Objectives: The goal of drug development is to produce a safe and efficacious drug that will thrive in a competitive marketplace. Cognitive engineering couples technology and human intelligence to generate and use knowledge to optimize drug approvability and marketability. Data management and analyses in drug development are often delayed with insufficient time to apply the knowledge generated for crucial program decisions. Real-time data assembly (RTDA) and population pharmacokinetics (POP PK) can facilitate this process so the relationships between dose selection, patient characteristics, and drug disposition are defined earlier.
Methods: RTDA is a structured quality assurance program for rapid retrieval, assembly, and analysis of data while a clinical trial is ongoing. Data transfers can be scheduled periodically (middle and end of study), monthly, or even daily to allow for continuous safety monitoring. RTDA can provide prompt feedback of drug exposure estimates for dose adjustments during the trial, as well as allow for early initiation of data scrubbing and site compliance monitoring.
Results: RTDA results in a comprehensive database for analysis of drug-drug interactions, lab data, and adverse events. Utilizing RTDA, additional time for analysis is generated and regulatory submission of integral POP PK results is expedited. Careful integration of RTDA and prospectively planning POP PK analyses into the drug development program can potentially influence decision-making, facilitate FDA review, and streamline development. Data must be available for decision-making to realize these benefits.
Conclusions: RTDA was advocated in the 1999 FDA Guidance on Population Pharmacokinetics and offers a strategy for data scrubbing and analysis before the end of the trial. When coupled with timely POP PK results it allows for cognitive engineering in drug development programs. Efficient data management and integration of results into a flexible, yet comprehensive program will expedite drug approval and ensure successful commercialization.
Drug Information Association (DIA); Denver, Colorado; July 2001
By Mary Eileen McPhee, Jill Fiedler-Kelly, Elizabeth A. Ludwig, Kathleen Reitz, Thaddeus H. Grasela