The development of novel TB multi-drug regimens that are more efficacious and of shorter induration requires a robust drug development pipeline. Advances in quantitative modeling and simulation can be used to maximize the utility of patient-level data from prior and contemporary clinical trials, thus optimizing study design for anti-TB regimens In this perspective article, we highlight work from seven project teams developing first-in-class translational and quantitative methodologies that aim to inform drug development decision-making dose selection, trial design and safety assessments, to achieve shorter and safer therapies for patients in need. These tools offer the opportunity to evaluate multiple hypotheses and provide a means to identify, quantify, and understand relevant sources of variability, to optimize translation and clinical trial design. When incorporated into the broader regulatory sciences framework, these efforts have the potential to transform the development paradigm for TB combination development, as well as other areas of global health.
Tuberculosis (TB); modeling; simulation; pharmacokinetic/pharmacodynamics (PK/PD); drug development; translational science
Citation: Debra Hannaa, Klaus Romeroa, Marco Schitoa Advancing TB Drug Regimen Development Through Innovative Quantitative Translational Pharmacology Methods and Approaches http://dx.doi.org/10.1016/j.ijid.2016.10.008
Received: 7 October 2016, Accepted: 11 October 2016, Available online: 24 October 2016
Copyright: © 2016 Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.
The Critical Path to TB Drug Regimens program is supported by the Bill & Melinda Gates Foundation. The CPTR program would like to thank and acknowledge all of our collaborators including our partners at Baylor University, Certera, Colorado State University, University of California San Francisco and the University of Florida.