Considerations for Use of Pharmacodynamic Biomarkers to Support Biosimilar Development - (II) A Randomized Trial with IL-5 Antagonists.

The US Food and Drug Administration (FDA) guidance describes how pharmacodynamic (PD) biomarkers can be used to address residual uncertainty and demonstrate no clinically meaningful differences between a proposed biosimilar and its reference product without relying on clinical efficacy end point(s). Pilot studies and modeling can inform dosing for such PD studies. To that end, we conducted a randomized, double-blinded, placebo-controlled, single-dose, parallel-arm clinical study in healthy participants to evaluate approaches to address information gaps, inform best practices for analysis of biomarker samples and study results, and apply emerging technologies in biomarker characterization. Seventy-two healthy participants (n = 8 per arm) received either placebo or 1 of 4 doses of the interleukin-5 inhibitors mepolizumab (3-24 mg) or reslizumab (0.1-0.8 mg/kg). A clinical study using doses lower than approved therapeutic doses was combined with modeling and simulation to evaluate the dose-response relationship of the biomarker eosinophils. There was no dose-response relationship for eosinophil counts due to variability, although the mepolizumab 24 mg and reslizumab 0.8 mg/kg doses showed clear effects. Published indirect-response models were used to explore eosinophil data across doses from this study and the unstudied therapeutic doses. Simulations were used to calculate typical PD metrics, such as baseline-adjusted area under the effect curve and maximum change from baseline. The simulation results demonstrate sensitivity of eosinophils as a PD biomarker and indicate doses lower than the approved doses would have PD responses overlapping with variability in the placebo arm. The simulation results further highlight the utility of model-based approaches in supporting use of PD biomarkers in biosimilar development.

Getting back on track: a group psychoeducational intervention for patients and families living with head and neck cancer.

PURPOSE: Head and neck cancer survivors are increasing in prevalence, and 60-70% still experience at least one unmet emotional and/or physical need after treatment has ended. The purpose of this study was to determine the efficacy of a brief post-treatment psychoeducational intervention on perceived preparedness for coping with recovery using post-session evaluations. METHODS: Between August 2013 and May 2018, a two-session, multidisciplinary "getting back on track" class was delivered to head and neck cancer patients approximately 2 months following radiation treatment at Princess Margaret Cancer Centre in Toronto, Canada. Three hundred and fifty attendees completed evaluations. Statistical analyses of the 310 patients surveyed measured change in level of preparedness to cope with recovery using the b-prepared scale. Qualitative analyses provided insight into potential benefits for future patients. RESULTS: Almost two-thirds (58%) of patients reported an increase in level of preparedness in post-intervention surveys. Comparing self-reported level of preparedness among patients from before to after the class showed an increase in feeling prepared from 50 to 58%, and of those feeling very prepared, from 6 to 34%. The proportion of patients who reported feeling unprepared (11%) or neutral (33%) before the class decreased post-intervention, with 0% feeling unprepared and 7% feeling neutral. There were statistically significant differences in the ideal timing of the class, but overall attendees agreed that the class is an essential part of their recovery. CONCLUSION: Results confirm the efficacy of this brief psychoeducational intervention to improve preparedness in head and neck cancer survivors following radiation treatment.

Supporting Change in Oncology Nursing Practice in Kuwait.

As countries around the world struggle to provide oncology care and treatment to their populations, nurses, as the largest healthcare workforce, are faced with the challenge of obtaining, maintaining, and developing specialized oncology nursing knowledge and expertise. Strategies that can be deployed at a local level to support nurses with integrating new knowledge into practice are important in meeting and overcoming this challenge. This article describes a theory-based model for implementing oncology nursing best practices in the Middle Eastern country of Kuwait. 
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