检索结果-内蒙古大学图书馆

Implementation of a phase 1 adaptive clinical trial in a treatment of type 2 diabetes

DRUG INFORMATION JOURNAL 2008年第5期42卷 455-465页

作者： Tibaldi, Fabian S. Beck, Benoit H. L., Jr. Bedding, Alun Eli Lilly & Co B-1348 Mont St Guibert Belgium GlaxoSmithKline Drug Dev Sci Biostat & Programming Dev Partners Harlow Essex England

Phase 1 clinical trials are in general conducted to determine the dose response of a new drug with respect to safety and tolerability (1). There is an increasing interest in reducing the trial time in order to have new and better drugs available to patients in a minimum amount of time. Adaptive designs for dose response have been intensively studied in recent years and have been considered as a novel approach to minimize the number of subjects or patients used in clinical trials and to reduce the risk of serious adverse events. Advantages and disadvantages of this kind of approach have been discussed in the literature and are not an object of discussion for this article (2). However, the implementation of this type of study is still challenging (3-7). This article focuses on the practical advantages of a Bayesian adaptive design and shows how it can be implemented using the R2WinBUGS freely downloadable software.

关键词： adaptive designs Bayesian models R software WinBUGS Markov chain Monte Carlo methods

来源：评论

学校读者我要写书评

暂无评论

Sample Size Calculation for Count Data in Comparative Clinical Trials with Nonuniform Patient Accrual and Early Dropout

引用

JOURNAL OF BIOPHARMACEUTICAL STATISTICS 2015年第1期25卷 1-15页

作者： Li, Huiling Wang, Lin Wei, Lynn Quan, Hui Harborside Financial Ctr Forest Res Inst Dept Stat Sci Jersey City NJ 07311 USA Sanofi Dept Biostat & Programming Bridgewater NJ USA

In clinical trials with counts of recurrent event data, it is often of particular interest to test whether the experimental treatment reduces the event rate in comparison with a control. The sample size calculation for such a trial often assumes fixed follow-up time for each patient. In many trials, however, we follow all patients for a predetermined follow-up time after the end of the accrual period, in which case the follow-up time is variable. This article provides methods for sample size calculation for clinical trials with ordinary Poisson count data and variable follow-up time allowing for nonuniform accrual and early dropouts. We also generalize the sample size formula to count data with overdispersion.

关键词： Overdispersion Nonuniform accrual Event rate Count data Sample size

来源：评论

学校读者我要写书评

暂无评论

"Who'll be the next in line?" The lung allocation score in patients with pulmonary arterial hypertension

引用

JOURNAL OF HEART AND LUNG TRANSPLANTATION 2013年第12期32卷 1165-1167页

作者： Miller, Dave P. Farber, Harrison W. ICON Clin Res Biostat & Programming San Francisco CA USA Boston Univ Sch Med Ctr Pulm Boston MA 02118 USA

来源：评论

学校读者我要写书评

暂无评论

On Analysis of Changes in Rates and Averaged Correlated Rates

引用

STATISTICS IN BIOPHARMACEUTICAL RESEARCH 2019年第3期11卷 252-265页

作者： Fan, Chunpeng Kuang, Chensheng Lu, Xin Zhang, Mei Sanofi US Inc Dept Biostat & Programming SS Corp Dr Bridgewater NJ 08807 USA Univ Wisconsin Dept Stat Madison WI 53706 USA

Changes in rates and averaged correlated rates are two common analyses for binary response data in longitudinal factorial studies. The traditional logistic regression for repeated measures can be used to obtain statistical inference for these two analyses, however, it has two potential deficiencies: first, the model may not converge, and second, the resulted statistical inference in terms of a linear contrast of odds ratios seems hard to be interpreted and understood by practitioners. The current article applies the methods in Fan and derives statistical inferential procedures for the analysis of changes in rates and averaged correlated rates in terms of the rate difference (RD), the odds ratio (OR), and the rate ratio (RR). Numerical assessments through simulation studies and examples were employed to demonstrate advantages of statistical inference in terms of the RD over the OR or the RR in different aspects including model convergence and interpretation of the results. The current article can be viewed as special case studies of the methods by Fan while it provides clearer and more direct comparisons of the methods when analyzing changes in rates and averaged correlated rates in longitudinal factorial studies.

关键词： GEE Generalized linear model MMRM Odds ratio Rate difference Rate ratio

来源：评论

学校读者我要写书评

暂无评论

Fully Liquid MenACWY-CRM Vaccine: Results from an Integrated Safety Analysis

引用

DRUG SAFETY 2023年第1期46卷 99-108页

作者： Singh, Puneet Vir Tiberi, Paola Di Domenico, Gabriele Filippo Romolini, Valerio Mzolo, Thembile Costantini, Marco Akhund, Tauseefullah Basile, Venere Lattanzi, Maria Pellegrini, Michele GSK Safety Evaluat & Risk Management Siena Italy GSK Biostat & Stat Programming Siena Italy GSK Biostat Amsterdam Netherlands GSK Clin Res & Dev Ctr Siena Italy GSK Global Clin Operat Siena Italy

Introduction The currently licensed quadrivalent MenACWY-CRM conjugate vaccine presentation consists of two vials (lyophilized MenA and liquid MenCWY) to be reconstituted before injection. A new fully liquid, single-vial formulation has been developed to simplify administration and prevent reconstitution errors. We present pooled safety data from two randomized, controlled, observer-blind phase 2b clinical trials, in which the fully liquid presentation was compared with the licensed presentation. Methods This is a post hoc analysis of two studies, in which safety data from participants aged 10-40 years who received one dose of either liquid MenACWY-CRM (1337 participants;MenACWY liquid group) or licensed MenACWY-CRM (1332 participants;MenACWY licensed group) were pooled. Frequencies were calculated for solicited adverse events (AEs) during 7 days post-vaccination and unsolicited AEs, including medically attended AEs and serious AEs (SAEs), during the 6-month safety follow-up period. Analysis results are presented by vaccine group, overall and by age category (10-17 and 18-40 years). Results Overall, AEs solicited for collection during the first 7 days after vaccination were reported by similar percentages of participants (69.2%, MenACWY liquid;68.2%, MenACWY licensed), and were generally mild/moderate in intensity. Solicited local AEs were reported by 46.0% of the MenACWY liquid group and 43.5% of the MenACWY licensed group and solicited systemic AEs by 55.2 and 54.1%, respectively. During the 6-month post-vaccination period, unsolicited AEs were reported by 32.2 and 31.2% of the MenACWY liquid group and MenACWY licensed group, respectively, and medically attended AEs by 18.6 and 17.3%, respectively. Overall, 14 participants in each group (1.0 and 1.1%, respectively) reported SAEs, none of which was considered vaccine-related by the investigator. The safety profiles of both MenACWY-CRM presentations were similar for each age group and overall. Conclusions This poole

关键词：

来源：评论

学校读者我要写书评

暂无评论

Consistency assessment with global and bridging development strategies in emerging markets

引用

CONTEMPORARY CLINICAL TRIALS 2013年第2期36卷 687-696页

作者： Li, Gang Chen, Josh Quan, Hui Yue Shentu Johnson & Johnson Co LifeScan W Chester PA 19380 USA Merck Rahway NJ 07065 USA Sanofi Biostat & Programming Bridgewater NJ 08807 USA

Global trial strategy with the participation of all major regions including countries from emerging markets surely increases new drug development efficiency. Nevertheless, there are circumstances in which some countries in emerging markets cannot join the original global trial. To evaluate the extrapolability of the original trial results to a new country, a bridging trial in the country has to be conducted. In this paper, we first evaluate the efficiency loss of the bridging trial strategy compared to that of the global trial strategy as a function of between-study variability from consistency assessment perspective. The provided evidence should encourage countries in emerging markets to make a greater effort to participate in the original global trial. We then discuss sample size requirement for desired assurance probability for consistency assessment based on various approaches for both global and bridging trial strategies. Examples are presented for numerical demonstration and comparisons. (C) 2013 Elsevier Inc. All rights reserved.

关键词： Consistency MRCT Global strategy Bridging strategy Assurance probability for consistency

来源：评论

学校读者我要写书评

暂无评论

A QUANTITATIVE METHOD FOR WEIGHT SELECTION IN SGDDP

引用

JOURNAL OF BIOPHARMACEUTICAL STATISTICS 2015年第6期25卷 1179-1189页

作者： Huang, Qin Chen, Gang Yuan, Zhilong Zhang, Ying Wenrich, Judy SFDA Off Biostat Ctr Drug Evaluat Beijing 100038 Peoples R China Johnson & Johnson Consumer Prod Inc Biostat & Programming Raritan NJ USA Penn State Univ Dept Stat State Coll PA USA

Ethnic factors pose major challenge to evaluating the treatment effect of a new drug in a targeted ethnic (TE) population in emerging regions based on the results from a multiregional clinical trial (MRCT). To address this issue with statistical rigor, Huang et al. (2012) proposed a new design of a simultaneous global drug development program (SGDDP) which used weighted Z tests to combine the information collected from the nontargeted ethnic (NTE) group in the MRCT with that from the TE group in both the MRCT and a simultaneously designed local clinical trial (LCT). An important and open question in the SGDDP design was how to downweight the information collected from the NTE population to reflect the potential impact of ethnic factors and ensure that the effect size for TE patients is clinically meaningful. In this paper, we will relate the weight selection for the SGDDP to Method 1 proposed in the Japanese regulatory guidance published by the Ministry of Health, Labour and Welfare (MHLW) in 2007. Method 1 is only applicable when true effect sizes are assumed to be equal for both TE and NTE groups. We modified the Method 1 formula for more general scenarios, and use it to develop a quantitative method of weight selection for the design of the SGDDP which, at the same time, also provides sufficient power to descriptively check the consistency of the effect size for TE patients to a clinically meaningful magnitude.

关键词： Bridging Ethnic factors Drug development MRCT Weighted Z test

来源：评论

学校读者我要写书评

暂无评论

Generalized semiparametric varying-coefficient model for longitudinal data with applications to adaptive treatment randomizations

引用

BIOMETRICS 2017年第2期73卷 441-451页

作者： Qi, Li Sun, Yanqing Gilbert, Peter B. Sanofi Biostat & Programming Bridgewater NJ 08807 USA Univ N Carolina Dept Math & Stat Charlotte NC 28223 USA Univ Washington Dept Biostat Seattle WA 98195 USA Fred Hutchinson Canc Res Ctr Seattle WA 98109 USA

This article investigates a generalized semiparametric varying-coefficient model for longitudinal data that can flexibly model three types of covariate effects: time-constant effects, time-varying effects, and covariate-varying effects. Different link functions can be selected to provide a rich family of models for longitudinal data. The model assumes that the time-varying effects are unspecified functions of time and the covariate-varying effects are parametric functions of an exposure variable specified up to a finite number of unknown parameters. The estimation procedure is developed using local linear smoothing and profile weighted least squares estimation techniques. Hypothesis testing procedures are developed to test the parametric functions of the covariate-varying effects. The asymptotic distributions of the proposed estimators are established. A working formula for bandwidth selection is discussed and examined through simulations. Our simulation study shows that the proposed methods have satisfactory finite sample performance. The proposed methods are applied to the ACTG 244 clinical trial of HIV infected patients being treated with Zidovudine to examine the effects of antiretroviral treatment switching before and after HIV develops the T215Y/F drug resistance mutation. Our analysis shows benefits of treatment switching to the combination therapies as compared to continuing with ZDV monotherapy before and after developing the 215-mutation.

关键词： ACTG 244 AIDS clinical trial Adaptive treatment randomization Covariate-varying effects Hypothesis tests Link function Longitudinal data analysis Profile weighted least squares

来源：评论

学校读者我要写书评

暂无评论

'Estimating a survival curve with unlinked entry and failure times'

引用

STATISTICS IN MEDICINE 2007年第27期26卷 5046-5046页

作者： Wu, Yujun Shih, Weichung J. Moore, Dirk E. Sanofi Aventis Biostat & Programming Bridgewater NJ 08807 USA Univ Med & Dent New Jersey Dept Biostat Piscataway NJ 08854 USA Univ Med & Dent New Jersey Dept Biometr Piscataway NJ 08854 USA

In monitoring a clinical trial or other observational study with a survivalendpoint, sometimes the numbers of patients entering and dying at each time point are presented, butthe connections between them are kept confidential. Hence, the exact time to failure or censoringfor each individual is missing. We refer to such a study monitoring table with missing pairinginformation between the entry and death times as a 'broken' survival data set. In this paper westudy the problem of estimating the survival distribution from a broken survival data set. We havedeveloped two methods, likelihood-based estimation and self-consistency estimation, to estimate thesurvival curve parametrically and empirically, respectively. We use simulations to study theproperties of these methods, and illustrate them with data from the STELLAR-3 trial.

关键词： survival aspects Personal failure estimation Preventive monitoring dataset

来源：评论

学校读者我要写书评

暂无评论

Confidence and Prediction in Linear Mixed Models: Do Not Concatenate the Random Effects. Application in an Assay Qualification Study

引用

STATISTICS IN BIOPHARMACEUTICAL RESEARCH 2020年第3期12卷 262-272页

作者： Francq, Bernard G. Lin, Dan Hoyer, Walter GSK TRD CMC Stat Sci Rixensart Belgium GSK Preclin & Res Biostat & Stat Programming Rixensart Belgium GSK TRD CMC Stat Sci Marburg Germany

In the pharmaceutical industry, all analytical methods must be shown to deliver unbiased and precise results. In an assay qualification or validation study, the trueness, accuracy, and intermediate precision are usually assessed by comparing the measured concentrations to their nominal levels. Trueness is assessed by using Confidence Intervals (CIs) of mean measured concentration, accuracy by Prediction Intervals (PIs) for a future measured concentration, and the intermediate precision by the total variance. ICH and USP guidelines alike request that all relevant sources of variability must be studied, for example, the effect of different technicians, the day-to-day variability or the use of multiple reagent lots. Those different random effects must be modeled as crossed, nested, or a combination of both;while concatenating them to simplify the model is often taken place. This article compares this simplified approach to a mixed model with the actual design. Our simulation study shows an under-estimation of the intermediate precision and, therefore, a substantial reduction of the CI and PI. The power for accuracy or trueness is consequently over-estimated when designing a new study. Two real datasets from assay validation study during vaccine development are used to illustrate the impact of such concatenation of random variables.

关键词： Accuracy Assay qualification Misspecified random effects Mixed model Power Prediction interval

来源：评论

学校读者我要写书评

暂无评论

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案：

请选择收藏分类：

通借通还

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：