Clinical Trials – better outside the European Union?

Angus Dalgleish, Professor of Oncology at St George’s, University of London, claims in the Daily Telegraph that “Brexit means we can revive clinical trials killed by the EU”. Departing slightly from my usual theme of pseudoscience, I would like to point out where Professor Dalgleish might be mistaken.

He blames the EU for all the difficulties he says he has had with trying to run clinical trials. The picture is in reality far bigger even than the EU, and goes back to the roots of Good Clinical Practice (GCP). The US Food and Drug Administration (FDA) in the 1960s congratulated itself for having never licensed thalidomide, but had rather a shock when it found that some 20,000 patients had received the drug, in clinical trials that the FDA knew nothing about. Hence a huge review was undertaken to bring clinical research into some sort of regulated environment. Note that the prime motivation was protection of patients. To achieve this, investigators (the people, usually doctors, doing the research on the patients) had a defined set of obligations, as did sponsors (the funders, usually a drug company). A new role was also defined, the monitors who checked and quality controlled everything that all participants did.

Each role was accountable to the regulator for the good conduct of the trial. There is still a widely followed adage, which says “If it isn’t documented, it didn’t happen”. The structure of study files was defined, as maintained by investigators and sponsors. The monitor checked and verified the files, as well as the actual data collected. The FDA had the right to inspect the files and to visit sponsors and investigators to verify what they were doing.

The first version of FDA GCP was published in 1977, and at that time was a voluntary code. But sponsors came to realise that non-compliance would not be helpful to any applications for product licences. It took a long time for GCP to percolate around the world, but it did. Various countries, and groups of countries (eg the Nordic states), introduced their own versions of GCP.

It all got a bit confusing, with so many flavours of GCP, even though they were all based on the fundamental principle of protecting patients. The EU made major strides in the 1980s to harmonise them across member states, and in 1989 the World Health Organisation triggered the process that would harmonise the major global markets of the Europe, USA, and Japan. This process emerged as the International Conference on Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). Today, virtually all developed countries, and most major developing ones, follow ICH GCP.

So what will happen to UK clinical trials post-Brexit? Will we suddenly be freed of the shackles of EU control? No, the point is that the regulatory regime we have right now is not primarily because of the EU, it is far bigger than that geographically and historically. Dalgleish I am afraid typifies the pusillanimous and parochial attitude of so many Brexiteers. He seems to have little understanding of the law we have and why we have it. The existing EU Directives on Clinical Trials and on GCP (two of them) had to be transposed into national law by all member states. This has caused some problems of interpretation, and indeed the UK implementation is seen as particularly rigorous. My almost 30-year experience of working under GCP highlighted far more problems related to lack of harmonisation than to over-rigorous red tape.

When the EU clinical trials and GCP directives came in, academics had apoplexy because they didn’t like having a level playing field between industry and academia. Overall, it’s not at all true that pre-study approvals were quicker before the EU directives. It may have been quicker to set up trials that had academic rather than industry sponsors, but that was because academic standards were much lower, for example for control of investigational drugs.

But the EU did listen to the concerns of academics, notably in relaxation of the rules surrounding Good Manufacturing Practice for investigational drugs – a major bone of contention for university and hospital sponsored trials. The new Regulation EU No 536/2014 is a regulation not a directive. There will be no transposition into national law. The transition period still prevails however, and the Regulation is not yet in force. When it does, there will be no confusion across member states as to what the law says – it will all be the same. Dalgleish complains about how long this is all taking, but clearly negotiating agreement from 28 national governments, and getting the draft law through the EU parliament, was never going to be quick. Do not forget that there is no piece of EU legislation that has not been voted on by our MEPs.

But let me remind you that both the existing Directives and the new Regulation are designed to comply with ICH GCP, which effectively governs most of the global clinical trials activity. Does Dalgleish really think we will be free of any of that post-Brexit? Let me also remind you that he supported the defunct Saatchi Bill, and likes anecdotal evidence. Well perhaps in this post I haven’t completely departed from the theme of pseudoscience.

Clinical research regulation is just one of the many areas of British law that are very deeply enmeshed within the EU, and for very good reasons. I am at a loss to understand how Theresa May’s idiotic Great Repeal Bill will resolve that. Whatever happens, we will carry on doing trials under ICH GCP, to the benefit of patients and no doubt to the dismay of the Little Englanders.

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