The European Medicines Agency (EMA) is proposing changes to its existing guideline on first-in-human clinical trials. The EMA explained that the draft text published on Tuesday 15 November takes into account the lessons learned following the death of a patient in Rennes, France.
In-human clinical trials using experimental medicines are currently based on 2007 guidelines. This document of around 10 pages provides advice to laboratories, particularly with regard to the type of data necessary for designing and launching a safe clinical trial. Nonetheless, following the incident in Rennes at the beginning of 2016, the EMA has undertaken to revise this guideline in an effort to strengthen certain provisions.
It should be pointed out that in January 2016, a clinical trial carried out in Rennes by the Biotrial research Centre on behalf of the Bial Laboratory was cut short, following the death of a patient. These tests constituted the phase I first-in-human clinical trial into a new molecule, BIA 10-2474, whose potential side effects were not clearly defined.
The revised draft guideline was drafted by a European group of experts sent by the national authorities in charge of authorising clinical trials in the EU. It outlines risk mitigation and management strategies for trial participants, including what principles should 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. Guidance is proposed on 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 EMA explains that the draft document was adopted last week by its Committee for Medicinal Products for Human Use (CHMP) and has been submitted for public consultation until 20 February 2017 so that it can finally be adopted “in the first half of next year”.
The draft can be consulted at:
http://www.ema.europa.eu/ema/index.jsp?curl=pages/includes/document/document_detail.jsp?webContentId=WC500216158&mid=WC0b01ac058009a3dc . (Original version in French by Sophie Petitjean)