The guideline, which was announced earlier this week and goes into effect January 2, 2018, was revised in collaboration with the European Commission and the representatives of the Member States of the European Union through the EU Clinical Trials Facilitation Group (CTFG).
According to the European Medicines Agency (EMA), the revision extends existing EU guidance to address first-in-human (FIH) and early phase clinical trials (CTs) with integrated protocols.
“The guideline now refers specifically to the calculation of the starting dose to be used in humans, the subsequent dose escalations and the criteria for maximum dose – in order to mitigate and manage risks for trial participants,” an EMA spokesperson told Outsourcing-Pharma.com.
“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,” they added.
Additionally, the guideline emphasizes the sponsor’s responsibility to define the uncertainty associated with the medicine tested “at each step of the development” and to describe how potential risks that might arise will be addressed within the trial’s design and conduct.
According to the EMA, this 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.”
Incorporating lessons learned
As Outsourcing-Pharma.com previously reported, the concept paper on first-in-human clinical trials was drafted following the French Phase I trial in which one volunteer died in January 2016.
Most recently, as part of the investigation into the Biotrial-run clinical trial of Bial Laboratory’s molecule BIA 10-2474, questions were raised on the extent to which the dosing regimen contributed to the trial’s compilations.
Notably, as above-mentioned, the revised guidance refers specifically to dosing. It also provides strategies for mitigating and managing risks and includes principles on starting dose calculations, dose escalations, the criteria for maximum dose, and the conduct of the trial.
According to the EMA, the revised guideline also took into consideration comments received during the public consultation period and a workshop that took place in March.
The comments received on the initial concept paper and revised guideline will be made available in September 2017.