Colour of Medicines and Children's Acceptability? A Systematic Literature Review of Children's Perceptions about Colours of Oral Dosage Forms.

The colour of a product plays an important role in consumer experiences, and in the context of pharmaceutical products, this could potentially affect a patient's expectations, behaviours, and adherence. Several studies have been conducted on adults, but little is known about children's opinions on colours of medicines and to what extent medicines' colour affects their acceptability. To address this gap, a systematic search in PubMed, Scopus, MEDLINE, and Web of Science was conducted. Two authors independently screened the titles, abstracts, and references of all articles and selected studies conducted on children (0-18 years old), assessing children's preferences or opinions about colour of oral dosage forms as either a primary or secondary objective or as an anecdotal record. A total of 989 publications were identified and, after screening, 18 publications were included in the review. Red and pink were the most liked colours and there appeared to be a relationship between the colour of a medicine and expected taste/flavour. The review also highlighted a scarcity of information, usually collected as an anecdotal record. Several gaps in the current knowledge were underlined, emphasizing the need of patient-centred studies to understand if the use of certain colours can improve or worsen the acceptability of a paediatric medicine. This will help inform pharmaceutical manufacturers and regulators on the role and need of colours in children's medicines beyond quality purposes.

Putting children first: Understanding caregivers' and children's perspectives on the usability of oral and respiratory administration devices for paediatric medication.

A multi-national online survey was developed to obtain feedback on users' experiences of administration devices for oral and inhaled paediatric medicines. The questionnaire was divided into two identical parts: 1) for caregivers looking after children aged 0-18 years, and 2) for children aged 10 years and above, with parental consent. Each part of the questionnaire consisted of a section regarding oral devices and the other about respiratory devices. All data were anonymous and handled and stored in compliance with GDPR. Ethics approval (REC4612-016) was obtained. The study involved eight countries: Albania, Italy, Israel, the Netherlands, Romania, Spain, UK, and USA. A total of 206 adults and 43 children agreed to take part in the survey. Oral dosage forms were more used than inhaled medicines. For oral liquid medicines, oral syringe was the device mostly used by European and Israeli participants. Measuring spoon was the second most common device used, and was also often used in the USA. For respiratory devices, manually actuated and breath actuated metered dose inhalers were the most common everywhere. All devices were deemed easy to use by most of respondents and instructions clear. However, a recurrent suggestion was to simplify device instructions by adding explanatory images and to summarise or highlight key points. Moreover, respondents proposed other improvements related to device appearance and design that would make the device more acceptable for them to use. Understanding paediatric patients and caregivers' experiences about oral and respiratory devices is key to provide industry with information that can help improve the use and acceptability of administration devices. Aspects that device suppliers and healthcare professionals would need to prioritise are the provision of simpler instructions in the form of images and key summaries, and to provide adequate training on device use. These improvements are essential to ensure that children and caregivers are able to use the device appropriately.

Usability of administration devices for oral and respiratory medicines: Views from a UK primary school.

The correct use of medicine administration devices is pivotal for optimal drug therapy in children. Little is known about end users' perspectives on administration device use. Thus, the aim of this study was to conduct a survey to gain information and opinions from caregivers and children regarding the usability of paediatric medicine administration devices. A survey was conducted at a primary school in the United Kingdom in children aged 10-12 years and their caregivers. It focused on oral and respiratory devices and comprised two identical parts: 1) for the caregivers, 2) for the children with parental consent. Ethics approval (REC4612-016) was obtained. A total of 57 caregiver-child pairs accessed the survey and it was completed by parents only (n = 4), children only (n = 31) or jointly (n = 22). Most participants (65 %) had taken liquid dosage forms (e.g., syrups/suspensions) compared to solid dosage forms (34 %). Oral devices most frequently used were oral syringes (42 %), measuring spoons (22 %), and household spoons (18 %), with parents most frequently demonstrating device use to their children. Respiratory devices were used less frequently, and pressurised metered-dose inhalers with/without spacer (pMDIs) were the most commonly used devices (11/13). Instructions on use were provided by healthcare professionals to both caregivers and children. Generally, oral and respiratory devices were considered easy to use and instructions were clear. However, for both oral and respiratory devices, some suggestions for device improvement were provided by participants. Education/training by healthcare professionals and clear supplier instructions (e.g., pictograms) may be especially effective in ensuring that caregivers and children are able to use administration devices appropriately and receive sufficient information on their correct use.

Risk-proportionate approach to paediatric clinical trials: The legal requirements, challenges, and the way forward under the European Union Clinical Trials Regulation.

BACKGROUND: It is now widely accepted that there is a need for safety and efficacy data on medicines used in children. In the European Union, legislation has provided the necessary framework obligating and incentivizing pharmaceutical companies to carry out appropriate paediatric research to support the development of new medicines. This change in research culture, that medicines used in children should be appropriately researched in children, has also led to the recognition of the importance of investigator-initiated clinical trials in furthering medical knowledge on the off-label use of authorized medicines for which paediatric data are often limited. However, medicines regulatory authorities of European Union countries have largely adopted a uniform approach to the regulation of both industry-sponsored and investigator-initiated trials and, in doing so, have added disproportionate burden to the conduct of paediatric clinical trials investigating authorized medicines. CASE STUDIES: Two European multinational paediatric clinical trials funded by the conect4children consortium are presented to provide a comparative insight into past challenges and to illustrate how the new framework provided by the European Clinical Trials Regulation (No. 536/2014) addresses these barriers in practice. CONCLUSION: The European Clinical Trials Regulation gives a strong impetus to a risk-proportionate approach and offers a path for more efficient delivery of investigator-initiated paediatric clinical trials.

Path towards efficient paediatric formulation development based on partnering with clinical pharmacologists and clinicians, a conect4children expert group white paper.

Improved global access to novel age-appropriate formulations for paediatric subsets, either of new chemical entities or existing drugs, is a priority to ensure that medicines meet the needs of these patients. However, despite regulatory incentives, the introduction to the market of paediatric formulations still lags behind adult products. This is mainly caused by additional complexities associated with the development of acceptable age-appropriate paediatric medicines. This position paper recommends the use of a paediatric Quality Target Product Profile as an efficient tool to facilitate early planning and decision making across all teams involved in paediatric formulation development during the children-centric formulation design for new chemical entities, or to repurpose/reformulate off-patent drugs. Essential key attributes of a paediatric formulation are suggested and described. Moreover, greater collaboration between formulation experts and clinical colleagues, including healthcare professionals, is advocated to lead to safe and effective, age-appropriate medicinal products. Acceptability testing should be a secondary endpoint in paediatric clinical trials to ensure postmarketing adherence is not compromised by a lack of acceptability. Not knowing the indications and the related age groups and potential dosing regimens early enough is still a major hurdle for efficient paediatric formulation development; however, the proposed paediatric Quality Target Product Profile could be a valuable collaborative tool for planning and decision making to expedite paediatric product development, particularly for those with limited experience in developing a paediatric product.

Children's Preferences for Oral Dosage Forms and Their Involvement in Formulation Research via EPTRI (European Paediatric Translational Research Infrastructure).

The paucity of evidence-based data on formulation characteristics preferred by the children is known to limit the design of tailored paediatric dosage forms. The European Paediatric Translational Research Infrastructure (EPTRI) commissioned a study to evaluate children's dosage forms perceived preferences in some European countries and explore the feasibility of using the young persons advisory groups (YPAGs) to involve children in formulation research. An online, age-adapted survey was developed and translated into six languages. The survey link was disseminated across seven European countries: Albania, Italy, the Netherlands, and Dutch-speaking part of Belgium, Romania, Spain, and the United Kingdom. Respondents' (n = 1172) perceived preferences for oral dosage forms primarily differed based on age, health status, and experience. Conventional dosage forms, i.e., liquid (35%), tablets (19%), and capsules (14%), were the most selected. Liquid was widely selected by children less than 12 years and by those healthy and taking medicines rarely. Monolithic solid forms were mostly chosen by adolescents and by children with a chronic disease taking medicines frequently. There was a clear lack of familiarity with more novel dosage forms (e.g., orodispersible films and granules). Noteworthy, granules were not appreciated, particularly by adolescents (52.8%). To rationalise the creation of paediatric formulations, it is important to involve children as active stakeholders and to apply tools assessing children's perspectives on medicines to inform acceptable dosage form development from the start.