Psychopharmacology in children and adolescents: unmet needs and opportunities.

Psychopharmacological treatment is an important component of the multimodal intervention approach to treating mental health conditions in children and adolescents. Currently, there are many unmet needs but also opportunities, alongside possible risks to consider, regarding the pharmacological treatment of mental health conditions in children and adolescents. In this Position Paper, we highlight and address these unmet needs and opportunities, including the perspectives of clinicians and researchers from the European College of Neuropsychopharmacology-Child and Adolescent Network, alongside those of experts by lived experience from national and international associations, via a survey involving 644 participants from 13 countries, and of regulators, through representation from the European Medicines Agency. We present and discuss the evidence base for medications currently used for mental disorders in children and adolescents, medications in the pipeline, opportunities in the development of novel medications, crucial priorities for the conduct of future clinical studies, challenges and opportunities in terms of the regulatory and legislative framework, and innovations in the way research is conducted, reported, and promoted.

Young patients' involvement in a composite endpoint method development on acceptability for paediatric oral dosage forms.

BACKGROUND: In line with the European Paediatric Regulation, the European Medicines Agency (EMA) asks for investigation of a medicine's acceptability in paediatric medicines development. A standardised acceptability testing method combining the outcome of "swallowability" and "palatability" assessments to a "composite endpoint on acceptability" was recently developed. Before this method's suitability for selection of the most acceptable drug formulation of a new medicine for children can be broadly recommended, the acceptance and relevance of such established acceptability needs the critical review and input from young patients with understanding of the medicines development methodology. The benefit of involving patients in drug product development, clinical research and innovation is well established. METHODS: During a focus group meeting with the KIDS Barcelona (young people advisory group, age 16-23 years) the suitability of the "composite endpoint on acceptability" methodology was assessed. Via electronic questionnaires the importance of involving patients in the medicines development and in the acceptability method development was investigated. Questions on how best to determine palatability and swallowability were asked. The relevance of all EMA-listed acceptability elements was assessed via coloured and numbered stickers and questionnaires. RESULTS: The results showed that the involvement of young people in the medicines and acceptability method development was rated high. The group worked out that a 5-point smiley Likert Scale is preferred for assessing acceptability by 6-11 year old patients, while a Visual Analogue Scale is preferred for collecting adolescents' opinion. The ranking of the EMA-listed acceptability elements showed that palatability and swallowability are the most relevant parameters, while colour of the medicine was rated as least relevant. These results, established face-to-face, were confirmed in a repeat of the ranking through an electronic questionnaire, completed by the participants individually and remotely, 5 weeks later. CONCLUSION: This work reinforced the need and value to involve young people in the medicines lifecycle, and specifically in this acceptability method development. As next step other focus group meetings with more young people from different European countries are planned.

Before a new medicine is authorized, its acceptability by children must be investigated according to law. An acceptability testing method combining the outcomes of "swallowability" and "palatability" assessments was recently developed. During a focus group meeting with KIDS Barcelona (young people advisory group, age 16­23 years) their opinion on the suitability of the method and the relevance of patient engagement in the medicines development process were assessed with paper-based and electronic questionnaires. Questions on how best to determine palatability and swallowability were asked. The importance of different elements that typically affect acceptability was rated. The order of relevance of those listed acceptability elements was assessed using coloured and numbered stickers and questionnaires. The results showed that the involvement of young people in the medicines and acceptability method development was rated high. The group worked out that a 5-point smiley Likert Scale that allows for marking a choice between total agreement and total disagreement is preferred for assessing acceptability by 6­11 year old patients. A Visual Analogue Scale (scale consisting of a 10 cm long line on which a mark has to be placed at the desired position, between total agreement and total rejection) is preferred for collecting adolescents' (12­18 years) opinion. The ranking of acceptability elements showed that palatability and swallowability of a new medicine are the most relevant parameters, and colour the least. The clarity of the outcome reinforced the benefit of involving young people in the development of medicines relevant for children.

Clinical, methodology, and patient/carer expert advice in pediatric drug development by conect4children.

Many medicines are used "off-label" in children outside the terms of the license. Feasible pediatric clinical trials are a challenge to design. Conect4children (c4c) is an Innovative Medicines Initiative project to set up a pan-European pediatric clinical trial network aiming to facilitate the development of new medicines for children. To optimize pediatric trial development by promoting innovative trial design, c4c set up a European multidisciplinary advice service, including the voice of young patients and families, tailored to industry and academia. A network of experts was established to provide multidisciplinary advice to trial sponsors. Experts were selected to join clinical and innovative methodology expert groups. A patient and public involvement (PPI) database, to include the expert opinion of patients and parents/carers was formed. A stepwise process was developed: (1) sponsors contact c4c, (2) scoping interview takes place, (3) ad hoc advice group formed, (5) advice meeting held, and (6) advice report provided. Feedback on the process was collected. Twenty-four clinical and innovative methodology expert groups (>400 experts) and a PPI database of 135 registrants were established. As of September 30, 2022, 36 advice requests were received, with 25 requests completed. Clinical and methodology experts and PPI representatives participated in several advice requests. Sponsors appreciated the advice quality and the multidisciplinary experts from different countries, including experts not known before. Experts and PPI participants were generally satisfied with the process. The c4c project has shown successful proof of concept for a service that presents a new framework to plan innovative and feasible pediatric trials.

Global Collaborative Social Network (Share4Rare) to Promote Citizen Science in Rare Disease Research: Platform Development Study.

BACKGROUND: Rare disease communities are spread around the globe and segmented by their condition. Little research has been performed on the majority of rare diseases. Most patients who are affected by a rare disease have no research on their condition because of a lack of knowledge due to absence of common groups in the research community. OBJECTIVE: We aimed to develop a safe and secure community of rare disease patients, without geographic or language barriers, to promote research. METHODS: Cocreation design methodology was applied to build Share4Rare, with consultation and input through workshops from a variety of stakeholders (patients, caregivers, clinicians, and researchers). RESULTS: The workshops allowed us to develop a layered version of the platform based on educating patients and caregivers with publicly accessible information, a secure community for the patients and caregivers, and a research section with the purpose of collecting patient information for analysis, which was the core and final value of the platform. CONCLUSIONS: Rare disease research requires global collaboration in which patients and caregivers have key roles. Collective intelligence methods implemented in digital platforms reduce geographic and language boundaries and involve patients in a unique and universal project. Their contributions are essential to increase the amount of scientific knowledge that experts have on rare diseases. Share4Rare has been designed as a global platform to facilitate the donation of clinical information to foster research that matters to patients with rare conditions. The codesign methods with patients have been essential to create a patient-centric design.