Can the UNCRC provide a framework to support scientific advancement?
Data from clinical trials is essential in the development of evidence-based medicines for children. With small patient numbers and many paediatric conditions considered ‘rare’ diseases (The UK Rare Diseases Framework - GOV.UK (www.gov.uk)) the sharing of data is essential in piecing together the natural history of a disease or the effectiveness of a treatment. The balance is to protect the human rights of the individual child whilst they contribute to the benefit to the whole paediatric population.
Paediatric research is the type of research that is conducted in a clinical setting, primarily concentrating on the recruitment of children with a specific condition, such as cancer, cystic fibrosis, diabetes and many others. Children’s medicines have been historically under researched for two main reasons: firstly, the school of thought that children needed to be protected from research and secondly, as a small population, they rarely offer an opportunity for industry to make a return on the investment needed to bring a new drug to market. These two components have led to an environment where children are routinely prescribed medicines off label and off license and where new therapies for conditions that specifically impact children, such as paediatric cancers, are rare.
For the new therapies that are in development, the data collected from clinical trials is relied upon by the regulatory agencies, including the MHRA (UK) and the EMA (Europe), to make decisions on whether drugs should be given the Marketing Authorisation allowing them to be used routinely. That data will include the results of blood tests taking during the trial, the results of physiotherapy and neurology assessments and any reactions that the child may have had to the medication. Also, before a child can be included on a trial then their eligibility must be confirmed, which is some cases includes the results of genetic testing, including for example genetic mutations that may impact on cancer treatment.
As an understanding of research has advanced it is now considered important that children participate in research and are protected through it rather than from it (Children and clinical research - The Nuffield Council on Bioethics (nuffieldbioethics.org). It is recognised that an increased knowledge and understanding of childhood conditions is needed to support the development of age appropriate medications and that this knowledge is essential to the advancement of the child’s right to the ‘highest attainable standard of health’ (UNCRC Article 24) and their right to participate in and benefit from scientific advancement (ICECSR Article 15(1)(b)). ICH GCP (ICH Official web site : ICH) already offers the rigorous standards for running research whilst the ICH GCP E11 offers additional support to those designing studies for the paediatric population. (GUIDELINE FOR GOOD CLINICAL PRACTICE (ich.org)). However, with the growing ways of collecting data, and the new information that can be collected the UNCRC offers a framework for collecting and sharing data in paediatric clinical trials.
First and foremost is the question of whether sharing data is in the best interests of the child (UNCRC Article 3)? This is where it is important that we get the views of children themselves so we can understand what they perceive to be in their best interests especially when it comes to sharing sensitive information, such as the results of genetic testing. We also need to know where they see the balance of sharing information with their other rights, such as the right to life, survival and development (Article 6), the right to health (Article 24). The time spent exploring this topic with children could provide the basis for guidance to research ethics committees when they are deciding which trials reach the ethical standards to commence in the population and also guidance to society as a whole, possibly challenging the pre conceived notion of vulnerability as a excluder to participation (Children and clinical research - The Nuffield Council on Bioethics (nuffieldbioethics.org)).
We also need to address the issue of diversity in clinical trials and clinical trial data. At the core of the UNCRC is non-discrimination (Article 2) and participation in clinical trials can be bias towards certain social groups and which means the data collected also only reflects the disease progression and reaction in those groups (Improving inclusion of under-served groups in clinical research: Guidance from INCLUDE project | NIHR). With increasing use of AI in the drug development decision making process this could have long term implications for children from, for example, different ethnic minority groups, increasing health inequality between different groups of children (Addressing Bias in Artificial Intelligence in Health Care | Health Disparities | JAMA | JAMA Network).
In addition to the standard clinical trial procedures, we are also now entering a world where there is an increased use of technology in delivering trials and the collection of data. This includes e-consent and e-Patient Reported Outcomes (e-PROs), video capture of trial procedures, together with a call from industry and regulators to increase the use real world evidence and real-world data in drug development (A vision for use of real-world evidence in EU medicines regulation | European Medicines Agency (europa.eu)). The UN Committee on the Rights of the Child General Comment 25 (OHCHR | General comment No. 25 (2021) on children’s rights in relation to the digital environment) recognises the increased role of technology in the lives of children and in addition recognises the opportunities that technology can bring in the healthcare environment but this has to be done with the rights of the child at the forefront.
There is and will continue to be an increased collection of data via wearables such as smart watches, where data can be continuous collected 24 hours a day, 7 days a week. This use of technology has been supporting a new form of data that comes in the form of digital biomarkers, an understanding of a child’s physiological or behavior through the monitoring that wearables offers. Although the use of this technology can be less intrusive and lower the burden of the trial participant, including a reduction of the time spent at a clinical trial site, children must be involved in the discussions around the use of this technology, what data is collected and how that data is protected and shared so that the child retains the opportunity to decide which picture of itself it presents to the world.
Data is integral to scientific advancement in paediatrics. Registries are common place (for example, Pediatric Cancer Data Commons - Pediatric Cancer Data Commons (uchicago.edu)) and used as a tool for the collection of data to support new research. The UNCRC is well placed to provide the framework for the collection of the data in way that also respects, protects and fulfils the human rights of children whilst they participate in life changing and often life saving research. There is already a network of Young People’s Advisory Groups (Home - eYPAGnet) that support children to shape health research. They will undoubtedly continue to support them to explore the impact of new forms of trial data collection and the impact this may have on their various rights including their right to benefit from scientific advancement.
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