A Key Component of the NIH Roadmap

1. Development of a Conceptual Model and Assessment of the Feasibility of the National Clinical Research Associates (NCRA) A Key Component of the NIH Roadmap

2. RAND Team Katherine Kahn, MD Principal Investigator Allen Fremont, MD Co-Principal Investigator John Adams, PhD Senior Statistician Megan Beckett, PhD Demographer Claude Berrebi, PhD Economist Michelle Cho, MEd Project Associate Harold Pincus, MD Senior Scientist Elaine Quiter, MS Project Manager Gery Ryan, PhD Senior Behavioral Scientist Stephanie Taylor, PhD Behavioral Scientist

3. Need to Close the Gap Between Scientific Advances and the Health of the American People Translation of Knowledge into Clinical Practice And Health Translation from Basic Science to Human Studies Basic Biomedical Research Clinical Science And Knowledge Potential Outcome: Improved Health for US Population Adapted from Sung JAMA 03

4. Challenges to Clinical Research Have Been Identified • Too slow • Insufficient # of providers, too many drop-outs, lack of coordination • Research not representative • Underrepresentation of key patient and provider groups • Research not responsive to needs of clinicians • Questions and study designs are not responsive to needs of practicing clinicians • Unclear link to patient health and outcomes

5. Need to Close the Gap Between Scientific Advances and the Health of the American People Translation of Knowledge into Clinical Practice And Health Translation from Basic Science to Human Studies Clinical Science And Knowledge Basic Biomedical Research Stable NCRA Infrastructure More and diverse set of studies More and diverse set of patients More and diverse set of providers

6. NIH Roadmap Proposes NCRA to Improve the Efficiency and Effectiveness of Clinical Research* • Provide a stable infrastructure •  # of providers and patients •  long term provider involvement •  provider understanding of clinical research findings •  effectiveness of provider as an agent for disseminating findings • A direct response to concerns about the lack of community provider involvement in clinical research • Helps ensure the relevance of clinical research to everyday practice *Zerhouni, 2003

7. Physician Participation in Clinical Research* • 53% of physicians have never participated in a clinical trial • 1 in 8 (13%) physicians currently participate in clinical research • Lower rates for dentists and nurse practitioners • 1/3 physician research participants , no longer participate *Harris Interactive June 2004 Survey

8. Factors That Influenced Physicians to Participate in Clinical Trials* Opportunity to help advance science 92% Benefit to patients 80% Desire to be thought of by peers, pts as a leader 60% Sufficient staff to support clinical trials 57% Provides access to drugs not yet approved 55% Monetary compensation 53% Personal recognition in clinical trials 31% Prospect of strong business opportunity 24% Institutional requirements 22% Other 4% *Harris Interactive Survey 2004; multiple responses allowed

9. Many Providers are Inclined to Clinical Research Participation • Contributes to the mission of medicine • Breeds community with other professionals • Facilitates affiliations with desirable colleagues, leaders • Supported by professional organizations • Allows participation with NIH • Good business sense (marketing advantage) • Patients prefer access to providers at the cutting edge • Research facilitates access to the best diagnostic and treatment options • Fulfills professional and personal goals • Potential 2° income stream • Provides means to remain current with new innovations • Intellectually stimulating • Provides prestige and recognition • Authorship, wall certificate, CME credits

10. Reason provided No opportunities to participate 38% Time commitment too significant 32% Insufficient personnel support 30% Inadequate resources 26% Paperwork too burdensome 24% No interest 17% Don’t know where to begin 11% Colleagues don’t participate 11% Rules/regulations too stringent 9% Reason provided Costs outweigh benefits 8% Insufficient grant/contract amts 8% Patients not interested 7% Group doesn’t meet requirements 7% Prior – research experience 2% Prior – sponsor experience 2% Not certain 2% Research trials are unethical 1% Other 10% Reasons Practicing Physicians Have Not /Are No Longer Clinical Investigators* *Harris Interactive 2004, >1 response is permitted, n=431

11. Disincentives for Providers Outweigh Incentives Incentives VS. Disincentives • Breeds community with other professionals • Facilitates affiliations with smart, successful colleagues, leaders • Fulfills professional and personal goals • Fear of adverse outcomes • Fear of losing patients to the university • Forms too complex • Research nurses too transient • Research too unpredictable • Time commitment too much

12. Disincentives VS. Incentives • Breeds community with other professionals • Facilitates affiliations with smart, successful colleagues, leaders • Consistent w goals of professional organizations • Allows participation with NIH • Fulfills professional and personal goals • Potential 2° income stream • Provides means to remain current with new innovations • Fear of adverse outcomes • Fear of losing patients to the university The Balance Needs to be Tipped

13. Who can Help Tip the Balance?(Using NCRA as a Response Mechanism) • NIH • Research Associated Organizations (RAOs)* • Principal Investigators • Other (National specialty organizations, other transgovernmental agencies) *RAOs include organizations who potentially can facilitate provider involvement with research. For example, community hospitals, multi-specialty groups, health management organizations, primary-care based research networks, CROs, academic medical centers, and consortiums.

14. Using NCRA Infrastructure for Providers NIH RAO PI NCRA Community providers recruiting patients

15. How can we Tip the Balance?(5 Feasible NCRA Strategies) 1.Align NIH proposals and NCRA goals 2. Introduce NCRA Structures • Registry of Providers and Studies (ROPS) • Data center(s) 3. Introduce NCRA Services • Training, dissemination, QA 4. Use strategies to further motivate provider involvement -RAOs 5. Introduce financial incentive models to support NCRA goals

16. I. Align NIH Proposal Ratings Systems and NCRA Goals • Study question • Trial design • Proposal content • Proposal evaluation • Proposal budgets • Principal investigator responsibilities • Criteria consistent with NCRA goals

17. Study Questions Appropriate for Community Providers: • Want • To participate in studies that represent their work, their patients, their settings • To study questions whose answers will facilitate their caring for their patients • To use equipment that functions in their practice settings • Intervention studies to compare feasible options for their practice • Do not want • To risk losing patients to academics because of research participation

18. Potential generators of questions • Questions posed by: • Guideline committees • Evidence based studies • Community providers • Patient advocates • Community organizations • Research networks • PBRN • Specialty society • Patients

19. Traditional explanatory clinical trials: These trials  the chance that the biological effect of a new Rx will be identified. Apply rigorous inclusion/ exclusion criteria to a homogeneous sample of pts to reveal the mechanism by which an intervention influences a well-specified outcome. Practical/ pragmatic clinical trials: The hypothesis and design are developed based upon information needed for a clinician or policy maker to make a decision. Enroll the full spectrum of patients and provider settings Introducing a new kind of trial design

20. Proposal Content If NCRA assumes responsibility for provider recruitment, • Proposals will need to be more explicit: • provider and patient inclusion/exclusion criteria • any restrictions on the number of providers and patients per strata • Protocols will need to be specific: • provider training, data collection strategies • quality assurance, data dissemination

21. Proposal Evaluations • Proposal Evaluations • Proposal study question is consistent with NCRA mission • Proposal design is: compatible with NCRA protocols, feasible given NCRA ongoing commitments • Design is responsive to community settings and priorities

22. Examples from Hypothetical Report Card Evaluating How Proposal Supports NCRA Goals

23. Proposal Budgets NIH Budget PI PI Budget NCRA unit Research- assoc org Provider

24. PI Responsibilities shared with NCRA PI responsibilities Study Specific Exec Comm RAOU NCRA Executive Committee ROPS TRAIN Prop Funding Data QA

25. NCRA Structures • Registry of Providers and Studies (ROPS) • Data centers

26. Registry of Providers and Studies (ROPS) • Lists all NCRA studies • Lists eligible providers and characteristics • training, certificates • Characterizes provider capacity • experience w research, provider performance • Characterizes provider practices and patients

27. Data Centers for Data Transfer and Management • Data collection and transfer facilitates standardized • forms, easy for community providers to use • data transfer mechanisms; ultimately it will all be electronic • provider transfer of data regardless of provider’s preferred method (fax, email, web-based) • Management facilitates • efficiencies and error reduction by using a standardized process • Anticipates long term data management and use • facilitates sharing of data across investigators *

28. NCRA Services • Training • Dissemination and Public Relations • Quality Assurance • (Informatics) • (IRB) ( ) indicates an NIH Roadmap activity other than NCRA

29. Standardized Training Function • Standardized training • Introduction to research participation (independent of particular study) • IRB, HIPAA, approach to research participation, QA training • Study specific protocol training • Subsequent study-specific training • Facilitates link to FDA standards and protocols • (Long-term) IRB committee for review of proposals

30. NCRA Serves a Dissemination Function • Dissemination of research study findings • ROPS tracks and makes available listings of study- related publications, meetings, reports • Notifies NCRA Associates of research results • Opportunities (web-based and w meetings) for providers to review research findings and have their voices heard *

31. Contributes to larger enterprise examining how research findings can best influence clinical care and outcomes • Includes a trials registry • assures all trial results, not just (+) findings are disseminated for review • Distributes research results for critical evaluation • in the context of knowledge for the discipline • Collective medical societies, clinical experts, methodologists (e.g., meta-analysts) • decide whether or not to endorse clinical changes

32. Research Associated Organizations (RAOs) • Organizations capable of providing infrastructure for provider participation in clinical research • Academic medical center, Practice based research network, medical group, IPA, health plan • Organizations compete for NCRA membership • RAOs gain start-up funds, annual funds, study specific funds • RAOs assure providers are reimbursed and productive

33. NCRA Designed to Support Community Provider Participation with Clinical Research • Administrative services • Estimation of study costs • Anticipation of provider and RAO costs • Outreach to providers • Quality control

34. Key Players Use NCRA Strategies to Further Motivate Provider Involvement • Explicit NCRA structure will address provider concerns • Access to studies, studies type (Q and design), costs, training, quality • NCRA with other Roadmap activities will address provider concerns • IRB, informatics, public trust • Snowball effect with more provider and patient participation breeding more interest in provider and patient participation