Estimating time to disease progression comparing transition models and survival methods – an analysis of multiple sclerosis data.

This article reports an analysis that aims to quantify the effect of fingolimod, an oral treatment for relapsing remitting multiple sclerosis (MS), on disability progression. The standard approach utilizes survival analysis methods, which may be problematic for MS studies that assess disability at only a few time points and include as a cardinal feature both […]

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Model-Based Drug Development in Oncology: What’s Next?

Model-based estimates of tumor growth inhibition (TGI) metrics have the potential to enhance learning in early (phase II) clinical studies. They can be used as end points and biomarkers to predict treatment effect on clinical outcome measures—e.g., overall survival (OS)—and support phase II study design, end-of-phase II decisions, and phase III planning and execution. Efforts […]

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Using historical control information for the design and analysis of clinical trials with overdispersed count data

Results from clinical trials are never interpreted in isolation. Previous studies in a similar setting provide valuable information for designing a new trial. For the analysis, however, the use of trial-external information is challenging and therefore controversial, although it seems attractive from an ethical or efficiency perspective. Here, we consider the formal use of historical […]

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Siponimod for patients with relapsing-remitting multiple sclerosis (BOLD): an adaptive, dose-ranging, randomised, phase 2 study.

Siponimod is an oral selective modulator of sphingosine 1-phosphate receptor types 1 and type 5, with an elimination half-life leading to washout in 7 days. We aimed to determine the dose-response relation of siponimod in terms of its effects on brain MRI lesion activity and characterize safety and tolerability in patients with relapsing-remitting multiple sclerosis. […]

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Temporal profile of lymphocyte counts and relationship with infections with fingolimod therapy

Reduction in peripheral blood lymphocytes is an expected pharmacodynamic outcome of fingolimod therapy. The objective of this article is to evaluate lymphocyte dynamics during and after fingolimod therapy and assess the relationship between lymphocyte counts and infections. Lymphocyte counts and their relationship with infections were evaluated in three multiple sclerosis (MS) populations: (Group A) FREEDOMS […]

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Evaluation of Tumor Size Response Metrics to Predict Survival in Oncology Clinical Trials

Model-based drug development in oncology is still lagging despite a good momentum in the clinical pharmacology and pharmacometry community in the past few years. The failure rate of late-stage oncology studies is one of the highest across therapeutic areas. The modeling of the relationship between longitudinal tumor size and overall survival has been proposed to […]

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Dealing with excess of zeros in the statistical analysis of magnetic resonance imaging lesion count in multiple sclerosis

Lesion count observed on brain magnetic resonance imaging scan is a common end point in phase 2 clinical trials evaluating therapeutic treatment in relapsing remitting multiple sclerosis (MS). This paper compares the performances of Poisson, zeroinflated poisson (ZIP), negative binomial (NB), and zero-inflated NB (ZINB) mixed-effects regression models in fitting lesion count data in a […]

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Dealing with excess of zeros in the statistical analysis of magnetic resonance imaging lesion count in multiple sclerosis

Lesion count observed on brain magnetic resonance imaging scan is a common end point in phase 2 clinical trials evaluating therapeutic treatment in relapsing remitting multiple sclerosis (MS). This paper compares the performances of Poisson, zeroinflated poisson (ZIP), negative binomial (NB), and zero-inflated NB (ZINB) mixed-effects regression models in fitting lesion count data in a […]

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