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Can harmonisation of outcomes bridge the translation gap for pre-clinical research? A systematic review of outcomes measured in mouse models of type 2 diabetes
BACKGROUND: In pre-clinical research, systematic reviews have the potential to mitigate translational challenges by facilitating understanding of how pre-clinical studies can inform future clinical research. Yet their conduct is encumbered by heterogeneity in the outcomes measured and reported, and...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727210/ https://www.ncbi.nlm.nih.gov/pubmed/33298112 http://dx.doi.org/10.1186/s12967-020-02649-6 |
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author | Harman, Nicola L. Sanz-Moreno, Adrián Papoutsopoulou, Stamatia Lloyd, Katie A. Ameen-Ali, Kamar E. Macleod, Malcolm Williamson, Paula R. |
author_facet | Harman, Nicola L. Sanz-Moreno, Adrián Papoutsopoulou, Stamatia Lloyd, Katie A. Ameen-Ali, Kamar E. Macleod, Malcolm Williamson, Paula R. |
author_sort | Harman, Nicola L. |
collection | PubMed |
description | BACKGROUND: In pre-clinical research, systematic reviews have the potential to mitigate translational challenges by facilitating understanding of how pre-clinical studies can inform future clinical research. Yet their conduct is encumbered by heterogeneity in the outcomes measured and reported, and those outcomes may not always relate to the most clinically important outcomes. We aimed to systematically review outcomes measured and reported in pre-clinical in vivo studies of pharmacological interventions to treat high blood glucose in mouse models of type 2 diabetes. METHODS: A systematic review of pre-clinical in vivo studies of pharmacological interventions aimed at addressing elevated blood glucose in mouse models of type 2 diabetes was completed. Studies were screened for eligibility and outcomes extracted from the included studies. The outcomes were recorded verbatim and classified into outcome domains using an existing outcome taxonomy. Outcomes were also compared to those identified in a systematic review of registered phase 3/4 clinical trials for glucose lowering interventions in people with type 2 diabetes. RESULTS: Review of 280 included studies identified 532 unique outcomes across 19 domains. No single outcome, or domain, was measured in all studies and only 132 (21%) had also been measured in registered phase 3/4 clinical trials. A core outcome set, representing the minimum that should be measured and reported, developed for type 2 diabetes effectiveness clinical trials includes 18 core outcomes, of these 12 (71%) outcomes were measured and reported in one or more of the included pre-clinical studies. CONCLUSIONS: There is heterogeneity of outcomes reported in pre-clinical research. Harmonisation of outcomes across the research pathway using a core outcome set may facilitate interpretation, evidence synthesis and translational success, and may contribute to the refinement of the use of animals in research. Systematic review registration: The study was prospectively registered on the PROSPERO Database, registration number CRD42018106831 |
format | Online Article Text |
id | pubmed-7727210 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-77272102020-12-11 Can harmonisation of outcomes bridge the translation gap for pre-clinical research? A systematic review of outcomes measured in mouse models of type 2 diabetes Harman, Nicola L. Sanz-Moreno, Adrián Papoutsopoulou, Stamatia Lloyd, Katie A. Ameen-Ali, Kamar E. Macleod, Malcolm Williamson, Paula R. J Transl Med Research BACKGROUND: In pre-clinical research, systematic reviews have the potential to mitigate translational challenges by facilitating understanding of how pre-clinical studies can inform future clinical research. Yet their conduct is encumbered by heterogeneity in the outcomes measured and reported, and those outcomes may not always relate to the most clinically important outcomes. We aimed to systematically review outcomes measured and reported in pre-clinical in vivo studies of pharmacological interventions to treat high blood glucose in mouse models of type 2 diabetes. METHODS: A systematic review of pre-clinical in vivo studies of pharmacological interventions aimed at addressing elevated blood glucose in mouse models of type 2 diabetes was completed. Studies were screened for eligibility and outcomes extracted from the included studies. The outcomes were recorded verbatim and classified into outcome domains using an existing outcome taxonomy. Outcomes were also compared to those identified in a systematic review of registered phase 3/4 clinical trials for glucose lowering interventions in people with type 2 diabetes. RESULTS: Review of 280 included studies identified 532 unique outcomes across 19 domains. No single outcome, or domain, was measured in all studies and only 132 (21%) had also been measured in registered phase 3/4 clinical trials. A core outcome set, representing the minimum that should be measured and reported, developed for type 2 diabetes effectiveness clinical trials includes 18 core outcomes, of these 12 (71%) outcomes were measured and reported in one or more of the included pre-clinical studies. CONCLUSIONS: There is heterogeneity of outcomes reported in pre-clinical research. Harmonisation of outcomes across the research pathway using a core outcome set may facilitate interpretation, evidence synthesis and translational success, and may contribute to the refinement of the use of animals in research. Systematic review registration: The study was prospectively registered on the PROSPERO Database, registration number CRD42018106831 BioMed Central 2020-12-09 /pmc/articles/PMC7727210/ /pubmed/33298112 http://dx.doi.org/10.1186/s12967-020-02649-6 Text en © The Author(s) 2020 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/. 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 in a credit line to the data. |
spellingShingle | Research Harman, Nicola L. Sanz-Moreno, Adrián Papoutsopoulou, Stamatia Lloyd, Katie A. Ameen-Ali, Kamar E. Macleod, Malcolm Williamson, Paula R. Can harmonisation of outcomes bridge the translation gap for pre-clinical research? A systematic review of outcomes measured in mouse models of type 2 diabetes |
title | Can harmonisation of outcomes bridge the translation gap for pre-clinical research? A systematic review of outcomes measured in mouse models of type 2 diabetes |
title_full | Can harmonisation of outcomes bridge the translation gap for pre-clinical research? A systematic review of outcomes measured in mouse models of type 2 diabetes |
title_fullStr | Can harmonisation of outcomes bridge the translation gap for pre-clinical research? A systematic review of outcomes measured in mouse models of type 2 diabetes |
title_full_unstemmed | Can harmonisation of outcomes bridge the translation gap for pre-clinical research? A systematic review of outcomes measured in mouse models of type 2 diabetes |
title_short | Can harmonisation of outcomes bridge the translation gap for pre-clinical research? A systematic review of outcomes measured in mouse models of type 2 diabetes |
title_sort | can harmonisation of outcomes bridge the translation gap for pre-clinical research? a systematic review of outcomes measured in mouse models of type 2 diabetes |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727210/ https://www.ncbi.nlm.nih.gov/pubmed/33298112 http://dx.doi.org/10.1186/s12967-020-02649-6 |
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