The 2017 CPTR Workshop included topical breakout sessions on a range of topics, including interactive training demonstrations on several tools developed through CPTR partnerships.
Demo: Interactive Tool for Optimal Positioning of Time-to-Positivity Results in Patients with TB
The CPTR modeling and simulation team, in partnership with Certara, developed a quantitative model that describes the longitudinal dynamic change (based on Phase II patient-level data), which gives the ability to generate interpretable parameters that can then be related to clinically-relevant endpoints (in Phase III data). The CPTR/CERTARA team developed an interactive interface (R-Shiny application) based on the patient-level TTP data collected in 11 clinical studies, which included a total of 30 treatments (dose-ranging, monotherapy and combination therapy) administered to patients with TB. This interactive tool allows users to compare the TTP behavior over time of two chosen treatments from the total of 30 different combinations that are included in the repository. Moreover, additional TTP data can be uploaded from new trials by a sponsor to perform strategic positioning of TTP against historical TTP information. This tutorial covered the basic use of this R-Shiny application and provided hands-on examples of use, interpretation of results, and optimal positioning of new TTP results uploaded into the repository.
Demo: Relational Sequencing TB Data Platform (ReSeqTB)
In this training session, CPTR reviewed the Data Browser and common tasks associated with online data exploration. CPTR highlighted the architecture of the underlying data for exploration and download, reviewed the terms and conditions for accessing the data, and discussed summary statistics for existing data in the repository. The new Visual Browser tools were reviewed, showing existing functionality as well as features in development. After the initial training overview, future enhancements and known challenges were discussed, and participants were given an opportunity to provide feedback.
Audio of Additional Breakout Sessions
Demo: Physiologically-based Pharmacokinetic (PBPK) Model and QT Prolongation Module
Attendees participated in a hands-on demo using the CPTR PBPK model in TB drug development scenarios. Following a short introduction to the PBPK model, attendees created a compound file for moxifloxacin and used this to simulate plasma and lung concentrations of the drug. The results were compared to available clinical data. The PBPK model for moxifloxacin will be refined by incorporation of P-glycoprotein transport data and the effects on the local drug concentration in the lung examined. In the last part of the session a demonstration of how the PBPK model can be coupled with the Cardiac Safety Simulator to predict QT prolongation was given. Using Moxifloxacin as an example, session chairs will discuss the use of QSAR models and in vitro ion channel data together with plasma/tissue concentration data from the PBPK model to predict changes in ionic currents and ultimately QT prolongation caused by drugs.
Breakout: Progressing the Preclinical Roadmap – Next Steps in Evaluating in vivo Models and Other Drug Development Tools
Attendees discussed currently available and emerging efficacy-based models for clinical trial design for TB regimen development, identified next steps needed to progress the preclinical roadmap, identified data gaps and needs, and prioritized animal models, other than the sterilizing mouse model to examine for evidence-based decisions for TB drug regimen development and qualification. The group also discussed and addressed the dichotomy in the field regarding employing in vivo models for preclinical and drug development purposes.
Breakout: Addressing Interoperability Between Data Platforms
Attendees participated in a group discussion of the disparate efforts to collect genotypic and phenotypic data for tuberculosis isolates as well as patient outcomes to address challenges in identifying mutations associated with drug resistance. Feedback from attendees will inform an assessment of technical challenges and opportunities associated with sharing these data between platforms and to identify opportunities to expand representation of geographic and genetic diversity in at least one repository.
Breakout: Stakeholder & Community Engagement Workgroup: Applying Community Outreach and Engagement Strategies to Inform Trial Design
Attendees received a briefing from the Stakeholder & Community Engagement Workgroup (SCE-WG) on work planned to examine the correlation of implementing outreach strategies for recruiting TB patients to ultimate retention throughout the trial. One goal of this work includes generating recommended best practices, or a template guide, for recruitment for TB trials. Attendees shares their perspectives and suggestions for additional areas—from clinical trials to diagnosis and delivery of care—that could benefit from enhanced community and stakeholder engagement.
Breakout: Fostering Industry and Regulatory Interactions to Advance Next Generation Sequencing for TB Diagnostics
Attendees participated in discussion and shared perspectives on what is needed to foster innovation and development in TB diagnostics, with a focus on the increased role of next generation sequencing in advancing the field. Further, participants discussed the role of regulatory oversight of databases and platforms that house sequencing data for use in research and clinical development. Input and feedback from this session will be used to outline future CPTR efforts in this space.