Application of modeling and simulation to integrate clinical pharmacology knowledge across a new drug application.
Typical drug development includes few studies to find the right dose/dosing regimen and several other bridging studies evaluating various prognostic factors (e.g.: co-administration of other drugs, organ failure). The drug sponsors and the regulators use this information to formulate labeling instructions for safe and effective use of the drug. In the current article, modeling and simulation are proposed as tools to integrate the knowledge from the effectiveness/safety studies and the bridging studies. Simulations allow exploring the impact of various prognostic factors on the effectiveness and safety. The concept is exemplified using the new drug application of an anti-migraine drug. The exercise aids in integrating all the knowledge across the drug development to suggest rationale dosing strategies; effectively communicating the impact of the prognostic factors to the clinicians/regulators; and protect against any intellectual losses due to development team changes.
Gobburu
J V S
JV
Office of Clinical Pharmacology and Biopharmaceutics, Center for Drug Evaluation and Research, United States Food and Drug Administration, Rockville, MD 20852, USA. gobburuj@cder.fda.gov
Sekar
V J
VJ
D003198:Computer Simulation; D004347:Drug Interactions; D015507:Drugs, Investigational / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D017387:Investigational New Drug Application / Q000379:methods*; D007654:Ketoconazole / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D008881:Migraine Disorders / Q000150:complications / Q000188:drug therapy; D008962:Models, Theoretical; D016032:Randomized Controlled Trials as Topic; D051437:Renal Insufficiency / Q000150:complications; D014481:United States; D014486:United States Food and Drug Administration
D015507:Drugs, Investigational; D007654:Ketoconazole