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Spiralling research costs combined with urgent pressures from the Coronavirus 2019 (COVID-19) pandemic and the consequences of climate disruption are forcing changes in drug discovery. Increasing the predictive power of in vitro human assays and using them earlier in discovery would refocus resources on more successful research strategies and reduce animal studies. Increasing laboratory automation enables effective social distancing for researchers, while allowing integrated data capture from remote laboratory networks. Such disruptive changes would not only enable more cost-effective drug discovery, but could also reduce the overall carbon footprint of discovering new drugs., Competing Interests: Declaration of Competing Interests The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: J.M.T. is a director of Talisman Therapeutics Limited and Ubiquigent Limited as well as a shareholder of Cellesce Limited. G.R.L. has no interests to declare., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Decades of costly failures in translating drug candidates from preclinical disease models to human therapeutic use warrant reconsideration of the priority placed on animal models in biomedical research. Following an international workshop attended by experts from academia, government institutions, research funding bodies, and the corporate and non-governmental organisation (NGO) sectors, in this consensus report, we analyse, as case studies, five disease areas with major unmet needs for new treatments. In view of the scientifically driven transition towards a human pathways-based paradigm in toxicology, a similar paradigm shift appears to be justified in biomedical research. There is a pressing need for an approach that strategically implements advanced, human biology-based models and tools to understand disease pathways at multiple biological scales. We present recommendations to help achieve this., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Much of Alzheimer disease (AD) research has been traditionally based on the use of animals, which have been extensively applied in an effort to both improve our understanding of the pathophysiological mechanisms of the disease and to test novel therapeutic approaches. However, decades of such research have not effectively translated into substantial therapeutic success for human patients. Here we critically discuss these issues in order to determine how existing human-based methods can be applied to study AD pathology and develop novel therapeutics. These methods, which include patient-derived cells, computational analysis and models, together with large-scale epidemiological studies represent novel and exciting tools to enhance and forward AD research. In particular, these methods are helping advance AD research by contributing multifactorial and multidimensional perspectives, especially considering the crucial role played by lifestyle risk factors in the determination of AD risk. In addition to research techniques, we also consider related pitfalls and flaws in the current research funding system. Conversely, we identify encouraging new trends in research and government policy. In light of these new research directions, we provide recommendations regarding prioritization of research funding. The goal of this document is to stimulate scientific and public discussion on the need to explore new avenues in AD research, considering outcome and ethics as core principles to reliably judge traditional research efforts and eventually undertake new research strategies., Competing Interests: CONFLICTS OF INTERESTS Gillian Langley is a consultant to Humane Society International. Francesca Pistollato, Ann Lam, Neal Barnard, Mei-Chun Lai, Ryan Merkley and P. Charukeshi Chandrasekera work at the Physicians Committee for Responsible Medicine, a non-profit medical advocacy organization. Thomas J. Novak is an employee of Cellular Dynamics International (CDI) and the PI on CDI's grant with the California Institute for Regenerative Medicine (CIRM) to generate 3000 patient-derived iPSC lines, including those from patients with late-onset AD.