Drug Safety in Translational Paediatric Research: Practical Points to Consider for Paediatric Safety Profiling and Protocol Development: A Scoping Review

Abstract

Translational paediatric drug development includes the exchange between basic, clinical and population-based research to improve the health of children. This includes the assessment of treatment related risks and their management. The objectives of this scoping review were to search and summarise the literature for practical guidance on how to establish a paediatric safety specification and its integration into a paediatric protocol. PubMed, Embase, Web of Science, and websites of regulatory authorities and learned societies were searched (up to 31 December 2020). Retrieved citations were screened and full texts reviewed where applicable. A total of 3480 publications were retrieved. No article was identified providing practical guidance. An introduction to the practical aspects of paediatric safety profiling and protocol development is provided by combining health authority and learned society guidelines with the specifics of paediatric research. The paediatric safety specification informs paediatric protocol development by, for example, highlighting the need for a pharmacokinetic study prior to a paediatric trial. It also informs safety related protocol sections such as exclusion criteria, safety monitoring and risk management. In conclusion, safety related protocol sections require an understanding of the paediatric safety specification. Safety data from carefully planned paediatric research provide valuable information for children, parents and healthcare providers.

Analysis of Paediatric Clinical Trial Characteristics and Activity Over 23 Years—Impact of the European Paediatric Regulation on a Single French Clinical Research Center

“…Significant initiatives have been undertaken at the European level to advance pediatric drug development including EPTRI (European Pediatric Translational Research Infrastructure) ( 21 ) and PEDCRIN (Pediatric Clinical Research Infrastructure Network) ( 22 ) and substantial financial support has been established to set up pediatric clinical research networks dedicated to trial management and to promote collaboration at the European and international level ( 23 – 25 ). However, difficulties still need to be overcome to harmonize methodological ( 26 ), regulatory ( 27 ), economic ( 28 ) and ethical ( 29 ) approaches to pediatric trials and validate tools for pediatric trial conduct ( 22 , 30 – 32 ). In addition, in our opinion, two difficulties require particular attention:…”

Designing Pediatric Nano-formulations Faces a slew of Obstacles: A Review

“…Use of alternative delivery systems, and 6. Appropriate packaging to improve efficiency and avoid the risk of dosage inaccuracy (22,23) .…”

Traction of 3D and 4D Printing in the Healthcare Industry: From Drug Delivery and Analysis to Regenerative Medicine

“…In most cases, inadequately satisfying the therapy adherence results in suboptimal health outcomes for these patients. In addition, most therapeutic agents are not recommended for pediatric use as children are excluded in the predevelopment stage of clinical trials . The administration of tablets is the most suitable method for pediatric patients (i.e., school age/infants given oral dosage forms < 2 mm), particularly those that can be effortlessly swallowed and dissolved in the oral cavity .…”

“…In addition, most therapeutic agents are not recommended for pediatric use as children are excluded in the predevelopment stage of clinical trials. 63 The administration of tablets is the most suitable method for pediatric patients (i.e., school age/infants given oral dosage forms < 2 mm), particularly those that can be effortlessly swallowed and dissolved in the oral cavity. 64 Organoleptic characteristics, including taste, appearance, smell, or texture, are also influential and foster adherence in pediatric patients.…”