2000年1月1日-2003年12月31日收治的戒毒人员中大专以上高学历者进行逐项登记,并对吸毒原因、毒品滥用等情况分析。结果:高学历吸毒者共计431例,占同期戒毒的4.52%,其中男265例(61.48%),女166例(38.52%)。婚姻状况:未婚289例(67.05%),已婚100例(23.20%);职业:以无业为主,219例(50.81%),其次为职员,73例(16.94%);吸毒主要原因:好奇264例(61.25%)、受他人(朋友)影响112例(25.99%);主要滥用毒品的种类:海洛因274例(63.57%)、“摇头丸”130例(30.16%);滥用方式:海洛因滥用者中烫吸155例(57.57%)、注射119例(43.43%),“摇头丸”均为口服,其中119例(91.54%)兑于酒或饮料中使用;大麻均为烟吸,“K粉”均为兑于饮料中使用。有86.92%(113/130)的“摇头丸”滥用者认为服用摇头丸不会成瘾。结论:高学历吸毒人群以未婚、无固定职业为主体,高学历者好奇心强,易受他人影响,对新型毒品(摇头丸)知识欠缺,有关部门应加强宣传教育。