Well, clinical research for children is terribly important in order for us to improve the treatment of children, both in terms of making a diagnosis correctly but especially in terms of the treatments available. An important figure is that half the medicines that we use in children haven’t been properly tested and tried in those age groups and we’re relying on the data from adult experience, which in the main can be safely used for children. But it is now time that children’s medicines were much better evidenced in terms of the quality of research that allows us to treat them properly.

I think the first thing I’d say is that children can behave differently in the way they respond to medicines and the way they handle medicines, that they’re not just small adults. The way that they absorb the medicine, metabolise it, break it down and get rid of it perhaps through the kidneys into the urine can be different than for adults. And this is even more evident for tiny babies or babies born before they’re due to be born, premature babies. And so for those reasons it’s important that the medicines that are used in those groups are very carefully checked within the right age group that they’re going to be used. There are different stages of bringing medicines to what’s called the market, different stages of preparing a medicine to be used in the general public. And these are different phases of clinical trials, starting with the first exposure of a medicine to, to a human person, which is called a phase 1 trial. And generally phase 1 trials are not undertaken in children for quite obvious reasons that it, the first exposure to the medicine should be in healthy adults. There are some situations in which the first exposure of a medicine should be in a child. For instance, in some critical genetic diseases which only affect young children, in which the effect can only be shown within that disease, there are sometimes situations in which the children will be the first people to receive the medicine. Thereafter properly designed children’s clinical studies are presented, and nowadays these have to be done as medicines are brought into use in, in the public. And what is called a, a paediatric investigation plan, a plan of how the medicine will be researched in children, has to be presented to the regulatory, the government authorities in order for that medicine to be developed. And studies of medicine will, of the medicine will start just to see if it has a useful effect. These are called phase 2 trials. And thereafter there will be studies on larger numbers of patients to judge the effect of, of how good that medicine is. And later still there are longer-term effects, longer-term studies of the medicine to see how it works in a much larger number of patients, in this case children. And even further then, there are long-term safety studies, because there are real, important concerns that medicines that we give to young children might have longer-term side effects, and we need to monitor those very carefully. So the law in Europe, the European law changed in 2007 to suggest and make companies, pharmaceutical companies undertake studies in children to enable children to be provided with better evidenced and hopefully safer and more effective medicines. So all new medicines that are now produced, with a very few exceptions, have to be researched in children. And part of our role as paediatricians is to help facilitate that, to provide best facilities and best methods of research so that children and young people can take part in this role, and for them and for other children in the future provide the better medicines that we all need.

Nearly all medicines are tested in adults before they’re tried in children. And it is true of all such research that the safety of the people taking part in research is the most important standard that we are all holding to. And great care is undertaken to provide a plan of the research, called a protocol that puts safety first. And the governing principles around the clinical research are even stronger than those that relate to clinical care for instance in the NHS. That is, the standards of research practice have to be even safer and more stringent to protect the safety of participants, be they adult or child.

There are real concerns about undertaking research in children. A feeling that is perhaps unethical to do that. That children shouldn’t be experimented upon is the sort of thing one might hear or read about. And families and young people and children themselves and health professionals working with children are equally extremely sensitive that the research that is done has to be done under strict ethical guidance. And there are very clear ways, in which independent ethics committees and boards can check and supervise that the research practice is correct. I think there is an important statement to make about the ethics of research in children, and that is that it is being done with a purpose, and the purpose is to improve the treatment and improve the knowledge and the safety of medicines for children. And overall about half the medicines that are used in children have not had proper evidence and are being used in what is called off-label or in an unlicensed way compared to the proper license that has been granted for adult use. And there is an ethical dilemma between continuing a situation in which we have untested and unproven medications for children against the other side of the coin, as it were, in terms of testing these medicines in children in proper situations to improve the evidence base and give us a, a better, a better set of therapies for children.

Do you think it’s important that you do take; young
people like your age do take part?

Yes.

Do you?

Yes.

Why is that?

Because
adults have different, see if adults were still getting migraines it would be
different so you get a couple of children then it would be better because their
brains are different.

So a Phase 1 trial is where the, is the riskiest one but that’s tested on people without the, normally tested on people without the condition. So that would just be to see if the drug is safe to deliver, and that’s done by any volunteer that wants to do it. The Phase 2 is then as similar to Phase 1 but they already know it’s probably safe to administer. And that’s done on a small group of people with the condition that they’re looking at and that’s to see if there are any side effects with the dosing or what’s the best method to do the dosing, how effective does it seem to be. And then once, and then Phase 3 is a much wider scale trial which is where, usually double blind and that’s where it’s to really see if across a large group of people with the condition whether they can see a general clinical benefit or not. And then Phase 4 is sort of ongoing, ongoing monitoring, of the drug once it’s been approved from the stage 3 just to make sure there’s no long term side effect that can’t be measured, you know, if there’s, if over 10 years something happens you can’t measure that in the earlier trials.

I’ve always taken part in clinical trials for as long as I can remember as a child I didn’t necessarily understand why I had to get on an exercise bike and go on it for 30 minutes while something was attached to me or why they wanted a breath sample. But as I grew older I began to realise the importance of medical research and clinical trials to directly benefit me. And when developing that point of view I saw how important it was that I had taken part in these trials and also it gave me the motivation to want to carry on in talking part in them. particularly when I think that the difference in the quality of life for people with cystic fibrosis now as opposed to when I was born is vastly different and so much better and solely due to medical research. And so I feel that because I’d benefitted from it then in a way I owe something back, you know, to future generations to help in whatever way I can.

There have been a few times where I’ve, it’s not been easy. As a child I was very needle phobic so and there was at least one occasion where I was asked to take part in a clinical trial and I didn’t because it would have meant having more blood tests and that was something I couldn’t really cope with back then. But now I’m older and I’ve learnt to deal with that then that’s not been a problem anymore.

How would you explain a clinical trial to another young person?

Well, it’s like they have a medicine, and then they sort of ask people to take part in this trial so they can like monitor the side effects and what happens and like how it works and stuff, just to get more information on the medicine.

Yeah, I say that taking part in research and clinical trials. There is quite a lot to think about and to consider, and for example, I suppose one of the big things is that you could be selected and you could have the placebo. So you may think that you’re taking part, for example, in the gene therapy trials if I had been selected or if I had chosen to take part in those trials, it’s I’m sure it’s a big undertaking and a big decision to make and a big commitment and it may have been for however long the trial lasts, every time you go to the hospital to receive what you think is gene therapy you may actually just be getting, you know, a blank copy of everything because you have to have that in a study. So you might be putting yourself through so much and hopefully thinking you’re going to have the benefit at the end of it but you may actually just be like the control. So that would be something you have got to consider that you know there are going to be people which aren’t actually receiving the drug or the treatment and that’s something you need to be aware of and that should be explained clearly.

But I think the main thing is thinking about, although it may be a time investment for you, or it may be something extra you have to do every day for a few days or a week or even a month, or a couple of months, think of how much it’s going to help people with your condition in the future, and think how much although you’re investing your time and effort into it, it will save whatever you’re doing could potentially like either save lives or save people time or give them you know longer to live in what you’re doing. So in the short term it may feel like a big undertaking but in the long term what you’re doing is yeah and even if you are a control in the study you’re still, they still, they need those people and it you’re still benefiting others in such a good way. I can imagine you may feel quite disappointed if you find out after that you have been used as a control or had that placebo but it’s, you’re still very much an important participant.

Yes some terms that we use are blinded which means that you don’t know what treatment is, the patients having. There is single blinded where just the family don’t know, double blinded where the family and the researchers at site don’t know. Randomised means where a patient is randomly allocated one arm of the treatment of the study or another. And there can be two arms to the treatment, there can be three arms and they are randomly allocated. There are lots of different ways that they do like and how they’ll be done electronically or it can be done by sending a fax and someone not related to the study, here at site, randomises them and picks the next consecutive envelope, as simple as that or enters it onto a spreadsheet and it randomly allocates them.

Placebo, there’s some studies what we call placebo controlled and some patients get a placebo. A lot of families like it explained as a dummy drug so it’s a drug that isn’t a drug. It can be a lactose tablet or something else. And it will always be made to look exactly the same as the actual active drug so that people don’t know. So if we had a girl and a boy both on the study they couldn’t look at the drug and say Oh well you’re on different than me. They would always look the same and the tablets would look the same as each other, liquid would look the same as each other and everything would look the same as each other. And the idea of a placebo is, is it that the active ingredient is helping the patient and the symptoms and the quality of life or is the fact that they feel that having something is helping them and that’s, it’s very interesting to see the placebo effect.

Did they explain that to you?

Not much.

What do you understand about that?

I didn’t understand it, first. I’m not sure about; I know bits of it but not all of the information about.

What do you know about trials? Would you be able to explain it to, if you had to tell one of your friends at school that you were, what, how would you tell them, say, I’m taking part in a trial and this is what it i?

A trial is just like, it’s not like the other drug I was on, which loads of people have and like most people start off with. it’s like just very few people are having it and the, and it was just, basically it’s a new drug and they weren’t sure if it worked or not. So I was trying, basically trying it out.

Well I would always remember that you know, things would be explained to me but I perhaps then just thought oh this is something else I’ve got to do for the hospital check up and maybe didn’t really understand what I was doing was a voluntary thing contributing to medical science. But you know, I, I trust my mother that she always made sure I was doing something that well hopefully that she would think that if I could have made that choice myself I would have wanted to do and as such when I’ve got older I have chosen to make those decisions. And yes from what I remember the ones I did when I was younger usually weren’t very involved as I say just be collecting sweat samples while I cycled on a bike or taking a sample of my breath to freeze it. Whereas when I’ve got older much had more involved ones like this gene therapy dose and I’ve also done, I did a clinical trial they had to stick a, a probe up my nose and then measured the measured the potential difference in the cells in my nose and so you had to sort of sit there with this tube in there while this liquid was dripping out of it. And in fact on that one I remember the, the doctor then said to me I know you might not want to do this but could you come back and do it again in a couple of hour’s time And I wasn’t doing anything I had a travel card in London and so I went Yes okay I’ll just go off for a bit and come bac so. So I like to think that I do give as much as I can.

And these are all clinical trials to do with cystic fibrosis and helping other people?

Yes and I’ve and, you know, sometimes I have seen a direct benefit from it, almost. I took part in one study where it was assessing whether a particular steroid flixotide, whether, it was assessing, it was known to have a good beneficial effect in people with asthma but it wasn’t really known if it was for people with Cystic Fibrosis. And as it happened in that trial I was on the placebo and there was no change so as a result of taking part in that trial I was able to come off a steroid that I was on effectively needlessly. So I have seen direct benefits in that way but then also sometimes it’s longer term like the one I’ve just told you about with the dripping through the nose because that’s run by one of the doctors at the hospital and I’ve seen him subsequently and he said, Oh yes we actually found some good results and it’s been written up in a paper and it should end up in a journa. So it’s nice to know that what I’ve taken part in has worked and it is making progress.

Do you know the result of the?

Yes, they’re
doing one block now.

they’re doing one block?

they’re doing
one block now because, I was quite, to be honest I was surprised that they
actually did the trial because they, this is what they do in Europe and America
already, that way Europe is quite ahead in research when it comes to cancer. So
now they’ve changed to one block across the country not the country, region or
whatever. You get what I mean.

That’s interesting really isn’t it?

Yes.

So in an end…

But I suppose
they had to prove it otherwise they would be like; they would have no reason to
change the trial because from different nationalities react differently to
drugs. Different ethnic backgrounds, your DNA is very different.

Yes and age.

Exactly.

So just, did that reassure you when you heard that,
when you found that out just doing the one block?

I mean for
patients now it’s very good because at the end of the day it’s less suffering.
it’s less chemo and its less toxins and it’s less suffering. So yes I mean
that’s a lot better.

And because it does affect a number of different organs in the body and it affects everyone in different ways and there is a lot of research going on currently and there has been over the last, you know, in last few decades into improving life expectancy and improving the condition of people who, with CF. Most recently what’s going on is the gene therapy trials which in very simple terms replacing the faulty gene in people with cystic fibrosis and this is something which is really interesting and that I’ve been reading about. it’s not something I’m directly involved with. I haven’t been on the trial but there are people, because this is the first time research and clinical trials like this have ever taken place anywhere in the World. And so it is really interesting.

And I think it’s for young people you have to realise that in order for things to develop and for progression to be made, like since, I can’t even describe the difference in like my treatments from when I was diagnosed at the age of eight to now when I’m twenty two. And like one of my friends was round last night and he looked and said Is that your nebulise he said Do you remember when you were like ten years old and it was like this big and you had to have tubes going out of the window and you had to have all this and it took like twenty, thirty minutes if not longer per session and now it’s about that big and it takes two minute and he’s just like, I can’t believe the difference.

And all that’s come from clinical trials and from research being done. And you know the different ways, my treatments that I do now are very different from the ones that I had when I was eight years old. And without people taking part in research none of that would have been able to have, you know, have been developed and I would still be stuck doing…

The huge nebuliser?

Yeah and the solution which I use now to help me loosen my mucus in the morning that wasn’t available when I was first diagnosed and that’s been developed through research and trials. And now I don’t think I could cope without it. So I don’t, it’s just you know the benefits of taking part although you may think on a personal level it might not benefit you immediately, in the future it will and it’s not just going to benefit you but so many people.

Do you think it’s good to take, for young people to actually take part in clinical trials?

In some ways yes, in some ways no. Because at that age they don’t really know what’s going on. Their parents will know what’s going on. So in that way I’d say yes, because they don’t have to worry about all this stuff. But when you’re a bit older, you do have, you do read it and you do try and understand it. And it’s, so you do worry about more, but you do know what’s going on. So it, kind of that catch. Would you want to know what’s going on? Or don’t you want to know what’s going on?

If I had to
define clinical trial I would say it is a way that doctors test new drugs or
new protocols etc by picking patients who are in the correct age range. I
wouldn’t say taking a risk with their life but taking a risk to see if this new
drug works and yes basically. So testing a new drug on a group of patients in
the correct age range in a controlled way. Is that about right?

No that’s fine, it’s how you.

it’s really
hard to define it though because you sort of know what it means, you’ve been
told so many times but when you try and say it yourself it’s really difficult.

And just thinking in terms of clinical trials in
general, I mean do you think it’s important that they’re now doing a lot more
clinical trials for young people?

I do because I think young people are like the perfect
candidate for them, because you’re much more likely to bounce back anyway. And
also that, I don’t know, you’re probably more likely to do a clinical trial
again in the future if you’ve been on one that’s been a success. So it kind of,
if you get sick again when you’re a bit older, it’s kind of prepping you for
contributing to another clinical trial.

And do you, what, how would you explain to somebody,
if you were explaining to another young person or to your friends what a
clinical trial is, how would you describe it?

I didn’t, actually I didn’t tell them I was on a
clinical trial. I just told them I was on the, the chemo. I just told them,
because it’s as toxic as that, and I just don’t think they’d really understand
it if it was the other thing. And so I just, I just said it was that. And, and
my mum does as well. it’s like people, we just say that I’m on, I was on that.
Because I think people are a lot more kind of aware of it, so they kind of
understand it more. I think they treat it a bit more seriously. Because what
used to get on my nerves is that because you look fine and you’re not in
hospital any more, and people think you’re okay. So the moment that you say,
you know, you’re on that, they kind of treat you a bit more seriously. And I
kind of, I always liked the kind of serious quality they gave it because I
think it made people take it more seriously. Because if someone just dismissed
it I’d be, I’d get, I would get quite angry, because it wasn’t something that I
could just dismiss and be like, Oh, well, you’re better now

So it was like, so other peoples understanding?

Yes other peoples understanding. If they understood
something a bit more, then I’d just let it be a bit simpler.

The importance of clinical research for patients’ health and well-being has been increasingly recognised in the last five to ten years. In the UK we have the National Institute for Health Research, which is part of the NHS and provides a superb research support structure to help families and patients take part in clinical research and to support health professionals undertake that research. And this has been outstandingly successful in many different areas of research. And importantly for children, a specific area, topic of interest for this National Institute for Health Research was in medicines for children. And this network has been developed since 2005 to support children taking part in these very important studies. And to date over 22,000 children have taken part in clinical research studies of medicines in children to help provide better medicines for them and for their, for future children.