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.
In order to overcome this dilemma a number of alternatives are currently discussed by the scientific and regulatory community. One of these alternatives are human challenge trials. Currently, this approach is mainly used for proof of concept studies but might also have the potential to replace large phase III efficacy studies or might compensate for lacking data in case efficacy studies cannot be conducted at all. However, design, conduct and validity of human challenge trials are associated with a series of extremely complex considerations including for example set up and design of the controlled human infection model (CHIM), the choice of the challenge strain, issues related to the manufacturing of the challenge strain as well as a wide range of ethical questions, etc. Nevertheless, human challenge trials have been conducted successfully in the past, mainly for malaria and cholera vaccines and a rapidly growing number of CHIMs is currently developed.
In order to address critical aspects associated with the conduct of human challenge studies the INTERNATIONAL ALLIANCE FOR BIOLOGICAL STANDARDIZATION (IABS) in collaboration with the World Health Organization (WHO) has recently held their second workshop on human challenge trials in Rockville, MD, USA as a follow-up workshop to the Strasbourg conference held several years ago. The recent workshop was attended by almost 200 participants discussing all aspects related to human challenge trials, thus signalling that the need to upgrade this option to a regulatory alternative is definitely urgent.
Dr. Michael Pfleiderer from Biopharma Excellence was deeply involved in the conducts of the present as well of the first workshop providing, amongst other important aspects, insight into the quality requirements for human challenge strains. As such we have developed a deep understanding of the value of human challenge trials and can assist you in case you plan to conduct such type of study and convey the value of the study to regulators in order to safe time and money for your vaccine development.
MORE (GET THE ABSTRACT)