Sustaining Institutional Support and Patient Engagement in Clinical Trials: Models and Messages from the NIH Clinical Center

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1 Sustaining Institutional Support and Patient Engagement in Clinical Trials: Models and Messages from the NIH Clinical Center John I. Gallin, MD Director, NIH Clinical Center November 7, 2011

2 Advancing Translational Sciences NIH Clinical Center Lasker~Bloomberg Public Service Award For serving since its inception as a model research hospital providing innovative therapy and high-quality patient care, treating rare and severe diseases, and producing outstanding physician-scientists whose collective work has set a standard of excellence in biomedical research.

3 NCI NHLBI NIAID OD NIDCR NEI NIA NLM CC NIDDK NIAMS NIDA FIC CIT NHGRI NICHD NCATS NIEHS NIBIB CSR NIAAA NIDCD NINDS NIMH NCCAM NINR NIGMS NIMHD

4 NIH TRND NIH RAID National Center for Advancing Translational Sciences Disease Target ID Assay Dev. HTS Probe to Lead Pre- Clinical FDA IND Ph. 0 Ph. I Ph. II Ph. III FDA Review Community NIH Molecular Libraries Initiative Pharma, Biotech, ORDR, NIH Clinical Center, CTSAs New NIH FDA Partnerships

5 NIH Clinical Center

6 Clinical Center Profile More than 450,000 patients since opening in beds ; Budget $384.8M Hospital surrounded by research labs Every patient is on a research protocol Care is free Patient travel/housing provided as needed 2,250 CC employees + ~4,000 employees from 17 ICs that use hospital 1,255 credentialed physicians 1,513 active protocols o 47% natural history studies o 47% clinical trials (92% phase 1 and 2)

7 Mission Science Training Patient Care/Safety

8 Standards for Clinical Research Essential principles & processes for the conduct of clinical research 7 standards: 1. Clinical Informatics, Data Management, & Protocol Tracking 2. Biostatistics Support 3. Quality Assurance and Quality Improvement 4. Protocol Review 5. Human Resources and Physical Plant 6. Training and Education 7. Research Participants Created 2000; Revised 2009

9 Major Emphasis First in human with new therapeutics

10 Two Approaches to Develop New Therapeutics 1-2 years? >400,000 compounds, yrs Target Screen Test chemicals on target Lead Product GMP Preclinical Clinical Trials FDA approval 3000 drugs Currently over 65 protocols testing the value of old drugs for new indications.

11 Problems Associated with Clinical Trials Studies of combination therapies Cost effectiveness trials WHO PAYS?

12 Drug Donations All investigational new drugs are donated. Through the Foundation of NIH, the Clinical Center received ~$1.6M in-kind drug donations in Pharma also provided (either through direct donation or through CRADAs) marketed drugs that are being studied for off-label indications ~$10.6M in 2010

13 Major Emphasis First in human with new therapeutics Study of patients with rare diseases ~400 cohorts currently

14 Clinical Center Infrastructure to Support Clinical Research Investigator Administrative Support Human Subjects Support Specialized Research Services

15 Clinical Center Infrastructure to Support Clinical Research Investigator Administrative Support Problem: Hassle Factors

16 Clinical Center Infrastructure to Support Clinical Research Investigator Administrative Support X Problem: Hassle Factors Office of Protocol Services Protocol Navigators ProtoType BTRIS

17 CC Office of Protocol Services Repository for all intramural clinical protocols Quality review of all protocol actions Compliance with 45 CFR 46 Consent documents Compliance with FDAAA (registration/reports) Notify PI of recurring reviews IND consultation (with Pharmaceutical Development Service) Prepare reports to Congress (with assistance from BTRIS) opatient demographics obiospecimens

18 Protocol Navigators at the NIH One of several initiatives in response to 2008 study of barriers to clinical research New positions to assist investigators in preparation and implementation of clinical protocols Structure varies somewhat across Institutes

19 The Protocol Navigator Interface NIAID Scientific Review APPROVED CONCEPT Hypothesis, Endpoints, Design Statistics Clinical Protocol Courtesy H. Clifford Lane, M.D. (NIAID)

20 The Protocol Navigator Interface NIAID IRB Office Medical Writers IND Scientific Review APPROVED CONCEPT Office Tech Dev Safety Office/ DSMB Hypothesis, Endpoints, Design Statistics Office of Ethics PROTOCOL NAVIGATORS Site Establishment/ Monitoring Clinical Protocol NIH Institutional Biosafety Committee/ Office Biotech Activities Case Report Form Production NIAID ORS NIAID RCHSPB OHSRP Courtesy H. Clifford Lane, M.D. (NIAID)

21 Protocol Navigation Program-NIAID initial reviews, 10 amendments, 7 international studies 29 discrete investigators; 10 different labs Current staffing: 1 Navigation Manager, 2 Protocol Navigators, 3 Medical Writers Annual Costs (approx): $600K

22 Protocol Navigator Training Program (under development) Intended as career path alternative for research nurses, scientific writers, and IRB professionals Planned one-year program, with didactic and mentored hands-on experience

23 ProtoType: A Protocol Development Tool at the NIH Clinical Center A web based protocol writing system for protocol authoring and management

24 What is ProtoType? Training Protocol Authoring Recommended Language Cassettes IND Wizard ProtoType Protocol Cost Projections (under development) Facilitates New Policies and Regulations Assists Protocol Review

25 NIH Biomedical Translational Information System (BTRIS) A web based resource that integrates clinical and research data. PI access to identifiable data within a protocol. All investigators access to de-identified data. Provides advanced search, filtering, and aggregation methods to create data sets to support ongoing studies and stimulate ideas for new research.

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27 What is BTRIS? EHR Institute System Personal System Lab System

28 What is BTRIS? EHR Institute System Personal System Lab System BTRIS

29 What Makes BTRIS Special? Interfaces patient care and research data Integrates data sources from multiple institutes Single unifying hybrid data model Ontology for representation, queries and alerting User empowerment Automated reporting o FDAAA o Congressional Reports (human subject demographics, biorepository) James J. Cimino, M.D.

30 Clinical Center Infrastructure to Support Clinical Research Investigator Administrative Support Human Subjects Support Specialized Research Services

31 Clinical Center Infrastructure to Support Clinical Research Human subjects support Problem: Recruitment, retention Office of Patient Recruitment and Public Liaison IT/Media Tools Human Subjects Perception Survey

32 Office of Patient Recruitment & Public Liaison Services to PIs Customized recruitment approaches to meet protocol objectives that complements Institute efforts Provides toll-free telephone information & prescreens referrals Recruits, registers, and compensates research volunteers

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34 Engaging the Public Using Traditional and New IT/Media Tools Press Releases Media Advisories CC News Internet/Intranet ClinicalTrials.gov Research match Home Page Slides Digital Screens YouTube Videos Twitter Facebook CC Radio Audio Podcasts s Flyers Posters

35 NIH Outreach in the Local Community NIAID Vaccine Research Center mobile clinic NIAMS Clinic in Rockville Suburban/Johns Hopkins Hospital Washington Hospital Center Children s National Medical Center Georgetown University George Washington University Bethesda Hospitals Emergency Preparedness Partnership D.C. Partnership for AIDS Research

36 Research Volunteer Survey To heighten Clinical Center awareness of research partners sensitivities we developed a human subject perception survey. Leaders: Laura Lee, R.N. David Henderson, M.D.

37 New Research Subject Survey Research subject perception survey initiated with Picker Institute Partnership with Rockefeller University (Barry Coller, M.D., Rhonda G. Kost, M.D.) Phase I: Focus groups to identify issues important to participants Phase II: Development/validation of survey questions and fielding of survey

38 Dimensions of Survey Informed Consent Did the informed consent form prepare you for what to expect during the study? Was the informed consent form written in a way you could understand? Respect Patient Preferences Did you feel like you were a valued partner in the research process? Trust Did you have confidence and trust in the research doctor leading the study?

39 Dimensions of Survey continued Coordination of Research Did you know how to reach the research team if you had a question? How often was the research team ready and on time for your visit? Information and Communication During the course of the study, was it easy to get answers to your questions from your research team?

40 Survey-Future Directions Survey tested in 15 CTSA sites o Baystate Medical Center o Boston University Medical Center o Duke University o Feinstein Medical Institute, LIJH o Johns Hopkins University o Massachusetts General Hospital o NIH Clinical Center o OHSU Women s Research Institute o OHSU Knight Cancer Institute o Oregon Clinical and Translational Research Unit o Rockefeller University o Stanford University Tufts New England Medical Center o University Hospitals Case MC o University of Rochester MC o University of Texas Southwestern o Vanderbilt University o Yale Center for Clinical Investigation

41 Survey-Future Directions Survey tested in 15 CTSA sites Clinical Center survey will drive local improvements othe CC will survey patients annually Aggregate data from the 15 centers will be analyzed to: oidentify best practices oprovide benchmarking data for institutions nationally

42 Clinical Center Infrastructure to Support Clinical Research Investigator Administrative Support Human Subjects Support Specialized Research Services

43 CC Specialized Services and Facilities Phenotyping o Biomechanics laboratory o Metabolic chambers Cell Processing/GMP Facility

44 Specialized Services and Facilities Imaging Capabilities MRI Center PET Program o 3 cyclotrons o Radiochemistry/GMP Facility o 3 scanners Multi-modality minimally-invasive procedural suite

45 Specialized Services and Facilities Pharmaceutical Development Service GMP Facility Product formulation Analytical and quality control Pharmacokinetics Manufacturing capability (8 hour day) o 75,000 capsules o 150,000 tablets o 220 liters o 5,000 syringes CC Pharmaceutical Development Section o 8,000 vials producing (includes green tea capsules vaccines for a study and biologics)

46 Clinical Research Healthy Volunteer Program Established in 1954 Opportunity for healthy volunteers; ~56,000 registrants to-date ~1,800 new healthy volunteers in

47 NIH Curriculum in Clinical Research Introduction to the Principles & Practice of Clinical Research 11,943 participants since course introduced in 1995 Principles of Clinical Pharmacology 7,492 participants since course began in 1998 Ethical and Regulatory Aspects of Human Subjects Research 4,362 participants since course began in 1999 October

48 San Juan, Puerto Rico Monterrey, Mexico Cali, Colombia Lima, Peru Bergen, Norway Moscow, Russia Athens, Greece Beirut, Lebanon Rabat, Morocco New Delhi, India Irbid, Jordan Karachi, Pakistan Riyadh, Saudi Arabia Pune, India Burkina Faso, West Africa Ghana, West Africa Bangalore, India Mysore, India Ibadan, Nigeria Malaysia Republic of Kenya Santa Maria, Brazil Salvador, Brazil Beijing, China Chengdu, China Wuhan, China Sui nin, China Seoul, S. Korea Busan, S. Korea Masan-City, S. Korea Singapore Santiago, Chile Buenos Aires, Argentina Pretoria, South Africa Since 1995, Over 30,000 students world-wide have participated in the NIH Curriculum in Clinical Research Live Archived

49 Standards in Clinical Research Required Training Nearly 25,000 students to date Target audience: All clinical investigators Available online: dex.html

50 NIH CC Sabbatical Clinical Research Management Modules Module 1: Critical Infrastructure Module 2: Support Services Module 3: Legal & Regulatory Infrastructure Module 4: Communications and Outreach Module 5: Strategic Management Module 6: Funding Opportunities Popular Electives Protocol Writing & Tracking (88%) CTSA (75%) Planning & Budget Development (63%) Patient Recruitment (50%) Quality and Performance Metrics (50%) Food & Drug Administration (38%) NIH Office of Human Subjects Research (38%) Average Length of Sabbatical: 3.5 months

51 The Future A New Vision for the Clinical Center

52 Congressional NIH Scientific Management Review Board The role of the NIH Clinical Center should be to serve as a state-of-the-art national resource, with resources optimally managed to enable both internal and external investigator use.

53 Goal of Opening Doors of Clinical Center Access to: Special services Partnerships with intramural investigators obench-to-bedside Awards

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55 Anticipated Future Bench-to-Bedside RFA Will address comments received from RFI Will complement NOT replace existing Intramural B2B Program

56 Anticipated Bench-to-Bedside RFA: Key Points Unique Requirements: Extramural investigator MUST have intramural collaborator; multiple PI model will be required Application will be submitted by extramural PI Project MUST utilize CC resources Budget: up to $500K/year in direct costs

57 Current Bench-to-Bedside Awards Program promotes new partnerships between basic science and clinical investigators Goals: Develop new clinical protocols Discover new therapeutics and devices Foster long standing collaborations $135K per year X 2 years In 2006 established intramural/extramural partnerships (~ 90%) www.

58 B2B Partnerships Partnerships at 67 U.S. & International Sites WA CA OR NV ID UT MT WY CO ND SD NE KS MN IA MO WI IL IN MI KY OH WV PA VA NY VT NH NJ DE MD DC ME MA RI CT AZ NM OK AR TN NC SC MS AL GA AK TX LA FL HI Participating Institutions CTSA site Non-CTSA partnership Hospital A.C. Camargo, Brazil Hospital for Sick Children, Canada Imperial College, London Intl. Agency for Research on Cancer, France Makerere University, Uganda Sackler Sch. of Med, Israel University of Toronto, Canada University of Oxford, UK Zaria, Nigeria

59 Clinical Center Infrastructure to Support Clinical Research Investigator Administrative Support Human Subjects Support Specialized Research Services

60 Through partnerships that capitalize on our respective strengths, NIH, academia, philanthropy, patient advocates, and the private sector can take full advantage of the promise of translational science to deliver solutions to the millions of people who await new and better ways to detect, treat, and prevent disease. Opportunities to advance the discipline of translational science have never been better. We must move forward now. Science and society cannot afford to do otherwise. F.S. Collins, Reengineering Translational Science: The Time Is Right. Science Transl. Med July 6; 3, 90cm17