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Workshop on Pharmacokinetic/Pharmacodynamic Imaging

The preliminary announcement can be downloaded in .jpg format (250KB) or .pdf format (3.3MB), and the overview of that workshop with information on its goals and objectives, as well as the conference agenda are presented below and are available for downloading. The full report of the recommendations from the workshop is now available for downloading in .pdf format (36KB)

The Conference Agenda is available for downloading.

Monday, January 22, 2007
6:00 – 8:00 pm Registration

Tuesday, January 23
7:00 am Continental Breakfast and Registration

8:00 am Welcome
Walter Wolf, PhD
Chair, Biomedical Imaging Science Initiative, USC

8:15-10:30 am

Inaugural session: What is working and what is not working in the use of pharmacokinetic imaging in drug development and in clinical studies
Chair/Rapporteur: Daniel Sullivan, MD

The NCI Cancer Imaging Program: its accomplishments and its unmet needs
Daniel Sullivan, MD
Associate Director, Cancer Imaging Program, National Cancer Institute, Bethesda, MD

The FDA Critical Path: current status and models for collaborations
Wendy Sanhai, PhD
Senior Scientific Advisor, Office of the Commissioner, US Food and Drug Administration, Rockville, MD

The UK Pharmacodynamic/Pharmacokinetic Technologies Advisory Committee: its accomplishments and its unmet needs
Eric Aboagye, PhD
Professor of Cancer Pharmacology & Molecular Imaging, Imperial College London, United Kingdom

A proposed systems approach to pharmacokinetic and pharmacodynamic studies that is possible using noninvasive imaging
Walter Wolf, PhD
Professor of Pharmaceutical Sciences and Chair, Biomedical Imaging Science Initiative, USC

10:45 am – 12:00 noon
Principles and roadblocks in the use of imaging for PK/PD studies
Chair/Rapporteur: David Z. D’Argenio, PhD

Can imaging methods expand our understanding of Pharmacokinetics and Pharmacodynamics?
Ruediger Port, MD
Senior Scientist, Genentech Inc, South San Francisco, CA

What are the main instrumental issues in generating PK/PD measurements?
Wilfried Loeffler, PhD
Head of R&D, Siemens Medical Solutions Molecular Imaging Group, Knoxville,TN

12:00 – 1:00 pm
Lunch

1:00 - 3:15 pm
Principles and roadblocks in the use of imaging methods for PK/PD studies
Chair/Rapporteur: Andrew Raubitschek, PhD
Chair, Cancer Immunotherapeutics & Tumor Immunology
Beckman Research Institute, City of Hope National Medical Center, Duarte, CA

Nuclear Imaging (PET, SPECT, w/o CT): Past, Present and Future in PK/PD
Henry Van Brocklin, PhD
Professor of Radiology, Director of Radiopharmaceutical Research, Center for Molecular and
Functional Imaging, UCSF, CA

Fundamental Differences of Pharmacokinetic Models for MRI and Nuclear Medicine
Charles Springer, PhD
Professor and Director, Advanced Imaging Research Center, Oregon Health and Science University,
Portland, OR

Optical and other Imaging methods: Past. Present and Future in PK/PD
Bruce Molitoris, PhD
Professor and Director, Indiana Center for Biological Microscopy, University of Indiana, Indianapolis, IN

3:30 - 5:45 pm
Principles and roadblocks in the use of imaging methods in PK/PD in drug development studies
Chair/Rapporteur: Robert Gillies, PhD

Imaging in Drug Development – an academic perspective
Robert Gillies, PhD
Professor and Director, Advanced Research Institute for Biomedical Imaging, University of Arizona, Tucson, AZ

Imaging in Drug Development – a perspective from the imaging industry
Jean Luc Vanderheyden, PhD
Global Molecular Imaging Leader, General Electric Healthcare, Waukesha, WI

Imaging in Drug Development – a perspective from the pharmaceutical industry
Raymond E. Gibson, PhD
Senior Research Scientist, Merck Research Laboratories, Rahway, NJ

6:30 pm
Dinner with presentations and discussion on:
Imaging in pharmaceutical research: how can we deliver more benefit to the public and get more bang for our buck?

Alexander Capron, LLB
University Professor, Scott H. Bice Chair in Healthcare Law, Policy and Ethics, and Professor of Law and Medicine, University of Southern California, Los Angeles, CA

Belinda Seto, PhD
Deputy Director, National Institute of Biomedical Imaging and Bioengineering, Bethesda, MD
Mauro Ferrari, PhD

Professor, Brown Institute of Molecular Medicine, University of Texas Health Sciences Center, Houston, TX

Wednesday, January 24

7:00 am Continental Breakfast

8:00-9:30 am Principles and roadblocks in the use of imaging methods in clinical PK/PD studies
Chair/Rapporteur: Patricia Cole, PhD, MD and Patrick M. Colletti, MD Professor of Radiology, Pharmaceutical Sciences and Biokinesiology, USC, Los Angeles, CA

Imaging in clinical studies – an academic perspective
Peter Conti, MD, PhD
Professor of Radiology, Biomedical Engineering and Pharmacy, USC, Los Angeles, CA

Imaging in clinical studies – a perspective from the imaging industry
Peter Martin, PhD
Director Business Development, Molecular Imaging, Philips Medical Systems

Imaging in clinical studies – a perspective from the pharmaceutical industry
Patricia Cole, PhD, MD
Senior Director and Head, Imaging Programmes, Eisai Medical Research, Ridgefield Park, NJ

9:45-11:30 am Economic, educational and other roadblocks in the use of imaging methods in PK/PD
Chair/Rapporteur: Peter Conti, MD, PhD

The Role of Open Source Imaging Toolkits in the Development of Dynamic Imaging Biomarkers
Rick Avila, MS
Director of Medical Applications, Kitware Inc, Clifton Park, NY

Economic considerations in the use of noninvasive imaging methods in drug development and drug monitoring
Gurinder Shahi, MD, PhD
Keck School of Medicine, University of Southern California, Los Angeles, CA

Educational needs in the expanded use of noninvasive imaging methods in drug development and drug monitoring
Panel Speakers:

Sarah Hamm-Alvarez, PhD, Professor and Chair, Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA

David Z. D’Argenio, PhD, Professor, Biomedical Engineering, University of Southern California, Los Angeles, CA

Cary A. Presant, MD, FACP, Wilshire Oncology Medical Group, West Covina, CA

11:30 am Report from working groups and review of recommendations

12:30 pm Adjourn meeting

Purpose and Objectives:

The current approaches to drug development start with in-vitro screening studies to select potential drug candidates, followed by in-vivo studies at the cellular and animal level, and are concluded with human studies performed in traditional Phase I, II and III sequences. This process has not changed fundamentally for decades. While it has resulted in the pharmaceutical drug products we have available today, this process is associated with an extremely high expense, lengthy delays and a limited amount of resources for treatment of many diseases. What is more, it is possible, even likely, that many potentially good drug candidates may have been lost in the process because the formulation, method of administration or other may have been incorrect, leading in some cases to limited delivery of the compound to the target site(s). And there has been a very poor understanding of the impact of patient variability, leading to very costly clinical studies which may include large masses of patients not likely to respond to a given therapy.

Similar considerations can be made for patient treatment once a drug has been approved for clinical use. The identification of which pathophysiological parameters may be critical in determining which drug and which dosage regimen is optimal for a given patient, and how this condition varies as a function of the effect of (or absence of effect of) treatment is rarely a high priority in the practice of medicine. Toxicities may appear in the post-marketing phase that were not detected in Phase III studies, and drugs that are very effective in one subset of a population may only be barely suitable in another subset. They may even be highly unsuitable in a further subset of the treated population. Thus, many promising methods are not readily available in the community, they are not likely to be widely utilized, even with adequate monitoring of side effects.

The development of Pharmacokinetics / Pharmacodynamics (PK/PD) has also been constrained by the availability of analyzable samples. As long as all analyses had to be done in laboratory settings, human specimens could only be obtained, reasonably, from accessible tissues and fluids – blood, urine, feces, saliva, etc. Target tissue was only available following biopsies, making any measurement of drug levels at their target sites something that could be achieved in only the most rare occasions, and making any kinetics at the target sites impossible to achieve under any realistic considerations.

Recent technological advances in biomedical research, not only in areas such as genomics and proteomics, but especially in dynamic and functional aspects of biomedical imaging, have made it easier to identify physiological parameters that could potentially identify those unique patient characteristics that could individualize and optimize treatment. And they have also allowed measurements, using noninvasive imaging, of the concentration, the dynamics, and the effects of drugs at their target sites. These techniques may be particularly valuable in Phase “0”, Phase I and Phase II trials. The pharmacokinetic and pharmacodynamic information learned in such early phase trials could then be used to design more successful phase III trials, in part because patients with the appropriate molecular phenotype for a given targeted therapy could be selected, and in part because drugs could be given in more appropriate doses and intervals. And such techniques could then be equally valuable in defining patient monitoring in Phase IV studies and in optimized, individualized patient management.

But there are still many obstacles to developing clinically useful functional and dynamic imaging tests, including technical challenges associated with validating such imaging methods, and challenges associated with developing, evaluating, and incorporating those tests into clinical practice. However, successful development of cost effective tests could have a profound impact on the way drugs are developed and patients are treated, on our knowledge of the precise mechanism of action of drugs and of drugs interactions. Such new information could reduce the economic burden of many diseases, especially by achieving the ultimate goal of pharmacokinetics – the right drug, at the right dose, at the right rate.

Workshop structure:

The goal of this workshop is to identify and discuss key questions regarding the development and use of dynamic, functional imaging-based tools. The workshop will include small group discussions during which participants will have the opportunity to present their experiences to be followed by proposing ways for overcoming obstacles to progress in this field.

The following sessions are planned:

Tuesday January 23, am: Inaugural presentations. What is working and what is not working in the use of pharmacokinetic imaging in drug development and in clinical studies.

Tuesday January 23, am: Principles and roadblocks of the use of imaging for PK/PD studies

Tuesday January 23, pm: Principles and roadblocks of the use of imaging methods for PK/PD studies

Tuesday January 23, pm: Principles and roadblocks in the use of imaging methods in Drug Development

Wednesday January 24, am: Principles and roadblocks in the use of imaging methods in clinical studies

Wednesday January 24, am: Regulatory, Economic and educational roadblocks in imaging studies in PK/PD

A detailed agenda is attached.

Participants:

To be effective, such a workshop needs to have active participation from scientists in academia, in industry and in government. Industrial participation must include both members from the pharmaceutical industry and the imaging industry. Government participation must include both funding agencies (NIH) and regulatory agencies (FDA). And academic participation must include both scientists in Universities as well as from foundations involved in policy development and analysis.

To be productive, the workshop must be structured to maximize interactions. Hence, the ideal number of participants should be in the 100-200 range. With 3 speakers per session, this should allow time for the desired discussion with proposals and ideas for how to surmount the various roadblocks. That should allow all attendees to participate actively in the discussions.

Location, timing and duration:

Southern California, January 23-24.

Last updated: Sunday, January 6, 2008, 10:03am PDT