The European Medicines Agency (EMA) has reconsidered its guidance on phase I clinical studies with the purpose of providing the organizations involved in conducting clinical trials to find out the potential risks for trial participants and therefore minimize it.
First-in-human trials have always been the crucial step in medicines development. The drugs which have previously been tested only in vitro, in vivo and ex vivo are administered to people for the very first time. However, people who take part in these clinical trials, normally healthy volunteers, cannot avoid an element of hazard as the ability of scientists to predict the effects of a newly developed drug on people is always limited. Though there have been registered fairly few cases when trial participants experienced serious health effects.
When researchers design early clinical trials they should always put safety and well-being of trial participants first. That’s why the new revised guideline is focused on the sponsor’s obligation to outline the uncertainty related to preclinical testing steps and to describe how the potential hazards that may result from this uncertainty will be considered in the design of the trial. What’s more, the new guideline says that this approach must be supported by a well-documented scientific rationale.
The revision of the guideline takes into consideration the fact that in the past 10 years trial protocols have become very complex. This led to the fact that now these protocols often include different parts within a single clinical trial protocol, with the aim of evaluating, for instance, single and multiple dosing regimens, food interactions, or testing the medications for people of different age.
The guideline puts special attention to the calculation of the starting dose to be used in humans, the following dose elevations and the criteria for determining the maximum dose. These aspects are considered to be the most important in terms of identifying the ways to stem and manage risks for trial participants. The guidance provides researchers with the criteria to terminate a study. It is also mentioned that the periodic review of emerging data with special attention to safety information and the management of adverse events are extremely significant.
This guideline has been revised in collaboration with the European Commission and the representatives of the Member States of the European Union through the EU Clinical Trials Facilitation Group (CTFG).