等价性试验中样本容量的量佳估计

本文简述了两均数等价性检验的方法，分别推导出了进行两均数等价性检验和两百分率等价性检验时，估计样本容量的公式，应用本文公式估计的样本容量进行等价性试验，可在满足要求的条件下使试验的总费用最低，文中还讨论了等价界值的确定等问题。     

对比试验中的最佳样本容量

在畜牧和生物试验中,需预先估计试验所需的样本大小。常见的估计样本大小的一些公式,都只考虑了犯Ⅰ、Ⅱ类错误的概率,而没有考虑到试验的费用。本文既考虑犯Ⅰ、Ⅱ类错误的概率,又考虑试验的总费用,提出了不同条件下估计样本大小的新公式。按照这些公式估计样本容量,可使试验的总费用最低。     

生物统计学单样本t检验的SPSS实现

生物统计学是认识世界的工具，其中单样本t检验适用于样本均数x与已知总体均数μ0的比较，其比较目的是检验样本均数x所代表的总体均数μ与已知总体均数μ0是否有差别，而已知总体均数μ0一般为标准值、理论值或是经大量检验得到的较稳定的指标。试验共收集74名男性和96名女性大学生的血压、脉搏、体温、身高、体重指标，根据文献资料所得的正常身体指标参考范围，利用SPSS程序对收集的数据进行整理、单样本t检验分析和推断总体，从而揭示以样本数据探索规律的分析方法。     

番鸭基因型与环境互作对屠宰性能影响的研究

本文以番鸭为研究对象，从出雏至70日龄屠宰，设计两种基因型，两种日粮，两种性别，两个试验场的试验，考虑主效应及互作效应进行方差分析和最小二乘均数估计，结果表明：屠宰率，全净膛率，胸肌率，腱肌率，瘦肉率的番鸭品种主效应，皮脂率的日粮主效应和瘦肉率的性别主效应达显著或极显著水平（P＜0．05或P＜0．01），腿肌率的品种与日粮互作，胸肌率，瘦肉率，腹脂率的品种与性别互作，屠宰率的品种与场互作显著。     

正确使用t检验与方差分析方法

正确使用ｔ检验与方差分析方法对于正态或近似正态分布且各组数据变异程度相近（具有方差齐性）的计量资料，常用ｔ检验和方差分析方法进行统计处理。ｔ检验主要适用于单因子两组间均数的比较，而不适合于单因子３组及更多组间均数的比较。方差分析则不仅适用于两组间均数...     

应用可信区间估计总体间差异的大小

应用可信区间估计总体间差异的大小通过由实验获得的几个均数（或率）的表面差异，来估计相应总体间差异的大小，常常是科研人员比较关心的问题。对这类资料常用的显著性检验方法，如ｔ检验、方差分析、χ２检验等，只能回答总体间是否存在差异，而不能说明差异的大小。要...     

最小二乘分析在畜牧试验中的应用

最小二乘分析法是本世纪40年代初，数理统计学家创立的，70年代以来，该法在国外广泛应用于家畜育种、饲养等科研中，国内应用较少。最少二乘分析的优点是；在进行方差分析时，不仅能检验各因素水平效应差异是否显著，而且当差异显著时，可估计其均数及各因素水平的效应值（后者用常规方差分析方法是无法解决的），并可求出各因素水平组合的最小二乘均数，对原始资料进行校正。此外，该方法还适用于在试验设计或试验中，因试验动物死亡缺失或初生时的性别等造成资料的次级样本含量不等，以及便于编制电算程序。     

微粒子病集团检验中批次病蛾率的估算及其误差分析

蚕种质量检验中需要根据家蚕微粒子病集团检验的结果对检验批次的病蛾率进行合理估计。推导了一个根据检验集团带毒率估算检验批次母蛾的病蛾率的公式,并采用计算机模拟抽样检验方法对该公式的无偏性、有效性及影响因素(检验批次大小、检验集团数量、检验集团大小、实际病蛾率、带毒集团检出率)进行分析。结果表明,采用该公式对检验批次病蛾率的估计具有统计无偏性,估计误差主要受到检验集团数量、带毒集团检出率的影响。     

MS Excel在畜牧兽医统计中的应用(四)——卡方检验(x2检验)

卡方检验（X^2检验）是次数资料的显著性检验方法，它包括适合性检验和独立性检验两类。适合性检验用于检验某性状观察次数与该性状的理论比率是否符合，如两对性状杂种后代的分离现象是否符合9：3：3：1的比例；而独立性检验是用于判断两类因子是彼此相关还是相互独立的，也是次数资料的相关性研究，如：注射某种疫苗与预防某种疾病的关系。下面，以明道绪主编《生物统计附试验设计》第159页例7．2，第172页例7．10和杨树勤主编的《卫生统计学》第79页例8．3为例，介绍Excel在卡方检验（X^2检验）中的应用。     

生物统计讲座(Ⅴ)

五、均数差异的显著性测定一般,在调查或试验研究中,人们都欲对所得两个样本(如对照与试验或互为对照的两个组)的均数进行比较,从均数间的差异来确定试验是否有效,或是否代表不同总体间的本质差异。但由前述我们知道,从同一总体中抽取一定大小的样本,每次抽样求得的均数都不完全相同;同一现象所做的试验,每次试验所得数据的均     

Veterinary drug bioequivalence determination

A bioequivalence trial is a statistically based comparison of two formulations to demonstrate with a controlled consumer (patient) risk that two formulated drug products are interchangeable. The basic assumption underlying a bioequivalence trial is that essentially the same plasma time-course leads to essentially the same effect allowing two formulations to be interchanged. Bioequivalence is generally assessed using kinetic end points and in practice, two formulations in which bioavailability parameters (rate and extent) differ by 20% or less, with a 90% degree of confidence, are considered to be bioequivalent. In this review, the design and evaluation of bioequivalence studies are presented with special attention given to scientific issues.     

The bioequivalence of a single intravenous administration of the anesthetic alfaxalone in cyclodextrin versus alfaxalone in cyclodextrin plus preservatives in cats

To demonstrate the bioequivalence of alfaxalone in cyclodextrin (Reference Product) to a formulation of alfaxalone in cyclodextrin also containing the preservatives ethanol, chlorocresol, and benzethonium chloride (Test Product) when administered for the purpose of inducing anesthesia in the cat. Blinded, single‐dose, randomized, two‐period, two‐sequence, cross‐over bioequivalence study with a 7‐day washout period between treatments. Twenty‐four (12 neutered males and 12 intact females), healthy, adult cats weighing 4.1±0.9 kg. Cats were administered 5 mg/kg IV of alfaxalone in the Reference or Test Product using a randomized cross‐over design. One‐milliliter venous blood samples were collected at predetermined time points to 12 hr after drug administration to determine alfaxalone plasma concentration over time. Alfaxalone concentrations were determined by a validated analytical testing method using HPLC‐MS/MS. Plasma profiles of alfaxalone concentration against time were analyzed by noncompartmental analysis. The pivotal variables for bioequivalence were AUC_last and C_max. Equivalence was achieved if the 90% confidence interval for AUC_last and C_max fell into the asymmetric ±20% interval (0.80–1.25). Physiological variables, quality of anesthesia visual analog scale (VAS) scoring and anesthetic event times were recorded. ANOVA or ANCOVA (single time point), RMANOVA or RMANCOVA (multiple time point) was used for normally distributed data. GLIMMIX was used for nonnormally distributed data. VAS scores were analyzed as for blood bioequivalence data. Variables were evaluated for safety and assessed at alpha = 0.10. C_max and AUC_last for Reference and Test Products were statistically bioequivalent. No physiological variables except for a drug by time interaction for respiratory rate differed between treatment groups, and this difference was not clinically relevant. No anesthetic event times or VAS scores for quality of anesthesia were different between treatment groups. Neither formulation caused pain upon injection. The Reference and Test Products are pharmaceutically bioequivalent formulations when administered as a single intravenous administration for the purpose of induction of anesthesia in cats.     

Prevalence estimation from pooled samples

Under certain conditions, prevalence can be estimated by testing samples from individual members or by pooling samples from members into a group and by testing the sample from the group as a single unit. Pooled tests are more accurate than individual tests when P is less than 10%. Optimal group size is 1.6/P. Efficiency decreases slowly with suboptimal size and rapidly with overly large size.     

Single versus double testing of meat-juice samples for Salmonella antibodies,in the Danish pig-herd surveillance programme

In Denmark, a national serological surveillance-and-control programme for Salmonella in pigs has been in operation since 1995. The programme is based on the Danish mix-ELISA and uses double testing (two ELISA-wells used per sample) of meat-juice samples taken in relation to slaughter. All herds are classified monthly into one of the three levels; the classification is based on the percentage of positive serological results in the previous 3 months. In connection with evaluation of the programme in 2001, we investigated whether single testing (testing in one well only) could be expected to be sufficiently precise compared to double testing. Data from the year 2000 were used, and mathematical modelling. Single testing was simulated by randomised selection of one of the two results in the double testing. A slight increase in the prevalence of Salmonella-positive samples (1.02-1.09 times more through the four quarters of the year 2000) was found in the simulated single testing, as compared to the double testing. Around 0.5% of the herds would be allocated to another herd level in single testing-almost equal numbers one level up and one level down. No herd being seronegative in double testing would be allocated to levels 2 or 3 (herds with >40 or >70%, respectively, serological reactors) in single testing. The prevalence of "false-positive" diagnoses (positive in single testing and negative in double testing) and inversely defined "false-negative" diagnoses varied from 4.2 to 8.7% and from 3.2 to 4.5%, respectively, through the four quarters of the year 2000. The probability of allocating a herd to a wrong level due to sampling error was on the average 6.2 (varying from 1.66 to over 100) times higher than the probability of allocating a herd to a wrong level due to the test inaccuracy introduced by going from double to single testing. This is, however, an average; a herd with a true prevalence close to one of the level border cut-offs (40 and 70% weighted seroprevalence, respectively) would have a higher risk of being allocated to a wrong level than a herd with a true prevalence far from the level border cut-offs. The results are based on the current Danish sample sizes in the surveillance scheme, which implies that 60, 75 or 100 samples are taken annually in a herd, depending on its size. Other sample sizes would produce other results.     

兽用化学药品血药浓度法生物等效性试验注册资料技术评审要点及常见问题

生物等效性试验作为兽药获批上市的关键试验,其研究过程和技术评审都要遵循特定的法规和指导原则。以药动学参数为终点的血药浓度法生物等效性试验是目前普遍采用的研究方法,适用于药物活性成分吸收进入体循环具有全身作用的剂型(大多数内服剂型和特殊注射剂)。本文根据生物等效性定义、相关法规和指导原则,结合近年来兽药注册资料,对血药浓度法生物等效性试验的技术评审要点及常见问题进行梳理,旨在为新兽药的研发和注册提供参考。     

Bioavailability in the rabbit of penicillin and dihydrostreptomycin from three commercial penicillin/aminoglycoside fixed combination products for intramuscular injection

The bioavailability of penicillin and dihydrostreptomycin from three penicillin/ aminoglycoside fixed combination products for intramuscular injection was investigated in a four-way, randomized, crossover experiment in rabbits. Attention is focused on bioequivalence based on plasma concentration vs. time profiles to study whether the rabbit is a good model to detect differences in in vivo delivery of penicillin and/or dihydrostreptomycin after intramuscular administration of different products. In all products, penicillin was present as a suspension. Although the extent of absorption of penicillin did not differ between the three products, large differences in the rates of absorption were observed. With respect to dihydrostreptomycin, no significant differences were observed between the products. The results from this study demonstrate that the rabbit is a good model to detect differences in bioavailability of suspended penicillin from penicillin/dihydrostreptomycin fixed combination products for intramuscular injection. A study with the same products is presently being carried out in calves to investigate whether bioequivalence studies in rabbits could replace studies in the target animals.     

Precision and accuracy of sward height distributions

Double normal distributions can be used to resolve many sward height frequency distributions into two components representing the 'short' (patches) and 'tall' (non～patches) areas in the sward. The effect of sample size on the precision and accuracy of parameters of sward height distributions was examined by drawing sub-samples (n=10) of increasing sample size (50 to 1 000) from simulated height data (n=10 000) from three different, typical height distributions, viz. normal (ungrazed), bimodal (leniently grazed) and positively skewed (intensely grazed). The coefficient of variation of components of all three distributions decreased sharply with increasing sample size and CVs for all means were <15% with 200 height measures, and <10% for all means, with the exception of the 'tall' mean in the bimodal distribution, at a sample size of 100. At a given sample size, proportions in the two components were less-precisely measured than the means, especially when the components are equally represented in the population (i.e. bimodal), where 500 measurements are required for a precision of 15%. Accuracy also increased with sample size, and with 400 samples, deviations were within 10% of the true values for most parameters of the three distributions. A sample size of 200 is recommended for quantifying the mean height of 'short' and 'tall' components of the sward whereas 400-500 samples are required to precisely estimate their relative proportions.     

Trichinella in horses: a low frequency infection with high human risk

After the initial report in 1976 of a trichinellosis epidemic caused by the consumption of infected horsemeat, 12 other outbreaks have been described in Europe. Since the first serious human outbreak several experiments have confirmed the susceptibility of horses to Trichinella species and the rapid disappearance of specific antibodies in this host that prevents the use of serological methods for routine screening. A review of the distribution of parasite burdens in muscles of naturally or experimentally infected horses indicates that the tongue is the most likely sample to contain detectable numbers of Trichinella larvae in low level infections. Requirements for testing of horsemeat are specified in legislation of the European Union, and other recommendations are published elsewhere. The EEC directives have evolved into very specific requirements which specify the testing of at least 5g of tongue, masseter or diaphragm per horse using a pooled digestion assay. More recently, France has revised the requirement for sample size to 10g for horsemeat originating from countries with high prevalence of Trichinella. To address the continuing outbreaks of human trichinellosis due to infected horsemeat, the development and implementation of a quality assurance system for testing is being considered.     

A comparison of the bioequivalence of 0.5% fenbendazole top dress pellets or 10% fenbendazole oral suspension against a spectrum of equine parasites.

A controlled test was conducted to assess the efficacy bioequivalence of a single dose of 0.5% fenbendazole (FBZ) top dress pellets to a 10% FBZ suspension formulation (Panacur suspension 10%, Hoechst Roussel Vet). Thirty horses with naturally-acquired parasite infections, in replicates of three, were used. Strongyle egg per gram counts were not significantly different (P>0.1) between groups pretreatment, but FBZ treated groups were significantly different from the control group post-treatment. At necropsy, which occurred seven to nine days post-treatment, two methods of nematode recovery were compared to assess whether a small aliquot can be used in a control test to determine efficacy against large as well as small strongyles. Both post mortem worm recovery techniques revealed similar efficacies of both formulations (>95%) against small and large strongyles, but large differences in the number of worms recovered. Six species of small strongyles comprised 96% of all the small strongyles recovered: Coronocyclus coronatus, Cylicocyclus insigne, Cylicostephanus longibursatus, Cylicocyclus brevicapsulatus, Cylicocyclus nassatus, and Cyathostomum catinatum. The results of this study demonstrated therapeutic bioequivalence between FBZ formulations and also the need to sample at least a 10% aliquot to accurately estimate number of large strongyles. No adverse reactions to treatment were detected.