Modern first-line TB treatment was developed more than thirty years ago in a very different regulatory environment from that of today. Any new agent faces an expensive and risky development path with numerous scientific pitfalls. While bringing even a single new drug to the clinic takes more than five years, developing a novel drug regimen sequentially would require at least 20 years under the current paradigm. Drug developers,clinicians and tuberculosis sufferers desperately need a new approach to finding the best new combinations of drugs in the most efficient and reliable way.
The drug development pathway in tuberculosis is incompletely integrated with important unanswered questions at every stage. It remains unclear to what extent many preclinical methods capture the right pharmacodynamic properties of a drug or reproduce the conditions under which it must act in the diseased host.In vitro methods may not accurately reflect the spectrum of physiological conditions found in natural populations of M tuberculosis while in vivo systems may not exhibit sufficiently human-like pathology.
Even in clinical development, the significance of early pharmacodynamic measures such as whole blood bactericidal and early bactericidal activity is open to differing interpretations. Bacteriological biomarkers remain incompletely evaluated in relation to long term measures of stable cure such as treatment failure and relapse and clinical PK-PD analysis is only now becoming a routine feature of Phase II studies.
PreDiCT-TB aims to overcome these disconnects in TB drug development by adopting a fully integrated multidisciplinary approach grounded in PK-PD analysis and calibrated by clinical outcomes. By effectively propagating preclinical information into the early clinical phase, we aim to provide a new framework and tools that will facilitate the transition of the best combinations of drugs to late phase development and maximise their chances of success.