Trimmed means for symptom trials with dropouts
This article is a U.S. Government work and is in the public domain in the USA (Source: Pharmaceutical Statistics)
Source: Pharmaceutical Statistics - August 14, 2016 Category: Statistics Authors: Thomas Permutt, Feng Li Tags: Special Issue Paper Source Type: research
Model averaging inconcentration –QT analyses
This article describes how a frequentist model averaging approach can be used for concentration–QT analyses in the context of thorough QTc studies. Based on simulations, we have concluded that starting from three candidate model families (linear, exponential, and Emax) the model averaging approach leads to treatment effect estimates that are quite robust with respect to the control of the type I error in nearly all simulated scenarios; in particular, with the model averaging approach, the type I error appears less sensitive to model misspecification than the widely used linear model. We noticed also few differences in te...
Source: Pharmaceutical Statistics - August 4, 2016 Category: Statistics Authors: Bernard S ébastien, David Hoffman, Clémence Rigaux, Franck Pellissier, Jérôme Msihid Tags: Main Paper Source Type: research
Choosing estimands in clinical trials with missing data
Recent research has fostered new guidance on preventing and treating missing data. Consensus exists that clear objectives should be defined along with the causal estimands; trial design and conduct should maximize adherence to the protocol specified interventions; and a sensible primary analysis should be used along with plausible sensitivity analyses. Two general categories of estimands are effects of the drug as actually taken (de facto, effectiveness) and effects of the drug if taken as directed (de jure, efficacy). Motivated by examples, we argue that no single estimand is likely to meet the needs of all stakeholders a...
Source: Pharmaceutical Statistics - August 4, 2016 Category: Statistics Authors: Craig Mallinckrodt, Geert Molenberghs, Suchitrita Rathmann Tags: Main Paper Source Type: research
A generalized analytic solution to the win ratio to analyze a composite endpoint considering the clinical importance order among components
A composite endpoint consists of multiple endpoints combined in one outcome. It is frequently used as the primary endpoint in randomized clinical trials. There are two main disadvantages associated with the use of composite endpoints: a) in conventional analyses, all components are treated equally important; and b) in time‐to‐event analyses, the first event considered may not be the most important component. Recently Pocock et al. (2012) introduced the win ratio method to address these disadvantages. This method has two alternative approaches: the matched pair approach and the unmatched pair approach. In the unmatched ...
Source: Pharmaceutical Statistics - August 1, 2016 Category: Statistics Authors: Gaohong Dong, Di Li, Steffen Ballerstedt, Marc Vandemeulebroecke Tags: Main Paper Source Type: research
Issue Information
Abstract
No abstract is available for this article. (Source: Pharmaceutical Statistics)
Source: Pharmaceutical Statistics - July 12, 2016 Category: Statistics Tags: Issue Information Source Type: research
Precise definitions of some terminology for longitudinal clinical trials: subjects, patient populations, analysis sets, intention to treat, and related terms
Biostatisticians recognize the importance of precise definitions of technical terms in randomized controlled clinical trial (RCCT) protocols, statistical analysis plans, and so on, in part because definitions are a foundation for subsequent actions. Imprecise definitions can be a source of controversies about appropriate statistical methods, interpretation of results, and extrapolations to larger populations. This paper presents precise definitions of some familiar terms and definitions of some new terms, some perhaps controversial. The glossary contains definitions that can be copied into a protocol, statistical analysis ...
Source: Pharmaceutical Statistics - June 30, 2016 Category: Statistics Authors: Ronald W. Helms Tags: Main Paper Source Type: research
Simulation ‐based sample‐sizing and power calculations in logistic regression with partial prior information
There have been many approximations developed for sample sizing of a logistic regression model with a single normally‐distributed stimulus. Despite this, it has been recognised that there is no consensus as to the best method. In pharmaceutical drug development, simulation provides a powerful tool to characterise the operating characteristics of complex adaptive designs and is an ideal method for determining the sample size for such a problem. In this paper, we address some issues associated with applying simulation to determine the sample size for a given power in the context of logistic regression. These include effici...
Source: Pharmaceutical Statistics - June 30, 2016 Category: Statistics Authors: Andrew P. Grieve, Shah ‐Jalal Sarker Tags: Main Paper Source Type: research
A novel approach to estimation of the time to biomarker threshold: applications to HIV
We present an application to human immunodeficiency virus‐positive individuals from a seroprevalent cohort in Durban, South Africa. Two thresholds are examined, and 95% bootstrap confidence intervals are presented for the estimated time to threshold. Sensitivity analysis revealed that results are robust to truncation of the series and variation in the number of visits considered for most patients. Caution should be exercised when interpreting the estimated times for patients who exhibit very slow rates of decline and patients who have less than three measurements. We also discuss the relevance of the methodology to the s...
Source: Pharmaceutical Statistics - June 30, 2016 Category: Statistics Authors: Tarylee Reddy, Geert Molenberghs, Edmund Njeru Njagi, Marc Aerts Tags: Main Paper Source Type: research
Randomized phase II cancer clinical trials
(Source: Pharmaceutical Statistics)
Source: Pharmaceutical Statistics - June 30, 2016 Category: Statistics Authors: Emma Yu Wang Tags: Book Review Source Type: research
Dynamical Biostatistical Models
(Source: Pharmaceutical Statistics)
Source: Pharmaceutical Statistics - June 30, 2016 Category: Statistics Authors: Jixian Wang Tags: Book Review Source Type: research
Generalized optimal design for two ‐arm, randomized phase II clinical trials with endpoints from the exponential dispersion family
For two‐arm randomized phase II clinical trials, previous literature proposed an optimal design that minimizes the total sample sizes subject to multiple constraints on the standard errors of the estimated event rates and their difference. The original design is limited to trials with dichotomous endpoints. This paper extends the original approach to be applicable to phase II clinical trials with endpoints from the exponential dispersion family distributions. The proposed optimal design minimizes the total sample sizes needed to provide estimates of population means of both arms and their difference with pre‐specified ...
Source: Pharmaceutical Statistics - June 30, 2016 Category: Statistics Authors: Wei Jiang, Jonathan D. Mahnken, Jianghua He, Matthew S. Mayo Tags: Main Paper Source Type: research
Model averaging in concentration –QT analyses
This article describes how a frequentist model averaging approach can be used for concentration–QT analyses in the context of thorough QTc studies. Based on simulations, we have concluded that starting from three candidate model families (linear, exponential, and Emax) the model averaging approach leads to treatment effect estimates that are quite robust with respect to the control of the type I error in nearly all simulated scenarios; in particular, with the model averaging approach, the type I error appears less sensitive to model misspecification than the widely used linear model. We noticed also few differences in te...
Source: Pharmaceutical Statistics - June 30, 2016 Category: Statistics Authors: Bernard S ébastien, David Hoffman, Clémence Rigaux, Franck Pellissier, Jérôme Msihid Tags: Main Paper Source Type: research
Bayesian adaptive patient enrollment restriction to identify a sensitive subpopulation using a continuous biomarker in a randomized phase 2 trial
With the development of molecular targeted drugs, predictive biomarkers have played an increasingly important role in identifying patients who are likely to receive clinically meaningful benefits from experimental drugs (i.e., sensitive subpopulation) even in early clinical trials. For continuous biomarkers, such as mRNA levels, it is challenging to determine cutoff value for the sensitive subpopulation, and widely accepted study designs and statistical approaches are not currently available. In this paper, we propose the Bayesian adaptive patient enrollment restriction (BAPER) approach to identify the sensitive subpopulat...
Source: Pharmaceutical Statistics - June 30, 2016 Category: Statistics Authors: Shoichi Ohwada, Satoshi Morita Tags: Main Paper Source Type: research
Bayesian predictive power: choice of prior and some recommendations for its use as probability of success in drug development
Bayesian predictive power, the expectation of the power function with respect to a prior distribution for the true underlying effect size, is routinely used in drug development to quantify the probability of success of a clinical trial. Choosing the prior is crucial for the properties and interpretability of Bayesian predictive power. We review recommendations on the choice of prior for Bayesian predictive power and explore its features as a function of the prior. The density of power values induced by a given prior is derived analytically and its shape characterized. We find that for a typical clinical trial scenario, thi...
Source: Pharmaceutical Statistics - June 30, 2016 Category: Statistics Authors: Kaspar Rufibach, Hans Ulrich Burger, Markus Abt Tags: Main Paper Source Type: research
Group sequential monitoring based on the weighted log ‐rank test statistic with the Fleming–Harrington class of weights in cancer vaccine studies
In recent years, immunological science has evolved, and cancer vaccines are now approved and available for treating existing cancers. Because cancer vaccines require time to elicit an immune response, a delayed treatment effect is expected and is actually observed in drug approval studies. Accordingly, we propose the evaluation of survival endpoints by weighted log‐rank tests with the Fleming–Harrington class of weights. We consider group sequential monitoring, which allows early efficacy stopping, and determine a semiparametric information fraction for the Fleming–Harrington family of weights, which is necessary for...
Source: Pharmaceutical Statistics - June 28, 2016 Category: Statistics Authors: Takahiro Hasegawa Tags: Main Paper Source Type: research
