Critical parameters in targeted drug development: the pharmacological audit trail.

Loading...
Thumbnail Image

Embargo End Date

Authors

Banerji, U
Workman, P

Document Type

Journal Article

Date

2016-08-01

Date Accepted

2015-10-23

Abstract

The Pharmacological Audit Trail (PhAT) comprises a set of critical questions that need to be asked during discovery and development of an anticancer drug. Key aspects include: (1) defining a patient population; (2) establishing pharmacokinetic characteristics; (3) providing evidence of target engagement, pathway modulation, and biological effect with proof of concept pharmacodynamic biomarkers; (4) determining intermediate biomarkers of response; (5) assessing tumor response; and (6) determining how to overcome resistance by combination or sequential therapy and new target/drug discovery. The questions asked in the PhAT should be viewed as a continuum and not used in isolation. Different drug development programmes derive different types of benefit from these questions. The PhAT is critical in making go-no-go decisions in the development of currently studied drugs and will continue to be relevant to discovery and development of future generations of anticancer agents.

Citation

Seminars in oncology, 2016, 43 (4), pp. 436 - 445

Source Title

Publisher

W B SAUNDERS CO-ELSEVIER INC

ISSN

0093-7754

eISSN

1532-8708

Research Team

Clinical Pharmacology – Adaptive Therapy
Medicine Drug Development Unit (de Bono)

Notes