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Title: | Evaluation of six months sputum culture conversion as a surrogate endpoint in a multidrug resistant-tuberculosis trial | Authors: | MEYVISCH, Paul Kambili, Chrispin Andries, Koen Lounis, Nacer Theeuwes, Myriam Dannemann, Brian Vandebosch, An VAN DER ELST, Wim MOLENBERGHS, Geert ALONSO ABAD, Ariel |
Issue Date: | 2018 | Publisher: | PUBLIC LIBRARY SCIENCE | Source: | PLOS ONE, 13(7) (Art N° e0200539) | Abstract: | 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. | Notes: | [Meyvisch, Paul; Andries, Koen; Lounis, Nacer; Theeuwes, Myriam; Vandebosch, An; Van der Elst, Wim; Alonso, Ariel] Janssen Pharmaceut, Beerse, Belgium. [Meyvisch, Paul; Molenberghs, Geert] Univ Hasselt, I BioStat, Diepenbeek, Belgium. [Kambili, Chrispin] Johnson & Johnson Global Serv, Raritan, NJ USA. [Dannemann, Brian] Janssen Res & Dev, Titusville, NJ USA. [Molenberghs, Geert] Katholieke Univ Leuven, I BioStat, Leuven, Belgium. [Theeuwes, Myriam] DURECT Corp, Cupertino, CA USA. | Document URI: | http://hdl.handle.net/1942/28723 | ISSN: | 1932-6203 | e-ISSN: | 1932-6203 | DOI: | 10.1371/journal.pone.0200539 | ISI #: | 000439120000028 | Rights: | Copyright: © 2018 Meyvisch et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2019 |
Appears in Collections: | Research publications |
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meyvisch 1.pdf | Published version | 1.93 MB | Adobe PDF | View/Open |
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