The European Medicines Agency (EMA) has revised its guidance on first-in-human clinical trials to further help stakeholders identify and mitigate risks for trial participants.

First-in-human trials are a key step in medicines development, where a medicine already tested in vitro, in animals or in other preclinical studies is administered to people for the first time. Participants in these trials, often healthy volunteers, face an element of risk as the ability of researchers to predict the effects of a new medicine on people is limited before it is actually studied in humans. Only on very rare occasions, however, have participants experienced serious harm.

The safety and well-being of trial participants should always be the utmost priority when designing early clinical trials. The guideline puts emphasis on the sponsor’s responsibility to define the uncertainty associated with the medicine tested at each step of the development and to describe how the potential risks that might arise from this uncertainty will be addressed within the design and conduct of the trial. The approach must be supported by a well-documented scientific rationale from the outset and be responsive to data emerging over the course of the trial itself.

The revision takes into account the fact that in the past 10 years trial protocols have become increasingly complex and now often include different parts within a single clinical trial protocol, aimed at assessing for example single and multiple ascending doses, food interactions, or different age groups.

The strategies to mitigate and manage risks for trial participants described in the guideline refer specifically to the calculation of the starting dose to be used in humans, the subsequent dose escalations and the criteria for maximum dose. Guidance is also provided on 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.

The revision considered the comments received during a public consultation and a follow-up workshop that took place in March 2017.

EMA will make available all comments received, both on the initial concept paper and on the revised guideline, in September 2017.

Clinical trials are essential for the development of medicines and without them patients cannot gain access to new, potentially life-saving medicines. EU and international guidelines are in place to ensure that first-in-human clinical trials are conducted as safely as possible.

This guideline was revised in cooperation with the European Commission and the representatives of the Member States of the European Union through the EU Clinical Trials Facilitation Group (CTFG).