A Rational Approach to Drug Development: The Exploratory Phase

Abstract

Drug development is a complex process, and added to it is the sophisticated new technologies and approaches to drug design, of which rational drug design is the epitome. A low success rate for investigational new drugs calls for improvement in drug discovery and development processes. Implementing knowledge driven drug development strategies founded on informative, powerful, and robust studies would greatly improve the drug discovery and development processes. Knowledge driven drug discovery and development that emphasizes a learn‐confirm‐learn paradigm is proposed as the rational basis for drug development. Although clinical drug development is usually divided into Phases I, II, III, and IV; it should rather be defined by those studies necessary to obtain data to answer the fundamental development decision questions: “Is the new molecular entity tolerated and at what dose range?” and “Does it show efficacy for intended use within the tolerated dose range?” In setting out to answer these questions during drug development, we propose that the learn‐confirm‐learn paradigm of drug development provides the most appropriate answers to these questions and hence a rational and optimal drug development process (DDP). The exploratory phase of drug development provides the answer to the first question, and answers the second question in part through a well‐designed proof of concept study.

Key words: :

• Drug discovery
• Pharmacokinetic/pharmacodynamic modeling
• Exploratory drug development
• Learn‐confirm‐learn paradigm
• Biomarkers
• Surrogate endpoints