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A Bayesian adaptive design for clinical trials in rare diseases

Development of treatments for rare diseases is challenging due to the limited number of patients available for participation. Learning about treatment effectiveness with a view to treat patients in the larger outside population, as in the traditional fixed randomised design, may not be a plausible g...

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Autores principales: Williamson, S. Faye, Jacko, Peter, Villar, Sofía S., Jaki, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5473477/
https://www.ncbi.nlm.nih.gov/pubmed/28630525
http://dx.doi.org/10.1016/j.csda.2016.09.006
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author Williamson, S. Faye
Jacko, Peter
Villar, Sofía S.
Jaki, Thomas
author_facet Williamson, S. Faye
Jacko, Peter
Villar, Sofía S.
Jaki, Thomas
author_sort Williamson, S. Faye
collection PubMed
description Development of treatments for rare diseases is challenging due to the limited number of patients available for participation. Learning about treatment effectiveness with a view to treat patients in the larger outside population, as in the traditional fixed randomised design, may not be a plausible goal. An alternative goal is to treat the patients within the trial as effectively as possible. Using the framework of finite-horizon Markov decision processes and dynamic programming (DP), a novel randomised response-adaptive design is proposed which maximises the total number of patient successes in the trial and penalises if a minimum number of patients are not recruited to each treatment arm. Several performance measures of the proposed design are evaluated and compared to alternative designs through extensive simulation studies using a recently published trial as motivation. For simplicity, a two-armed trial with binary endpoints and immediate responses is considered. Simulation results for the proposed design show that: (i) the percentage of patients allocated to the superior arm is much higher than in the traditional fixed randomised design; (ii) relative to the optimal DP design, the power is largely improved upon and (iii) it exhibits only a very small bias and mean squared error of the treatment effect estimator. Furthermore, this design is fully randomised which is an advantage from a practical point of view because it protects the trial against various sources of bias. As such, the proposed design addresses some of the key issues that have been suggested as preventing so-called bandit models from being implemented in clinical practice.
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spelling pubmed-54734772017-09-01 A Bayesian adaptive design for clinical trials in rare diseases Williamson, S. Faye Jacko, Peter Villar, Sofía S. Jaki, Thomas Comput Stat Data Anal Article Development of treatments for rare diseases is challenging due to the limited number of patients available for participation. Learning about treatment effectiveness with a view to treat patients in the larger outside population, as in the traditional fixed randomised design, may not be a plausible goal. An alternative goal is to treat the patients within the trial as effectively as possible. Using the framework of finite-horizon Markov decision processes and dynamic programming (DP), a novel randomised response-adaptive design is proposed which maximises the total number of patient successes in the trial and penalises if a minimum number of patients are not recruited to each treatment arm. Several performance measures of the proposed design are evaluated and compared to alternative designs through extensive simulation studies using a recently published trial as motivation. For simplicity, a two-armed trial with binary endpoints and immediate responses is considered. Simulation results for the proposed design show that: (i) the percentage of patients allocated to the superior arm is much higher than in the traditional fixed randomised design; (ii) relative to the optimal DP design, the power is largely improved upon and (iii) it exhibits only a very small bias and mean squared error of the treatment effect estimator. Furthermore, this design is fully randomised which is an advantage from a practical point of view because it protects the trial against various sources of bias. As such, the proposed design addresses some of the key issues that have been suggested as preventing so-called bandit models from being implemented in clinical practice. 2017-09 2016-09-28 /pmc/articles/PMC5473477/ /pubmed/28630525 http://dx.doi.org/10.1016/j.csda.2016.09.006 Text en https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Williamson, S. Faye
Jacko, Peter
Villar, Sofía S.
Jaki, Thomas
A Bayesian adaptive design for clinical trials in rare diseases
title A Bayesian adaptive design for clinical trials in rare diseases
title_full A Bayesian adaptive design for clinical trials in rare diseases
title_fullStr A Bayesian adaptive design for clinical trials in rare diseases
title_full_unstemmed A Bayesian adaptive design for clinical trials in rare diseases
title_short A Bayesian adaptive design for clinical trials in rare diseases
title_sort bayesian adaptive design for clinical trials in rare diseases
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5473477/
https://www.ncbi.nlm.nih.gov/pubmed/28630525
http://dx.doi.org/10.1016/j.csda.2016.09.006
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