Treatment effect quantification for time ‐to‐event endpoints–Estimands, analysis strategies, and beyond
A draft addendum to ICH E9 has been released for public consultation in August 2017. The addendum focuses on two topics particularly relevant for randomized confirmatory clinical trials: estimands and sensitivity analyses. The need to amend ICH E9 grew out of the realization of a lack of alignment between the objectives of a clinical trial stated in the protocol and the accompanying quantification of the “treatment effect” reported in a regulatory submission. We embed time‐to‐event endpoints in the estimand framework and discuss how the four estimand attributes described in the addendum apply to time‐to‐event e...
Source: Pharmaceutical Statistics - November 26, 2018 Category: Statistics Authors: Kaspar Rufibach Tags: MAIN PAPER Source Type: research
On estimands and the analysis of adverse events in the presence of varying follow ‐up times within the benefit assessment of therapies
The analysis of adverse events (AEs) is a key component in the assessment of a drug's safety profile. Inappropriate analysis methods may result in misleading conclusions about a therapy's safety and consequently its benefit ‐risk ratio. The statistical analysis of AEs is complicated by the fact that the follow‐up times can vary between the patients included in a clinical trial. This paper takes as its focus the analysis of AE data in the presence of varying follow‐up times within the benefit assessment of therape utic interventions. Instead of approaching this issue directly and solely from an analysis point of view,...
Source: Pharmaceutical Statistics - November 20, 2018 Category: Statistics Authors: Steffen Unkel,
Marjan Amiri,
Norbert Benda,
Jan Beyersmann,
Dietrich Knoerzer,
Katrin Kupas,
Frank Langer,
Friedhelm Leverkus,
Anja Loos,
Claudia Ose,
Tanja Proctor,
Claudia Schmoor,
Carsten Schwenke,
Guido Skipka,
Kristina Unnebrink,
Flori Tags: MAIN PAPER Source Type: research
Phase II trial design with growth modulation index as the primary endpoint
Molecularly targeted, genomic ‐driven, and immunotherapy‐based clinical trials continue to be advanced for the treatment of relapse or refractory cancer patients, where the growth modulation index (GMI) is often considered a primary endpoint of treatment efficacy. However, there little literature is available that considers the trial design with GMI as the primary endpoint. In this article, we derived a sample size formula for the score test under a log‐linear model of the GMI. Study designs using the derived sample size formula are illustrated under a bivariate exponential model, the Weibull frailty model, and the g...
Source: Pharmaceutical Statistics - November 20, 2018 Category: Statistics Authors: Jianrong Wu,
Li Chen,
Jing Wei,
Heidi Weiss,
Rachel W. Miller,
John L. Villano Tags: MAIN PAPER Source Type: research
Bayesian sample size determination for phase IIA clinical trials using historical data and semi ‐parametric prior's elicitation
SummaryThe Simon's two ‐stage design is the most commonly applied among multi‐stage designs in phase IIA clinical trials. It combines the sample sizes at the two stages in order to minimize either the expected or the maximum sample size.When the uncertainty about pre ‐trial beliefs on the expected or desired response rate is high, a Bayesian alternative should be considered since it allows to deal with the entire distribution of the parameter of interest in a more natural way.In this setting, a crucial issue is how to construct a distribution from the available summaries to use as a clinical prior in a Bayesian desig...
Source: Pharmaceutical Statistics - November 15, 2018 Category: Statistics Authors: Paola Berchialla,
Sarah Zohar,
Ileana Baldi Tags: MAIN PAPER Source Type: research
Issue Information
AbstractNo abstract is available for this article. (Source: Pharmaceutical Statistics)
Source: Pharmaceutical Statistics - November 12, 2018 Category: Statistics Tags: ISSUE INFORMATION Source Type: research
Calculation of confidence intervals for a finite population size
SummaryFor any estimate of response, confidence intervals are important as they help quantify a plausible range of values for the population response. However, there may be instances in clinical research when the population size is finite, but we wish to take a sample from the population and make inference from this sample.Instances where you can have a fixed population size include when undertaking a clinical audit of patient records or in a clinical trial a researcher could be checking for transcription errors against patient notes.In this paper, we describe how confidence interval calculations can be calculated for a fi...
Source: Pharmaceutical Statistics - November 8, 2018 Category: Statistics Authors: Steven A. Julious Tags: CONSULTANTS' FORUM Source Type: research
A simple test for the treatment effect in clinical trials with a sequential parallel comparison design and negative binomial outcomes
In placebo ‐controlled, double‐blinded, randomized clinical trials, the presence of placebo responders reduces the effect size for comparison of the active drug group with the placebo group. An attempt to resolve this problem is to use the sequential parallel comparison design (SPCD). Although there are SP CDs with dichotomous or continuous outcomes, an SPCD with negative binomial outcomes—with which investigators deal eg, in clinical trials involving multiple sclerosis, where the investigators are still concerned about the presence of placebo responders—has not yet been discussed. In this article , we propose a si...
Source: Pharmaceutical Statistics - November 8, 2018 Category: Statistics Authors: Gosuke Homma,
Takashi Daimon Tags: MAIN PAPER Source Type: research
Treatment policy estimands for recurrent event data using data collected after cessation of randomised treatment
SUMMARYIn the past, many clinical trials have withdrawn subjects from the study when they prematurely stopped their randomised treatment and have therefore only collected ‘on‐treatment’ data. Thus, analyses addressing a treatment policy estimand have been restricted to imputing missing data under assumptions drawn from these data only. Many confirmatory trials are now continuing to collect data from subjects in a study even after they have prematurely discontin ued study treatment as this event is irrelevant for the purposes of a treatment policy estimand. However, despite efforts to keep subjects in a trial, some wi...
Source: Pharmaceutical Statistics - November 8, 2018 Category: Statistics Authors: James H. Roger,
Daniel J. Bratton,
Bhabita Mayer,
Juan J. Abellan,
Oliver N. Keene Tags: MAIN PAPER Source Type: research
How can we make better graphs? An initiative to increase the graphical expertise and productivity of quantitative scientists
Pharmaceutical Statistics, EarlyView. (Source: Pharmaceutical Statistics)
Source: Pharmaceutical Statistics - October 31, 2018 Category: Statistics Authors: Marc Vandemeulebroecke,
Mark Baillie,
David Carr,
Linda Kanitra,
Alison Margolskee,
Andrew Wright,
Baldur Magnusson Source Type: research
Controlling type 1 error rate for sequential, bioequivalence studies with crossover designs
Pharmaceutical Statistics, EarlyView. (Source: Pharmaceutical Statistics)
Source: Pharmaceutical Statistics - October 29, 2018 Category: Statistics Authors: Hans E. Rasmussen,
Rick Ma,
Jessie J. Wang Source Type: research
Strategies for composite estimands in confirmatory clinical trials: Examples from trials in nasal polyps and steroid reduction
Pharmaceutical Statistics, EarlyView. (Source: Pharmaceutical Statistics)
Source: Pharmaceutical Statistics - October 29, 2018 Category: Statistics Authors: Oliver N. Keene Source Type: research
Lessons from meta ‐analyses of randomized clinical trials for analysis of distributed networks of observational databases
Pharmaceutical Statistics, EarlyView. (Source: Pharmaceutical Statistics)
Source: Pharmaceutical Statistics - October 26, 2018 Category: Statistics Authors: Andrew Bate,
Christy Chuang ‐Stein,
Andrew Roddam,
Byron Jones Source Type: research
Blinded continuous monitoring in clinical trials with recurrent event endpoints
Pharmaceutical Statistics, EarlyView. (Source: Pharmaceutical Statistics)
Source: Pharmaceutical Statistics - October 22, 2018 Category: Statistics Authors: Tim Friede,
Dieter A. H äring,
Heinz Schmidli Source Type: research
Applications of Bayesian statistical methodology to clinical trial design: A case study of a phase 2 trial with an interim futility assessment in patients with knee osteoarthritis
Pharmaceutical Statistics, EarlyView. (Source: Pharmaceutical Statistics)
Source: Pharmaceutical Statistics - October 15, 2018 Category: Statistics Authors: Claire L. Smith,
Yan Jin,
Eyas Raddad,
Terry A. McNearney,
Xiao Ni,
David Monteith,
Roger Brown,
Mark A. Deeg,
Thomas Schnitzer Source Type: research
A statistical method to convert published response rates into marginal distributions with an example application in psoriasis
Pharmaceutical Statistics, EarlyView. (Source: Pharmaceutical Statistics)
Source: Pharmaceutical Statistics - September 27, 2018 Category: Statistics Authors: Helmut Petto,
Ulrich Mrowietz,
Stefan Wilhelm,
Alexander Schacht Source Type: research
