camd gbsc update - alzheimer's association | alzheimer's
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CAMD GBSC UPDATE Diane Stephenson
Executive Director, CAMD Critical Path Institute Tucson, AZ
July 11, 2014
Overall Goal of CAMD CSF
AD Biomarker Team
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FDA Biomarker Qualification of CSF analytes (Aβ42, tau, p-tau)
for the purpose of enrichment in AD clinical trials at the
pre-dementia stage
Out of Scope:
• Regulatory approval/clearance of CSF biomarkers as diagnostic agents
• Approval of CSF biomarkers as companion diagnostics (IVD)
• Use of CSF biomarkers as pharmacodynamic biomarkers
• Use of CSF biomarkers as surrogates of efficacy
CAMD AD CSF Biomarker Team Members
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AbbVie-- Devan (Viswanath) Devanarayan, Bradford Navia
Alzheimer’s Association—Maria Carrillo, Jim Hendrix
Biomarkable—Hugo Vanderstichele
Boerhinger Ingelheim– Mark Gordon
Cerora– Adam Simon
Critical Path Institute—Diane Stephenson, Klaus Romero, Hemaka Rajapakse, Robin Shane
Eisai—June Kaplow
Eli Lilly & Company—Peng Yu, Bob Dean, Janice Hitchcock, Brian Willis
FDA—Marc Walton, Jim Kaiser
Innogenetics—John Lawson
Janssen—Jerry Novak, Mahesh Samtani
Merck—Omar Laterza
Meso Scale Discovery—Bob Umek
Novartis–Richard Meibach
Orion-Kristiina Haasio
Pfizer-Kaori Ito
Quanterix—Andreas Jeromin
ICON—David Raunig
University of California, UC Davis—Laurel Beckett, Huanli Wang
University of Pennsylvania—Les Shaw
Boehringer Ingelheim--Mark Gordon
Maastricht University—Pieter Jelle Visser
University of Göteborg, Henrik Zetterberg, Kaj Blennow
Washington University—Anne Fagan, Betsy Grant
University of Antwerp—Sebastiaan Engelborghs
Biomarker Qualification Process
- Consultation phase is iterative 4
Woodcock et al.,
Expert Opin. Med. Diagn.
(2011) 5(5):369-374
FDA feedback: what is the path to biomarker qualification?
CSF Assays Performance and Biomarker Performance
• Precision-based vs accuracy-based assays
• Cutoff values and how to define
• Variability: Intra- & inter-lab, lot-to-lot, reference standards
• Assay analytic performance features defined
Data Analysis and Interpretation
• Define and describe confirmatory datasets
• Concern for bias
• Detailed statistical analysis plan with learn and confirm phases
Guidelines/SOPs to help sponsors effectively use
biomarkers for enrichment
Current challenges: Need for more data especially clinical trial data
CSF Assay Design, Characterization & Standardization: the impact of consortia
ASSAY
LAB SAMPLE
accuracy
External QC Programs (Alzheimer Association)
Proficiency panels
Regulatory guidance(s)
Operator training
Reference
methods/materials
(GBSC, IFCC)
Lab SOPS
(Customer)
Robustness
Lot consistency
Raw Materials Qualified
Stability Run Validation
Modified according to Vanderstichele et al. Alzheimer & Dementia 2012
SOP for collection & storage
(ADNI, JPND, AIBL, ...)
No matrix interference
Improved precision
Selective & specific
(Vendor)
Harmonization The needs for the future
biotin
SV Biomarker Qualification
Clinical Data Standards
Enable pooling of data that can generate new insights and reveal subtle signals
Value Proposition 2010 C-Path CAMD –AD database
April 2012 FDA presentation at CDISC International Interchange
Improve the efficiency and effectiveness of regulatory reviews (Standards will be required by 2017)
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What is CDISC?
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• Nonprofit standards development organization, founded 1997
• Publishes global open standards for clinical and non-clinical data
• Accepted and soon to be required by regulatory agencies
for new submissions
• CDISC offers a system of standards that addresses end to end
need for data researchers
Concepts covered by the Alzheimer's CDISC User Guide (v2.0) ApoE Genotype Family History of AD Volumetric MRI PET, PET/CT (FDG, Florbetapir, PiB) CSF Biomarkers and Sampling Outcome Assessment Scales ADAS-COG MMSE CDR AVLT FAQ Modified Hachinski DAD ADCS-ADL MCI NPI CGI GDS
AD CDISC standards
CSF Biomarker Concept Map
CSF
COLLECTION
AND
BIOMARKER
TESTING
COMPLEX
but . . .
possible to
standardize in
the near future
Summary
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• CAMD’s AD CSF team is aiming for qualification of CSF biomarkers
with FDA for the purposes of enrichment in pre-dementia trials. More
data and resources are needed for success.
• CAMD and CDISC have developed globally accepted therapeutic
area specific CDISC standards for AD, including biomarkers
• Adoption of CDISC data standards in clinical trials will enable
efficient regulatory review and is the format that will be required
in the future
• CDISC standards enable pooling of diverse sources of clinical data
to address research questions and look for subtle signals in large
data
• Proactive agreement to adopt biomarker standards in planning
clinical trials in the future will facilitate learnings and enable
harmonization of ongoing and prospective data
Acknowledgements
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C-Path Staff • Martha Brumfield, CEO
• Lynn Hudson, CSO
• Steve Broadbent, COO
• Klaus Romero, Director, Clinical Pharmacology
• Data Team
Jon Neville, Bob Stafford, Emily Hartley, Bess LeRoy, Marty Cisneroz
C-Path gratefully acknowledges the support of
The Tucson Community
• Robin Shane, CAMD Project Coordinator
• Hemaka Rajapakse, CAMD Senior PM
Experts contributing to CDISC standards development NINDS, Andreas Jeromin, Hugo Vanderstichele, Jerry Novak, Mark Gordon,
Patricia Cole, Mark Austin, Steve Kopko, Susan De Santi, Ken Marek,
Jessica Langbaum, Kewei Chen and Adam Fleisher