Details of French trial must be released urgently, say UK expertsBMJ 2016; 352 doi: https://doi.org/10.1136/bmj.i319 (Published 18 January 2016) Cite this as: BMJ 2016;352:i319
All rapid responses
This is an article on the need for transparency in research. It appears in a subscription journal that seeks to charge the neck end of £30 to purchase it. As an unfunded critic of the research governance system in the United Kingdom, I do not have the inclination to scale this particular paywall. So I have made an educated guess as to the gist of the article and respond to it accordingly.
What I think is being suggested is that the public interest value in early disclosure of certain key elements of the Rennes protocol transcends the public interest value in allowing criminal and regulatory investigations to take their course. That is a bold claim. What if key witnesses decline to come forward and evidence fails to come to light because the case is being conducted in the full glare of the media spotlight? What if the real issues for the investigating authorities are obfuscated and diverted by a 'free-for-all' of professional academics from outside the regulatory loop who may have grasped the wrong end of the stick? Can every systematic review of the Tamiflu drug claim to have been a good one?
The first question is one of public safety. If the incident at Rennes might show that subjects in similar trials of similar compounds under similar dosing regimens are at risk of harm then the correct course is for the regulators to issue a public safety alert and to consider suspension of all similar projects. That is for the regulators to decide.
If the regulators are not smart enough to decide who is at risk in the current pipeline for research, then the correct course is for the national competent authorities or the European Medicines Agency to issue a call for skilled experts to come forward and answer the questions that need to be answered in a collaborative "safe haven" environment. In this safe haven, legal issues surrounding the protection of trade secrets and the need for public interest disclosure can be thrashed out. If people want disclosure of the outcome of safe haven deliberations, then they can apply to the domestic regulators under national Freedom of Information laws or to the EMA under the EU regulations governing access to public documents. There is a right of appeal from this. This is a better solution than having to listen to months of 'tub thumping' about the need for universality of access to other people's research data when there may be legal impediments to that access that can only be resolved by the courts or the legislators.
The final question is the most important. Disasters in clinical trials would not happen if those clinical trials had never been approved in the first place. Not every accident in a clinical trial is the fault of a relevant approval body. But some of them might be. By 'relevant approval bodies', I mean national competent authorities and ethics committees under the 2001 Directive. Are there systemic failings in the French regulatory system that resulted in errors in the approval of the protocol and was that protocol responsible for what happened in the drug trial disaster in Rennes? These are questions that are still to be answered and I profess no concluded view upon them. But I do contend that there are systemic safety weaknesses in the ethics committee system in the United Kingdom that were extant at the time of the TGN1412 Disaster at the Northwick Park Hospital in May 2006 and which have never been put right. It is correct to re-examine the TGN1412 Disaster and to ask if regulatory failings lay at the root of it. These matters have been touched upon in my evidence to Parliamentary Select Committees dealing with clinical trials and the role of the UK Health Research Authority. These can be accessed via a word search of the UK Parliament website. The role of ethics committees in the approval of drug trials in the United Kingdom requires critical re-evaluation in the light of what happened at Northwick Park. The need for re-evaluation of European ethics committees is even more manifest in the light of this new disaster in Rennes.
Competing interests: No competing interests
British specialists called for further details about the French trial disaster and Hawkes rightly stressed this is urgent.(1)
Too much time has been lost: the first patient, who died, was hospitalized on Sunday for stroke but the French Drug Agency (Agence nationale de sécurité du médicament et des produits de santé) was only informed on Wednesday and the inspection only began on Friday.
Adverse drug reactions are poorly reported globally. In the case of healthy people participating to phase I trials it is beyond understanding that adverse events are not systematically reported. Information and education as monitoring and identification of phase I trial participants must be improved. Would it be so complicated to use information technology for real-time monitoring of events where the social security number is used (eg hospitalisation, prescription …)?
Dr Ben Goldacre, co-founder of the AllTrials campaign for clinical trial transparency, said: “… The medical, academic and regulatory community have still not fixed the known problems around phase 1 trial transparency that were identified during the UK government’s own inquiry into the TGN1412 trial.(In 2006 six people were left critically ill) But for as long as we continue to allow dangerous secrecy to persist around such trials, we make these disasters more likely.”(http://www.alltrials.net/news/comment-from-ben-goldacre-on-the-phase-1-c...)
1 Hawkes N. Details of French trial must be released urgently, say UK experts. BMJ 2016; 352 doi: http://dx.doi.org/10.1136/bmj.i319 (Published 18 January 2016)
Competing interests: No competing interests