Comparison of RECIST 1.0 and 1.1 - Impact on Data Management Kevin Shea Senior Solutions Architect C3i, Inc.
Jan 17, 2015
Comparison of RECIST 1.0 and 1.1 - Impact on Data Management
Kevin Shea Senior Solutions Architect C3i, Inc.
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Objectives
• Describe RECIST • Independent imaging review • Manage external imaging data
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Agenda
• Background • RECIST
– Overview – Parameters – RECIST V 1.0 vs. 1.1
• Independent Review • Data Management Considerations • Conclusions
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Background
• Oncology clinical trials utilize imaging assessment as surrogate endpoint
• Imaging involves variations in modality, techniques, and reader assessment, training
• Standardization – variability, repeatability • RECIST – well-adopted standard • Data Management processes can be used to
monitor assessment data to track quality and safety
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RECIST Overview
• Response Evaluation Criteria In Solid Tumors • Establish referenceable, repeatable standards • Based on WHO criteria (1981) • Established 2000 (v.1.0), Updated 2009 (v.1.1) • PII focus, PIII applicability • Endpoints – ORR, PFS • Well-adopted in ICLs • Challenges at AROs and local imaging sites
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RECIST Parameters
• Serial review – baseline to completion • Quantify tumor burden • Qualitative assessment of remaining lesions • Lesion classification • Consistent assessment categories • Associate changes with efficacy
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Evaluation Process
• Baseline – key to establish as comparator of subsequent timepoints – Target – Sum of Longest Diameters – Non-Target – document all other disease
• Post-Baseline – Target
• Sum Diameters • Compare to BSL/Prev TPs, Establish nadir
– Non-Target – evaluate for substantial change – New – Review for presence
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RECIST Lesion Classifications
• Target – representative of disease, able to reproducibly measure and track over time
• Non-target – all other lesions or sites of disease, tracked qualitatively
• New – post-baseline presence of new disease
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RECIST Response Criteria
• CR – Complete Response – Disappearance of all target lesions
• PR – Partial Response – 30% reduction in SLD
• SD – Stable Disease – Neither response or progression
• PD – Progressive Disease – 20% increase in SLD – Presence of new lesion
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RECIST End Points
• Response – Timepoint response – Best overall response – Confirmation – 4-6 weeks (maybe required)
• Progression – Target SLD > 20% of nadir – Non-target – unequivocal progression – Date of progression
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RECIST V 1.0 and 1.1
• Uni-dimensional measurement • Tumor burden based on sum of diameters • Lesion classification scheme • Response categories
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Consistencies
RECIST V 1.0 and 1.1 Differences
V 1.0 (2000)
• Max 10 Target / Max 5 per organ
• ≥ 10 mm LD (spiral CT) ≥ 20 mm LD (other)
• Lymph Nodes not specified
V 1.1 (2009)
• Max 5 Target / Max 2 per organ
• ≥ 10 mm LD or 2x slice (extranodal)
≥15 mm SAD (nodal)
• Lymph Nodes >10 mm pathological
≥ 15 mm measureable
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RECIST V 1.0 and 1.1 Differences
V 1.0 (2000)
• CR – disappearance all lesions
• Targ-PD – SLD ≥ 20% of nadir
NTarg-PD – unequivocal progression
• New – not specifically
defined
V 1.1 (2009)
• CR – disappearance all extranodal lesions, nodal < 10 mm
• Targ-PD – SoD ≥ 20% and ≥ 5 mm from nadir
NTarg-PD – unequivocal progression w/substantial worsening
• New – unequivocal, not based on imaging tech.
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Central Review of Images
• Focus on consistency, repeatability • Limited reader pool • Training and review of cases • BICR - typical process: dual reader w/
adjudication – Two primary readers – Adjudication for discordance on end points
• Various quality processes incorporated
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BICR Process
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Site and Central Review
Imaging Site • Clinical focus • Do not generally utilize
RECIST • Not blinded • Access to all clinical data • Limited protocol training
Central Review • Focus on imaging • RECIST w/ limited pool of
readers • Blinded • Limited access to clinical
data • Image Review Charter
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Data Management Considerations
• RECIST version challenges • Site vs. Central Review data • Central Review
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RECIST Version Challenges
• Impact of migrating to v. 1.1 or maintaining v.1.0 and v. 1.1 studies
• Target lesions – Total number – Number per organ
• Lymph nodes • Sum of Diameters • Non-target progression • New Lesions
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RECIST Version Impact
• CRF Design • Derivation procedures • Edit checks • Data quality reviews • Emphasis on training and quality control • Focus on non-target progression and new
lesions
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Site vs. Central Review
• Comparison of endpoint results • Concordance noted in previous studies • Not based on consistent techniques • Intra-study comparisons should be established
early
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Site vs. Central Review (2)
• Develop processes to analyze: – Previous study data – Consistency of sites with central
• Distinguish trends • Establish “normal discordance” rate
– Identify outlier sites • Outlier sites can be reviewed further
– Re-training – Imaging technique
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Central Review Data
• Win-Loss Adjudication Rates • Intra-Reader Variability • Inter-Reader Variability • Monitor BICR discordance and adjudication • Analyze variability
– Tumor type – Intervention
• Evaluate quality between RECIST 1.0 and 1.1 studies
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Central Review Data (2)
• Establish normal levels of variability and discordance for v. 1.0 and v. 1.1
• Analyze for variables • Assess for suitability in future studies • Establish parameters for site and central
review data in future studies
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Conclusions
• RECIST 1.1 – attempt to improve and simplify • Comparisons between 1.0 and 1.1 data should be closely
monitored • Follow-on studies may remain at v. 1.1 • Fewer target lesions dictates attention to discordance and
variability • Non-target progression and new lesions should be reviewed
for adherence to standard • Incorporation of PET for confirmation should be considered • Protocol-specific requirements may drive DM process and
QA controls
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Acknowledgements
I’d like to thank the following people for their help in preparing this presentation
• Robert Ford • Eric Perlman • Tomomi Dyer
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