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

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

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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...

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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

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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

| P-metrics beyond drug development | Kern 6 Sept 2012 | WCoP Seoul Korea 2

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from where have we come...to where we should go

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A Chronology of Quantitative Analysis used to support Pharmacotherapy and Drug Development

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Quantitative pharmacologists have been prescient for some time...

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Annu Rev Pharmacol. 1968;8:67-94.

| P-metrics beyond drug development | Kern 6 Sept 2012 | WCoP Seoul Korea

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Learning versus confirming... It’s the patient that matters!

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Why does this matter? Because few drugs work in all people

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A Make Believe Example: The P-metrics Community solves anticoagulation

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Dose – Effect relationship fit to extensive data: PK, PD, Biomarker, Endpoint

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Pharmacogenetics, the missing covariate?

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Population assessment of dose – effect relationship

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Are the outliers worth the extra effort?

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Modeling with a parsimonious approach

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Model improves prediction but there still unexplained residual variability...

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Post-PK variability is the focus for consistent effect

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Prospective assessment of adaptive therapy

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Time to effective treatment improved

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Adaptation of dose to a priori conditions helps

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Hard to show benefit/risk balance...

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Pharmacometrics towards finding the Right Dose: charting our progress on the “Hype Cycle”

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http://en.wikipedia.org/wiki/Hype_cycle www.gartner.com

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Moving forward on the Plateau of Productivity through education

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Tools for moving along the Plateau of Productivity

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Necessary “evils” along the Plateau of Productivity

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Novartis Modeling & Simulation Group Training

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Plateau still has innovation and excitement

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Why use modeling and simulation?

Supporting decision making under uncertainty (idea credit D. Bottino)

Informs decision

  • Stay put
  • Check again in 12 hours
  • Board up windows
  • Evacuate
  • Stay on current dose
  • Monitor more closely
  • Increase dose
  • Change therapies

Weather model

Doppler Satellite Balloons

Drug-disease model

Cellular Molecular Diagnosis

100 200 300 400 500 600

  • 5
  • 4
  • 3
  • 2
  • 1

1 2 Disease Burden (log) days

model  simulate 

700

Informs decision

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Simple means to efficiently relay quantitative information

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VPCs alone are not the answer...

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With established credibility with clinical partners, integration of information in a display is possible

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Integrated clinical pharmacology on a topography – flying on an exposure landscape

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Population 2100 Population 2010

The changing shape of global population

31 | Novartis Research Partnerships in SA | Colin Pillai | 30 Aug 2012

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Source: http://www.worldmapper.org/

Mismatch between disease burden…

Malaria deaths

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Source: http://www.worldmapper.org/

…and available medical care…

Physicians

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…or biomedical research

Source: http://www.worldmapper.org/

Research

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Research Physicians Malaria deaths

We need more research scientists in Africa

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Scientific and clinical capability development

Hands-on training and collaboration Scientific education and clinical training Building infrastructure

36 | Novartis Research Partnerships in SA | Colin Pillai | 30 Aug 2012

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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
  • n neglected diseases in the

developing world (e.g., NITD TB symposium in Cameroon)

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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

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Going forward...

  • Individualization
  • Education
  • Communication
  • Globalization

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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

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