Funding Opportunities for Clinical Research

1
Funding Opportunities for Clinical Research

• Henry P. Parkman, MD
• Professor of Medicine
• Gastroenterology Section, Department of Medicine
• Temple University School of Medicine
  Philadelphia, PA
• Director - Clinical Research Unit
• Member - Temple IRB, IRB AE

2
Types of Research Performed by Clinicians

• Basic research
• laboratory studies
• fundamental studies on people
• Clinical research
• Clinical studies
• descriptive cohort studies
• comparative cohort (risk factor) studies
• randomized, controlled, trials of diagnostic or
• therapeutic interventions
• Translational studies
• lab studies on clinically-relevant problems
  Bench to Bedside
• Community-based research Bedside to Practice
• medical practices
• Access, delivery, utilization, outcomes
• health care policy studies

3
What is Needed for Clinical Research?

• Investigator(s)
• Coordinators
• Infrastructure at Institution
• IRB, Sponsored Projects (Budget, Contracts)
• Project
• Space
• Funds (Clinical trials or Grants)
• Patients

4
Overview of Funding Opportunities for Clinical
Research Studies

• Temple Faculty Awards Programs at Temple
• Soprano Tobacco Settlement Funds
  (Multidepartmental, New area, Bridge grants)
• Richter Department of Medicine Awards (Young
  Investigator)
• Industry Initiated Funded Clinical Trial
  (Pharmaceutical Device Companies)
• Phase I
• Phase II
• Phase III
• Phase IV
• Investigator-Initiated Industry Funded
• Society/Foundation Funded
• NIH R01, R21, R03, STTR, K23, K24, etc
• Institutionally-Supported (Unfunded) Research

5
Goals for a Clinical Research Career

• Series of Clinical Research Projects
• along a common theme to address important areas.
• Implement and Complete Clinical Research Projects
• Generate more ideas, hypotheses
• Get another grant

6
Career Progression for MDs for a Research Career

• Clinical Fellowship Training Mentored Clinical
  Projects
• Postdoctoral Mentored Research T32, F32
• Medical School Grants
• Advance/Nurture Career Industry-Supported
  Studies
• Societal Research Grants
• K23
• Independent Investigator R01, U01
• Expand Areas of Research R21, R03
• Mentor Others in Clinical Research K24

7
NIH Institutes and Study Sections

• The NIH is comprised of Institutes and Centers
  that support specific areas of health-related
  research.
• Each Institute and Center maintains a web site
  with funding opportunities and areas of interest.
  
• Contact an Institute or Center representative may
  help focus the research plan based on an
  understanding of the mission of the Institute or
  Center.

8
NIH Grants Activity code groups

• F Fellowships (all levels)
• G Resource programs
• K Research Career
• M M01 GCRCs - - CTSAs
• P Research Program Projects Centers
• R Research Projects
• S Research-related
• T Training Programs
• U Cooperative Agreements

9
Career progression for MDs in research

• Finish clinical training

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

Fellowships
advance/nurture your career (3 - 5 years)
Career Development Awards (K)
Research grants
become an independent investigator
10
NIH R01 Research Project Grant Program

• The classic, time honored NIH grant.
• Used as a marker of independence in research and
  criteria for academic promotion.
• Provides support for health-related research and
  development based on the mission of the NIH.
• Supports a discrete, specified, project to be
  performed by the investigator(s) in an area
  representing the investigator's interest and
  competencies.
• Can be investigator-initiated or can be in
  response to a program announcement (PA) or
  request for application (RFA).

11

• 25 page Research Plan (Specific Aims, Background
  and Significance, Preliminary Studies, and
  Research Design/Methods) Instructions provided in
  PHS 398 Grant Application kit
• Applicants should seek advice from an experienced
  investigator and to contact the Institute or
  Center most likely to review/fund their
  application. NIAID provides an annotated R01 and
  attached summary statement on their website
  http//www.niaid.nih.gov/ncn/grants/app/default.ht
  m.
• Standard receipt dates for grant applications are
  February 1, June 1, and October 1.
• All Institutes and most Centers at NIH support
  the R01 grant mechanism.
• Submitted research grant applications are
  assigned to an Institute or Center based on
  receipt and referral guidelines.
• On submission, applicant can provide cover
  letter for grant to suggest a study section.

12
Budget for NIH R01

• Applicants for an R01 award are not limited in
  dollars but need to reflect the actual needs of
  the proposed project.
• Modular applications are most prevalent with
  modules of 25,000, up to the modular limit of
  250,000.
• Applications that exceed this level must be
  submitted as non-modular and provide detailed
  budget information.
• Applications are generally awarded for 1 - 5
  budget periods, each normally 1 year in duration.
  
• Allowable Costs
• Salary and fringe benefits for Principal
  Investigator, key personnel, essential personnel
• Equipment and supplies
• Consultant costs
• Alterations and Renovations
• Publications and miscellaneous costs
• Contract services
• Consortium costs
• Facilities and Administrative costs (indirect
  costs)
• Travel expenses

13
R21s

• Exploratory grants
• Institute-specific
• Not renewable
• Budgets limited to no more than 275,000 for a 2
  year period
• Reviewed in standard study sections in CSR

http//grants.nih.gov/grants/funding/r21.htm
14
R03s

• Small grants
• 50,000 per year for 2 years
• some Institutes use 100,000 for some R03s
• Not renewable
• Reviewed (usually) in Institute study sections

http//grants.nih.gov/grants/funding/r03.htm
15
Career Development Awards (K awards)

• Designed primarily to protect time provide
  salary to free up time currently spent on
  clinical, teaching, or administrative duties
• Most are for early career development
• K01 Mentored Research Scientist Development
  Award
• K08 Mentored Clinical Scientist Development
  Award
• (Basic Science Research)
• K23 Mentored Patient-oriented Research Career
  Development Award
• (Clinical Research)
• K24 Mid Career Investigator Award in
  Patient-oriented Research

16
For K awards

• Should already know your scientific area
• Pick a true mentor (s)
• Identify your research project
• Design a research project that will allow you to
  learn new techniques AND differentiate your from
  your mentor
• Design a career development plan to move your
  career forward.

17
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)

-- use co-mentors )
18
Application details Ks

• NIH Guide K08 PA-00-003 (NIH)
• K23 PA-00-004 (NIH)
• K24 PA-04-107 (NIH)
• Application form PHS 398
• See the special instructions at the end (Section
  4)
• Receipt dates
• February 1, June 1, October 1
• Reviewed in Institute-organized study sections

19
Searching the NIH

• NIH Guide for Grants and Contracts
• All NIH Notices, RFAs, and PAs are published on
  line
• CRISP (Computerized Retrieval of Information on
  Scientific Projects)
• Searches Current and Past NIH Funding
• Abstracts of funded grants
• http//crisp.cit.nih.gov

20
Request for Applications (RFA)

• One receipt date
• Money is committed AND amount is indicated in
  RFA
• Review usually organized by Institute
• Scores not percentiled
• Often
• More than one Institute involved (i.e. more
  chances, more money).

21
Program Announcement (PA)

• Shows Institute has an interest in area
• Multiple receipt dates
• Active for 3 years (unless otherwise stated)
• Funds are not set-aside, but PA is considered
  when making funding decisions
• Review usually in CSR study sections
• Sometimes more than one Institute.

22
unsolicited R01 vs. RFA-R01
R01
RFA-R01
3x/year
1 time

• Receipt Date
• Review
  Committee
• Funding

CSR -- multiple
Single study section reviews all applications
-ile program relevance balance budget, new
investigator (geography)
rank RFA specifics and stated in RFA
23
Investigator-Initiated Industry-Funded Research
Grant

• One year project
• Budget from 25,000 to 150,000
• The research generally needs to help the company
  and their products
• Discuss idea/project with the Companys Medical
  Science Liaison assigned to Temple. They will
  discuss your idea with you and then with others
  to provide helpful suggestions to get the project
  funded.
• Grants reviewed in the Industrys Research
  Committee

24
Steps in an Investigator-Initiated Clinical
Research Study

• Create an Idea / State a Hypothesis
• Review the Literature
• Design the Methodology for the Study
• Write the Protocol (Study protocol, Grant
  request, IRB)
• Develop the Budget
• Obtain funding
• Regulatory Review Sponsor, FDA, IRB/others, CTA
• Perform the Study
• Site Visit Monitoring Maintaining Time Lines
  and Quality Control
• Analyze the Data
• Test the Hypothesis

25
Essential Elements of a Clinical Study Grant and
Protocol

• Research objective
• Hypothesis
• Background
• Preliminary Data
• Eligibility criteria
• Treatment plan
• Risks and Benefits
• Alternative Treatments
• Data collection
• Statistical Analysis
• Sample Size Determination
• Regulatory Issues
• Bibliography
• Budget
• Informed Consent Form, HIPAA

26
What Shall I Study?"

• Willingness to question what we do as clinicians
  and what we teach our students.
• We do clinical research because we really do not
  know the best answers to the research questions.
• Importance of the issue
• 1. Is this an important clinical issue?
• a. Is it important to practitioners?
• b. Is it important to patients?
• 2. Public health impact
• a. Size of population at risk
• b. Morbidity and mortality

27
How Do We Convince Others, especially the
Reviewers?"

• Build the leadership team -- clinicians,
  biometricians
• Create the consensus (but avoid regression to
  mediocrity)
• Key ingredients in convincing others
• Documentation of the clinical, scientific, and
  public-health importance of the problem
• High quality research plan that explicitly
  addresses well-stated hypotheses and that has
  high likelihood of definitively answering the
  clinical question
• Pilot data to demonstrate feasibility
• Detailed discussion of strengths and weaknesses
  of the proposed approach
• Detailed discussion of strengths and weaknesses
  of alternative approaches

28
Enlist the Help of Expert Collaborators

• Every clinical proposal should include a
  biostatistics or bioinformatics expert, as
  follows
• Experienced
• Involved from the start
• Responsible for
• Design of Experiments
• Study Organization
• Statistics design, power, sample size
• Data -- accrual, flow, storage, management,
  analysis, reports
• Quality Control -- eligibility, treatments,
  follow-up, data management
• Writing portions of the grant application and
  Manual of Procedures

29
Some Bottom Lines

• Plan ahead
• Start writing/organizing a grant 6-9 months
  before the due date
• Build a network
• Talk across departments, across disciplines
• Be persistent
• Never take a review personally
• Never respond in anger to a review
• Never ignore a reviewers concerns
• Take a chance
• An application that isnt submitted cant be
  FUNDED

30
(No Transcript)
31
Sponsor-Initiated vs. Investigator-InitiatedClini
cal Research

• Sponsor
• Project Director
• Clinical Project Manager
• CRO
• Clinical Project Manager
• Monitor/CRA
• Data Management Team
• Clinical Laboratory
• Study Site
• Investigator
• Study Coordinator
• Patients

• Organizing institution(s)
• Principal Investigator
• Clinical Project Manager
• Study Coordinator
• Data Manager
• Biostatistician
• Clinical Laboratory Scientist
• Patients
• Participating Institutions
• Investigator
• Study Coordinator

For Investigator-Initiated research studies, the
PI is the leader! Determines rationale and
study design. Responsible for study
implementation and successful completion.
32
Data Collection, Statistics, and Sample Size

• Identify the studys primary outcome
• How will this be measured what are the units
• Comparing treatments/populations?
• What statistical test will be used to compare?
• Determine the appropriate sample size
• How much of a difference is clinically
  important?
• What is the variability of the measure in the
  study population?

33
Sample Size Determination(Power Calculation)
Significance (?) (type-I)
Effect Size -------------- Variation (SD)
Power (1-?) (type-II)
Sample Size
34
Power Calculation Trade-Offs in the Real World
Sample Size
Significance (?) (type-I)
Constraints
Effect Size -------------- Noise (SD)
Power (1-?) (type-II)
Funding Time Personnel SD is unknown
35
Registration of Clinical Trials

• The members of the International Committee of
  Medical Journal Editors have implemented a
  requirement that all clinical trials must be
  entered in a public registry before the onset of
  patient enrollment as a condition of
  consideration for publication in member
  journals. Journals participating in this
  clinical trial registration include NEJM, Annals
  Internal Medicine, JAMA. Our several GI journals
  did not endorse this.
• The public clinical trials registries are to help
  ensure that key information about clinical trials
  are readily available and to promote public good.
  
• For multi-center trials, it is usually the lead
  sponsor who should take responsibility for
  registration. Investigators and sponsors should
  work together so that a trial is registered only
  once.
• For single-center studies, the PI needs to ensure
  trial registration.
• Protocol Registration System at
  www.Clinicaltrials.gov
• There are two types of PRS accounts 1)
  Organization accounts generally have multiple
  users and are used to register trials conducted
  at an organization 2) Individual accounts are
  used to register trials conducted by a single
  investigator.

36
Common Problems with Implementation/Completion
of Clinical Studies

• Poor infrastructure of PI/institution to support
  clinical studies
• Lack of clinical trials to support personnel
  needed
• Clinical coordinators, etc
• IRB taking too long for approval
• Understand how the IRB works to help speed up
  approval
• Contract taking too long for approval
• Recruitment of study subjects/patients can be
  slow
• Protocol when implemented is too difficult

37
Set up your Research Team

• Mentor
• Common area of research interest
• ?Both trainee and mentor with something to gain
• Regular meetings
• Collaborators
• Other interested individuals
• Multidisciplinary, translational research
• Research coordinators
• Research meetings/conferences
• Review data
• Review progress on studies
• New ideas/studies