by Dr. Michael Pfleiderer
Clinical trials in vaccine development are often hugely dimensioned sometimes comprising several ten thousands of individuals for phase III safety and efficacy studies. These sample sizes are required in order to demonstrate efficacy of vaccines for which no correlate of protection exists or for which very rare severe adverse effects need to be investigated pre-licensure. Besides the ongoing debate whether regulatory practice should ask for even more extended studies or whether there should be an upper limit of study sizes in order to ensure that clinical studies continue to be feasible, controllable and affordable there is an increasing number of vaccines that cannot be investigated for efficacy for several reasons.
These belong to the growing group of vaccines against newly emerging or regularly re-emerging pathogens such as Chikungunyavirus, Ebolavirus, MERS and SARS Coronavirus, West Nil Flavivirus, Zikavirus as well as against numerous microbial pathogens and parasites. Diseases caused by many of these pathogens do not occur regularly but appear and disappear in unpredictable epidemiological patterns making it virtually impossible to design a field efficacy trial since the region of emergence or re-emergence is unknown.