PT  - JOURNAL ARTICLE
AU  - Hunter, Harriet
AU  - de Gracia Hahn, Dana
AU  - Duret, Amedine
AU  - Im, Yu Ri
AU  - Cheah, Qinrong
AU  - Dong, Jiawen
AU  - Fairey, Madison
AU  - Hjalmarsson, Clarissa
AU  - Li, Alice
AU  - Lim, Hong Kai
AU  - McKeown, Lorcán
AU  - Mitrofan, Claudia-Gabriela
AU  - Rao, Raunak
AU  - Utukuri, Mrudula
AU  - Rowe, Ian A.
AU  - Mann, Jake P.
TI  - What influences treatment response in animal models of non-alcoholic fatty liver disease? A meta-analysis with meta-regression
AID  - 10.1101/2019.12.31.887919
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2019.12.31.887919
4099  - http://biorxiv.org/content/early/2020/02/25/2019.12.31.887919.short
4100  - http://biorxiv.org/content/early/2020/02/25/2019.12.31.887919.full
AB  - 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.