standards-driven oncology studies

© CDISC 2014

Kevin Lee

Clinical Data Strategist, Senior Consultant

Accenture Life Sciences

2

Standards-driven Oncology Studies

© CDISC 2014

Agenda

• Introduction of Oncology

• Oncology-specific Standards -

Response Criteria guidelines, CDISC

• Standards-driven Oncology Studies

• Conclusion/ Questions

3

© 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.

4

© 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 5

© 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)

6

© 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

7

© 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

8

© CDISC 2014

What are measured in Solid Tumor

Studies according to RECIST 1.1

• Tumor measurements in CT / MRI

Target

Non-target

New

9

© 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)

© 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 SUMDIAM Sum of Diameter 35 mm Cycle 1

001-01-001 Non-Target NT01 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

© CDISC 2014

What are measured in Lymphoma

Studies according to Cheson 2007


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

12

© 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)

© CDISC 2014

What are measured in Leukemia

Studies according to IWCLL 2008


Lymph Node

• Spleen and Liver Enlargement Assessment

• Bone Marrow Assessment

• Blood Count Assessment – Lymphocytes,

Neutrophils, Platelets, and Hemoglobin.

14

© 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

© 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)

16

© 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 SUMDIAM Sum of Diameter Measurement 70 mm Screening

USUBJID TRLI

NKID

TRTE

STCD

TRTEST TRCAT TROR

RES

TROR

RESU

VISIT


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

© 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

© 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

© 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

© 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

21

© CDISC 2014

Contact Information and Questions

22

Email address :

[email protected]

Linkedin Profile :

www.linkedin.com/in/HelloKevinLe

e/

Tweet : @HelloKevinLee

Slide share :

http://www.slideshare.net/KevinLe

e56

Blogs : HiKevinLee.tumbrl.com

http://www.linkedin.com/in/kevinlee1995/




standards-driven oncology studies

Healthcare