1. Mentored Research & Professional Development Eugene P. Orringer, MD April 14, 2003 New Career Opportunities for Clinician/Scientists

2. Problems for Clinician-Scientists “The clinical investigator as an endangered species” James Wyngaarden - NEJM, 1979

3. Problems for Clinician-Scientists Crisis in Clinical Research Ahrens: Oxford Press, 1992

4. Problems for Clinician-Scientists “Investigator-initiated applications for patient oriented research (POR) are not reviewed equitably at the NIH………” Williams et al. - JAMA, 1997.

5. Problems for Clinician-Scientists “The four P’s that are relevant to patient- oriented research include: ” Patience Patients Passion Poverty Brown & Goldstein – JCI 1997.

6. Problems for Clinician-Scientists “The number of first-time MD applicants for NIH research support has plummeted over the past few years……” Rosenberg - Science, 1999

7. Problems for Clinician-Scientists Rosenberg - Science, 1999. MDs MD-PhDs

8. Problems for Clinician-Scientists Report from the Clinical Research Roundtable Four key challenges facing the US clinical research enterprise Workforce training Public participation Information systems Funding Sung et al. - JAMA, 2003

9. Problems for Clinician-Scientists Translating Biomedical Research to the Bedside: A National Crisis & a Call to Action Rosenberg – JAMA, 2003

10. The Promise of Basic Research The Human Genome Project Stem cell research The procurement of suitable organs &/or the development of artificial organs Novel, target-based drugs New vaccines

11. Delivering on the Promise Clinical Research could.… a) Be a powerful vehicle to deliver to the public the promises of basic science or alternatively it could …. b)Emerge as the rate limiting step in the translation of basic science to benefit the greater public health

12. Problems for Clinician-Scientists Is there truth to these various predictions of Gloom & Doom? Can something be learned from the career of a slightly graying clinican-scientist? What has been/is being done to facilitate the efforts of today’s young people? How have we at UNC sought to take advantage of these new opportunities?

13. Eugene P. Orringer My career – provides evidence that: The right mentors &/or role models are critically important to ones future success It certainly pays to be at the right place at the right time

14. Eugene P. Orringer Mentors & Role Models Medical School -Jack Myers Fellowship -John C. Parker Junior Faculty -Wendell Rosse GCRC Director -Michael Thorner MD-PhD Program -Sal Pizzo Dean’s Office -Jeff Houpt

15. John C. Parker, MD: 1935-1993

16. Fellowship Training Eugene P. Orringer Fellowship Training Clinical Hematology Red Cell Physiology  Membrane Transport  Volume Regulation  Metabolism

17. Initial NIH Funding Eugene P. Orringer Initial NIH Funding Co-I on Dr. John C. Parker’s R01

18. Eugene P. Orringer Subsequent NIH Funding PI: RCDA from NHLBI PI: R01 from NHLBI

19. Eugene P. Orringer Evolution as a Clinical Investigator Realized that I was not a basic scientist Looked for an opportunity to apply my understanding of RBC membrane transport to an important medical problem Identified sickle cell disease as an ideal model of disordered RBC physiology Recognized the institutional need for a clinical program that focused on patients with this genetic disorder

20. The UNC Sickle Cell Program  Identified those sickle cell patients who were receiving their care at UNC  Created an institutional program committed to the comprehensive care of children & adults with sickle cell disease  Started a clinical research program, one that initially relied on industry-supported clinical trials  Used these studies to generate interest among the patients & to recruit and fund the staff needed to begin to build a program

21. Wendell F. Rosse, MD

22. The UNC Sickle Cell Program Began a long-standing collaboration with Wendell F. Rosse The support & encouragement of Dr. Rosse were instrumental in my long- term success as a clinical investigator

23. The UNC Sickle Cell Program Developed a variety of joint efforts with Duke Duke & UNC helped to form and became key components of the North Carolina Sickle Cell Consortium Built a Duke-UNC database which contains over 1000 sickle cell patients

24. The UNC Sickle Cell Program 1988 - Prepared our 1 st joint Duke-UNC application & received NIH funding for the Duke-UNC Comprehensive Sickle Cell Center

25. General Clinical Research Center 1980’s: As a clinical investigator, I often used our NIH-funded GCRC 1988: Invited to serve on the GCRC Study Section 1989: Selected to serve as UNC’s GCRC Program Director

26. General Clinical Research Center As Program Director (1989-1999), I took a very institutional approach to the GCRC Particular emphasis on junior faculty development  Training programs focused on both clinical research & research ethics  Institutional clinical research fellowship  CAP & M-CAP Programs  NIEHS Contract

27. UNC MD-PhD Program In 1995, I agreed to assume the leadership of UNC’s MD-PhD Program At that time, this was a modest program recruiting 1-2 students per year without benefit of an MSTP grant Based on the substantial support we received from UNC and on two excellent recruiting classes, we wrote a successful MSTP application in mid-1997 In early 1999, we were able to recruit our initial class of students as an NIH-funded MSTP Program

28. UNC MD-PhD Program 1995 to the Present

29. UNC MD-PhD Program The current year (2003) was an important one for UNC’s MD-PhD Program Wrote a renewal application for MSTP award Eight of our current students will defend their PhDs Four of our current students will graduate  1 going to Stanford in Internal Medicine  1 going to Baylor in Medical Genetics  2 going to Yale in Dermatology

30. Institutional Philosophy - I The best medical centers benefit from individuals with varying skills  Superb investigators  Excellent leaders  Effective administrators

31. Executive Associate Dean In 1999, I agreed to give up the GCRC Directorship & assume the role of Executive Associate Dean My acceptance of this role was based, in part, on the opportunity to lead the recruitment of numerous chairs and center directors for our clinical and basic science departments

32. School of Medicine UNC-Chapel Hill Over the past four years, we have recruited to UNC a cadre of new leaders who have together brought to the School of Medicine a vibrancy and a sense of excitement that is truly palpable

33. UNC School of Medicine New Chairs & Center Directors CLINICAL LEADERS Runge - Medicine Stiles - Pediatrics Meyer - Surgery Diaz - Dermatology Pillsbury - ENT Longo - Neurology Meredith - Ophthalmology Newton - Family Medicine Watkins - GCRC BASIC SCIENCE LEADERS Magnuson - Genetics Snider - Neuroscience Bankaitis - Cell Biology Anderson - Physiology Johnson - Pharmacology Patel - Arthritis Center

34. Institutional Philosophy - II At the end of the day, it is really the young people that are absolutely critical to the growth and the ultimate success of a School of Medicine

35. Executive Associate Dean In 1999, I agreed to give up the GCRC Directorship & assume the role of Executive Associate Dean Based on my experiences with the GCRC and the MD-PhD Program, I realized how much I enjoyed helping young people succeed I felt that this was a particularly good time for young people whose focus was clinical research

36. NIH Directors Panel (The Nathan Committee) Key Recommendations Creation of several new awards in the “K series” (see K Kiosk Website) Re-evaluation of the NIH Review Process

37. Public Law #106-505 Clinical Research Enhancement Act Public Law #106-505 Statutory language for the GCRC Program Infastructure support for clinical research Loan forgiveness for clinical investigators http://lrp.info.nih.gov/extramural/FAQ_CRE.htm) (http://lrp.info.nih.gov/extramural/FAQ_CRE.htm)

38. Eugene P. Orringer Executive Associate Dean In negotiating for this position, I presented the Dean with the concept of developing a new office, the purpose of which would be to enhance the grant portfolio of the School of Medicine “Office of Research & Faculty Development”

39. UNC-CH School of Medicine Office of Research & Faculty Development Using central resources, the School has created an Office of Research & Faculty Development, the primary purpose of which is to assist our faculty and to enhance the grant portfolio in the School of Medicine

40. Office of Research & Faculty Development Since its inception, the focus of this office has been two-fold: Assist with proposals that are multidisciplinary, multi-school, and/or multi-institutional Assist with junior faculty grant proposals

41. Office of Research & Faculty Development A few examples of the multidisciplinary and/or multi-institutional proposals include: Mutant Mouse Regional Resource Center Two NCRR Renovation Grants K30 & Two K12 Awards (BIRCWH & MCRSP) Neonatal Research Network Doris Duke Clinical Research Grant Numerous Training Grants Joint Duke-UNC Grant Proposals Minority Center of Excellence Application

42. NIH Support UNC School of Medicine Office of Research

43. Office of Research & Faculty Development Evidence of its success came in the spring of 2002 when a re-engineering task force was asked by Dean Houpt to review all centrally-funded programs & to recommend specific areas for budget cuts. The Task Force suggested that the budget of this office should NOT be cut: in fact, they suggested that it be increased!!!

44. Office of Research & Faculty Development Work with junior faculty to facilitate the submission of: l K applications (K01, K08, K23) l Career applications to professional societies, foundations, and other non- governmental organizations (NGOs)

45. Office of Research & Faculty Development Over the past 3+ Years, we have also created a “grant library” that has helped to coordinate & facilitate the submission of numerous research grant applications, particularly those of young people

46. Independent Investigator Internship/Residency Specialty Medical School Mentored Patient-Oriented Research CDA (K23 Research CDA (K23) K23 - Patient-Oriented Research CDA NIH Goal for K23: To fund at least 100 new awards/year

47. Total # of K23 Awards made by the NIH

48. NIH Support to UNC # of K23 Awards K23 Awards to junior faculty members at UNC Year (#)(%) 1998 0n/a 1999 2 1.4 2000 8 2.4 2001 15 3.0 2002 22 3.3

49. Total NIH Support to the Extramural Community NIH Support to UNC NIH $’s NIH $’s NIH (Millions) (%) Ranking 1999 131 1.02 17 2000 144 0.98 15 2001 170 1.08 15

50. UNC School of Medicine Total NIH $’s vs K23 Awards NIH GrantsK23 Awards * (%) (%) 1999 1.02 1.4 2000 0.98 2.4 2001 1.08 3.0 2002 n/a 3.3 * Junior faculty at UNC also still hold 3 CAP awards, there are 6 people on the K12 (BIRCWH) award, & 3 people on the K12 (Clinical Research), and 6 additional pending K23 applications at the NIH

51. Office of Research & Faculty Development Assumed a leadership role in a variety of institutional education & training programs: Medical Student Research Programs K30 Program K12: BIRCWH Program RWJ Clinical Scholars Program K12: Mentored Clinical Research Program

52. UNC-Chapel Hill Medical Student Research Programs The School of Medicine at UNC-Chapel Hill enrolls 160 students per year Each year, over 50% of these students take part in some form of biomedical research

53. UNC-Chapel Hill Medical Student Research Short Term (3 month) Experiences  Holderness Foundation ~ 10  Short Term Training Program (NIH) ~ 35 Year-Long Experiences  Doris Duke Clinical Research Program 5  Distinguished Medical Scholars Program 6  NIDDK Minority Fellowship Program (NIH) 3 Combined Degree Programs  MD-PhD (NIH MSTP award) 8  MD-MPH ~ 23 TOTAL # of Students / Year ~ 90

54. Office of Research & Faculty Development Contributions to Medical Student Research NIGMS Short Term Medical Student Training Program Doris Duke Clinical Research Scholar Program NIDDK Minority Medical Student Research Program Individual (F30 & F31) awards to MD-PhD students NHLBI Minority Medical Student Short Term Training Program

55. Doris Duke Medical Student Clinical Research Program Five students per year Full year of patient-oriented research (POR) Solicit applications from student-mentor pairs Require a GCRC-based project Recruit both UNC & external candidates Emphasis on minority candidates

56. Office of Research & Faculty Development Contributions to Medical Student Research NIGMS Short Term Medical Student Training Program Doris Duke Clinical Research Scholar Program NIDDK Minority Medical Student Research Program Individual (F30 & F31) awards to MD-PhD students NHLBI Minority Medical Student Short Term Training Program

57. UNC-Chapel Hill Career Development for Clinician-Scientists

58. School of Medicine UNC-Chapel Hill The School of Medicine at UNC has a passionate commitment to the development of its junior faculty, particularly those with a career focus on translational and patient-oriented research

59. UNC Seeks to Foster the Development of Clinician-Scientists Programs for Career Development K30 Program K12 Awards Minority Cohort Program

60. K30 - Clinical Research Curriculum K30 Award UNC received funding as 1 of the initial cohort of 35 This grant provides funds for infrastructure No funds for the trainees

61. K30 - Clinical Research Curriculum Most K30 Programs placed emphasis on a new degree-granting program (e.g., MS or an MPH in Clinical Research or the equivalent) Typical ‘product’ of our K30 Program is not a degree, but rather a grant (e.g., K23 or the equivalent)

62. K30 - Clinical Research Curriculum Broad-Based Program  Schools of Medicine, Pharmacy, & Public Health Two-year duration  Yr 01 = didactics, design the research project, develop a grant proposal  Yr 02 = Conduct of the research project Submit a grant proposal

63. Structure K30 - Clinical Research Curriculum Structure Coursework Seminar Series Research Project Work-in-Progress Presentations Grant Preparation Mock Study Section Reviews Mentoring Panels

64. K30 - Clinical Research Curriculum Status of the Trainees Funding status of the K30 Trainees (n = 13) * who have enrolled between July 2000 & the present Funded Pending K23 Awards 6 3 K23 Awards 6 3 * Note that 2 of these individuals are Professors on sabbatical. The others, fellows in their initial year of the K30 Program, are not yet ready to write a K23.

65. UNC Seeks to Foster the Development of Clinician-Scientists Programs for Career Development K30 Program K12 Awards Minority Cohort Program

66. K12 Award A K12 grant is an institutional award designed to provide protected time to a group of scientists committed to academic research careers. A K12 Award is very much like a training grant, but one that is designed for junior faculty rather than for post-doctoral fellows

67. The BIRCWH Program K12 Award B uilding I nterdisciplinary R esearch C areers in W omen’s H ealth

68. UNC BIRCWH Program The BIRCWH Award brought to UNC 5 years of support @ $500,000/year Almost all $’s are available to support the salary of junior faculty, thereby providing them with 75% protected time for research Our goal in the BIRCWH is to assist each Scholar obtain an NIH award (e.g., K23, K08, R01) & thus achieve research independence within 2 years

69. UNC BIRCWH Program Developed the concept that if funded, the UNC BIRCWH Program would have both: BIRCWH Scholars BIRCWH Associates

70. BIRCWH Scholar An individual who is receiving salary support from the BIRCWH grant

71. BIRCWH Associate An individual who had previously received salary support from the BIRCWH grant but subsequently went on to compete successfully for his/ her own, independent grant support - or - An individual who would have been competitive for BIRCWH funding, but simply had too much independent funding

72. UNC BIRCWH Program critical mass By developing this concept of both Scholars and Associates, the UNC BIRCWH Program has now grown substantially. Upon entering year - 03, we have a critical mass of approximately 15 young people with interests and backgrounds that are remarkably diverse.

73. K12 Awards A very inexpensive way to fund the next generation of academic researchExample Using the BIRCWH model, $5 Million supports 10 programs & 50 Trainees/year

74. K12 Awards A K12 can have a big multiplier effectExample We have found that if they are used effectively, each K12 slot can be turned over 2-3 times in a 5 year cycle

75. K12 – BIRCWH Program Status of the Trainees Status of the BIRCWH Scholars & Associates (n = 15) who have been a part of our Program between October 2000 & the present Funded Pending K23 Awards 3 - K08 Awards 3 - K01 Awards 1 - R01 Awards 2 2 R03 Awards 3 - Doris Duke Award 1 - Pfizer Award 1 - Others 8 4

76. K12 - Mentored Clinical Research Scholars Program (MCRSP) A new K12 Program developed by NCRR Designed to provide salary support for young people (including many K30 trainees) The salary support will bring with it the protected time that is so important for the conduct of patient-oriented research NCRR received ~ 45 applications & funded 11

77. K12 - Mentored Clinical Research Scholars Program (MCRSP) Structure of UNC’s K12 Application Close Linkage to the GCRC, to the K30 Program, & to the Dean’s Office Gene Orringer - Principal Investigator Paul Watkins - Program Director

78. K12 - Mentored Clinical Research Scholars Program (MCRSP) Extremely pleased with the quality of the initial candiates Initially selected three from a total of 15 applicants As with the BIRCWH:  Each Scholar was promised 2 years of support  Require a minimum of 75% protected time Too early to say how successful this program will be

79. Minority Cohort Program (MCP) Scholars UNC is fully committed to having a faculty with as much ethnic and gender diversity as possible The MCP was established in 1994 by then Dean Michael Simmons Each faculty member selected as an MCP awardee receives up to 6 years of support

80. MCP Scholars An Advisory Committee (3 department chairs) selects the awardees and provides guidance re. faculty development Each Scholar is expected to:  Be a visible and available role model  Exhibit progress along an academic path Each Department Chair with a Scholar submits an annual report that reviews the Scholar’s progress and summarizes his/her career development.

81. MCP Scholars Total # of awardees in the program = 10 # of awardees currently receiving support = 6 8 women and 2 men 8 African-Americans and 2 Hispanics Departments receiving support: Family Medicine (1); Medicine (2); Nutrition (1); Pediatrics (4); Pharmacology (1);Social Medicine (1) 16% of School’s URM faculty 38% of School’s URM at the Assistant Professor Level.

82. MCP Scholars MCP has played a major role in increasing the diversity of our junior faculty The MCP has had a major impact on the institution by helping to:  Build new programs that further increase the diversity of the School  Provide protected time and thereby enhance the academic development and retention of our junior faculty

83. MCP Scholars Funding Status of the Scholars Independent funding status of the Scholars (n = 10) who have received support from the MCP between 1994 & the present Award TypeFunded RO1 Awards 3 K23 Awards 1 K01 Awards 1 P60 Project 1 NIH Minority Supplement 2 RWJ Minority Faculty Development Award 3 Other CDA 2 Co-I Research Grant 4 PI: NIH T32 Award 1

84. Center of Excellence - HRSA Awarded to UNC in the Fall of 2002 Among the criteria responsible for UNC’s success in competing for this COE Grant:  Rank 9th nationally in number of African-American physicians graduated  Rank 5th nationally in number of Native American physicians graduated  More than 15% of students are URM  More than 4% of faculty members are URM The COE provides funds for two additional URM faculty members each year

85. At UNC, we have developed a model that we believe has assisted our faculty and expanded the grant portfolio throughout the School of Medicine We are convinced that this is actually a very good time for young people with a career-commitment to clinical & patient-oriented research Perhaps the most tangible benefit of this program has been a major increase the number of young people with extramural funding & protected time New Career Opportunities for Clinician/Scientists