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 better set of therapies for children.

Yes I think when families do say that they want to take part in the study it’s a two way thing really. We’re obviously offering them the chance of potentially better treatment or not and that’s what the study is about. And at the end of the day that’s something that we, we always explain the fact it is a trial means that it’s never been proven which of the drugs, say for example, is better. Because if it had been proven it wouldn’t still be a trial so we, you know, we don’t know for sure. We, sometimes people can say oh I think, you know I’ve used this for years and I’m sure it’s better and I’ve done my own bit of, or sometimes I give this and sometimes I give that and certain children do better. But the fact that it’s had to go to a clinical trial means that it’s never been proven which is a key point that families need to, you know, be aware of really.

And there’s like I was saying the Phase 1 study, it was a targeted Phase 1 study because they ethically they had to give it to patients who already had CF [cystic fibrosis] because they couldn’t possibly go treating normal members, ordinary members of the public, normal ones, unaffected of the population. Ethically they would not have got it agreed to have given it to unaffected members of the population. So that’s why they had the big run-in study to get their database and to carefully select some Phase 1 type sort of patients.

Twenty-seven and they were actually given this single dose of, you know, gene therapy and that’s been done now and then they’re and they’re now ready to move onto the next stage of giving [a multi-dose].

So do they monitor that, are they monitoring that?

For the twenty-seven I mean, well yes they were monitored within the month period. Because if you give a single, single dose of it was, the effects of it were going to last for a certain number of days. But because the, the lungs always renew themselves it’s not going to be, you know a permanent change in there so. So that they just wanted to see, you know, test it in, on a single delivery and then, but then they then move on to do the multi dose trial where it is done over a sustained period of time to see whether it would, any benefit had been maintained over the time.

Well, as far, as far as I know the purpose of the trial was, they explained to us that there, there had never been a trial done on children for migraine. There wasn’t really anything out there as, as we’ve learnt along the way of, Just give him Calpol. Give him Brufen And our problem with Daniel is he can’t keep water down for twelve hours, so he can’t keep drugs down. So it, that, that was, there, there was nothing, there’s nothing really out there for, for children that’s used as a, as a wide range. And a lot of kids do suffer from it as, as, even though it’s not a common thing. I think they said 1 in 30, to which Dan said, Oh, that’s one in every clas, which is right. That’s a lot of children.

Yes, we, I know that placebo means just, it could be candy for anything, it could be sweets. It does, it just, it, if sometimes the brain thinks it’s getting help then the body heals itself. Some people believe that. The other two drugs that were on it were, were, we were assured that they, they were well-used drugs. The trial in itself, we, we’d been through a lot with Dan’s migraines and there was no one, there was never any solution or never anyone there to help.

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 that it can either 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.

And I guess I’m all, I’m all for medical research because there was a point where I was looking at you know if, if there wasn’t for, if people did not participate in medical research then there might not have been a neonatal unit and I might not have a baby now. So I sort of I get all the positives of it so it was like anything that can help move things forward for people then I’m all for that really so yeah.

I just think although we had our complications I was very fortunate that although very small, Mikey was very healthy. Had there been something wrong with him and he’d needed surgery or drugs I, you know, the more people who, who do, even the non intrusive sort of research, means that they’d have experience or know more, the more knowledge medical staff have that they could have helped him then yeah so.

I would say firstly as long as it doesn’t do your child any harm, you knew that guarantee. And secondly I’d say that, you know, considering from the time that Alexander Fleming invented penicillin, all the drugs and all the advances we’ve got now to help our children have been based on people being prepared to put their children forward or themselves forward and that for, you know, our children’s benefits. I remember very well when my little girl was born they said to me, you know, the longer we can stave off her heart surgery the more techniques are being perfected and perfected. And they said you’ll be surprised that in ten years time we’ll be able to do things that we can’t do now. Which is true because I know in France they’re certainly replacing the valves by just going through the groin which, you know, 20 years ago people would have not been able to do or even ten years ago. And so it is, you know, I would say unless it’s going to do your child any harm to, for us to progress in medicine and find cures for things that now are you know, life threatening we unfortunately just have to bite the bullet and, you know, [laughter]. And unfortunately, you know, subject our children and ourselves to these tests so.

We had the approach of the only way to make progress it requires you to, for them to have, you know, live data to work on and you’ve got to have people take part in these things, if you don’t! And we’d also seen even up to that point because he was probably seven or eight by the time of his first, you know what he did. We’d already known by then that significant advances had been made in the treatment of CF [cystic fibrosis] and those don’t happen just totally remotely, you know, in the lab. When he was born they didn’t, they hadn’t discovered the gene, the actual gene defect, you know, they knew it was a genetic defect but not the actual location of it on the, you know, the DNA chain. And that happened very, very soon after he was born actually, I think. And then at the time they were saying Oh in five years time we’ll have a cur. Well here we are 22 years later. And you know you understand, from a scientific and medical point of view, that knowledge in one part in theory in a lab is a total, totally different prospect from actually implementing it and knowing how to deliver it. But we, nevertheless, we’d seen the improvements in drugs we’d seen various different approaches to treatment. I mean the most notable one that happened up to that point was the improvement in the digestive enzymes that they use because they can’t digest food so. When he was first born they were on a low fat diet although they need lots of calories because they couldn’t cope with digesting the fat. Well all of a sudden this miracle new enzyme, you know, drug came on and it totally transformed the eating lives for CF, you know sufferers. And so, and we’d seen all kinds of, you know, progress, you know, in that way.

Oh yes, yes but we also understand too that you don’t always know or see any of the benefits that might be, you know, derived. As I say the gene was found in ’87 and then, you know, you read in the paper and people come over Oh I see they’ve found a cure for it so you’re alright no. Yes actually they’ve found a cure but they know putting it into practice is something else. Even when they put it into practice those, it might not help those who are already of a certain age or living with it because of it’s too late basically. Because if they’ve already got lung damage then you can’t reverse it so and that’s I think Robert sort of touched on that. That a lot of the treatments, well they won’t necessarily help him the most, new babies born, it will give them the best, yes in the same way how he’s benefitted from changes in drugs. They were probably trialled on older people who probably are no longer with us but they did that and that’s helped the present, you know, generation so.

The second trial that we were signed up to, I can’t remember the name of it. And that was to look at preterm babies under a kilo, so we, you know, fitted that perfectly, and to look at the use of antibiotics to reduce sepsis. So our understanding of it was that sepsis is a kind of a, really a primary cause for neonatal mortality and it’s a, a big concern for any neonate, and we want to do what we can to minimise that risk as parents. So it was a randomised trial where you were either picked to have the antibiotic or you weren’t. it’s used in paediatric medicine and has been extremely successful, so it was now looking at whether it could be applicable and transferable to a neonatal unit. Everyone was really positive about this and the vibes we got was that it was a really important trial and it was great to be part of. And it would be great actually if we got given the antibiotic because we had a very small low birth weight baby who, as everyone led us to believe, would benefit from this. So we were quite happy to do that, because actually from all the reading and all the background material I’d done, you know, sepsis seemed to be a huge, huge risk, especially to us. So actually if we could do anything to minimise that risk then, you know, that was great. So we signed up for this, and we were given the antibiotic. Now we were approached by a consultant and also a registrar as well, who explained very, very well what we, what we had to do. So I don’t feel that we didn’t get given enough information. I felt that there, there was a lot of information there. And our child was given the antibiotic and everyone was very pleased about that. I didn’t really think too, too much about that. Now we knew as part of that trial they were also going to follow up development at two years and then again at five years. Looking at dosage, we were given good information and the vibes we got that, was that it was a really, was really good that our child had, had been picked to, to have the antibiotic. And I was aware in the neonatal unit of other parents being invited to take part in, in the trials as well and also aware when people weren’t picked to, to have the antibiotic as well.

There was a follow-up at two years and then a follow-up at five years to look at development. So we had a two-year follow-up in [hospital name] actually. And then we got the results of those all printed out and all written up and posted to us. We had copies to give to our GP. And then the trial itself, they were brilliant at communicating actually. So you get, I think kind of two, yes, probably every six months a newsletter comes out, you know, about the number of people who’ve been recruited, what’s going on, what they thinks’ happening. They even send us Christmas cards I do believe. I think they might have stopped that now. But it, it was, the communication, you know, was really very good. And actually what they found with the antibiotics is that it doesn’t make any difference whatsoever. So that antibiotic is not going to be used in neonatal medicine. So that was quite surprising actually, because that wasn’t what we’d been led to believe. So that’s quite an interesting turn on, you know, why you need clinical trials actually to, even though everyone had a good feeling and it had been very successful in paediatric medicine, for, for neonates that wasn’t applicable. So that was quite interesting. So we had the antibiotics for nothing. But never mind. I’ll put that down to, that’s just the way it goes. That was the purpose of it.

Research trials take a long time to develop because of the safety checks and the quality checks. They may take several years before they’re ready to start. They then may go on for months or years, and then there’s a process of analysis. So overall the whole study process can take a very long time before results are known. In general these results are presented in the public domain through scientific literature and other ways. And of course people who’ve taken part in research ask their doctors with whom they worked in the process for those results. Clinical research in children has given outstanding results and improved the health of children. Perhaps the best example is in children with cancer, where in the 1950s the survival rate for children with cancer was around 10 to15 per cent. Otherwise children died. Nowadays the overall survival is well over 75 per cent. And this outstanding success has come through a series of carefully constructed clinical research studies of using new agents and medicines for cancer and new therapies for cancer, step by step improving the quality of outcome and improving the safety of the children in the studies at each stage in order to improve the care. That’s a great example of how children’s research has benefited and saved lives.

And another example of children’s research that has made a, a difference came in the swine flu pandemic in 2009. At that time there was no vaccination for swine flu, and vaccines were developed. And an important clinical trial of two vaccines for swine flu was undertaken in around 1000 children in the UK within around a four to five week period. The National Institute for Health Research, through the Medicines for Children Research Network, supported this trial and mobilised staff and facilities to help children take part. And the results came through very quickly and very significantly, which enabled a new vaccine to be licensed and used to children, used in children to protect them from swine flu. These sorts of trials and other vaccine trials have literally saved thousands of lives and are great examples of how children’s participation in research has really improved the health of the children.

I’ve discovered that that the beauty of this trial, this one trial is that we’ve finally got class one evidence for this. There was a lot of anecdotal evidence, there was a lot of, you know, you know reports written. But not this class one evidence that these doctors so desperately want. But now because we’ve got that, never again can a doctor turn around and say there is no clinical evidence. There is, there is clinical evidence this diet works. So that has dispelled that. And it has made a huge difference globally. That trial that [the] Professor led is, has gone around the world, and it has benefitted a lot of, a lot of the families and a lot of the doctors because all of a sudden people are taking notice. So there are sound clinical trials I think, that make a huge difference, and this was one of them. This has changed opinions. There’s still a long way to go.

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, for future children.

What’s your understanding of a clinical trial? What does it mean to you?

Well, it’s, a clinical trial is just where obviously they’re keeping an eye on how things are like react, like how things are working and reacting to certain things and stuff. So to me it’s a good thing because you, it’s like in, for the future sort of thing, to make it better, to make it, you know, to make diabetes, as I say, not better but, you know, a lot easier for you to do and like to the, how do you put it on, put your finger on it like to get it perfect. Do you know what I mean? Just like your whole body and the insulin, the amount of insulin you have. Like they have the stuff now where you can wear like a belt and it’s got a little box on which like if you need it, it’ll just inject it itself. So there’s a lot, you know, it’s good resource because it works in the end.

But if there was anything to improve your experience, you know, taking part in the clinical trial, thinking of that bit of the treatment, is there anything that can be done to improve it?

Well no, not really, not that I can think of anyway, because everything to me was good. But, you know, they’ve just got to keep doing what they’re doing, obviously the research, because it all helps in the long run, years to come. You know, they might actually get a cure for it, which would be amazing. But they could. Because, you know, they’re finding cures for everything these days. So that’s why they do so much research, because, you know, it helps.

So in a sense are you supportive generally of clinical trials?

Well, yes, because in the long run, you know, it’s better for the people, better for all diabetics really. Because they, you know, with the research they’d be able to control it more. And, as I say, one day they could have a cure, maybe can get rid of it. Which would be a, would be an amazement but be brilliant.