A Systematic Review Comparing Experimental Design of Animal and Human Methotrexate Efficacy Studies for Rheumatoid Arthritis: Lessons for the Translational Value of Animal Studies
Cathalijn Leenaars,
Frans Stafleu,
David de Jong,
Maikel van Berlo,
Tijmen Geurts,
Tineke Coenen-de Roo,
Jan-Bas Prins,
Rosalie Kempkes,
Janneke Elzinga,
André Bleich,
Rob de Vries,
Franck Meijboom,
Merel Ritskes-Hoitinga
Affiliations
Cathalijn Leenaars
SYRCLE, Department for Health Evidence (Section HTA), Radboud Institute for Health Sciences, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands
Frans Stafleu
Ethics Institute, Utrecht University, 3508 TC Utrecht, The Netherlands
David de Jong
SYRCLE, Department for Health Evidence (Section HTA), Radboud Institute for Health Sciences, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands
Maikel van Berlo
SYRCLE, Department for Health Evidence (Section HTA), Radboud Institute for Health Sciences, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands
Tijmen Geurts
SYRCLE, Department for Health Evidence (Section HTA), Radboud Institute for Health Sciences, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands
Tineke Coenen-de Roo
Central Animal Facility, Leiden University Medical Centre, 2300 RC Leiden, The Netherlands
Jan-Bas Prins
Biological Research Facility, The Francis Crick Institute, London NW1 1AT, UK
Rosalie Kempkes
SYRCLE, Department for Health Evidence (Section HTA), Radboud Institute for Health Sciences, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands
Janneke Elzinga
SYRCLE, Department for Health Evidence (Section HTA), Radboud Institute for Health Sciences, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands
André Bleich
Institute for Laboratory Animal Science, Hannover Medical School, 30625 Hannover, Germany
Rob de Vries
SYRCLE, Department for Health Evidence (Section HTA), Radboud Institute for Health Sciences, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands
Franck Meijboom
Department of Population Health Science, Unit Animals in Science and Society, Utrecht University, 3508 TD Utrecht, The Netherlands
Merel Ritskes-Hoitinga
SYRCLE, Department for Health Evidence (Section HTA), Radboud Institute for Health Sciences, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands
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.
