Pharmacometrics beyond drug development: from where have we - PowerPoint PPT Presentation

Pharmacometrics beyond drug development: from where have we come....to where should we go Steven E. Kern, Ph.D. Head of Pharmacology Modeling Modeling & Simulation Novartis Pharma AG, Basel Switzerland

Beyond Drug Development...  Individualization • Selecting the right dose for the right patient • The original motivation for all our activity still very relevant today  Education • Teaching quantitative pharmacology to clinicians and students • Clever opportunities to integrate back into patient care  Communication • To a broader community of non-experts • Beyond the Uppsala-Paris-Auckland-San Francisco-Buffalo-Leiden pathway 2 | P-metrics beyond drug development | Kern 6 Sept 2012 | WCoP Seoul Korea

from where have we come...to where we should go 3 | P-metrics beyond drug development | Kern 6 Sept 2012 | WCoP Seoul Korea

A Chronology of Quantitative Analysis used to support Pharmacotherapy and Drug Development 4 | P-metrics beyond drug development | Kern 6 Sept 2012 | WCoP Seoul Korea

Quantitative pharmacologists have been prescient for some time... Annu Rev Pharmacol. 1968;8:67-94. 5 | P-metrics beyond drug development | Kern 6 Sept 2012 | WCoP Seoul Korea

Learning versus confirming... It’s the patient that matters! 6 | P-metrics beyond drug development | Kern 6 Sept 2012 | WCoP Seoul Korea

Why does this matter? Because few drugs work in all people 7 | P-metrics beyond drug development | Kern 6 Sept 2012 | WCoP Seoul Korea

A Make Believe Example: The P-metrics Community solves anticoagulation 8 | P-metrics beyond drug development | Kern 6 Sept 2012 | WCoP Seoul Korea

Dose – Effect relationship fit to extensive data: PK, PD, Biomarker, Endpoint 9 | P-metrics beyond drug development | Kern 6 Sept 2012 | WCoP Seoul Korea

Pharmacogenetics, the missing covariate? 10 | P-metrics beyond drug development | Kern 6 Sept 2012 | WCoP Seoul Korea

Population assessment of dose – effect relationship 11 | P-metrics beyond drug development | Kern 6 Sept 2012 | WCoP Seoul Korea

Are the outliers worth the extra effort? 12 | P-metrics beyond drug development | Kern 6 Sept 2012 | WCoP Seoul Korea

Modeling with a parsimonious approach 13 | P-metrics beyond drug development | Kern 6 Sept 2012 | WCoP Seoul Korea

Model improves prediction but there still unexplained residual variability... 14 | P-metrics beyond drug development | Kern 6 Sept 2012 | WCoP Seoul Korea

Post-PK variability is the focus for consistent effect 15 | P-metrics beyond drug development | Kern 6 Sept 2012 | WCoP Seoul Korea

Prospective assessment of adaptive therapy 16 | P-metrics beyond drug development | Kern 6 Sept 2012 | WCoP Seoul Korea

Time to effective treatment improved 17 | P-metrics beyond drug development | Kern 6 Sept 2012 | WCoP Seoul Korea

Adaptation of dose to a priori conditions helps 18 | P-metrics beyond drug development | Kern 6 Sept 2012 | WCoP Seoul Korea

Hard to show benefit/risk balance... 19 | P-metrics beyond drug development | Kern 6 Sept 2012 | WCoP Seoul Korea

Pharmacometrics towards finding the Right Dose: charting our progress on the “Hype Cycle” http://en.wikipedia.org/wiki/Hype_cycle www.gartner.com 20 | P-metrics beyond drug development | Kern 6 Sept 2012 | WCoP Seoul Korea

Moving forward on the Plateau of Productivity through education 21 | P-metrics beyond drug development | Kern 6 Sept 2012 | WCoP Seoul Korea

Tools for moving along the Plateau of Productivity 22 | P-metrics beyond drug development | Kern 6 Sept 2012 | WCoP Seoul Korea

Necessary “evils” along the Plateau of Productivity 23 | P-metrics beyond drug development | Kern 6 Sept 2012 | WCoP Seoul Korea

Novartis Modeling & Simulation Group Training 24 | P-metrics beyond drug development | Kern 6 Sept 2012 | WCoP Seoul Korea

Plateau still has innovation and excitement 25 | P-metrics beyond drug development | Kern 6 Sept 2012 | WCoP Seoul Korea

Why use modeling and simulation? Supporting decision making under uncertainty (idea credit D. Bottino) Diagnosis Cellular Molecular Doppler Satellite Balloons Drug-disease model Weather model 2 model  simulate  1 Disease Burden (log) 0 -1 -2 -3 -4 -5 0 100 200 300 400 500 600 700 days Informs Informs decision decision   Stay put Stay on current dose   Check again in 12 hours Monitor more closely   Board up windows Increase dose  Evacuate  Change therapies 26 | P-metrics beyond drug development | Kern 6 Sept 2012 | WCoP Seoul Korea

Simple means to efficiently relay quantitative information 27 | P-metrics beyond drug development | Kern 6 Sept 2012 | WCoP Seoul Korea

VPCs alone are not the answer... 28 | P-metrics beyond drug development | Kern 6 Sept 2012 | WCoP Seoul Korea

With established credibility with clinical partners, integration of information in a display is possible 29 | P-metrics beyond drug development | Kern 6 Sept 2012 | WCoP Seoul Korea

Integrated clinical pharmacology on a topography – flying on an exposure landscape 30 | P-metrics beyond drug development | Kern 6 Sept 2012 | WCoP Seoul Korea

The changing shape of global population Population 2100 Population 2010 31 | Novartis Research Partnerships in SA | Colin Pillai | 30 Aug 2012

Mismatch between disease burden… Malaria deaths Source: http://www.worldmapper.org/ 32 | Novartis Research Partnerships in SA | Colin Pillai | 30 Aug 2012

…and available medical care… Physicians Source: http://www.worldmapper.org/ 33 | Novartis Research Partnerships in SA | Colin Pillai | 30 Aug 2012

…or biomedical research Research Source: http://www.worldmapper.org/ 34 | Novartis Research Partnerships in SA | Colin Pillai | 30 Aug 2012

We need more research scientists in Africa Malaria deaths Physicians Research 35 | Novartis Research Partnerships in SA | Colin Pillai | 30 Aug 2012

Scientific and clinical capability development Building infrastructure Hands-on training and Scientific education collaboration and clinical training 36 | Novartis Research Partnerships in SA | Colin Pillai | 30 Aug 2012

Novartis Efforts to build Scientific/Clinical Capability in the Developing World  Research internship & post-doctoral programs for scientists/physicians in the developing world (e.g., NIBR Kenya equipment donation and exchange program; NITD post-doc program)  Research and academic training programs for scientists/physicians in the developing world (e.g., Siena University/NVGH Certificate in Vaccinology)  International scientific/clinical symposia on neglected diseases in the developing world (e.g., NITD TB symposium in Cameroon)

Novartis Research Internship and Postdoctoral Programs  Goal: 1) Support talented, previously disadvantaged and motivated students to advance their career in biomedical research; 2) Mentorship opportunities for Novartis scientists  Program Description – Internship: 3-6 month research internship in a Novartis research lab for undergraduate or graduate students with previous lab experience; assignment of Novartis research mentor; participation in seminars and poster presentation  Program description – Postdoctoral Program: 2-3 years research internship in a Novartis research lab for individuals who are interested in pharmaceutical discovery; assignment of academic and Novartis mentor; focus of work is on non- proprietary, publishable research

Going forward...  Individualization  Education  Communication  Globalization 39 | P-metrics beyond drug development | Kern 6 Sept 2012 | WCoP Seoul Korea

With thanks....  Kyungsoo Park and WCoP organizers  Colin Pillai and colleagues at Novartis  The rest of you whose work I shamelessly cobbled together to address this challenging topic 40 | P-metrics beyond drug development | Kern 6 Sept 2012 | WCoP Seoul Korea