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Recent advances in methodology for clinical trials in small populations: the InSPiRe project

Where there are a limited number of patients, such as in a rare disease, clinical trials in these small populations present several challenges, including statistical issues. This led to an EU FP7 call for proposals in 2013. One of the three projects funded was the Innovative Methodology for Small Po...

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Autores principales: Friede, Tim, Posch, Martin, Zohar, Sarah, Alberti, Corinne, Benda, Norbert, Comets, Emmanuelle, Day, Simon, Dmitrienko, Alex, Graf, Alexandra, Günhan, Burak Kürsad, Hee, Siew Wan, Lentz, Frederike, Madan, Jason, Miller, Frank, Ondra, Thomas, Pearce, Michael, Röver, Christian, Toumazi, Artemis, Unkel, Steffen, Ursino, Moreno, Wassmer, Gernot, Stallard, Nigel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6203217/
https://www.ncbi.nlm.nih.gov/pubmed/30359266
http://dx.doi.org/10.1186/s13023-018-0919-y
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author Friede, Tim
Posch, Martin
Zohar, Sarah
Alberti, Corinne
Benda, Norbert
Comets, Emmanuelle
Day, Simon
Dmitrienko, Alex
Graf, Alexandra
Günhan, Burak Kürsad
Hee, Siew Wan
Lentz, Frederike
Madan, Jason
Miller, Frank
Ondra, Thomas
Pearce, Michael
Röver, Christian
Toumazi, Artemis
Unkel, Steffen
Ursino, Moreno
Wassmer, Gernot
Stallard, Nigel
author_facet Friede, Tim
Posch, Martin
Zohar, Sarah
Alberti, Corinne
Benda, Norbert
Comets, Emmanuelle
Day, Simon
Dmitrienko, Alex
Graf, Alexandra
Günhan, Burak Kürsad
Hee, Siew Wan
Lentz, Frederike
Madan, Jason
Miller, Frank
Ondra, Thomas
Pearce, Michael
Röver, Christian
Toumazi, Artemis
Unkel, Steffen
Ursino, Moreno
Wassmer, Gernot
Stallard, Nigel
author_sort Friede, Tim
collection PubMed
description Where there are a limited number of patients, such as in a rare disease, clinical trials in these small populations present several challenges, including statistical issues. This led to an EU FP7 call for proposals in 2013. One of the three projects funded was the Innovative Methodology for Small Populations Research (InSPiRe) project. This paper summarizes the main results of the project, which was completed in 2017. The InSPiRe project has led to development of novel statistical methodology for clinical trials in small populations in four areas. We have explored new decision-making methods for small population clinical trials using a Bayesian decision-theoretic framework to compare costs with potential benefits, developed approaches for targeted treatment trials, enabling simultaneous identification of subgroups and confirmation of treatment effect for these patients, worked on early phase clinical trial design and on extrapolation from adult to pediatric studies, developing methods to enable use of pharmacokinetics and pharmacodynamics data, and also developed improved robust meta-analysis methods for a small number of trials to support the planning, analysis and interpretation of a trial as well as enabling extrapolation between patient groups. In addition to scientific publications, we have contributed to regulatory guidance and produced free software in order to facilitate implementation of the novel methods.
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spelling pubmed-62032172018-11-01 Recent advances in methodology for clinical trials in small populations: the InSPiRe project Friede, Tim Posch, Martin Zohar, Sarah Alberti, Corinne Benda, Norbert Comets, Emmanuelle Day, Simon Dmitrienko, Alex Graf, Alexandra Günhan, Burak Kürsad Hee, Siew Wan Lentz, Frederike Madan, Jason Miller, Frank Ondra, Thomas Pearce, Michael Röver, Christian Toumazi, Artemis Unkel, Steffen Ursino, Moreno Wassmer, Gernot Stallard, Nigel Orphanet J Rare Dis Review Where there are a limited number of patients, such as in a rare disease, clinical trials in these small populations present several challenges, including statistical issues. This led to an EU FP7 call for proposals in 2013. One of the three projects funded was the Innovative Methodology for Small Populations Research (InSPiRe) project. This paper summarizes the main results of the project, which was completed in 2017. The InSPiRe project has led to development of novel statistical methodology for clinical trials in small populations in four areas. We have explored new decision-making methods for small population clinical trials using a Bayesian decision-theoretic framework to compare costs with potential benefits, developed approaches for targeted treatment trials, enabling simultaneous identification of subgroups and confirmation of treatment effect for these patients, worked on early phase clinical trial design and on extrapolation from adult to pediatric studies, developing methods to enable use of pharmacokinetics and pharmacodynamics data, and also developed improved robust meta-analysis methods for a small number of trials to support the planning, analysis and interpretation of a trial as well as enabling extrapolation between patient groups. In addition to scientific publications, we have contributed to regulatory guidance and produced free software in order to facilitate implementation of the novel methods. BioMed Central 2018-10-25 /pmc/articles/PMC6203217/ /pubmed/30359266 http://dx.doi.org/10.1186/s13023-018-0919-y Text en © The Author(s) 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License(http://creativecommons.org/licenses/by/4.0/), 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. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Review
Friede, Tim
Posch, Martin
Zohar, Sarah
Alberti, Corinne
Benda, Norbert
Comets, Emmanuelle
Day, Simon
Dmitrienko, Alex
Graf, Alexandra
Günhan, Burak Kürsad
Hee, Siew Wan
Lentz, Frederike
Madan, Jason
Miller, Frank
Ondra, Thomas
Pearce, Michael
Röver, Christian
Toumazi, Artemis
Unkel, Steffen
Ursino, Moreno
Wassmer, Gernot
Stallard, Nigel
Recent advances in methodology for clinical trials in small populations: the InSPiRe project
title Recent advances in methodology for clinical trials in small populations: the InSPiRe project
title_full Recent advances in methodology for clinical trials in small populations: the InSPiRe project
title_fullStr Recent advances in methodology for clinical trials in small populations: the InSPiRe project
title_full_unstemmed Recent advances in methodology for clinical trials in small populations: the InSPiRe project
title_short Recent advances in methodology for clinical trials in small populations: the InSPiRe project
title_sort recent advances in methodology for clinical trials in small populations: the inspire project
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6203217/
https://www.ncbi.nlm.nih.gov/pubmed/30359266
http://dx.doi.org/10.1186/s13023-018-0919-y
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