A composite endpoint for acceptability evaluation of oral drug formulations in the pediatric population

Introduction: A medicine9s acceptability is likely to have significant impact on pediatric compliance. EMA and FDA guidance on this topic ask for investigation of acceptability. Although palatability and deglutition are denoted as elements of acceptability, the impact of both on acceptability remains unclear as an unambiguous definition of acceptability is lacking. Actually, globally applied standards for acceptability definition, testing methodology and assessment criteria do not exist. A definition of acceptability establishing a composite endpoint that combines deglutition and palatability in different age groups is presented here. Methods: This composite acceptability endpoint is based on validated assessment methods for deglutition and palatability in children of different age groups with different galenic placebo formulations, in line with criteria EMA proposed for assessing acceptability in children from newborn to 18 years. Data from two studies investigating mini-tablets, oblong tablets, orodispersible films and syrup were used to investigate the validity, expediency and applicability of the suggested composite acceptability assessment tool. Results: The new composite endpoint is highly suitable and efficient to distinguish preferences of oral formulations: Mini-tablets and oblong tablets were significantly better accepted than syrup and orodispersible film. Conclusion: Since the suggested acceptability criterion takes both deglutition and palatability into account as composite endpoint, it is highly sensitive to detect acceptability differences between oral formulations. It is a well-defined, valid approach, which particularly meets regulatory requirements in an appropriate and comprehensive manner and may in future serve as an easy, standardized method to assess and compare acceptability of pediatric formulations with active substances.