克林霉素磷酸酯氯化钠注射液细菌内毒素检查的研究

目的 探讨用鲎试剂检查克林霉素磷酸酯氯化钠注射液(商品名：恒新，以下简称恒新注射液)中细菌内毒素的可行性。方法 对家兔热原检查合格的恒新注射液作细菌内毒素检查的干扰试验。结果 恒新注射液对鲎试剂的细菌内毒素检查无干扰。结论 鲎试剂可用于恒新注射液的细菌内毒素检查。     

氟康唑氯化钠注射液细菌内毒素检查法的可行性研究

目的建立氟康唑氯化钠注射液的细菌内毒素检查法。方法参照中国药典2005年版二部附录XI E细菌内毒素检查法对氟康唑氯化钠注射液进行研究。结果不同企业的氟康唑氯化钠注射液对鲎试剂凝集反应的干扰作用不同，样品稀释12倍（0．17g·L^-1），可完全排除干扰因素的影响；采用0．125 EU·ml^-1以下标示灵敏度的鲎试剂进行细菌内毒素检查是有效的。结论采用细菌内毒素检查法检查氟康唑氯化钠注射液中内毒素是有效可行的。     

帕拉米韦氯化钠注射液细菌内毒素检查方法的建立

目的:建立帕拉米韦氯化钠注射液细菌内毒素的检查方法。方法:按2010年版《中国药典》(二部)附录细菌内毒素凝胶检查法,采用不同厂家的鲎试剂,通过干扰试验对不同批号的样品最大不干扰质量浓度及细菌内毒素进行检查。结果:样品质量浓度为2.5 mg/ml时对鲎试剂与细菌内毒素的凝集反应无干扰;样品的细菌内毒素限值为0.5 EU/ml。结论:本方法可用于帕拉米韦氯化钠注射液的细菌内毒素检查。     

布洛芬氯化钠注射液细菌内毒素检查方法的建立

目的:建立布洛芬氯化钠注射液细菌内毒素的检查方法。方法:按2015年版《中国药典》(四部)通则1143"细菌内毒素检查法"项下凝胶法的要求,通过干扰试验确定样品主成分最大无干扰质量浓度,并进行方法学验证。结果:样品稀释至含布洛芬质量浓度为1 mg/mL及以下时对细菌内毒素检查无干扰作用。结论:所建立的方法可用于布洛芬氯化钠注射液的细菌内毒素检查,其细菌内毒素限值确定为0.5 EU/mL。     

甲磺酸帕珠沙星氯化钠注射液细菌内毒素检查方法

目的考察甲磺酸帕珠沙星氯化钠注射液的细菌内毒素检查法。方法采用不同厂家、不同批号、不同灵敏度的鲎试剂对甲磺酸帕珠沙星氯化钠注射液进行干扰试验。结果甲磺酸帕珠沙星氯化钠注射液经7倍稀释后,用入为0．25Eu·ml的鲎试剂,对细菌内毒素检查无干扰。结论甲磺酸帕珠沙星氯化钠注射液的热原检查可以被内毒素检查法取代。     

奥硝唑氯化钠注射液细菌内毒素检查法的实验

目的建立奥硝唑氯化钠注射液细菌内毒素检查法。方法参照《中国药典》2010年版附录中细菌内毒素检查方法进行实验,用不同批号的鲎试剂,对奥硝唑氯化钠注射液进行干扰实验。结果奥硝唑氯化钠注射液经2倍稀释后,用标示灵敏度为0.25EU.mL-1的鲎试剂检测细菌内毒素是有效的,奥硝唑氯化钠注射液可用细菌内毒素检查法检测。     

盐酸左氧氟沙星氯化钠注射液的细菌内毒素检查

目的：建立盐酸左氧氟沙星氯化钠注射液的细菌内毒素检查法。方法：根据《中华人民共和国药典（二部）》（2005版）细菌内毒素检查方法,用不同厂家的鲎试剂对不同批号的样品分别进行干扰试验,建立盐酸左氧氟沙星氯化钠注射液的细菌内毒素检查法。结果：盐酸左氧氟沙星氯化钠注射液稀释至质量浓度为0.5mg·mL-1时对细菌内毒素检查无干扰。结论：可用细菌内毒素检查法检查盐酸左氧氟沙星氯化钠注射液的细菌内毒素。     

阿奇霉素氯化钠注射液中细菌内毒素的检查

目的建立阿奇霉素氯化钠注射液细菌内毒素的检查方法。方法用不同厂家的鲎试剂对阿奇霉素氯化钠注射液分别进行干扰实验。结果阿奇霉素氯化钠注射液与鲎试剂反应无干扰。结论用细菌内毒素法检查阿奇霉素氯化钠注射液中的内毒素是可行的。     

甲磺酸帕珠沙星氯化钠注射液细菌内毒素检查方法学确证

目的建立甲磺酸帕珠沙星氯化钠注射液细菌内毒素检查方法。方法按《中国药典》2010年版二部附录ⅪE细菌内毒素检查法中凝胶法干扰实验原则,分别用2个厂家鲎试剂对3批甲磺酸帕珠沙星氯化钠注射液进行凝胶法干扰实验和细菌内毒素检查。结果将甲磺酸帕珠沙星氯化钠注射液稀释8倍,可消除干扰作用。结论采用凝胶法对甲磺酸帕珠沙星氯化钠注射液进行细菌内毒素检查可行。     

甲磺酸帕珠沙星氯化钠注射液细菌内毒素检查

目的考察甲磺酸帕珠沙星氯化钠注射液的细菌内毒素检查法。方法采用不同厂家、不同批号、不同灵敏度的鲎试剂对甲磺酸帕珠沙星氯化钠注射液进行干扰试验。结果该注射液经12倍稀释后,用λ为0.25EU·mL-1的鲎试剂,对细菌内毒素检查无干扰。结论甲磺酸帕珠沙星氯化钠注射液可以采用内毒素检查法。     

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.