A review of the two RECIST versions, noting similarities and differences, highlighting the improvements in v.1.1. This information is used to discuss how some of the challenges RECIST presents to data management can be addressed.

1. Comparison of RECIST 1.0
and 1.1 -
Impact on Data Management
Kevin Shea
Senior Solutions Architect
C3i, Inc.

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3. Objectives
• Describe RECIST
• Independent imaging review
• Manage external imaging data
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4. Agenda
• Background
• RECIST
– Overview
– Parameters
– RECIST V 1.0 vs. 1.1
• Independent Review
• Data Management Considerations
• Conclusions
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5. 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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6. 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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7. 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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8. 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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9. 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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10. 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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11. 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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12. 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

13. 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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14. 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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15. 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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16. BICR Process
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17. 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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18. Data Management Considerations
• RECIST version challenges
• Site vs. Central Review data
• Central Review
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19. 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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20. 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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21. 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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22. 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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23. 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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24. 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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25. 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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26. 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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