Developing biomarkers assays to accelerate tuberculosis drug development: defining target product profiles

Stephen Henry Gillespie*, Andrew R. DiNardo, Sophia B. Georghiou, Wilber Sabiiti, Makashmi Kohli, Ursula Panzner, Irina Kontsevaya, Norbert Hittel, Leiven J. Stuyver, Jia Bin Tan, Reinout van Crevel, Christoph Lange, Thuong Thuy Thuong Nguyen, Jan Heyckendorf, Morten Ruhwald, Norbert Heinrich

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

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Abstract

Drug development for tuberculosis is hindered by the methodological limitations in the definitions of patient outcomes, particularly the slow organism growth and difficulty in obtaining suitable and representative samples throughout the treatment. We developed target product profiles for biomarker assays suitable for early-phase and late-phase clinical drug trials by consulting subject-matter experts on the desirable performance and operational characteristics of such assays for monitoring of tuberculosis treatment in drug trials. Minimal and optimal criteria were defined for scope, intended use, pricing, performance, and operational characteristics of the biomarkers. Early-stage trial assays should accurately quantify the number of viable bacilli, whereas late-stage trial assays should match the number, predict relapse-free cure, and replace culture conversion endpoints. The operational criteria reflect the infrastructure and resources available for drug trials. The effective tools should define the sterilising activity of the drug and lower the probability of treatment failure or relapse in people with tuberculosis. The target product profiles outlined in this Review should guide and de-risk the development of biomarker-based assays suitable for phase 2 and 3 clinical drug trials.
Original languageEnglish
Number of pages11
JournalThe Lancet Microbe
VolumeIn Press
Early online date9 May 2024
DOIs
Publication statusE-pub ahead of print - 9 May 2024

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