Still room for improvement when researchers publish the results of animal experiments

It’s not that veterinarian Birgitte Kousholt and Professor Gregers Wegener are losing their patience, but they do look a little tired when they talk about the progress that has been made in the reporting of animal experiments at Danish universities over the past decade.

“The preclinical literature is still deficient. If the researchers are introducing measures to ensure the quality of the animal tests, this has been very poorly reported, and there has only been a modest improvement in the period 2009-2018,” says Birgitte Kousholt, who is also head of the surgical research laboratories at AU.

Together with Professor Gregers Wegener of the Department of Clinical Medicine, she has just published the study Reporting quality in preclinical animal experimental research in 2009 and 2018: A nationwide systematic investigation in the peer-reviewed open access journal Plos One.

The conclusion gives food for thought. The article shows that the way in which the reporting takes place is poor – you often cannot read what has been done in the individual experiments.

“It’s a question of, for example, sample size calculation – where, as a researcher, you calculate how many animals you need to be able to document a well-defined statistical probability that your findings are valid. Too few animals can give a random result, while too many are a waste,” explains Professor Wegener, who is also chair of the Animal Welfare Committee at Health.

Only one area has improved significantly

In the study of preclinical literature, the author group has assessed 500 publications from 2009 and 2018. The nationwide study shows how much the researchers report from animal experiments, and it looks at the level of detail.

The total incidence of reporting is still low, although minor improvements have been noted:

• The reporting of randomisation has risen from 24.0% in 2009 to 40.8% in 2018
• Blinded experiments have risen from 2.4% to 4.4%
• Blinded result assessment has risen from 23.6% to 38.0%
• Sample size calculation has risen from 3.2% to 14.0%
• Reporting the sample size calculation method was 2.4% in 2009, and 7.6% in 2018.

The only major improvement has been in the reporting of conflicts of interest, which rose from 37.6% in 2009 to 90.4% in 2018 – because it became an absolute requirement from the scientific journals during this period.

If researchers fail to report animal testing adequately, it has several consequences , says Birgitte Kousholt.

“Amongst other things, it becomes difficult to assess the actual value of the results. It makes it impossible to compare studies, and the lack of reproducibility creates a ‘translational gap’. Neither is it satisfactory from a 3R perspective,” she says.

Gregers Wegener also stresses that poor reporting makes the research less useful.

“An exciting result is less valid if it is not replicable by others. It loses the value that it might otherwise easily have had, and you have wasted an opportunity to move the experiment on to clinical research,” he says.

In many areas, clinical research is far ahead, because clinical researchers are used to reporting to a completely different degree, says Birgitte Kousholt.

“The first systematic review of clinical research came in the 1980s, while that of preclinical research came in 2001. There is more of the ‘wild west’ about preclinical research, and in some respects that is a shame. When systematic reviews are done, they always look at the quality of the studies that are available, and if the study is of low quality, it’s rejected. So if your science is to contribute something to the bigger picture, it’s necessary to report it better,” she says.

The checklist is available

In autumn 2022, Gregers Wegener reported to Health’s Research Forum about the status of the pre-clinical research quality. He argued that an obvious way to ensure quality is to follow the ARRIVE guidelines, which provide a checklist to meet all relevant criteria for describing your research.

The members of the Research Forum agreed that a better implementation of the ARRIVE guidelines would make the quality of the research clearer and give the research greater impact.

Vice-Dean for Research Hans Erik Bøtker therefore encourages all researchers at Health to use the ARRIVE guidelines to improve the quality of their research and increase the translational potential to clinical trials.

“Animal experimental studies are a necessary step on the way from cell-based experiments to human application, so we need to keep track of all the sub-elements of the process. Fortunately, there are good guidelines available on how to achieve high quality and high levels of ethics when experimenting with animals, but the study shows that there is still room for improvement in the reporting. The new study should therefore be heeded,” he says.

“I hope that Aarhus University’s experimental researchers will adopt ARRIVE. The checklist is available and it tells you exactly what needs to be done. By complying with the guidelines – which is not difficult – you can ensure rigorous experiments and help to improve the quality of scientific research,” says Hans Erik Bøtker.

Birgitte Kousholt and Gregers Wegener welcome this announcement.

“When ARRIVE is followed, it tells the reader how much value they can ascribe to a result. It’s a seal of approval. Right now, it’s not something that universities or journals require – you have to do it for your own sake and the sake of the research,” says Gregers Wegener.

“If we don’t do it now, there will be 3-5 years more of low reporting quality, until it becomes a requirement from the journals and foundations. And that is going to happen, so we might as well get started now.”

The ARRIVE guidelines

• (Animal Research: Reporting of In Vivo Experiments) is a checklist of recommendations for improving the reporting of ​research involving animals. The recommendations must be applied right from the start-up phase of the project.
• The guidelines maximise the quality and reliability of ​published research and enable others to better scrutinise, evaluate and reproduce it.
• Read more: https://arriveguidelines.org/

AUGUST

In 2015, Veterinarian Birgitte Kousholt and Professor Gregers Wegener formed the August consortium , which works to promote more ​systematic reviews and meta-analyses of preclinical research, thereby improving standards in the area.

The idea is that systematic reviews and meta-analyses of animal experiments have several advantages: They can improve scientific quality, lead to improved implementation of the 3R principles (replacement, reduction and refinement), and increase the translation value of ​animal experiments.

August holds regular symposia and seminars.

Read more: https://august.au.dk/

Behind the research results

• The research study is based on the systematic review methodology.
• The study was carried out in collaboration with Professor Marel Ritskes-Hoitinga, who founded SYRCLE (SYstematic Review Centre for Laboratory Animal Experimentation) in 2012, and today is Professor of Evidence-based Transition to Animal-free innovation at Utrecht University. She has a professorship at Aarhus University.
• External funding: Denmark’s 3R Centre.
• Learn more: Reporting quality in preclinical animal experimental research in 2009 and 2018: A nationwide systematic investigation | PLOS ONE

Contact:

Birgitte Saima Kousholt, Veterinarian and head of the surgical research laboratories.
Aarhus University
birgitte.kousholt@clin.au.dk
Tel.: +45 2398 7790

Professor Gregers Wegener
Aarhus University, Department of Clinical Medicine
wegener@clin.au.dk
Tel.: +45 5171 7403