The funding from the UFAW has been key in advancing two significant projects that align with the 3R principles (Replace, Reduce, Refine) in animal research and contribute to the broader goal of enhancing animal welfare.

The first was evaluating animal models in multiple sclerosis (MS) drug development through a comprehensive review. The goal was to examine how well animal studies predict the success of MS drugs in human trials. This involved a detailed review and analysis of animal studies related to both successful and unsuccessful MS drugs. We conducted a systematic search to identify drugs for MS, both successful and failed. The research involved analyzing studies from PubMed and EMBASE. We employed machine-learning techniques for efficient screening and data extraction, followed by a statistical analysis (meta-analysis) to compare the outcomes of drugs in animal models. Our research included 477 animal studies, involving about 30,000 animals, focusing on 15 approved and 11 failed MS drugs. Interestingly, most studies (90%) occurred post-regulatory approval. Our analysis showed that varied experimental conditions in animal studies correlate with successful drug approval. However, standard animal study outcomes did not necessarily predict clinical success. This study highlights the challenges in transferring findings from animal research to clinical applications. We suggest diversifying experimental methods and enhancing collaboration between preclinical and clinical researchers to improve the relevance and ethical responsibility of animal research.

The second project involved analyzing the transition of biomedical therapies from animals to humans. We aimed to address the ongoing debate about the relevance of animal studies in developing human therapies. Our focus was on measuring how effectively these studies translate to human applications. We performed an umbrella review of systematic reviews that evaluated this transition. Data was collated from Medline, Embase, and the Web of Science Core Collection. The study assessed the progression rate of therapies from animal models to human trials and regulatory approval. We also analyzed the correlation between animal and human study outcomes. Our review encompassed 122 articles, detailing therapies for 54 human diseases. About 50% of therapies from animal studies progressed to human trials, with a smaller percentage reaching regulatory approval. Notably, there was a high consistency (86%) between positive outcomes in animal and human studies. However, the overall rate of final approval was low. Our findings suggest a higher success rate in translating animal research to human applications than commonly assumed. However, the low approval rate points to potential improvements needed in the design of both animal studies and early human trials. We advocate for more robust study designs to enhance the translation of therapies from laboratory to clinical settings.

Systematic reviews, which synthesize existing scientific evidence to address specific questions using explicit and unbiased methods, have become increasingly recognized as an effective approach. They play a critical role in identifying issues in preclinical research, informing best practice guidelines, reducing research waste, improving reproducibility, and guiding translational research. Additionally, systematic reviews of preclinical studies enhance ethical animal use by maximizing the utility of existing data, thereby supporting animal welfare. However, poorly conducted systematic reviews can yield unreliable results, leading to incorrect interpretations of the literature. We have written a comprehensive Primer which provides guidance for performing rigorous systematic reviews, with or without meta-analysis, for preclinical studies, including those involving animal and in vitro research. It also highlights the limitations of systematic reviews and discusses emerging developments, such as automation tools. By following this guidance, researchers can ensure their systematic reviews are robust and impactful, ultimately improving decision-making and outcomes in preclinical research.

With help from UFAW, we were also able to organize the second summer school of animal systematic review in collaboration with Norecopa in Bergen, Norway in August 2024 (https://norecopa.no/summer-school-on-systematic-reviews-of-animal-studies/).

Our work was awarded with both the Swiss 3RCC award and the University of Zurich 3R award.

We are very thankful for the support from UFAW, which has been very important in achieving these milestones which have made a relevant contribution to the 3Rs.

Berg I, Härvelid P, Zürrer WE, Rosso M, Reich DS, Ineichen BV 2024 Which experimental factors govern successful animal-to-human translation in multiple sclerosis drug development? A systematic review and meta-analysis. eBioMedicine, 110, 105434. https://doi.org/10.1016/j.ebiom.2024.105434

Hild BF, Bruschweiler D, Hild STK, Bugajska J, von Wyl V, Rosso M, Wever KE, Furrer E, Ineichen BV (2025) Quality, topics, and demographic trends of animal systematic reviews – an umbrella review. Journal of Translational Medicine 23:21. https://doi.org/10.1186/s12967-024-05992-0

Ineichen BV, Furrer E, Grüninger SL, Zürrer WE, Macleod MR 2024 Analysis of animal-to-human translation shows that only 5% of animal-tested therapeutic interventions obtain regulatory approval for human applications. PLoS ONE Biology https://doi.org/10.1371/journal.pbio.3002667

Ineichen BV, Held U, Salanti G, Macleod MR, Wever KE (2024) Systematic review and meta-analysis of preclinical studies. Nature Reviews Methods Primers 4:72. https://doi.org/10.1038/s43586-024-00347-x