Issue Information
Abstract
No abstract is available for this article. (Source: Pharmaceutical Statistics)
Source: Pharmaceutical Statistics - July 14, 2015 Category: Statistics Tags: Issue Information Source Type: research
Bayesian adaptive dose‐escalation procedures for binary and continuous responses utilizing a gain function
One of the main aims of early phase clinical trials is to identify a safe dose with an indication of therapeutic benefit to administer to subjects in further studies. Ideally therefore, dose‐limiting events (DLEs) and responses indicative of efficacy should be considered in the dose‐escalation procedure. Several methods have been suggested for incorporating both DLEs and efficacy responses in early phase dose‐escalation trials. In this paper, we describe and evaluate a Bayesian adaptive approach based on one binary response (occurrence of a DLE) and one continuous response (a measure of potential efficacy) per subjec...
Source: Pharmaceutical Statistics - July 1, 2015 Category: Statistics Authors: Wai Yin Yeung, John Whitehead, Bruno Reigner, Ulrich Beyer, Cheikh Diack, Thomas Jaki Tags: Main Paper Source Type: research
Choice of estimand and analysis methods in diabetes trials with rescue medication
The analysis of clinical trials aiming to show symptomatic benefits is often complicated by the ethical requirement for rescue medication when the disease state of patients worsens. In type 2 diabetes trials, patients receive glucose‐lowering rescue medications continuously for the remaining trial duration, if one of several markers of glycemic control exceeds pre‐specified thresholds. This may mask differences in glycemic values between treatment groups, because it will occur more frequently in less effective treatment groups. Traditionally, the last pre‐rescue medication value was carried forward and analyzed as th...
Source: Pharmaceutical Statistics - July 1, 2015 Category: Statistics Authors: Björn Holzhauer, Mouna Akacha, Georgina Bermann Tags: Main Paper Source Type: research
Bayesian inference in two‐arm trials using relative belief ratios
Various methodologies proposed for some inference problems associated with two‐arm trails are known to suffer from difficulties, as documented in Senn (2001). We propose an alternative Bayesian approach to these problems that deals with these difficulties through providing an explicit measure of statistical evidence and the strength of this evidence. Bayesian methods are often criticized for their intrinsic subjectivity. We show how these concerns can be dealt with through assessing the bias induced by a prior model checking and checking for prior‐data conflict. Copyright © 2015 John Wiley & Sons, Ltd. (Source: Ph...
Source: Pharmaceutical Statistics - July 1, 2015 Category: Statistics Authors: Saman Muthukumarana, Michael Evans Tags: Main Paper Source Type: research
Bioassay case study applying the maximin D‐optimal design algorithm to the four‐parameter logistic model
Cell‐based potency assays play an important role in the characterization of biopharmaceuticals but they can be challenging to develop in part because of greater inherent variability than other analytical methods. Our objective is to select concentrations on a dose–response curve that will enhance assay robustness. We apply the maximin D‐optimal design concept to the four‐parameter logistic (4PL) model and then derive and compute the maximin D‐optimal design for a challenging bioassay using curves representative of assay variation. The selected concentration points from this ‘best worst case’ design adequately...
Source: Pharmaceutical Statistics - July 1, 2015 Category: Statistics Authors: Todd Coffey Tags: Main Paper Source Type: research
A powerful test for Balaam's design
In this study, we develop a new estimator of the treatment effect and a new test statistic using the estimator. The aim is to improve the statistical inference in Balaam's design. Simulation studies indicate that the type I error of the proposed test is well controlled, and that the test is more powerful and has more suitable characteristics than other existing tests when interactions are substantial. The proposed test is also applied to analyze a real dataset. Copyright © 2015 John Wiley & Sons, Ltd. (Source: Pharmaceutical Statistics)
Source: Pharmaceutical Statistics - July 1, 2015 Category: Statistics Authors: Joji Mori, Yutaka Kano Tags: Main Paper Source Type: research
Short notes on maximum likelihood inference for control‐based pattern‐mixture models
A likelihood‐based analytical approach has been proposed for the control‐based pattern‐mixture model and its extension. In this note, we derive equivalent but simpler analytical expressions for the treatment effect and its variance for these control‐based pattern mixture models. Our formulae are easier to use and interpret. An application of our formulae to an antidepressant trial is provided, in which the likelihood‐based analysis is compared with the multiple imputation approach. Copyright © 2015 John Wiley & Sons, Ltd. (Source: Pharmaceutical Statistics)
Source: Pharmaceutical Statistics - July 1, 2015 Category: Statistics Authors: Yongqiang Tang Tags: Main Paper Source Type: research
Carryover negligibility and relevance in bioequivalence studies
The carryover effect is a recurring issue in the pharmaceutical field. It may strongly influence the final outcome of an average bioequivalence study. Testing a null hypothesis of zero carryover is useless: not rejecting it does not guarantee the non‐existence of carryover, and rejecting it is not informative of the true degree of carryover and its influence on the validity of the final outcome of the bioequivalence study. We propose a more consistent approach: even if some carryover is present, is it enough to seriously distort the study conclusions or is it negligible? This is the central aim of this paper, which focus...
Source: Pharmaceutical Statistics - July 1, 2015 Category: Statistics Authors: Jordi Ocaña, Maria P. Sanchez O, Josep L. Carrasco Tags: Main Paper Source Type: research
Bayesian response adaptive randomization using longitudinal outcomes
The response adaptive randomization (RAR) method is used to increase the number of patients assigned to more efficacious treatment arms in clinical trials. In many trials evaluating longitudinal patient outcomes, RAR methods based only on the final measurement may not benefit significantly from RAR because of its delayed initiation. We propose a Bayesian RAR method to improve RAR performance by accounting for longitudinal patient outcomes (longitudinal RAR). We use a Bayesian linear mixed effects model to analyze longitudinal continuous patient outcomes for calculating a patient allocation probability. In addition, we aim ...
Source: Pharmaceutical Statistics - June 23, 2015 Category: Statistics Authors: Tomoyoshi Hatayama, Satoshi Morita, Kentaro Sakamaki Tags: Main Paper Source Type: research
Structured Benefit –risk assessment: a review of key publications and initiatives on frameworks and methodologies
Conclusions
This 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 14, 2015 Category: Statistics Authors: Shahrul Mt ‐Isa, Mario Ouwens, Veronique Robert, Martin Gebel, Alexander Schacht, Ian Hirsch Tags: Literature Review Source Type: research
Issue Information
No abstract is available for this article. (Source: Pharmaceutical Statistics)
Source: Pharmaceutical Statistics - May 12, 2015 Category: Statistics Tags: Issue Information Source Type: research
Flexible modelling of simultaneously interval censored and truncated time‐to‐event data
This paper deals with the analysis of data from a HET‐CAMVT experiment. From a statistical perspective, such data yield many challenges. First of all, the data are typically time‐to‐event like data, which are at the same time interval censored and right truncated. In addition, one has to cope with overdispersion as well as clustering. Traditional analysis approaches ignore overdispersion and clustering and summarize the data into a continuous score that can be analysed using simple linear models. In this paper, a novel combined frailty model is developed that simultaneously captures all of the aforementioned statisti...
Source: Pharmaceutical Statistics - May 7, 2015 Category: Statistics Authors: Sammy Chebon, Christel Faes, Ann De Smedt, Helena Geys Tags: Main Paper Source Type: research
Risk patterns in drug safety study using relative times by accelerated failure time models when proportional hazards assumption is questionable: an illustrative case study of cancer risk of patients on glucose‐lowering therapies
Observational drug safety studies may be susceptible to confounding or protopathic bias. This bias may cause a spurious relationship between drug exposure and adverse side effect when none exists and may lead to unwarranted safety alerts. The spurious relationship may manifest itself through substantially different risk levels between exposure groups at the start of follow‐up when exposure is deemed too short to have any plausible biological effect of the drug. The restrictive proportional hazards assumption with its arbitrary choice of baseline hazard function renders the commonly used Cox proportional hazards model of ...
Source: Pharmaceutical Statistics - May 1, 2015 Category: Statistics Authors: Edmond S.‐W. Ng, Olaf H. Klungel, Rolf H. H. Groenwold, Tjeerd‐Pieter Staa Tags: Main Paper Source Type: research
A temporal correlation function for the association between patient‐reported outcome and clinical endpoints
For clinical trials with multiple endpoints, the primary interest is usually to evaluate the relationship of these endpoints and treatment interventions. Studying the correlation of two clinical trial endpoints can also be of interests. For example, the association between patient‐reported outcome and clinically assessed endpoint could answer important research questions and also generate interesting hypothesis for future research. However, it is not straightforward to quantify such association. In this article, we proposed a multiple event approach to profile such association with a temporal correlation function, visual...
Source: Pharmaceutical Statistics - May 1, 2015 Category: Statistics Authors: Qi Gong, Liang Fang Tags: Main Paper Source Type: research
Characterization of dose‐response for count data using a generalized MCP‐Mod approach in an adaptive dose‐ranging trial
We present the results of an adaptive model‐based dose‐ranging trial in multiple sclerosis that motivated this research and was conducted using the presented methodology. Copyright © 2015 John Wiley & Sons, Ltd. (Source: Pharmaceutical Statistics)
Source: Pharmaceutical Statistics - May 1, 2015 Category: Statistics Authors: Francois Mercier, Bjoern Bornkamp, David Ohlssen, Erik Wallstroem Tags: Main Paper Source Type: research
