EMA Issues Update on First-in-Human Trials Guideline

The European Medicines Agency (EMA) has released an update on its plans to revise the existing guideline on first-in-human clinical trials.

The existing guideline, released in 2007, provides advice on first-in-human clinical trials, particularly on the data needed to enable their appropriate design and allow initiation of treatment in trial participants. Between July and September 2016, the EMA released for public consultation a concept paper that outlined the major areas that needed to be revised in the guideline. The draft revised guideline was adopted last week by the EMA’s Committee for Medicinal Products for Human Use (CHMP).

According to the EMA, “This revised guideline aims to address the increasing complexity of protocols of first-in-human clinical trials in recent years. While the 2007 guideline focused on the single-ascending-dose design used at that time, the practice for conducting first-in-human clinical trials has evolved towards a more integrated approach, with sponsors conducting several steps of clinical development within a single clinical trial protocol (e.g. to assess single and multiple ascending doses, food interactions, or different age groups).”

The authors have outlined strategies to mitigate and manage risks for trial participants, including principles to be used for the calculation of the starting dose in humans, the subsequent dose escalation, and the criteria for maximum dose, as well as principles on the conduct of the clinical trial including the conduct of studies with multiple parts. They have also covered non-clinical aspects such as the better integration of pharmacokinetic and pharmacodynamic data and toxicological testing into the overall risk assessment, as well as the role of non-clinical data in the definition of the estimated therapeutic dose, maximal dose, and dose steps and intervals.

“Guidance is also provided on clinical aspects, including 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 explained.

The EMA will make available all comments received, both on the concept paper and the revised guideline, after the final guideline is released. The aim is to publish a final revised guideline for the conduct of first-in-human clinical trials in the first half of 2017.

The revised guideline is open for public consultation until February 28th, 2017. Comments should be sent to FIH-rev@ema.europa.eu using the template provided.