Since cases of clinical smallpox no longer exist, efficacy testing of new vaccines in humans is not really possible. The old method of human testing, which involved vaccination and revaccination + an assessment of the patient's reaction (or lack of) to secondary challenge (usually a skin lesion), encountered the problem of patients developing heart problems (also, it was quantitative).
Thus smallpox vaccine development had to use the FDA's "animal rule," which allowed for animal models (two or more) to be surrogates for human testing, assuming the effectiveness, dosage, and responses to the vaccine can be extrapolated from the animal trials. But even here, vaccine development encounters another problem: there isn't a suitable animal model that would model human smallpox infection. So, researchers have been looking at the immunity given by their vaccines toward variola-like mice and monkey strains. Protection new vaccines such as MVA (uses attenuated vaccinia) confers onto humans might never truly be known until smallpox reemerges.
2004;291(15):1825. doi: 10.1001/jama.291.15.1825