Introduction to Clinical Research Understanding the Essentials for Starting a Study

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Introduction to Clinical ResearchUnderstanding
the Essentials for Starting a Study

• December 4, 2003 Henry P. Parkman, MD
• Investigator-Initiated Grants at the NIH
  Something for Everyone.
• December 11, 2003 Steve Houser, PhD
• Planning a Successful NIH Research Grant
• December 18, 2003 Bill Hirschhorn, MS
• Investigator-Initiated Clinical Studies Funded
  by Industry Applying for Research Support

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Investigator-Initiated Research Grants at the
NIH Something for Everyone

• Henry P. Parkman, MD
• With help from
• Judith Podskalny, Ph.D.
• Program Director, NIDDK, NIH
• NIH Funding Opportunities for Young Investigators

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Overview of Important Points

• Decide which NIH Institute or Center
• bests suits your research.
• Know the different types of grants
• for your career stage.
• Subscribe to NIH Guide for Grants and Contracts.

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Where To Go at the NIH

• Decide where you fit.
• Go to http//www.nih.gov
• Identify the several most likely Institutes for
  funding based on your specialty/scientific
  interests
• Become familiar with those Institutes websites
• Contact appropriate staff early in the process of
  applying for any grant

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National Institutes of Health -1 (Institutes or
Centers)

• National Institute of Diabetes and Digestive and
  Kidney Diseases (NIDDK)
• National Cancer Institute (NCI)
• National Institute on Alcohol Abuse and
  Alcoholism (NIAAA)
• National Institute of Allergy and Infectious
  Diseases (NIAID)
• National Institute of General Medical Sciences
  (NIGMS)
• National Institute for Biomedical Imaging and
  Bioengineering (NIBIB)

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National Institutes of Health -2 (Institutes or
Centers)

• National Institute of Child Health and Human
  Development (NICHD)
• National Institute on Drug Abuse (NIDA)
• National Institute on Deafness and Other
  Communication Disorders (NIDCD)
• National Institute of Dental and Craniofacial
  Research (NIDCR)
• National Institute of Environmental Health
  Sciences (NIEHS)
• National Eye Institute (NEI)

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National Institutes of Health -3 (Institutes or
Centers)

• National Heart, Lung and Blood Institute (NHLBI)
• National Human Genome Research Institute (HGRI)
• National Institute on Aging (NIA)
• National Institute of Mental Health (NIMH)
• National Institute of Neurological Disorders and
  Stroke (NINDS)
• National Institute of Arthritis and
  Musculoskeletal and Skin Diseases (NIAMS)

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National Institutes of Health -4 (Institutes or
Centers)

• National Institute of Nursing Research (NINR)
• National Center for Complementary and Alternative
  Medicine (NCCAM)
• National Center for Research Resources (NCRR)
• National Library of Medicine (NLM)
• Fogarty International Center (FIC)
• National Center on Minority Health and Health
  Disparities (NCMHD)

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Types of Grant Support

• Consider your career stage

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Career progression for MDs in research --

• Finish clinical training

• Do postdoctoral research (mentored)
• (1 3 years)

Fellowships (F,T)
Advance/nurture your career (3 - 5 years)
Career Development Awards (K)
Research grants (R)
Become an independent investigator
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Typical NIH-funded Research Career Pathway

• Medical Postgraduate Junior Experienced
• School (Post-fellowship) Faculty Faculty
• T32 T32 K01 R01
• F31 F32 K08, K23 K24
• T35 K25 R03, R21

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Ruth L. Kirschstein National Research Service
Awards (NRSA) T32 NRSA Institutional Training
GrantF32 NRSA Individual Fellowship Award

• This category of training support provides a
  stipend, or 'living expenses' allowance, to
  predoctoral students while they work toward their
  research degree, or to postdoctoral fellows while
  they obtain additional research experience in a
  mentor's laboratory.
• Applicants must be U.S. citizens or permanent
  U.S. residents.

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NRSAs
T32s
F32s

• Individual award
• Fellow is PI
• 416-application form
• Receipt dates
• April 5
• August 5
• Dec. 5
• Funding 6-9 months later

• Institutional award
• A senior mentor is PI
• Pre- and/or Post-doc slots awarded
• Appointments left up to PI at institution
• Grant is 5 years, renewable

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NRSA (i.e. T32 F32) features

• U.S. citizen or permanent residents ONLY
• Must be full-time training
• 3 year limit on postdoctoral support
• Stipend, not salary
• First 12 months of support subject to payback

• no exceptions

• MDs only 75-80

• MDs can usually get a waiver

• supplementation and compensation allowed

• 2nd year pays back 1st year

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Institutional Training Grants (T32s)

• all NIH-supported training grants can be found
  at
• http//grants1.nih.gov/training/outcomes.htm
• all NIDDK-supported training grants can be found
  at
• http//www.niddk.nih.gov/fund/training/T32table.ht
  m

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Career Development AwardsThe K Awards

• Career development awards provide salary and
  laboratory support for individuals who have
  completed their postdoctoral training, or who
  merely need 'protected time' at critical periods
  of their research careers.
• NIH Clinical Research Career Development programs
  of help maintain a cadre of biomedical
  researchers in the US.
• These grant programs are designed to attract
  talented medical students, physicians, dentists,
  and similar professionals to the challenges of
  clinical research or to help clinical
  investigators transition to independent research
  careers.

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NIH Director's Panel on Clinical Research (CRP)
1997 Report

• The Panel's three-part definition "clinical
  research is
• (a) Patient-oriented research. Research conducted
  with human subjects (or on material of human
  origin such as tissues, specimens and cognitive
  phenomena) for which an investigator (or
  colleague) directly interacts with human
  subjects. This area of research includes
• Mechanisms of human disease
• Therapeutic interventions
• Clinical trials.
• Development of new technologies
• (b) Epidemiologic and behavioral studies
• (c) Outcomes research and health services
  research.

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Recommendations Concerning Training and Support
for Clinical Investigators

• Recommendation 3. The NIH should initiate
  training programs that will enhance the
  attractiveness of careers in clinical research to
  medical students.
• Recommendation 4. The NIH should improve the
  quality of training for clinical researchers by
  requiring grantee organizations to provide formal
  training experiences in clinical research and
  careful mentoring by experienced clinical
  investigators.
• Recommendation 5. The NIH should initiate
  substantial new support mechanisms for young and
  mid-term clinical investigators, if possible in
  collaboration with the private sector.
• Recommendation 6. A loan repayment program for
  clinical investigators should be instituted.

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Career Development Awards or K-series Awards

• designed to protect time, i.e., free up time
  currently spent in clinic or on administrative
  duties
• most are for early career development
• provide salary not stipend
• meant to train U.S. citizens/permanent residents
• limited to U.S. research/clinical institutions

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K-series Awards

• K01 Mentored Research Scientist Development
  Award
• K08 Mentored Clinical Scientist Development
  Award
• K23 Mentored Patient-oriented
• Research Career Development Award
• K24 Mid Career Investigator Award in
  Patient-oriented Research

PhD, non-clinical MD
MD, bench research
MD, clinical research
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K23 Mentored Patient-Oriented Research Career
Development Award

• Provide physicians with up to 5 years of support
  to pursue more clinically oriented research
  careers directly involving patients. For early
  career physicians who have made a commitment to
  clinical/patient-oriented research.
• The three to five years of supervised study and
  research supported by this award provide
  clinically trained professionals with an
  opportunity to develop independent research
  skills and to gain experience in advanced methods
  and experimental approaches needed to carry out
  patient-oriented research.
• An eligible candidate must have (1) an M.D.,
  D.D.S., or equivalent (2) a mentor (3) a career
  development plan.

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Mentored Clinical Scientist Development Awards
(K08)

• Provide physicians with up to 5 years of support
  to pursue research careers. Generally to work in
  a basic science laboratory, not for clinical
  research.
• The Small Grant Program for NIDDK K08/K23
  Recipients allows NIDDK K08-holders to apply for
  up to 50,000 per year of extra research support
  in the final 2 years of their K08 to help in
  their transition to independence.

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K24 Midcareer Investigator Award in
Patient-Oriented Research

• Provides support to established clinical
  investigators who are actively engaged in
  patient-oriented research and who serve as
  mentors for new clinical investigators.
• Allows them protected time to (1) devote to
  clinical/patient-oriented research, (2) enhance
  their clinical research skills in order to
  conduct meritorious patient-oriented research,
  and (3) mentor beginning clinical investigators.
• Target candidates are outstanding clinical
  scientists who are engaged in patient-oriented
  research, are within 15 years of their specialty
  training, can demonstrate the need for a period
  of intensive-research focus as a means of
  enhancing their clinical research careers, and
  committed to mentoring.

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Elements Reviewed in K applications

• Qualifications of candidate (prior training,
  letters of recommendation, publications)
• Mentors (previous mentoring experience, expertise
  in area of research)
• Research project (hypothesis driven, preliminary
  data, reasonable in time frame, logical sequence
  of studies, appropriate safeguards)
• Career development plan and Environment
  (enrichment, training, future plans)

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2002 K-award success rate
Total 1169
Total 664
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Research Project grants R-series awards

• R01s Research project grants unsolicited and
  in response to PAs and RFAs
• R21s Exploratory/Developmental grants
  usually only in response to PAs or RFAs
• R03s Small grants only in response to PAs or
  RFAs
• R34s Clinical trials planning grants

New
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New Funding Opportunities

• Sign up to receive the NIH Guide for Grants and
  Contracts. Join the List Serve at
• http//grants.nih.gov/grants/guide/listserv.htm

• Once a week receive the Table of Contents with
  active links to all
• Notices,
• Request for Applications (RFA), and
• Program Announcements (PA, PAR)

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NIH Loan Repayment Program (LRP)

• Seeks to retain an adequate national pool of
  physicians and dentists who are trained to be
  independent clinical investigators.
• Provides for repayment of the educational loan
  debt of physicians and dentists.
• Individuals must hold peer-reviewed research
  funding and have educational debt that exceeds
  20 of their salary.

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NIH Budget Growth 1993 to 2003
2003E 27.0 billion 1.98 fold
5
4
3
2
1
1998 start of doubling of NIH Budget 13.7
billion
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A final take home message --

• If you dont apply, you cant be funded
• Contact the NIH before you start preparing
  application
• AND while writing it
• AND after you submit

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Loan Repayment Programs

• Two new programs began in 2002
• for Clinical Researchers
• (Public Health Act of November 2000)
• for Pediatric Research
• (Childrens Health Act of 2000)

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LRP features

• Provides up to 35,000 per year for 2 years to
  pay principal and interest on educational debt
• NIH pays the taxes on this amount directly to the
  IRS
• Institutes prioritize their own applications

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LRP Eligibility

• Dependent upon indebtedness
• Owe more than 20 of annual income
• Must be an educational loan

DO NOT refinance or combine loans

• Engaged in research at least 50 of the
  time for at least
• 2 years (concurrent with loan repayment)
• U.S. citizen or permanent resident

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LRP Time-line for 2003 (2004)

• November application forms available on NIH
  homepage
• January 31 applications due at LRP office
• February applications sent to ICs
• April applications peer-reviewed and then IC
  staff develop pay plans
• May/June results reported to Advisory Councils
• July contracts issued

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• Why should you apply for LRP?

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LRP in 2002

• Goal in 2002 was 250 contracts NIH-wide, 28
  million
• minimum of 20 for pediatric, the rest for
  clinical researchers
• NIDDK was allocated 15 contracts (1.5 mill)
• NIDDK Director allocated more funds to award 20
  (2 mill)

.actually
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LRP 2002

• NIDDK received 66 LRP applications
• We issued 58 contracts
• Success rate 87

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LRP 2003 changes

• Open to non NIH-grantees as long as engaged at
  least 50 of the time in research
• NIH obtained waiver to delay payback obligation
  for NRSA recipients so they can apply

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LRP 2003 current status

• NIH received 1700 applications
• NIDDK assigned 166

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LRP information

• www.lrp.nih.gov

• Sign up to receive information

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GCRC Mentored Medical Student Clinical Research
Program

• NCRR provides supplemental funding to the General
  Clinical Research Centers (GCRCs) that it already
  supports so the GCRCs can establish institutional
  programs that will introduce medical students to
  potential careers in clinical research.
• GCRCs are the focal point of this award program
  because they provide the necessary infrastructure
  and environment to expose medical students to
  both didactic training and the clinical practice
  of patient-oriented research.

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Short-term Institutional Training Grants (T35)

• Awarded to medical or other health professional
  schools to support summer research experiences
  for students between the first and second years
  of school.

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Individual Postdoctoral Fellowships (F32)

• Provide up to three years of support for
  qualified individuals who have received a Ph.D.,
  M.D., or equivalent degree.
• The award supports supervised research to enable
  biomedical scientists and clinicians to broaden
  their scientific backgrounds and expand their
  potential for research in health-related areas.
• Prior to submission, an applicant must arrange
  for an appointment to an appropriate institution
  and acceptance by a sponsor who will supervise
  the training and research experience.
• The institutional setting may be a domestic or
  foreign nonprofit, private or public institution,
  including the NIH. The postdoctoral fellow is the
  applicant on the application and award, and must
  participate in the planning of the research
  project proposed.

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Individual Predoctoral Fellowships (F31) for
Minority Students and for Students with
Disabilities

• Provide up to 5 years of support for research
  training leading to the Ph.D., or equivalent,
  research degree.
• The intent of both programs is to encourage
  students from these groups to seek graduate
  degrees and thus increase the number of minority
  investigators and of persons with disabilities
  who are prepared to pursue careers in biomedical
  and behavioral science research.

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Institutional Training Grants (T32)

• Awarded to institutions with strong research
  programs to support a designated number of pre-
  or postdoctoral fellows, appointed by the
  training director at the institution.

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K12 Mentored Clinical Research Scholar (CRS) Award

• Provides support to institutions to establish
  career development for physicians and dentists so
  they may develop the research skills necessary to
  become independent, clinical/patient-oriented
  investigators.
• Candidates for the program are selected from
  among the recently trained physicians and
  dentists. Funds may be used to support full or
  partial completion of an advanced degree such as
  an MS, PhD, MPH.
• The program must include activities that will
  provide candidates with a comprehensive
  understanding of clinical research approaches
  that are fundamental and not necessarily
  disease-specific.
• The lead mentor, an established clinical
  researcher who holds a faculty position, will
  work closely with the candidate to develop a
  tailored career development plan.

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Individual Senior Fellowships (F33)

• Provide the opportunity for experienced
  scientists to make major changes in the direction
  of their research careers, to broaden their
  research capabilities, or to enlarge their
  command of an allied research field.
• Candidates must have received a doctoral (Ph.D.,
  M.D.), or equivalent degree, and must have had at
  least 7 subsequent years of relevant research or
  professional experience by the time the award is
  made.
• The total period of the award will not exceed 24
  months, although 12 months is more usual.
• These awards are not made for study leading to
  any of the professional degrees (M.D., O.D.,
  D.D.S., etc.) or for residency or other clinical
  training.

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Mentored Research Scientist Development Awards
(K01)

• Provide Ph.D., or other comparable researchers,
  with support for up to 3-5 years following
  postdoctoral training to transition into
  independence and obtain regular research grant
  (R01) funding.