COVID-19, children, clinical trials and compassion: The ethical case for using innovative or compassionate treatments.

AIM: Safe, effective SARS-CoV-2 treatment has not yet been determined, though some drugs have favourable mortality and morbidity benefits in specific situations. No treatments have been explicitly tested in children, who are, therefore, once again therapeutic orphans. METHOD: We echo calls to enrol patients, including children, into trials but those children recruited to date have largely been additions to adult studies. Few were recruited during the initial pandemic despite the emergence of PIMS-TS/MIS-C, which surely demands paediatric-specific research. RESULT: Must children be proscribed treatments effective in adults until child-specific data emerges, even in a pandemic? Will appropriately powered dedicated trials ever determine specific child-COVID-19 treatment pathways? Is the protracted time frame to assemble such data acceptable to children with severe COVID-19 today? Such factors are relevant in considering whether children should have access to compassionate, innovative, pandemic-disease treatment. CONCLUSION: We argue that children should be permitted, indeed have a right, to access innovative treatments early in any future pandemic, following an individual best interests consideration. This will remain the case until formal studies powered to determine children's optimal treatment commence, when the moral duty switches to ensuring children are enrolled, with any preceding innovative-use data made available to researchers.

The Birkenhead drill suggests 'women and children first': government and society's reversal of the drill during the COVID-19 pandemic, left children last and cannot be allowed to continue.

The Birkenhead drill states that in the time of crisis, the correct action is to prioritise the weakest and most vulnerable, in that example, women and children. Ethically this has been well analysed in terms of the intrinsic value of the human versus any utilitarian calculus of worth to society's function. We do not attempt to re-analyse this but do note that standard pandemic planning often disadvantages the weak and vulnerable in terms of allocation of resources to those with a greater chance of functional survival. We more argue from a debt that society owes its children in terms of the sacrifices they have made in terms of school, social life, healthcare and overall welfare during the pandemic from which they were at markedly less risk than adults. Society owes a debt to its young, and this on top of pre-existing commitments to the them that most nations fail to realise, calls for prioritisation of children and young people's issues as society rebuilds. The effects of poverty and systemic racism on many children must be tackled; so too the existential threats of climate change and pollution. COVID-19 provides a once in a generation opportunity to create a kinder, fairer society. Early signs are not good: Pub re-opening prioritised over school re-opening; no significant investment in children's services or women's health, a significant determinant of children's welfare. We highlight the way COVID-19 has, and continues, to harm children and argue that the contemporary erosion of the Birkenhead principle is simply amoral.

Medical Innovation in a Children's Hospital: 'Diseases desperate grown by desperate appliance are relieved, or not at all'.

A balance needs to be struck between facilitating compassionate access to innovative treatments for those in desperate need, and the duty to protect such vulnerable individuals from the harms of untested/unlicensed treatments. We introduced a principle-based framework (2009) to evaluate such requests and describe its application in the context of recently evolved UK, US and European regulatory processes. 24 referrals (20 individual; four group) were received by our quaternary children's hospital Clinical Ethics Committee (CEC) over the 5-year period (2011-16). The CEC-rapid response group evaluated individual cases within 48-hours; the main referrers being haematology/oncology, immunology or transplant services (14). Most requests were for drug/vaccine/pre-trial access (13) or biological/cellular therapies (8). The majority of individual requests were approved (19/20); neutral or negative opinions were given in 5, including 3 group requests. Recently evolved regulatory processes share common criteria and conditions to our framework including: demonstration of clinical need; sound scientific basis with lack of viable alternative; risks-benefit/best interests evaluation; arrangements for fully informed consent; no compromise of arrangements to test treatment for licensing purposes; consideration of resource implications. There are differences between individual processes and with our framework, with respect to procedures, scope, application format, costs and obligation to make available all outcome data. Our experience has emphasized the need for an independent, principled, consistent, fair and transparent response to the increasing demand for innovative treatment on a compassionate basis. We believe that there is a need for harmonization of the recent proliferation of regulation and legislation in this area.

European Academy of Paediatrics statement on the clinical management of children and adolescents with gender dysphoria.

Gender issues have become a polarised and political subject in modern paediatrics and indeed, in broader society. These include the management of infants with disorders of sex development and transgender sports participation, but especially recently regarding the management of gender dysphoria. The European Academy of Paediatrics (EAP) acknowledges that there are deeply held beliefs about this issue based on conscience and social norms. Several European countries, led by the UK, have recently reviewed the management of gender dysphoria in children and young people. Recognising the need for far more research into treatments such as pubertal suppression and cross-sex hormones in children and young people, we review the current ethical and legal dilemmas facing children with gender dysphoria, their families and the clinical teams caring for them. We suggest an approach that maintains the child's right to an open future whilst acknowledging that the individual child is the crucial person affected by decisions made and must receive appropriate support in decision-making and care for any associated mental health or psychological issues. Noting that national approaches to this vary and are in flux, the EAP advocates a child-centred individual rights-based analytical approach.

Emergency research in children: options for ethical recruitment.

The paucity of research data to guide current paediatric practice has led to children being termed therapeutic orphans. This difficulty is especially pertinent to research in emergency situations, such as acute resuscitation or critical care, where accepted ethical standards for overall research, have historically created practical difficulties for researchers. The welcome establishment of organisations to support UK paediatric research is helping to ensure safer and more effective medications for children, however as the balance between protection and access at the heart of the paediatric research ethical debate shifts to ever increasing access for researchers to children, it remains crucial to ensure the protection for these vulnerable participants. The fundamental protection for research subjects, namely their full informed consent before any recruitment, is not tenable in true emergency situations and so other approaches are warranted if standards are to be improved by human subjects research in such areas. Proxy, deferred and retrospective consent have all been advocated as solutions to this difficulty and this paper explores the ethical justification for these approaches and their utility in safeguarding children and families in emergency situations when traditional informed consent, as currently defined, cannot be obtained in the necessary time frame to enable research.

Organ donation from children: time for legal, ethical and cultural change.

UNLABELLED: Successful transplantation has lead to increasing need for donated organs from children; however, contemporaneously decreased brain-death rates means optimization of donation processes is crucial. Although excellent palliative care and organ donation are compatible, discrepancies exist both between and within European countries in abilities to offer families donation opportunities. Change will require address of legal, ethical and cultural barriers, and this review aims to explore such changes pertinent to both dead and living organ donation. CONCLUSION: We argue that across Europe it is surely time for legal, ethical and cultural change to facilitate parents, families and of course children in having the choice of donation.

Young people's views on their role in the COVID-19 pandemic and society's recovery from it.

OBJECTIVE: There has been little formal exploration of how young people see their role in the COVID-19 pandemic. DESIGN/SETTING: Focus-group discussion with 15 Children's Hospital Young People's Forum members (23/5) to explore their perspective on the impact of COVID-19 on both their lives and those of their community, on school closures, and the role they wished to play in society's recovery from the pandemic. Audio recordings were transcribed verbatim using NVivo Software and analysed using an inductive thematic analysis approach. OUTCOME: Four major themes identified: (1) Awareness of pandemic's impact on others: participants showed mature awareness of the effects on broader society, especially the elderly, socially disadvantaged and parents. (2) Perceived impact on their own lives: principal concerns were the educational and practical repercussions of school closures and social isolation, including effects on educational prospects. (3) Views about school reopening: young people understood the broader rationale for school reopening and were generally positive about it, but expressed concerned about their safety and that of others. (4) Communication issues: a need for clear, concise, understandable information readily accessible for young people was expressed. Up to now, they felt passive recipients rather than participants. CONCLUSION: Young people were concerned about their future, their family and broader society, consistent with a high level of moral development. They want to be active participants in social recovery, including concepts around return to school but require appropriate information and a means by which their voices can be heard. The alternative suggested roles as pawns or pathfinders were discounted.

Developing guidance for pregnancy testing of adolescents participating in research: ethical, legal and practical considerations.

Adolescents need safe effective drugs that have undergone ethically approved testing in clinical trials; such studies often require pregnancy testing in 'women of childbearing age' which includes children/adolescents. There is a lack of consistent standard operating procedures for pregnancy testing in these individuals, in either research or clinical (ie, both preprocedure and clinical emergency) settings. Some harmonisation between a selective or universal testing approach based on a risk analysis of the trial drug or procedure would seem sensible. The need for pregnancy testing and the reasons for the method chosen (universal or selective) should be clearly defined in the research protocol. Research ethics committees (RECs) need to satisfy themselves that the selection of subjects to be tested, the procedures for obtaining consent and the respecting of the young person's confidentiality are appropriate and that management of any positive tests are in accord with local safeguarding policies and procedures. Researchers should have core competencies necessary to manage sensitive questioning and child safeguarding training. Clinical trials of medicinal product (CTIMP) pregnancy testing in females 13-15 years of age requires parental consent and the child's active involvement in the decision-making process ('assent') the implications of a positive test should be discussed in advance Children under 13 years should not normally be subject to pregnancy testing in CTIMPs, unless there are exceptional circumstances, for example, a trial of contraceptive agents of a high teratogenicity risk, as reviewed by a specialist paediatric REC. We analyse the ethical, legal and practical aspects of this issues and supply guidance to support those involved.

Ethical considerations in neonatal end-of-life care.

Decisions regarding the end-of-life care of neonates, especially those at the limits of viability, cannot be made on the basis of clinical facts alone. They should take into account the values and beliefs of all concerned. Application of classical moral theories may take insufficient account of the interests of small babies. Due consideration needs to be given to the value and quality of babies' lives, their best interests, and the interests of their parents in practical decision-making. Life-sustaining treatments can be withheld or withdrawn if they no longer serve the baby's best interests, but active euthanasia (though an acceptable practice in The Netherlands) remains illegal in the UK. Withdrawal of clinically assisted nutrition and hydration can be ethical but remains controversial. If organ donation in UK neonates is to become established it will need to respond to the changing characteristics of neonatal deaths in ways that are ethically and socially sensitive.

How should paediatricians assess Gillick competence?

Competence is an essential legal requirement for valid consent to medical treatment. Children under 16 may be considered 'Gillick competent' to make treatment decisions, but may need to demonstrate this. Applied tests for competence are wide-ranging and context dependent. Competence is related to cognitive ability and experience and may be enhanced by education, encouragement etc.; there is a general duty for professionals to enhance the competence of children in their care. The need to assess a child's competence may occur when s/he wishes to make a controversial decision whose wisdom others dispute. Potential assessors should have the necessary practical skills and an understanding of the child in their social and medical context. Assessments should be developmentally appropriate, explore systemic influences, and consider the child's emotional state, cognitive development and ability to balance risks and benefits. The involvement of a psychologist or other independent third party should be considered in cases that raise serious concerns about competency, or that involve complex decisions or conflict between the various parties. In rare cases courts may be involved.