A new paper by Safer Medicines scientific consultant Rebecca Ram, Dr. Domenico Gadaleta of the Mario Negri Institute, Italy and Dr. Tim Allen of the MRC Toxicology Unit, Cambridge discusses the progress of in-silico methods in New Approach Methodologies (NAMs) as well as the increasing need for use of ‘big data’ and artificial intelligence (AI) approaches in safety testing and biomedical research.
In silico, or computer-based research methods continue to emerge as part of a robust 21st century public health strategy, vital to improving the efficiency of preclinical drug discovery, as well as safety testing in the chemicals industry. They can be used alongside other methods e.g., human-based in vitro (cell or tissue derived) models as components of human-relevant New Approach Methodologies (NAMs).
Despite resisting scientific scrutiny for decades, animal studies have, over the last twenty years, been revealed by systematic reviews to be poorly conducted and unreliable, with the result that humans have, on occasion, been seriously harmed. Such troubling exposures have prompted several initiatives to improve the quality of animal studies and their reporting, but these have had little impact so far on improving their translation to humans. Could it be that fundamental differences between species constitute an insurmountable problem for biomedical research? Given that transformative human relevant technologies such as organ-chips and organoids are now available, could now be the time for a new paradigm?
March 22: The All Party Parliamentary Group for Human Relevant Science launches their report in Parliament, entitled: BRINGING BACK THE HUMAN: TRANSITIONING FROM ANIMAL RESEARCH TO HUMAN RELEVANT SCIENCE IN THE UK. MPs say human relevant science is essential to medical progress, and make recommendations including the creation of a dedicated ministerial-level post to ‘lead an ambitious and detailed programme of work’ cutting across Government to drive the UK’s transition to human relevant science.
Evidence given to the APPG stressed that now is the time for government leadership to put the human first and modernise medical research.
It emerged during the inquiry that ‘funding for human relevant technologies represents just 0.02% of the total public expenditure on research and development.’ The group is therefore urging the Government to increase the funding of human relevant approaches by strategically diverting resources away from traditional animal-based approaches which have a high failure rate and directing funding to transformative human relevant technologies.
Read the report and/or a separate brief summary here:
Our Pharmaceutical Director, Dr Gerry Kenna, recently presented a virtual seminar on “In vitro models for assessment of drug-induced liver injury (DILI): a personal perspective” to the Liver Toxicity Working Group of the US regulator, the FDA. The illustrated talk is 45 minutes long and gives a valuable insight, from an expert with decades of experience, into the state of the art of drug safety testing to avoid the risk of DILI. DILI is an important cause of drug-related ill health, which can be serious and even fatal, and is a leading reason for failed development and use of many otherwise promising new drugs.
The talk is technical, so you may wish to focus just on the Summary in the final 7 minutes. Here, Gerry explains that numerous methods which use human-derived cells are available, and provide data that are much more useful than animal safety studies. Because DILI is complicated, no single method can be used and multiple endpoints need to be analysed. Gerry highlights that there is an urgent need for scientists to reach consensus on which assays to use and how best to analyse and interpret the data that they provide. There is also a need for strong regulatory guidance that requires in vitro methods be used to assess the risk of DILI, thus reducing the incidence of this serious but often avoidable adverse drug reaction.
Our Patron, Sir David Amess MP, was a great friend to the Alliance for Human Relevant Science, as well as to Safer Medicines. We are all devastated by his tragic loss and send our heartfelt condolences to his family. The volume of tributes being paid to Sir David goes to show what a wonderfully kind, caring and delightful human being he was.
He was a prominent spokesperson on health issues and served for 10 years on the House of Commons Health Select Committee. In 2012, he received the “Outstanding Achievement Award” at the Charity Champion Parliamentary reception, in recognition of his lifetime commitment to charitable work. He was a powerful champion of many good causes and had an unequalled backbench record for introducing new bills into law.
Sir David supported our work for many years, and on becoming our Patron, he said: “I am passionate about both human health and animal welfare, and I applaud Safer Medicines Trust for showing that there is no contradiction between the two, as we are so often led to believe.”
The availability of data from both preclinical and clinical studies of drugs is key to understanding the effectiveness and safety of any treatment before it is approved for use in patients. In a recent webinar our Director Dr Jan Turner, described why gaps in this data either through selective reporting or omission of significant data all together, can have profound effects on the decision-making of regulatory agencies and ultimately lead to unsafe drugs being placed on the market. Jan’s slides are available here.
“The future of medicines regulation in the UK” was the subject of a recent Westminster Health Forum meeting at which our Director, Dr Jan Turner described why innovation and the development of methods to ensure safe and effective medicines, is imperative for the UK. The talk drew on a previous meeting in July 2020 where Jan also spoke but included some reflections this time on lessons learned from the COVID pandemic which may be exploited to develop safer medicine, and post-Brexit opportunities for the UK regulatory body MHRA to support the approval and inclusion of human relevant methods into medicines testing. Dr Turner’s slides are available here..
The collaboration conducted a comprehensive comparison of the in vivo (animal and human) and in vitro tests currently available to assess drug safety and compared their findings against ‘real world data’ on adverse drug reactions. They focused on two diabetes drugs: troglitazone (Rezulin), which was withdrawn from the market due to severe and fatal liver toxicity and rosiglitazone (Avandia), which remains on the market in the US.
Neither drug indicated a strong hazard signal in either preclinical animal studies or human trials. In contrast, in vitro data (using human cells and tissues) found that Rezulin exhibited strong signals for off-target effects on the liver, while Avandia did not.
This world-first comparative approach found that preclinical animal and clinical human trials – despite being mandatory – did not predict Rezulin’s potential to cause harm. Tests on human cells and tissues could have clearly revealed the hazard, which caused hundreds of liver injuries and killed at least 63 people. Sophisticated human-relevant technologies now offer a new paradigm for preventing adverse drug reactions and saving patients’ lives.
Our research consultant Dr Pandora Pound recently guest edited a special issue of the journal ‘Animals’ entitled “Are Animal Models Needed to Discover, Develop and Test Pharmaceutical Drugs for Humans in the 21st Century?” The key question she posed is whether there is value in refining animal models for medical research, or whether these should be relinquished in favour of new, human-focused research approaches. The seven open access, scientific papers that attempt to address this question, including Dr Pound’s editorial, can be found below.
A new All-Party Parliamentary Group for Human Relevant Sciences held its first AGM on Tuesday 6th October 2020, with the aim of accelerating the development and uptake of human relevant life sciences in the UK.
The APPG will be a discussion forum for politicians, the human relevant life sciences sector, third sector groups, scientists and stakeholders to promote new approach methodologies that provide unique insights into human biology, transform our ability to understand human disease and can develop effective new medicines more quickly and without the use of animals.
Speaking at the launch, the APPG’s Chair and Safer Medicines Trust Patron, Labour MP Grahame Morris, said, “I am delighted to Chair the new All-Party Parliamentary Group on Human Relevant Science. The COVID-19 pandemic has demonstrated that the current approach to developing new treatments is simply not fast enough to meet humanity’s needs. We urgently need a moonshot to transition to new approach methodologies which promise to deliver safer and more effective medicines, more quickly and at less cost.”
APPG Vice Chair and Safer Medicines Trust Patron, Conservative MP Sir David Amess said, “I am thrilled to be Vice Chair of the new All-Party Parliamentary Group on Human Relevant Science. With the cancellation of the Autumn Budget, the Government now has more time to think about what it can do to provide much-needed financial support to boost growth in the human relevant life sciences sector and enable the UK to remain an innovative science superpower.
“As the country seeks a COVID-19 vaccine, this is the perfect time for parliamentarians to take seriously the growing evidence in favour of the pioneering human relevant medical research techniques that are replacing the outdated use of animals.”
“The future for UK regulation of medicines, medical devices and clinical trials – transparency and public trust, safety and enforcement, and support for innovation” was the subject of a recent Westminster Health Forum meeting at which our Director, Dr Jan Turner described why innovation and the development of methods to ensure safe and effective medicines, is imperative for the UK now and importantly, post Brexit. A recording of the talk is here and Dr Turner’s slides are here
We are calling for a change of mindset and a clear timetable for regulatory change to enable accelerated development of medicines which are likely to be safer, more effective and cheaper, without the use of animals. Investment in human relevant science offers a golden opportunity to revitalise medical research, save money, create wealth and improve public health.
We find ourselves in a time of global health emergency, one that will challenge our healthcare, social fabric and economy for years to come. Hard choices today have been borne out of great and immediate need. Yet there are patterns emerging in the scientific response that will have far reaching consequences for how we progress medical science in the future.
Hosted by the Physicians Committee for Responsible Medicine, in conjunction with US Congresswoman Lucille Roybal-Allard, our Pharmaceutical Director, Dr Gerry Kenna, recently spoke on why “Human-relevant models are needed to understand and treat human COVID-19 disease” at PCRM’s Congressional hearing “Confronting COVID-19: A Briefing on Prioritizing Human-Based Research”. A recording of the event is here and Dr Kenna’s slides are here.
Coronavirus: we’ve never had a better opportunity to harness the power of human relevant approaches
Unprecedented research efforts are underway across the world to combat the covid-19 pandemic. Much of this work involves testing potential treatments or vaccines in various animal species, both for safety and effectiveness. What is the likelihood that these animal studies will help us to find a vaccine or treatment within the ambitious timescale of 12 to 18 months?
On November 6 2019, Merel Ritskes-Hoitinga, Professor of Evidence-Based Laboratory Animal Science at SYRCLE (Systematic Review Center for Laboratory (animal) Experimentation www.syrcle.nl) in the Netherlands, was appointed Officer in the Order of Orange-Nassau, a civil and military Dutch order of chivalry open to “everyone who has earned special merits for society”. This honour, bestowed upon Professor Ritskes-Hoitinga following her inspirational inaugural lecture at the University (transcript here), comes after 30 years of improving the quality of animal research in the Netherlands and elsewhere, and dedicating herself to developing systematic review* methodology in the field of preclinical research.
Our latest newsletter contains brief summaries of our recent publications and some thoughts on progress towards more widespread use of human relevant technologies: what are the major barriers and ways to overcome them. Read it here and if you would like free hard copies, just let us know how many: email email@example.com or call 0300 302 0521
As a member of the Alliance for Human Relevant Science, Safer Medicines Trust calls for a fresh approach to biomedical research and drug discovery.
New approach methodologies (NAMs) that are human relevant have the potential to improve the efficiency of drug research and development and to deliver safer, cheaper and more effective medicines to patients.
In the new White paper ‘Accelerating the Growth of Human Relevant Life Sciences in the United Kingdom’, the Alliance calls for support from the Government to assist businesses in the transition to NAMs by providing supportive infrastructure, strategic funding, education, collaboration between industries and regulatory engagement.
There is an opportunity for the UK to be a world leader in developing and evaluating NAMs. Investment in human relevant methods is good for both business and public health.
A new paper by Safer Medicines scientific consultant Rebecca Ram, Dr. Domenico Gadaleta of the Mario Negri Institute, Italy and Dr. Tim Allen of the MRC Toxicology Unit, Cambridge discusses the progress of in-silico methods in New Approach Methodologies (NAMs) as well as the increasing need for use of ‘big data’ and artificial intelligence (AI) […]
One of our partner charities in the Alliance for Human Relevant Science is Animal Free Research UK. They have initiated an annual World Animal Free Research Day on the anniversary of their founding, 27th May. Our goals are very complementary: Animal Free Research UK’s vision is “To create a world where human diseases are cured faster without animal suffering”, while […]