EMA’s revised guidelines on first-in-human clinical trials to increase safety of trial participants
The European Medicines Agency (EMA) has published its revised guideline on first-in-human clinical trials. The revision of the guideline is the result of the EMA’s initiative to update its previous guideline, which dates back to 2007. With the revision, the EMA intends to offer further assistance to stakeholders in the transition from non-clinical to early clinical development and in the identification and mitigation of risks for trial participants.
The EMA stresses that the safety of trial participants is of the utmost importance. Although participants rarely experience serious harm, an element of risk nevertheless remains as researchers cannot fully predict the effects of a new medicine prior to the medicine being studied in humans. Therefore, the revised guideline puts an emphasis on the sponsor’s responsibility to define the degree of uncertainty of the medicine being tested. It also requires the sponsor to describe how the potential risks will be mitigated within the design and conduct of the trial. The sponsor must also provide supporting scientific documents which should make it possible to asses whether the risk minimization efforts are adequate.
Increased complexity of protocols
The revision extends the existing EU guidance with integrated protocols by taking into account the increased complexity of protocols of first-in-human clinical trials in recent years. For instance, within only a single trial, a multitude of factors are to be considered such as patient age groups, multiple ascending doses and food interactions. It includes considerations on quality aspects, non-clinical and clinical testing strategies, study design as well as conduct of trials. The guideline also outlines the strategies to mitigate and manage risks for trial participants. It specifically refers to the principles on the calculation of the starting dose to be used in humans, the subsequent dose escalations, and the criteria for the maximum dose. It also states that the trial protocol should define the rules to suspend or cancel a study. Finally, the guideline requires the trial design to provide a specific plan for monitoring adverse events or adverse reactions.
The guideline was adopted by the EMA’s Committee for Medicinal Products for Human Use and will come into effect on 1 February 2018.