英汉公示语及其语义信息的传递

作为一个全新的通用流行词语,公示语的语义信息异常丰富。英汉公示语之间偶有部分对应,完全对应的情况极少,其语义信息的传递方式可根据具体的题旨情境或直译、或意译、或借译、或仿译、或反译、或图示、或图示并辅以文字标识,以实现交际意图。     

Estimating Dose Equivalence for New Routes of Drug Administration

Abstract

For patient's convenience, dose administration of insulin via oral inhalation is often considered as an alternative to subcutaneous administration. An important statistical problem is to estimate dose equivalence, which is the amount of drug needed to be delivered by inhalation to generate an equivalent pharmacokinetic (PK) response produced by a therapeutic dose of subcutaneous insulin. Because of high intersubject variability, a crossover design clinical trial is typically used where data from both routes of administration are obtained from the same subject. A linear mixed effects model is proposed to describe the relationship between AK response and insulin dose for the two routes of administration. Estimation of dose equivalence in this setting has not been discussed in the statistical literature. Several competing methods for estimating dose equivalence are proposed and contrasted. A formula for calculating an approximate sample size necessary to estimate dose equivalence with a desired precision for the new route of administration is also provided.     

Exact and Approximate Power and Sample Size Calculations for Analysis of Covariance in Randomized Clinical Trials With or Without Stratification

ABSTRACT

Analysis of covariance (ANCOVA) is commonly used in the analysis of randomized clinical trials to adjust for baseline covariates and improve the precision of the treatment effect estimate. We derive the exact power formulas for testing a homogeneous treatment effect in superiority, noninferiority, and equivalence trials under both unstratified and stratified randomizations, and for testing the overall treatment effect and treatment × stratum interaction in the presence of heterogeneous treatment effects when the covariates excluding the intercept, treatment, and prestratification factors are normally distributed. These formulas also work very well for nonnormal covariates. The sample size methods based on the normal approximation or the asymptotic variance generally underestimate the required size. We adapt the recently developed noniterative and two-step sample size procedures to the above tests. Both methods take into account the nonnormality of the t statistic, and the lower order variance term commonly ignored in the sample size estimation. Numerical examples demonstrate the excellent performance of the proposed methods particularly in small samples. We revisit the topic on the prestratification versus post-stratification by comparing their relative efficiency and power. Supplementary materials for this article are available online.     

Effects of computerized match-to-sample training on emergent fraction-decimal relations in individuals with fragile X syndrome

Individuals diagnosed with fragile X syndrome (FXS), the most common known form of inherited intellectual disability, are reported to exhibit considerable deficits in mathematical skills that are often attributed to brain-based abnormalities associated with the syndrome. We examined whether participants with FXS would display emergent fraction-decimal relations following brief, intensive match-to-sample training on baseline relations. The performance profiles on tests of symmetry and transitivity/equivalence of 11 participants with FXS, aged 10-23 years, following baseline match-to-sample training were compared to those of 11 age- and IQ-matched controls with idiopathic developmental disability. The results showed that both groups of participants showed significant improvements in the baseline (trained) relations, as expected. However, participants with FXS failed to show significant improvements in the (untrained) symmetry and transitivity/equivalence relations compared to those in the control group. A categorical analysis of the data indicated that five participants with FXS and eight controls showed at least “intermediate” emergence of symmetry relations, whereas one individual with FXS and three controls showed at least intermediate emergence of transitivity/equivalence relations. A correlation analysis of the data indicated that improvements in the symmetry relations were significantly associated with improvements in the transitivity/equivalence relations in the control group (r = .69, p = .018), but this was not the case in the FXS group (r = .34, p > .05). Participant IQ was significantly associated with improvements in the symmetry relations in individuals with FXS (r = .60, p = .049), but not in controls (r = .21, p > .05). Taken together, these results suggest that brief, computerized match-to-sample training may produce emergent mathematical relations for a subset of children with FXS and developmental disabilities. However, the ability of individuals with FXS to form transitivity/equivalence relations may be impaired relative to those with idiopathic developmental disabilities, which may be attributed to neurodevelopmental variables associated with the syndrome.     

A new permutation-based method for assessing agreement between two observers making replicated binary readings

A new coefficient for assessing agreement between two observers using a permutation-based method is introduced in this article. When observations are binary, this coefficient compares the observed disagreement (probability of discordance) between the observers with its expected value under the hypothesis of individual equivalence. This hypothesis states that for each subject, the conditional distributions of the readings of the two observers are identical, and therefore from a statistical viewpoint it does not matter which observer makes the reading on this subject. Let K and L denote the numbers of replicated observations that are available from observers X and Y, respectively, on a given subject. Then the expected disagreement under individual equivalence for a subject is based on the (K + L) choosing K possible assignments of X's and Y's to the K + L observations made on this subject. Simple methods for the estimation of the new coefficient and its standard error are derived. The new coefficient is compared with kappa and the coefficient of individual agreement, which is based on comparing the inter and intra observer disagreements. Simulation studies confirm the validity of the estimated coefficient and its standard error. Data from a study involving the evaluation of mammograms by 10 radiologists are used to illustrate this new approach to the evaluation of observer agreement.     

Algorithms for evaluating reference scaled average bioequivalence: power,bias, and consumer risk

The determination of the bioequivalence between highly variable drug products involves the evaluation of reference scaled average bioequivalence. The European and US regulatory authorities suggest different algorithms for the implementation of this approach. Both algorithms are based on approximations reflected in lower than the achievable power or higher than the nominal consumer risk of 5%. To overcome these deficiencies, a new class of algorithms, the so‐called Exact methods, was earlier introduced. However, their applicability was limited. We propose 2 modifications which make their computation simpler and also applicable with any study design. Four algorithms were evaluated in simulated 3‐period and 4‐period bioequivalence studies: Hyslop's approach recommended by the US FDA, the method of average bioequivalence with expanding limits requested by the European EMA, and 2 versions of the new Exact methods. At small sample sizes, the Exact methods had substantially higher statistical power than Hyslop's algorithm and had lower consumer risk than the method of average bioequivalence with expanding limits. Similarly to the Hyslop's algorithm, higher than 5% consumer risk was observed only with either unbalanced study design or with additional regulatory requirements. The improved Exact algorithms compare favorably with the alternative procedures. They are based on the bias correction method of Hedges. The recognition that the scaled difference statistics is measured with bias has important practical implications when results of pilot bioequivalence studies are evaluated and, at the same time, calls for the revision of the statistical theory of RSABE and its related methods.     

Sample size requirement in analytical studies for similarity assessment

ABSTRACT

For the assessment of biosimilar products, the FDA recommends a stepwise approach for obtaining the totality-of-the-evidence for assessing biosimilarity between a proposed biosimilar product and its corresponding innovative biologic product. The stepwise approach starts with analytical studies for assessing similarity in critical quality attributes (CQAs), which are relevant to clinical outcomes at various stages of the manufacturing process. For CQAs that are the most relevant to clinical outcomes, the FDA requires an equivalence test be performed for similarity assessment based on an equivalence acceptance criterion (EAC) that is obtained using a single test value of some selected reference lots. In practice, we often have extremely imbalanced numbers of reference and test lots available for the establishment of EAC. In this case, to assist the sponsors, the FDA proposed an idea for determining the number of reference lots and the number of test lots required in order not to have imbalanced sample sizes when establishing EAC for the equivalence test based on extensive simulation studies. Along this line, this article not only provides statistical justification of Dong, Tsong, and Weng’s proposal, but also proposes an alternative method for sample size requirement for the Tier 1 equivalence test.