Comparable Pharmacokinetics, Safety, and Tolerability of Etrolizumab Administered by Prefilled Syringe or Autoinjector in a Randomized Trial in Healthy Volunteers.

Introduction: Etrolizumab is a novel, dual-action anti-β7 integrin antibody studied in phase 3 trials in patients with inflammatory bowel disease. An autoinjector (AI) is being developed in parallel to complement the prefilled syringe with needle safety device (PFS-NSD) for subcutaneous (SC) administration in these trials. Here we demonstrate the comparable pharmacokinetics, tolerability, and safety of both devices.

Assessing Time-Varying Causal Effect Moderation in Mobile Health.

In mobile health interventions aimed at behavior change and maintenance, treatments are provided in real time to manage current or impending high risk situations or promote healthy behaviors in near real time. Currently there is great scientific interest in developing data analysis approaches to guide the development of mobile interventions. In particular data from mobile health studies might be used to examine effect moderators-individual characteristics, time-varying context or past treatment response that moderate the effect of current treatment on a subsequent response.

A derived and validated score to predict prolonged mechanical ventilation in patients undergoing cardiac surgery.

Objectives: Prolonged mechanical ventilation after cardiac surgery imposes a significant burden on the patient in terms of morbidity as well as a financial burden on the hospital. We undertook a retrospective analysis of 2 prospectively collected databases developed in tertiary cardiac care centers to derive and validate a risk index predicting prolonged mechanical ventilation after cardiac surgery.

Methods: We studied a retrospective cohort of 32,045 patients undergoing cardiac surgery in 2 hospitals in Toronto, Canada.

Microrandomized trials: An experimental design for developing just-in-time adaptive interventions.

Objective: This article presents an experimental design, the microrandomized trial, developed to support optimization of just-in-time adaptive interventions (JITAIs). JITAIs are mHealth technologies that aim to deliver the right intervention components at the right times and locations to optimally support individuals' health behaviors. Microrandomized trials offer a way to optimize such interventions by enabling modeling of causal effects and time-varying effect moderation for individual intervention components within a JITAI.

Sieve estimation in a Markov illness-death process under dual censoring.

Semiparametric methods are well established for the analysis of a progressive Markov illness-death process observed up to a noninformative right censoring time. However, often the intermediate and terminal events are censored in different ways, leading to a dual censoring scheme. In such settings, unbiased estimation of the cumulative transition intensity functions cannot be achieved without some degree of smoothing.

Bias in progression-free survival analysis due to intermittent assessment of progression.

Cancer clinical trials are routinely designed to assess the effect of treatment on disease progression and death, often in terms of a composite endpoint called progression-free survival. When progression status is known only at periodic assessment times, the progression time is interval censored, and complications arise in the analysis of progression-free survival. Despite the advances in methods for dealing with interval-censored data, naive methods such as right-endpoint imputation are widely adopted in this setting.