13 April 2016 - For more than half a century, the clinical development of anti-cancer drugs has followed a predictable and orderly set of sequential stages.

Phase 1 trials were designed to determine the drug’s safety, tolerability, and dose; phase 2 trials then explored the drug’s activity in a variety of cancers; and phase 3 trials compared the new drug with existing treatments and served as the basis for regulatory approval.

Advances in our understanding of cancer biology in the past decade have led to both development of more effective drugs and improved patient selection made possible by early biomarker discovery and companion diagnostic development. Desire for early access to transformative new anticancer drugs has resulted in increased demand for patient entry into first-in-human trials, as well as calls for expediting the drug development and approval process. The three distinct sequential phases of drug development have therefore become increasingly blurred.

For more details, go to: http://www.nejm.org/doi/full/10.1056/NEJMp1603747?query=TOC