The European Medicines Agency (EMA), which evaluates medicinal products for use in Europe, has released revised guidance on first-in-human clinical trials, to reduce the risk for participants.
Participants in first-in-human trials, who are usually healthy volunteers, will always face a certain level of risk as it is impossible to fully predict the effects of a new medicine before it is actually studied in humans. As a result, on very rare occasions, participants can experience serious adverse effects.
The EMA guidance is intended to assist sponsors — that is individuals, institutions or companies responsible for the trial — in the transition from non-clinical to early clinical development. The revisions to the guidance put further emphasis on the responsibility of the sponsor to define the uncertainty associated with the medicine being tested and describe how the potential risks that might arise from this uncertainty, will be addressed within the design of the trial.
Mitigating and managing risk
Strategies for mitigating and managing risk for trial volunteers are also given, including calculating the starting dose to be used, the subsequent dose escalation, and maximum doses, taking into account criteria of risks such as the novelty of the active substance, its biological potency and mode of action.
The guidelines also say that the protocol for a trial should define stopping rules for the cohort and trial, what to do if adverse events occur and the safety information that should be made available to trial volunteers.
The revision takes into account the increasing complexity of trial protocols over the past ten years, for example when single trials are used to consider a multitude of factors, such as patient age groups and single and multiple ascending doses.
The changes were the outcome of a public consultation which began in November 2016. The EMA’s commitment to improving the safety of first-in-human clinical trials was triggered by the death of a male volunteer and hospitalisation of five others who took part in a phase I clinical trial in Rennes, France, in January 2016.
Full comments on the revised guideline will be made available by the EMA in September 2017.