Clinical Trials

The value of human challenge trials in vaccine development

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.

The European GMO legislation for gene therapy products in clinical trials and its pitfalls

Advanced Therapy Medicinal Products (ATMPs) such as Gene and Cell Therapy medicinal products are innovative biopharmaceuticals with the potential to bring high therapeutic value. Especially the new gene editing tools such as CRISPR-Cas9 are expected to shift the focus of medicine from treating symptoms to curing diseases. However, especially their clinical development faces specific challenges. For products containing genetically modified organisms (GMOs), an additional risk assessment step in the clinical trial authorisation (CTA) procedure is required. Although a European regulatory framework for this matter exists, it has been implemented differently into the Member State (MS) national legislation, leading to different documentation requirements and review and approval frameworks between the Member States.

In this article, Theodor Tiko and Annegret Vaggelas review the current status of the European GMO legislation for gene therapy products in clinical trials, including its pitfalls for clinical trial applicants.