Ethical frameworks are the foundation for any research with humans or nonhuman animals. Human research is
guided by overarching international ethical principles, such as those defined in the Helsinki Declaration by the
World Medical Association. However, for nonhuman animal research, because there are several sets of ethical
principles and national frameworks, it is commonly thought that there is substantial variability in animal
research approaches internationally and a lack of an animal research ‘Helsinki Declaration’, or the basis for one.
We first overview several prominent sets of ethical principles, including the 3Rs, 3Ss, 3Vs, 4Fs and 6Ps. Then
using the 3Rs principles, originally proposed by Russell & Burch, we critically assess them, asking if they can be
Replaced, Reduced or Refined. We find that the 3Rs principles have survived several replacement challenges, and
the different sets of principles (3Ss, 3Vs, 4Fs and 6Ps) are complementary, a natural refinement of the 3Rs and are
ripe for integration into a unified set of principles, as proposed here. We also overview international frameworks
and documents, many of which incorporate the 3Rs, including the Basel Declaration on animal research. Finally,
we propose that the available animal research guidance documents across countries can be consolidated, to
provide a similar structure as seen in the Helsinki Declaration, potentially as part of an amended Basel Declaration on animal research. In summary, we observe substantially greater agreement on and the possibility for
unification of the sets of ethical principles and documents that can guide animal research internationally
