TY - JOUR

T1 - A Systematic Review Comparing Experimental Design of Animal and Human Methotrexate Efficacy Studies for Rheumatoid Arthritis

T2 - Lessons for the Translational Value of Animal Studies

AU - Leenaars, Cathalijn

AU - Stafleu, Frans

AU - Jong, David de

AU - Berlo, Maikel van

AU - Geurts, Tijmen

AU - Roo, Tineke Coenen-de

AU - Prins, Jan-Bas

AU - Kempkes, Rosalie

AU - Elzinga, Janneke

AU - Bleich, André

AU - Vries, Rob de

AU - Meijboom, Franck

AU - Ritskes-Hoitinga, Merel

PY - 2020

Y1 - 2020

N2 - Increased awareness and understanding of current practices in translational research is required for informed decision making in drug development. This paper describes a systematic review of methotrexate for rheumatoid arthritis, comparing trial design between 147 animal and 512 human studies. Animal studies generally included fewer subjects than human studies, and less frequently reported randomisation and blinding. In relation to life span, study duration was comparable for animals and humans, but included animals were younger than included humans. Animal studies often comprised males only (61%), human studies always included females (98% included both sexes). Power calculations were poorly reported in both samples. Analyses of human studies more frequently comprised Chi-square tests, those of animal studies more frequently reported analyses of variance. Administration route was more variable, and more frequently reported in animal than human studies. Erythrocyte sedimentation rate and c-reactive protein were analysed more frequently in human than in animal studies. To conclude, experimental designs for animal and human studies are not optimally aligned. However, methotrexate is effective in treating rheumatoid arthritis in animal models and humans. Further evaluation of the available evidence in other research fields is needed to increase the understanding of translational success before we can optimise translational strategies.

AB - Increased awareness and understanding of current practices in translational research is required for informed decision making in drug development. This paper describes a systematic review of methotrexate for rheumatoid arthritis, comparing trial design between 147 animal and 512 human studies. Animal studies generally included fewer subjects than human studies, and less frequently reported randomisation and blinding. In relation to life span, study duration was comparable for animals and humans, but included animals were younger than included humans. Animal studies often comprised males only (61%), human studies always included females (98% included both sexes). Power calculations were poorly reported in both samples. Analyses of human studies more frequently comprised Chi-square tests, those of animal studies more frequently reported analyses of variance. Administration route was more variable, and more frequently reported in animal than human studies. Erythrocyte sedimentation rate and c-reactive protein were analysed more frequently in human than in animal studies. To conclude, experimental designs for animal and human studies are not optimally aligned. However, methotrexate is effective in treating rheumatoid arthritis in animal models and humans. Further evaluation of the available evidence in other research fields is needed to increase the understanding of translational success before we can optimise translational strategies.

U2 - 10.3390/ani10061047

DO - 10.3390/ani10061047

M3 - Journal article

VL - 10

JO - Animals

JF - Animals

SN - 2076-2615

IS - 6

M1 - 1047

ER -