| Category | 
        Criteria | 
      
      
        | Level 1 | 
        Study quickly terminated by euthanasia, prior to any clinical signs of    disease or distress. | 
      
      
        | Level 2 | 
        Comparative study; experimental groups given novel drugs or vaccines    compared with positive ‘‘gold-standard’’ controls. Non-lethal infection with    only transient mild symptomology. Probably lethal infections terminated    before the onset of the most debilitating symptoms. | 
      
      
        | Level 3 | 
        Studies resulting in lasting deleterious effects on animal health and    welfare, not alleviated by means of refinement. | 
      
      
        | Level 4 | 
        All studies having spontaneous death or ‘‘moribund’’ state as    experimental endpoints and/or resulting in severe distress non-alleviated by    means of refinement. | 
      
    
    * It is adapted from Ref. 14.