Limited role of culture conversion for decision-making in individual patient care and for advancing novel regimens to confirmatory clinical trials

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dc.contributor.authorPhillips, Patrick P. J.en_ZA
dc.contributor.authorMendel, Carl M.en_ZA
dc.contributor.authorBurger, Divan A.en_ZA
dc.contributor.authorCrook, Angela M.en_ZA
dc.contributor.authorNunn, Andrew J.en_ZA
dc.contributor.authorDawson, Rodneyen_ZA
dc.contributor.authorDiacon, Andreas H.en_ZA
dc.contributor.authorGillespie, Stephen H.en_ZA
dc.date.accessioned2017-07-31T06:35:26Z
dc.date.available2017-07-31T06:35:26Z
dc.date.issued2016-02-04
dc.descriptionCITATION: Phillips, P. P. J., et al. 2016. Limited role of culture conversion for decision-making in individual patient care and for advancing novel regimens to confirmatory clinical trials. BMC Medicine, 14:19, doi:10.1186/s12916-016-0565-y.en_ZA
dc.descriptionThe original publication is available at https://bmcmedicine.biomedcentral.comen_ZA
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 decisionmaking 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 ClinicalTrials.gov number: NCT00864383.en_ZA
dc.description.urihttps://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-016-0565-y
dc.description.versionPublisher's versionen_ZA
dc.format.extent11 pages : illustrationsen_ZA
dc.identifier.citationPhillips, P. P. J., et al. 2016. Limited role of culture conversion for decision-making in individual patient care and for advancing novel regimens to confirmatory clinical trials. BMC Medicine, 14:19, doi:10.1186/s12916-016-0565-yen_ZA
dc.identifier.issn1741-7015 (online)
dc.identifier.otherdoi:10.1186/s12916-016-0565-y
dc.identifier.urihttp://hdl.handle.net/10019.1/102030
dc.language.isoen_ZAen_ZA
dc.publisherBioMed Centralen_ZA
dc.rights.holderAuthors retain copyrighten_ZA
dc.subjectTuberculosis -- Treatmenten_ZA
dc.subjectTuberculosis -- Clinical trialsen_ZA
dc.subjectTuberculosis -- Microbiologyen_ZA
dc.subjectTuberculosis -- Patients -- Careen_ZA
dc.titleLimited role of culture conversion for decision-making in individual patient care and for advancing novel regimens to confirmatory clinical trialsen_ZA
dc.typeArticleen_ZA
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