Mentored Research & Professional Development Eugene P. Orringer, MD April 14, 2003

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

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 MDs MD-PhDs Rosenberg- Science, 1999.

8. Problems for Clinician-ScientistsReport 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. OrringerMentors & 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. Eugene P. OrringerFellowship Training • Clinical Hematology • Red Cell Physiology • Membrane Transport • Volume Regulation • Metabolism

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

18. Eugene P. OrringerSubsequent NIH Funding • PI: RCDA from NHLBI • PI: R01 from NHLBI

19. Eugene P. OrringerEvolution 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 1st 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 Program1995 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. 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 UNC School of Medicine New Chairs & Center Directors

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. Clinical Research Enhancement ActPublic 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)

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. 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 UNC-CH School of Medicine Office of Research & Faculty Development

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: • K applications (K01, K08, K23) • 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. K23 - Patient-Oriented Research CDA • NIH Goal for K23: To fund at least 100 new awards/year Independent Investigator Medical School Internship/Residency Specialty Mentored Patient-Oriented Research CDA (K23)

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 0 n/a 1999 2 1.4 2000 8 2.4 2001 15 3.0 2002 22 3.3

49. Total NIH Support to theExtramural 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 MedicineTotal NIH $’s vs K23 Awards NIH Grants K23 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