On 26 July, the European Medicines Agency (EMA) presented a first revision of the guideline on first-in-human clinical trials, which outlines strategies to identify and mitigate risks for trial participants.
First-in-human trials are a key step in medicine development, where a medicine already tested in vitro, in animals or in other preclinical studies is administered to people for the first time.
As safety is crucial, the guideline emphasises 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. Based on this guideline, the approach must be supported by thoroughly documented scientific rationale from the outset and be responsive to data emerging over the course of the trial itself. In this revision account is being taken of the fact that in the past 10 years trial protocols have become increasingly complex and often include different parts within a single clinical trial protocol aimed at assessing for example single and multiple ascending doses, food interaction interactions, or different age groups.
elements such as strategies to mitigate and manage risks for trial
participants, criteria to stop a study, the rolling review of emerging
data and the handling of adverse events in relation to stopping rules and
rules guiding progress to the next dosing level are also provided in the
The revision of the guidelines took into account comments that were received during a public consultation and a workshop in March 2017. The revision took place in cooperation with the European Commission and the EU Clinical Trials Facilitation Group (CTFG).
The previous guideline adopted in 2007 can be found here.
The first revision of the guideline published on 25 July 2017 will come into force on 1 February 2018 and can be found here.
A first-in-man study is a clinical trial where a medical procedure, previously developed and assessed through in vitro or animal testing is tested on human subjects for the first time. As for the voluntary patients in these trials, they are sometimes exposed to the risk of very serious undesirable side effects. Consequently, there are ethical issues related to this. Computer modelling could help address these issues by refining clinical trials through more detailed information on potential outcomes and greater explanatory power in interpreting any adverse effects that might emerge.