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

Mentored Research & Professional Development

Eugene P. Orringer, MDApril 14, 2003

New Career Opportunities for Clinician/Scientists

Problems for Clinician-Scientists

“The clinical investigator as an

endangered species”

James Wyngaarden - NEJM, 1979


Crisis in Clinical ResearchCrisis in Clinical Research

Ahrens: Oxford Press, 1992


“Investigator-initiated applications for patient oriented research (POR) are not reviewed equitably at the NIH………”

Williams et al. - JAMA, 1997.


“The four P’s that are relevant to patient-oriented research include: ”

• Patience• Patients• Passion• Poverty

Brown & Goldstein – JCI 1997.


“The number of first-time MD applicants for NIH research support has plummeted over the past few years……”

Rosenberg - Science, 1999


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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


Translating Biomedical Research to the Bedside: A National Crisis & a Call to Action

Rosenberg – JAMA, 2003

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

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


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?

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

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

John C. Parker, MD: 1935-1993

Eugene P. OrringerFellowship TrainingFellowship Training

• Clinical Hematology

• Red Cell Physiology

Membrane Transport

Volume Regulation

Metabolism

Eugene P. Orringer Initial NIH FundingInitial NIH Funding

Co-I on Dr. John C. Parker’s R01

Eugene P. Orringer Subsequent NIH Funding

• PI: RCDA from NHLBI

• PI: R01 from NHLBI

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

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

Wendell F. Rosse, MD


• 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


• 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


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

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

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

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

UNC MD-PhD Program1995 to the Present

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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

Institutional Philosophy - I

The best medical centers benefit from individuals with varying skills

Superb investigators

Excellent leaders

Effective administrators

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

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

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

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

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

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

Clinical Research Enhancement ActPublic Law #106-505Public 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)

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”

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

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


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

NIH Support UNC School of Medicine

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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!!!


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)


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

IndependentInvestigatorInternship/Residency SpecialtyMedical

School

Mentored Patient-Oriented Mentored Patient-Oriented Research CDA (K23Research CDA (K23)

K23 - Patient-Oriented Research CDA

NIH Goal for K23: To fund at least 100 new awards/year

Total # of K23 Awards made by the NIH

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K23 Awards to junior faculty members at UNC

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1998 0 n/a 1999 2 1.4 2000 8 2.4 2001 15 3.0 2002 22 3.3

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NIH Support to UNC

NIH $’s NIH $’s NIH (Millions) (%) Ranking

1999 131 1.02 172000 144 0.98 152001 170 1.08 15

NIH - Total Extramural Awards

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UNC School of MedicineTotal NIH $’s vs K23 Awards

NIH Grants K23 Awards * (%) (%)

1999 1.02 1.42000 0.98 2.42001 1.08 3.02002 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


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

UNC-Chapel HillMedical 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

UNC-Chapel HillMedical 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


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

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


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

UNC-Chapel HillUNC-Chapel Hill

Career Development Career Development

for Clinician-Scientistsfor Clinician-Scientists

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

UNC Seeks to Foster the Development of Clinician-Scientists

Programs for Career Development

• K30 Program

• K12 Awards

• Minority Cohort Program

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


• 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)


Broad-Based ProgramSchools of Medicine, Pharmacy, & Public Health

Two-year durationYr 01 = didactics, design the research project,

develop a grant proposal

Yr 02 = Conduct of the research project Submit a grant proposal

K30 - Clinical Research CurriculumStructureStructure

• Coursework

• Seminar Series

• Research Project

• Work-in-Progress Presentations

• Grant Preparation

• Mock Study Section Reviews

• Mentoring Panels

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 AwardsK23 Awards 6 6 3 3 * * Note that 2 of these individuals are Professors on sabbatical. The Note that 2 of these individuals are Professors on sabbatical. The

others, fellows in their initial year of the K30 Program, are not yet others, fellows in their initial year of the K30 Program, are not yet ready to write a K23.ready to write a K23.

UNC Seeks to Foster the Development of Clinician-Scientists

Programs for Career Development

• K30 Program

• K12 Awards

• Minority Cohort Program

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

The BIRCWH Program K12 Award

Building

Interdisciplinary

Research

Careers in

Women’s

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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

UNC BIRCWH Program

Developed the concept that if funded, the UNC BIRCWH Program would have both:

• BIRCWH Scholars

• BIRCWH Associates

BIRCWH Scholar

An individual who is receiving salary support from the BIRCWH grant

BIRCWH AssociateAn 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

UNC BIRCWH Program

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 masscritical mass of approximately 15 young people with interests and backgrounds that are remarkably diverse.

K12 Awards

A very inexpensive way to fund the next generation of academic research

ExampleExample

Using the BIRCWH model, $5 Million supports 10 Using the BIRCWH model, $5 Million supports 10 programs & 50 Trainees/yearprograms & 50 Trainees/year

K12 AwardsA K12 can have a big multiplier effect

ExampleExampleWe have found that if they are used We have found that if they are used effectively, each K12 slot can be turned effectively, each K12 slot can be turned over 2-3 times in a 5 year cycleover 2-3 times in a 5 year cycle

K12 – BIRCWH ProgramStatus 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 2R03 Awards 3 -Doris Duke Award 1 -Pfizer Award 1 -Others 8 4

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


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


• 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

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

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

.

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

.

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

MCP ScholarsFunding Status of the Scholars

Independent funding status of the Scholars (n = 10) who have received support from the MCP between 1994 & the present

Award Type Funded

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

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

• 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

Documents

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