Role of the General Clinical Research Center GCRC in Clinical Research October 31, 2006

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Role of the General Clinical Research Center
(GCRC) in Clinical ResearchOctober 31, 2006
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The General Clinical Research Center

• dedicated to the advancement of scientific
  investigation of normal and abnormal human
  physiology with the goal of advancing knowledge
  of causes, prevention, control and cure of human
  diseases.

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The University of Virginia GCRC

• Serves as a laboratory in which to conduct
  clinical investigation
• Provides both practical and didactic education
  opportunities for M.D.s and Ph.D.s interested
  in clinical investigation

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About the GCRCs...

• There are 78 GCRCs nationwide, all supported by
  the National Institutes of Health
• The GCRCs are funded for up to five years with a
  competitive renewal required
• The UVA GCRC will receive 22,030,026 in funding
  during our current 5 year renewal
• The GCRC Programs are scheduled to become part of
  the larger NIH Clinical Translational Science
  Awards (CTSA)

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The UVA GCRC Consists of

• 10 inpatient beds
• outpatient facilities
• a Metabolic Kitchen
• a research nurse staff functioning 24/7
• a Core Assay Laboratory
• an Informatics Core
• a Biostatistical Core
• a Biomathematics Core
• an Exercise Physiology Laboratory
• a Sleep-Monitoring Laboratory

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GCRC Protocols

• A Investigator-initiated, pure research
  studies subjects/patients admitted solely for
  purpose of participating in the research study
• B Investigator-initiated studies utilizing
  patients admitted to hospital for medical care
• D Industry-initiated or sponsored studies
  sponsor pays expenses

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UVA GCRC New A Protocols by Theme
Diabetes, Neurology, Cystic Fibrosis, G.I.
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GCRC Administrative Structure

• Principal Investigator Arthur Tim Garson,
  M.D., M.P.H.
• Program Director Eugene J. Barrett, M.D., Ph.D.
• Associate Program Directors
• William S. Evans, M.D.
• Dan Haisenleder, Ph.D.
• Mary Lee Vance, M.D.
• Administrator Pamela F. Sprouse

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GCRC Nursing Services

• Nursing Coordinator Sandra Ware-Jackson, R.N.
• Provide technical support and clinical care to
  subjects and patients participating in both
  inpatient and outpatient protocols
• Act as primary contact between PI and
  subjects/patients

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GCRC Assay Core Laboratory I.

• Director Dan Haisenleder, Ph.D.
• Manager Pattie Hellmann
• Technicians David Smith, Sally Rittenhouse
• ..to provide cost-effective assay services to
  GCRC investigators with exemplary quality
  assurance

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GCRC Assay Core Laboratory II.

• Services offered include
• Immunoradiometric, immunoflurometric,
  chemiluminescent, and Elisa assays of 40
  individual substances
• Automated data management
• Development of new assays as needed by
  investigators

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The Metabolic Kitchen

• Dietitian Jessica Rodriguez, R.D.
• Chefs Rick Friend, Dornita Herndon, Vanda
  Mattysse
• Develops and prepares metabolically-balanced,
  controlled nutrient research diets for protocol
  subjects
• Provides software for analysis of nutrient intake
• Instructs subjects in specialized diets

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The Informatics Core

• Informatics Manager Martin T. Phillips, B.S.
• Provides investigators with computer tools to
  facilitate analysis/publication of research data
• Networks with other UVA GCRC Cores
• Facilitates interactions among research centers
  including other GCRCs.

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The Biostatistics Core I.

• Biostatisticians RD Abbott, Ph.D., DG Boyd,
  M.S.,
• JT Patrie, M.S.
• Assists in protocol development by
• Helping to formulate hypotheses that can be
  analyzed statistically
• Identifying experimental designs and efficient
  statistical procedures
• Recommending sample size
• Analyzing data
• Interpreting statistical results for clinical
  investigation

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The Biostatistics Core II.

• Reviews all protocols submitted to the GCRC
  Advisory Committee
• Contributes to training through coursework,
  tutorials and symposia focussed on biostatistics

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The Biomathematics Core

• Biomathematician Michael L. Johnson, Ph.D.
• Provides support to address biological issues
  using advanced mathematical approaches
• Develops/modifies specific biomathematical
  techniques such as
• -Cluster -Pulse -HyperGeo -Cross ApEn
• -Deconv -Pulse2 -ApEn
• Organizes an annual workshop for clinical
  investigators interested in applying
  sophisticated mathematical approaches to biologic
  questions

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The Exercise Physiology Laboratory I.

• Director Arthur L. Weltman, Ph.D.
• Provides consultation regarding protocol
  development and training of investigators
  interested in exercise physiology techniques

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The Exercise Physiology Laboratory II.

• Provides support for procedures related to
• exercise (e.g., training and evaluation)
• metabolism (e.g., calorimetry)
• body composition (hydrostatics weighing DEXA
  bioelectrical impedance)
• strength/balance function

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The Sleep Research Laboratory

• Director Paul M. Suratt, M.D.
• Provides consultation for protocol development
  for investigators interested in monitoring
  subjects during sleep
• Provides monitoring of sleep stages, breathing,
  ECG and other physiological signals during sleep
• Provides integration of sleep stages with other
  parameters such as hormone secretion during sleep
• Provides interpretation of data collected using
  the above techniques

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Training in Clinical Investigation

• An optimal training program would include
• practical, hands-on experience
• appropriate didactic work
• mentoring

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Approaches to the Training of Clinical
Investigators

• Highly structured, thesis-requiring graduate
  programs resulting in the granting of a Masters
  Degree or Ph.D.
• Relatively flexible, certificate granting
  programs with emphasis on highly relevant
  didactic work and mentoring

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1997
HES
GCRC
Multidisciplinary Training Program in Clinical
Investigation (MTPCI)
Masters Program in Public Health Sciences
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1997 Multidisciplinary Training Program in
Clinical Investigation (MTPCI)

• Targets senior fellows and junior faculty
• Tuition is via the Community Scholar Program
• 3-6 year part-time training effort
• Emphasis on grant submissions peer-reviewed
  publications rather than a thesis
• Certificate in Clinical Investigation awarded
  upon successful completion of program
  requirements
• Acquisition of grant support is a major objective

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The Didactic Program

• Required Core Courses
• Introduction to Clinical Investigation
• Introduction to Biostatistics
• Fundamentals of Epidemiology
• Research Ethics
• Elective Courses
• Chosen with guidance from the trainees
  Mentoring Committee from any school within the
  University of Virginia

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The Mentoring Process

• Each trainee has a committee comprising 3 senior
  faculty members, each of whom brings something
  to the table
• The full committee trainee meet twice a year
• Structure of the meeting
• Goals objectives from the last mentoring are
  reviewed
• Progress since last mentoring is discussed
• Goals objectives for the next six months are
  agreed upon including specific coursework
  recommendations
• Formal summary report is generated
• The trainee schedules a post-mentoring session
  review with the Program Director

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Grant Preparation Resources I.
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Grant Preparation Resources II.

• Grant-specific notebooks contain
• NIH and University forms and instructions
• completed applications from UVa funded grants to
  serve as examples.

• Collection includes K-01, K-08, K-23, K-24,
  K-25 and F-32

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GCRC Protocol Preparation and Review I.

• Protocols Consent forms are built interactively
  using the HIC PROTOCOL BUILDER
• Access is via the IRBOnline website
  (http//www.healthsystem.virginia.edu/internet/hi
  c/)
• An account and login are required

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GCRC Protocol Preparation and Review II.

• Required information includes
• TITLE
• PI
• SUB-INVESTIGATORS
• HYPOTHESIS
• BACKGROUND

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GCRC Protocol Preparation and Review III.

• PROCEDURES
• BIOSTATISTICAL ANALYSIS
• ANALYTICAL METHODS
• INVESTIGATIONAL DRUGS

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GCRC Protocol Preparation and Review IV.

• HUMAN SUBJECTS
• Characteristics
• Special Notes women/minorities
• Criteria for inclusion/exclusion
• Special classes
• Source of research material

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GCRC Protocol Preparation and Review V.

• HUMAN SUBJECTS
• Recruitment
• Risks
• Alternatives
• Protections
• Risk/benefit

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GCRC Protocol Preparation and Review VI.

• GCRC APPLICATION (template within HIC Protocol
  Builder)
• Justification
• Numbers of patients/days
• Resource use
• Bibliography in support of current previous
  work by PI
• SUMMARY SHEET

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The Review Process I.
Protocol Consent form(s) sent to GCRC
Administrative pre-review changes (GCRC
Protocol Manager, IRB Coordinator
biostatistician)
Primary reviewer assigned
Reviewer discusses concerns with PI and sends
review to GCRC Advisory Committee
PI meets with Advisory Committee to present the
protocol and address concerns raised in review
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The Review Process II.
GCRC Advisory Committee votes on protocol
GCRC approval
Protocol disapproved or tabled
Sent to HIC (IRB)
Review modifications
Concerns appropriately addressed by PI
Protocol withdrawn
HIC approval
GCRC develops physician orders flow sheets
Protocol initiated