CE accreditation and barriers to CE marking of paediatric drug calculators for mobile devices: a scoping review and qualitative analysis (Preprint)

BACKGROUND Paediatric drug calculators (PDCs) intended for clinical use qualify as medical devices under the Medical Device Directive and the Medical Device Regulation. The extent to which they comply with European standards on quality and safety is unknown. OBJECTIVE Determine the number of PDCs available as mobile applications for use in the Netherlands that bear a CE mark and explore the factors influencing the CE marking of such devices among application developers. METHODS A scoping review of the Google Play and App stores was conducted to identify PDCs available for download in the Netherlands. CE accreditation of the sampled applications was determined by consulting the application landing pages on application stores, by screening the United Kingdom Medicines and Healthcare products Regulatory Agency online registry of medical devices and by surveying application developers. The barriers to CE accreditation were also explored through a survey of application developers. RESULTS Out of 632 screened applications, 74 were eligible, including 60 paediatric drug dosage calculators and 14 infusion rate calculators. One application was CE marked. Of the twenty (34%) respondents to the survey, eight considered their application not to be a medical device based on its intent of use or functionality. Three developers had not aimed to make their application available for use in Europe. Other barriers that may explain the limited CE accreditation of sampled PDC applications included poor awareness of European regulations among developers and a lack of restrictions when placing PDCs in application stores. CONCLUSIONS The compliance of paediatric drug calculators with European standards on medical devices is poor. This puts clinicians and their patients at risk of medical errors resulting from the largely unrestricted use of these applications.

C4C - Paediatric pharmacovigilance: Methodological Considerations in Research and Development of Medicines for Children – A c4c Expert Group White Paper

Children frequently respond differently to therapies compared to adults. Differences also exist between paediatric age groups for pharmacokinetics and pharmacodynamics in both efficacy and safety. Paediatric pharmacovigilance requires an understanding of the unique aspects of children with regards to, for example, drug response, growth and development, clinical presentation of adverse drug reactions (ADRs), how they can be detected and population specific factors (e.g. more frequent use of off-label/unlicensed drugs). In recognition of these challenges a group of experts has been formed in the context of the conect4children (c4c) project to support paediatric drug development. This expert group collaborated to develop methodological considerations for paediatric drug safety and pharmacovigilance throughout the life-cycle of medicinal products which is described in this article. These considerations include practical points to consider for the development of the paediatric section of the risk management plan (RMP), safety in paediatric protocol development and safety data collection and analysis. Furthermore, they describe the specific details of post-marketing pharmacovigilance in children using, for example, spontaneous reports, electronic health care records, registries and record-linkage, as well as the use of paediatric pharmacoepidemiology studies for risk characterisation. Next the details of the assessment of benefit-risk and challenges related to medicinal product formulation in the context of a Paediatric Investigation Plan (PIP) are presented. Finally, practical issues in paediatric signal detection and evaluation are included. This paper provides practical points to consider for paediatric pharmacovigilance throughout the life-cycle of medicinal products for RMPs, protocol development, safety data collection and analysis and PIPs.

Development and Evaluation of a Web-Based Paediatric Drug Information System for Germany

Background: Off-label use is frequent in paediatrics but that does not necessarily mean that the risk-benefit ratio is negative. Nevertheless, evidence-based data is essential for safe drug therapy. In Germany, there is no publicly available compendium providing transparent, evidence-based information for paediatric pharmacotherapy to date. This work describes the development of a web-based paediatric drug information system (PDIS) for Germany and its evaluation by health care professionals (HCP). Methods: Since 2012, a PDIS is being developed by the authors and is supported by the Federal Ministry of Health since 2016. Dosing recommendations were established based on systematic literature reviews and subsequent evaluation by clinical experts. The prototype was evaluated by HCP. Based on the results, the further development was concluded. Results: 92% of HCP believed that the PDIS could improve the quality of prescribing, as currently available information is deficient. Besides the license and formulations, dosing recommendations were the most relevant modules. A dosage calculator was the most wanted improvement. To facilitate sustainability of future development, a collaboration with the Dutch Kinderformularium was established. As of 2021, the database will be available to German HCP. Conclusion: The fundamentals for a German PDIS were established, and vital steps were taken towards successful continuation.

Child health

This chapter covers managing the acutely ill or injured child. It starts with taking a history from a child, and ways of communicating with the child. Direct questions to ask from carers are also listed. The assessment of children is detailed, and recognition of <C>ABC problems is covered, alongside the management of ABC emergencies. Paediatric emergencies and their treatment are explained, and life support of children is included. Trauma in children (the leading cause of death in children over 1 year of age) and management, consent, analgesia, and child abuse and neglect are all contained in this chapter. Finally, paediatric drug doses are tabulated.

Change in National Dosing Advice of Nitroprusside After Potentially Fatal Cyanide Intoxication

The aim of this brief communication is to provide a short overview of cyanide intoxication following infusion of sodium nitroprusside (SNP). SNP is a fast-acting antihypertensive drug frequently used in of hypertensive emergencies. Although SNP is widely known as a safe to use drug, it can cause a potentially lethal cyanide intoxication. The difficulty to diagnose cyanide intoxication and pharmacological principles will be discussed. Hereby, we like to regain attention for this severe complication. As a result of our experience, the Dutch national paediatric drug formulary has been updated with additional warnings and recommendations. Cyanide intoxication due to sodium nitroprusside is a severe and difficult to recognize complication with potentially lethal outcome. Clinicians prescribing sodium nitroprusside should always be aware of its toxic effects.

Paediatric drugs trials in China

ObjectiveClinical trials of children’s drugs are of great significance to rational drug use in children. However, paediatric drugs trials in China are facing complex challenges. At present, the investigation data on registration status of paediatric drug trials in China are still relatively lacking, and relevant research is urgently needed.MethodsThe advanced retrieval function is used to retrieve clinical trials data in the Clinical Trial.gov and Chinese Clinical Trial Registry databases in 22 April 2019. Fifteen key items were analysed to describe trial characteristics, including: registration number, study start date (year), mode of funding, type of disease, medicine type, research stage, research design, sample size, number of experimental groups, placebo group, blind method, implementation centre, child specific, newborn specific and participant age.ResultsA total of 1388 clinical trials of paediatric drugs conducted in China were registered. The number of paediatric drug trials grew steadily over time, from less than 20 per year before 2005 to more than 100 per year after 2012. Most clinical trials were postmarketing (n=800, 57.6%), single-centre (n=1045, 75.3%), intervention studies (n=1161, 83.6%) without blinded methods (1169, 84.2%) and funded by non-profit organisations (n=838, 60.4%). The number of clinical trials for antineoplastic agents (n=254, 18.3%), anti-infectives (n=156, 11.2%) and vaccines (n=154, 11.1%) is the largest.ConclusionPaediatric drug trials in China made a significant progress in recent years. Innovative method and trial design optimisation should be encouraged to accelerate paediatric clinical research. Pharmaceutical companies need to be further stimulated to carry out more high-quality paediatric clinical trials with support of paediatric drug legislation.