A New Paradigm in Pediatric Drug Development: The Application of Cognitive Engineering

Authors: Rubino CM, Cirincione B, Sokolowski M, McPhee ME
Conference: DIA
Keywords: cognitive engineering, database, drug development process, ethics, internet communication, knowledge portal, pediatrics, PERSPECTIVE, real-time data assembly, RTDA, study design
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Abstract

Objectives: Design of clinical trials in pediatrics is complicated by sensitive ethical considerations, a small pool of appropriate study subjects, and difficulty in determining drug dosing regimens. Cognitive engineering is the coupling of technology and human intelligence to generate and use knowledge in real time. Using real-time data assembly (RTDA), population pharmacokinetic/ pharmacodynamic (PK/PD) data analysis and Internet communication technology, cognitive engineering can be applied to pediatric drug development in order to address the above issues.

Methods: RTDA is an automated quality assurance program designed to monitor drug dosing and concentration-time data acquired during clinical trials. This process has been further extended by linking dosing and concentration data with safety data, allowing for preparation of timely, blinded interim reports which enhance drug safety monitoring. Critical to this process is the use of electronic communication to facilitate data management and knowledge dissemination. Private, secure Internet web sites are used to communicate data management and analysis activities to the sponsor. In addition, these web sites are used to communicate interim reports (blinded or unblinded) to independent data safety monitoring boards.

Results: Population PK/PD analysis of data from pediatric studies of an investigational drug suggested that dosage adjustment was necessary for children below a certain age. A multicenter, Phase III trial will evaluate this dosage adjustment in children. Using RTDA and an Internet-based communication strategy, an interim analysis dataset will be constructed, allowing estimation of drug exposure using a minimum of PK samples. This interim analysis will be used as evidence supporting the chosen dosing regimen (i.e., higher daily doses in
young children).

Conclusion: Cognitive engineering, as implemented using RTDA, population PK/PD data analysis and Internet communication technology, can improve the process of pediatric drug development. In this example, this model allows for the conduct of a robust interim analysis to support the selected dosing regimen.

Drug Information Association (DIA); Denver, Colorado; July 2001

By Christopher M. Rubino, PharmD, Brenda Cirincione, M.A., Monika Sokolowski, B.A., Mary Eileen McPhee, R.N., M.S.