Download - Digital Pathology in the Era of Global Clinical Trials: Improving Quality and Consistency
1CLINICAL TRIALS
Digital Pathology in
the Era of Global Clinical
Trials:
Improving Quality and Consistency Ron Luff, MD, MPH
2CLINICAL TRIALS
Global Reach
USA
UK
Singapore
Australia
Belgium
China
Quest Diagnostics Clinical Trials Laboratories & Offices
Affiliate Laboratories
India
3CLINICAL TRIALS
• 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– >300 US employees– Service Areas include:
o North Americao Central Americao South Americao Australiao South East Asia
Proprietary Facilities: US, UK, and India
• Two facilities near London (Heston – Lab; Hounslow – Proj. Mgmt), plus Project Mgmt in Wavre, Belgium– ~300 EU employees– Multiple language expertise– Services Areas include:
o Europeo Middle Easto Africao India
• New 65,000 sq.ft. laboratory in Gurgaon, India (New Delhi); supporting local investigators / trials and global clinical trials – Service Areas include:
o India o Pacific Region
4CLINICAL TRIALS
Core Competencies by Therapy
Experience (# Studies completed from 1996-2007)
633
506
427
407
392
390
336
286
214
206
108
335CNS
ONCOLOGY / HEMATOLOGY
CARDIOVASCULAR
NUTRITIONAL & METABOLIC
IMMUNO / INFECTIOUSDISEASEPULMONARY
PSYCHIATRIC
GENITOURINARY-OB/GYN
ARTHRITIS
GASTRIINTESTINAL
DERMATOLOGICAL
OTHER
5CLINICAL TRIALS
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
6CLINICAL TRIALS
Digital Cellular Pathology, circa 1996-present
QDC
146 GBSQL/ServerMeta DataDatabase
CLARiiON
• Quest Diagnostics’ reference laboratory placed 4 scanners in 2007 (Nichols Institute)
• Primary use
−Remote viewing ofreference IHC cases ina faster, yet equallyaccurate manner
−Digital analysis whenrequested (eg, Ki67quantitation)
Digital Pathology
WAN
Chantilly, VA
NS40 PSI
San JuanCapistrano, CA
NAS NAS
NS40 PSI
5tb CIFSShare
5 tb CIFS Share
7CLINICAL TRIALS
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
8CLINICAL TRIALS
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
9CLINICAL TRIALS
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
10CLINICAL TRIALS
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
11CLINICAL TRIALS
IHC Staining for EGFR
Strongly Positive ??Positive
20X
400X
12CLINICAL TRIALS
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.