Developing biomarkers assays to accelerate tuberculosis drug development : defining target product profiles
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.
Citation
Gillespie , S H , DiNardo , A R , Georghiou , S B , Sabiiti , W , Kohli , M , Panzner , U , Kontsevaya , I , Hittel , N , Stuyver , L J , Tan , J B , van Crevel , R , Lange , C , Nguyen , T T T , Heyckendorf , J , Ruhwald , M & Heinrich , N 2024 , ' Developing biomarkers assays to accelerate tuberculosis drug development : defining target product profiles ' , The Lancet Microbe , vol. In Press . https://doi.org/10.1016/S2666-5247(24)00085-5
Publication
The Lancet Microbe
Status
Peer reviewed
ISSN
2666-5247Type
Journal item
Description
Funding: This study is supported by the UNITE4TB consortium (www.unite4tb.org). UNITE4TB has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 101007873. The JU receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA, Deutsches Zentrum für Infektionsforschung e. V. (DZIF), and Ludwig-Maximilians-Universität München (LMU; Munich, Germany). EFPIA/AP contribute to 50% of funding, whereas the contribution of DZIF and the LMU Hospital Munich has been granted by the German Federal Ministry of Education and Research. CL is supported by DZIF under grant TTU-TB 02.709.Collections
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