146 • J Clin Pharmacol 2008;48:146-156 REGULATORY SCIENCE The End-of-Phase 2A meetings are proposed to identify opportunities to make innovative medical products avail- able sooner and to increase the quality of drug applica- tions through early meetings between sponsors and the FDA. This article summarizes the overall experience across 11 pilot End-of-Phase 2A meetings since 2004. Four case studies are presented in more detail to demonstrate the various issues and methods encountered at these meetings. Overall, industry and FDA scientists ranked these meetings to be “very helpful” (average score of 4 on a scale of 1 to 5). In almost all the instances the sponsors changed their drug development plans subsequent to these extensive quantitative analyses–based meetings. A draft Guidance is being developed to be issued in 2008, and we hope this initiative will be resourced by then. Keywords: Regulatory decisions; EOP2A meeting; modeling; simulation; FDA; drug develop- ment; pharmacokinetics; pharmacodynamics; pharmacometrics Journal of Clinical Pharmacology, 2008;48:146-156 © 2008 the American College of Clinical Pharmacology Leveraging Prior Quantitative Knowledge to Guide Drug Development Decisions and Regulatory Science Recommendations: Impact of FDA Pharmacometrics During 2004-2006 Yaning Wang, A. Venkatesh Bhattaram, Pravin R. Jadhav, Lawrence J. Lesko, Rajanikanth Madabushi, J. Robert Powell, Wei Qiu, He Sun, Dong S. Yim, Jenny J. Zheng, and Jogarao V. S. Gobburu T he Food and Drug Administration (FDA) has publicly stated its desire to participate in improving drug development productivity and qual- ity in providing safe and effective medicines to American patients. 1 The End-of-Phase 2A (EOP2A) meetings are proposed to identify opportunities to make innovative medical products available sooner and to increase the quality of New Drug Applications (NDA) through early meetings with sponsors. 2 The phase that occurs following the completion of phase 1 and the first set of exposure-response studies in patients and before beginning phase 2B and phase 3 clinical studies is defined as EOP2A. The overall purpose of these EOP2A meetings is to discuss the exposure-response information during early drug development with the objectives of improving the efficiency of drug development. The specific objec- tive of these meetings is to facilitate interaction between the FDA and sponsors who seek guidance related to trial design employing pharmacometric techniques such as modeling and clinical trial simu- lation. Our experience suggests that it may be impor- tant for sponsors and the FDA to discuss the use of quantitative drug development methods before con- ducting phase 2B and phase 3 clinical trials. 3-5 Under a pilot program starting in 2004, FDA con- ducted a series of EOP2A meetings where knowl- edge was modeled to simulate the next trial. The modeling used information from prior clinical trials From Pharmacometrics, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland. The views expressed in this article are those of the authors and do not necessarily reflect the official views of the FDA. Submitted for publication August 28, 2007; revised version accepted October 11, 2007. Address for correspon- dence: Yaning Wang, PhD, Team Leader, Pharmacometrics, Office of Clinical Pharmacology, Office of Translational Sciences, CDER, FDA, 10903 New Hampshire Avenue, Building 21, Room 3662, Silver Spring, MD 20993-0002; e-mail: yaning.wang@fda.hhs.gov. DOI: 10.1177/0091270007311111