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dc.contributor.authorPhillips, Patrick P. J.
dc.contributor.authorMendel, Carl M.
dc.contributor.authorBurger, Divan A.
dc.contributor.authorCrook, Angela
dc.contributor.authorNunn, Andrew J.
dc.contributor.authorDawson, Rodney
dc.contributor.authorDiacon, Andreas H.
dc.contributor.authorGillespie, Stephen Henry
dc.identifier.citationPhillips , P P J , Mendel , C M , Burger , D A , Crook , A , Nunn , A J , Dawson , R , Diacon , A H & Gillespie , S H 2016 , ' Limited role of culture conversion for decision-making in individual patient care and for advancing novel regimens to confirmatory clinical trials ' , BMC Medicine , vol. 14 , 19 .
dc.identifier.otherPURE: 240893266
dc.identifier.otherPURE UUID: abcb54ad-1b8d-4a07-925f-7ef965224aab
dc.identifier.otherScopus: 84961059451
dc.identifier.otherORCID: /0000-0001-6537-7712/work/39477832
dc.identifier.otherWOS: 000369227000001
dc.descriptionSupported by the European and Developing Country Clinical Trials Partnership (grant IP.2007.32011.011) and the Global Alliance for TB Drug Development, with support from the Bill & Melinda Gates Foundation, US Agency for International Development, UK Department for International Development, Directorate-General for International Cooperation of the Netherlands, Irish Aid and Australian Department of Foreign Affairs and Trade.en
dc.description.abstractBackground Despite recent increased clinical trials activity, no regimen has proved able to replace the standard 6-month regimen for drug-sensitive tuberculosis. Understanding the relationship between microbiological markers measured during treatment and long-term clinical outcomes is critical to evaluate their usefulness for decision-making for both individual patient care and for advancing novel regimens into time-consuming and expensive pivotal phase III trials. Methods Using data from the randomized controlled phase III trial REMoxTB, we evaluated sputum-based markers of speed of clearance of bacilli: time to smear negative status; time to culture negative status on LJ or in MGIT; daily rate of change of log10(TTP) to day 56; and smear or culture results at weeks 6, 8 or 12; as individual- and trial-level surrogate endpoints for long-term clinical outcome. Results Time to culture negative status on LJ or in MGIT, time to smear negative status and daily rate of change in log10(TTP) were each independent predictors of clinical outcome, adjusted for treatment (p <0.001). However, discrimination between low and high risk patients, as measured by the c-statistic, was modest and not much higher than the reference model adjusted for BMI, history of smoking, HIV status, cavitation, gender and MGIT TTP. Conclusions Culture conversion during treatment for tuberculosis, however measured, has only a limited role in decision-making for advancing regimens into phase III trials or in predicting the outcome of treatment for individual patients. REMoxTB number: NCT00864383.
dc.relation.ispartofBMC Medicineen
dc.rights© 2016 Phillips et al. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.en
dc.subjectClinical trialsen
dc.subjectSurrogate endpointsen
dc.subjectR Medicineen
dc.subjectRA0421 Public health. Hygiene. Preventive Medicineen
dc.titleLimited role of culture conversion for decision-making in individual patient care and for advancing novel regimens to confirmatory clinical trialsen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews. School of Medicineen
dc.contributor.institutionUniversity of St Andrews. Global Health Implementation Groupen
dc.contributor.institutionUniversity of St Andrews. Gillespie Groupen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.contributor.institutionUniversity of St Andrews. Infection Groupen
dc.description.statusPeer revieweden

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