End to end standards driven oncology study (solid tumor, Immunotherapy, Leukemia, Lymphoma)
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The document discusses the importance of standards in oncology studies, highlighting the economic impact and increasing prevalence of cancer. It details various oncology-specific standards, such as response criteria guidelines and CDISC standards, necessary for conducting complex oncology studies effectively. The presentation concludes with an emphasis on the benefits of a standardized approach to enhance regulatory compliance and improve efficiency in oncology research.
End to end standards driven oncology study (solid tumor, Immunotherapy, Leukemia, Lymphoma)
- 1. End to End Standards driven Oncology Study Kevin Lee, Data Scientist
- 2. The Agenda ➢ Introduction of Oncology ➢ Why Standards? ➢ Oncology-specific Standards: Subtype, Response Criteria guideline, CDISC, Analysis ➢ Standards-driven Oncology Studies ➢ Final Thoughts / Q&A
- 3. 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. ➢ 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. ➢ Men who are married are up to 35% less likely to die from cancer than those who are not married.
- 4. FDA CDER NMEs and BLAs Approval ➢ 2012 - 39 Approval, 13 Oncology (33 %) ➢ 2013 - 27 Approval, 8 Oncology (30 %) ➢ 2014 - 41 Approval, 9 Oncology (22%) ➢ 2015 - 45 Approval, 13 Oncology (29%) ➢ 2016 – 22 Approval, 6 Oncology (27%) ➢ 2017 – 46 Approval, 12 Oncology (26%) Note: based on the reports of NMEs and BLAs approved by CDER
- 5. Many Pharma Companies Turns their Focus to Cancer ➢ A cornerstone to the success ➢ Unmet medical needs ➢ Profitable
- 6. TOP Oncology Companies J&J $4.1B BMS $4.5B Celgene $8.5B Novartis $10.4B Roche $25.7B Global oncology revenue by top ten pharmaceutical companies 2015 $107B in 2015 to +$150B in 2020
- 7. We live in the oncology drug development environment.
- 8. What do we feel about oncology studies?➢ ➢ Different ➢ Complex ➢ Difficult
- 9. Difference in Oncology 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 by ECOG, stage) ➢ Toxicity (Lab and AE) ➢ Time to Event Analysis (e.g., OS, PFS, TTP and ORR, Kaplan Meier Curves)
- 11. How to scale for oncology studies How to conduct complex oncology studies
- 12. The more complex problem is, the easier the winner be distinguished.
- 13. If ( x + 2 ) = 1000, what is x2 – 4 =? x = 1000 – 2 Complex problem for 6th grader
- 14. Complex Simple Standards How can we solve the complex problem?
- 15. Oncology- specific Standards ➢ Study Sub-type ➢ Response Criteria Guidelines ➢ CDISC ➢ Analysis
- 16. Oncology specific Standards • Oncology clinical trial study types Study Subtype • What to collect • How to measure tumor • How to determine responses Response Criteria Guideline • How to store/submit the data CDISC • How to analyze/report the data Analysis
- 17. Oncology Study Subtypes ➢ Solid Tumor ➢ Lymphoma ➢ Leukemia
- 18. Solid Tumor ➢ An abnormal mass of tissue that are not cysts or liquid ➢ Most common ➢ Type – breast, prostate, lung, liver and pancreatic cancer and melanoma
- 19. Lymphoma ➢ Cancer that starts in Lymph Node ➢ Tumor types: ➢ Enlarged Lymph Node ➢ Nodal Mases ➢ Extra Nodal Masses
- 20. Leukemia ➢ Cancer that usually begins in the bone marrow and result in high number of WBC ➢ Types: ➢ Chronic Lymphocytic Leukemia(CLL) ➢ Chronic Myeloid Leukemia(CML) ➢ Acute Lymphoblastic Leukemia (ALL) ➢ Acute Myeloid Leukemia (AML)
- 21. Response Criteria Guidelines Solid Tumor •RECIST (Response Evaluation Criteria in Solid Tumor) 1.1 •irRC(Immune- related RECIST) 2009 Lymphoma •Cheson 2007 •Cheson 2014 (2014 Lugano classification) Leukemia •IWCLL 2008 •IWAML 2003 •NCCN Guideline 2012 on ALL •CML ESMO Guidelines
- 22. CDISC Oncology specific Standards ➢ CDASH ➢ SDTM ➢ TU : Tumor Identification ➢ TR : Tumor Results ➢ RS : Response ➢ ADaM ➢ -TTE : Time to Event Analysis Datasets
- 23. CDISC Oncology specific Standards ➢ CT ➢ Response Criteria : CR, PR, PD, SD, irCR, irPR, irPD, irSD ➢ Tumor Measurements : LDIAM, SUMDIA, LPERP, AREA, SUMAREA, TUMSTATE ➢ Response : TRGRESP, NTRGRESP, NEWLPROG, OVRLRESP, BESTRESP
- 24. Oncology specific Analysis ➢ OS – Overall Survival ➢ PFS – Progression Free Survival ➢ ORR – Objective Response Rate
- 25. Standards Implemented Oncology Studies Study Subtypes Response Criteria Guidelines CDISC Analysis
- 26. Solid Tumor RECIST 1.1 Tumor Collection Use Case for Solid Tumor
- 27. RECIST 1.1 based data collections and response measurements Response (RS) Target lesions assessment (TU, TR) Non-target lesions assessment (TU, TR) New lesions (TU, TR)
- 28. USUBJID TULINKID TUTESTCD TUTEST TUORRES TULOC TUMETHOD VISIT 001-01- 001 T01 TUMIDENT Tumor Identification TARGET ABDOMEN CT SCAN Cycle 1 001-01- 001 T02 TUMIDENT Tumor Identification TARGET ABDOMEN CT SCAN Cycle 1 001-01- 001 T03 TUMIDENT Tumor Identification TARGET THYROID CT SCAN Cycle 1 001-01- 001 NT01 TUMIDENT Tumor Identification NON-TARGET LIVER CT SCAN Cycle 1 001-01- 001 NT02 TUMIDENT Tumor Identification NON-TARGET KIDNEY CT SCAN Cycle 1 001-01- 001 NT03 TUMIDENT Tumor Identification NON-TARGET SPLEEN CT SCAN Cycle 1 CDISC SDTM TU based on RECIST 1.1 data collection Key points to note: • Subject 001 has 3 target and 3 non-targets at Cycle 1 • TU.TULINKID is connected TR.TRLINKID using RELREC.
- 29. CDISC SDTM TR based on RECIST 1.1 data collection USUBJID TRGRID TRLINKID TRTESTCD TRTEST TRCAT TRORRES TRORRESU VISIT 001-01-001 Target T01 LDIAM Longest Diameter Measure ment 10 mm Cycle 1 001-01-001 Target T02 LDIAM Longest Diameter Measure ment 10 mm Cycle 1 001-01-001 Target T03 LDIAM Longest Diameter Measure ment 15 mm Cycle 1 001-01-001 Target SUMDIAM Sum of Diameter Measure ment 35 mm Cycle 1 001-01-001 Non-Target NT01 TUMSTATE Tumor State Qualitativ e PRESENT Cycle 1 001-01-001 Non-Target NT02 TUMSTATE Tumor State Qualitativ e PRESENT Cycle 1 001-01-001 Non-Target NT03 TUMSTATE Tumor State Qualitativ e PRESENT Cycle 1 • Sum of Diameter changed from 70 mm to 35 mm • No changes in non-target. • No new lesion
- 30. Response Assessment at Cycle 1 for RECIST 1.1 (TR to RS) USUBJID TRGRID TRLINKID TRTESTCD TRTEST TRORRES TRORRESU 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 RSTESTCD 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
- 31. Oncology Specific Efficacy Time to Event Analysis ➢ Time to Event ADaM datasets ➢ OS – Overall Survival ➢ PFS – Progression Free Survival ➢ Kaplan Meier Curves
- 32. Time to Event Analysis in ADaM USUBJID TRTP PARAM AVAL STARTDT ADT CNSR EVNTDESC 001-01-001 Study Drug 1 Time to Death (Days) 157 2011-01- 04 2011-06- 10 1 COMPLETED THE STUDY 001-01-002 Study Drug 2 Time to Death (Days) 116 2011-02- 01 2011-05- 28 1 LOST TO FOLLOW-UP 001-01-003 Study Drug 2 Time to Death (Days) 88 2011-02- 05 2011-05- 04 0 DEATH 001-01-004 Study Drug 1 Time to Death (Days) 102 2011-03- 20 2011-06- 30 1 ONGOING 001-01-005 Study Drug 1 Time to Death (Days) 101 2011-03- 26 2011-07- 05 1 ONGOING Overall Survival analysis by Kaplan Meier plot, log rank test or Cox Regression Analysis.
- 34. Oncology-specific Standards Library Response Criteria Guidelines RECIST 1.1 Cheson 2014 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, irCR, irPR, irPD, irSD, LDIAM, SUMDIA, LPERP, AREA, SUMAREA, TUMSTATE, TRGRESP, NTRGRESP, NEWLPROG Analysis OS, PFS,TTP, ORR, DFS Reporting – Tables, Listings and Graphs SAS Macros / R Packages Algorithms (Industry, Company) Documents Links Traceability Trainings SOP / WG
- 35. E2E Standards-driven automated process of Oncology Study Protocol Cheson 2014 Collection Tumor Measuremen t SDTM TR Analysis Progression Free Survival Time to Even Analysis Report ADaM ADTTEPFS Bone Marrow Assessment Spleen and Liver Enlargement FA TU LB Response PE RS
- 36. Why Standards driven process in oncology studies? ➢ Regulatory compliance ➢ Easy to understand ➢ Scalable ➢ 20/80 ➢ Time Saving ➢ Effective/ efficient
- 37. If ( x + 2 ) = 1000, what is x2 – 4 =? ( x + 2 ) ( x - 2 ) = 1000* 996 = 996,000 Standardized way to solve the complex problem
- 38. Final Thoughts ➢ Benefits of Standards in Oncology Studies ➢ Oncology-specific standards ➢ E2E Standards-driven process