The World Medical Association’s Declaration of Helsinki and Statement on Animal Use in Biomedical Research : Why reliable and valid preclinical evidence and

The 2024 revision of the World Medical Association’s Declaration of Helsinki requires that medical research involving human participants be scientifically sound, capable of generating reliable and valid knowledge, and designed to avoid research waste. Because the Declaration also requires that human research be based on preclinical evidence, the quality of the preclinical evidence used to justify clinical studies is fundamental to its ethical framework. However, substantial evidence indicates that preclinical animal research frequently suffers from poor methodological quality, publication and reporting bias, limited reproducibility and poor translation to human health. These shortcomings can result in a preclinical evidence base that is unreliable, insufficiently predictive, or of limited relevance to humans, thereby undermining assessments of scientific validity and risk–benefit that underpin decisions to initiate human studies. Within the broader framework of biomedical research waste, avoidable deficiencies in research prioritisation, design, conduct, reporting and translation also result in the unnecessary use of animals, financial resources and scientific effort. We therefore argue that the Declaration should more explicitly require that decisions to initiate human research be supported by a reliable, valid and relevant preclinical evidence base. Strengthening this requirement would improve the protection of research participants, while creating incentives to reduce avoidable animal research waste. We further argue that the World Medical Association’s Statement on Animal Use in Biomedical Research should be revised in parallel, to explicitly recognise animal research waste as an ethical and scientific concern, and to promote scientifically robust and ethically justified preclinical research.