The ability of animal studies to detect serious post marketing adverse events is limited

Meer, Peter J.K. van; Kooijman, M.; Wied, Christine C. Gispen‐de; Moors, Ellen H.M.; Schellekens, Huub

doi:10.1016/j.yrtph.2012.09.002

Cited by 53 publications

(27 citation statements)

References 13 publications

(12 reference statements)

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“…Those few analyses that have been done, tend to reflect unfavourably on animal models, including the dog. In 2012, a study that expressly set out to minimise bias, showed that 63% of serious ADRs had no counterparts in animals, and less than 20% of serious ADRs had a true positive corollary in animal studies (15). Other similar examples exist for testing generally (e.g.…”

Section: Discussionmentioning

confidence: 99%

An Analysis of the Use of Dogs in Predicting Human Toxicology and Drug Safety

Bailey¹,

Thew²,

Balls

2013

Altern Lab Anim

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Dogs remain the main non-rodent species in preclinical drug development. Despite the current dearth of new drug approvals and meagre pipelines, this continues, with little supportive evidence of its value or necessity. To estimate the evidential weight provided by canine data to the probability that a new drug may be toxic to humans, we have calculated Likelihood Ratios (LRs) for an extensive dataset of 2,366 drugs with both animal and human data, including tissue-level effects and Medical Dictionary for Regulatory Activities (MedDRA) Level 1-4 biomedical observations. The resulting LRs show that the absence of toxicity in dogs provides virtually no evidence that adverse drug reactions (ADRs) will also be absent in humans. While the LRs suggest that the presence of toxic effects in dogs can provide considerable evidential weight for a risk of potential ADRs in humans, this is highly inconsistent, varying by over two orders of magnitude for different classes of compounds and their effects. Our results therefore have important implications for the value of the dog in predicting human toxicity, and suggest that alternative methods are urgently required.

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Section: Discussionmentioning

confidence: 99%

An Analysis of the Use of Dogs in Predicting Human Toxicology and Drug Safety

Bailey¹,

Thew²,

Balls

2013

Altern Lab Anim

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“…Furthermore, the time, cost, and ethical concerns associated with animal models add to the limitations of their use as models of disease and screening platforms for potential therapeutics. Additionally, animal models are also limited in detecting post market adverse events [6]. Traditionally, in vitro cell culture systems have allowed for more rapid disease modeling and drug discovery studies.…”

Section: Introductionmentioning

confidence: 99%

Organoid and Organ-on-a-Chip Systems: New Paradigms for Modeling Neurological and Gastrointestinal Disease

et al. 2017

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Purpose of review The modeling of biological processes in vitro provides an important tool to better understand mechanisms of development and disease, allowing for the rapid testing of therapeutics. However, a critical constraint in traditional monolayer culture systems is the absence of the multicellularity, spatial organization, and overall microenvironment present in vivo. This limitation has resulted in numerous therapeutics showing efficacy in vitro, but failing in patient trials. In this review, we discuss several organoid and “organ-on-a-chip” systems with particular regard to the modeling of neurological diseases and gastrointestinal disorders. Recent findings Recently, the in vitro generation of multicellular organ-like structures, coined organoids, has allowed the modeling of human development, tissue architecture, and disease with human-specific pathophysiology. Additionally, microfluidic “organ-on-a-chip” technologies add another level of physiological mimicry by allowing biological mediums to be shuttled through 3D cultures. Summary Organoids and organ-chips are rapidly evolving in vitro platforms which hold great promise for the modeling of development and disease.

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“…By presenting an overview of EU FP-funded TA to non-human primate models for immune-mediated and neurodegenerative preclinical research performed at BPRC, we want to provide insight into these processes. By including unpublished studies in our analysis, we provide a different view on the contribution of non-human primate research to the development of new therapies as compared to an analysis of the drug registration files (9, 10). Such analyses underestimate the value of non-human primate preclinical research, as drugs that are not registered because of failure in non-human primate studies are usually not included.…”

Section: Introductionmentioning

confidence: 99%

An Evaluation of 20 Years of EU Framework Programme-Funded Immune-Mediated Inflammatory Translational Research in Non-Human Primates

2016

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Aging western societies are facing an increasing prevalence of chronic inflammatory and degenerative diseases for which often no effective treatments exist, resulting in increasing health-care expenditure. Despite high investments in drug development, the number of promising new drug candidates decreases. We propose that preclinical research in non-human primates can help to bridge the gap between drug discovery and drug prescription. Translational research covers various stages of drug development of which preclinical efficacy tests in valid animal models is usually the last stage. Preclinical research in non-human primates may be essential in the evaluation of new drugs or therapies when a relevant rodent model is not available. Non-human primate models for life-threatening or severely debilitating diseases in humans are available at the Biomedical Primate Research Centre (BPRC). These have been instrumental in translational research for several decades. In order to stimulate European health research and innovation from bench to bedside, the European Commission has invested heavily in access to non-human primate research for more than 20 years. BPRC has hosted European users in a series of transnational access programs covering a wide range of research areas with the common theme being immune-mediated inflammatory disorders. We present an overview of the results and give an account of the studies performed as part of European Union Framework Programme (EU FP)-funded translational non-human primate research performed at the BPRC. These data illustrate the value of translational non-human primate research for the development of new therapies and emphasize the importance of EU FP funding in drug development.

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The ability of animal studies to detect serious post marketing adverse events is limited

Cited by 53 publications

References 13 publications

An Analysis of the Use of Dogs in Predicting Human Toxicology and Drug Safety

An Analysis of the Use of Dogs in Predicting Human Toxicology and Drug Safety

Organoid and Organ-on-a-Chip Systems: New Paradigms for Modeling Neurological and Gastrointestinal Disease

An Evaluation of 20 Years of EU Framework Programme-Funded Immune-Mediated Inflammatory Translational Research in Non-Human Primates

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