Each therapeutic area has its own unique data collection and analysis. Especially, Oncology has a unique way to collect and analyze the data. Response criteria of oncology studies dictate what to collect and analyze data. Three oncology studies follow the different guidelines standards. The Solid Tumor studies usually follow RECIST (Response Evaluation Criteria in Solid Tumor), Lymphoma studies usually follow Cheson and Leukemia studies follow study specific guidelines (IWCLL for Chronic Lymphocytic Leukemia, IWAML for Acute Myeloid Leukemia, NCCN Guidelines for Acute Lymphoblastic Leukemia and ESMO clinical practice guides for Chronic Myeloid Leukemia). CDISC also introduced data collection, analysis and coding standards. Oncology data are collected and stored as SDTM domains - TU (Tumor Identification), TR (Tumor Results) and RS (Response). CDISC also introduces oncology terminology. For example, tumor responses are CR (Complete Response), Partial Response (PR), Stable Disease (SD), Progression Disease (PD) and Not Evaluable (NE). Oncology studies also have different efficacy end-points. CDISC introduces oncology specific ADaM data set – Time to Event (--TTE) data set for OS (Overall Survival) and PFS (Progression Free Survival). Using response criteria and CDISC standards, oncology-specific standards will be define and integrated from protocol to analysis. These standards will also derive the automated oncology artifiact developments.

1. 1

2. © CDISC 2014
Kevin Lee
Clinical Data Strategist, Senior Consultant
Accenture Life Sciences
2
Standards-driven Oncology Studies

3. © CDISC 2014
Agenda
• Introduction of Oncology
• Oncology-specific Standards -
Response Criteria guidelines, CDISC
• Standards-driven Oncology Studies
• Conclusion/ Questions
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4. © CDISC 2014
Cancer Facts
• The word ‘cancer’ is related to the Greek word “crab” because
its finger-like projections were similar to the shape of the crab
• In 2010, the economic cost of the disease worldwide was
estimated at $1.16 trillion.
• One in eight deaths in the world are due to cancer.
• Cancer is the leading cause of death in developed countries.
• WHO predicts new cancer cases of 14 million in 2012 to 22
million in 2030 and cancer deaths from 8.2 million a year to 13
million annually.
• There are 28 million cancer survivors worldwide.
• Men who have never married are up to 35% more likely to die
from cancer than those who are married. In terms of surviving
cancer, women also benefited from being married, but to a
lesser extent.
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5. © CDISC 2014
FDA CDER NMEs and BLAs Approval
• 2012
 39 Approval
 13 Oncology (33 %)
• 2013
 27 Approval
 8 Oncology (30 %)
• 2014 ( as of the end of October)
 34 Approval
 7 Oncology (18%)
• Note: based on the reports of NMEs and BLAs approved by
CDER
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6. © CDISC 2014
Introduction of Oncology
• How are the oncology studies different from other studies?
 Tumor measurements and their response to drug
 Oncology-specific measurements for response criteria
(e.g., Liver and Spleen Enlargement, Bone Marrow
Infiltrate and Blood Counts)
 Oncology-diagnosis measurements (e.g.,
immunophenotype, performance status on ECOG,
staging)
 Toxicity (Lab and AE)
 Time to Event Analysis (e.g., OS, PFS, TTP and ORR)
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7. © CDISC 2014
Types of Oncology Studies and their
Response Guidelines Standards
• Masses of abnormal tissue that originate in organs or soft
tissues that typically do not include fluid areas and cysts. (e.g.,
breast cancer, liver cancer, pancreatic cancer and melanoma)
• RECIST (Response Evaluation Criteria in Solid Tumor) 1.1
Solid Tumor
• Cancer that starts in lymph nodes
• Cheson 2007
Lymphoma
• Cancer that usually begins in the bone marrow and result in
high numbers of abnormal white blood cells(lymphocytes).
• IWCLL 2008, IWAML 2003, NCCN Guideline 2012 on ALL, CML
ESMO Guidelines
Leukemia
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8. © CDISC 2014
CDISC Oncology-specific Standards
• SDTM
 TU : Tumor Identification
 TR : Tumor Results
 RS : Response
• ADaM
 -TTE : Time to Event Analysis Datasets
• CT
 Response Criteria : CR, PR, PD, SD
 Tumor Measurements : LDIAM, SUMDIA, LPERP,
AREA, SUMAREA, TUMSTATE
 Response : TRGRESP, NTRGRESP, NEWLPROG,
OVRLRESP, BESTRESP
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9. © CDISC 2014
What are measured in Solid Tumor
Studies according to RECIST 1.1
• Tumor measurements in CT / MRI
 Target
 Non-target
 New
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10. © CDISC 2014
Response Assessment at given visit for
RECIST 1.1
10
Response
(RS)
SUMDIA of
target lesions
by CT SCAN
(TR)
Non-target
lesions
assessment
(TR)
New lesions
(TR)

11. © CDISC 2014
Response Assessment at Cycle 1 for
RECIST 1.1 (TR to RS)
11
USUBJID TRGRID TRLI
NKID
TRTESTC
D
TRTEST TRORRE
S
TROR
RESU
VISIT
001-01-001 Target T01 LDIAM Longest Diameter 10 mm Cycle 1
001-01-001 Target T02 LDIAM Longest Diameter 10 mm Cycle 1
001-01-001 Target T03 LDIAM Longest Diameter 15 mm Cycle 1
001-01-001 Target SUMDIAM Sum of Diameter 35 mm Cycle 1
001-01-001 Non-Target NT01 TUMSTATE Tumor State PRESENT Cycle 1
001-01-001 Non-Target NT02 TUMSTATE Tumor State PRESENT Cycle 1
001-01-001 Non-Target NT03 TUMSTATE Tumor State PRESENT Cycle 1
USUBJID RSTESTC
D
RSTEST RSCAT RSORRES VISIT
001-01-001 TRGRESP Target Response RECIST 1.1 PR Cycle 1
001-01-001 NTRGRESP Non-target Response RECIST 1.1 NonCR/NonPD Cycle 1
001-01-001 NEWLPROG New Lesion Progression RECIST 1.1 N Cycle 1
001-01-001 OVRLRESP Overall Response RECIST 1.1 PR Cycle 1

12. © CDISC 2014
What are measured in Lymphoma
Studies according to Cheson 2007
• Tumor measurements in CT / MRI
 Lymph Node, Nodal Masses and Extra
Nodal Masses
• PET scan on lesions (to distinguish
viable tumor from fibrosis)
• Bone Marrow Assessment
• Spleen and Liver Enlargement
Assessment
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13. © CDISC 2014
Response Assessment at given visit for
Cheson 2007
13
Response
(RS)
Tumor
measurement
in SPD by CT
SCAN (TR)
Tumor
Assessment
by PET (TR)
Bone Marrow
Infiltrate (LB,
FA)
Spleen and
Liver
Enlargement
(PE)

14. © CDISC 2014
What are measured in Leukemia
Studies according to IWCLL 2008
• Tumor measurements in CT / MRI
 Lymph Node
• Spleen and Liver Enlargement Assessment
• Bone Marrow Assessment
• Blood Count Assessment – Lymphocytes,
Neutrophils, Platelets, and Hemoglobin.
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15. © CDISC 2014 15
Response
(RS)
Tumor
measurement
in SPD by CT
SCAN (TR)
Bone Marrow
(LB, FA)
Spleen and
Liver
Enlargement
(PE, FA)
Blood Counts
(LB)
Response Assessment at given visit
for IWCLL 2008

16. © CDISC 2014
Tumor Measurement in Oncology Studies
• Solid Tumor Studies (RECIST 1.1)
 > 10 mm by CT Scan
 One-dimensional measurement
(longest diameter) – 25 mm
 Sum of Diameters
• Lymphoma (Cheson 2007) and Leukemia (IWCLL
2008)
 Enlarged Lymph Nodes (Long axis > 15 mm)
 Two-dimensional measurement : product of longest
diameter and its greatest perpendicular axis (e.g., 25
mm * 15 mm =375 mm^2)
 Sum of Products of Diameters (SPD)
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17. © CDISC 2014
Tumor measurements – SDTM TR
17
USUBJID TRLI
NKID
TRTESTC
D
TRTEST TRCAT TROR
RES
TROR
RESU
VISIT
001-01-001 T01 LDIAM Longest Diameter Measurement 23 mm Screening
001-01-001 T02 LDIAM Longest Diameter Measurement 22 mm Screening
001-01-001 T03 LDIAM Longest Diameter Measurement 25 mm Screening
001-01-001 SUMDIAM Sum of Diameter Measurement 70 mm Screening
USUBJID TRLI
NKID
TRTE
STCD
TRTEST TRCAT TROR
RES
TROR
RESU
VISIT
002-01-001 T01 LDIAM Longest Diameter Measurement 25 mm Screening
002-01-001 T01 LPERP Longest Perpendicular Measurement 15 mm Screening
002-01-001 T01 AREA Area Measurement 375 mm^2 Screening
…..
002-01-001 SUMAR
EA
Sum of Products of
Perpendicular Diameters
Measurement 2560 mm^2 Screening
Solid Tumor according to RECIST 1.1
Lymphoma according to Cheson 2007

18. © CDISC 2014
Oncology-specific Standards
18
Response
Criteria
guidelines
RECIST 1.1
Cheson 2007
IWCLL 2008
Collection
Tumor
Measurement
Bone Marrow
Assessment
Spleen and
Liver
Enlargement
Assessment
Blood Counts
Response
Assessment
CDISC
SDTM : TU, TR,
RS
ADaM : --TTE
CT : CR, PR,
PD, SD,
LDIAM,
SUMDIA,
LPERP, AREA,
SUMAREA,
TUMSTATE,
TRGRESP,
NTRGRESP,
NEWLPROG
Analysis
OS, PFS,TTP,
ORR, DFS

19. © CDISC 2014
Standards-driven Oncology Studies
19
Protocol
Cheson
2007
Collection
Tumor
Measurement
SDTM
TR
Analysis
Progression
Free Survival
Time to Even
Analysis
ADaM
ADTTEPFS
Bone Marrow
Assessment
Spleen and
Liver
Enlargement
FA
TU
LB
Response
PE
RS
• Integration from Protocol to
Analysis through linking all
Standards
• End to End Standardization
• System using Standards
could automate oncology-
specific artifacts
developments

20. © CDISC 2014
Questions/ Conclusion
20
• What are oncology-specific standards?
 Response criteria guidelines.
 CDISC
• What are oncology-specific standards on each process?
 Protocol – oncology types and its response criteria guidelines
 Collection – tumor measurements & oncology-specific measurements
 SDTM – TU, TR, RS
 ADaM - TTE
 Analysis – Time to Event, Censor, Hazard Ratio and Kaplan Meier
plots
• How could these standards be utilized?
 Standards ( metadata / data ) driven oncology study development

21. © CDISC 2014
Additional Information on each
standards
• CDISC Journey in Solid Tumor Studies using RECIST
1.1 in http://www.slideshare.net/KevinLee56/cdisc-
journey-using-recist-11
• CDISC Journey in Lymphoma Studies using Cheson
2007 in http://www.slideshare.net/KevinLee56/cdisc-
journey-using-cheson-2007
• CDISC Journey in Leukemia Studies using IWCLL 2008
in http://www.slideshare.net/KevinLee56/cdisc-journey-in-
leukemia-studies-using-iwcll-2008
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22. © CDISC 2014
Contact Information and Questions
22
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