What influences treatment response in animal models of non-alcoholic fatty liver disease? A meta-analysis with meta-regression.

Hunter, H.; de Gracia Hahn, D.; Duret, A.; Im, Y. R.; Cheah, Q.; Dong, J.; Fairey, M.; Hjalmarsson, C.; Li, A.; Lim, H. K.; McKeown, L.; Mitrofan, C.-G.; Rao, R.; Utukuri, M.; Rowe, I. A.; Mann, J. P.

doi:10.1101/2019.12.31.887919

bioRxiv · 10.1101/2019.12.31.887919

What influences treatment response in animal models of non-alcoholic fatty liver disease? A meta-analysis with meta-regression.

Hunter, H.·de Gracia Hahn, D.·Duret, A.·Im, Y. R.·Cheah, Q.·Dong, J.·Fairey, M.·Hjalmarsson, C.·Li, A.·Lim, H. K.·McKeown, L.·Mitrofan, C.-G.·Rao, R.·Utukuri, M.·Rowe, I. A.·Mann, J. P.

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Abstract

The classical drug development pipeline necessitates studies using animal models of human disease to gauge future efficacy in humans, however, there is a comparatively low conversion rate from success in animals to in humans. Non-alcoholic fatty liver disease (NAFLD) is a complex chronic disease without any licensed therapies and hence a major field of animal research. We performed a meta-analysis of 414 interventional rodent studies (6,575 animals) in NAFLD to assess the mean difference in hepatic triglyceride content. 20 of 21 studied drug classes had similar efficacy with a mean difference of -30% hepatic triglyceride. However, when publication bias was accounted for, this reduced to -16% difference. Study characteristics were only able to account for a minority of variability on meta-regression, and we replicated previous findings of high risk of bias across 82% of cohorts. These findings build on previous work in preclinical neuroscience and help to explain the challenge of reproducibility and translation within the field of metabolism.

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Hunter, H., de Gracia Hahn, D., Duret, A., Im, Y. R., Cheah, Q., Dong, J., Fairey, M., Hjalmarsson, C., Li, A., Lim, H. K., McKeown, L., Mitrofan, C.-G., Rao, R., Utukuri, M., Rowe, I. A., Mann, J. P.. 2019-12-31. What influences treatment response in animal models of non-alcoholic fatty liver disease? A meta-analysis with meta-regression.. https://doi.org/10.1101/2019.12.31.887919

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