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A Composite Endpoint for Acceptability Evaluation of Oral Drug Formulations in the Pediatric Population
Manfred Wargenau1, Sibylle Reidemeister2, Ingrid Klingmann3
1M.A.R.C.O. GmbH & Co. KG, Institute for Clinical Research and Statistics, Schirmerstrasse 71, 40211, Düsseldorf, Germany.
Insights
A new composite endpoint for pediatric medicine acceptability was developed, considering palatability and swallowability. Mini-tablets and oblong tablets showed significantly better acceptability than syrups and films.
Area of Science:
- Pharmaceutical Sciences
- Pediatric Medicine
- Regulatory Science
Background:
- Pediatric medicine acceptability significantly impacts treatment adherence, a key regulatory expectation from agencies like the EMA and FDA.
- Assessing pediatric medicine acceptability is challenging due to the lack of standardized definitions, methodologies, and criteria.
- Palatability and swallowability are recognized as crucial components of overall medicine acceptability in children.
Purpose of the Study:
- To propose a novel, composite endpoint for assessing the acceptability of oral pediatric formulations.
- To establish a standardized and pragmatic method for evaluating medicine acceptability across all pediatric age groups.
- To meet regulatory expectations for acceptability testing in pediatric drug development.
Main Methods:
- A composite acceptability endpoint was developed using validated assessment methods for swallowability and palatability in children.
- The methodology aligns with European Medicines Agency (EMA) criteria for assessing acceptability in pediatric populations (newborn to 18 years).
- Data from two studies involving placebo formulations (mini-tablets, oblong tablets, orodispersible films, syrup) were analyzed to validate the assessment tool.
Main Results:
- The proposed composite endpoint effectively differentiates preferences for various oral formulations.
- Mini-tablets and oblong tablets demonstrated significantly higher acceptability compared to syrups and orodispersible films.
- The assessment tool proved valid, expedient, and applicable across different pediatric age groups and formulation types.
Conclusions:
- The composite acceptability endpoint, integrating swallowability and palatability, is highly sensitive for detecting formulation differences.
- This well-defined, valid approach meets regulatory requirements comprehensively.
- The method offers a standardized, pragmatic future standard for assessing and comparing pediatric oral formulations.
Introduction:
A medicine's acceptability is likely to have significant impact on pediatric adherence. The importance is underlined in EMA and FDA guidance on this topic where investigation of acceptability is stated as a regulatory expectation. Demonstrating acceptability can be challenging given there is no globally recognized definition and no standardized testing methodology or assessment criteria. Palatability and swallowability are generally recognized as important elements of acceptability, and this work proposes a definition of acceptability using these elements to give a composite endpoint for acceptability for pediatric subjects across all age ranges.
Methods:
This composite acceptability endpoint is based on validated assessment methods for swallowability and palatability in children of different age groups using different galenic placebo formulations, in line with criteria proposed by EMA for assessing acceptability in children from newborn to 18 years of age. Data from two studies investigating mini-tablets, oblong tablets, orodispersible films, and syrup were analyzed to establish the validity, expediency, and applicability of the suggested composite acceptability assessment tool.
Results:
The new composite endpoint is an efficient and suitable way to distinguish preferences of oral formulations: Mini-tablets and oblong tablets had significantly better acceptability than syrups and orodispersible films.
Conclusion:
Since the suggested acceptability criteria takes both swallowability 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 meets regulatory requirements in an appropriate and comprehensive manner and may in future serve as a pragmatic, standardized method to assess and compare acceptability of pediatric formulations with active substances.
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