A Systematic Review Comparing Experimental Design of Animal and Human Methotrexate Efficacy Studies for Rheumatoid Arthritis: Lessons for the Translational Value of Animal Studies

Abstract

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.

Insufficient transparency of statistical reporting in preclinical research: a scoping review

“…Clinical journals were excluded although they may include publications with some preclinical experiments. This was justified to prevent the possible bias created by both the presumed small proportion of such articles in clinical periodicals which would have prompted a larger sampling and the supposed compliance of these studies with clinical guidelines whose standards may be different 29,30 . Fifteen articles per journal were collected by sampling the online contents of each journal, starting from the last issue released in 2019 and browsing backward.…”

Does Low-Magnitude High-Frequency Vibration (LMHFV) Worth for Clinical Trial on Dental Implant? A Systematic Review and Meta-Analysis on Animal Studies

“…Indeed, all experiments might have certain limitations and it is important to report all factors, no matter contributive or destructive, so that readers or even the “artificial intelligence” can learn the facts genuinely. For the published data, prospective systematic review on animal studies was indeed recently advocated that can produce sound and actual clinical knowledge (Pound and Ritskes-Hoitinga, 2020 ), under the circumstances proper designs and valid models which can be found in methotrexate (Leenaars et al, 2020 ) and dental implant (Manzano et al, 2014 ) studies that were with meta-analysis. Thus, our current study can give a frank, fair, and open opinion to all readers.…”

Reviewing the animal literature: how to describe and choose between different types of literature reviews

“… 62 However, a systematic review can also be used to answer a different type of review question, for example ‘are the experimental designs of preclinical animal studies comparable to those of the clinical trials?’. 63 …”