A Systematic Review of Potential Biomarkers for Bacterial Burden and Treatment Efficacy Assessment in Tuberculosis Platform-Based Clinical Trials.

Autor:	Espinosa-Pereiro J; Infectious Diseases Department, Vall d'Hebrón University Hospital, Universitat Autónoma de Barcelona, Barcelona, Spain.; International Health Program, Catalan Institute of Health, Barcelona, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Infeccioass, Instituto de Salud Carlos III, Madrid, Spain., Alagna R; San Raffaele Scientific Institute, Milan, Italy.; Qiagen, Srl, Milan, Italy., Saluzzo F; San Raffaele Scientific Institute, Milan, Italy., González-Moreno J; Janssen Cylag, SA, Janssen Pharmaceutical Companies, Madrid, Spain., Heinrich N; Center for International Health, University Hospital, Ludwig Maximilian University Munich, Munich, Germany.; German Center for Infection Research, Munich, Germany.; Division of Infectious Diseases and Tropical Medicine, University Hospital, Ludwig Maximilian University Munich (DZIF), Partner Site Munich, Munich, Germany., Sánchez-Montalvá A; Infectious Diseases Department, Vall d'Hebrón University Hospital, Universitat Autónoma de Barcelona, Barcelona, Spain.; International Health Program, Catalan Institute of Health, Barcelona, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Infeccioass, Instituto de Salud Carlos III, Madrid, Spain.; Grupo de Estudio de Micobacterias, Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica, Madrid, Spain., Cirillo DM; San Raffaele Scientific Institute, Milan, Italy.
Jazyk:	angličtina
Zdroj:	The Journal of infectious diseases [J Infect Dis] 2024 May 15; Vol. 229 (5), pp. 1584-1595.
DOI:	10.1093/infdis/jiad482
Abstrakt:	Adaptive platform trials can be more efficient than classic trials for developing new treatments. Moving from culture-based to simpler- or faster-to-measure biomarkers as efficacy surrogates may enhance this advantage. We performed a systematic review of treatment efficacy biomarkers in adults with tuberculosis. Platform trials can span different development phases. We grouped biomarkers as: α, bacterial load estimates used in phase 2a trials; β, early and end-of treatment end points, phase 2b-c trials; γ, posttreatment or trial-level estimates, phase 2c-3 trials. We considered as analysis unit (biomarker entry) each combination of biomarker, predicted outcome, and their respective measurement times or intervals. Performance metrics included: sensitivity, specificity, area under the receiver-operator curve (AUC), and correlation measures, and classified as poor, promising, or good. Eighty-six studies included 22 864 participants. From 1356 biomarker entries, 318 were reported with the performance metrics of interest, with 103 promising and 41 good predictors. Group results were: α, mycobacterial RNA and lipoarabinomannan (LAM) in sputum, and host metabolites in urine; β, mycobacterial RNA and host transcriptomic or cytokine signatures for early treatment response; and γ, host transcriptomics for recurrence. A combination of biomarkers from different categories could help in designing more efficient platform trials. Efforts to develop efficacy surrogates should be better coordinated. Competing Interests: Potential conflicts of interest. R. A. is employed by Quiagen. J. G. M. is employed by Janssen Pharmaceuticals. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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