New paper by Dr Gerry Kenna published by Expert Opinion on Drug Metabolism & Toxicology:
"Human biology-based drug safety evaluation: scientific rationale, current status and future challenges"
Abbreviated abstract: Animal toxicity studies used to assess the safety of new candidate pharmaceuticals prior to their progression into human clinical trials are unable to assess the risk of non-pharmacologically mediated idiosyncratic adverse drug reactions (ADRs), the most frequent of which are drug-induced liver injury and cardiotoxicity... The chemical insults can be detected using in vitro assays. These enable useful discrimination between drugs that cause high versus low levels of idiosyncratic ADR concern... Widespread acceptance and use of such assays has been hampered by the lack of correlation between idiosyncratic human ADR risk and toxicities observed in vivo in animals.
Sir David Amess MP, plus two of our Science Advisers: Dr Kelly BéruBé and Professor Geoff Pilkington
Sir David Amess MP hosted the launch event, which was full to capacity with senior scientists and MPs whose enthusiasm and support were palpable.
Working together, the Alliance will help to speed the transition away from animal testing, towards more efficient and predictive models based on human biology. Many breakthroughs are lost in translation from animals to humans. There is now a tremendous opportunity to make drug development faster and safer, using human relevant technologies. Some exciting technologies were highlighted at the meeting, including cutting-edge models of the liver, linked together with other organs to realistically mimic the human body.
Sir David said: “Britain is a world leader in life science research. But we had better look to our laurels if we do not want to be left behind, while others take the lead in embracing more predictive tools based on human biology. I wish the new Alliance every success with this hugely important initiative.”
Dods conducted an online survey of 2,512 UK health and care professionals in March 2016.
They were asked one question about their perception of pharmaceutical testing regulations on behalf of Safer Medicines Trust.
The overwhelming majority of health professionals (79 per cent) agree that pharmaceutical companies should be legally obliged to test new medicines using methods demonstrated to be the most predictive of safety for humans.
Just three per cent of health professionals disagreed that pharmaceutical companies should be legally obliged to test new medicines using methods demonstrated to be the most predictive of safety for humans.
See full results here
Safer Medicines Trust is delighted to announce the appointment of Professor Barbara Pierscionek, PhD, MBA, LLM as our Scientific Director and Professor Chris Foster, MD, PhD, DSC, FRCPath as our Medical Director. They are both distinguished experts in human-focused biomedical research, who will lead the charity towards our goal of improving the safety of medicines and the future of biomedical research, by accelerating the paradigm shift from animal-based to human-relevant models.
Professor Pierscionek is Associate Dean of Research and Enterprise at Kingston University's Faculty of Science, Engineering and Computing. She qualified with clinical and scientific degrees (PhD in protein chemistry and optics) from the University of Melbourne and obtained an MBA and legal qualifications in the UK including the theoretical degree required for practice as a solicitor in England and Wales as well as a Masters degree in Law (LLM). Her scientific expertise is in the area of eye and vision research. She is a pioneer of multidisciplinary approaches leading to new insights into the vision and the ageing eye that have potential to improve outcomes for cataract patients in the design of new intraocular implants. She also works on the ethico-legal aspects of medical and biomedical research.
Professor Foster is the Medical Director of HCA Healthcare Laboratories, London, and Emeritus Professor of Pathology at the University of Liverpool. He is a leading specialist in the pathology of human cancers, particularly of the prostate, bladder and breast. Professor Foster received his BSc in Biochemistry at University College London and qualified in Medicine at the Westminster Medical School. He received his PhD from the Institute of Cancer Research and his MD at the Children’s Hospital of Philadelphia and the National Institutes of Health, Washington DC. In 2002, Professor Foster was awarded a DSc for his contribution to understanding “The Cellular and Molecular Biology of the Metastatic Process”.
Both professors have been Scientific Advisers to Safer Medicines Trust for several years and we are delighted that they are now taking on these leading roles. We welcome them both very warmly and look forward to them helping to lead the transition from animal models to human-relevant models.
Our article, written with Center for Responsible Science and published in ATLA, identifies some of the reasons for the glacial uptake of new, improved methods of safety assessment, and suggests ways forward, such as:
"...validation needs to become relative, rather than absolute. If a new test, or tests, can be shown to outperform what is currently required, that alone should suffice to ensure the continual and incremental replacement of underperforming tests with better ones, even if they are not yet perfect themselves. Unless this system of gradual improvement (which operates in almost every other sphere of endeavour) is adopted, the perfect will remain forever the enemy of the good."
"Perhaps the greatest barrier to the replacement of animal tests is the legal protection that they afford to pharmaceutical companies in litigation regarding adverse drug reactions. It is therefore imperative to increase awareness of the fallacy of such protection: unpredictive tests do not protect patients, and should no longer protect companies who continue to use them, when more-predictive methods not reliant on interspecies extrapolation are available."
Everyone understands that failing to update computer software leads to serious damage to computers. Yet we allow outdated protections for human health to go unfixed for decades. Is it any wonder that adverse drug reactions are now our fourth leading cause of death?
Editor in Chief of the Turkish Journal of Gastroenterology, Professor Hakan Sentürk, challenges other scientific journals to follow his lead and avoid publishing animal research, saying:
“Given the limitations of animal models, publishing animal studies would mislead the scientific community into futile research and give the general public false hope. This is unethical.”
He says: “Human-relevant approaches should be more aggressively developed and utilized instead. Fortunately, non-animal research methods like established clinical, computational and in vitro models abound, and new technologies like guts and other organs-on-chips are constantly being developed and validated.”
Safer Medicines Trust, as part of a coalition led by US charity Center for Responsible Science, has filed a Citizen Petition asking the FDA to update preclinical testing requirements, so as to ensure safer and more effective medical products are available to patients.
At the International Conference of Alternatives to Animal Experimentation in Portugal, on 8th May 2015, Dr Philip Low presented - to unanimous support - the 'Declaration of Lisbon':
''While recognizing that animal testing has long been a traditional component of biomedical research, it has become clearly apparent that the returns on investment in animal research are increasingly meager. To the extent that this type of research may continue, it is our recommendation that it be carried out after giving institutional committees, independent expert third party animal ethics committees, funding organizations and relevant regulatory authorities evaluating the proposed research (collectively 'The Parties') a more realistic and evidence-based estimate of the likely costs and benefits of the proposed protocols.'' - view the declaration in full
Dr Bob Coleman, UK Science Director of Safer Medicines Trust, also spoke at the Conference on 'Humanising Drug Safety Testing' - view his presentation
A report by the Oxford Centre for Animal Ethics, supported by more than 150 leading academics and intellectuals, including Nobel Laureate J. M. Coetzee, concludes that animal experimentation is "one of the major moral issues of our time". Safer Medicines would add that it is also a major moral issue for patients and all of us affected by biomedical research; i.e. all of us.
It is worth examining what the various political parties have pledged with respect to this issue in their 2015 election manifestos.
The Conservatives say they will: "work to accelerate the global development and take-up of alternatives to animal testing where appropriate.”
Labour does not mention the issue at all in their manifesto.
The Liberal Democrats say they will: "minimise the use of animals in scientific experimentation, including by funding research into alternatives. We remain committed to the three Rs of humane animal research: Replace, Reduce, Refine."
The Green Party make clear commitments towards ending all animal experimentation, saying they would take immediate action to: "Introduce a comprehensive system for reviewing animal experiments and initiate a comparison of currently required animal tests with a set of human-biology based tests.”
UKIP say they will: "Challenge companies using animals for testing drugs or other medical treatments on the necessity for this form of testing, as opposed to the use of alternative technology."
Of course, actually delivering on these pledges is another matter. The current coalition Government pledged in 2010 to "work to reduce the use of animals in scientific research". Yet the number of animal experiments is now at its highest level since the current recording system began. The recently published Delivery Report shows that this Government made little attempt to honour its pledge, preferring instead to focus on efforts to communicate the importance of animal research to the public.
Let us hope that the next government will take the issue as seriously as it deserves.
"With growing evidence of the shortcomings of laboratory animal testing to reliably predict human responsiveness to chemicals, questions are now being asked as to whether it is appropriate to use animals as human surrogates at all."
Dr Robert A. Coleman
ATLA is FRAME’s peer-reviewed scientific journal, published six times a year
A landmark study published on 28 July reveals how animal tests create a false sense of security, putting patients at risk.
The Observer published our letter, signed by many expert scientists, commenting on the study and urging governments to replace animal-testing requirements with an obligation to use the most reliably proved methods available.
The Sunday Times also published our (different) letter, which began: "We hope the exciting technology mentioned in your article will become mainstream within three years as predicted. Meanwhile, other human-based technologies are already available that could be improving patient safety here and now. The impediment is not science but political will."
Our latest newsletter shows how close we are to reaching a tipping point, with science shifting inexorably towards human-focused research to deliver advances in medicine and more reliable safety tests.
Our mission is to accelerate this transition. Our comparative studies are designed to hasten this long-awaited shift. We have reached an exciting point, with partners ready to conduct our studies: the one thing we need now is funding, to get these studies underway.
Please help us if you can: the sooner we can demonstrate the superiority of human-based tests, the sooner they will be used routinely, in place of animal tests, to improve the safety of medicines.
Whatever you can afford to give will be extremely valuable and greatly appreciated - thank you!