Proof of concept: a PhRMA position paper with recommendations for best practice

Clinical Pharmacology and Therapeutics
Mark E CartwrightS A Williams

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.

References

Mar 1, 1997·Clinical Pharmacology and Therapeutics·L B Sheiner
Jun 3, 2000·Annual Review of Pharmacology and Toxicology·N H HolfordC C Peck
Mar 10, 2001·Clinical Pharmacology and Therapeutics·UNKNOWN Biomarkers Definitions Working Group.
Feb 28, 2003·Journal of Health Economics·Joseph A DiMasiHenry G Grabowski
Aug 3, 2004·Nature Reviews. Drug Discovery·Ismail Kola, John Landis
Aug 2, 2005·Nature Reviews. Drug Discovery·Bruce H Littman, Stephen A Williams
Dec 16, 2005·The AAPS Journal·Jaap W MandemaDaniel Hartman
Dec 19, 2006·BMJ : British Medical Journal·Pablo PerelKhalid S Khan
Oct 17, 2007·Annual Review of Pharmacology and Toxicology·John A Wagner
May 29, 2009·Clinical Pharmacology and Therapeutics·C D LathiaJ A Wagner

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Citations

Dec 8, 2010·Biomarkers in Medicine·Rajesh Krishna, John A Wagner
Oct 4, 2013·Science Translational Medicine·Rahul P BakshiTheresa A Shapiro
Jan 18, 2012·Expert Opinion on Drug Metabolism & Toxicology·Mario Pellegatti
Jul 28, 2013·CPT: Pharmacometrics & Systems Pharmacology·K E KarlssonM O Karlsson
Jun 21, 2012·Pharmaceutical Statistics·Xin Wang, Naitee Ting
Jul 9, 2013·Drug Discovery Today·Zhihui Wang, Thomas S Deisboeck
Dec 17, 2014·Nature Reviews. Drug Discovery·Paul K OwensJoel C Scherer
Jul 6, 2016·PharmacoEconomics·William C N DunlopLouise Heron
Feb 7, 2017·Journal of Biopharmaceutical Statistics·Erik PulkstenisJianliang Zhang
Dec 15, 2016·Pilot and Feasibility Studies·Sandra M EldridgeUNKNOWN PAFS consensus group
Sep 25, 2014·World Journal of Psychiatry·Oleg V TcheremissineDineen R Gardner
Mar 21, 2016·Current Protocols in Chemical Biology·Emily CatonTheresa A Shapiro
Sep 27, 2015·Clinical Chemistry·Xuemei ZhaoOmar F Laterza
Sep 1, 2019·Alzheimer's Research & Therapy·Jeffrey CummingsPhilip Scheltens
Sep 1, 2014·Therapeutic Innovation & Regulatory Science·Oren Cohen, Frederic Sax
Jan 1, 2015·Therapeutic Innovation & Regulatory Science·Oleksandr SverdlovSheng Wu
Sep 12, 2018·Clinical Trials : Journal of the Society for Clinical Trials·Satrajit RoychoudhuryBeat Neuenschwander
Jan 1, 2015·Therapeutic Innovation & Regulatory Science·Roland FischHeinz Schmidli
Jan 8, 2020·Pharmaceutical Statistics·Hui QuanGautier Paux
Jul 1, 2013·Therapeutic Innovation & Regulatory Science·Kazuhiro Kanmuri, Mamoru Narukawa
May 1, 2014·Therapeutic Innovation & Regulatory Science·Kazuhiro Kanmuri, Mamoru Narukawa
Dec 1, 2015·Journal of Food and Drug Analysis·Mannching Sherry Ku
Sep 15, 2010·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Keiji Yamamoto

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