An update to the European Medicines Agency (EMA) guidance on first in-human clinical trial has been released and will be implemented on 1st February 2018. The revision is intended to aid in the identification and mitigation of risks to trial participants. The revised guidance followed a public consultation and follow-up workshop in March 2017.
Without clinical trials it would not be possible to develop and allow patients access to new medicines that may offer life-saving treatments. EU and international guidelines are intended to facilitate medicine development while ensuring that the potentially risky first in-human clinical trials are managed as safely as possible.
During the medicine development process, preclinical studies (in vitro and in animal models) cannot identify all adverse effects that may occur in humans and it is difficult to accurately predict the side effects for a new medicine that has not been taken by humans. Therefore an element of risk to the participants (often healthy volunteers) for the first in-human studies is unavoidable – and in a very few cases serious harm has occurred.
The revised guideline places increased importance on the responsibility of the trial sponsor to identify potential risks during each development step and describe how the trial is designed to address these. Priority is given to the safety of trial participants during the design of early clinical trials and includes a well-documented scientific rationale from the start. The design must be also responsive to data that becomes available during the course of the trial.
The design of clinical trial protocols has evolved in the past 10 years and may include different parts within a single protocol (such as assessing single and multiple doses, different age groups).
The revised guideline includes strategies to mitigate and manage the potential risks for trial volunteers:
- Calculation of first in-human starting dose, dose escalations and maximum dose criteria
- Criteria to stop a study
- Rolling review of emerging data with the safety of trial participants at the forefront
- Handling of adverse events with regard to stopping rules and rules allowing dose escalations.
The full revised guidance can be accessed here.