Clinical trials: Parents’ experiences

 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.

 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 class”, which is right. That’s a lot of children.

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.

 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 cure”. 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.

 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.

 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.