Can harmonisation of outcomes bridge the translation gap for pre-clinical research? A systematic review of outcomes meas
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Journal of Translational Medicine Open Access
RESEARCH
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 Nicola L. Harman1* , Adrián Sanz‑Moreno2 , Stamatia Papoutsopoulou3 , Katie A. Lloyd4 , Kamar E. Ameen‑Ali5 , Malcolm Macleod6 and Paula R. Williamson1
Abstract 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 encum‑ bered 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-clini‑ cal 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 diabe‑ tes 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 transla‑ tional 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 Keywords: Type 2 diabetes, Pre-clinical research, Mouse models of type 2 diabetes, Core outcome set, Translational research, Clinical research, Pre-clinical systematic review
*Correspondence: [email protected] 1 Department of Health Data Science, University of Liverpool, Liverpool L69 3GL, UK Full list of author information is available at the end of the article
Background Clinical trials are undertaken to evaluate the effectiveness and safety of treatments in defined populations, and use pre-defined outcome measures. However, there is
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