November 4-5, 2013 | Boston Marriott Cambridge | Cambridge, MA
Timely implementation of companion diagnostics alongside therapeutic products has put pressure on validation of predictive biomarkers earlier in drug development. Choosing an appropriate assay platform and designing an analytical validation strategy for exploratory predictive biomarkers that is in line with downstream requirements for companion diagnostics is becoming more important. Cambridge Healthtech Institute’s Inaugural Clinical Biomarker Assay Development meeting will address analytical validation strategies and choices of assays/platforms for companion diagnostics, including development time and technical performance, regulatory and reimbursement plans, and commercial and clinical access.
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Monday, November 4
7:30 am Conference Registration and Morning Coffee
8:30-8:40 Welcome Remarks from Conference Director
8:40-8:45 Chairperson’s Opening Remarks
8:45-9:10 Bridging Research and “Clinical” Assays in Pharmaceutical Research & Development
John L. Allinson, FIBMS, Vice President, Biomarker Laboratory Services, ICON Development Solutions
Many biomarker assays used in drug development are research assays (i.e., not accredited diagnostic devices). This presentation will look at the following: basic validation experiments across assays in research and diagnostics, differences and assay evolution as methods progress through different uses of results data, the requirements for accreditation of assays to be used in diagnostics, and a brief look at the development of a companion diagnostic and its implications from the laboratory perspective.
9:10-9:35 Real-Time Multiplexed Cancer Pharmacodynamics in Patients
S. Michael Rothenberg, M.D., Ph.D., Instructor, Medicine, Massachusetts General Hospital
A major shortfall in patient care is the difficulty in assessing for early response to anti-cancer therapy. We have developed a methodology using multispectral imaging (MSI) immunofluorescence microscopy to quantify the effects of therapy on individual treatment biomarkers in tumor cells from patient-derived biopsies and circulating tumor cells (CTCs) in real time, while patients are undergoing therapy, weeks before radiographic response can be measured. I will discuss applying this approach to patients with diverse cancers undergoing treatment with targeted therapies.
9:35-10:05 Assay and Kit Lot Bridging Considerations for Single and Multiplex Biomarker Analysis in Support of Clinical Studies
Afshin Safavi, Ph.D., Senior Vice President, Bioanalytical Operations, BioAgilytix Labs
Biomarker analysis has become a common practice by many pharmaceutical companies to help PK/PD modeling. The reliability of outcomes is heavily influenced by the quality of the reagents. One of the challenges that bioanalytical labs face when running biomarker studies is the control of lot-to-lot variability of critical reagents and commercial immunoassay kits. Case studies will be presented to highlight the key bioanalytical considerations involved in running successful biomarker analyses in support of clinical studies.
10:05-10:45 Coffee Break
10:45-11:10 Development Strategies to Achieve a True Free Target Assay
Martin Schwickart, Ph.D., Scientist, Clinical Pharmacology and DMPK, MedImmune
To support biologics development, free target assays are routinely used to monitor drug effect and to predict an appropriate dose. In many assays, free target is overestimated due to dilution of the sample and re-equilibration in presence of a capture reagent. We present here a structured strategy and assay development to measure true free target and compare the effect of two drugs with different affinities.
11:10-11:35 The Central Role of Human Tissue in Diagnostic Assay Development
Carol Cheung, M.D., Ph.D., Department of Pathology, University Health Network, Canada
Reliable sources of appropriately processed and annotated human tissue are required for diagnostic assay development. As such, requests for materials from clinical care institutions, where tissues are fixed and processed according to strict laboratory protocols, are ever increasing. Understanding the regulatory requirements that institutions must abide by with respect to different classes of tissue is paramount to the responsible and safe acquisition of human tissue for development and validation of innovative new tests.
11:35-11:50 Diagnostic Classifiers for the Detection of Bladder Cancer
Scott McKeown, Ph.D., Research & Development Consultant, Randox Laboratories, Ltd.
Patients presenting with hematuria require investigations, including cystoscopy and imaging of their upper urinary tract, to identify the source of bleeding. This is a significant health burden, which is set to increase because of our aging population. Using Randox Biochip Array Technology (BAT), we have identified diagnostic classifiers for detecting bladder cancer.
11:50-1:30 Enjoy Lunch on Your Own
1:30-1:35 Chairperson’s Opening Remarks
1:35-2:00 Leaping the Valley between Research and Medicine: Notes from the First Two Years in a CAP-Certified NGS Lab
Seth Crosby, M.D., Director, Partnerships & Alliances, Washington University School of Medicine
Are clinical standards of evidence/annotation different than those of research? How is a clinical NGS test validated? In a clinical lab, what needs to be in the analysis tool chest? What has Washington University built that allows a physician to interpret sequencing data?
2:00-2:25 College of American Pathologists’ Standards and Proficiency Testing for Next-Generation Sequencing for the Clinical Laboratory
Nazneen Aziz, Ph.D., Director, Molecular Medicine, Transformation Program Office, College of American Pathologists
The rapid and ongoing advances in the genetic test market, spurred by the opportunities of Next-Generation Sequencing (NGS), necessitate many facets of the healthcare industry to work cohesively. Adoption of NGS as a clinical test requires the adoption of many processes and procedures, such as the analytic and clinical validation of the test, CLIA certification/CAP accreditation, standards for reference materials, availability for proficiency testing, genetic counseling, and questions regarding reimbursement, informed consent and incidental findings. This talk will focus on the laboratory requirements developed at CAP for CLIA/CAP accreditation and the plans for proficiency testing for NGS.
2:25-2:50 Discovery of Predictive Biomarkers to Resolve Clinical Dilemmas Using Next-Generation Sequencing
George Vasmatzis, Ph.D., Assistant Professor, Laboratory Medicine and Pathology, College of Medicine, Mayo Clinic
Identification of causal DNA rearrangements is critical to the understanding of cancer development and progression, and is important clinically for accurate prognosis and efficient treatment. Mixed grade tumors portend a significantly more aggressive phenotype than phenotypically pure highly differentiated tumors. It is critical to understand the molecular relationship of adjacent low-grade and high-grade tumor cell populations and relate these molecular abnormalities to disease progression. To decipher molecular relatedness, we used laser capture microdissection (LCM) and whole-genome amplification (WGA) to separately collect and amplify DNA from adjacent cell populations with different patterns in both prostate and lung adenocarcinomas. We then carried out massively parallel mate-pair NGS to examine the landscape of large chromosomal alterations. Our findings indicate that while patterns from the same tumor each possess unique breakpoints, they also share identical ones, pointing to a common origin. Hierarchical clustering analysis revealed that low-grade pattern has greater breakpoint similarity to its high-grade partner than to similar pattern from a different patient. Our studies provide evidence that LCM, WGA, and NGS of adjacent tumor regions are important tools in deciphering lineage relationships and discovering chromosomal alterations associated with tumor progression.
2:50-3:50 Refreshment Break in the Exhibit Hall with Poster Viewing
3:50-3:55 Chairperson’s Opening Remarks
3:55-4:20 Personalized Medicine and Shrinking Patient Populations: Rethinking the Value of Companion Diagnostics
Alan T. Wright, M.D., MPH, CMO, Roche Diagnostics Corporation
Despite the critical role diagnostic tests play in personalized medicine, they are significantly undervalued, and the disparity that exists between current investment models and reimbursement policies for diagnostics is not tenable long-term. As science helps define the uniqueness of each person’s condition, the potential volume for specific tests will be less. To maintain investment from the private sector in diagnostics—which contributes significantly to medical innovation and helps demonstrate the clinical utility of FDA-approved tests—a more attractive path to market is needed.
4:20-4:35 Panel Discussion: Making Precision Medicine More "Precise"
Panelists to be Announced
5:00-6:00 Welcome Reception in the Exhibit Hall with Poster Viewing
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