Guidance on the way first-in-human (FIH) trials should be conducted and managed needs to be updated to reduce the risks to study participants, says the EMA.
The EU drugs regulator has just published a new concept paper – open for comment until 30 September – that lays out a framework for revision of the current 2007 guidelines on FIH trials.
The move comes in the wake of the trial in France earlier this year that resulted in one volunteer’s death and put five others in hospital.
A subsequent inquiry by the French government put contract research organisation (CRO) Biotrial and pharmaceutical sponsor Bial at fault for the failings in the study and led to calls for tightened up FIH regulations in Europe – although this is disputed by the companies.
The 2007 guideline covers strategies to “identify and mitigate risk” in FIH trials but no longer accommodates increasingly complex trial protocols, including a shift towards combining safety analysis with preliminary proof-of-concept measures, using both single and multiple ascending doses and recruiting patients across wider age ranges, says the concept paper.
“In recent years, 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,” said the EMA in a statement.
The concept paper describes use of incremental decisions – based on the data collected at each previous step – to help mitigate risks. It also calls for greater sophistication in the guideline to take into account “the specificities of each medicine, its mechanism of action, and intended therapeutic use”.
The EMA makes specific reference to the French trial, saying the review “takes into account the lessons learnt from the tragic incident”.
The paper was developed by the EMA in collaboration with the European Commission and regulatory experts from EU member states, and will be used along with comments to prepare a new draft of the 2007 guideline, likely before the end of the year.