hildren and young people have been historically excluded from participating in clinical trials to protect them from any potential harm. Considering that there are many conditions that only affect the pediatric population, the only way to study them and to investigate novel potential treatments is by designing clinical trials addressed to this targeted population.

In the near future, in Europe, new strategies will be implemented to design and conduct pediatric clinical trials based on the revision of the Pharmaceutical Legislation that will have an impact on Pediatric & Orphan Drug Development.

Worldwide, the WHO is promoting proper and ethical conduct of clinical trials with children to study treatments for conditions that only affect children or that affect beyond the adult population children and young people. This is the mission of the WHO International Clinical Trials Registry Platform.

Specific regulations, such as the European Pediatric Regulation (EC No 1901/2006) published in 2007, encourage clinical research teams to investigate health conditions that affect children and young people, and established as mandatory the design of Pediatric Investigation Plans. This initiative has parallels in other regulatory frameworks such as the Initial Pediatric Study Plans (iPSP) in the context of the Food and Drug Administration (FDA) in the US.

Patients need to be partners of study teams in clinical investigations, so that patients’ perspectives and preferences are taken into account early on in all phases (1–4) of clinical trial designs. Although the benefits of patients’ involvement can be considered common sense in clinical research, this is still a fragmented practice, especially in pediatric settings.

The European Clinical Trials Regulation (EU No 536/2014) establishes in the Annex I, article 17 (e) the following: “where patients were involved in the design of the clinical trial, a description of their involvement must be provided in the clinical protocol.” Despite this effort, this is not a compulsory instruction, but a nonbinding guidance that promotes the patient’s involvement in clinical trial protocol design and considers patients’ contributions when the clinical trial applications are regulatory evaluated. Small steps have been taken during the last few years to promote and support the participation of patients as advisors early on in the key phase of any clinical trial which is the protocol design.

Children and young people have the same rights as adults regarding their involvement as active partners in clinical trials to test novel medications. Usually, young patients participate in trial-related decisions at an age in which they have the emotional and psychological maturity to understand the consent process. In Europe, there is no standard age across countries at which it is mandatory to request the opinion of young people when deciding to participate in a clinical trial. There is significant age-related variability in the consent process of trials across countries and geographic jurisdictions. Enpr-EMA (European Network of Paediatric Research at the European Medicines Agency) analyzed this difference between European countries in this study.

Besides the legal age of a pediatric patient-to-be for which the principal investigator has to ask for agreement from the minor along with the involvement of the caregiver, the parents, or the legally authorized representative, it is necessary to consider the maturity level of young people to be part of decisions that will affect them. This is established in the Convention on the Rights of the Child (UNICEF, 1989) that includes two important rights relative to the health of children and young people:

• Article 12 establishes the right of every child to freely express her or his views, in all matters affecting her or him, and the subsequent right for those views to be given due weight, according to the child’s age and level of maturity.
• Article 24, States Parties recognize the right of the child to the enjoyment of the highest attainable standard of health and to facilities for the treatment of illness and rehabilitation of health. States Parties shall strive to ensure that no child is deprived of his or her right of access to such healthcare services.

Considering these two Articles specifically, several areas are essential to address to respect the opinions and decisions of children and young people. This applies to any health decision-making process, not only in the context of a clinical trial, but also in regard to all activities that may be performed as part of participation or in general clinical care.

It is particularly critical to include the opinion and preferences of children when trials involve invasive medical procedures. These procedures need to be conducted by professionals with pediatric expertise, considering the legal rights of the children. In this sense, the iSupport project, which was initiated in the context of COVID-19, has delivered a set of standards developed with children, young people, caregivers, and professionals. The iSupport standards aim to improve the care that children receive when they undergo clinical treatment, by reducing harm and establishing trust.

Negative experiences of medical procedures in pediatric populations may have a long-term impact on their well-being and can also affect adherence to future medical procedures. The respect for decisions made, timing, and needs of children represent legal rights, and pediatric professionals need to be trained in these areas. Putting patients at the center of healthcare and clinical research means:

1. Involving patients and caregivers in decisions that matter to them. Professionals can use tools and resources to inform the patients and parents about all the details of the medical procedures. An innovative example, that is accessible in this link, explains the use of 3D tumor printed models to explain a surgery to oncology patients.
2. Including their preferences and opinions in the design of medical interventions. To achieve this goal is key to involve patients and families in co-creation of tools, informative resources, and other resources that can help the medical professionals to incorporate the perspective of patients in the design of medical interventions. It is becoming more common in children’s hospitals to have experts in patient experience design or patient involvement to facilitate these co-creation methods.
3. Humanizing the healthcare to be provided by considering not only the nature of the disease, but also its psychological and social impact. Interdisciplinary teams organized around complex and rare conditions usually include psychologists and other professionals taking care of the emotional care of the patients.

Clinical research and healthcare involving children and young people need to be based on children’s legal rights. The latter is applied to different dimensions including the rights to access information that children can understand, children’s involvement in the decision-making process, and the rights to have access to research-related health outcomes properly shared at a children-friendly level.

Specifically in the context of the consent process of the minor, it’s important to take into account these considerations:

1. The need for agreement between the child and parents’/guardians’ decision. According to the national or international laws in regard to the legal age in which the consent of the minor is mandatory that apply to the country where the study is performed, you cannot include a child in a clinical study based only on the consent of their parent or guardian.
2. The information in the informed consent form addressed to pediatric patients has to be presented based on the health literacy level suitable for the child, and with the format and content accessible to the child.
3. The child has the right to ask questions if the information is not clear and to have the time to make a decision.
4. Educational complementary resources, such as videos or cartoons, can help to understand better the information of the study. In this sense, multimedia electronic consent tools can provide a more holistic experience to the children and access to friendly information.

As a conclusion, in pediatric clinical research there are many opportunities to perform patient-centered trials, design suitable trials considering patients’ needs, and involve them as key partners. This will be more effectively achieved if pediatric professionals treat patients and their families as part of trial teams. To achieve this goal it is essential to work closely with patient organizations and expert networks in pediatric patients’ involvement such as eYPAGnet that operates providing services to academic and commercial sponsors, involving children, young patients, and families using ethical methods.