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 They focused on two diabetes drugs: troglitazone (Rezulin), which was withdrawn from the market due to severe and fatal liver toxicity and rosiglitazone (Avandia), which remains on the market in the US.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 firstname.lastname@example.org 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.
This new study by Pandora Pound and Rebecca Ram from Safer Medicines, published in BMJ Open Science, analyses the opinions of scientists who conduct animal studies of stroke. At present there is only one drug available for patients with acute stroke, a ‘clot buster’ called Alteplase (and this drug was not directly dependent upon animal research for its development). Alteplase can only be given to a minority of stroke patients, half of whom will not benefit from it, so there is an urgent need for effective treatments in this area. Given the failure to develop treatments for acute stroke despite decades of animal research in this field, the study aimed to explore scientists’ views about the way forward.
We found that scientists conducting animal studies of stroke agreed that the field was in crisis, and many robustly criticised the science in this area. When it came to identifying the causes of this crisis, most scientists focused on the poor quality of animal studies. Similarly, when it came to solutions, most proposed improving the quality of animal studies in the hope that this would ultimately translate into benefits for stroke patients. A small number of researchers proposed using human in vitro methods alongside animal studies and one proposed using human focused methods instead of animal studies. Although there is evidence then, that a minority of scientists are beginning to consider human focused approaches, our study indicates a strong resistance to relinquishing the use of animal models in stroke research, despite decades of their failure to produce any benefits for stroke patients. Read the paper in full here
A systematic review is a way of systematically bringing together the findings from research studies in a particular field and this paper is about the appropriate use of systematic reviews in the field of animal studies. Some researchers suggest that systematic reviews of animal studies conducted prior to human trials (i.e. prospective systematic reviews of animal studies) would allow scientists to scrutinise data on the safety and efficacy from animal studies, helping them decide whether or not human trials should proceed. However Pandora Pound from Safer Medicines Trust, together with Merel Ritskes-Hoitinga from Radboud University in the Netherlands, argue that while prospective systematic reviews can make the evidence obtained from animal studies more transparent, individual studies in animals are not necessarily able to reliably predict the safety and efficacy of an intervention when trialled in humans, and so systematic reviews of these individual studies would likewise fail to offer reliable predictions of safety and efficacy. As a result they would not be able to reliably safeguard humans participating in clinical trials. The authors also note that animal and human studies are often conducted concurrently, which not only makes prospective systematic reviews of animal studies impossible, but suggests that animal studies do not inform human studies in the expected way. They argue that it is time to review expectations of what animal studies can deliver and focus instead on investigating how clinical knowledge is actually produced. Read the full paper here
The open access journal ‘Animals’ is running a Special Issue guest edited by Pandora Pound of Safer Medicines. The topic for the Special Issue is ‘Are Animal Models Needed to Discover, Develop and Test Pharmaceutical Drugs for Humans in the 21st Century?’ Original manuscripts that address this question are invited for the Special Issue. The deadline is May 15th 2020. More information can be found here: http://www.mdpi.com/journal/animals/special_issues/animal_models_2020
Background to call for papers
Despite many decades of research, much of which has focused on studies in animals, humans continue to suffer from diseases and illnesses for which there are no cures or treatments. It is now clear that insights provided by animal studies do not often translate to humans, explaining the very high failure rate observed when new medicines are evaluated in human clinical trials. In addition, there is increasing evidence that animal studies are frequently conducted so poorly that no clear conclusions may be drawn from them. Some claim that if only the quality of animal studies was improved, and animal models were made to more faithfully capture the relevant human disease, then these models would begin to translate and deliver clinical benefits. Others argue that research focusing on humans is necessary to gain a better understanding of human disease and to develop safe and effective drug treatments.These scientists point to developments in human biology during the last decade that have yielded in vitro and in silico techniques capable of providing novel insights into human disease mechanisms, as well as human-relevant disease models for developing and testing drug treatments for humans. A key question is whether there is value in refining animal models, or whether these should be relinquished in favour of new, human-focused research approaches.
A chapter on the problem with animal models has just been published in the Routledge Handbook of Animal Ethics, by Pandora Pound from Safer Medicines. The handbook is intended as a resource for philosophers and the chapter on animal models aims to bring readers up to date with developments in the field. It discusses recent evidence relating to weaknesses in the design, conduct and reporting of animal studies and explores how these weaknesses raise significant doubts about the validity of animal study findings and their translation to humans. The chapter argues that the evidence relating to poor scientific conduct and lack of human relevance challenges the existing ethical frameworks that govern animal research, such as the harm-benefit assessment. The hope is that this chapter will provide philosophers with the evidence necessary to develop a reinvigorated and updated ethics of animal research. https://www.routledge.com/The-Routledge-Handbook-of-Animal-Ethics-1st-Edition/Fischer/p/book/9781138095069
Hear our Director Dr Jan Turner speak about barriers and progress to adoption of human relevant in vitro models in drug discovery at the Advances in Cell and Tissue Culture conference in Cardiff, June 2019