Children and Clinical Research: Ethical Issues

"Unless ethical concerns about asking children to take part in research are addressed, our understanding of childhood disorders and ability to provide evidence based care will remain limited....Central to the report is the idea that from a young age, children have a role in determining their own lives and should be seen as active participants in research."

This report by the Nuffield Council on Bioethics calls for a change in culture across all areas of children's health research, so that children's and young people's views and opinions can help to shape how research is prioritised, designed, and reviewed. While the practical recommendations in the report focus on the United Kingdom (UK), the report makes a number of conceptual recommendations relevant to all those concerned with research with children and young people, in the UK and beyond (see chapter 7). The report is the result of a 2-year inquiry that involved over 500 professionals, parents, children, and young people in the UK and internationally, including a community consultation activity in Kenya [PDF] and call for evidence distributed through the Global Health Network.

As the Council explains, there are many different kinds of research that children and young people might be asked to take part in. Some studies involve children who are healthy, and others involve children who have an illness or disability. Researchers can't just carry out this research with adults, because children's bodies respond to treatments differently due to the fact that they are still growing. They may also have different opinions about what matters to them. The role of research ethics committees (RECs) is to assess the value, risks, and benefits of all research proposals. However, members of RECs told the Council's Working Party that they can feel anxious about approving research with children. This is because the main aim of research is to find out how to help people in the future, rather than to help the person taking part. Sometimes, research studies may involve burdens or risks.

"The central ethical challenge in carrying out clinical research with children and young people might, at first sight, be presented as how best to balance two competing threats to their welfare: on the one hand from the risks and burdens of research, and on the other from the risks inherent in treatments or services for which there is an inadequate evidence base. However, there is a crucial third factor to add to this equation. What role do children and young people have in all this? How should their voices, and the voices of their parents, be heard? The question of how children, young people and their parents can influence and help shape the whole research agenda, from the initial choice of research topic and the design of a study, through to their own role in deciding whether or not to take part, is a central theme throughout this report. In brief, we argue that it is only through this involvement, through respecting children and young people as valued partners in a joint endeavour of research, that a proper balance between the risks and benefits of carrying out research can be found."

The premise of the report is that good research with children and young people is essential - it is unacceptable to continue to offer healthcare to children without seeking to improve the evidence base for many of the treatments provided - and should become part of routine care in hospitals and in other places where children are looked after. Researchers shouldn't feel they are doing anything wrong when they ask children and young people to take part in research. However, research must be carried out with children and young people, not on them. If they choose to take part, they must be listened to, and feel that they are actively involved. "Being invited to take part in research can come at very difficult times in children's and parents' lives", said Professor Bobbie Farsides, Chair of the Council and Professor of Bioethics at Brighton and Sussex Medical School. However, "children told us time and time again that it was important they should be asked to take part in research, particularly as it may help other children in future." The assumption that all children are necessarily vulnerable may prevent worthwhile research from going ahead, according to the report.

The structure of this document is as follows:

• Chapter 1 sets out the ethos of the report, providing an introduction to the main issues, as identified by the Working Party, and presenting the fundamental attitudes to research and to children and young people that have underpinned the Working Party's approach throughout its work.
• Chapter 2 gives an overview of the empirical evidence of children's, young people's, and parents' experiences of clinical research at the point of potential recruitment to a study, which is followed by a summary of the regulatory approaches that govern this recruitment process.
• Chapter 3 provides further background, stepping back chronologically from the moment of recruitment to research to consider all the factors that influence research up to that point: in the initial prioritisation of research topics; in the process of study design; and in the scientific and ethical review procedures that are designed to act as safeguards in the development of research protocols.
• Chapter 4 develops the Working Party's ethical analysis, which is rooted in consideration of the position of children and young people within their families and the responsibilities of their parents towards them in the context of decision-making about research. Its central concern is to articulate the circumstances in which children and young people may ethically participate in research, suggesting a new approach to concepts such as the "best" interests of a child, and the presumed vulnerability of children and young people in research.
• Chapter 5 explores the professional responsibilities of those engaged in shaping the research agenda: in determining the priority given (or not given) to particular research areas; in developing study design; and through the processes of scientific and ethical scrutiny. It should be read as a companion chapter to Chapter 3.
• Chapter 6 returns to the professional encounter between researchers and children/young people and their families in a research study, exploring the implications of the ethical analysis in Chapter 4 for practitioners at the point of recruitment. It makes a number of practical recommendations, designed primarily for a UK audience, but with potential resonance further afield.
• Chapter 7 draws together the main threads and conceptual recommendations of the report.

The Working Party explains that the risk of children being placed in vulnerable situations can be minimised by ensuring that researchers engage with children's and parents' views when it comes to:

• Developing and reviewing research proposals
  • RECs should require researchers to involve children and parents in the development of their studies, unless there are good reasons not to. INVOLVE, the National Institute for Health Research (NIHR) Design Service and the Medicines & Healthcare Products Regulatory Agency, should explore how the design and scrutiny of clinical trials can better take into account the experiences of children and their families.
  • Young Persons' Advisory Groups (YPAGs) are often asked to review researchers' proposals and information sheets. Industry partners should contribute to the costs of running YPAGs without undermining their independence.
  • RECs should have access to relevant expertise when making decisions about research involving children. The National Research Ethics Service, Royal Colleges, and professional bodies should establish a database of experts who can fulfil this role.
  • The UK Departments of Health, National Health Service (NHS), and Universities UK should protect the time needed for experts in children's healthcare to contribute to RECs.
• Shared decision making: partnerships between children, parents, and researchers
  • Wherever possible, decisions about research should be shared decisions by children and their parents. Children should be as involved in decisions as they wish, and are able to be.
  • Where children and young people have sufficient maturity and understanding, but are not yet treated legally as adults, professionals should seek consent both from children and from their parents. In certain cases, RECs may be asked to agree that parental consent is not needed.
  • In the case of children who are in the care of authorities, the UK children's research networks should work with Children and Family Court Advisory and Support Service (Cafcass) to develop good practice guidance for social services departments and researchers to ensure this group is not excluded from research.
• Promoting clinical research in children and young people: The European Medicines Agency should review the class waiver system to ensure that where a medicine's mechanism of action is potentially relevant for children, research with children goes ahead. Research sponsors should choose to include children in trials if the mechanism of action may be relevant for them, even if a class waiver applies.
• Making research part of everyday life and increasing awareness: The All Party Parliamentary Group on Medical Research should work with others to explore ways of increasing general public awareness of clinical research, including the benefits for children's health and healthcare.

Communication is core to this entire process, from the very first stage: inviting children and young people to take part in research (for more information, see Chapter 6 of the full report). Children and young people need clear information about the research before they can decide if they want to take part. Good communication and good relationships with researchers are very important. One child advised: "Just to be quite genuine, and just like, not sticking to a script... just chatting to you nice, not push you into anything, give you all the details. Like I said - don't overwhelm you just when they're coming to you and asking you at first, you don't need everything at that point - but when they start to show interest, just give you all the details, be honest with you, not try to like hide things from you." Researchers need to make sure that they explain the research in a way that is easy to understand - for example, with information leaflets, games, videos, social networking sites, or apps. Researchers should ask themselves questions like these: "Are you able to demonstrate how you will communicate, and discuss, information about the study appropriately and sensitively with potential participants and their parents, so that they are able to make free and informed choices about whether to take part? Does everyone in your team who will be interacting with children, young people and parents have the necessary communication skills?"

A concluding reflection: "Research should always be subject to robust scientific and ethical review, but by speaking to children and their families, researchers can design studies which are more suited to their needs, and ultimately more acceptable," says Hugh Whittall, Director of the Council. "Throughout our project, we've heard from children with strong opinions on complex ethical and scientific issues. We shouldn't underestimate them. Alongside appropriate regulation, we need a change in culture to ensure that children have a say in the whole research process."

Editor's notes: To complement the full report, the Council has produced an illustrated magazine version [PDF] designed for young people and parents, an 18-page summary [PDF], which includes a list of points to consider when carrying out research with children and young people and links to various related resources, and a short animation (see below) to convey some of the key themes of the Council's report from the perspective of Mia, a character who goes through some of the questions and issues that might be raised when a young person is invited to take part in clinical research. The script was developed following a workshop with 14 young people aged 10-18 who had previously been in contact with the Council, but were not "experts" in clinical research. Also available:

• Click here for the summary in Spanish [PDF].
• Click here for the magazine in Spanish [PDF].
• Click here for the key recommendations in Spanish [PDF].
• Click here to order a printed copy of the report or magazine.

In addition, visit the Nuffield Council on Bioethics website for access to additional information about the report and related resources, such as a blog, films sharing young people's perspectives on clinical ethics reviews, and an update from July 2016 (when a report highlighting some of the developments and activities related to this report was published) onward.