<i>In Silico</i> Organ Modelling in Predicting Efficacy and Safety of New Medicines

Rodríguez, Blanca

doi:10.1039/9781782620136-00219

Cited by 2 publications

(2 citation statements)

References 90 publications

(144 reference statements)

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“…In silico methods will undoubtedly contribute increasingly to drug testing paradigms, as significant efforts are being made to develop improved methods, both to predict drug effects in various organs of the human body (15), and, excitingly, also to model the organs themselves (16). However, since these can only be based on what we know, their ultimate value will depend heavily on the availability of the clinical data on which models can be built.…”

Section: The Challenge Of Humanising the Processmentioning

confidence: 99%

Barriers to the Uptake of Human-based Test Methods, and how to Overcome Them

Archibald

Drake²,

Coleman

2015

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Although there is growing concern as to the questionable value of animal-based methods for determining the safety and efficacy of new medicines, which has in turn led to many groups developing innovative human-based methods, there are many barriers to their adoption for regulatory submissions. The reasons for this are various, and include a lack of confidence that the available human-based methods, be they in vivo, in silico or in vitro, can be sufficiently predictive of clinical outcomes. However, this is not the only problem: the issue of validation presents a serious impediment to progress, a particularly frustrating situation, in view of the fact that the existing animal-based methods have never themselves been formally validated. Superimposed upon this is the issue of regulatory requirements, where, although regulators may be willing to accept non-animal approaches in place of particular animal tests, nowhere is this explicitly stated in their guidelines. Such problems are far from trivial, and represent major hurdles to be overcome. In addition, there are a range of other barriers, real or self-imposed, that are hindering a more-predictive approach to establishing a new drug's clinical safety and efficacy profiles. Some of these barriers are identified, and ways forward are suggested.

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Section: The Challenge Of Humanising the Processmentioning

confidence: 99%

Barriers to the Uptake of Human-based Test Methods, and how to Overcome Them

Archibald

Drake²,

Coleman

2015

Altern Lab Anim

View full text Add to dashboard Cite

show abstract

“…These incorporate a wide range of aspects of structure and function of the organ in question, and allow the modelling of responses to agents that interact with known processes within that organ. This approach has been particularly well developed in modelling the human heart -in terms of single cardiomyocytes and also the whole heart (35). This is a hugely complex exercise, which requires in-depth understanding of cardiac architecture and of the elements contributing to the electrophysiological control of cardiac function.…”

Section: In Silico Approachesmentioning

confidence: 99%

Human-based Systems in Drug and Chemical Safety Testing — toward Replacement, the ‘Single R’

Coleman

2014

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The Three Rs was a concept originally conceived as a means of reducing the suffering of laboratory animals that are used largely in identifying any potential safety issues with chemicals to which humans may be exposed. However, with growing evidence of the shortcomings of laboratory animal testing to reliably predict human responsiveness to such chemicals, questions are now being asked as to whether it is appropriate to use animals as human surrogates at all. This raises the question of whether, of the original Three Rs, two — Reduction and Refinement — are potentially redundant, and whether, instead, we should concentrate on the third R: Replacement. And if this is the best way forward, it is inevitable that this R should be based firmly on human biology. The present review outlines the current state-of-the-art regarding our access to human biology through in vitro, in silico and in vivo technologies, identifying strengths, weaknesses and opportunities, and goes on to address the prospect of achieving a single R, with some suggestions as to how to progress toward this goal.

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In Silico Organ Modelling in Predicting Efficacy and Safety of New Medicines

Cited by 2 publications

References 90 publications

Barriers to the Uptake of Human-based Test Methods, and how to Overcome Them

Barriers to the Uptake of Human-based Test Methods, and how to Overcome Them

Human-based Systems in Drug and Chemical Safety Testing — toward Replacement, the ‘Single R’

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