Poor Translatability of Biomedical Research Using Animals — A Narrative Review

Abstract

The failure rate for the translation of drugs from animal testing to human treatments remains at over 92%, where it has been for the past few decades. The majority of these failures are due to unexpected toxicity — that is, safety issues revealed in human trials that were not apparent in animal tests — or lack of efficacy. However, the use of more innovative tools, such as organs-on-chips, in the preclinical pipeline for drug testing, has revealed that these tools are more able to predict unexpected safety events prior to clinical trials and so can be used for this, as well as for efficacy testing. Here, we review several disease areas, and consider how the use of animal models has failed to offer effective new treatments. We also make some suggestions as to how the more human-relevant new approach methodologies might be applied to address this.

Generation of a Perfusable 3D Lung Cancer Model by Digital Light Processing

“…This chimeric constellation is unlikely to represent the physiology of a human patient. The failure rate for the translation of drug candidates from animal testing to human treatments remains over 92% [ 14 ], and for anticancer drug candidates, even up to 97% of all substances that underwent successful pre-clinical development fail during clinical testing [ 15 ]. Although the reasons for terminating clinical trials are manifold, the high failure rate illustrates the need for better models for the pre-clinical characterization of potential anticancer drugs.…”

Editorial

“…The review of Marshall et al, 8 gives a critical overview of the need to move away from previous practices in drug development, because of the lack of translatability of animal experiments to the responses observed in humans.…”

“…The review of Marshall et al, 8 gives a critical overview of the need to move away from previous practices in drug development, because of the lack of translatability of animal experiments to the responses observed in humans. Reporting that the rate of failure in translating animal testing to human treatments remains at 92%, the authors provide details regarding a number of key disease areas where this is particularly problematic.…”

How to improve translatability and clinical relevance of preclinical studies in rheumatoid arthritis

“…These animal models include the induced arthritis models that require immunisation with antigens (i.e., collagen-induced arthritis [CIA], proteoglycan-induced arthritis, streptococcal cell wallinduced arthritis, methylated bovine serum albumin model), arthritis models induced by adjuvants (i.e., oilinduced arthritis, zymosan-induced arthritis), arthritis models induced by transfer of antibodies (i.e., collagen antibody-induced arthritis, K/BxN serum-transfer arthritis) and the genetically engineered or spontaneous arthritis models (i.e., tumour necrosis factor [TNF]-transgenic, K/BxN T-cell receptor transgenic, SKG mice) [7]. Each of these animal models of arthritis mimic only aspects of the complex pathogenesis of human RA [7,8]. Notwithstanding this progress in animal model development, the failure rate in human diseases of drugs successfully tested in animal models remains high [8], suggesting poor translatability of animal models to human diseases [8][9][10].…”

“…Each of these animal models of arthritis mimic only aspects of the complex pathogenesis of human RA [7,8]. Notwithstanding this progress in animal model development, the failure rate in human diseases of drugs successfully tested in animal models remains high [8], suggesting poor translatability of animal models to human diseases [8][9][10]. Along these lines, although there was a strong indication from studies in CIA about a pathogenic role of interleukin-17 (IL-17) [11][12][13], three IL-17 inhibitors (ixekizumab, brodalumab and secukinumab) have failed to prove clinical efficacy in human RA [14][15][16].…”