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Adaptive clinical trials in tuberculosis: applications, challenges and solutions

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Adaptive clinical trials in tuberculosis : applications, challenges and solutions. / Davis, G. R.; Phillips, P. P.; Jaki, Thomas.

In: International Journal of Tuberculosis and Lung Disease, Vol. 19, No. 6, 01.06.2015, p. 626-634.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Davis, GR, Phillips, PP & Jaki, T 2015, 'Adaptive clinical trials in tuberculosis: applications, challenges and solutions', International Journal of Tuberculosis and Lung Disease, vol. 19, no. 6, pp. 626-634. https://doi.org/10.5588/ijtld.14.0988

APA

Davis, G. R., Phillips, P. P., & Jaki, T. (2015). Adaptive clinical trials in tuberculosis: applications, challenges and solutions. International Journal of Tuberculosis and Lung Disease, 19(6), 626-634. https://doi.org/10.5588/ijtld.14.0988

Vancouver

Davis GR, Phillips PP, Jaki T. Adaptive clinical trials in tuberculosis: applications, challenges and solutions. International Journal of Tuberculosis and Lung Disease. 2015 Jun 1;19(6):626-634. https://doi.org/10.5588/ijtld.14.0988

Author

Davis, G. R. ; Phillips, P. P. ; Jaki, Thomas. / Adaptive clinical trials in tuberculosis : applications, challenges and solutions. In: International Journal of Tuberculosis and Lung Disease. 2015 ; Vol. 19, No. 6. pp. 626-634.

Bibtex

@article{35a2eea2d0a0432a8b1bfd0eee78452f,
title = "Adaptive clinical trials in tuberculosis: applications, challenges and solutions",
abstract = "Drug development for tuberculosis (TB) faces numerous practical obstacles, including the need for combination treatment with at least three drugs, reliance on possibly unrepresentative animal models which may not reproduce key features of human disease and the lack of a well-validated surrogate endpoint for stable cure. Pivotal Phase III trials are large, lengthy and expensive, and the funding and capacity to conduct them are limited worldwide. More rational methods for the selection of priority regimens for Phase III are urgently needed to avoid costly late-stage failures. We examine the suitability of adaptive clinical trial designs for drug development in TB, focusing on designs for Phase IIB and III trials, where we believe the biggest gains in efficiency can be made. Key areas that may be addressed by such designs are improvements in the selection of doses and combinations of drugs in early clinical development and in maximising the power of confirmatory trials in multidrug-resistant TB, where patient numbers and complexity pose practical limitations. We encourage trialists and regulators in this area to consider the advantages that may be offered by these designs and their potential to more effectively and rapidly identify better treatment regimens for TB patients worldwide.",
keywords = "drug development, sequential trials, statistics, tuberculosis",
author = "Davis, {G. R.} and Phillips, {P. P.} and Thomas Jaki",
year = "2015",
month = jun,
day = "1",
doi = "10.5588/ijtld.14.0988",
language = "English",
volume = "19",
pages = "626--634",
journal = "International Journal of Tuberculosis and Lung Disease",
issn = "1027-3719",
publisher = "International Union against Tubercul. and Lung Dis.",
number = "6",

}

RIS

TY - JOUR

T1 - Adaptive clinical trials in tuberculosis

T2 - applications, challenges and solutions

AU - Davis, G. R.

AU - Phillips, P. P.

AU - Jaki, Thomas

PY - 2015/6/1

Y1 - 2015/6/1

N2 - Drug development for tuberculosis (TB) faces numerous practical obstacles, including the need for combination treatment with at least three drugs, reliance on possibly unrepresentative animal models which may not reproduce key features of human disease and the lack of a well-validated surrogate endpoint for stable cure. Pivotal Phase III trials are large, lengthy and expensive, and the funding and capacity to conduct them are limited worldwide. More rational methods for the selection of priority regimens for Phase III are urgently needed to avoid costly late-stage failures. We examine the suitability of adaptive clinical trial designs for drug development in TB, focusing on designs for Phase IIB and III trials, where we believe the biggest gains in efficiency can be made. Key areas that may be addressed by such designs are improvements in the selection of doses and combinations of drugs in early clinical development and in maximising the power of confirmatory trials in multidrug-resistant TB, where patient numbers and complexity pose practical limitations. We encourage trialists and regulators in this area to consider the advantages that may be offered by these designs and their potential to more effectively and rapidly identify better treatment regimens for TB patients worldwide.

AB - Drug development for tuberculosis (TB) faces numerous practical obstacles, including the need for combination treatment with at least three drugs, reliance on possibly unrepresentative animal models which may not reproduce key features of human disease and the lack of a well-validated surrogate endpoint for stable cure. Pivotal Phase III trials are large, lengthy and expensive, and the funding and capacity to conduct them are limited worldwide. More rational methods for the selection of priority regimens for Phase III are urgently needed to avoid costly late-stage failures. We examine the suitability of adaptive clinical trial designs for drug development in TB, focusing on designs for Phase IIB and III trials, where we believe the biggest gains in efficiency can be made. Key areas that may be addressed by such designs are improvements in the selection of doses and combinations of drugs in early clinical development and in maximising the power of confirmatory trials in multidrug-resistant TB, where patient numbers and complexity pose practical limitations. We encourage trialists and regulators in this area to consider the advantages that may be offered by these designs and their potential to more effectively and rapidly identify better treatment regimens for TB patients worldwide.

KW - drug development

KW - sequential trials

KW - statistics

KW - tuberculosis

U2 - 10.5588/ijtld.14.0988

DO - 10.5588/ijtld.14.0988

M3 - Journal article

VL - 19

SP - 626

EP - 634

JO - International Journal of Tuberculosis and Lung Disease

JF - International Journal of Tuberculosis and Lung Disease

SN - 1027-3719

IS - 6

ER -