Comparative Effectiveness Research An Update

1. Comparative Effectiveness Research An Update Robert T. Croyle, Ph.D., Director NCI Division of Cancer Control and Population Sciences NCI Cancer Center Directors Annual Retreat May 14, 2010

2. Presentation Overview • Overview • CER and ARRA • ARRA Funded CER Projects • FY 2010 CER priorities and funding opportunities • Other efforts to conduct and support CER • Key issues: CER and cancer research • CER in the policy spotlight

3. CER overview

4. Importance of CER • February, 2009: $1.1 billion in funds through ARRA • CER and evidence-based medicine addressed in healthcare reform law • In total dollars, NIH funds the largest amount of CER in HHS • The cancer research community has substantial experience, expertise, and infrastructure relevant to CER

5. HHS Definition of CER The conduct and synthesis of research comparing the benefits and harms of different interventions and strategies to prevent, diagnose, treat and monitor health conditions in “real world” settings. The purpose of this research is to improve health outcomes by developing and disseminating evidence-based information to patients, clinicians, and other decision-makers, responding to their expressed needs, about which interventions are most effective for which patients under specific circumstances. • To provide this information, comparative effectiveness research must assess a comprehensive array of health-related outcomes for diverse patient populations and subgroups. • Defined interventions compared may include medications, procedures, medical and assistive devices and technologies, diagnostic testing, behavioral change, and delivery system strategies. • This research necessitates the development, expansion, and use of a variety of data sources and methods to assess comparative effectiveness and actively disseminate the results.  

6. Types of CER • Some randomized clinical trials • e.g. practical head-to-head trials • Observational studies • Modeling • Systematic reviews

7. Emphases in CER • Patient representativeness • Variation across practice settings • Physician and patient behavior outside of RCT setting • Clinical utility • Role of incentives, systems and policies • Patient-reported outcomes

8. CER & ARRA

9. Allocation of ARRA CER Funds

10. NIH and ARRA CER • Active leadership role in Federal Coordinating Council and the HHS Coordinating and Implementation Team (CER CIT) • NIH CER Coordinating Committee facilitates NIH CER programs and develops funding recommendations for the NIH Director • CER CC Subcommittees to coordinate and integrate Inter-Agency activities: • NIH-AHRQ CER Workgroup • NIH-VA CER Workgroup • NIH-FDA CER Workgroup • Discussions underway with CDC

11. IOM CER Report • Required under ARRA Legislation • Lists 100 national priorities for CER • Informed by testimonials given by advocacy, industry, and other groups • Informed HHS ARRA CER funding decisions

12. IOM CER Report: Examples of Cancer Priorities

13. ARRA Funded CER Projects

14. FY 2009 ARRA Awards In FY 2009, NIH Allocated 85% of the $400M received for CER NCI received over 20% of all funds allocated

15. FY 2009 Spending *All dollars in millions and rounded. “Other” category includes contracts and grants, for example NIH signature projects.

16. Examples of Funded Challenge Grants Breast Cancer • Role of Advanced Screening Technologies in Early Detection of Breast Cancer (Dana-Farber) Colon Cancer • Comparative effectiveness of FIT vs. colonoscopy for colon cancer screening (University of Iowa) Prostate Cancer • Comparative Analysis of Surgical Treatment Options for Localized Prostate Cancer (Sloan Kettering)

17. Examples of Funded GO Grants In response to NCI CER FOA in Genomic and Personalized Medicine • Center for Comparative Effectiveness Research in Cancer Genomics (CANCERGEN) (Fred Hutchinson) • Clinical validity and utility of genomic targeted chemoprevention of Pca (Wake Forest University Health Sciences) • Programs in Clinical Effectiveness of Cancer Pharmacogenomics (Duke University) • Comparative Effectiveness in Genomic Medicine (University of Pennsylvania)

18. Examples of Funded GO Grants In response to NCI CER FOA in Cancer Prevention, Screening and Treatment • Building CER Capacity: Aligning CRN, CMS, and State Resources to Map Cancer Care (Dana Farber) • CYCORE: Cyberinfrastructure for Comparative effectiveness Research (MD Anderson) • ADVancing Innovative Comparative Effectiveness research-cancer diagnostics (ADVICE) (University of Washington) • Comparative Effectiveness of Advanced Imaging in Cancer (Dartmouth)

19. Examples of Grants Funded using other Mechanisms • Cancer Center Support Grant Supplement aimed at promoting cancer CER through targeted faculty support, pilot projects, shared resources, and technology methodology innovation (Dartmouth) • Clinical Trial - Multicenter Selective Lymphadenectomy Trials, MSLT I and MSLT II (John Wayne Cancer Institute)

20. FY 2010 ARRA CER Initiatives

21. ARRA in FY10 - CER

22. NIH and AHRQ have Complementary Roles NIH Evidence Generation • AHRQ • Research Analysis • Systematic Reviews • Evidence Synthesis Informs Payers and Providers

24. AHRQ Spending • $300M AHRQ $9.5M - Horizon Scanning: Establish and use an efficient approach to investigate and prioritize areas for investigation relevant to the 14 priority conditions that guide AHRQ's Effective Health Care Program $25M - Evidence Synthesis: Expand the Agency's Effective Health Care Program (EHC). This program supports research activities that use rigorous scientific methods within an established process that emphasizes stakeholder involvement and transparency. $25M – Evidence Gap Identification: Initiate an enhanced capacity for identifying and prioritizing evidence needs $34.5M – Translation and Dissemination: Support grantees in developing and implementing innovative approaches to integrating CER findings into clinical practice and health care decision-making http://www.ahrq.gov/fund/cerfactsheets/

25. AHRQ Spending • $300M AHRQ • Evidence Generation • $100M CHOICE Studies: The Clinical and Health Outcomes Initiative in Comparative Effectiveness (CHOICE) will represent the first coordinated national effort to establish a series of pragmatic clinical CER in the United States • $48M Request for Registries: Clinical areas within the 14 AHRQ priority conditions, which include cancer, will be targeted. • $24M DEcIDE Network: Enhance investments in establishing a learning health care system by funding the DEcIDE (Developing Evidence to Inform Decisions about Effectiveness) Network to expand multicenter research consortia comprised of academic, clinical, and practice-based centers. • $1M Unfunded Meritorious Applications • $20M Training and Career Development • $10M Citizen Forum on Effective Health Care: will formally engage stakeholders, through a variety of transparent and inclusive mechanisms, at the critical stages of identifying research needs, study design, interpretation of results, development of products, and research dissemination. • $3M – Administrative oversight/miscellaneous http://www.ahrq.gov/fund/cerfactsheets/

26. FY 2010 – AHRQ Funding Opportunities

27. FY 2010 – AHRQ Funding Opportunities

28. HHS Spending Plan • $219M for Data Infrastructure • Includes projects at CMS, AHRQ, SAMHSA, FDA, HRSA and OS. Examples: • Enhance Availability and Use of Medicare Data to Support CER • Build a Medicaid Analytic eXtract (MAX) Data Repository Designed to Support CER for Medicaid and Children's Health Insurance Program Populations • Creation of an All-Payer, All-Claims Database to Enable Innovative CER • Building FDA CER Clinical Data and Standards Infrastructure, Tools, Skills, and Capacity • Expansion of Research Capability to Study Complex Patients http://www.ahrq.gov/fund/cerfactsheets/osfsinfra.htm • $400M HHS OS

29. HHS Spending Plan • $93.1M Dissemination, Translation, and Implementation • Includes projects at AHRQ and OS. Examples: • Enhancing the Adoption CER in the Treatment of Serious Mental Illnesses in Medicaid • Assessing and Accelerating Implementation Strategies in Agency for Healthcare Research and Quality Networks • Enhancing the Adoption of CER in the Treatment of Serious Mental Illnesses in Medicaid • $75.5MResearch • Includes projects at NIH, CDC, OS,AHRQ • Optimizing the Impact of CER Findings through Behavioral Economic Randomized Controlled Trial Experiments • Informing Clinical and Public Health Approaches to Chronic Disease Prevention • Centers for Racial and Ethnic Minority-Focused CER http://www.ahrq.gov/fund/cerfactsheets/osfsinfra.htm • $400M HHS OS

30. Other Efforts to Conduct & Support CER

31. SEER –Medicare Linkage • Created by linking two population-based sources • cases from SEER and Medicare claims from CMS • Over 1.5 million persons with cancer • Can be used to examine health care before, during and after cancer diagnosis • SEER data: detailed clinical, demographic and cause of death information for persons with cancer • Medicare: longitudinal, claims for all covered health services from the time of eligibility to death • Details at: http://healthservices.cancer.gov/seermedicare/

32. The linked data can be used for a number of analyses that span the course of cancer control activities Diagnosis/ Tx Survivorship Second Occurrence  Terminal Care Rates of recurrence/ second primaries Relationship of second events to initial treatment and ongoing surveillance Patterns of care Peri-operative complications Volume outcomes studies Extent of staging Comorbidities Late effects of treatment Post-diagnostic surveillance Treatment of prevalent cancers Survival Use of hospice services Patterns of care during the last year of life Health disparities, quality of care and cost of treatment

33. Breast Cancer Surveillance Consortium • Assesses the delivery and quality of breast cancer screening and related patient outcomes in U.S. • Links to pathology and/or tumor registries • Database of over 7.5M screening mammographic examinations of over 2M women • 86,700 breast cancer cases • Examines variation in radiologists’ interpretative performance • Co-funded by American Cancer Society

34. CISNET - Cancer Intervention & Surveillance Modeling Network • NCI Sponsored Collaborative Consortium (U01) of Modelers in Breast, Prostate, Colorectal and Lung Cancer • Focused on bringing sophisticated evidence-based decision tools to: • Understand the impact of cancer control interventions (screening, treatment, prevention) on current and future trends in incidence and mortality • Extrapolate evidence from RCTs, epidemiologic, and other observational studies to determine the most efficient and cost-effective strategies for implementing technologies in the population • Helps to determine which new technologies are the most promising when scaled up to the population level

35. Physician Surveys • Survey on Cancer Susceptibility Testing • Survey of Physician Attitudes Regarding the Care of Cancer Survivors (SPARCCS) • National Survey of Primary Care Physicians' Recommendations & Practice for Breast, Cervical, Colorectal, & Lung Cancer Screening

36. Cancer Care Outcomes Research and Surveillance Consortium (CanCORS) • Goal: Understand variation in care delivered to 5,000 patients with lung cancer and 5,000 with colorectal cancer • Evaluates how characteristics of physicians, patients, caregivers, and delivery systems affect quality of care and outcomes

37. CanCORS Data Sources and Linkages VA Encounters Cancer Registries Medicare Claims HMO Encounters Physician Survey (n=4,456) Medical Record Abstraction Patient/Surrogate Survey (n=10,071) Multiple Providers Caregivers Survey (n=1,637) National Death Index Geocoding CMS POS File Area Resource File AMA Masterfile US Census

39. Patient-Reported Outcomes Measurement Information System (PROMISTM) • Goal: Improve assessment of self-reported symptoms and other health-related quality of life domains across many chronic diseases. • Domains available include pain, fatigue, depression, anxiety, physical function, social function, and overall general health • Pediatric PROMIS: same domains as above • PROMIS will enhance our understanding of the physical and emotional sequelae of experimental and standard cancer treatments on cancer patients • NIH Roadmap Initiative: Re-engineering the Clinical Research Enterprise • PROMIS I: 2004-2009 (7 Research Sites) • PROMIS II: 2009-2013 (15 Research Sites)

40. Multiple Delivery Platforms Hand-heldDevice Self Administered PersonalInterview PROMIS Dynamic Assessments InteractiveVoiceResponse Internet Administered Telephone Interview

41. Integrating Patient Safety Monitoring to Improve Quality of Cancer Care Patient-Reported Outcomes version of the CTCAE • More than one-third of adverse events in drug labels are symptoms (nausea, fatigue, sensory neuropathy) • In clinical trials, adverse symptom information is reported by research staff, not directly by patients • Scientific evidence finds health professionals underestimate incidence and severity of symptoms compared to patients’ own accounts • Staff-based adverse symptom assessments occur at clinic visits, missing remote between-visit events • Increased regulatory focus on use of patient-reported outcomes (PROs) for subjective domains such as adverse symptoms in clinical research

42. PRO-CTCAE Network CBIIT DCCPS DCP DCTD Dana-Farber Christiana N E T W O R K N C C C P NCI MD Anderson Hartford Mayo OLOL MSKCC Coordinating Center Duke Spartanburg Penn St. Joseph - Orange SemanticBits ADVISORS T E C H Cooperative Groups FDA Industry Patient Advocates Perceptive

43. NIH Priorities: HMORN • Common fund initiative to enhance HMORN’s scientific, data and operational infrastructure. • Components: • Epidemiology studies • Pragmatic trials • Virtual data warehouse • Pilot studies

45. CER in the Policy Spotlight

46. Roles of the Patient-Centered Outcomes Research Institute (PCORI)

47. PCORI Funding • Direct appropriations: • FY 2010: $10M • FY 2011: $50M • FY 2012: $150M • FY 2013 - 2019: PCORI trust fund, $150M plus per capita charge per enrollee (per year)

48. Key Issues for the future • Cost • Current spending on health care • 18% of GDP in 2009 (2.5 trillion) • Insurance Coverage/Reimbursement • Personalized Medicine and CER • The extent to which PM can be incorporated into CER will result in more relevant and useful evidence

49. Synergy of CER and Personalized Medicine • “Population-based evidence must be complemented by personalized evidence that accounts for how patients’ genomic and other personal traits affect their responses to health care. Considered alone, neither population-based evidence derived from CER nor personalized evidence derived from PGx and other research suffice. Research priorities, design and conduct of data collection, reporting of results, and translation of CER and PM into practice and policy should be fully integrated. This can achieve alignment, and even synergy, of CER and PM.” Goodman, C. Comparative Effectiveness Research and Personalize Medicine: From Contradiction to Synergy. The Lewin Group, 2009

50. What’s Happening Now • HHS Secretary’s initiatives • Nomination of Don Berwick as CMS Administrator • Further discussions re PCORI establishment • NIH decisions regarding Common Fund FY2011 • AHRQ/NIH/ECRI Personalized Med Workshop • AHRQ/NIH CER Methodology Workshop