Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/28723
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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