Some areas of research may be perceived as challenging to refine because of concerns that refinement may not be compatible with the desired experimental endpoint. For example; in rheumatoid arthritis research, there is debate as to whether analgesia can be given to animals experiencing joint pain, in case this will interfere with the inflammatory process being studied.
However, it is essential to consider a wide range of factors when deciding whether refinement might introduce confounds, and if so how to deal with this. In the case of arthritis studies, the presence of uncontrolled pain and the inability to express a full range of natural behaviour are also confounding factors - which could have a greater negative effect on data than providing analgesia.
It is critically important to review the literature in order to establish current understanding of the impact of inclusion and exclusion of refinement on an experimental paradigm.