Psychometric Analyses and Quantitative Study Report for Qualification of the Pediatric Asthma Diary-Child (PAD-C) and the Pediatric Asthma Diary-Observer (PAD-O) (DDT COA #000099) - ABSTRACT Asthma is one of the most common childhood chronic conditions worldwide. In the United States (US), asthma presents in 8.3% of children under 18 years of age and 9.5% of children between the ages of 5 through 11. For U.S. children, asthma is one of the leading causes of school absenteeism and the third ranking cause of hospitalization. Development of better treatments for children under 12 years old is needed to improve symptom control and reduce these burdens. Pediatric asthma clinical trials face challenges due to the poor reliability of the traditional endpoint based on lung function assessment in young children, highlighting a need for novel methods for trials in children under 12 years old. To assess clinical benefit, a positive effect of a treatment on how children with asthma feel and function, clinical outcome assessments (COAs) for self-report (patient- reported outcome [PRO] measures) as well as observer report for children under age 8 need to be developed following rigorous patient-focused drug development approaches specifically to support endpoints in pediatric asthma clinical trials. The Center for Drug Evaluation and Research’s (CDER’s) COA Qualification Program accepted a Letter of Intent (LOI) to qualify the Pediatric Asthma Diary-Child (PAD-C) and the Pediatric Asthma Diary-Observer (PAD-O) to assess severity of asthma symptoms and signs under DDT #000099 on June 9, 2017. A Qualification Plan (QP) was prepared and submitted to FDA on December 15, 2022. The QP includes the Pediatric Asthma Working Group’s research plan for obtaining the quantitative evidence necessary to support qualification of the measures for a limited context of use in pediatric asthma drug development. The QP Determination Letter was received on November 22, 2023, indicating that the QP had been accepted. It included a request for significant revisions to the statistical analysis plan (SAP). A SAP, Version 2.0, was submitted for FDA review and confirmation on April 15, 2025, addressing the concerns raised in the QP Determination Letter and including modifications to reflect best practices in our field since the SAP was originally prepared in 2022. Once FDA feedback on the QP is received, additional modifications to the SAP may be necessary and analyses can proceed. Our application includes 4 aims. For Aim 1, we will finalize the SAP for cross-sectional analyses in response to FDA feedback. For Aim 2, we will conduct missing data simulation analyses per the finalized SAP. For Aim 3, we will review PAD-C and PAD-O quantitative analysis results to ensure they reflect the analyses proposed in the finalized SAP, are of high quality, and can be used to draw actionable conclusions. For Aim 4, we will review and revise a quantitative study report documenting the PAD-C and PAD-O quantitative pilot study methods, results, and interpretation for future submission with the PAD-C and PAD-O Full Qualification Package. The long-term result of this project will be to qualify the PAD-C and PAD-O for the assessment of symptom and sign severity in pediatric asthma treatment trials, according to the most recent, rigorous standards and best practices to develop fit-for-purpose COAs for regulatory decision making.
