NCI Trial Complexity Elements & Scoring Model

1. NCI Trial Complexity Elements & Scoring Model A Step by Step Overview of Scoring a Cooperative Group Trial Updated April 16, 2009

2. Background Information In 2005, the National Cancer Advisory Board’s Clinical Trials Working Group Report, Restructuring the National Cancer Trials Enterprise, recommended several Operational Efficiency Initiatives, including: • Improve Cost-Effectiveness and Accrual Rates • Speed Trial Initiation at Sites http://integratedtrials.nci.nih.gov/Final CTWG report to the National Cancer Advisory Board, “Restructuring the National Cancer Clinical Trials Enterprise”

3. Background Information (continued) Some objectives of the Operational Efficiency Initiative included: • Align reimbursement with trial complexity as one component for an improved funding model • Develop a simple, standardized model to score various trial elements that are related to the most time-consuming tasks at participating sites

4. Background Information (continued) • A Working Group consisting of staff from the Cooperative Groups and the NCI was formed to address the trial complexity recommendation • Ten elements were identified and included in the complexity model and scoring system • Studies deemed complex per this scoring may be eligible to receive additional funds (beyond the base capitation)

5. Trial Complexity Elements • Elements subdivided into standard, moderate, or high levels of complexity

6. Scoring System for the Trial Complexity Model 0 1 2 0 1 2 0 1 2 0 Trial: X Final Trial Complexity Score = 9

7. More Detailed Explanation of Model • Each of these elements are defined in detail in the following slides • The model is further illustrated using NSABP-B40 as an example

8. The Trial Elements Element # 1 – Number of Study Arms Score 0 1 2 Level 0 – (standard): 1-2 study armsLevel 1 – (moderate): 3-4 study armsLevel 2 – (high): >4 study arms

9. The Trial Elements Element # 2 – Informed Consent Process 012 Score Level 0 – (standard): - Straightforward - 1-step randomization - Standard of Care vs. InvestigationalLevel 1 – (moderate): - Simple trial with placebo arm - Observation only arms - 2-step rando/registration - Requires assent processLevel 2 – (high): - Highly complex to explain to pts (predictive markers, crossover, extra mandated consents/tests forms) - Multiple steps / randomizations - Intra-operative randomization

10. NSABP-B-40 Element 1 > 4 arms,Therefore, Score = 2 Element 2 Simple & 1-step,Therefore, Score = 0

11. The Trial Elements Element # 3 – Registration or Randomization Steps 012 Score Level 0 – (standard): - 1-step registration / randomizationLevel 1 – (moderate): - Separate registration / randomization - Central pathology reviewLevel 2 – (high): - Multiple steps / randomizations - Intra-operative randomization - Complex central path review prior to randomization (ie. tumor genotyping)

12. The Trial Elements Element # 4 – Complexity of Investigational Therapy 012 Score Level 0 – (standard): - outpatient, single modality - similar to standard of careLevel 1 – (moderate): - combined modality - conventional chemo + biologics - simple inpatient treatmentsLevel 2 – (high): - therapy with high risk of toxicity (eg. gene transfer, stem cell tx) - special credentialing required

13. NSABP-B-40 Element 3 Pre-rando Path Review,Therefore, Score = 2 Element 4 Combination modality,Therefore, Score = 1

14. The Trial Elements Element # 5 – Length of Investigational Treatment 012 Level 0 – (standard): - regimens with defined # of cycles - routine/standard hormonal therapy Level 1 – (moderate): - lengthy regimens (until progression) - long hormone &/or maintenance rx (in addition to investigational agent)Level 2 – (high): - extended investigational treatment (eg. >6 mos, or q21 days x 22 cycles) Score

15. The Trial Elements Element # 6 – Feasibility & Personnel Impact 012 Score Level 0 – (standard): - 1 typical research team - one disciplineLevel 1 – (moderate): - moderate number of med disciplinesLevel 2 – (high): - high number of disciplines needed - > 2 disciplines with significant need for complex coordination of activities

16. NSABP-B-40 Element 5 Extended invest. agent >6 mos,Therefore, Score = 2 Element 6 Multi-disciplines, surg/chemo/path radiologyTherefore, Score = 2

17. The Trial Elements Element # 7 – Data Collection Complexity 012 Score Level 0 – (standard): - standard AE reporting - prospective, standard regulatory data - adjuvant study with standard CRFsLevel 1 – (moderate): - specific AE reported expedited means - retrospective addt’l regulatory data - prospective addt’l reg data (labs norm) - additional data (eg. concomitant meds) - RECIST criteria - multiple step studyLevel 2 – (high): - real time reporting of AE (> AdEERS) - real time data reporting - signif data under a SPA / registration trial - complex hematological - retro/prospect scan collection - central imaging review dictates rx decisions

18. The Trial Elements Element # 8 – Follow-up Requirements 012 Score Level 0 – (standard): - payment for follow-up data (Tier 1) - up to 2 years follow-upLevel 1 – (moderate): - payment for follow-up data (Tier 2) - 2 to 5 years follow-upLevel 2 – (high): - payment for follow-up data (Tier 3) - greater than 5 years follow-up - requiring rx and toxicity data for pts off study / post disease progression

19. NSABP-B-40 Element 7 RECIST measurements,Therefore, Score = 1 Element 8 > 5 yrs, complex scans Therefore, Score = 2

20. The Trial Elements Element # 9 A and B – Ancillary Studies Score Level 0 – (standard): - no studies - Ancillary / Correlative Science (Tier 1) - Ancillary Tiers for HRQOL, Ca Control, Health Services or other (Tier 1)Level 1 – (moderate): - Ancillary Tiers for Correlative Science (Tier 2, 3 I & II) - Ancillary Tiers for HRQOL, Ca Control, Health Services or other (Tier 2/3)Level 2 – (high): - Ancillary Tiers for Correlative Science (Tier 2, 3 III & 4) - Ancillary Tiers for HRQOL, Ca Control, Health Services or other (Tier 4) 12 0 For a description of the Ancillary Tiers, please visit:http://ctep.cancer.gov/protocolDevelopment/docs/tier_ancillary_studies.pdf

21. The Trial Elements Element # 10 – Participant Feasibility & Enrollment 012 Score Level 0 – (standard): - target population routinely seenLevel 1 – (moderate): - target population is uncommon cancer - target is common ca, but rare trials for - trial has highly selective eligibility (eg. molecular screening criteria)Level 2 – (high): - target population includes groups often underrepresented (elderly, minorities)

22. NSABP-B-40 Element 9 Moderate, Tier 2/3 on the Ancillary Tiers, Therefore, Score = 1 Element 10 Moderate molecular screening,Therefore, Score = 1

23. Enter the Complexity Score in Section 7 of the PSW Please note: in the event that a study amendment significantly alters a trial design, an updated complexity score can be submitted. PSW at: http://ctep.cancer.gov/protocolDevelopment/docs/psw.pdf

24. Authors of the Model ACOSOG Beth Martinez CALGB Kathy Karas Mary Sherrell COG Maura O’Leary CTSU Martha Herring Karen Kolbe Ruth Lambersky Donna Marinucci Steve Riordan ECOG Mary Steele Deb Strandberg GOG Larry Copeland Kia Neff Laura Reese Mary Sharp Betty Stonebraker NCCTG Aimee Fjelstad Desirae Sagdalen NCIC Belinda Vandersluis NSABP Walt Cronin Barbara Harkins Donna Szczepankowsi RTOG Tom Wudarski SWOG Abbie Brown Nathan Eriksen Marj Godfrey Joy Reilly Anne Schott Zoe Vanella NCI Robyn Burns (EMMES) Andrea Denicoff Shanda Finnigan Steve Friedman LeeAnn Jensen Elise Kreiss Jean Lynn Joan Mauer Lori Minasian Gary Smith Cynthia Whitman