Introduction

As a reader of the Archives of Diseases in Childhood, you will most probably believe that research on the healthcare of neonates, children and young people (CYP) is a good thing. That it is practical to undertake, can be done ethically, effectively, and make meaningful differences to the well-being and survival of CYP with a range of disorders. There are some people who hold different views though. They are concerned and protective. It is not uncommon for people to be horrified of the idea of research being conducted ‘on’ CYP, without a clear understanding of the nature of what clinical research is, or entails. Examples of malfeasance receive prominent coverage to support this position. As evidenced in a recent survey, 58% of those asked thought CYP were not allowed to take part in research1 and even in early 2018, a major UK Children’s Hospital received a horrified phone complaint from a member of the public who had learnt they were ‘experimenting on children’. The hospital was engaged in a large number of perfectly valid, ethical, approved clinical trials. Beyond this, pragmatic issues present a barrier to research. There are healthcare providers who believe research is valid and useful, but not practical or possible in their setting. Even those engaged in research may be restricting access based on their mistaken beliefs around protecting families.2 We understand and are sensitive to these views but believe they are based on a misconception that fails to recognise the dual vulnerability of CYP—to possible research harm, yes, but more widely and more commonly with much consequent harm, to unresearched care. How do we present our case to such audiences? This first article in our series offers an insight into some of the complexities of undertaking research with CYP, how we can move forward and how we can work together to ensure a better understanding of the need to involve CYP in health research.

Complexities of involving CYP in research

The argument for involving CYP in research can be found all around us. The thirst for answers to the broad common questions of ‘How do I diagnose this?‘, ‘How do I treat this?‘, ‘What caused this?’ and ‘What is the likely outcome of this?’ echoes nearly every month in the Archimedes section of this journal.3 These questions outline the first pair of our beliefs: Care not informed by good quality evidence can be dangerous; though good quality evidence that is not implemented into practice is wasteful and can be just as dangerous. Poor quality research can harm CYP for years after publication,4 and it is obvious poor quality research is a risk to whomever it is undertaken on.

How then to move forward?

Research will only succeed if it is a true partnership involving those with legitimate interest. CYP (and all patients and public in general) should be active partners in research, with their views sought when relevant. Their involvement should map across the entire research process, including prioritisation, design, conduct and dissemination of research. As with other research methods, it should be a subject of research itself to determine its value and improve its contribution. We also need to actively recognise that clinical delivery of care may differ from the clinical researchers undertaking studies; this practical aspect of ‘making research work for people’ needs addressing. How then might we develop and conduct these partnerships successfully? This needs us to:

1. Identify all stakeholders with a legitimate interest.

2. Then engage with all stakeholders in fair debate.

CYP and families who have the health conditions under study will most likely share the professionals’ view that research is of benefit. They are likely to be ‘research friendly’ and are often the champions of promoting research and the need for funding, encompassing the entire spectrum of prioritisation through to dissemination and further priority setting. The practicalities of how this can work will be explored further in a later paper, but in summary, include ongoing CYP research advocacy groups like Generation R15; specific prioritisation project groups, such as condition-relevant James Lind Alliance Priority Setting Partnerships16; and project-based groups like the BRIGHTLIGHT study Youth Advisory Panel.17

However, the emotional aspects of engaging and involving CYP and their families in research can be underestimated. Families, especially those whose CYP are currently in good health, are likely to more cautious in their approach, but there is support available. In a recent survey conducted by the Health Research Authority (HRA), 83% of members of the public said that health research is important.1 Focus group discussions have demonstrated that a major reason for caution is misunderstanding of the place and risks of research (HRA unpublished information). They are likely to share the view that research and care are separate activities, and should remain so.

To work with these concerns requires us to have an emotional understanding of research, while following some practical guidance. The UK has worked extensively in this area and can provide clear examples and guidance, such as through the National Institute for Health Research INVOLVE organisation, who provide further guidance on PPIE in research. Furthermore, a detailed report on the ethical elements to be considered with research can be enlightening.18

When research into research is examined, it is found clinical teams, while likely to voice statements supportive to the concept of research, can often find good reasons why it cannot be undertaken in their area or these particular cases.19 This may be a simple resource-stretch, emotional and mental overload of ‘Too much to do…’; research is imperative but providing clinical care for CYP is more important.

Work from Professor Bridget Young at the University of Liverpool demonstrated that professionals are more of a barrier than patients.2 Despite saying little during trial discussions, parents described feeling comfortable and involved and they valued the way that practitioners explained the trials, but practitioners were often concerned that families were overwhelmed with information. When the parents were asked about this, they did not object to being asked about trials and many positively wanted to be approached.

Parents were more positive about being approached to enter their child into a clinical trial than practitioners anticipated. The concerns of some practitioners, that parents would be overburdened, were unfounded. Educating practitioners about how families perceive clinical trials and providing them with ‘moral’ support in approaching families may benefit paediatric research and, ultimately, patients.

Our inclusion of trials that recruited children who were severely or critically ill has confirmed that recruitment to such trials is more challenging for both parties. However, even in these circumstances, parents did not construe the trial approach as an unwelcome burden.

If you add to this some ‘bad apple’ stories of when the experience of healthcare professionals of research being unwieldy, impractical and unusable in the ’real world' of clinical practice along with ethical knots that may be tied20 there is a chunky barrier to overcome. It can be possible though—and there are several examples to demonstrate that it is practical. We would point to the example of children’s haematology and oncology to show a specialty that was born with an integration of trials into everyday practice and continues to advance care through many different studies.21 This may be considered a golden bubble with the media, researchers and patients all with a heightened awareness of the need for research. Other parts of paediatrics have shown similar success though, with a range of huge neonatal trials undertaken across very large numbers of centres22 23 and the explosion of productive research networks, like Pediatric Emergency Research in the UK and Ireland in paediatric emergency care, which has demonstrated that emergency and acute paediatrics can be research active24 in the same fashion as their subspecialist or critical care cousins. Children’s palliative and end of life care is not a research-free zone either, with research hubs producing work developing this.25

Research needs regulators and ethical reviewers to ‘sign off’ on studies. Historically, ethics research committees have been viewed as the cautious gatekeepers,26 focused on children’s status as ‘vulnerable’. This is not often the case anymore, with regulators promoting a balanced approach, and valuing children’s researchers becoming engaged with developing regulation. An ethically conducted study is recognised as providing ‘no or minimal’ risk to participants; that is, no greater than everyday life. This series goes on to advise how best to clearly think through and place the arguments for a smooth ethical review of your paediatric study, and the authors are working to develop resources and skills in the same zone for those sat on the other side of the table.

Moving forward can only occur with appropriate funding for research too. We are not delving deep into this aspect of making research happen, but agree with a strategy of planning to improve the quantity and quality of paediatric research, recognising while a minority interest, creating happy and healthy children may have a significant impact on adult health and life-course healthcare burden.27

The future: agreeing on how to work together

The future will be brighter if we can bring these multiple stakeholder groups, views and competing interests together. Considering how to proactively enter into discussions, and to do this fairly and honestly, we could consider two recent models in health and bioethics—‘Democratic deliberation’ and ‘Accountability for Reasonableness’.28–30

Democratic deliberation holds five principles:

1. Evidence informed: Arguments should be supported by appropriate and reasonably accurate factual claims. Cherry picking facts and ‘straw man’-based arguments are polemical not honest.

2. Balanced: Arguments should be met by contrary arguments.

3. Conscientious: The participants should be willing to talk and listen, with civility and respect.

4. Substantive: Arguments should be considered sincerely on their merits, not on how they are made or by who is making them.

5. Comprehensive: All points of view held by significant portions of the population should receive attention.

Accountability for Reasonableness, developed by Daniels and Sabin in the setting of managing fair distribution of a limited health resource, adds two further principles propose three elements of fair process:

1. Transparency about the grounds for decisions.

2. Procedures for revising decisions in light of challenges.

Together these approaches lead us to suggest that good research will build on the past, take alternative views and opinions into account, learn from errors and mistakes and work with changing systems to make research safer, more efficient and more relevant. (See online supplementary appendix: Minor Carta.)

The conclusion

Engaging and undertaking research with CYP and their families can happen successfully. It takes detailed planning, enthusiasm, the application of resources, thinking, meaningful discussion, people skills, cake, a sprinkle of good luck and lots of effort… but research can occur as part of real life clinical practice. It is unethical for it not to be an integral offering of modern, effective healthcare in the 21st century.