奥沙利铂注射液细菌内毒素检查方法的研究

目的:对奥沙利铂注射液进行细菌内毒素检查的干扰试验,并建立其细菌内毒素检查方法.方法:参照2000年版<中国药典(二部)>附录细菌内毒素检查法和细菌内毒素检查法应用指导原则进行试验.结果:通过干扰试验确证,按拟定标准检验,本品1个规格共3批供试品的细菌内毒素检查结果均符合规定.结论:本品1 mL含奥沙利铂2 mg的供试品及其稀释液对细菌内毒素检查无干扰.可用鲎试验法代替家兔热原检查法控制奥沙利铂注射液的热原.     

硫酸罗通定注射液细菌内毒素检查法的研究

目的:建立硫酸罗通定注射液细菌内毒素检查方法.方法:按<中国药典>2005年版二部附录Ⅺ E细菌内毒素检查法,对不同生产厂家的样品进行了干扰试验和细菌内毒素检查.结果:本品最大不干扰浓度为0.94 g·L-1.结论:可采用细菌内毒素检查法对硫酸罗通定注射液进行质量控制.     

注射用盐酸丁咯地尔细菌内毒素检查法的研究

研究注射用盐酸丁咯地尔对细菌内毒素检查试验的干扰情况 ,并建立其细菌内毒素检查的方法。按《中国药典》 2 0 0 0年版二部附录ⅪE细菌内毒素检查法和附录ⅪⅩF细菌内毒素检查法应用指导原则进行试验。本品在 0 33mg·ml-1稀释浓度下无干扰作用 ,L =1 5EU·mg-1。本品可用细菌内毒素检查法替代热原检查法     

注射用盐酸头孢吡肟细菌内毒素检查法

目的 :研究注射用盐酸头孢吡肟对细菌内毒素检查试验的干扰情况 ,并建立其细菌内毒素检查的方法。方法 :参照中国药典 2 0 0 0年版二部附录XIE细菌内毒素检查法和附录XIXF细菌内毒素检查法应用指导原则进行试验。结果 :供试品在 3.33mg·ml-1稀释浓度下无干扰作用。结论 :获得了可靠的实验数据和结果并建立了本品的细菌内毒素检查法。     

氨茶碱注射液细菌内毒素检查方法的建立

目的:建立氨茶碱注射液细菌内毒素检查方法。方法:按《中国药典》2005年版二部附录细菌内毒素检查法,对不同批号的样品进行了干扰试验和细菌内毒素检查。结果:高浓度氨茶碱注射液溶液对TAL与细菌内毒素的凝集反应有干扰作用,经稀释后可排除干扰。结论:本品不干扰浓度为7.81 mg.mg-1,可采用细菌内毒素检查法进行质量控制。     

阿莫西林钠细菌内毒素检查法的可行性探讨

目的　建立阿莫西林钠细菌内毒素检查的方法。方法　按《中国药典》2 0 0 0年版二部附录细菌内毒素检查法和细菌内毒素检查法应用指导原则进行试验。结果　本品在5 .0mg·m-1稀释浓度以下无干扰作用,L=0.2EU·mg-1。结论　本品可用细菌内毒素检查法代替热原检查法     

乳酸环丙沙星注射液细菌内毒素检查法的研究

目的建立乳酸环丙沙星细菌内毒素检查的方法。方法按《中国药典》2000年版二部附录细菌内毒素检查法和细菌内毒素检查法应用指导原则进行试验。结果本品在5.0mg/ml稀释浓度以下无干扰作用,L=0.42EU/ml。结论本品可用细菌内毒素检查法代替热原检查法。     

应用鲎试剂检测吡拉西坦葡萄糖注射液中的细菌内毒素

建立吡拉西坦葡萄糖注射液的细菌内毒素检查法.参照<中国药典>2005年版二部附录"细菌内毒素检查法"进行干扰试验和结果判断.样品的最大无干扰浓度为16mg·ml-1,用浓度为6.4mg·ml-1的样品液进行细菌内毒素检查,结果无干扰作用.本品可以用细菌内毒素检查法代替家兔热原检查法.     

注射用头孢噻肟钠的细菌内毒素定量检测

目的建立定量检测注射用头孢噻肟钠的细菌内毒素检查法,以替代热原检查法。方法按《中国药典》2000年版二部附录中的细菌内毒素动态浊度法,制定本品细菌内毒素限值,并研究注射用头孢噻肟钠对鲎试剂的干扰情况,以确定本品是否适用细菌内毒素检查法。结果注射用头孢噻肟钠用于细菌内毒素定量检测的几个浓度稀释液,对鲎试剂无干扰影响,内毒素回收率均在50%~200%范围内。结论本品可采用细菌内毒素动态浊度法进行定量检测。     

硫酸头孢匹罗细菌内毒素检查法的建立

目的:建立硫酸头孢匹罗细菌内毒素检查的方法。方法:参照《中国药典》2005年版(二部)附录细菌内毒素检查法及其指导原则进行干扰试验。结果:调节本品pH值至5.5左右,其浓度稀释在2.5mg.ml-1时无干扰作用。结论:硫酸头孢匹罗可用细菌内毒素检查法控制其质量。     

对临床试验中显著性检验、区间检验及置信区间检验之间关系一致性的认识

显著性检验是最基本的统计假设检验,它的基本思想是小概率原理;区间检验是传统显著性检验的延伸,它用来检验两个总体的差异是否在某范围之内;置信区间检验是先找到药物疗效差值的置信区间,通过置信区间下限或(和)上限与界值的关系来判断两种药物非劣效、等效、优效的关系。通过公式推导发现,区间检验与显著性检验的主要区别是前者的假设中包含了有临床意义的界值△,而区间检验和置信区间检验是一致的,可以用置信区间检验实现区间检验的目的。     

谈谈两总体比较的非参数检验方法

针对不同的数据类型,探讨选用不同的非参数检验方法,并通过实例说明这些非参数检验方法的应用。     

A Comparison of Two-Sample Tests of Significance When Used With Variable Treatment Effects

This article compares the performance of many two-sample tests of significance that might be used to test the equality of means when the effect of the treatment is variable. Of the 19 tests that were compared, the normal scores test is recommended for general use in testing the null hypothesis of no treatment effect against the alternative that the distributions are stochastically ordered when the ratio of the larger standard deviation to the smaller standard deviation does not exceed 1.3. The Baumgartner-Weiß-Schindler tests and an adaptive test also have higher power than the pooled t-test, the unequal variance t-test, and the rank-sum test for many distributions. In the simulation studies, data in the first sample are generated from nine distributions, including long-tailed and skewed distributions. Data in the second sample are generated by adding a random treatment effect to a random variable that was generated from the same distribution that was used in the first sample. Because we restricted our power studies to treatment effects that are positive or zero, the population distributions will be stochastically ordered. The results of these studies demonstrate that the normal scores test is often more powerful than the t-tests and the rank-sum test. If the ratio of the standard deviations does exceed 1.3, then one of the t-tests is recommended.     

Testing equality of proportions for correlated binary data in ophthalmologic studies

In ophthalmologic studies, bilateral correlated data often arise when information involving paired organs (e.g., eyes) are measured from each subject. Adjusted chi-square approach for testing the equality of proportions has been proposed in the literature. In this article, we investigate and derive three alter- native testing procedures for the problem. Our simulation results show the score testing procedure usually produces satisfactory type I error control with higher power, and therefore is recommended. Examples from ophthalmologic studies are used to illustrate our proposed methods.     

中国药品上市后抽验模式现状及问题

目的在综合分析中国药品上市后抽验模式现状及问题的基础上,提出药品上市后抽验的建议。方法通过文献研究的方法,发现中国药品上市后抽验模式中存在的问题,并提出相关建议。结果与结论在药品抽验中引入以风险为基础的抽验模式,将药品上市后抽验结果与药品监管相衔接。     

Mutagenicity testing of quinine with submammalian and mammalian systems

Quinine hydrochloride was assayed for genotoxic activity by using 4 different test systems with distinct genetic endpoints. No indications for point mutations were observed in the Ames system. In 3 cytogenetic tests performed on small rodents, Chinese hamsters showed no genotoxic activity, while inbred strains of mice revealed a dose dependent increase of SCEs, enhanced incidence of micronuclei and elevated chromatid breaks.     

刹毒草口服液的药理作用研究

目的:研究刹毒草口服液对小鼠的药理作用。方法:用小鼠分别进行爬杆实验、炭粒廓清实验、耳肿胀实验和墨汁推进实验,观察刹毒草口服液对小鼠的抗疲劳作用、非特异性免疫功能的影响、抗炎作用和抗腹泻作用。结果:刹毒草口服液能显著延长小鼠爬杆时间,有较好的抗疲劳作用;高剂量刹毒草口服液能显著提高小鼠对惰性炭粒的吞噬指数及吞噬活性,可提高小鼠免疫功能;刹毒草口服液3个剂量组均对二甲苯致小鼠耳炎症有较好的抑制作用,且能显著降低墨汁推进的速率,有较好的抗腹泻作用。结论:刹毒草口服液具有一定抗疲劳、抗炎、提高非特异性免疫功能和抗腹泻作用。     

Simultaneous Test for Superiority and Noninferiority Hypotheses in Active-Controlled Clinical Trials∗

The primary objective of the dose-escalation trial for NGX267 was to estimate the maximally tolerated dose (MTD) and to gather detailed clinical and pharmacokinetic observations near the MTD. The MTD was defined based on the weighted average of moderate and severe adverse events. An adaptive design was employed to concentrate dosage assignments at or near the MTD. Favoring the acquisition of data near the MTD, at the expense of information at lower dosage levels, resulted in a shorter trial and no loss of the type of information required to inform subsequent studies where larger normal volunteer or patient samples are evaluated.     

氢溴酸山莨菪碱注射液细菌内毒素检查法的建立

目的:建立氢溴酸山莨菪碱注射液的细菌内毒素检查方法。方法:按《中国药典》2010年版(二部)附录相关方法确定本品细菌内毒素限值,分别进行细菌内毒素检查凝胶法和动态浊度法的干扰试验。结果:凝胶法结果表明,样品稀释2倍(5 mg/ml)时对试验无干扰作用;动态浊度法结果表明,本品稀释2倍(5 mg/ml)时外加内毒素的回收率在50%²00%之间。每1 mg氢溴酸山莨菪碱中含内毒素应小于0.35 EU。结论 :本文初步建立的氢溴酸山莨菪碱注射液细菌内毒素检查方法,可为《中国药典》增订该制剂的细菌内毒素检查项提供参考。     

Bootstrap inference in a linear equation estimated by instrumental variables

Summary We study several tests for the coefficient of the single right‐hand‐side endogenous variable in a linear equation estimated by instrumental variables. We show that writing all the test statistics—Student's t, Anderson–Rubin, the LM statistic of Kleibergen and Moreira (K), and likelihood ratio (LR)—as functions of six random quantities leads to a number of interesting results about the properties of the tests under weak‐instrument asymptotics. We then propose several new procedures for bootstrapping the three non‐exact test statistics and also a new conditional bootstrap version of the LR test. These use more efficient estimates of the parameters of the reduced‐form equation than existing procedures. When the best of these new procedures is used, both the K and conditional bootstrap LR tests have excellent performance under the null. However, power considerations suggest that the latter is probably the method of choice.