March 16, 2016

expert reaction to editorial commenting on lessons that can be learned from the French clinical drug trial tragedy

The British Journal of Clinical Pharmacology has published an editorial which discusses possible failings and implications of the French drug trial earlier in the year which led to the death of one volunteer and the hospitalisation of several participants.

Prof. Stephen Evans, Professor of Pharmacoepidemiology, London School of Hygiene & Tropical Medicine, said:

“This editorial, written by people who really understand the need for and the benefits and potential harms of ‘First-in-Man’ studies, makes it clear that risks can never be zero, but that they can be minimised. It is clear that the protocol had some limitations in the way that doses are given successively to the same individuals (multiple dosing) which can result in different effects from a single dose at the same level.

“The Editorial has several important aspects. Firstly that the information about all the details of what went on and the relevant documentation are not yet publicly available. This is unfortunate but we do not know the reasons why the information is not available. We can hope that eventually we will have full information.

“The second is whether the current system of checks carried out within and outside the trial organisers are adequate. A third issue is whether in this trial the checks were done correctly or whether what happened was totally unpredictable. It seems likely that there were some inadequacies in the process of doing the trial, as noted in the Editorial.

“Are there lessons to be learnt? Clearly there may be some when we know more, but the authors say “A process for systematic risk assessment currently used in the Netherlands could be applied routinely to all trials with novel compounds.” This seems entirely sensible. What the authors do not say is that the regulatory requirements for low risk clinical trials require so much assessment that the resources for high risk studies and for deciding what is a high risk study may be too limited. The UK regulator (MHRA) has set out its own guidance and it seems likely that this helps in the UK at least.

“The desire for speed in bringing products to market may require to be moderated and need a slower approach with high risk products, and as the authors say “We can insist on longer delays between patients and between cohorts”.”

‘Implications of the BIA-102474-101 study for review of first-into-human clinical trials’ by Michael Eddleston et al. published in the British Journal of Clinical Pharmacology on Wednesday 16 March 2016. 

Declared interests

Prof. Stephen Evans: “No conflicts of interest; I am an independent expert member of the Drug Safety Committee at the European medicines Agency, but my comments are entirely personal.”