The European Medicines Agency in cooperation with the European Commission and the Member States of the European Union is proposing changes to its existing guideline on first-in-human clinical trials, to further improve the safety of trial participants.

This revised guideline aims to address the following:

• the increasing complexity of protocols of first-in-human clinical trials with a special focus on dose ascending.
• strategies to assess, mitigate and manage risks for trial participants. Several points are outlined, such as principles to be used for the calculation of the starting dose in humans, the subsequent dose escalation, and the criteria for maximum dose.
• non-clinical aspects, such as the better integration of pharmacokinetic and pharmacodynamic data and toxicological testing into the overall risk assessment, as well as the role of non-clinical data in the definition of the estimated therapeutic dose, maximal dose, and dose steps and intervals.
• clinical aspects, including criteria to stop a study, the rolling review of emerging data with special reference to safety information for trial participants, and the handling of adverse events in relation to stopping rules and rules guiding progress to the next dosing level.

More information and the concept paper can be found here.