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Evaluation of six months sputum culture conversion as a surrogate endpoint in a multidrug resistant-tuberculosis trial
The emergence of multidrug resistant-tuberculosis (MDR-TB), defined as Mycobacterium tuberculosis strains with in vitro resistance to at least isoniazid and rifampicin, has necessitated evaluation and validation of appropriate surrogate endpoints for treatment response in drug trials for MDR-TB. The...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6053142/ https://www.ncbi.nlm.nih.gov/pubmed/30024924 http://dx.doi.org/10.1371/journal.pone.0200539 |
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author | Meyvisch, Paul Kambili, Chrispin Andries, Koen Lounis, Nacer Theeuwes, Myriam Dannemann, Brian Vandebosch, An Van der Elst, Wim Molenberghs, Geert Alonso, Ariel |
author_facet | Meyvisch, Paul Kambili, Chrispin Andries, Koen Lounis, Nacer Theeuwes, Myriam Dannemann, Brian Vandebosch, An Van der Elst, Wim Molenberghs, Geert Alonso, Ariel |
author_sort | Meyvisch, Paul |
collection | PubMed |
description | The emergence of multidrug resistant-tuberculosis (MDR-TB), defined as Mycobacterium tuberculosis strains with in vitro resistance to at least isoniazid and rifampicin, has necessitated evaluation and validation of appropriate surrogate endpoints for treatment response in drug trials for MDR-TB. The trial that has demonstrated efficacy of bedaquiline, a diarylquinoline that inhibits mycobacterial ATP synthase, possesses the requisite features to conduct this evaluation. Approval of bedaquiline for use in MDR-TB was based primarily on the results of the controlled C208 Stage II study (ClinicalTrials.gov number, NCT00449644) including 160 patients randomized 1:1 to receive bedaquiline or placebo for 24 weeks when added to an 18–24-month preferred five-drug background regimen. Since randomization in C208 Stage II was preserved until study end, the trial results allow for the investigation of the complex relationship between sustained durable outcome with either Week 8 or Week 24 culture conversion as putative surrogate endpoints. The relationship between Week 120 outcome with Week 8 or Week 24 culture conversion was investigated using a descriptive analysis and with a recently developed statistical methodology for surrogate endpoint evaluation using methods of causal inference. The results demonstrate that sputum culture conversion at 24 weeks is more reliable than sputum culture conversion at 8 weeks when assessing the outcome of adding one new drug to a MDR-TB regimen. |
format | Online Article Text |
id | pubmed-6053142 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-60531422018-07-27 Evaluation of six months sputum culture conversion as a surrogate endpoint in a multidrug resistant-tuberculosis trial Meyvisch, Paul Kambili, Chrispin Andries, Koen Lounis, Nacer Theeuwes, Myriam Dannemann, Brian Vandebosch, An Van der Elst, Wim Molenberghs, Geert Alonso, Ariel PLoS One Research Article The emergence of multidrug resistant-tuberculosis (MDR-TB), defined as Mycobacterium tuberculosis strains with in vitro resistance to at least isoniazid and rifampicin, has necessitated evaluation and validation of appropriate surrogate endpoints for treatment response in drug trials for MDR-TB. The trial that has demonstrated efficacy of bedaquiline, a diarylquinoline that inhibits mycobacterial ATP synthase, possesses the requisite features to conduct this evaluation. Approval of bedaquiline for use in MDR-TB was based primarily on the results of the controlled C208 Stage II study (ClinicalTrials.gov number, NCT00449644) including 160 patients randomized 1:1 to receive bedaquiline or placebo for 24 weeks when added to an 18–24-month preferred five-drug background regimen. Since randomization in C208 Stage II was preserved until study end, the trial results allow for the investigation of the complex relationship between sustained durable outcome with either Week 8 or Week 24 culture conversion as putative surrogate endpoints. The relationship between Week 120 outcome with Week 8 or Week 24 culture conversion was investigated using a descriptive analysis and with a recently developed statistical methodology for surrogate endpoint evaluation using methods of causal inference. The results demonstrate that sputum culture conversion at 24 weeks is more reliable than sputum culture conversion at 8 weeks when assessing the outcome of adding one new drug to a MDR-TB regimen. Public Library of Science 2018-07-19 /pmc/articles/PMC6053142/ /pubmed/30024924 http://dx.doi.org/10.1371/journal.pone.0200539 Text en © 2018 Meyvisch et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Meyvisch, Paul Kambili, Chrispin Andries, Koen Lounis, Nacer Theeuwes, Myriam Dannemann, Brian Vandebosch, An Van der Elst, Wim Molenberghs, Geert Alonso, Ariel Evaluation of six months sputum culture conversion as a surrogate endpoint in a multidrug resistant-tuberculosis trial |
title | Evaluation of six months sputum culture conversion as a surrogate endpoint in a multidrug resistant-tuberculosis trial |
title_full | Evaluation of six months sputum culture conversion as a surrogate endpoint in a multidrug resistant-tuberculosis trial |
title_fullStr | Evaluation of six months sputum culture conversion as a surrogate endpoint in a multidrug resistant-tuberculosis trial |
title_full_unstemmed | Evaluation of six months sputum culture conversion as a surrogate endpoint in a multidrug resistant-tuberculosis trial |
title_short | Evaluation of six months sputum culture conversion as a surrogate endpoint in a multidrug resistant-tuberculosis trial |
title_sort | evaluation of six months sputum culture conversion as a surrogate endpoint in a multidrug resistant-tuberculosis trial |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6053142/ https://www.ncbi.nlm.nih.gov/pubmed/30024924 http://dx.doi.org/10.1371/journal.pone.0200539 |
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