NHLBI and Clinical Trials: Current Activities and New Directions. NIH Collaboratory Grand Rounds

Transcription

1 NHLBI and Clinical Trials: Current Activities and New Directions NIH Collaboratory Grand Rounds Gail D. Pearson, MD, ScD Director, NHLBI Office of Clinical Research Associate Director, Division of Cardiovascular Sciences July 31, 2015

2 Disclosure The information presented here reflects my views, and not necessarily those of NHLBI or NIH. 2

3 NHLBI: Building on Tradition 3 Controlled Clinical Trials 1988

4 Greenberg Report Such studies should be initiated only if an important problem needs a rapid solution, the study is feasible and likely to answer the problem, and strong and stable leadership are assured. Protocol and operating procedures must be kept as simple as possible. Control of performance at all levels must be built into the structure. 4

5 Greenberg Report Such studies should be initiated only if an important problem needs a rapid solution, the study is feasible and likely to answer the problem, and strong and stable leadership are assured. Protocol and operating procedures must be kept as simple as possible. Control of performance at all levels must be built into the structure. 5

6 Greenberg Report Such studies should be initiated only if an important problem needs a rapid solution, the study is feasible and likely to answer the problem, and strong and stable leadership are assured. Protocol and operating procedures must be kept as simple as possible. Control of performance at all levels must be built into the structure. 6

7 Greenberg Report Such studies should be initiated only if an important problem needs a rapid solution, the study is feasible and likely to answer the problem, and strong and stable leadership are assured. Protocol and operating procedures must be kept as simple as possible. Control of performance at all levels must be built into the structure. 7

8 Greenberg Report A discussion of their organization, review, and administration is all the more pertinent at the present time because of the increasing need for a sharper definition of research goals and opportunities and the present and possibly continuing shortage of funds coupled with a growing need to translate research progress into clinical practice. 8

9 Greenberg Report A discussion of their organization, review, and administration is all the more pertinent at the present time because of the increasing need for a sharper definition of research goals and opportunities and the present and possibly continuing shortage of funds coupled with a growing need to translate research progress into clinical practice. 9

10 Greenberg Report A discussion of their organization, review, and administration is all the more pertinent at the present time because of the increasing need for a sharper definition of research goals and opportunities and the present and possibly continuing shortage of funds coupled with a growing need to translate research progress into clinical practice. 10

11 Greenberg Report A discussion of their organization, review, and administration is all the more pertinent at the present time because of the increasing need for a sharper definition of research goals and opportunities and the present and possibly continuing shortage of funds coupled with a growing need to translate research progress into clinical practice. 11

12 Dollars (Mllions) $40,000 $35,000 Current $ (Millions) 1995 Constant $ (Millions) $35,745 $36,438 $30,000 With Supplemental Appropriation (ARRA) $27,167 $30,070 $30,311 $31,311 $25,000 $21,080 President's Budget $20,000 $16,594 $16,508 $15,000 $11,300 $16,366 $10,000 $5,000 $0 12

13 Dollars (Mllions) $40,000 $35,000 Current $ (Millions) 1995 Constant $ (Millions) $35,745 $36,438 $30,000 With Supplemental Appropriation (ARRA) $27,167 $30,070 $30,311 $31,311 $25,000 $21,080 Clinical Trials ~10-11% President's Budget $20,000 $16,594 $16,508 $15,000 $11,300 $16,366 $10,000 $5,000 $0 13

14 Dollars (Mllions) $40,000 $35,000 Current $ (Millions) 1995 Constant $ (Millions) $35,745 $36,438 $30,000 With Supplemental Appropriation (ARRA) $27,167 $30,070 $30,311 $31,311 $25,000 $21,080 Clinical Trials ~10-11% President's Budget $20,000 $16,594 $16,508 $15,000 $11,300 $16,366 $10,000 $5,000 $0 14

15 Dollars (Mllions) $40,000 $35,000 Current $ (Millions) 1995 Constant $ (Millions) $35,745 $36,438 $30,000 With Supplemental Appropriation (ARRA) $27,167 $30,070 $30,311 $31,311 $25,000 $21,080 Clinical Trials ~10-11% President's Budget $20,000 $16,594 $16,508 $15,000 $11,300 $16,366 $10,000 $5,000 $0 15

16 Clinical trial costs going the other direction : Costs of clinical trials rose 8% per year Twice the rate of inflation in NIH Biomedical R&D Price Index Mean cost/patient rose ~340% ($3,772 -> $16,566) Source: MediData, >24,000 Phase I-4 trials Berndt ER, Cockburn IM, Prices Indexes for Clinical Trial Research: A Feasibility Study, Dec 26,

17 Clinical trial costs going the other direction : Costs of clinical trials rose 8% per year Twice the rate of inflation in NIH Biomedical R&D Price Index Mean cost/patient rose ~340% ($3,772 -> $16,566) Source: MediData, >24,000 Phase I-4 trials Berndt ER, Cockburn IM, Prices Indexes for Clinical Trial Research: A Feasibility Study, Dec 26, Roy, ASA, Stifling New Cures: The True Costs of Lengthy Clinical Drug Trials, Manhattan Institute for Policy Research, April 2012,

18 Clinical trial costs going the other direction : Costs of clinical trials rose 8% per year Twice the rate of inflation in NIH Biomedical R&D Price Index Mean cost/patient rose ~340% ($3,772 -> $16,566) Source: MediData, >24,000 Phase I-4 trials Berndt ER, Cockburn IM, Prices Indexes for Clinical Trial Research: A Feasibility Study, Dec 26, Roy, ASA, Stifling New Cures: The True Costs of Lengthy Clinical Drug Trials, Manhattan Institute for Policy Research, April 2012,

19 So what s an NIH Institute to do? Take a closer look at how to optimize public health impact Squeeze most science out of every dollar Ensure we are managing our trials for success

20 So what s an NIH Institute to do? Take a closer look at how to optimize public health impact Squeeze most science out of every dollar Ensure we are managing our trials for success

21 So what s an NIH Institute to do? Take a closer look at how to optimize public health impact Squeeze most science out of every dollar Ensure we are managing our trials for success

22 Charge to NHLBI staff Imagine a clinical research process that meets all of NHLBI s strategic needs 22

23 Charge to NHLBI staff Imagine a clinical research process that meets all of NHLBI s strategic needs 23

24 Charge to NHLBI staff Imagine a clinical research process that meets all of NHLBI s strategic needs 24

25 Charge to NHLBI staff Imagine a clinical research process that meets all of NHLBI s strategic needs 25

26 Office of Clinical Research OCR Steering Committee IMPACT Task Force I 26

27 Strategic Visioning And SVID Streamlining and Coordination of Ongoing NHLBI Clinical Trial Activities espa Risk Management Council OCTET Office of Clinical Research Resource Management WG CSCC Forum NHLBI Grants Modernization WG 27 Trans-NIH Grants Modernization Trans-NIH CT Reforms Task Force & WGs NIH-FDA Leadership Council

28 28 IMPACT Task Forces Recommend how to optimize scientific impact, timeliness, and efficiency of NHLBI clinical trials Pre-award: Identifying Highest Priority Trials Identifying scientific and public health priorities Delineating expectations for performance milestones Establishing application review criteria Post-award: Managing for Trial Success Metrics-driven monitoring and oversight of trials Promoting data analysis and sharing and results dissemination

29 Next Steps Types of Funding Opportunity Announcements (FOA) Parent Announcements Program Announcements Requests for Applications Use our Funding Opportunity Announcements Re-engineer the process of what comes in the door: Delineate expectations for performance Delineate review criteria related to performance Articulate specific scientific priorities 29

30 Publication of NHLBI Trials 30 Gordon D et al. N Engl J Med 2013;369:

31 Publication of NHLBI Trials < 2/3 of trials published within 30 months of trial completion Median time to publication: 25 months 31 Gordon D et al. N Engl J Med 2013;369:

32 Role of Trial Design 32 Gordon D et al. N Engl J Med 2013;369:

33 Pragmatic Trial RFA Focus on trials that are Pragmatic Patient-centered Low-cost Five participating institutes NHLBI, NIA, NIDCD, NIDA, NINR, NCCAM Unique Mechanism: UH2/UH3 Individual and trial-specific metrics Administrative coordinating center NHLBI funded 4 trials 33

34 NHLBI-funded grants Daniel Buysse Behavioral Interventions for Insomnia in Hypertensive Patients Michelle Gong, Ognjen Gajic Prevention of Severe Acute Respiratory Failure Electronic Checklist to Prevent Organ Failure Delia Scholes Ian de Boer Calcitriol in Patients with Chronic Kidney Disease Henry Wang Airway Management of Out-of- Hospital Cardiac Arrest

35 Next Steps Create a clinical trials dashboard 35

36 Next Steps Create a clinical trials dashboard 36

37 The Solution

38 The Solution

39 The Solution

40 The Solution

41 The Solution

42 The Solution Trials NHLBI MyTrials View Trial Summary Trial Documents and Monitoring Tools Current Issue Summary Current Status Accrual Adverse Events Financial Data Action Plan

43 The Data Data Warehouse 43

44 Pediatric Heart Network (PHN), 2015 Children s Hospital Seattle, WA Children s Hospital Milwaukee, WI Children s Hospital Minneapolis, MN University of Michigan Ann Arbor, MI Hospital for Sick Children Toronto, CA Toronto Gen. Hospital Toronto, CA New England Research Inst Watertown, MA Children s Hospital Boston, MA Mt. Sinai Hospital New York, NY Presbyterian Hospital New York, NY Primary Children s Medical Center Salt Lake City, UT Stanford University Stanford, CA Cedars-Sinai Los Angeles, CA Children s Hospital Los Angeles, CA Rady Children s Hospital San Diego, CA Children s Memorial Chicago, IL Prairieland Consortium Cincinnati Children s, OH Riley Children s, IN Washington University St. Louis, MO Vanderbilt University Nashville, TN Johns Hopkins Baltimore, MD NHLBI Bethesda, MD North Carolina Consortium Children s Hospital New York, NY Children s Hospital Philadelphia, PA University of Pennsylvania Philadelphia, PA Nemours Children's Clinic Wilmington DE Children s National Medical Center, Washington, DC Children s Hospital Pittsburgh, PA Funding Agency (NHLBI) Clinical Sites Auxiliary Sites Data Coordinating Center Protocol Chair Protocol Chair, UTSW Dallas, TX Texas Children s Hospital Houston, TX Children s Hospital of Atlanta Atlanta, GA All Children's Hospital St. Petersburg, FL Medical University of SC Charleston, SC University of Ghent Belgium

45 Budget sites, DCC $23 M sites, DCC $46 M sites, DCC $64 M Total NHLBI Investment $133 M

46 Programmatic Review August 25-26, 2014 Charge Review PHN progress through the first 3 funding cycles Propose the most important areas for future investigation Propose new ways for PHN to operate in a fiscally constrained environment

47 New Model: Platform for Clinical Research Industry External Funding or R01s Non-PHN Investigators Proposals PHN Investigators PHN Funding DCC Clinical Sites High Quality Clinical Research and Training

48 PHN Partnerships with Industry Mr. Dean Park Chairman

49 Children and Clinical Studies Campaign

50 A peek at the future

51 National Institutes of Health Watson Proof of Concept Final Readout Presentation July 2015

52 Spinoff from RCDC s Evaluation of Watson s Text-Mining Capabilities

53 Modeled 8 trial characteristics to predict time to publication 32% error rate Model based on information at time of application Machine learning, natural language processing, ontologies New variables identified Error rate ~26%, 20% improvement

54 * Adverse events are coded in yellow. 54

55 * Adverse events are coded in yellow. 55

56 Imagine 56

57 Imagine 57