Mitchell Schnall MD, PhD Professor of Radiology University of Pennsylvania ACRIN Network Chair

1. State of ACRIN : Working to secure our future Mitchell Schnall MD, PhD Professor of Radiology University of Pennsylvania ACRIN Network Chair

2. Review of ACRIN Scientific Strategy • Develop and evaluate strategies for imaging surveillance of populations at high risk for cancer. • Develop and validate imaging biomarkers to predict and monitor therapy response. • Evaluate the effectiveness of imaging directed therapy on improving patient management and associated outcomes. This includes comparative effectiveness studies of existing imaging methods.

3. Steering Committee Network Chair Mitchell Schnall, MD, PhD University of Pennsylvania Deputy Chairs Anat/Fxn Imaging Denise Aberle, MD UCLA Molecular Imaging Barry Siegel, MD Washington University Biostatistical & Data Management Center Chair Constantine Gatsonis, PhD Brown University Organization ACRIN Organizational Chart ACRIN Foundation Jim Thrall, MD MGH NCI Jim Tatum, MD Cancer ImagingProgram Leadership Council Mitchell Schnall, MD, PhD University of Pennsylvania Advisory Panel Daniel Sullivan, MD Duke University Data & SafetyMonitoring Committee Daniel Sargent, PhD Mayo Clinic Network Administration Charles Apgar ACR Philadelphia Outcomes & Economics Core Laboratory William Black,MD Dartmouth Medical School Non NCI Disease Site Committees Scientific Support Committees Support Committees Disease Site Committees Cardiovascular Pam Woodard, MD Washington University Breast Connie Lehman, MD University of Washington Informatics Daniel Rubin, MD Stanford University Patient Advocacy Barbara LeStage, MHP Media / Publications and Dissemination Committee Vice Chair Laurie Fajardo, MD University of Iowa Institutional Participants Committee Vice Chair Chris Comstock, MD Memorial Sloan Kettering Quality Control Mitchell Schnall, MD, PhD University of Pennsylvania ACRIN PA Mitch Schnall, MD, PhD University of Pennsylvania Abdominal Terri Wong, MD Duke University Core Laboratory PET/Nuc Medicine Barry Siegel, MD Washington University MR/CT Mark Rosen, MD, PhD University of Pennsylvania Research Associates Wendy Smith, RT Rhode Island Hospital ACRIN Projects Mitch Schnall, MD, PhD University of Pennsylvania Gynecological Susanna Lee, MD Massachusetts General Hosp Special Populations Elizabeth Patterson, MD Head/Neck/CNS Greg Sorensen, MD MassachusettsGeneralHosp Neuroscience Greg Sorensen, MD Massachusetts General Hosp Ultrasound Working Group Barry Goldberg, MD Thomas Jefferson University Thoracic Caroline Chiles, MD Wake Forest University Experimental Imaging David Mankoff, MD University of Washington

4. Progress over Past year • Have 12 studies open to accrual • 3 ACRIN PA (4005 accrued 663 to date) • 9 ACRIN CORE (Modest Accrual) • 4 concepts approved, preparing to open, 4 concept submitted • Cancer Center imaging qualification initiative under way • Successfully competed for a grant from AHRQ • CER of CTA vs SPECT in the initial evaluation of stable angina (10 million)

5. Open Studies • 4003/4004: Evaluation of a Novel PET Radiopharmaceutical to Identify Patients with Alzheimer’s Disease • 4005: CT Coronary Angiogram vs Traditional Care for Low-Risk ED Pts with Potential Acute Coronary Syndromes • 6671: Cervical and Endometrial Cancers: Staging with PET/CT • 6678: Lung Cancer: Evaluation of Treatment Response with PET • 6682: Cervical Cancer:64Cu-ATSM PET/CT Assessment of Tumor Hypoxia • 6684: Newly Diagnosed Glioblastoma: Assessment of Tumor Hypoxia with FMISO PET, DCE MRI and MRS • 6685: Staging of Head and Neck Cancer: Assessment of FDG-PET/CT and the Impact on N0 Neck Surgical Treatment

6. Open Studies Cont. • 6686: Newly Diagnosed Glioblastoma: Substudy of Tumor Assessment with Advanced MRI • 6687: 18F-Fluoride PET as a Biomarker for Prostate Cancer and Bone Metastases • 6688: Phase II Study of FLT PET in Invasive Breast Cancer • 6689:Newly Diagnosed Glioblastoma: Substudy of Tumor Assessment with FLT PET and DCE MRI and MRS

7. Unique ACRIN Accrual Challenges • Studies of markers for clinical trials associated with less immediate impact on care, reducing site/patient enthusiasm • Complex studies • Operational challenges at site level (scheduling!) • Funding limitations • The “VEN” diagram problem Clinical Imaging

8. Approaches • More emphasis on site / patient accrual in review • Reduce study complexity • Earlier involvement of RA committee and advocates • Collaboration with treatment groups • Complement portfolio with clinical diagnostic studies (6685/6690) • Accrual Strategy Session: Friday 1:00-2:30

9. Critical Time for ACRIN • Nearing preparation for the next grant cycle • IOM report calling for reorganization and consolidation of the groups • OEWG implements hard timelines • Change in leadership at NIH, NCI and CIP • Clinical effectiveness of imaging relative to cost and exposure being challenged • Funding opportunities changing (NLST, ARRA ending; CER/PCORI starting)

10. OEWG Guidelines Timeline pauses if industry negotiations cause delay If registration trial, FDA review in 30 days Concept Protocol Protocol revision/review Protocol Concept revision/ Review review cycles review cycles development Forms development 0 30 90 300 180 210 Time (days)

11. Other Notable OEWG Activities • Cost effectiveness sub-study funding now available through the BIQSFP mechanism • Imaging Steering committee to be established • Medidata license • Financial analysis of cooperative groups complete

13. IOM Study • Requested by NCI to address several issues regarding the NCI clinical trials program • The infrastructure has not evolved to adequately incorporate the rapid pace of scientific discovery • The process is inefficient (delays, incomplete trials) • Government oversight overly complex • Funding is inadequate • Industry trials are moving overseas • Biomarker driven selection of appropriate treatment will enhance outcomes (at increased cost)

14. Key Recommendations • Increase speed and efficiency of study development and conduct • Consolidate “Front office” through peer review • Consolidate “Back office”/improve operations • Streamline regulation • International Coordination/Collaboration • Innovation in science and design • Central tissue (imaging) repositories • Innovative trials including biomarkers • National standards for imaging procedures and biomarker tests

15. Key Recommendations Improve trial prioritization, selection, and support Evaluate role of NCI Increase accrual volume Increase funding to cooperative group program Incentivize participation Support investigators Cover cost of patient care in clinical trials

16. Next Steps • NCI considering response • Input from NCAB expected • Discussed at CTAC • 50% of the costs of trials are contributed by “volunteerism” some related to group association • Consolidation unlikely to reduce cost • Cooperative group leadership developing proposal • Multiple professional societies etc weighing in (generally in support of groups)

17. Leadership Transition • New leadership of NCI comes from a bench science background • Focused on removing barriers to translation of genomics (and other “omics”) to medical care • Highlight value of correlative science in clinical trials • Transition of leadership at CIP • Paula Jacobs to serve as interim Associate Director • Lalitha Shankar Chief of the Clinical Trials Branch

18. Positioning of ACRIN • Unique niche in trials system • We are collaborative: RTOG, GOG, ACOSOG, NCCTG, SWOG, CALGB, QARC, ABTC, ECOG • Biomarkers are important part of NCI vision • However: • Can we accrue these trials? • Whose science is it? • Strategic alliances with treatment groups • Is there support for trials of contemporary questions in radiology practice? • AHRQ/PCORI to support CER research • Compete for CER research funding (RESCUE model)

19. Challenges for 2011 • Accrue / publish open studies • Simplify studies to increase chances for success • Continue to nurture international collaborations • Develop strategic partnerships with therapy groups around marker development • Harmonize data management and IT with the rest of the cooperative groups • Continue to diversify funding sources

20. Continue to build support for ACRIN in imaging and cancer community Continue to expand internationally Enhance site support Maintain a pipeline of trials in development Challenges for 2011