High time that regulatory authorities adopted a more assertive position

He has a critical view regarding Regulatory Science. More should be happening, explains Prof. Dr Adam Cohen, professor of clinical pharmacology at Leiden University Medical Centre (LUMC) and founder of the Centre for Human Drug Research (CHDR). "I believe it is high time that regulatory authorities showed a willingness to adopt a more assertive stance. In the end, authorisation follows the science."

It's a vicious circle we really have to break. If what you call 'Regulatory Science' can help in this endeavour, then so be it."

Up until 1 January 2018 Cohen was the director of the CHDR. These days he is the director of Innovation Services. He advises and is involved in new product development to see whether medicines are effective. According to Cohen the regulations relating to the development and authorisation of medicines is too complicated. "As a result the industry is retaliating with extremely high prices for medicines. It's a vicious circle we really have to break. If what you call 'Regulatory Science' can help in this endeavour, then so be it."

According to him, there could be a role for the MEB in this. "As a country we always think we are leading the way in lots of areas, so perhaps it's time we start doing that. I certainly think there is a problem that needs resolving. However, I cannot think of any Regulatory Science research that has revealed how many pointless rules there are. Although we and others have published reports on the pointlessness of the system, too little is still being done. If science leads to innovation, it should lead to a much simpler authorisation process that is in keeping with today's world."

In this video Adam Cohen shares his view regarding the MEB within Regulatory Science.

(The letters CHDR on a building. Inside, a man goes up some stairs. Adam Cohen:)


ADAM COHEN: So, we think about the idea of regulatory science now, and we never did.
So, that in itself is important.

(Cohen leafs through a book.)

I personally wouldn't call it regulatory science,
because science tends to be a way of finding new concepts
that simplify a complicated biological or scientific process.
But it's more a regulatory audit
and organisational research into how it has worked.
So, it's important that this is being done.
Well, the MEB has started a very laudable programme
in doing this sort of audit in the Escher programme,
and Chairman Leufkens, of course, has been instrumental in doing that.
They do differentiate themselves from the other regulatory authorities,
who do less, I think, but of course they have to operate in the European space
to be able to do that properly, and I think they do.
I think it's very important if it leads to changes.
Now, this is where I have a certain amount of criticism, and this may be too early.
It's possible that we're going to experience this later,
but we have to be honest that a clinical trial,
which used to cost about a million dollars when I started,
now costs close to a billion.
So, whatever we've done in regulation, that hasn't made it a lot easier to do this work.
And I'm not sure it has become safer or more reliable
in proportion to the amount of money it actually costs to do it.
So, the value of it, the value should be that it becomes easier to develop good drugs
and that you find the bad ones quicker.
I'm not sure that's happened.
So, there is lots of work to be done. That's quite important.
As a citizen, I would say,
they have to focus really on judging the data that were produced
and actually making sure that we get safe drugs that are, at least,
drugs where the safety outweighs the risks.
As a scientist, I think that the most important function they could have
is to make public as much of the data as they have.
Both for science, or audit or whichever way you'd like to call it,
but more importantly even, for education.
If you think about the openness of the files of a regulatory authority,
then the immediate response would be, from everyone:
this is secret, and it belongs to the companies that have delivered it to them,
so it should remain a secret. That's how it is at the moment.
But if you think about the value of it for future drug development and for education,
it's enormous, and it shouldn't remain in the archives.
And even files that are ten years old
would be of immense value to train future drug regulators
or to train future drug developers.
And so, I think they should be as open as possible,
and I'm sure it's possible, if you think about it.

(The MEB's logo, next to: Medicines Evaluation Board.)


If things can be made more efficient, the MEB may help, but not in an exclusive, dominant role.

Regulatory Science or audit

"I'm critical about all this. If things can be made more efficient, the experience of, for example, the MEB may help, but not in an exclusive, dominant role. A research programme has to be integrated into a university environment and implemented in all the clinical specialisms. Ultimately the MEB regulates access to medicines on the medicines market on the behalf of the government. And then the question is to what extent research should be part of that. If the MEB performs research, it can create a position for itself based on greater powers of persuasion. However, I think you have to make sure things are kept under control. Authorising medicines for the market is a hugely important task and one that generates billions for the pharmaceutical companies."

"I see Regulatory Science not so much as a science, but rather an audit. It's very important that you keep an eye on the process and on the performance of a company in order to make improvements. The first trials I was involved in cost a million guilders and that same research now costs a billion euros. The resulting data is not massively different. What have we been doing all those years? If you look at the process, you realise it is full of completely senseless rules, tests, barriers and safety principles which are causing problems for people in our organisation. It would be great if an authority made things simpler."

He believes even more improvements can be made within the regulatory field. "It's strange that we isolate medicines from the rest of healthcare. These days medicines are part of a mix of treatments, for example in the context of a surgery. Although technology is being integrated more and more, regulation is lagging behind. At the moment there are no regulations at all for surgeries, while for a medical device you have to plough through an unreadable 175 page document. Let's get this right first of all so that it doesn't matter whether you are getting a replacement hip or swallowing a capsule."

Clinical Trial Regulation: too complicated

The European Medicines Agency (EMA) is aiming to implement the new Clinical Trial Regulation in the second half of 2019. The regulation is intended to harmonise the evaluation and supervision processes for clinical trials throughout the whole of the EU. This is being done via an EU portal and database. Cohen has just read the draft of the new Guideline. "As is often the case the principle is fine, in that all research should be regulated in the same way. However, we are now trying to use this guideline to regulate medicines approval in Europe and that is a disaster. The deadlines are ridiculous. Although every European Member States can approve a trial, with all due respect for the member states they are not the same in terms of medical science. The Dutch regulatory authority has done nothing to simplify the Clinical Trial Regulation. That's a missed opportunity because the Netherlands could have adopted an entirely different position. Now we have to deal with whatever comes our way and that is going to place enormous pressure on the Dutch system.

The Clinical Trial Regulation was going to be implemented as soon as a software package became available that could be used to administer all the trials. That software package has still not been validated and that shows how complicated it is to get things done. But I think it's just that we have made it all too complicated! Make it the same for all medical interventions. For implants and medicines. It is difficult to keep up with the technological developments. There will always be a need for an institution like the MEB to monitor the situation, study everything calmly and do so without having commenting in advance."

Disease is not gender-neutral

Some people have expressed criticism that women are allegedly disadvantaged in pharmaceutical research. However, Cohen asserts that a disease does not make any distinction between men and women. Research by the CHDR has shown that diseases in trials participated in by men and women occur in exactly the same way as they do in men and women generally. "Although there is a slight imbalance, it is not significant. As soon as the medicine has been authorised, the difference is so minuscule that it is negligible. Men and women are extremely similar to each other, certainly from a physiological point of view. We can easily transplant a kidney from a woman to a man and vice versa. Zolpidem is the only medicine in the world for which a different dosage is recommended for women than for men. The difference between men and women is much smaller than the difference between men and women individually. Sometimes people claim that women complain differently about their health. People used to think that women could not get heart attacks. Although symptoms appear in different ways, this has nothing to do with the effect of medicines."

In pharmaceutical research there are 75% more male participants during the first research phase. "This has to do with regulations. Some regulations prescribe that you are not allowed to conduct trials on women without reproductive toxicology. This means that most companies tend to exclude women because they can become pregnant. That is, of course, not a good idea if the trial involves taking an experimental medicine. However, women can take part if they are properly protected. Companies often choose the easy way and that is not necessarily a bad thing because it makes little difference for the research itself."

Read more about the MEB Science Day 2018