caBIG Biospecimen and Pathology Tools

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caBIG Biospecimen and Pathology Tools

• Ian Fore, D.Phil.
• NCI Center for Biomedical Informatics and
  Information Technology

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Outline

• Role of biospecimens
• NCI biospecimen initiatives
• Best Practices for NCI supported biorepositories
• Explaining caBIG
• Biospecimen Research Network
• caBIG Applications developed
• Other areas of interest

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The Foundation of Science Reproducibility

• First rule of science Valid data are
  reproducible
• The enemy of reproducibility is variation
• Because of biological complexity, some variation
  cannot be eliminated
• Much of the variation seen in omics studies in
  results from sources other than biological
  complexity

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The Discovery PipelinePotential Sources of
Variation
Analytical tools areinadequate tocomplexity of
data orflawed at core
Hypothesisiswrong
Experimental materials, e.g., biospecimens,
arehighly variable in quality
Experimentaldesign is flawed
Tools are inadequate,not applicable
toexperimental design,or even broken
Data Collection and Analysis
ExperimentalTechnologies
Hypothesis
ExperimentalDesign
ExperimentalMaterials
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Molecular Research and Analyte Variation

• The challenges
• Varying methods of collection, processing, and
  storage can alter the physical/biologic state of
  the specimen
• Varying associated specimen data elements alter
  what the scientist knows about the
  character/nature of the specimen
• Variable clinical information alters what the
  scientist knows about the patient (biologic
  context of the specimen)
• Variable restrictions (patient consent other
  ethical, legal, and policy issues) alter what the
  scientist may do with the specimen and/or data

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NCI Best Practices for Biospecimen Resources

• Objective
• Unify policies and procedures for NCI-supported
  biospecimen resources
• Previously published as First Generation
  Guidelines for NCI-Supported Biospecimen
  Resources
• Public comments received and addressed
• Final to be published as NCI Best Practices for
  Biospecimen Resources and awaiting approval of
  the NCAB

http//biospecimens.cancer.gov
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Informatics in the NCI Best Practices

• General Functionality
• Tracking the life cycle of a biospecimen
• QA/QC
• Monitoring and reporting biospecimen quality
• Security of sites
• Identification of Biospecimens
• Unique identification to each biospecimen
• Biospecimen tracking
• Integration with Local Systems
• Interoperability
• Ethical and Legal Issues
• Meet privacy and human subjects regulations
• Meet State and Federal requirements

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Informatics Systems are a Key Tool for
Biospecimen Resources

• Informatics systems should be robust and reliable
  to sustain day-to-day operation of a biospecimen
  resource
• Informatics systems should be able to meet
  changing scientific needs
• Interoperability of system is key to exchanging
  data and biospecimens
• System should support all aspects of biospecimen
  resource operation
• Use informatics systems that support the linking
  of specimens with associated data and protect the
  health information of patients
• Adhere to or initiate review of NCI Center for
  Bioinformatics guidelines and tools caBIG
  silver-level compatibility is recommended

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Biospecimen Best Practices Toolkit Written
Background Materials

• Items for distribution at meetings and through
  the OBBR Web site
• NCI Best Practices for Biospecimen Resources
• Biospecimen Basics An Overview of the NCI Best
  Practices for Biospecimen Resources
• Implementing caBIG for Biospecimen Resources An
  Overview
• Implementing caBIG for Biospecimen Resources
  Next Steps
• Providing Your Tissue for Research
• Other biospecimen-related articles, publications,
  and news stories of interest

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Implementing caBIGTM for Biospecimen Resources
An Overview

• One-page document with broad overview of caBIGTM
  for Biospecimen Resources
• Target audiences include
• Patients and Patient Advocates
• NCI-designated Cancer Center Directors
• Strategic Thinkers at Institutes and Biospecimen
  Resources
• Topics Covered
• What is caBIGTM and What does it offer
  Biospecimen Resources?
• Strategic Considerations
• Benefits to patients and advocates
• Benefits to researchers and resource directors

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Implementing caBIGTM for Biospecimen Resources
Next Steps

• 9-page document highlighting The Road to caBIGTM
  Compatibility
• Designed for resources interested in the specific
  steps required for implementing caBIGTM
  compatibility
• Addresses public comments and frequently asked
  questions
• Setting the Stage
• Core Concepts
• How does caBIGTM compatibility work
• FAQs
• Turning to Solutions
• Available software tools
• Overview of Alternatives
• Skills, Technology, and Resources Required

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Many SOPs Around the WorldWhich are the best?

• Impossible to call any one best (even NCIs)
• All have strengths and weaknesses
• No single set of SOPs are applicable to all
  clinical and research analytical platforms
• Very few SOPs are based on scientific evidence

Where we need to go
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Biospecimen ResearchWhat Needs to Be Understood?

• Variables (examples)
• Time at room temperature
• Temperature of room
• Type of fixative
• Time in fixative
• Rate of freezing
• Size of aliquots

• Variables (examples)
• Antibiotics
• Other drugs
• Type of anesthesia
• Duration of anesthesia
• Arterial clamp time

Time 0
Post-acquisition
Pre-acquisition
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Biospecimen Research ProgramProjects Related to
Goals

• Bridging the gap between existing clinical
  practice for biospecimens and emerging
  technologies for personalized diagnostics and
  therapies
• Tissue preservation variables and their impact on
  downstream applications
• Robotic surgery vs. manual surgery for prostate
• Defining the most significant variables for
  prospective collection of tissues, blood, and
  body fluids
• Effects of pre-acquisition variables and
  biomolecule extraction methods on biomolecule
  analysis results in blood
• Developing evidence-based biospecimen quality
  indicators for specific analytical platforms
• In conjunction with above study, with accepted
  proper and improper conditions for collection and
  biomolecule analysis in blood

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BRN Pilot Project ExampleHER2 Testing

• HER2 (ERBB2) gene is amplified in 20 of breast
  cancers
• HER2 over-expression (positive status)
  important measure of clinical outcome and
  recommended therapy
• Clinical testing for HER2 status
• Formalin-fixed paraffin-embeddedexcised breast
  tissue
• Immunohistochemical test (0-3)
• 2 cases FISH
• Pathologist uses scoring systemto report status
• Positive result triggers therapy 55K/year
• False-positive risk of cardiotoxicity, no
  clinical benefit
• False-negative missing potentially beneficial
  treatment
• Genentech estimates 5,000 false positives and
  7,000 false negatives occur per year problem not
  the tests but where they are performed.

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Short List of Critical VariablesHER2
Immunohistochemistry

• Was the tissue fixed in formalin? Buffered
  formalin?
• How long was it fixed?
• How long was it in the processing machine?
• How long was it processed through each step in
  the processing machine?
• What temperature was the paraffin in the
  processing machine?
• Additional factors include
• different immunostaining protocols/automated
  processors
• Differential pathologist readings of the stained
  tissue
• Collaboration underway with Walter ReedArmy
  Medical Center (WRAMC) to evaluateHER2 fixation
  variables

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Other BRN Pilot Projects

• Effect of warm ischemic time on gene expression
  for colon and renal cancers
• Effect of resected specimen size and weight on
  RNA and protein analyses
• Comparison of RNA and protein yields and quality
  from different laser microdissection platforms
• Effect of necrotic tissue on DNA analyses
• Effect of tumor tissue DNA extraction
  methodologies on downstream analyses
• Determination of FineFIX on histologic quality
  and recovery of RNA from human prostate tissue
• Effect of different formalin fixation times on
  DNA analyses
• Effect of variations in urine collection and
  storage on ELISA detection of VEGF

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Defining a minimal clinical dataset

• Specified in the Best Practices document
• Minimal set of clinical data that should be
  recorded with Biospecimens
• Drafted by NCI Biorepository Coordination
  Committee
• Seeking review with various groups
• Including ISBER

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Minimal clinical dataset (1)
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Minimal Clinical Dataset (2)
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Tissue Banks and Pathology Applications

• caTISSUE Core (WU) Core specimen handling and
  tracking functions
• caTIES (UPMC) - Text extraction and
  de-identification of surgical pathology reports
• caTISSUE Clinical Annotation Engine (UPMC) -
  Annotation of specimens with clinical data

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caTissue Core

• Version 1.0 - March 2006
• Version 1.1 - February 2007
• Version 1.2 - June 2007
• Developed by Washington University in St Louis
• Requirements and testing
• Thomas Jefferson University
• Indiana University
• University of Pennsylvania
• University of Pittsburgh

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caTissue Core 1.2 enhancements

• Usability enhancements
• Easy access to edit from any search
• ... but only if you are authorized to edit
• Support for a Collection Calendar
• Named events
• Default addition of planned specimens
• User interface improvements
• Propagate collection values for all specimens in
  a group
• More intelligent storage container allocation
• Default pages now relevant to logged in user

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Login
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Admin blank
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Add container type
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Add container
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Add CP
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Collection events
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Biospecimen menu
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Full screen option
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Patient list
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Search
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Search Results
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caTIES Query
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caTIES - Surgical Pathology Report coding
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caTissue Suite 1.0

• Integration
• caTissue Core
• caTIES
• Clinical Annotation
• Much work already done
• Put on hold in preference to caTissue Core 1.2
  usability
• Due March 2008

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caTissue Suite 1.0 - features

• Dynamic Extension
• Data models
• Data elements
• Ability to add and share custom data
• Saved queries and reports
• Consent tracking
• Ordering
• Shipping
• Query across multiple caTissue sites
• Site configurable security scheme

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Specimen Locator
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Reporting mechanism - Cooperative Groups

• By Clinical Trial Protocol
• No. of patients enrolled
• No. of specimens stipulated
• FFPE
• Frozen tissue
• Whole blood
• Total
• No. of specimens collected
• FFPE
• Frozen tissue
• Whole blood
• Total
• Specimens distributed by type and protocol

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How is the grid relevant to biorepositories?

• Aim is to enable interoperation of Tissue Banks
• Proposal
• Establish a simple standard for a web service to
  allow communication of summary level information
• Numbers and types of specimens
• Directory of banks offering this information
• Ability to query multiple banks
• Mapping to terminology

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Integrating data from repositories
Report aggregator
Common model
Service implementation
Service implementation
Service implementation
Text File
Local system
caTissue
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How is the grid relevant to biorepositories?

• Aim is to enable interoperation of Tissue Banks
• Proposal
• Establish a simple standard for a web service to
  allow communication of summary level information
• Numbers and types of specimens
• Directory of banks offering this information
• Ability to query multiple banks
• Mapping to terminology
• Keep it simple

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This is complex!
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This is simple
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How is the grid relevant to biorepositories?

• Aim is to enable interoperation of Tissue Banks
• Proposal
• Establish a simple standard for a web service to
  allow communication of summary level information
• Numbers and types of specimens
• Directory of banks offering this information
• Ability to query multiple banks
• Mapping to terminology
• Keep it simple
• Keep it agile
• Try it out
• Be ready to modify it based on feedback
• Can/Should we make it international?

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Strategic plan

• Virtual microscopy
• Distributed review
• Tissue microarray (TMA) support
• TMA Design
• Image Analysis
• Annotation
• Imaging
• TMA Facility management
• Image query
• Expt design
• Data Stds
• Image scoring

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Additional Information

• http//biospecimens.cancer.gov

• https//cabig.nci.nih.gov/workspaces/TBPT