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Innovative trial approaches in immune-mediated inflammatory diseases: current use and future potential

BACKGROUND: Despite progress that has been made in the treatment of many immune-mediated inflammatory diseases (IMIDs), there remains a need for improved treatments. Randomised controlled trials (RCTs) provide the highest form of evidence on the effectiveness of a potential new treatment regimen, bu...

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Autores principales: Grayling, Michael J., Bigirumurame, Theophile, Cherlin, Svetlana, Ouma, Luke, Zheng, Haiyan, Wason, James M. S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252241/
https://www.ncbi.nlm.nih.gov/pubmed/34210348
http://dx.doi.org/10.1186/s41927-021-00192-5
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author Grayling, Michael J.
Bigirumurame, Theophile
Cherlin, Svetlana
Ouma, Luke
Zheng, Haiyan
Wason, James M. S.
author_facet Grayling, Michael J.
Bigirumurame, Theophile
Cherlin, Svetlana
Ouma, Luke
Zheng, Haiyan
Wason, James M. S.
author_sort Grayling, Michael J.
collection PubMed
description BACKGROUND: Despite progress that has been made in the treatment of many immune-mediated inflammatory diseases (IMIDs), there remains a need for improved treatments. Randomised controlled trials (RCTs) provide the highest form of evidence on the effectiveness of a potential new treatment regimen, but they are extremely expensive and time consuming to conduct. Consequently, much focus has been given in recent years to innovative design and analysis methods that could improve the efficiency of RCTs. In this article, we review the current use and future potential of these methods within the context of IMID trials. METHODS: We provide a review of several innovative methods that would provide utility in IMID research. These include novel study designs (adaptive trials, Sequential Multi-Assignment Randomised Trials, basket, and umbrella trials) and data analysis methodologies (augmented analyses of composite responder endpoints, using high-dimensional biomarker information to stratify patients, and emulation of RCTs from routinely collected data). IMID trials are now well-placed to embrace innovative methods. For example, well-developed statistical frameworks for adaptive trial design are ready for implementation, whilst the growing availability of historical datasets makes the use of Bayesian methods particularly applicable. To assess whether and how these innovative methods have been used in practice, we conducted a review via PubMed of clinical trials pertaining to any of 51 IMIDs that were published between 2018 and 20 in five high impact factor clinical journals. RESULTS: Amongst 97 articles included in the review, 19 (19.6%) used an innovative design method, but most of these were relatively straightforward examples of innovative approaches. Only two (2.1%) reported the use of evidence from routinely collected data, cohorts, or biobanks. Eight (9.2%) collected high-dimensional data. CONCLUSIONS: Application of innovative statistical methodology to IMID trials has the potential to greatly improve efficiency, to generalise and extrapolate trial results, and to further personalise treatment strategies. Currently, such methods are infrequently utilised in practice. New research is required to ensure that IMID trials can benefit from the most suitable methods. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s41927-021-00192-5.
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spelling pubmed-82522412021-07-06 Innovative trial approaches in immune-mediated inflammatory diseases: current use and future potential Grayling, Michael J. Bigirumurame, Theophile Cherlin, Svetlana Ouma, Luke Zheng, Haiyan Wason, James M. S. BMC Rheumatol Research Article BACKGROUND: Despite progress that has been made in the treatment of many immune-mediated inflammatory diseases (IMIDs), there remains a need for improved treatments. Randomised controlled trials (RCTs) provide the highest form of evidence on the effectiveness of a potential new treatment regimen, but they are extremely expensive and time consuming to conduct. Consequently, much focus has been given in recent years to innovative design and analysis methods that could improve the efficiency of RCTs. In this article, we review the current use and future potential of these methods within the context of IMID trials. METHODS: We provide a review of several innovative methods that would provide utility in IMID research. These include novel study designs (adaptive trials, Sequential Multi-Assignment Randomised Trials, basket, and umbrella trials) and data analysis methodologies (augmented analyses of composite responder endpoints, using high-dimensional biomarker information to stratify patients, and emulation of RCTs from routinely collected data). IMID trials are now well-placed to embrace innovative methods. For example, well-developed statistical frameworks for adaptive trial design are ready for implementation, whilst the growing availability of historical datasets makes the use of Bayesian methods particularly applicable. To assess whether and how these innovative methods have been used in practice, we conducted a review via PubMed of clinical trials pertaining to any of 51 IMIDs that were published between 2018 and 20 in five high impact factor clinical journals. RESULTS: Amongst 97 articles included in the review, 19 (19.6%) used an innovative design method, but most of these were relatively straightforward examples of innovative approaches. Only two (2.1%) reported the use of evidence from routinely collected data, cohorts, or biobanks. Eight (9.2%) collected high-dimensional data. CONCLUSIONS: Application of innovative statistical methodology to IMID trials has the potential to greatly improve efficiency, to generalise and extrapolate trial results, and to further personalise treatment strategies. Currently, such methods are infrequently utilised in practice. New research is required to ensure that IMID trials can benefit from the most suitable methods. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s41927-021-00192-5. BioMed Central 2021-07-02 /pmc/articles/PMC8252241/ /pubmed/34210348 http://dx.doi.org/10.1186/s41927-021-00192-5 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Grayling, Michael J.
Bigirumurame, Theophile
Cherlin, Svetlana
Ouma, Luke
Zheng, Haiyan
Wason, James M. S.
Innovative trial approaches in immune-mediated inflammatory diseases: current use and future potential
title Innovative trial approaches in immune-mediated inflammatory diseases: current use and future potential
title_full Innovative trial approaches in immune-mediated inflammatory diseases: current use and future potential
title_fullStr Innovative trial approaches in immune-mediated inflammatory diseases: current use and future potential
title_full_unstemmed Innovative trial approaches in immune-mediated inflammatory diseases: current use and future potential
title_short Innovative trial approaches in immune-mediated inflammatory diseases: current use and future potential
title_sort innovative trial approaches in immune-mediated inflammatory diseases: current use and future potential
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252241/
https://www.ncbi.nlm.nih.gov/pubmed/34210348
http://dx.doi.org/10.1186/s41927-021-00192-5
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