Accelerating the transition of new tuberculosis drug combinations from Phase II to Phase III trials: New technologies and innovative designs

Davies, Geraint; Boeree, Martin; Hermann, Dave and Hoelscher, Michael (2019): Accelerating the transition of new tuberculosis drug combinations from Phase II to Phase III trials: New technologies and innovative designs.
In: PLOS Medicine 16(7), e1002851

Abstract

Preclinical models of tuberculosis have significant limitations in selecting composition and duration of regimens for tuberculosis. Innovative early-phase clinical trial methodologies and technologies have the potential to reduce risk and accelerate drug development in tuberculosis. Phase IIA monotherapy studies are optional for proof of concept but may be useful for dose-finding in conjunction with pharmacokinetic-pharmacodynamic methods. Innovative Phase IIB designs are increasingly common in tuberculosis drug development, utilising multiarm selection designs, sometimes in an adaptive format. Novel biomarkers including liquid culture and nucleic acid amplification appear capable of replacing conventional solid culture in early-phase development. Phase IIC and ultrashort noninferiority designs attempt to mitigate the problem of estimating duration of treatment regimens from Phase II results alone.

• Item Type: Journal article
• Faculties: Medicine
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 1549-1277
• Language: English