The European Medicines Agency (EMA) has announced proposals to revise the current guidance on first-in-human (FIH) clinical trials . A draft concept paper has been released for public consultation, with comments due by 30 September 2016. A draft revision to current guidelines is expected to be released by the end of 2016.

The EMA, the EU regulatory body for clinical trials, asserts that these proposed revisions will “improve strategies to identify and mitigate risks to trial participants”. In FIH clinical trials researchers test a new drug or treatment in a small group of healthy volunteers in order to assess the safety of the drug, identify its side effects and determine a safe dosage range. There is an inevitable risk to life. As such, appropriate regulation and best-practice guidance is crucial.

The proposed revisions partly follow the FIH French clinical trial which caused the death of one patient and left seven others hospitalised, four with brain injuries, in January 2016. Following two in-depth investigations into what had gone wrong, the EMA launched a review of FIH trials in late May 2016.

Sadly, this revision to guidance prompted by tragedy mirrors the events of the TGN412 drug trial (the ‘Northwick Park trial’) in 2006 which led to the EMA’s 2007 FIH guidelines.

Leigh Day partner Gene Matthews represented claimants who suffered severe and life-threatening reactions in response to the novel monoclonal antibody drug tested in the Northwick Park trial. Following the trial, an Expert Scientific Group published a report on lessons learned, leading the EMA to publish the current guidance: “Guidelines to identify and mitigate risk for First-In-Human Clinical Trials” in 2007.

This time, as well as lessons learnt, the EMA states the proposed revisions reflect the developments in conduct and practice of FIH trials over the past nine years. The EMA reports practice 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 2016 EMA consultation paper sets out discussion points for reviewing the current guidelines, including extension to:

  • Early phase clinical trial design (including single study or integrated protocol designs);
  • Non-clinical aspects, including the integration of non-clinical pharmacology and toxicology data; translation of non-clinical data to human use; and the role of non-clinical data for the estimated therapeutic dose, maximum dose level, dose escalation steps etc.
  • Clinical aspects, such as integrated clinical trial designs and study endpoints; clarification of the choice of trial subjects; overall dose/ exposure range; and rolling review of emerging human data during the study.

Gene Matthews, partner at Leigh Day, comments:

“Clinical trials are essential for the development of new, often life-saving, medicines. Inevitably, when tragic events occur (like those in those in the recent French clinical trial of the painkiller BIA 10-2474) hindsight allows holes in regulation, conduct and practice to be identified and it is right, and crucial, that lessons are learnt from this.

"However, as the outcome of the French trial shows, we must do more than simply learn from past mistakes. Responses to the consultation, including by our UK regulatory body the Medicines and Healthcare Products Regulatory Agency, must focus on anticipating future mistakes in order to prevent serious adverse events”