News

New study shows researchers’ reluctance to abandon animal research despite decades of failure

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


New paper questions whether systematic reviews of animal studies can help translation to humans

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


Contributions are invited for a Special Issue in the journal ‘Animals’

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.


New publication on problems with animal models

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


Why cancer research should focus on patients

Dr Azra Raza, Professor of Medicine at Columbia University in New York, international authority on leukaemia, and Science Adviser to Safer Medicines Trust, has written a remarkable and highly recommended new book published in October 2019: The First Cell: And the human costs of pursuing cancer to the last

In amongst highly moving stories of her patients, including her own husband, Dr Raza explains why the global cancer research effort should make two major changes of direction:

1) to focus on prevention and early detection, to find the first malignant cell instead of attacking late-stage disease; and

2) to focus research exclusively on humans and their tissues, rather than on mice, rats and other futile animal models.

To that end, she has founded the First Cell Center, to study her tissue repository of more than 60,000 samples collected from her patients over the past 35 years.

Many articles and interviews are available from https://azraraza.com. This video: Early Footprint and this news article: Here’s why we’re losing the war on cancer, according to this doctor are a great place to start, along with this powerful and moving 13-minute TEDx Talk from 2014.


Why is patient safety compromised in the development of new medicines?

By Dr Jan Turner

Today is the inaugural #WorldPatientSafetyDay, the objective of which is to raise global awareness about patient safety and encourage global solidarity and action. So, from my perspective as Director of the Safer Medicines Trust, I would like to raise the subject of the safety of patients taking medicines. Continue reading “Why is patient safety compromised in the development of new medicines?”





Animal Experimentation: Working Towards a Paradigm Change

Open Access (free) E-book, also available to buy in hard copy from scholarly publisher Brill

In this important new book, 51 authors critically review current animal use in science, present new and innovative non-animal approaches to address urgent scientific questions, and offer a roadmap towards an animal-free world of science.

Edited by Drs Kathrin Herrmann and Kimberley Jayne

Featuring a chapter by Kathy Archibald, Tamara Drake and Dr Robert Coleman, entitled: Replacing Animal Tests to Improve Safety for Humans

Watch a 30 minute presentation of the chapter, from the recent London Book Launch Conference, by Dr Jan Turner

 


Advancing nonclinical innovation and safety in pharmaceutical testing

Researchers, academics and representatives from the pharmaceutical industry and advocacy groups have joined together to call for a significant and urgent shift to prioritise predictive, human-based nonclinical tests.

Drug Discovery Today has published the call from participants of the Nonclinical Innovation and Patient Safety Initiative, including Dr Gerry Kenna of Safer Medicines Trust.

Read the Open Access paper


Paul Flynn 1935 – 2019

We are deeply saddened by the death of Paul Flynn MP. It was a great honour for us to have his support as a Patron. He was a politician of courage and conviction and a fearsomely talented communicator, which made him a powerful advocate for causes he cared passionately about, including social justice and improving the safety of medicines. He was a towering figure in the House of Commons and in his beloved Welsh homeland and will be greatly missed.



Safer Medicines Trust welcomes new Director

We are delighted to announce the appointment of Dr Jan Turner as our new Director. She brings with her a wealth of experience in developing and promoting human-relevant in vitro technologies, including directing validation studies and influencing organisations such as the FDA to introduce such technologies into the early safety testing of drugs.

Dr Jan Turner

After completing her BSc in Biochemistry & Pharmacology, followed by a PhD and postdoctoral research in Genetic Toxicology, Dr Turner worked for Amersham Biosciences, subsequently GE Healthcare Life Sciences. Her roles included Development Scientist, Project Leader, Global Product Manager and Product Management Operations Leader. For the past 18 months she has been Senior Product Manager at BBI Solutions, directing global cross-functional teams and driving adoption of innovative technologies.

Jan is passionate about human-focused biomedical research and we look forward to her leadership in making medicines safer by accelerating the transition from animal-based to human-relevant drug development and testing. She says:

“I am thrilled to join Safer Medicines Trust and to work with so many talented and inspirational people towards our shared vision of a future where safe and effective treatments for patients will be delivered by scientifically valid, human-focused research.”

Kathy Archibald, our founder and Director for the past 14 years, remains the Chair of Trustees and will continue to manage Supporter Communications as the charity moves from strength to strength. She says:

“We are excited to welcome Jan to lead our team at this important time. I believe our expert team and the many visionary scientists and others with whom we collaborate will help to realise a future where better science will improve our health and save lives.”



Better science for safer medicines: the human imperative

Commentary by Kathy Archibald, Katya Tsaioun, Gerry Kenna and Pandora Pound published in the Journal of the Royal Society of Medicine

Our commentary warns that the UK must not fall behind in the race to ‘humanise’ drug discovery. Current research models and regulation are blocking the development of human-relevant approaches to drug discovery and perpetuating animal-based approaches. The UK has world-leading research in this area but significant investment in non-animal technologies is taking place in the US and Europe. The UK should seize the initiative to revolutionise medicine through more intelligent, human-relevant research.

Read the full paper here


Is it possible to overcome issues of external validity in preclinical animal research? Why most animal models are bound to fail

New article by Dr Pandora Pound and Professor Merel Ritskes-Hoitinga published in Journal of Translational Medicine

The authors make a compelling argument that preclinical animal models can never be fully valid due to the uncertainties introduced by species differences. They suggest that to improve clinical translation and ultimately benefit patients, research should focus instead on human-relevant research methods and technologies.

Read the full paper here

 


Human cell-based assays vital to assess risk of drug-induced liver injury

New review article coauthored by Dr Gerry Kenna published in the journal Clinical Pharmacology & Therapeutics:

Can BSEP Inhibition Testing In Drug Discovery And Development Reduce Liver Injury Risk? An International Transporter Consortium Perspective

Medicines can cause serious unwanted side effects in some patients. These include drug-induced liver injury (DILI), which is poorly predicted by the currently used safety test methods. Assays that focus on human-relevant mechanisms can provide more useful data. One important mechanism is inhibition of a liver cell membrane transport protein called the Bile Salt Export Pump (BSEP). This article reviews the evidence linking BSEP inhibition with DILI and describes methods to evaluate and interpret BSEP inhibition. It also recommends how these data can be used to aid the design and selection of safer medicines. The authors from Safer Medicines Trust, major pharmaceutical companies, universities and biotechnology companies were brought together by the International Transporter Consortium.


Predicting drug-induced liver injury risk


New paper published in the journal Drug Metabolism and Disposition: Do In Vitro Assays Predict Drug Candidate Idiosyncratic Drug-Induced Liver Injury Risk?

Our Pharmaceutical Director, Dr Gerry Kenna co-authored the paper with Dr Jack Uetrecht, Professor of Pharmacy and Medicine at the University of Toronto and the Canada Research Chair in Adverse Drug Reactions

Many new medicines cause undesired side effects in humans that are not predicted by the drug safety studies performed currently. This review focuses on liver injury, which is an especially important human adverse drug effect. It highlights both the promising progress made in developing human-relevant in vitro methods that can anticipate and reduce drug induced liver injury risk, and outstanding challenges which remain to be addressed.


Dr Pandora Pound guest blogs for Animals in Science Policy Institute

Our Research Consultant, Dr Pandora Pound, gives a fascinating insight into the introduction of the use of systematic reviews in preclinical animal research, in which she played an instrumental role.

Systematic reviews have become accepted as powerful tools that should be deployed routinely to improve the quality of the evidence base in clinical research. Although their use is not yet routine in preclinical research, they have been instrumental in provoking debate about the reliability, validity, and value of preclinical animal research.

Read the article: The problem of evidence in pre-clinical animal research: how systematic reviews can help


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