Partial Residual Plots as an Integrated Model Diagnostic Tool in Model-Based Meta-Analysis.

The use of partial residual plots (PRPs) was explored as a model diagnostic tool in Model-based Meta-Analysis (MBMA). Mathematical derivations illustrating the concepts were followed by an MBMA example using publicly available literature data of anti-depressive treatments with fluoxetine and venlafaxine. An E dose-response model was identified for venlafaxine while a constant drug effect combining all dose levels vs.

A method to estimate probability of disease and vaccine efficacy from clinical trial immunogenicity data.

Vaccine efficacy is often assessed by counting disease cases in a clinical trial. A new quantitative framework proposed here ("PoDBAY," Probability of Disease Bayesian Analysis), estimates vaccine efficacy (and confidence interval) using immune response biomarker data collected shortly after vaccination. Given a biomarker associated with protection, PoDBAY describes the relationship between biomarker and probability of disease as a sigmoid probability of disease ("PoD") curve.

Systematic Literature Review and Meta-Analysis of Response to First-Line Therapies for Advanced/Metastatic Urothelial Cancer Patients Who Are Cisplatin Ineligible.

Objective: The purpose of this systematic literature review (SLR) and meta-analysis was to compile the response of historic treatment options in first-line settings for patient populations who are cisplatin ineligible.

Materials And Methods: SLR was conducted to compile objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) of historic therapies for this population based on stringent criteria. Clinical trials published in English from January 1991 to June 2016 were identified by searching the PubMed (Medline), Cochrane, and Embase databases.

Translational Pharmacokinetic/Pharmacodynamic Modeling of Tumor Growth Inhibition Supports Dose-Range Selection of the Anti-PD-1 Antibody Pembrolizumab.

Pembrolizumab, a humanized monoclonal antibody against programmed death 1 (PD-1), has a manageable safety profile and robust clinical activity against advanced malignancies. The lowest effective dose for evaluation in further dose-ranging studies was identified by developing a translational model from preclinical mouse experiments. A compartmental pharmacokinetic model was combined with a published physiologically based tissue compartment, linked to receptor occupancy as the driver of observed tumor growth inhibition.