AstraZeneca’s Henrik Forsman will be speaking on the subject at PCT Europe in Barcelona, Spain later this month. Forsman, who is the director of scientific project management at AstraZeneca Sweden, said the First-in-human (FIH) guidelines released by European Medicines Agency (EMA) in November 2017 can affect the progression and speed of early phase clinical trials.
“A guideline is not regulation and therefore gives some room for interpretation. It is our experience that we need to submit a few trial applications to more than one regulatory authority to understand how the guideline will be interpreted,” Forsman told us.
He further explained, “We have already seen that the guidelines are interpreted differently by different regulatory authorities.”
The ‘most important risk managed’
The guidelines outline risk management strategies to address the uncertainty associated with FIH trials. It stresses that sponsors should describe how potential risks will be addressed within the trial’s design.
“The most important risk that needs to be managed is to protect the participants in a study while still being able to explore a wide enough dose spectrum. This is also the main purpose of the FiH guidance,” Forsman said.
“As first in human trials are becoming increasingly more complex, with the aim to study more than pharmacokinetic (PK) and safety and tolerability, the industry is in need of FiH guidelines to preserve the safety of participating subjects and to ensure an efficient approval process with regulators,” he added.
Revision and scientific rationale
In 2016, a revised concept paper on FIH trials was drafted by the Committee for Medicinal Products for Human Use (CHMP), following the death of a clinical trial participant. The EMA thus set out the framework for review and assessment of preclinical drug candidates, and clinical trial design.
A spokesperson for the EMA told us previously that per the guidelines, sponsors are provided with criteria about when 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.
The EMA’s approach to FIH must be supported by a “well-documented scientific rationale from the outset and be responsible to data emerging over the course of the trial itself.”