Studies show that most families and young people would like to be told about research that’s relevant to their condition or their family. But often health professionals, doctors or nurses are reluctant to place an extra burden of research on a family that may have a lot of other worries about the disease or their child at that time. Indeed there are studies coming through now which indicate that families who wanted to take part were not given that opportunity. it’s really important that families and young people who want to know or are interested if there are research opportunities to improve their care speak up and indicate to their doctors and other health professionals that they are interested in hearing about the research. It doesn’t mean they have to take part, but they may well want to know what’s going on and think about the opportunity to participate in that study. And doctors and nurses need to recognise that families are increasingly interested in hearing about the research opportunities and giving, being given their own choice to decide whether or not they can participate.

In many trials or studies of medicines, part of the proper practice is that the participants, in this case children are not aware whether they’re taking the new medicine or perhaps a dummy medicine called placebo or another medicine. Because if they were aware or their doctors were aware which one they were taking, this might influence the results and give a false answer, which none of us want. And so in many trials like this the term blinding is used and this refers to the patients, the families and/or doctors not knowing which of the medicines the child is on. Is it the new medicine or is it the comparator medicine? Now these are very useful and, and in a way the gold standard to provide the best research answer. But thereafter longer-term studies can be done when the medicine is known to the family and to the doctor. This is a, a, a phase of a trial that we call open-label, in which they are aware which medicine they’re having and may continue to take a medicine if it’s been shown to have a benefit.

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.

Clinical research is different to ordinary care in the way that it is governed and the standards of research practice, and they generally are much stricter. Research will often involve some extra things to do, perhaps an extra medicine to take or a different medicine to take, and perhaps extra visits to a hospital or a clinic, or an extra blood sample or things like that. And part of this, these extra visits and extra tests are there to check how well the medicine might be working, but also to check on the safety of the patient, in this case a child. it’s important when a research plan or protocol is explained to a family that they have a clear understanding of what the plan is and can see which parts of the study, of the trial are different to the ordinary care that they would receive. it’s very important that families and children know that they are, have a complete opportunity to take part, yes or no. it’s a voluntary action. And they should remember that that voluntary action can be stopped at any point. They can withdraw from the study if they’re uncomfortable and don’t want to do it or their child expresses a wish not to go further. It is a voluntary act, for which researchers are extremely grateful that they are taking part in studies to help for the health and treatment of, of their child or other children as well.

And so parents might expect to attend more appointments or they may have to, the child may have to have more tests done than perhaps would be in their normal treatment plan?

Often research studies will involve extra visits to the hospital or extra tests. And it’s important when considering whether to take part that the families understand clearly what their obligations in that study would be. And the researcher has a duty to explain what parts of the study are extra to the normal care they have and which parts would be part of their routine clinical care.

In clinical trials for adults, the adult gives consent to take part. But for children taking part in studies the situation is very different, because the consent is given by an adult parent or carer who is not themselves the person who is going to undergo the trial and the benefits and the risks. So the situation is different. And researchers need to explain that carefully to families to under-, to, ensure that they understand that. Of course parents and carers consent for their child’s care in general, and this process of consent is similar for research. But it’s important that they receive and understand carefully the written or other information that’s provided to them, so they’re clear which parts of the care are research and which parts are part of routine care. Older children who understand what is being suggested can also take part in the process of agreeing for research. We call this assent, and it’s a process whereby a child gives a positive response about taking part in research. And this concept of assent varies actually from different countries. Some countries don’t even recognise it. And the age at which assent is appropriate varies from country to country. But in general terms, assent is something, is a process that should be sought by a researcher in a child who has a, an understanding of the research process. It’s also important to recognise that this process of consent and assent is an ongoing process. It’s not just a one-off yes’ at the time of signing a piece of paper. It’s ongoing through the study and can be withdrawn at any stage, and researchers will respect that.

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.

Nearly all medicines are tested in adults before they’re, 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, in, 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, that 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.

In clinical trials for adults, the adult gives consent to take part. But for children taking part in studies the situation is very different, because the consent is given by an adult parent or carer who is not themselves the person who is going to undergo the trial and the benefits and the risks. So the situation is different. And researchers need to explain that carefully to families to under-, to, to ensure that they understand that. Of course parents and carers consent for their child’s care in general, and this process of consent is similar for research. But it’s important that they receive and understand carefully the written or other information that’s provided to them, so they’re clear which parts of the care are research and which parts are part of routine care. Older children who understand what is, is being suggested can also take part in the process of agreeing for research. We call this assent, and it’s a process whereby a child gives a positive response about taking part in research. And this, this concept of assent varies actually from different countries. Some countries don’t even recognise it. And the age at which assent is appropriate varies from country to country. But in general terms, assent is something, is a process that should be sought by a researcher in a child who has a, an understanding of the research process. It’s also important to recognise that this process of consent and assent is an ongoing process. It’s not just a one-off yes’ at the time of signing a piece of paper. It’s ongoing through the study and can be withdrawn at any stage, and researchers will respect that.

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.

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.