A note on sample size determination for bioequivalence studies with high-order crossover designs

Similar to Liu and Chow, approximate formulas for sample size determination are derived based on Schuirmann's two one-sided tests procedure for bioequivalence studies for the additive and the multiplicative models under various higher order crossover designs for comparing two formulations of a drug product. The higher order crossover designs under study include Balaam's design, the two-sequence dual design, and two four-period designs (with two and four sequences), which are commonly used for assessment of bioequivalence between formulations. The derived formulas are simple enough to be carried out with a pocket calculator. The number of subjects required for each of the four higher order designs are tabulated for selected powers and various parameter values.     

Power and sample size calculations for studies involving linear regression

This article presents methods for sample size and power calculations for studies involving linear regression. These approaches are applicable to clinical trials designed to detect a regression slope of a given magnitude or to studies that test whether the slopes or intercepts of two independent regression lines differ by a given amount. The investigator may either specify the values of the independent (x) variable(s) of the regression line(s) or determine them observationally when the study is performed. In the latter case, the investigator must estimate the standard deviation(s) of the independent variable(s). This study gives examples using this method for both experimental and observational study designs. Cohen's method of power calculations for multiple linear regression models is also discussed and contrasted with the methods of this study. We have posted a computer program to perform these and other sample size calculations on the Internet (see http://www.mc.vanderbilt.edu/prevmed/psintro+ ++.htm). This program can determine the sample size needed to detect a specified alternative hypothesis with the required power, the power with which a specific alternative hypothesis can be detected with a given sample size, or the specific alternative hypotheses that can be detected with a given power and sample size. Context-specific help messages available on request make the use of this software largely self-explanatory.     

Presentation of the intrasubject coefficient of variation for sample size planning in bioequivalence studies

Bioequivalence studies are generally performed as crossover studies and, therefore, information on the intrasubject coefficient of variation is needed for sample size planning. Unfortunately, this information is usually not presented in publications on bioequivalence studies, and only the pooled inter- and intrasubject coefficient of variation for either test or reference formulation is reported. Thus, the essential information for sample size planning of future studies is not made available to other researchers. In order to overcome such shortcomings, the presentation of results from bioequivalence studies should routinely include the intrasubject coefficient of variation. For the relevant coefficients of variation, theoretical background together with modes of calculation and presentation are given in this communication with particular emphasis on the multiplicative model.     

Computer simulation of sample size and experimental design in human psychogenetics.

Applied a method of computer simulation to the investigation of problems connected with the genetic analysis of continuously variable behavioral characters in human populations. The efficiency with which various components of genetic and environmental variation could be detected was related to sample size. Results indicate that a convincing partition of the genetic variance into its additive and nonadditive components required much larger samples than those frequently employed in human psychogenetics. (15 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Establishing equivalence of two treatments and sample size requirements in matched-pairs design

To investigate the role of putative virulence factors of Streptococcus pyogenes (group A streptococcus; GAS) in causing disease, we introduced specific mutations in GAS strain B514, a natural mouse pathogen, and tested the mutant strains in two models of infection. To study late stages of disease, we used our previously described mouse model (C3HeB/FeJ mice) in which pneumonia and systemic spread of the streptococcus follow intratracheal inoculation. To study the early stages of disease, we report here a model of long-term (at least 21 days) throat colonization following intranasal inoculation of C57BL/10SnJ mice. When the three emm family genes of GAS strain B514-Sm were deleted, the mutant showed no significant difference from the wild type in induction of long-term throat colonization or pneumonia. We inactivated the scpA gene, which encodes a complement C5a peptidase, by insertion of a nonreplicative plasmid and found no significant difference from the wild type in the incidence of throat colonization. However, there was a small but statistically significant decrease in the incidence of pneumonia caused by the scpA mutant. Finally, we demonstrated a very important effect of the hyaluronic acid capsule in both models. Following intranasal inoculation of mice with a mutant in which a nonreplicative plasmid was inserted into the hasA gene, which encodes hyaluronate synthase, we found that all bacteria recovered from the throats of the mice were encapsulated revertants. Following intratracheal inoculation with the hasA mutant, the incidence of pneumonia within 72 h was significantly reduced from that of the control strain (P = 0.006). These results indicate that the hyaluronic acid capsule of S. pyogenes B514 confers an important selective advantage for survival of the bacteria in the upper respiratory tract and is also an important determinant in induction of pneumonia in our model system.     

A method for sequential analysis of survival data with nonproportional hazards

Positron emission tomography in three-dimensional acquisition mode was used to identify the neural populations involved in tactile-visual cross-modal transfer of shape. Eight young male volunteers went through three runs of three different matching conditions: tactile-tactile (TT), tactile-visual (TV), and visual-visual (VV), and a motor control condition. Fifteen spherical ellipsoids were used as stimuli. By subtracting the different matching conditions and calculating the intersections of statistically significant activations, we could identify cortical functional fields involved in the formation of visual and tactile representation of the objects alone and those involved in cross-modal transfer of the shapes of the objects. Fields engaged in representation of visual shape, revealed in VV-control, TV-control and TV-TT, were found bilaterally in the lingual, fusiform, and middle occipital gyri and the cuneus. Fields engaged in the formation of the tactile representation of shape, appearing in TT-control, TV-control and TV-VV, were found in the left postcentral gyrus, left superior parietal lobule, and right cerebellum. Finally, fields active in both TV-VV and TV-TT were considered as those involved in cross-modal transfer of information. One field was found, situated in the right insula-claustrum. This region has been shown to be activated in other studies involving cross-modal transfer of information. The claustrum may play an important role in cross-modal matching, because it receives and gives rise to multimodal cortical projections. We propose here that modality-specific areas can communicate, exchange information, and interact via the claustrum.     

A control-conditional test for assessing HIV vaccine efficacy in small sample preclinical studies

In this paper, we discuss the analysis of data from small sample animal studies intended to evaluate HIV vaccine efficacy. The focus is on the chimpanzee model with HIV infection, a binary outcome, of primary interest. The problem becomes that of testing for a difference in independent binomial proportions, but aspects of the study design call into question the use of standard approaches. As sample sizes may be as small as one or two per group in this context, it is tempting to utilize previous data; such usage, however, carries a high price in terms of additional assumptions. We present a test, referred to as the control-conditional test, which conditions on the control data and assumes (in a manner of Bayesian estimation) only vague prior information. Comparisons are made with Fisher's exact test and an exact unconditional test. The control-conditional test is also generalized to allow the analysis of data from a differential dose design.     

空间网格结构分析设计软件MSTCAD的应用

介绍了空间网格结构分析设计软件的特点,阐述了其设计要点,提供了4个工程应用实例,可供工程设计参考。     

Quantification of biomedical NMR data using artificial neural network analysis: lipoprotein lipid profiles from 1H NMR data of human plasma

Artificial neural network (ANN) analysis is a new technique in NMR spectroscopy. It is very often considered only as an efficient "black-box' tool for data classification, but we emphasize here that ANN analysis is also powerful for data quantification. The possibility of finding out the biochemical rationale controlling the ANN outputs is presented and discussed. Furthermore, the characteristics of ANN analysis, as applied to plasma lipoprotein lipid quantification, are compared to those of sophisticated lineshape fitting (LF) analysis. The performance of LF in this particular application is shown to be less satisfactory when compared to neural networks. The lipoprotein lipid quantification represents a regular clinical need and serves as a good example of an NMR spectroscopic case of extreme signal overlap. The ANN analysis enables quantification of lipids in very low, intermediate, low and high density lipoprotein (VLDL, IDL, LDL and HDL, respectively) fractions directly from a 1H NMR spectrum of a plasma sample in < 1 h. The ANN extension presented is believed to increase the value of the 1H NMR based lipoprotein quantification to the point that it could be the method of choice in some advanced research settings. Furthermore, the excellent quantification performance of the ANN analysis, demonstrated in this study, serves as an indication of the broad potential of neural networks in biomedical NMR.     

A sample size correction for Pearson chi-square in 2?×?2 contingency tables.

A test statistic that is asymptotically equivalent to the Pearson chi-square, but which is more conservative by a factor of (N?–?1)/N, is proposed for use with small samples when testing for homogeneity of response probabilities in 2?×?2 tables. Evaluation of this test statistic indicates that it produces actual Type I error probabilities that are less often and less seriously nonconservative than the Pearson chi-square, although it does not result in the severely conservative bias previously reported for Yates's correction or Fisher's exact probability test. Other recent evaluations of bias in the Pearson chi-square test for 2?×?2 tables have resulted in conflicting recommendations, primarily because the evaluations have been based on different assumptions concerning the degree of experimenter control over marginal frequencies. Three conditions of control over the marginal frequencies are identified, and the results of exact probability evaluations for the Pearson chi-square under different assumptions are discussed. (9 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Application of GEE procedures for sample size calculations in repeated measures experiments

Derivation of the minimum sample size is an important consideration in an applied research effort. When the outcome is measured at a single time point, sample size procedures are well known and widely applied. The corresponding situation for longitudinal designs, however, is less well developed. In this paper, we adapt the generalized estimating equation (GEE) approach of Liang and Zeger to sample size calculations for discrete and continuous outcome variables. The non-central version of the Wald Chi 2 test is considered. We use the damped exponential family of correlation structures described in Mu?oz et al. for the 'working' correlation matrix among the repeated measures. We present a table of minimum sample sizes for binary outcomes, and discuss extensions that account for unequal allocation, staggered entry and loss to follow-up.     

Power analysis and determination of sample size for covariance structure modeling.

A framework for hypothesis testing and power analysis in the assessment of fit of covariance structure models is presented. We emphasize the value of confidence intervals for fit indices, and we stress the relationship of confidence intervals to a framework for hypothesis testing. The approach allows for testing null hypotheses of not-good fit, reversing the role of the null hypothesis in conventional tests of model fit, so that a significant result provides strong support for good fit. The approach also allows for direct estimation of power, where effect size is defined in terms of a null and alternative value of the root-mean-square error of approximation fit index proposed by J. H. Steiger and J. M. Lind (1980). It is also feasible to determine minimum sample size required to achieve a given level of power for any test of fit in this framework. Computer programs and examples are provided for power analyses and calculation of minimum sample sizes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Nomograms for obtaining a necessary, minimum sample size. II. When distribution of proportions from binomial data is approximately normal

111 patients are studied in order to find possible relations between the endoscopic images and histopathological findings in the chronic maxillary sinusitis. The clasification of the different types of sinusitis is based on the aspect of the mucosa (normoplastic, hypoplastic, polypous, polypoido-polypous) and on the histological features (lymphoplasmocytic, eosinophilic, eosino-lymphoplasmocytic infiltration, low cellularity). The confrontation of the sinusoscopic and histopathological observations give interesting information, such as differenciation between stabilized and evolutive sinusitis, simple and complicated inflammation. This information facilitates our therapeutic choice.     

Design considerations for estimation of exposure effects on disease risk, using aggregate data studies

Previously we proposed an aggregate data study design for estimation of exposure effects from population-based disease rates and covariate data from risk factor surveys in each population group. A basic relative rate model specified for individuals is aggregated to produce a random effects relative rate model for the disease rates. Relative rate parameter estimates from aggregate data studies target the same parameters as individual-level studies but use between-group information in the data. We distinguish aggregate data studies from ecologic studies. Considerations in the design of aggregate studies are motivated by the need to gain clearer understanding of the role of diet in cancer aetiology. Simulation studies show that increasing the number of populations included in an aggregate data study from about 20 to 30-40 gives greater improvement in power than corresponding increases in the size of the survey sample in each population over an initial size of 100 individuals.     

MMPI studies of counselors: A review.

Presents a current, systematic review of published MMPI research on counselor characteristics and effectiveness and discussed the importance of continuing research in this area. Counselors appear different from the general norms on the L, K, Hy, Pd, Mf, Ma, Si, Es, Do, Re, St, and Pr scales but only the L, K, Ma, and Si scales distinguish between counselors and persons in other professions. Only the Ma and Sc scales show promise of discriminating between effective and ineffective counselors in training. Weaknesses of the existing research are indicated and 2 basic questions are raised regarding inventory research on counselor effectiveness. (22 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

面向传统大型制造企业的大数据平台解决方案研究与设计

在分析业界大数据技术背景及大数据平台重要作用的基础上,结合传统大型制造企业的大数据平台建设现状调研,提出了一种面向传统大型制造企业的大数据平台解决方案设计方法。阐述了该解决方案的整体架构以及整体架构中数据采集、数据计算与存储、数据服务、数据应用、数据运营、数据治理所涉及的关键点,以此来探索传统大型制造企业在实施大数据平台建设方面的最佳实践。     

Particle size analysis of dilute environmental colloids by flow field-flow fractionation using an opposed flow sample concentration technique

An on-line concentration method has been developed for the analysis of dilute suspensions of macromolecules and particles by flow field-flow fractionation (FFF). This method, termed opposed flow sample concentration (OFSC), uses two opposing flowstreams to focus sample into a narrow band near the inlet of the flow FFF channel. Large sample volumes (up to 1 L) have been successfully loaded, concentrated, and separated in a 1 mL volume flow FFF channel. Concentration factors as high as 10(5) have been achieved. The effectiveness of OFSC flow FFF was demonstrated using mixtures of monodispersed standards such as proteins and polystyrene latex beads. Retention times, peak areas, and resolution are comparable for a 10 mL and a typical 10 microL injection volume. The applicability of the method to environmental studies was demonstrated by a separation of river water colloids.     

Evaluation of recommended methods for radioisotopes red cell survival studies

Mean red cell life-span in normal subjects and in patients with various hematological disorders was examined with 51Cr and DF32P. The results with 51Cr were corrected for 51Cr elution using correction factors. The results by the two methods agreed fairly well with each other. Elution rate in various hematological disorders was 2.3% per day or less except for the patients with extracorpuscular hemolytic agents such as autoimmune hemolytic anemia or congestive splenomegaly. It is concluded that estimates of mean red cell life-span by corrected 51Cr method are more useful and sufficient than uncorrected 51Cr or DF32P method in general hematological disorders.     

减振复合板阻尼测试样品模态分析及尺寸确定

针对减振复合板样品在阻尼测试中样品尺寸标准不一,样品尺寸在确定时缺乏理论依据,无法确定测试样品尺寸的问题,利用有限元方法对减振复合板进行模态分析,用悬臂梁法进行阻尼实测。有限元模拟结果表明,在一定的宽度和厚度下,随着试样长度的增加,其1阶到6阶共振频率均出现降低的规律;在一定的长度和厚度下,随着样品宽度的增加,前4阶共振频率有略微增加的趋势;在一定的长度和宽度下,随着样品厚度的增加,1阶到3阶的共振频率基本保持稳定。实测结果表明,选取自由端长度为216 mm、宽度为12.7 mm的样品,利用2阶和3阶共振频率下的损耗因子进行阻尼表征较为合理。