Non‐inferiority and networks: inferring efficacy from a web of data
In the absence of placebo‐controlled trials, the efficacy of a test treatment can be alternatively examined by showing its non‐inferiority to an active control; that is, the test treatment is not worse than the active control by a pre‐specified margin. The margin is based on the effect of the active control over placebo in historical studies. In other words, the non‐inferiority setup involves a network of direct and indirect comparisons between test treatment, active controls, and placebo. Given this framework, we consider a Bayesian network meta‐analysis that models the uncertainty and heterogeneity of the histo...
Source: Pharmaceutical Statistics - November 1, 2015 Category: Statistics Authors: Junjing Lin, Margaret Gamalo‐Siebers, Ram Tiwari Tags: Main Paper Source Type: research
A visualization method measuring the performance of biomarkers for guiding treatment decisions
Biomarkers that predict efficacy and safety for a given drug therapy become increasingly important for treatment strategy and drug evaluation in personalized medicine. Methodology for appropriately identifying and validating such biomarkers is critically needed, although it is very challenging to develop, especially in trials of terminal diseases with survival endpoints. The marker‐by‐treatment predictiveness curve serves this need by visualizing the treatment effect on survival as a function of biomarker for each treatment. In this article, we propose the weighted predictiveness curve (WPC). Based on the nature of the...
Source: Pharmaceutical Statistics - November 1, 2015 Category: Statistics Authors: Hui Yang, Rui Tang, Mike Hale, Jing Huang Tags: Main Paper Source Type: research
Do single‐arm trials have a role in drug development plans incorporating randomised trials?
Often, single‐arm trials are used in phase II to gather the first evidence of an oncological drug's efficacy, with drug activity determined through tumour response using the RECIST criterion. Provided the null hypothesis of ‘insufficient drug activity’ is rejected, the next step could be a randomised two‐arm trial. However, single‐arm trials may provide a biased treatment effect because of patient selection, and thus, this development plan may not be an efficient use of resources. Therefore, we compare the performance of development plans consisting of single‐arm trials followed by randomised two‐arm trials w...
Source: Pharmaceutical Statistics - November 1, 2015 Category: Statistics Authors: Michael J. Grayling, Adrian P. Mander Tags: Main Paper Source Type: research
Practical guide to sample size calculations: non‐inferiority and equivalence trials
A sample size justification is a vital part of any trial design. However, estimating the number of participants required to give a meaningful result is not always straightforward. A number of components are required to facilitate a suitable sample size calculation. In this paper, the steps for conducting sample size calculations for non‐inferiority and equivalence trials are summarised. Practical advice and examples are provided that illustrate how to carry out the calculations by hand and using the app SampSize. Copyright © 2015 John Wiley & Sons, Ltd. (Source: Pharmaceutical Statistics)
Source: Pharmaceutical Statistics - November 1, 2015 Category: Statistics Authors: Laura Flight, Steven A. Julious Tags: Teacher's Corner Source Type: research
Practical guide to sample size calculations: an introduction
A sample size justification is a vital step when designing any trial. However, estimating the number of participants required to give a meaningful result is not always straightforward. A number of components are required to facilitate a suitable sample size calculation. In this paper, the general steps are summarised for conducting sample size calculations with practical advice and guidance on how to utilise the app SampSize. Copyright © 2015 John Wiley & Sons, Ltd. (Source: Pharmaceutical Statistics)
Source: Pharmaceutical Statistics - November 1, 2015 Category: Statistics Authors: Laura Flight, Steven A. Julious Tags: Teacher's Corner Source Type: research
Addressing potential prior‐data conflict when using informative priors in proof‐of‐concept studies
Bayesian methods are increasingly used in proof‐of‐concept studies. An important benefit of these methods is the potential to use informative priors, thereby reducing sample size. This is particularly relevant for treatment arms where there is a substantial amount of historical information such as placebo and active comparators. One issue with using an informative prior is the possibility of a mismatch between the informative prior and the observed data, referred to as prior‐data conflict. We focus on two methods for dealing with this: a testing approach and a mixture prior approach. The testing approach assesses pri...
Source: Pharmaceutical Statistics - November 1, 2015 Category: Statistics Authors: Timothy Mutsvari, Dominique Tytgat, Rosalind Walley Tags: Main Paper Source Type: research
Teaching examples for the design of experiments: geographical sensitivity and the self‐fulfilling prophecy
We describe two, simple, two‐dimensional spaces. These two spaces give rise to, and at the same time appear to generate supporting data for, scientific intuitions that are deeply flawed or wholly incorrect. We find these spaces useful in unfreezing scientific thinking and challenging the misplaced confidence in scientific intuition. Copyright © 2015 John Wiley & Sons, Ltd. (Source: Pharmaceutical Statistics)
Source: Pharmaceutical Statistics - November 1, 2015 Category: Statistics Authors: Dennis W. Lendrem, B. Clare Lendrem, Ruth Rowland‐Jones, Fabio D'Agostino, Matt Linsley, Martin R. Owen, John D. Isaacs Tags: Teacher's Corner Source Type: research
Sensitivity analyses for partially observed recurrent event data
Recurrent events involve the occurrences of the same type of event repeatedly over time and are commonly encountered in longitudinal studies. Examples include seizures in epileptic studies or occurrence of cancer tumors. In such studies, interest lies in the number of events that occur over a fixed period of time. One considerable challenge in analyzing such data arises when a large proportion of patients discontinues before the end of the study, for example, because of adverse events, leading to partially observed data. In this situation, data are often modeled using a negative binomial distribution with time‐in‐study...
Source: Pharmaceutical Statistics - November 1, 2015 Category: Statistics Authors: Mouna Akacha, Emmanuel O. Ogundimu Tags: Main Paper Source Type: research
Model free audit methodology for bias evaluation of tumour progression in oncology
Many oncology studies incorporate a blinded independent central review (BICR) to make an assessment of the integrity of the primary endpoint, progression free survival. Recently, it has been suggested that, in order to assess the potential for bias amongst investigators, a BICR amongst only a sample of patients could be performed; if evidence of bias is detected, according to a predefined threshold, the BICR is then assessed in all patients, otherwise, it is concluded that the sample was sufficient to rule out meaningful levels of bias. In this paper, we present an approach that adapts a method originally created for defin...
Source: Pharmaceutical Statistics - October 5, 2015 Category: Statistics Authors: Andrew Stone, Euan Macpherson, Ann Smith, Christopher Jennison Tags: Main Paper Source Type: research
Issue Information
Abstract
No abstract is available for this article. (Source: Pharmaceutical Statistics)
Source: Pharmaceutical Statistics - September 21, 2015 Category: Statistics Tags: Issue Information Source Type: research
Adaptive truncated weighting for improving marginal structural model estimation of treatment effects informally censored by subsequent therapy
Randomized clinical trials are designed to estimate the direct effect of a treatment by randomly assigning patients to receive either treatment or control. However, in some trials, patients who discontinued their initial randomized treatment are allowed to switch to another treatment. Therefore, the direct treatment effect of interest may be confounded by subsequent treatment. Moreover, the decision on whether to initiate a second‐line treatment is typically made based on time‐dependent factors that may be affected by prior treatment history. Due to these time‐dependent confounders, traditional time‐dependent Cox m...
Source: Pharmaceutical Statistics - September 1, 2015 Category: Statistics Authors: Xiaofei Bai, Jingyi Liu, Li Li, Douglas Faries Tags: Main Paper Source Type: research
Sample size planning for phase II trials based on success probabilities for phase III
We present an approach for planning a phase II trial in a time‐to‐event setting that considers the whole phase II/III clinical development programme. We derive stopping boundaries after phase II that minimise the number of events under side conditions for the conditional probabilities of correct go/no‐go decision after phase II as well as the conditional success probabilities for phase III. In addition, we give general recommendations for the choice of phase II sample size. Our simulations show that unconditional probabilities of go/no‐go decision as well as the unconditional success probabilities for phase III are...
Source: Pharmaceutical Statistics - September 1, 2015 Category: Statistics Authors: Heiko Götte, Armin Schüler, Marietta Kirchner, Meinhard Kieser Tags: Main Paper Source Type: research
A Bayesian adaptive blinded sample size adjustment method for risk differences
Adaptive sample size adjustment (SSA) for clinical trials consists of examining early subsets of on trial data to adjust estimates of sample size requirements. Blinded SSA is often preferred over unblinded SSA because it obviates many logistical complications of the latter and generally introduces less bias. On the other hand, current blinded SSA methods for binary data offer little to no new information about the treatment effect, ignore uncertainties associated with the population treatment proportions, and/or depend on enhanced randomization schemes that risk partial unblinding. I propose an innovative blinded SSA metho...
Source: Pharmaceutical Statistics - September 1, 2015 Category: Statistics Authors: Andrew Montgomery Hartley Tags: Main Paper Source Type: research
Optimal composite scores for longitudinal clinical trials under the linear mixed effects model
Clinical trials of chronic, progressive conditions use rate of change on continuous measures as the primary outcome measure, with slowing of progression on the measure as evidence of clinical efficacy. For clinical trials with a single prespecified primary endpoint, it is important to choose an endpoint with the best signal‐to‐noise properties to optimize statistical power to detect a treatment effect. Composite endpoints composed of a linear weighted average of candidate outcome measures have also been proposed. Composites constructed as simple sums or averages of component tests, as well as composites constructed usi...
Source: Pharmaceutical Statistics - July 30, 2015 Category: Statistics Authors: M. Colin Ard, Nandini Raghavan, Steven D. Edland Tags: Main Paper Source Type: research
Bias and precision of measures of survival gain from right‐censored data
In cost‐effectiveness analyses of drugs or health technologies, estimates of life years saved or quality‐adjusted life years saved are required. Randomised controlled trials can provide an estimate of the average treatment effect; for survival data, the treatment effect is the difference in mean survival. However, typically not all patients will have reached the endpoint of interest at the close‐out of a trial, making it difficult to estimate the difference in mean survival. In this situation, it is common to report the more readily estimable difference in median survival. Alternative approaches to estimating the mea...
Source: Pharmaceutical Statistics - July 27, 2015 Category: Statistics Authors: Karen E. Lamb, Elizabeth J. Williamson, Michael Coory, John B. Carlin Tags: Main Paper Source Type: research
