Digital Pathology in the Era of Global Clinical Trials: Improving Quality and Consistency

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Digital Pathology in the Era of Global Clinical
TrialsImproving Quality and Consistency
Ron Luff, MD, MPH
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Global Reach
UK
Belgium
USA
China
India
Singapore
Australia
Quest Diagnostics Clinical Trials Laboratories
Offices
Affiliate Laboratories
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Proprietary Facilities US, UK, and India

• Two facilities in Los Angeles (Lab and Project
  Mgmt), plus a lab in San Juan Capistrano, CA
  (Nichols Institute), a lab in Teterboro, NJ and
  an administrative facility in Collegeville, PA
• gt300 US employees
• Service Areas include
• North America
• Central America
• South America
• Australia
• South East Asia

• Two facilities near London (Heston Lab
  Hounslow Proj. Mgmt), plus Project Mgmt in
  Wavre, Belgium
• 300 EU employees
• Multiple language expertise
• Services Areas include
• Europe
• Middle East
• Africa
• India

• New 65,000 sq.ft. laboratory in Gurgaon, India
  (New Delhi) supporting local investigators /
  trials and global clinical trials
• Service Areas include
• India
• Pacific Region

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Core Competencies by Therapy
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Cellular Pathology, circa 1858-present

• Light microscopy art-form
• Variation of diagnoses among
• experts
• Truth often determined by
• majority rule in adjudication
• for clinical trials cases

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Digital Cellular Pathology, circa 1996-present

• Quest Diagnostics reference laboratory placed 4
  scanners in 2007 (Nichols Institute)
• Primary use
• Remote viewing of
• reference IHC cases in
• a faster, yet equally
• accurate manner
• Digital analysis when
• requested (eg, Ki67
• quantitation)

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Digital Pathology for Clinical Trials,circa
1996-present

• Reduce variation of diagnoses and allow for
  remote prospective reads by central
  pathologist(s)
• Standardization among different labs

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Digital Pathology for Clinical TrialsAdditional
Advantages

• Long-term storage of images
• Digital slide
• No risk of breakage and stain fade
• Enables use of tissue section for other purposes
  (eg, DNA studies)
• Remote anytime access to digital slides
• Enables trial sponsors to study slides
• Conferencing capabilities
• Multiple people can review slides simultaneously

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Digital Pathology for Clinical TrialsAdditional
Advantages

• Digitized slides can substitute for tissue/
  cytology samples when global trial host country
  restricts exportation
• Digital analysis can be used for
• Quantifying stains
• Microvessel density assessment
• Rare event detection
• Protein quantitation within cellular compartments
  when used in conjunction with immunofluorescence

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Epidermal Growth Factor Receptor (EGFR)

• Part of a family of four related cell surface
  tyrosine kinase receptors
• Often mutated and upregulated in epithelial
  cancers (NSSC of lung, head and neck squamous
  carcinoma, colon adenocarcinoma)
• Overexpression predicts response to certain
  therapies (eg, gefitinib)
• EGFR status determined by FISH or
  immunohistochemistry (IHC) staining until
  recently, subjective interpretation

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IHC Staining for EGFR
20X
400X
Strongly Positive
??Positive
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Digital Assessment

• Digital computerized assessment of membrane
  receptor
• 3 Cells 174
• 2 Cells 153
• 1 Cells 78
• 0 Cells 36
• Total Cells 441

Analysis provided by Trevor Johnson, Aperio.