Statistical tests for bioequivalence

The application of statistical tests of hypotheses in the evaluation of bioavailability studies is discussed. The necessity of correctly indicating the risk of false decisions in accordance with the hypothesis to be tested is emphasized. The procedure of evaluation presented here is performed analogously to the methods of the statistical quality control and always takes errors of the 1st kind and the 2nd kind into account. The advantageous use of the operating characteristic is pointed out. It is possible to read from these curves the effects which the size of the random sample and the experimental variation have on the reliability of the statement. The procedure is illustrated by means of numerical examples from literature.     

Statistical model in tests for eye irritants

A test used to classify substances for eye irritancy, as required by the Consumer Product Safety Commission, is performed on 1-3 groups of 6 albino rabbits in a sequential manner. When the statistical implications of the test are realized, it is possible for a substance to be classified as an irritant with fewer reactions than the number required for it to be classified as not an irritant. A procedure is given for correcting the inconsistency in the current test, and an alternative test, which considerably reduces the number of animals required, is proposed. Probability models and expected sample size calculations have been derived.     

葡萄糖筛查对妊娠期孕妇的价值

目的探讨葡萄糖筛查在妊娠期的临床意义。方法对1516例24—28周的孕妇进行50g葡萄糖筛查（GCT）,血糖≥7．8mmol/L再进一步做糖耐量试验（OGTT）以明确诊断。结果妊娠期糖尿病发生率3．17％,妊娠期糖耐量受损发生率2．64％。结论孕妇葡萄糖筛查可及早诊断妊娠期糖尿病,从而降低围生儿死亡率。     

Statistical versus quantitative significance in the socioeconomic evaluation of medicines

This article examines the twin concepts of the statistical significance and quantitative importance of observed differences in studies comparing medicines in terms of economic parameters such as cost-effectiveness and measures of health-related quality of life (HRQOL). Central to the design and interpretation of any comparative study, such as a randomised controlled trial, is some prior judgement about the order of magnitude of a difference that would make one switch from one therapy to another. Starting with current definitions of clinically important differences we argue by analogy that the importance of differences in HRQOL require a shift of focus from the physician to the patient for preferences and judgements concerning what is important to them. Whether an intervention offers sufficient value for money (cost effectiveness or cost utility) to warrant resources being reallocated to it is a collective decision requiring the input of public preferences about the relative importance of alternative therapies and health benefits. Ultimately, the importance of the health benefits offered by a new drug is revealed by societal willingness-to-pay. This may be stated implicitly through committees using cost-effectiveness 'league tables' for decision making, or explicitly by consumer surveys of willingness-to-pay in the context of cost-benefit analysis and stemming from the theoretical foundation of welfare economics.     

A comment concerning one-sided tests of significance in new drug applications.

One-sided tests provide actual type I error probabilities that are consistent with specified alpha levels in situations where differences in only one direction will ever be the basis for a consequential claim of significance. A drug-placebo comparison presented to the FDA in support of a new drug application is clearly a case in point. It is important to use the correct one-sided tests in all cases where they are appropriate in order to avoid the suspicion that they are only used to relax criteria so that marginal results can be reported as significant. The choice of a one-sided test should be a design consideration with consequent reduction in sample sizes commensurate with greater power against consequential alternatives.     

Controlling the significance levels of prediction error tests for linear regression models

This paper provides evidence on problems associated with using standard tests for predictive failure when the errors of a linear regression model are not normally distributed. The ability of a simple bootstrap procedure to give a useful degree of control over the significance levels is examined.     

动态监测尿毒症血液透析患者超声心动图的意义

目的观察尿毒症血液透析患者超声心动图 (UCG)的动态变化 ,并探讨相关危险因素。方法采用UCG对83例尿毒症患者左房内径(LAD)、左室内径(LVD)、室间隔厚度(IVST)、左室后壁厚度(IVPWT)、E/A值进行动态检测 ,并探讨UCG多次异常与透析间期体重增加过多、高血压、营养不良、透析不充分等因素的相关关系。结果尿毒症患者左室内径、左房内径、室间隔厚度、左室后壁厚度明显增高 ,E/A值降低 ,与正常对照组比较存在显著性差异 (P<0.05) ;UCG多次异常与患者透析间期体重增加过多、高血压、营养不良、透析不充分等密切相关。结论尿毒症患者存在UCG的异常 ,动态监测UCG对指导尿毒症血液透析患者的治疗有一定的价值     

C反应蛋白、降钙素原和D-二聚体检测在急性白血病中的意义

目的：探讨C反应蛋白（CRP）、降钙素原（PCT）及D-二聚体检测在急性白血病（AL）中的临床意义。方法采用免疫比浊法检测50例AL患者以及50例健康体检者的CRP、D-二聚体,采用电化学发光法检测PCT含量。结果 AL组的CRP、PCT和D-二聚体水平显著高于健康体检组（P〈0.05）;ALL组与ANLL组比较,差异无统计学意义（P〉0.05）;50例AL患者中, CRP阳性率为92%, PCT阳性率为68%, D-二聚体阳性率为74%。结论 CRP、PCT和D-二聚体的检测可反映AL患者机体感染及纤溶系统状况,为临床追踪病情进展及疗效观察提供重要依据。     

病毒性肝炎四项凝血指标联合检测的临床意义

目的 探讨多项凝血功能指标联合检测对准确反映病毒性肝炎患者凝血功能状况及预后判断的价值。方法 选择正常人和慢性肝炎重度（慢肝重度）、重型肝炎（重肝）、肝炎后肝硬化（肝硬化）患者，联合检测凝血酶原时间（PT）、白陶土部分凝血活酶时间（KPTT）、凝血酶时间（TT）以及纤维蛋白原（Fg)含量。结果 所有患者上述四项指标的均值均明显高于正常组（P＜0．001）；其中慢肝重度和肝硬化患者Fg含量的异常率明显高于其它二项或三项指标（P＜0．01或0．05）；重型肝炎死亡患者PT均数及KPTT异常率均明显高于存活者（P＜0．05）。结论 四项凝血功能指标联合检测可以从多个角度更客观、准确地反映严重肝损害的肝炎患者凝血功能状况及其预后。     

Blood coagulation tests in toxicological studies--review of methods and their significance for drug safety assessment

In general toxicological studies, prothrombin time and activated partial thromboplastin time are routinely measured to assess blood coagulation. Special (problem-driven) tests for blood coagulation are of significance to detect abnormalities and investigate the mechanism of toxicity in detail. In this review, we compiled widely scattered information on blood coagulation testing from different fields in the biological area, and reviewed the methods available and their significance in toxicological studies. The relevant literature cited here reports large species differences in platelet aggregation, coagulation factors or fibrinolysis, and technical limitations. However, the following tests are basically applicable to laboratory animals; (1) assays for individual coagulation factors and protein induced by vitamin K absence or antagonists (PIVKA) to investigate coagulation factor abnormalities; (2) platelet aggregation-, platelet adhesion-, platelet release-tests and von Willebrand factor assay to screen and/or investigate platelet dysfunction; (3) fibrin/fibrinogen degradation products (FDP), D-dimer and thromboelastogram to detect fibrinolitic abnormalities, and assays for plasminogen, plasmin and their activator/inhibitor to investigate fibrinolysis in detail; and (4) bleeding-time to grossly evaluate blood coagulation capability in vivo. An appropriate battery of these tests provides significant information for risk assessment of drugs.     

Preclinical detection of nephrotoxicity: description of the tests and appraisal of their health significance

The prevention of renal diseases induced by chemicals requires the use of tests with which adverse renal effects can be detected at a stage when removal from exposure to the offending agent(s) may lead to complete recovery or may at least prevent an accelerated decline in renal function. The screening tests used in clinical medicine for assessing the functional integrity of the kidney are not sufficiently sensitive to attain this objective. In this review, we describe the tests currently available for detecting incipient renal damage and attempt to assess their health significance. A minimal battery of tests is recommended for the detection of groups in industry or in the general population who are at risk. If an increased prevalence of abnormal values for these parameters is found repeatedly in a population, efforts should be made to identify the causal agent(s) and, if possible, to reduce the exposure. Follow-up examinations of subjects identified in this way are also indicated, in order to define the predictive value of the detected changes better.     

117例健康儿童心肌酶谱统计临床分析

目的 探讨健康儿童心肌酶谱变化规律及其临床意义.方法 选取健康儿童117名,分为两组：≤6岁组82例,7～13岁组35例.对比分析两组儿童心肌酶谱检测结果.结果 ≤6岁组各项心肌酶谱检测结果较6～13岁组明显增高,差异有极显著性（P＜0.01）：≤6岁组α-HBDH、LDH-L升高例数为最多,分别占74.39%、47.56%,其次为AST占13.41%,但AST升高主要集中在婴儿,CK、CK-MB升高例数最少,分别占3.66%、6.10%;7～13岁组心肌酶谱检测结果大多在正常范围,仅α-HBDH升高2例,占5.71%,LDH-L升高1例,占2.86%.结论 婴幼儿、学龄前儿童心肌损伤的诊断要考虑到年龄因素,CK-MB/CK、α-HBDH/LDH和cTnI不受年龄影响,可供选择.     

同型半胱氨酸、hs-CRP在冠心病患者血液检测中的推广意义

目的探讨同型半胱氨酸(Hcy)和超敏C-反应蛋白(hs-CRP)在冠心病患者血液中的表达及检测意义。方法选取2016年10月～2018年4月我院收治的冠心病患者100例为观察组,另选取同期健康体检者50例为对照组。以水解酶法和免疫比浊法分别测定患者血液中Hcy和hs-CRP水平。结果观察组患者血液Hcy、hs-CRP水平均较对照组升高,差异均有统计学意义(P 0.05);冠心病患者随着其冠状动脉狭窄程度的加重,血液Hcy、hs-CRP水平亦随之升高,差异有统计学意义(P 0.05);不同冠状动脉狭窄程度的冠心病患者血液Hcy、hs-CRP水平联合检出率与单独检出率相比,差异均有统计学意义(P 0.05)。结论冠心病患者血液Hcy、hs-CRP呈现异常状态,且二者联合检测对冠心病的诊断及预后的判断具有重要意义。