Reducing sample sizes in two-stage phase II cancer trials by using continuous tumour shrinkage end-points

Reducing the number of patients required for a clinical trial is important for shortening development time. Phase II cancer trials assess the tumour-shrinking effect of a novel compound through a binary end-point formed from the percentage change in total lesion diameter. We compare single-arm two-stage designs which use the binary end-point to those which directly use the continuous end-point.Using the continuous end-point results in lower expected and maximum sample sizes. For larger trials the reduction is around 37%. This assumes that the dichotomisation point of the continuous end-point is chosen to give the best sample size, with the trial design using the binary end-point performing even worse otherwise. We consider a previous trial designed using a Simon two-stage design and show that if the continuous end-point had been used, the expected and maximum sample sizes of the trial would be reduced by around 50%.Using the continuous end-point in a two-stage cancer trial results in large sample size reductions. The methods discussed in this paper work best when the number of complete responses is low, as is true in several types of cancer. We discuss what could be done if this is not the case.     

Experimental and statistical approaches in method cross-validation to support pharmacokinetic decisions

A case study of experimental and statistical approaches for cross-validating and examining the equivalence of two ligand binding assay (LBA) methods that were employed in pharmacokinetic (PK) studies is presented. The impact of changes in methodology based on the intended use of the methods was assessed. The cross-validation processes included an experimental plan, sample size selection, and statistical analysis with a predefined criterion of method equivalence. The two methods were deemed equivalent if the ratio of mean concentration fell within the 90% confidence interval (0.80–1.25). Statistical consideration of method imprecision was used to choose the number of incurred samples (collected from study animals) and conformance samples (spiked controls) for equivalence tests. The difference of log-transformed mean concentration and the 90% confidence interval for two methods were computed using analysis of variance. The mean concentration ratios of the two methods for the incurred and spiked conformance samples were 1.63 and 1.57, respectively. The 90% confidence limit was 1.55–1.72 for the incurred samples and 1.54–1.60 for the spiked conformance samples; therefore, the 90% confidence interval was not contained within the (0.80–1.25) equivalence interval. When the PK parameters of two studies using each of these two methods were compared, we determined that the therapeutic exposure, AUC_(0-168) and C_max, from Study A/Method 1 was approximately twice that of Study B/Method 2. We concluded that the two methods were not statistically equivalent and that the magnitude of the difference was reflected in the PK parameters in the studies using each method. This paper demonstrates the need for method cross-validation whenever there is a switch in bioanalytical methods, statistical approaches in designing the cross-validation experiments and assessing results, or interpretation of the impact of PK data.     

山东省聊城市精神疾病抽样调查

聊城市1984年与1994年两次参加山东省精神疾病流行病学调查项目,均在框架区内统一抽取莘县、阳谷、茌平县3个调查样本,两年分别调查6218人和4836人.本次抽样调查为WHO在山东省实施的精神卫生流调项目的一部分,旨在了解各类精神疾病的患病水平、分布特征、致残情况,为制定精神卫生工作规划提供决策依据.     

A NONPARAMETRIC PROCEDURE OF THE SAMPLE SIZE DETERMINATION FOR SURVIVAL RATE TEST

Inthesurvivalstudiesofchronicdiseases,themostfrequentlyusedmethodsofdataanalysisarethenonparametricestimationsandcomparisonsofsurvivalratesatdifferenttimesbuttherehavebeennomatchedmethodsfordeterminingtherequiredsamplesizesofar.Insteadhavebeenoftenusedtheparametricmethodsbasedontheassumptionofexponentialdistributions[1～7]suchthattherelevantsamplesizesmaynotbesatisfiedwiththeprescribedpower.Thispaperreportsanonparametricprocedureofthesamplesizedeterminationforsurvivalratetest.1　SurvivalRateT…     

Determination of potentially hallucinogenic N-dimethylated indoleamines in human urine by HPLC/ESI-MS-MS

A new method for the determination of N,N-dimethyl-5-hydroxytryptamine (bufotenine), N,N-dimethyltryptamine (DMT)*, 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), and N-methyltryptamine (NMT) was developed using highperformance liquid chromatography-mass spectrometry (HPLC-MS). Identification of the analytes is based on liquid chromatographic retention times of analytes and two fragment ions produced by a triple quadrupole mass spectrometer. Quantification is based on electrospray ionization (ESI), and multiple reaction monitoring (MRM) was also utilized for getting better selectivity. The analytes and internal standard were separated from the urine matrix by solid-phase extraction (SPE). The method was applied for the determination of these compounds in urine samples of patients from surgical, medical and psychiatric wards. Of the dimethylated amines, only bufotenine was found in significant amounts (up to 34 &#119 g/L). In keeping with our earlier results, the bufotenine excretion of psychiatric patients was found to be higher than that of the somatic patients. Method, procedure, considerations, statistical evaluations and urine sample spectra are presented.     

病例对照研究评价疫苗效力的样本含量

目的 提出一种病例对照研究设计中可调区可信区间精度的评价疫苗效力（VE）所需样本含量的计算公式。方法：应用可信区间相对宽度原理推导计算公式。结果 预设的相对宽度可调节和控制可信区间精度并决定样本含量的大小。结论 使研究者能较为准确地掌握VE点估计值接近总体真实值的程度。     

“大学生生活满意度评定量表（CSLSS）”的编制

目的 为了编制适用于中国大学生的个人生话满意度评定量表。方法 根据大学生对各类生话事件评分的权重，归纳出影响其生活的五大类生活问题作为量表项目，选择全国24所高校的近1900名学生作为样本进行测试。结果 样本均数为正态分布，该量表内部一致性较高，4周重测信度在0．69—0．84之间，与SCL-90及消极应对的负相关、与积极应对的正相关，显示了该量表的效标效度和理论效度。结论 该量表可以作为我国大学生个人生活满意度及生活质量的评定工具。     

疾病易感基因研究样本量的确定

目的：探讨疾病易感基因研究样本量的确定。方法：计算在不同参数时的样本大小，分析各参数对样本大小的影响和变化规律。结果：主要影响样本大小的参数为易感基因频率、环境因素暴露率、基因遗传方式，而疾病的发生率对样本量影响很小。易感基因频率小于30％时隐性遗传研究样本量大，而大于30％则显性遗传研究样本量大。结论：疾病易感基NN究样本量的计算取决于各参数对拟合回归模型的影响。     

Poisson分布设计时样本含量的估算

Ｐｏｉｓｓｏｎ分布是一种离散分布，它在临床、预防、基础医学，及计划生育研究中有广泛应用。文中对提出的几种Ｐｏｉｓｓｏｎ分布设计时样本含量估算方法，以妇幼卫生、计划生育研究的实例介绍，并讨论了有关问题。