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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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Limited role of culture conversion for decision-making in individual patient care and for advancing novel regimens to confirmatory clinical trials. / Phillips, Patrick P. J. ; Mendel, Carl M. ; Burger, Divan A. ; Crook, Angela ; Nunn, Andrew J. ; Dawson, Rodney; Diacon, Andreas H.; Gillespie, Stephen Henry.

In: BMC Medicine, Vol. 14, 19, 04.02.2016, p. 1-11.

Research output: Contribution to journalArticle

Harvard

Phillips, PPJ, Mendel, CM, Burger, DA, Crook, A, Nunn, AJ, Dawson, R, Diacon, AH & Gillespie, SH 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, pp. 1-11. https://doi.org/10.1186/s12916-016-0565-y

APA

Phillips, P. P. J., Mendel, C. M., Burger, D. A., Crook, A., Nunn, A. J., Dawson, R., ... 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, 14, 1-11. [19]. https://doi.org/10.1186/s12916-016-0565-y

Vancouver

Phillips PPJ, Mendel CM, Burger DA, Crook A, Nunn AJ, Dawson R et al. Limited role of culture conversion for decision-making in individual patient care and for advancing novel regimens to confirmatory clinical trials. BMC Medicine. 2016 Feb 4;14:1-11. 19. https://doi.org/10.1186/s12916-016-0565-y

Author

Phillips, Patrick P. J. ; Mendel, Carl M. ; Burger, Divan A. ; Crook, Angela ; Nunn, Andrew J. ; Dawson, Rodney ; Diacon, Andreas H. ; Gillespie, Stephen Henry. / Limited role of culture conversion for decision-making in individual patient care and for advancing novel regimens to confirmatory clinical trials. In: BMC Medicine. 2016 ; Vol. 14. pp. 1-11.

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@article{abcb54ad1b8d4a07925f7ef965224aab,
title = "Limited role of culture conversion for decision-making in individual patient care and for advancing novel regimens to confirmatory clinical trials",
abstract = "BackgroundDespite 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.MethodsUsing 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.ResultsTime 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.ConclusionsCulture 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.",
keywords = "Tuberculosis, Clinical trials, Surrogate endpoints, Moxifloxacin",
author = "Phillips, {Patrick P. J.} and Mendel, {Carl M.} and Burger, {Divan A.} and Angela Crook and Nunn, {Andrew J.} and Rodney Dawson and Diacon, {Andreas H.} and Gillespie, {Stephen Henry}",
note = "Supported 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.",
year = "2016",
month = "2",
day = "4",
doi = "10.1186/s12916-016-0565-y",
language = "English",
volume = "14",
pages = "1--11",
journal = "BMC Medicine",
issn = "1741-7015",
publisher = "Wiley-Blackwell",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Limited role of culture conversion for decision-making in individual patient care and for advancing novel regimens to confirmatory clinical trials

AU - Phillips, Patrick P. J.

AU - Mendel, Carl M.

AU - Burger, Divan A.

AU - Crook, Angela

AU - Nunn, Andrew J.

AU - Dawson, Rodney

AU - Diacon, Andreas H.

AU - Gillespie, Stephen Henry

N1 - Supported 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.

PY - 2016/2/4

Y1 - 2016/2/4

N2 - BackgroundDespite 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.MethodsUsing 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.ResultsTime 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.ConclusionsCulture 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.

AB - BackgroundDespite 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.MethodsUsing 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.ResultsTime 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.ConclusionsCulture 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.

KW - Tuberculosis

KW - Clinical trials

KW - Surrogate endpoints

KW - Moxifloxacin

U2 - 10.1186/s12916-016-0565-y

DO - 10.1186/s12916-016-0565-y

M3 - Article

VL - 14

SP - 1

EP - 11

JO - BMC Medicine

JF - BMC Medicine

SN - 1741-7015

M1 - 19

ER -

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