Issue Information
Abstract
No abstract is available for this article. (Source: Pharmaceutical Statistics)
Source: Pharmaceutical Statistics - March 16, 2016 Category: Statistics Tags: Issue Information Source Type: research
An optimal stratified Simon two ‐stage design
In Phase II oncology trials, therapies are increasingly being evaluated for their effectiveness in specific populations of interest. Such targeted trials require designs that allow for stratification based on the participants' molecular characterisation. A targeted design proposed by Jones and Holmgren (JH) Jones CL, Holmgren E: ‘An adaptive Simon two‐stage design for phase 2 studies of targeted therapies’, Contemporary Clinical Trials 28 (2007) 654‐661.determines whether a drug only has activity in a disease sub‐population or in the wider disease population. Their adaptive design uses results from a single inter...
Source: Pharmaceutical Statistics - March 1, 2016 Category: Statistics Authors: Deepak Parashar, Jack Bowden, Colin Starr, Lorenz Wernisch, Adrian Mander Tags: Main Paper Source Type: research
Sensitivity to censored‐at‐random assumption in the analysis of time‐to‐event endpoints
Over the past years, significant progress has been made in developing statistically rigorous methods to implement clinically interpretable sensitivity analyses for assumptions about the missingness mechanism in clinical trials for continuous and (to a lesser extent) for binary or categorical endpoints. Studies with time‐to‐event outcomes have received much less attention. However, such studies can be similarly challenged with respect to the robustness and integrity of primary analysis conclusions when a substantial number of subjects withdraw from treatment prematurely prior to experiencing an event of interest. We dis...
Source: Pharmaceutical Statistics - March 1, 2016 Category: Statistics Authors: Ilya Lipkovich, Bohdana Ratitch, Michael O'Kelly Tags: Main Paper Source Type: research
Modelling PK/QT relationships from Phase I dose‐escalation trials for drug combinations and developing quantitative risk assessments of clinically relevant QT prolongations
In current industry practice, it is difficult to assess QT effects at potential therapeutic doses based on Phase I dose‐escalation trials in oncology due to data scarcity, particularly in combinations trials. In this paper, we propose to use dose‐concentration and concentration‐QT models jointly to model the exposures and effects of multiple drugs in combination. The fitted models then can be used to make early predictions for QT prolongation to aid choosing recommended dose combinations for further investigation. The models consider potential correlation between concentrations of test drugs and potential drug–drug...
Source: Pharmaceutical Statistics - March 1, 2016 Category: Statistics Authors: Karen Sinclair, Els Kinable, Kai Grosch, Jixian Wang Tags: Main Paper Source Type: research
Statistical issues in the analysis of adverse events in time‐to‐event data
The aim of this work is to shed some light on common issues in the statistical analysis of adverse events (AEs) in clinical trials, when the main outcome is a time‐to‐event endpoint. To begin, we show that AEs are always subject to competing risks. That is, the occurrence of a certain AE may be precluded by occurrence of the main time‐to‐event outcome or by occurrence of another (fatal) AE. This has raised concerns on ‘informative’ censoring. We show that, in general, neither simple proportions nor Kaplan–Meier estimates of AE occurrence should be used, but common survival techniques for hazards that censor t...
Source: Pharmaceutical Statistics - March 1, 2016 Category: Statistics Authors: Arthur Allignol, Jan Beyersmann, Claudia Schmoor Tags: Special Issue Paper Source Type: research
Statistical issues in the analysis of adverse events in time ‐to‐event data
The aim of this work is to shed some light on common issues in the statistical analysis of adverse events (AEs) in clinical trials, when the main outcome is a time‐to‐event endpoint. To begin, we show that AEs are always subject to competing risks. That is, the occurrence of a certain AE may be precluded by occurrence of the main time‐to‐event outcome or by occurrence of another (fatal) AE. This has raised concerns on ‘informative’ censoring. We show that, in general, neither simple proportions nor Kaplan–Meier estimates of AE occurrence should be used, but common survival techniques for hazards that censor t...
Source: Pharmaceutical Statistics - February 29, 2016 Category: Statistics Authors: Arthur Allignol, Jan Beyersmann, Claudia Schmoor Tags: Special Issue Paper Source Type: research
The analysis of incontinence episodes and other count data in patients with overactive bladder by Poisson and negative binomial regression
(Source: Pharmaceutical Statistics)
Source: Pharmaceutical Statistics - February 29, 2016 Category: Statistics Authors: R. Martina, R. Kay, R. van Maanen, A. Ridder Tags: Erratum Source Type: research
Why are two mistakes not worse than one? A proposal for controlling the expected number of false claims
Multiplicity is common in clinical studies and the current standard is to use the familywise error rate to ensure that the errors are kept at a prespecified level. In this paper, we will show that, in certain situations, familywise error rate control does not account for all errors made. To counteract this problem, we propose the use of the expected number of false claims (EFC). We will show that a (weighted) Bonferroni approach can be used to control the EFC, discuss how a study that uses the EFC can be powered for co‐primary, exchangeable, and hierarchical endpoints, and show how the weight for the weighted Bonferroni ...
Source: Pharmaceutical Statistics - February 29, 2016 Category: Statistics Authors: Thomas Jaki, Alice Parry Tags: Main Paper Source Type: research
A Bayesian hierarchical surrogate outcome model for multiple sclerosis
The development of novel therapies in multiple sclerosis (MS) is one area where a range of surrogate outcomes are used in various stages of clinical research. While the aim of treatments in MS is to prevent disability, a clinical trial for evaluating a drugs effect on disability progression would require a large sample of patients with many years of follow‐up. The early stage of MS is characterized by relapses. To reduce study size and duration, clinical relapses are accepted as primary endpoints in phase III trials. For phase II studies, the primary outcomes are typically lesion counts based on magnetic resonance imagin...
Source: Pharmaceutical Statistics - February 29, 2016 Category: Statistics Authors: Luca Pozzi, Heinz Schmidli, David I. Ohlssen Tags: Main Paper Source Type: research
Using Bayesian analysis in repeated preclinical in vivo studies for a more effective use of animals
We describe two case studies of animal models: the lipopolysaccharide‐induced cytokine release model used in inflammation and the novel object recognition model used to screen cognitive enhancers, both of which show the advantage of a Bayesian approach over the standard frequentist analysis. We conclude that using Bayesian methods in stable repeated in vivo studies can result in a more effective use of animals, either by reducing the total number of animals used or by increasing the precision of key treatment differences. This will lead to clearer results and supports the “3Rs initiative” to Refine, Reduce and Replac...
Source: Pharmaceutical Statistics - February 29, 2016 Category: Statistics Authors: Rosalind Walley, John Sherington, Joe Rastrick, Eric Detrait, Etienne Hanon, Gillian Watt Tags: Main Paper Source Type: research
Issue Information
Abstract
No abstract is available for this article. (Source: Pharmaceutical Statistics)
Source: Pharmaceutical Statistics - January 13, 2016 Category: Statistics Tags: Issue Information Source Type: research
A win ratio approach to comparing continuous non‐normal outcomes in clinical trials
Clinical trials are often designed to compare continuous non‐normal outcomes. The conventional statistical method for such a comparison is a non‐parametric Mann–Whitney test, which provides a P‐value for testing the hypothesis that the distributions of both treatment groups are identical, but does not provide a simple and straightforward estimate of treatment effect. For that, Hodges and Lehmann proposed estimating the shift parameter between two populations and its confidence interval (CI). However, such a shift parameter does not have a straightforward interpretation, and its CI contains zero in some cases when M...
Source: Pharmaceutical Statistics - January 1, 2016 Category: Statistics Authors: Duolao Wang, Stuart Pocock Tags: Main Paper Source Type: research
Empirical likelihood based detection procedure for change point in mean residual life functions under random censorship
The mean residual life (MRL) function is one of the basic parameters of interest in survival analysis that describes the expected remaining time of an individual after a certain age. The study of changes in the MRL function is practical and interesting because it may help us to identify some factors such as age and gender that may influence the remaining lifetimes of patients after receiving a certain surgery. In this paper, we propose a detection procedure based on the empirical likelihood for the changes in MRL functions with right censored data. Two real examples are also given: Veterans' administration lung cancer stud...
Source: Pharmaceutical Statistics - January 1, 2016 Category: Statistics Authors: Ying‐Ju Chen, Wei Ning, Arjun K. Gupta Tags: Main Paper Source Type: research
An optimal stratified Simon two‐stage design
In Phase II oncology trials, therapies are increasingly being evaluated for their effectiveness in specific populations of interest. Such targeted trials require designs that allow for stratification based on the participants' molecular characterisation. A targeted design proposed by Jones and Holmgren (JH) Jones CL, Holmgren E: ‘An adaptive Simon two‐stage design for phase 2 studies of targeted therapies’, Contemporary Clinical Trials 28 (2007) 654‐661.determines whether a drug only has activity in a disease sub‐population or in the wider disease population. Their adaptive design uses results from a single inter...
Source: Pharmaceutical Statistics - January 1, 2016 Category: Statistics Authors: Deepak Parashar, Jack Bowden, Colin Starr, Lorenz Wernisch, Adrian Mander Tags: Main Paper Source Type: research
Biometrical issues in the analysis of adverse events within the benefit assessment of drugs
The analysis of adverse events plays an important role in the benefit assessment of drugs. Consequently, results on adverse events are an integral part of reimbursement dossiers submitted by pharmaceutical companies to health policy decision‐makers. Methods applied in the analysis of adverse events commonly include simple standard methods for contingency tables. However, the results produced may be misleading if observations are censored at the time of discontinuation due to treatment switching or noncompliance, resulting in unequal follow‐up periods. In this paper, we present examples to show that the application of i...
Source: Pharmaceutical Statistics - January 1, 2016 Category: Statistics Authors: Ralf Bender, Lars Beckmann, Stefan Lange Tags: Special Issue Paper Source Type: research
