Flow diagrams of drug / biologics development

Breaking Eroom’s Law

Financing Biomedical Innovation (Health Finance)

• Lo model
• Time To Reboot Biotech

Estimation of clinical trial success rates and related parameters

Emerging technologies and their impact on regulatory science

NIH Request for Information on Catalyzing the Development and Use of Novel Alternative

Methods to Advance Biomedical Research

Improving target assessment in biomedical research – the GOT-IT recommendations

Artificial Organs | FDA Modernization Act 2.0 allows for alternatives to animal testing

Poor Translatability of Biomedical Research Using Animals — A Narrative Review

• A standardised framework to identify optimal animal models for efficacy assessment in drug development
• Tradition, Not Science, Is the Basis of Animal Model Selection in Translational and Applied Research
• Animal to human translation: a systematic scoping review of reported concordance rates

FDA Alternatives report January 2021

• Advancing New Alternative Methods at FDA
• New Alternative Methods Science Board Presentation
• Perspectives on Evaluating New Tools for Regulatory Use
• Focus Areas of Regulatory Science report

Roche Institute for Human Biology – Modeling the Future

• VIDEO
• Roche – Reducing animal testing

Human organs-on-chips for disease modelling, drug development and personalized medicine

• MPS Model-Omics & Context-Use
• Microphysiological Systems (MPS) flow chart
• Performance assessment and economic analysis of a human Liver-Chip for predictive toxicology
• Is it Time for Reviewer 3 to Request Human Organ Chip Experiments Instead of Animal Validation Studies?

NIH NCATS (National Center for Advancing Translational Sciences) Microphysiological Systems Program Tissue-on-chips for Safety and Efficacy Studies in Drug Development

• NIH NCATS Tissue Chip factsheet
• NIH microphysiological systems program Developing in vitro tools for safety and efficacy in drug development

CAAT

• Organoid Intelligence (OI) workshop

FDA Modeling & Simulation

• FDA How Simulation Can Transform Regulatory Pathways (VIDEO)
• Insilico Medicine – Biotech begins human trials of drug designed by artificial intelligence (Financial Times)

AI for Drug Discovery Landscape

• Accuracy of a Generative Artificial Intelligence Model in a Complex Diagnostic Challenge (JAMA)
• Towards Expert-Level Medical Question Answering with Large Language Models | MedPALM-2

Rethinking organoid technology through bioengineering

• Ethical issues in human organoid and gastruloid research

What’s Wrong with Human/Nonhuman Chimera Research?

• Ethical considerations for human animal neurological chimera research mouse models and beyond

Toward Guidelines for Research on Human Embryo Models Formed from Stem Cells

• The responsibility for ethical procurement of human embryos and gametes
• New monkey embryo models—it’s getting complicated

CLINICAL IMPACT OF ANIMAL STUDIES

Retrospective studies

• Bailey J, Balls M. Clinical impact of high-profile animal-based research reported in the UK national press. BMJ Open Sci. 2020;4(1):e100039. doi:10.1136/bmjos-2019-100039
• Contopoulos-Ioannidis DG, Ntzani EE, Ioannidis JPA. Translation of highly promising basic science research into clinical applications. Am J Med. 2003;114(6):477-484. doi:10.1016/S0002-9343(03)00013-5
• Pound P, Nicol CJ. Retrospective harm benefit analysis of pre-clinical animal research for six treatment interventions. PLoS One. 2018 Mar 28;13(3):e0193758.
• Grant J. Evaluating “payback” on biomedical research from papers cited in clinical guidelines: applied bibliometric study. BMJ. 2000;320(7242):1107-1111. doi:10.1136/bmj.320.7242.1107
• Wooding S, Hanney S, Pollitt A, Buxton M, Grant J. Project Retrosight: Understanding the Returns from Cardiovascular and Stroke Research: The Policy Report. Rand Heal Q. 2011;1(1):16.
• Steven Wooding, Alexandra Pollitt, Sophie Castle-Clarke, Gavin Cochrane, Stephanie Diepeveen, Susan Guthrie, Marcela Horvitz-Lennon, Vincent Larivière, Molly Morgan Jones, Siobhan Ni Chonaill, Claire O’Brien, Stuart S. Olmsted, Dana Schultz, Eleanor Winpe and JG. Mental Health Retrosight Understanding the returns from research (lessons from schizophrenia): Policy Report. Rand Heal Q. 2014;4(1).
• Guthrie S, Kirtley A, Garrod B, Pollitt A, Grant J, Wooding S. A “DECISIVE” Approach to Research Funding Lessons from Three Retrosight Studies.; 2016.
  

Poor translation to human patients

• Wall RJ, Shani M. Are animal models as good as we think? Theriogenology. 2008;69(1):2-9. doi:10.1016/j.theriogenology.2007.09.030
• Geerts H. Of mice and men. Bridging the translational disconnect in CNS drug discovery. CNS Drugs. 2009;23(1):915-926.
• Hackam, Daniel Redelmeier D. Translation of Research Evidence From Animals to Humans. JAMA. 2006;296(14):1731-1732.
• Langley GR. Considering a new paradigm for Alzheimer’s disease research. Drug Discov Today. 2014;19(8):1114-1124. doi:10.1016/j.drudis.2014.03.013
• LaFollette H, Shanks N. Animal experimentation: The legacy of Claude Bernard. Int Stud Philos Sci. 1994;8(3):195-210. doi:10.1080/02698599408573495
• Marshall LJ, Triunfol M, Seidle T. Patient-Derived Xenograft vs. Organoids: A Preliminary Analysis of Cancer Research Output, Funding and Human Health Impact in 2014 – 2019. Animals. 2020;10(1923). doi:10.3390/ani10101923
• O’Collins VE, Macleod MR, Donnan GA, Horky LL, van der Worp BH, Howells DW. 1,026 Experimental treatments in acute stroke. Ann Neurol. 2006;59(3):467-477. doi:10.1002/ana.20741
• Perel P, Roberts I, Sena E, et al. Comparison of treatment effects between animal experiments and clinical trials: systematic review. BMJ. 2007;334(7586):197. doi:10.1136/bmj.39048.407928.BE
• Perlman RL. Mouse Models of Human Disease: An Evolutionary Perspective. Evol Med Public Heal. Published online April 27, 2016:eow014. doi:10.1093/emph/eow014
• Pound P, Ram R. Are researchers moving away from animal models as a result of poor clinical translation in the field of stroke? An analysis of opinion papers. BMJ Open Sci. 2020;4(1):e100041. doi:10.1136/bmjos-2019-100041
• Pound P, Bracken MB. Is animal research sufficiently evidence based to be a cornerstone of biomedical research?. Bmj. 2014 May 30;348.
• Pound P, Ritskes-Hoitinga M. Is it possible to overcome issues of external validity in preclinical animal research? Why most animal models are bound to fail. Journal of translational medicine. 2018 Dec;16(1):1-8.
• Howells DW, Sena ES, O’Collins V, Macleod MR. Improving the Efficiency of the Development of Drugs for Stroke. Int J Stroke. 2012;7(5):371-377. doi:10.1111/j.1747-4949.2012.00805.x
• Cummings JL, Morstorf T, Zhong K. Alzheimer’s disease drug-development pipeline: few candidates, frequent failures. Alzheimers Res Ther. 2014;6(4):37. doi:10.1186/alzrt269
• Akhtar A. The flaws and human harms of animal experimentation. Camb Q Healthc Ethics. 2015 Oct;24(4):407-19. doi: 10.1017/S0963180115000079. PMID: 26364776; PMCID: PMC4594046.
  

Citation analyses showing rare clinical citation of animal studies

• Constança Carvalho, Filipa Peste, Tiago A Marques, Andrew Knight LV. The Contribution of Rat Studies to the Current Knowledge of Major Depressive Disorder: Results from Citation Analysis. Front Psychol. 2020;11(July):1-8. doi:10.3389/fpsyg.2020.01486
• Carvalho C, Varela SAM, Bastos LF, et al. The Relevance of In Silico , In Vitro and Non-human Primate Based Approaches to Clinical Research on Major Depressive Disorder. Altern to Lab Anim. 2019;47(3-4):128-139. doi:10.1177/0261192919885578
• Knight A. The Poor Contribution of Chimpanzee Experiments to Biomedical Progress. J Appl Anim Welf Sci. 2007;10(4):281-308. doi:10.1080/10888700701555501

The Center for Contemporary Sciences (CCS) is a non-profit organization dedicated to advancing the health and well-being of humans, animals, and the planet. Core to our mission is supporting innovative scientific and technological advancements that accelerate drug development and the discovery of cures.