Human Research Protection Program 101

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Human Research Protection Program 101

• March 19-20
• Cincinnati, OH

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Structure of Oversight of Human Subjects Research
Presented by Marisue Cody, PhD, RN
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Objectives

• Describe the oversight structure of human
  subjects research in the VA
• Describe the responsibilities of the institution
• Describe the responsibilities of the investigator

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HRPPP (Human Research Participant Protection
Programs)

• Institute of Medicine report 2001
• Preserving the Public Trust
• Broader system with multiple functional elements
• Advocated accreditation of the HRPPP

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New model
Old model
Director
RD
QA/QI
Patient Advocates
ACOS/Education
IRB
Chief of Staff
ACOS/R
RCO
RD Committee
AO
Medical Records
HPA
Clinical managers
Public Affairs
IRB
Fiscal Office
Pharmacy
Investigators
DSMB
Radiation Safety
Study Coordinators
Subjects
Conflict of Interest Committee
Grants Contracts
Source Joan Porter, ORO
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Authority Responsibilities

• United States Code (U.S.C.)
• Code of Federal Regulations (CFR)
• Directives
• Handbooks
• Manuals
• Memorandums
• Professional standards

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Oversight Authority
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• All research covered by the Common Rule
• FWA option (all research that is not exempt)
• Who?
• Institution
• IRB

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• FDA regulated drugs, biologics and devices
• Who?
• Investigators
• IRBs

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Under Secretary for Health
Office of Research Oversight
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Regulations vs. guidance

• When does guidance not have to be followed?
• Suggested practice?
• Must practice?
• Must vs. should?

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Institutional Responsibilities
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Regulatory Guidelines for the Institution

• DHHS FWA
• FDA none
• VA
• VHA Directive 2003-031 (funding of the facility
  HRP)
• VHA Directive 1200 (Facility RD program)
• M-3 Part I, Chapter 2 (Organizational Structure
  of RD Committee)
• M-3 Part I, Chapter 3 (Functions)

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Assurance of Compliance (.103)

• Statement of principles governing the institution
• Designation of one or more IRBs
• List of IRB members
• Written procedures the IRB will follow
• Written procedures for reporting unanticipated
  problems involving risk, and any suspension or
  termination of IRB approval
• Executed by individual authorized to act for the
  institution (in the VA this is the Medical Center
  Director)

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Federalwide Assurance (FWA)

• This documents your institutional commitment to
  comply with the Common Rule.
• It is required from each institution engaged in
  covered research
• http//www.hhs.gov/ohrp/policy/index.htmlengage
  ment
• Turn to Tab 8 in your notebook.

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Review by institution (.112)

• Research approved by an IRB may be subject to
  further review by official of the institution
• Those officials MAY NOT approve the research if
  it is not approved by the IRB

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Medical Center Director Responsibilities (VHA
Directive 1200)

• Responsible for RD program, advised and assisted
  by RD Committee
• RD funds used for research
• Research reimburses medical care appropriation
  for research participation
• Ensure ethical conduct of research

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RD Responsibilities
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Scope of RD Committee

• Responsible through the COS to the Medical Center
  Director, for oversight of the research program
• Responsible for maintaining high standards
  throughout the RD program
• Assuring scientific ethical quality of research
• ACOS/RD AO/RD assist the Committee with its
  duties

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Scope (Cont.)

• RD Committee approval must be obtained prior to
  initiating any research
• Applicable subcommittee approvals must be
  obtained prior to final RD Committee approval
• A RD Committee may serve as the RD Committee of
  record for another VA only
• MOU required
• Local accountability is a key point

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Specific Areas

• Plan develop broad objectives
• Determine extent to which RD committee has met
  its objectives
• Review budgetary other resource needs
• Oversee all RD activities
• Review certain written agreements
• Review evaluate all subcommittees

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Subcommittees

• Required subcommittees
• IRB
• IACUC
• Biosafety
• Option for other subcommittees
• Scientific review
• Continuing review
• Others as needed

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Responsibilities Related to the Facilitys
Research Program

• Have oversight responsibilities, not
  responsibilities for day to day management
• Need to receive sufficient information (annual,
  quarterly reports or other information) to
  fulfill areas of responsibility
• Information on compliance, QA, requests for WOC
  appointments, special programs such as
  Biosafety, Animal Welfare, HRPP

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Review of Research

• Initial review of research
• Final approval only after receive approval from
  applicable subcommittees
• Continuing review to occur each year
• Review during a convened meeting
• Quorum required to approve research
• Majority of voting members present for discussion
  vote

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Review of Research (Cont.)

• Review includes
• Budget
• Personnel
• Equipment needs
• Supply needs
• Relevance to VA
• PIs qualifications
• Scientific merit
• Conflicts of Interest

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Just-In-Time

• Concurrence from RD Committee to submit after a
  preliminary review
• Appropriateness of scientific methodology
• Relevance of the research to VAs mission
• Investigators qualification
• Adequacy of resources
• Review by full board or expedited procedure

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Just-In-Time Continued

• Develop SOPs on how to conduct preliminary review
• Concurrence ? approval to initiate research
• Prior to initiating research PI must
• Submit to required subcommittees (IRB, IACUC
  etc,)
• Submit to RD Committee
• Obtain approvals from all

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Institutional Review Board
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Institutional Review Board (IRB)

• Fulfill regulatory requirements set forth in
  Common Rule (38 CFR 16)
• Authority and responsibilities detailed in VHA
  Handbook 1200.5
• FDA (21 CFR 56)

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Common Rule and VHA 1200.5

• Common Rule
• Establish IRBs
• Ensure Informed Consent of Subjects
• VHA Handbook 1200.5
• Medical Center Responsibilities
• IRB Composition Responsibilities
• Investigator Responsibilities
• Investigational Drugs Devices in VA

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What is covered? (.101)

• All research involving human subjects conducted,
  supported or otherwise subject to regulation by
  any federal department or agency which takes
  action to make this policy application.
• In the VA, that is all research involving human
  subjects conducted completely or partially in VA
  facilities, approved off-site locations,
  facilities, and/or by VA researchers while on
  official VA duty time (VHA Handbook 1200.5, p. 6).

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Research
a systematic investigation, including research
development, testing and evaluation, designed to
develop or contribute to generalizable
knowledge. (45 CFR 46.102d)
Widespread information
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Human subject

• means a living individual about whom an
  investigator (whether professional or student)
  conducting research obtains(1) data through
  intervention or interaction with the
  individual, or(2) identifiable private
  information

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Investigator Responsibilities
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Investigators Responsibilities

• Common Rule
• Obtain legally effective informed consent
• VHA 1200.5 Paragraph 10
• Training and credentialing
• Research plan
• Consent process
• Reporting of SAEs and/or AEs
• Amendments
• IRB Review
• Record retention
• HIPAA

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Study Staff

• Delegated authority
• Training and credentialing

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FDA and GCP (ICH E6)

• Investigator qualifications and agreements
• Permit auditing and inspection
• Maintain list of appropriately qualified
  personnel to whom delegated significant
  trial-related duties
• Adequate resources (patients, time, staff)
• Medical care of trial subjects
• Communicate with the IRB
• Compliance with the protocol
• Investigational product accountability
• Informed consent of trial subjects

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FDA and GCP (ICH E6)

• Accurate, complete, legible timely reports
• Written progress reports
• Safety reporting
• Appropriate follow-up for trial subjects
• Submit final report to institution

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Responsible Conduct of Research

• Nine core components
• data acquisition, management, sharing, and
  ownership
• mentor/trainee responsibilities
• publication practices and responsible authorship
• peer review
• collaborative science
• human subjects
• research involving animals
• research misconduct
• conflicts of interest and commitment

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IOM Recommendations for PI Responsibilities

• Appropriate training and credentials
• Training in ethics and regulatory requirements
• Scientifically and ethically sound protocol
• Submit for scientific and ethical review
• Disclosure of potential conflicts of interest
• Voluntary and effective informed consent
• Conduct study according to approved protocol
• Submit all amendments

Institute of Medicine. 2003. Responsible
Research A Systems Approach to Protecting
Research Participants. Washington DC The
National Academies Press.
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IOM Recommendations (continued)

• Ensure appropriate safety monitoring and
  continuing review activities
• Acknowledge and report violations, errors,
  problems
• Report results in a responsible manner
• When appropriate, communicate results to
  participants or participant communities

Institute of Medicine. 2003. Responsible
Research A Systems Approach to Protecting
Research Participants. Washington DC The
National Academies Press.
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QUESTIONS