Workshop I - Agenda

December 13, 2012

7:30 a.m. - 8:00 a.m.
Breakfast
OVERALL MEETING CHAIR: ANN BARKER (ANN) (FIRST NAMES ONLY MEETING)

8:00 a.m. - 8:30a.m.
NBDA Background, Goals for the Workshop and Agenda
Anna D. Barker, Ph.D., ASU; Carolyn Compton, M.D., Ph.D., C-Path; Robert Penny, M.D., Ph.D., IGC

8:30 a.m. – 9:15 a.m.
State Setting Keynote Presentation
A Status Report on Biomarkers. Biomarkers that are not, standards that are forgotten, and the need to transform the system we’ve got!
George Poste, DVM, Ph.D., ASU.
In this opening presentation, George Poste (George) will lay out myriad challenges, problems, and issues that make the successful development of biomarkers a challenge not to be undertaken by the faint of heart. We are awash in biomarkers, yet the FDA has approved fewer than 1.5 per year since the mid 1990s (Anderson, et.al., Genome Technology, April 2010), despite over 1500 submissions. There are a dozen biomarker meetings a week—hundreds of millions of dollars being spent—and yet most biomarker driven phase III clinical trials fail, especially in an area like oncology. Precision medicine will limp along but never proceed at scale or at a rate that will really benefit the patients who need targeted interventions. George will also offer some perspectives on what has to be done and provide some direction for rethinking this entire system—which isn’t really a system.

9:15 a.m. – 10:00 a.m.
Discussion: The One Thing (Change, Standard, etc.) That Could Make the Difference in Biomarker Development (Your Best Idea)

10:00 a.m. – 10:20 a.m.
Break

10:20 a.m. – 11:30 a.m.
Panel/Discussion
(Panel Moderator, Carolyn Compton)
Early and Late (Translatable Biomarker Discovery)
It’s a eureka moment—you have discovered a biomarker. What exactly does that mean? There is no real guidebook to tell you that yes, it’s a biomarker. What evidence would you need to decide to go forward? What is the “chain of custody” for the discovery? Is documentation of process and procedures, etc. really there? Really this slows down discovery—is all of that really necessary? How should we determine to move forward into late or translatable discovery, e.g., assay development (not inexpensive)? These first two critical phases of biomarker development are the root of most biomarker failures. Why—and what needs to be done to move this beyond a black box? Hopefully, we have given the panelists a place to start!

10:20 a.m. – 11:30 a.m.
Panel/Discussion (continued)
(Panel Moderator, Carolyn Compton)

  • The really critical stuff – what makes the biomarker discovery process robust? When in the process does it have to become robust (e.g., reproducible)? Why should we care? George Vasmatzis, Ph.D., Mayo Clinic
  • Finding biomarkers in really, really big multi-generational data sets – is this going to work – and how many genes (and/or the RNA, proteome, epigenome) make a biomarker? Or is it a signature? Are we discovering or digging larger deeper holes? Joe Vockley, Ph.D., Inova Translational Medicine Institute
  • Not so fast, show me the biomarker.  A view from the industry. Anahita Bhathena, Ph.D., Abbot Laboratories

11:30 a.m. – 12:15 p.m.
Discussion
In an end-to-end model of biomarker development, what are the major questions (read “level of evidence”) that must be answered in early discovery to make an informed decision to proceed to translatable (late) discovery? Are the standards and decision points going to be very specific for every biomarker class?

12:15 p.m. – 1:15 p.m.
Lunch

1:15 p.m. – 2:15 p.m.
Panel Discussion
Assay Development and Assay Performance
(Panel Moderator, Robert Penny, IGC)

  • Assay development – When and how do you know you have a winner? Have you ever seen a biomarker you didn’t like? When do you say no? Is assay development too important to leave in the hands of novices? The world of Laboratory Developed Tests is exploding. If some of our FDA colleagues were here, they would tell you that they just don’t really care, as they don’t recognize LDTs. What is the role of these tests vs. 510Ks or PMAs? Why is analytical validation important if you want to use the test in patients—or is it? Head spinning stuff: Can a diagnostic be a biomarker? Can a biomarker be a diagnostic?
  • The HER-2 assay story (FISH – IHC) – Are there major lessons to learn about assay development and can they be used here? Patrick Roche, Ph.D., Ventana Medical Systems
  • We are all beginning to think (and no doubt worry) about complex assay development (e.g., gene/other “signatures,” multiplexed assays). Will this mean new levels of evidence requirements? Kevin Halling, M.D. , Ph.D., Mayo Clinic
  • Developing assays in the translational medicine space – Could biomarker qualification serve in this space? If a biomarker doesn’t “qualify” in FDA-ease, is it done? Jannick Anderson, Ph.D., M.D., Anderson

2:15 p.m. – 2:40 p.m.
Discussion

2:40 p.m. – 3:00 p.m.
Break

3:00 p.m. – 4:15 p.m.
The Biomarker Complexity Conundrum
(Panel Moderator, Ken Buetow, Ph.D., ASU) Just when we think we know something about biomarkers, they are biomolecular entities, right? Wrong! If you can dream it, discover it, measure it, and demonstrate that it is clinically relevant, it can be called, and may even be, a biomarker. In fact if it is “fit for the purpose” it may be used to predict of clinical response, monitor therapy, stratify patients for trials, etc. It can become a biomarker. How many classes of biomarkers are there? Is it infinite? As we move into the mystical world of molecularly based medicine we face new challenges—complex signatures,  nanotechnologies, advanced imaging. Let’s discuss what this means, especially in terms of levels of evidence requirements.

  • Is imaging the ultimate contemporary biomarker? Given the looming “epidemic” in Alzheimer’s disease, will biomarkers be critical? Are there lessons to learn from Alzhimers? Eric Reiman, M.D., Banner Health
  • We are all focused on the genome, proteome, etc. Are there potentially better more quantifiable biomarkers waiting to take their place? Ariel Anbar, Ph.D., ASU
  • Algorithms as biomarkers. Precision medicine almost demands that we be able to make sense of multi-dimensional “big data.” Is this the future of biomarkers? Andy Hospodor, Ph.D., UC Santa Cruz

4:15 p.m. – 4:45 p.m.
Qualifying vs. validating a biomarker – Can this work so that it isn’t a “where’s Waldo” experience? Laura Van ‘t Veer, Ph.D., UCSF

4:45 p.m. – 5:15 p.m.
Summing Up and Tomorrow – Ann Barker

6:00 p.m.
Reception and Dinner,
(Cholla Dining Room)

 

December 14, 2012

7:30 a.m. - 8:00 a.m.
Breakfast

8:00 a.m. - 8:30 a.m.
Mind-Bending Presentation
Designing and Implementing Biomarker Driven Clinical Trials: Reflections on the ISPY-2 and other Experiences
Donald Berry, Ph.D., University of Texas, M.D., Anderson Cancer Center

8:30 a.m. – 9:00 a.m.
Discussion

9:00 a.m. – 10:15 a.m.
Panel Discussion
(Panel Moderator, Karen Anderson, M.D., Ph.D., ASU)

Biomarker Driven Clinical Trials – The Last Stop on the Way to Regulatory Submission
If you’ve gotten this far—and it’s all good—you may be ready to design and undertake a biomarker-driven clinical trial. If so, extract your wallet and prepare to fail! Coming back to a familiar theme, biomarker trials have to work; otherwise, very little personalized medicine will materialize, and the statistics currently don’t look that good. If level of evidence standards got you this far,  should you expect to succeed?
This panel has an assignment – three questions: (1) As you look at the biomarker field today, what is the single biggest barrier to use these advances to enable smaller, better trials? (2) If you had total control, how would you develop a system for biomarker-enabled clinical trials that was faster/cheaper and obviously produced better drugs? (It goes without saying that you can’t remove the FDA) (3) Will biomarkers make the randomized clinical trial irrelevant?

  • Ray Dubois, M.D., Ph.D, ASU (Colon Cancer)
  • Rafael Fonseca, M.D., Mayo Clinic (Multiple Myeloma)
  • Michael Berens, Ph.D., TGEN (GBM)
  • Randy Nelson, Ph.D., ASU (Diabetes)

10:15 a.m. – 10:30 a.m.

Break

10:30 a.m. – 11:30 a.m.
Individual Group Discussions – The end-to-end pipeline – recommendations for level of evidence standards (be as specific and detailed as you feel appropriate).

  • Mesquite Boardroom
  • Executive Boardroom
  • Peace Pipe Ballroom

11:30 a.m. – 12:15 p.m.
Recommendations for the NBDA and the field – A convergent facilitated discussion (goal of publishing our recommendations)

12:30 p.m.
Lunch and/or Depart

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