Proof of Concept: A PhRMA Position Paper With Recommendations for Best Practice

TLDR

Proof of concept (POC) is the earliest point in drug development where evidence suggests key success attributes are present and failure causes absent, focusing on safety, efficacy, pharmaceutics, and regulatory aspects, and is evaluated through mathematical models and multidisciplinary integration, though challenges include limited skilled personnel and demand for certainty. Tools for POC include biomarkers, targeted populations, PK/PD modeling, simulation, and adaptive study designs. Published in Clinical Pharmacology & Therapeutics, 2010, 87(3):278–285; doi:10.1038/clpt.2009.286.

Abstract

Proof of concept (POC) may be defined as the earliest point in the drug development process at which the weight of evidence suggests that it is "reasonably likely" that the key attributes for success are present and the key causes of failure are absent. POC is multidimensional but is focused on attributes that, if not addressed, represent a threat to the success of the project in crucial areas such as safety, efficacy, pharmaceutics, and commercial and regulatory issues. The appropriate weight of evidence is assessed through the use of mathematical models and by evaluating the consequences of advancing a candidate drug that is not safe, effective, or commercially viable, vs. failing to advance a candidate that possesses these attributes. Tools for POC include biomarkers, targeted populations, pharmacokinetic (PK)/pharmacodynamic (PD) modeling, simulation, and adaptive study designs. Challenges to the success of POCs include a shortage of skilled personnel, failure to integrate multiple disciplines and information, and the demand made by organizations for certainty. Clinical Pharmacology & Therapeutics (2010) 87 3, 278–285. doi:10.1038/clpt.2009.286