Assessing the treatment effect in a randomized controlled trial with extensive non‐adherence: the EVOLVE trial
(Source: Pharmaceutical Statistics)
Source: Pharmaceutical Statistics - May 1, 2015 Category: Statistics Authors: Yumi Kubo, Lulu Ren Sterling, Patrick S. Parfrey, Karminder Gill, Kenneth W. Mahaffey, Ioanna Gioni, Marie‐Louise Trotman, Bastian Dehmel, Glenn M. Chertow Tags: Erratum Source Type: research
A Bayesian estimate of the concordance correlation coefficient with skewed data
In this study, we propose a Bayesian method for the estimation of the CCC of skewed data sets and compare it with the best method previously investigated. The proposed method has certain advantages. It tends to outperform the best method studied before when the variation of the data is mainly from the random subject effect instead of error. Furthermore, it allows for greater flexibility in application by enabling incorporation of missing data, confounding covariates, and replications, which was not considered previously. The superiority of this new approach is demonstrated using simulation as well as real‐life biomarker ...
Source: Pharmaceutical Statistics - May 1, 2015 Category: Statistics Authors: Dai Feng, Richard Baumgartner, Vladimir Svetnik Tags: Main Paper Source Type: research
Assessing switchability for biosimilar products: modelling approaches applied to children's growth
The present paper describes two statistical modelling approaches that have been developed to demonstrate switchability from the original recombinant human growth hormone (rhGH) formulation (Genotropin®) to a biosimilar product (Omnitrope®) in children suffering from growth hormone deficiency. Demonstrating switchability between rhGH products is challenging because the process of growth varies with the age of the child and across children. The first modelling approach aims at predicting individual height measured at several time‐points after switching to the biosimilar. The second modelling approach provides an estimate...
Source: Pharmaceutical Statistics - May 1, 2015 Category: Statistics Authors: Rossella Belleli, Roland Fisch, Didier Renard, Heike Woehling, Sandro Gsteiger Tags: Main Paper Source Type: research
Structured Benefit–risk assessment: a review of key publications and initiatives on frameworks and methodologies
ConclusionsThis article may serve as a starting point for discussions and to reach a mutual consensus for methodology selection in a particular situation. Regulators and pharmaceutical industry should continue to collaborate to develop and take forward BRA methodologies, and by clear communication develop a mutual understanding of the key issues. Copyright © 2015 John Wiley & Sons, Ltd. (Source: Pharmaceutical Statistics)
Source: Pharmaceutical Statistics - May 1, 2015 Category: Statistics Authors: Shahrul Mt‐Isa, Mario Ouwens, Veronique Robert, Martin Gebel, Alexander Schacht, Ian Hirsch Tags: Literature Review Source Type: research
Testing drug additivity based on monotherapies
Under the Loewe additivity, constant relative potency between two drugs is a sufficient condition for the two drugs to be additive. Implicit in this condition is that one drug acts like a dilution of the other. Geometrically, it means that the dose‐response curve of one drug is a copy of another that is shifted horizontally by a constant over the log‐dose axis. Such phenomenon is often referred to as parallelism. Thus, testing drug additivity is equivalent to the demonstration of parallelism between two dose‐response curves. Current methods used for testing parallelism are usually based on significance tests for diff...
Source: Pharmaceutical Statistics - May 1, 2015 Category: Statistics Authors: Harry Yang, Steven J. Novick, Wei Zhao Tags: Main Paper Source Type: research
To adjust or not to adjust for baseline when analyzing repeated binary responses? The case of complete data when treatment comparison at study end is of interest
The benefits of adjusting for baseline covariates are not as straightforward with repeated binary responses as with continuous response variables. Therefore, in this study, we compared different methods for analyzing repeated binary data through simulations when the outcome at the study endpoint is of interest. Methods compared included chi‐square, Fisher's exact test, covariate adjusted/unadjusted logistic regression (Adj.logit/Unadj.logit), covariate adjusted/unadjusted generalized estimating equations (Adj.GEE/Unadj.GEE), covariate adjusted/unadjusted generalized linear mixed model (Adj.GLMM/Unadj.GLMM). All these met...
Source: Pharmaceutical Statistics - April 10, 2015 Category: Statistics Authors: Honghua Jiang, Pandurang M. Kulkarni, Craig H. Mallinckrodt, Linda Shurzinske, Geert Molenberghs, Ilya Lipkovich Tags: Main Paper Source Type: research
Single‐arm phase II trial design under parametric cure models
The current practice of designing single‐arm phase II survival trials is limited under the exponential model. Trial design under the exponential model may not be appropriate when a portion of patients are cured. There is no literature available for designing single‐arm phase II trials under the parametric cure model. In this paper, a test statistic is proposed, and a sample size formula is derived for designing single‐arm phase II trials under a class of parametric cure models. Extensive simulations showed that the proposed test and sample size formula perform very well under different scenarios. Copyright © 2015 ...
Source: Pharmaceutical Statistics - April 1, 2015 Category: Statistics Authors: Jianrong Wu Tags: Main Paper Source Type: research
Letter to the editor by the authors of Exact Calculation of Power and Sample Size in Bioequivalence Studies Using Two One‐sided Tests, Pharmaceutical Statistics, DOI: 10.1002/pst.1666
This article reflects the views of the authors and should not be construed to be those of the US Food and Drug Administration. Copyright © 2015 John Wiley & Sons, Ltd. (Source: Pharmaceutical Statistics)
Source: Pharmaceutical Statistics - March 21, 2015 Category: Statistics Authors: Meiyu Shen, Estelle Russek‐Cohen, Eric V Slud Tags: Letter to the Editor Source Type: research
Issue Information
No abstract is available for this article. (Source: Pharmaceutical Statistics)
Source: Pharmaceutical Statistics - March 19, 2015 Category: Statistics Tags: Issue Information Source Type: research
A Phase I/II adaptive design for heterogeneous groups with application to a stereotactic body radiation therapy trial
Dose‐finding studies that aim to evaluate the safety of single agents are becoming less common, and advances in clinical research have complicated the paradigm of dose finding in oncology. A class of more complex problems, such as targeted agents, combination therapies and stratification of patients by clinical or genetic characteristics, has created the need to adapt early‐phase trial design to the specific type of drug being investigated and the corresponding endpoints. In this article, we describe the implementation of an adaptive design based on a continual reassessment method for heterogeneous groups, modified to ...
Source: Pharmaceutical Statistics - March 1, 2015 Category: Statistics Authors: Nolan A. Wages, Paul W. Read, Gina R. Petroni Tags: Main Paper Source Type: research
An alternative parameterization of Bayesian logistic hierarchical models for mixed treatment comparisons
Mixed treatment comparison (MTC) models rely on estimates of relative effectiveness from randomized clinical trials so as to respect randomization across treatment arms. This approach could potentially be simplified by an alternative parameterization of the way effectiveness is modeled. We introduce a treatment‐based parameterization of the MTC model that estimates outcomes on both the study and treatment levels. We compare the proposed model to the commonly used MTC models using a simulation study as well as three randomized clinical trial datasets from published systematic reviews comparing (i) treatments on bleeding a...
Source: Pharmaceutical Statistics - March 1, 2015 Category: Statistics Authors: Petros Pechlivanoglou, Fentaw Abegaz, Maarten J Postma, Ernst Wit Tags: Main Paper Source Type: research
Influenza vaccine efficacy trials: a simulation approach to understand failures from the past
The success of a seasonal influenza vaccine efficacy trial depends not only upon the design but also upon the annual epidemic characteristics. In this context, simulation methods are an essential tool in evaluating the performances of study designs under various circumstances. However, traditional methods for simulating time‐to‐event data are not suitable for the simulation of influenza vaccine efficacy trials because of the seasonality and heterogeneity of influenza epidemics. Instead, we propose a mathematical model parameterized with historical surveillance data, heterogeneous frailty among the subjects, survey‐ba...
Source: Pharmaceutical Statistics - March 1, 2015 Category: Statistics Authors: Anne Benoit, Catherine Legrand, Walthère Dewé Tags: Main Paper Source Type: research
Identification of drug‐induced toxicity biomarkers for treatment determination
Drug‐induced organ toxicity (DIOT) that leads to the removal of marketed drugs or termination of candidate drugs has been a leading concern for regulatory agencies and pharmaceutical companies. In safety studies, the genomic assays are conducted after the treatment so that drug‐induced adverse effects can occur. Two types of biomarkers are observed: biomarkers of susceptibility and biomarkers of response. This paper presents a statistical model to distinguish two types of biomarkers and procedures to identify susceptible subpopulations. The biomarkers identified are used to develop classification model to identify susc...
Source: Pharmaceutical Statistics - March 1, 2015 Category: Statistics Authors: Tzu‐Pin Lu, James J. Chen Tags: Main Paper Source Type: research
A novel test to compare two treatments based on endpoints involving both nonfatal and fatal events
In a clinical trial comparing two treatment groups, one commonly‐used endpoint is time to death. Another is time until the first nonfatal event (if there is one) or until death (if not). Both endpoints have drawbacks. The wrong choice may adversely affect the value of the study by impairing power if deaths are too few (with the first endpoint) or by lessening the role of mortality if not (with the second endpoint). We propose a compromise that provides a simple test based on the time to death if the patient has died or time since randomization augmented by an increment otherwise. The test applies the ordinary two‐sampl...
Source: Pharmaceutical Statistics - March 1, 2015 Category: Statistics Authors: Richard F. Potthoff, Susan Halabi Tags: Main Paper Source Type: research
Advantages of a wholly Bayesian approach to assessing efficacy in early drug development: a case study
This paper illustrates how the design and statistical analysis of the primary endpoint of a proof‐of‐concept study can be formulated within a Bayesian framework and is motivated by and illustrated with a Pfizer case study in chronic kidney disease. It is shown how decision criteria for success can be formulated, and how the study design can be assessed in relation to these, both using the traditional approach of probability of success conditional on the true treatment difference and also using Bayesian assurance and pre‐posterior probabilities. The case study illustrates how an informative prior on placebo response c...
Source: Pharmaceutical Statistics - March 1, 2015 Category: Statistics Authors: Rosalind J. Walley, Claire L. Smith, Jeremy D. Gale, Phil Woodward Tags: Main Paper Source Type: research
