Changing the Clinical Trials System: An NCI Update. Michigan Cancer Consortium Annual Meeting November 5, Marge Good, RN, MPH, OCN

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1 Changing the Clinical Trials System: An NCI Update Marge Good, RN, MPH, OCN Michigan Cancer Consortium Annual Meeting November 5, 2014 These slides are the property of the presenter. Do not reproduce without express written consent. 1

2 Points to be Discussed Background Overview of changes to NCI clinical trials system Cooperative groups to NCTN Efforts to improve efficiencies CTSU Common data management systems NCI CIRB New precision medicine treatment trials CCOP/MBCCOP/NCCCP to NCORP These slides are the property of the presenter. Do not reproduce without express written consent. 2

3 Interventional Clinical Trials in U.S. Cancer Incidence 1.6 million cancers annually in U.S. NCI-Network treatment trials - ~20,000 NCI- Network control/prevention - ~5,000 NCI Investigator-initiated trials - ~ 20,000 Industry - ~ 50,000 Other funders - ~ 5,000 About 6% of patients diagnosed with cancer annually go on trial in U.S. These slides are the property of the presenter. Do not reproduce without express written consent. 3

4 Selected Major Accomplishments of Program: Over 30 Practice-Changing Clinical Trials including therapeutic agents and other modalities, with 4 announced in first 6 months of 2011 ACOSOG-Z0011 Surgery: SLND not inferior to Axillary Dissection in SLN+ BC NCIC-CTG MA.20 RT: Regional Nodal RT reduces LR & improves DFS in Node+ BC COG-AALL0232 Pediatrics: High Dose MTX improves EFS in pediatric ALL RTOG Multimodality: Short-term ADT with RT improves OS in prostate cancer Over 10 FDA Indications - New Oncology Agents (Yr FDA Approval) Bevacizumab CRC (2006); NSCLC (2006); Renal Cell Cancer (2009) Imatinib mesylate Pediatric CML (2006); Adjuvant GIST (2008) Nelarabine T-ALL and T-LBL (2005) Rituximab Diffuse Large B-cell Lymphoma (2006); Follicular NHL (2006) Trastuzumab - Adjuvant Therapy for Early-stage Her2+ Breast Cancer (2006) Thalidomide Newly Diagnosed Multiple Myeloma (2006) Anti-GD2 Antibody (ch14.18) in Neuroblastoma (BLA Currently in Preparation) These slides are the property of the presenter. Do not reproduce without express written consent. 4

5 Overview of Changes to the NCI Clinical Trials System National Clinical Trials Network (NCTN) Trial Efficiency and Quality Support Infrastructure Development NCI Central IRB New Trial Designs NCI Community Oncology Research Program (NCORP) These slides are the property of the presenter. Do not reproduce without express written consent. 5

6 Why Support a Standing, Publicly Funded Clinical Trials Network? Advance science & patient care, especially on important research questions that are not priorities for industry, including evaluating: Integration of new agents into standard regimens Combinations of novel agents developed by different sponsors Multi-modality regimens (e.g., Surgery, Radiotherapy, IP therapy) Therapies for pediatric cancers, rare cancers, and uncommon presentations Screening, diagnostic, & prevention strategies Optimal duration and dose of drugs & radiotherapy Different treatment approaches already approved for clinical care Trials oriented toward disease-management, not agent- specific or limited by marketing constraints, with inclusion of research related to: Correlative science, Imaging, Quality of Life, Symptom Management Special Populations (e.g., analyis by sex, age, race/ethnicity) Extensive, direct involvement of entire oncology community in the design, development, & conduct of trials with data-sharing of clinical data and banked biospecimens These slides are the property of the presenter. Do not reproduce without express written consent. 6

7 Progress Toward Consensus Goals for a Transformed System Improve speed & efficiency of development & conduct of trials Implementation of operational efficiency timelines Implementation of Common Data Mgt System for all trials Incorporate innovative science and trial design Implementation of BIQSFP program for integral & integrated biomarkers, imaging, and quality of life studies in trials Encourage randomized phase 2 trials Improve trial prioritization, selection, support, & completion Disease-specific and specialty Steering Committees prioritize trials Implementation of slow accrual guidelines Ensure participation of patients & physicians in system Pilot initiatives for increased reimbursement for phase 2 and 3 trials Pilot initiatives to assess physician & patient feedback on trials to enhance accrual These slides are the property of the presenter. Do not reproduce without express written consent. 7

8 Strategic Planning for the New NCTN Program Treatment trial accrual has been dominated by Breast and GI Cancer trials, especially large adjuvant trials, over past decade The new funding model will require Network organizations and Steering Committees to monitor the balance of trials prioritized for development and help develop a strategic consensus about the diseases in which to encourage more trials as scientific opportunities arise New review criteria should facilitate more trials in disease areas which have been typically underrepresented, relative to their incidence, and portfolio balance will be monitored closely by CTAC s NCTN Strategic Planning Subcommittee to ensure that scientific opportunities in less common tumors are not missed These slides are the property of the presenter. Do not reproduce without express written consent. 8

9 Structure of Program: As of January 2011 These slides are the property of the presenter. Do not reproduce without express written consent. 9

10 Progress: New Program with 4 adult & 1 pediatric Network Groups Peer-review focused on overall research strategy, collaboration, & operational efficiency Support for trials designed with integral molecular screening Integrated translational science & Lead Academic Participating Site awards Core RT/Imaging services Strategic planning & trial prioritization at national level Adult and pediatric Central IRBs Common IT data mgt system Centralized 24/7 patient registration IOM Goal 1: Improve Speed & Efficiency of the Design, Launch, and Conduct of Clinical Trials Recommendation 1: Facilitate some consolidation of Group front-office operations by reviewing & ranking Groups with defined metrics on similar timetable & by linking funding to review scores NCI Division of Extramural Activities Review New Program: NCI National Clinical Trials Network (NCTN) CTAC Clinical Trials Strategic Planning Subcommittee NCI Disease/Imaging Steering Committees: Evaluation/Prioritization of Trials Network Research Support Services Network RT & Imaging Core Services Centers Canadian Network Adult Group #2 Ops & Stats Network Group Integrated Translational Science Centers 4 Adult and 1 Pediatric U.S. Network Groups Adult Group #1 Ops & Stats Adult Group #3 Ops & Stats Pediatric Ops & Stats Tumor Banks Adult Group #4 Ops & Stats NCI National Clinical Trials Network Network Lead Academic Participating Sites CCOPS & MB-CCOPs Other Academic Centers Community Practices International Members Administrative Support Services NCI Central IRB CTSU Central Access to NCI Clinical Trials (Cancer Trials Support Unit) These slides are the property of the presenter. Do not reproduce without express written consent. 10

11 Overview of the NCTN Program 2,400 Institutions 14,000 Investigators 21,000+ patients enrolled/year 120 phase 3 & 215 early phase trials open for enrollment at any one time 11 Enrollment to Adult & Pediatric Trials All Phases: Treatment & Primary Imaging Trials FY2007 FY2008 FY2009 FY2010 FY2011 FY2012 FY ,619 25,682 29,221 23,446 19,775 21,164 21,810 These slides are the property of the presenter. Do not reproduce without express written consent. 11

12 CTSU: A National Infrastructure for Patient Enrollment on NCI-Supported Clinical Trials Cancer Trials Support Unit (CTSU) has expanded centralized administrative & regulatory functions for clinical trials Over 70,000 patients enrolled via CTSU since 1999 Cross-Group accrual available for all phase 3 & select phase 2 tx trials Expansion of services to other NCI trial networks & collaborative trials Provides a range of critical services in support of the national system As of 2011, 24/7 enrollment for all Group Tx trials Patient registration Accrual reimbursement Protocol Coordination Clinical Data Operations Regulatory Support Service Financial Management Site Auditing Site QA CTSU Help Desk CTSU Web Site Education & Trial Promotion These slides are the property of the presenter. Do not reproduce without express written consent. 12

13 Common IT Data Management System (CDMS) Electronic tool(s) or processes that support Data collection: Remote Data Capture (RDC) Data coding: Standard libraries - Common Toxicity Criteria Data management: Discrepancy, delinquency, communication, correction & preparation of data for analysis Core benefits of CDMS on NCI-supported multicenter trials Reduces training costs & cost of overall cost of data management Reduces risk of data delinquency and/or discrepancy Reduces time/effort to correct/complete data Reduces delays in obtaining Science and Safety results & improves trial management & decisionmaking Other Benefits to NCI-supported multicenter trials Supports/complements transformation of Groups into new Network program Meets FDA & other Federal requirements for e- data capture, security & transfer Promotes data sharing Sets stage for further infrastructure improvements such as integration with expedited Serious AE reporting, remote auditing, electronic filing for FDA reports These slides are the property of the presenter. Do not reproduce without express written consent. 13

14 Implementation of Operational Efficiency Timelines Absolute = 540 Absolute = 450 Protocol terminated if absolute timelines not achieved These slides are the property of the presenter. Do not reproduce without express written consent. 14

15 NCI Central Institutional Review Board (CIRB) NCI s CIRB established in 1999 Mission: reduce the administrative burden on local IRBs and investigators by partnering with local IRBs to provide a high level of protection for study participants in NCI s Cooperative Group clinical trials. Current Boards: Adult Late Phase Emphasis Board Adult Early Phase Emphasis Board Pediatric Treatment & Cancer Control Board Current as of 7/31/2014 These slides are the property of the presenter. Do not reproduce without express written consent. 15

16 CIRB Profile - Enrollment Enrollment is open to IRBs reviewing Cooperative Group/NCTN Studies Number of Signatory Institutions Enrolled 350 Number of Institutions using Adult CIRB only 174 Number of Institutions using Pediatric CIRB only 37 Total Number of Enrolled Signatory Institutions, Affiliates, and Components 1,844 Number of NCI Designated Cancer Centers 47 Number of CCOPs 35 Number of MBCCOPs 10 These slides are the property of the presenter. Do not reproduce without express written consent. 16

17 CIRB Profile - Utilization Number of Studies Available on CIRB menu 351 Adult 221 Pediatric 130 Total Studies ever opened in Independent Model 14,529 Current as of 7/31/2014 These slides are the property of the presenter. Do not reproduce without express written consent. 17

18 U.S. Clinical Trials Treatment Sites Current as of 7/31/2014 CTEP Total Sites = 2,109 (# of Sites by State that Currently have Patients Enrolled on an Open Trial) CIRB Total Sites = 1,844 (# of CIRB enrolled Signatory Institutions, including affiliates and components) These slides are the property of the presenter. Do not reproduce without express written consent. 18

19 Metrics: Adult Initial Review Timeline Comparison Timeline to Adult CIRB Approval of Initial Reviews (Median Number of Days) (N=12) * (N=15) C-PIRAT implemented 05/01/ (N=16) 98 Number of Days (N=7) 2012 (N=12) 2013 (N=4) Time from CIRB Receipt to Review Time from CIRB Review to Approval Time from CIRB Receipt to Approval These slides are the property of the presenter. Do not reproduce without express written consent

20 NCI Adult & Pediatric CIRB Independent Model Received full accreditation by Association for Accreditation of Human Research Participant Protection Programs (AAHRPP) in December 2012 New institutions being added and current institutional members of CIRB being transitioned to independent model Participation in NCTN trials will require use of CIRB (with waiver exemption possible for sites demonstrating similar local IRB review timelines) Being expanded to include study review of other NCIsupported clinical trials networks & potential expansion to other types of studies Experimental Therapeutics Clinical Trials Network DCP-supported cancer control & preventions studies These slides are the property of the presenter. Do not reproduce without express written consent. 20

21 Cancer Prevention and Control CIRB How will it work? Structured within NCIs CIRB Initiative 4 th Board Adult Late Phase Emphasis Board Adult Early Phase Emphasis Board Pediatric Treatment & Cancer Control Board Part of NCIs AAHRPP-accredited Human Research Protection Program Follows same SOPs, processes and procedures These slides are the property of the presenter. Do not reproduce without express written consent. 21

22 Cancer Prevention and Control CIRB CIRB Operations Office contract Full operations, administrative and regulatory support from the contractor RFP released May 2014 Award September 2014 DCP Board begins early 2015 New protocols: initial review, amendments, continuing review These slides are the property of the presenter. Do not reproduce without express written consent. 22

23 Molecular Profiling in NCI-sponsored Clinical Treatment Trials Entrance of molecularly targeted agents into clinical trials. Trials will depend on defining targets and developing biomarkers. SWOG Lung-MAP (MASTER) Alliance/ECOG ALCHEMIST ECOG MATCH Exceptional Responders Initiative These slides are the property of the presenter. Do not reproduce without express written consent. 23

24 NCI Community Oncology Research Program Overview (NCORP) A Collaboration of NCI s Divisions of Cancer Prevention, Cancer Control and Population Sciences, Cancer Treatment and Diagnosis, and Center to Reduce Cancer Health Disparities These slides are the property of the presenter. Do not reproduce without express written consent. 24

25 What is NCORP? A community-based research program Builds upon the scope and activities of NCI s previously supported community networks NCI Community Clinical Oncology Program (Community Clinical Oncology Programs, Minority-Based Clinical Oncology Programs, Research Bases) NCI Community Cancer Centers Program Integrates these prior networks into one new program to preserve and enhance cancer research in the community Receives support through UG1 grant awards Funding of $93 million annually for 5 years These slides are the property of the presenter. Do not reproduce without express written consent. 25

26 Why Support Cancer Research in the Community Setting? Majority of cancer care is provided in the community Increase the generalizability of study findings Access to large diverse patient populations Access to real world healthcare delivery settings Testing feasibility of new interventions/processes Accelerates the uptake of evidence-based practice, new interventions, and processes into routine practice These slides are the property of the presenter. Do not reproduce without express written consent. 26

27 Past Research Achievements in the Community Setting Contributed 40% of the overall treatment accrual to NCI s clinical trials network Significant minority population accrual MBCCOP: 63% CCOP: 10% Incorporated cancer control, symptom management, risk reduction, and toxicity management Engaged primary care providers into the management of cancer/at-risk-of cancer patients Adopted new agents and technologies into clinical practice These slides are the property of the presenter. Do not reproduce without express written consent. 27

28 NCORP Overall Goal To bring cancer clinical trials and cancer care delivery research (CCDR) to people in their own communities, thereby generating a broadly applicable evidence base that contributes to improved patient outcomes and a reduction in cancer disparities. These slides are the property of the presenter. Do not reproduce without express written consent. 28

29 NCORP Structure NCORP consists of 3 components: Research Bases Community Sites Minority/Underserved Community Sites These slides are the property of the presenter. Do not reproduce without express written consent. 29

30 NCORP Structure (Cont.) 7 Research Bases Serve as NCORP research hubs Design and conduct multi-center cancer prevention, control and screening/posttreatment surveillance clinical trials and Cancer Care Delivery Research (CCDR) studies These slides are the property of the presenter. Do not reproduce without express written consent. 30

31 NCORP Structure (Cont.) 34 Community Sites Accrue participants to NCORP clinical trials and CCDR; NCTN treatment and imaging trials and quality of life studies 12 Minority/Underserved Community Sites Accrue participants to NCORP clinical trials and CCDR; NCTN treatment and imaging trials and quality of life studies Have a patient population comprising at least 30% racial/ethnic minorities or rural residents These slides are the property of the presenter. Do not reproduce without express written consent. 31

32 NCORP Sites These slides are the property of the presenter. Do not reproduce without express written consent. 32

33 NCORP Sites: Components & Subcomponents These slides are the property of the presenter. Do not reproduce without express written consent. 33

34 NCORP Sites: Components & Subcomponents These slides are the property of the presenter. Do not reproduce without express written consent. 34

35 State of Michigan NCORP Coverage These slides are the property of the presenter. Do not reproduce without express written consent. 35

36 NCORP Network Characteristics 842 Components and subcomponents Health Care Systems Kaiser, Essentia, Aurora, Catholic Health Initiatives, Geisinger, Sanford, Nemours 7 Consolidated community programs Multiple cancer care delivery research sites within 46 programs These slides are the property of the presenter. Do not reproduce without express written consent. 36

37 NCORP Approach Design and conduct: Cancer prevention, control, and screening/post-treatment surveillance clinical trials Multi-level CCDR studies (e.g., patient, clinician, organization, system level) Enhance patient/provider access to treatment/imaging trials under the reorganized NCTN These slides are the property of the presenter. Do not reproduce without express written consent. 37

38 NCORP Approach (Cont.) Facilitate minority/underserved participation in clinical research Increase integration of disparities research questions across all study types/settings Integrate the expertise of primary/specialty care providers, health services and behavioral researchers with oncologists Accelerate knowledge transfer into clinical practice and healthcare systems/organizations These slides are the property of the presenter. Do not reproduce without express written consent. 38

39 NCORP Research Areas CCDR is an area of research expansion These slides are the property of the presenter. Do not reproduce without express written consent. 39

40 Cancer Care Delivery Research (CCDR) A multidisciplinary field of scientific investigation Examines how social factors, financing systems, organizational structures/processes, health technologies, and healthcare provider and individual behaviors affect: Cancer outcomes Access to and quality of care Cancer care costs Health and well-being of cancer patients and survivors NCORP s CCDR focus encompasses individuals, families, organizations, institutions, providers, communities, populations, and their interactions. These slides are the property of the presenter. Do not reproduce without express written consent. 40

41 Why Include Cancer Care Delivery Research in NCORP? Precision medicine is adding to the complexity of care Rapidly changing health care system Affordable Care Act Accountable Care Organizations Merging of practices Diverse, often fragmented, provision of care Urgent need for evidence about how these changes influence: Patient outcomes Disparities in care The dynamic healthcare environment demands a better understanding of routine oncology care delivery. These slides are the property of the presenter. Do not reproduce without express written consent. 41

42 NCORP Disparities Research Persistent disparities exist Cancer incidence, mortality, and quality of life Access to and quality of care Increase in the number of minority/underserved populations Determinants of disparities (social factors, health care systems, co-morbidities) disproportionately affect outcomes for underserved populations Challenge to fully and equitably implement new technologies and targeted therapies for the underserved Further research is needed to reduce disparities and improve outcomes for underserved populations across the continuum of care These slides are the property of the presenter. Do not reproduce without express written consent. 42

43 Disparities Research Crosses All NCORP Areas Addresses clinical trial and CCDR questions related to the more serious, prevalent cancers and cancer-related problems which disproportionately affect racial/ethnic minorities and other underserved populations Studies to enhance racial/ethnic minority and underserved participation in clinical trials Studies addressing determinants of disparities (e.g. social and health care system factors, comorbidities, and genomics) Studies that evaluate differential outcomes in minority/underserved populations These slides are the property of the presenter. Do not reproduce without express written consent. 43

44 NCORP Clinical Trials Research Agenda Type Cancer Prevention Cancer Control Cancer Screening NCTN Treatment Trials Focus Identify/evaluate interventions to reduce cancer risk and incidence Reduce incidence/co-morbidity of cancer and its treatment, enhance quality of life Evaluate early diagnosis interventions and cancer recurrence Identify secondary endpoints of health-related quality of life or patientreported outcomes These slides are the property of the presenter. Do not reproduce without express written consent. 44

45 Examples of Topics of Interest Mechanisms of symptoms and treatment-related toxicities Observational and longitudinal studies to understand natural history of symptoms and toxicities Post-treatment surveillance (e.g., tumor markers of recurrence, optimal screening modalities) Under and over-diagnosis Management of pre-cancerous lesions These slides are the property of the presenter. Do not reproduce without express written consent. 45

46 NCORP Organizational Structure These slides are the property of the presenter. Do not reproduce without express written consent. 46

47 NCTN and NCORP Relationship NCTN Focus (CTEP): Late-Phase Treatment Trials Advanced Imaging Trials NCORP Focus (DCP): Cancer Prevention and Control Trials CCDR Comparative Effectiveness Research Site participation in treatment, cancer control/ prevention clinical trials & CCDR NCTN / NCORP CENTRALIZED FUNCTIONS These slides are the property of the presenter. Do not reproduce without express written consent. 47

48 Vision for Transformation of NCI Clinical Trials System 2014 and Beyond Provide essential infrastructure for NCI trials in treatment, control, screening, diagnosis and prevention across all NCI research programs Launch trials rapidly & complete accrual per defined guidelines through integrated national network of sites Promote user-friendly, harmonized processes to extramural community (investigators, patients, advocates, & industry) Provide functional platforms to perform large scale testing of increasingly smaller subsets of molecularly-defined cancers & focus on questions not well supported in a commercial environment These slides are the property of the presenter. Do not reproduce without express written consent. 48

49 These slides are the property of the presenter. Do not reproduce without express written consent. 49