Human Research Protection Program 101

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Human Research Protection Program 101

• March 19, 2007
• Cincinnati, OH

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The Common Rule and VHA 1200.5 One and the Same?

• Presented by
• Marisue Cody

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Objectives

• Evaluate applicability of the Common Rule
• Define the scope of regulations described in VHA
  1200.5
• Describe the areas of overlap between the Common
  Rule and VHA 1200.5

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17 Federal Agencies that Signed the Common Rule

• Dept of Agriculture
• Dept of Energy
• Dept of Commerce
• Dept of Justice
• Dept of Defense
• Dept of Education
• Dept of Transportation
• Dept of HHS
• HUD
• National Science
• Foundation

• NASA
• AID
• Social Security Administration
• CIA
• Consumer Product Safety
• EPA
• Dept of Veterans Affairs

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Code of Federal Regulations

• 38 CFR 16 refers to the VA
• 21 CFR 56 (IRB) and 50 (informed consent) refers
  to the FDA
• 45 CFR 46 refers to DHHS

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Subparts

• B Additional Protections for Pregnant Women,
  Human Fetuses and Neonates involved in Research
• C Additional Protections Pertaining to
  Biomedical and Behavioral Research Involving
  Prisoners as Subjects
• D Additional Protections for Children Involved
  as Subjects in Research

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What are the Common Rule and VHA 1200.5?

• Common Rule
• Federal Policy for the Protection of Human
  Subjects
• Originally issued in 1974 as Part 46 of Title 45
  of the Code of Federal Regulations (Subpart A) by
  DHEW
• Adopted in 1991 by 17 agencies
• VA Part 16 of Title 38 of the Code of Federal
  Regulations

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What is VHA Handbook 1200.5?

• Handbook describing procedures for the protection
  of human subjects
• VHA 1200.5 issued July 15, 2003
• Handbook vs. Federal Regulations
• Same regulatory weight (not optional)
• Applicability

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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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IRB Composition Responsibilities
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IRB Membership (.107)

• At least 5 members with varying backgrounds
• Gender balance, more than one profession
• At least 1 scientist, at least 1 non-scientist
• At least 1 member not affiliated
• May not participate if has a COI
• Invite consultant if require expertise

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IRB Composition VHA 1200.5

• Licensed Physician for FDA regulated products
• ACOS/AO/RCO
• MAY serve as non-voting members
• Members of a VA IRB
• Appointed by the Medical Center Director
• Initial appointment 3-years
• Chair of a VA IRB
• Initial appointment 1-year
• Affiliate IRB (Paragraph 5)
• Two VA IRB voting members
• One VA IRB voting member must have scientific
  expertise

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IRB Functions Operations

• Follow written procedures
• Review must take place at a convened meeting with
  a majority present, including a non-scientist.
  Approval must be by the majority present.

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VHA 1200.5 Written procedures for operation (turn
to page 13-14)

• More detail, plus some extras
• Reporting to the RD Committee
• Projects needing verification from sources other
  than the investigator
• Reporting requirements
• Conducting audits
• Education requirements
• Reporting to Privacy Officer
• Reporting to VHA Information Security Officer

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IRB Review of Research (.109)

• Authority to Approve, require modifications to
  seek approval, or disapprove
• Require that information given to subjects is in
  compliance with .116
• Shall require documentation of informed consent
  or waive documentation
• Notify investigators in writing of its decision
• Conduct continuing review and have authority to
  observe consent process and research

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Additional VHA 1200.5 requirements

• Prior to initiation
• Research reviewed and approved by IRB AND RD
• If approval is contingent on substantive
  modifications, subsequent review must be by the
  convened IRB
• If approval is contingent on specific minor
  conditions, the IRB chair or designee may approve
  it on behalf of the IRB

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Continuing Review in VHA 1200.5

• Requires submission of a written progress report
  that includes
• Brief summary
• Number of subjects entered and withdrawn
• Gender and minority status
• Number of subjects vulnerable populations
• Copy of proposal and all approved amendedments
• Copy of current consent document for the IRB to
  review

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Continuing Review

• Written Progress Report (cont.)
• Copy of current HIPAA Authorization document
• Information that may impact on risk benefit ratio
• Research findings to date
• Summary of DSMB or DMC meetings
• Assurance that all SAEs and UAEs have been
  reported
• New scientific findings in the literature, or
  other relevant findings

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Lapse of approval

• Automatically suspended
• Local research office to notify the PI
• IRB in consultation with COS may allow
  continuation of research interventions if it is
  in the best interest of individual subjects
• Inform other agencies as appropriate
• Re-approval must occur prior to re-initiation

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Expedited Review (.110)

• List of categories is published in the Federal
  Register (on OHRP website is the same as
  Appendix B)
• Must be no more than minimal risk, OR minor
  change in already approved protocol
• Carried out by IRB Chair or designee, cannot
  disapprove the research
• Have a process to inform the IRB members
• May be restricted by agency head

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VHA 1200.5

• No differences except the labeling of the
  expedited categories

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Criteria for IRB Approval (.111)

• Risks to subjects are minimized
• Risks are reasonable in relation to benefits
• Selection of subjects is equitable
• Informed consent will be sought prospectively
• Informed consent is appropriately documented
• Research plan makes adequate provisions for
  safety monitoring
• There are adequate provisions to protect privacy
  and confidentiality
• Protection of Vulnerable Subjects
• 9. Conflict of Interest
• 10. Ensure Investigator educational requirements
  and certifications

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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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Suspension or termination of IRB approval (.113)

• IRB has authority to suspend or terminate a
  project not being conducted in accordance with
  its requirements or is associated with unexpected
  harms to subjects
• Must be reported

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Cooperative research (.114)

• With approval of the department or agency head,
  an institution participating in a cooperative
  project may enter into a joint review
  arrangement, rely upon the review of another
  qualified IRB, or make similar arrangements for
  avoiding duplication

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IRB records (.115)

• Proposals reviewed, scientific evaluations (if
  any), sample consent documents, progress reports,
  reports of injuries
• Minutes of IRB meetings
• Continuing review activities
• Correspondence
• List of IRB members
• Written procedures
• Statements of significant new findings
• Shall be retained for at least 3 years

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Extras in IRB records (1200.5)

• Minutes must include
• Minutes available in 3 weeks
• Additional safeguards to protect vulnerable
  subjects
• Determination of level of risk
• Correspondence with RD Committee
• Retain records for 5 years
• Records are the property of the VA
• Non-redacted minutes of affiliate IRB

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Informed Consent
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General requirements for informed consent (.116)

• Basic elements
• Study involves research
• Description of risks
• Description of benefits
• Disclosure of alternative procedures
• Extent of confidentiality
• If more than minimal risk, compensation for
  injury
• Whom to ask questions of
• Statement that it is voluntary

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General requirements for informed consent (.116)

• Additional elements
• Unforeseeable risks
• Anticipated circumstances where participation may
  be terminated
• Additional costs
• Consequences of withdrawal
• Significant new findings
• Approximate number of subjects

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General requirements for informed consent (.116)

• Alteration or waiver (c)
• The research is conducted by or subject to the
  approval of state or local government officials
  and is designed to study, evaluate or otherwise
  examine a public benefit program, AND
• It could not practicably be carried out without
  the waiver or alteration

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General requirements for informed consent (.116)

• Alteration or waiver (d)
• Involves no more than minimal risk
• Will not adversely affect the rights and welfare
  of subjects
• Could not be practicably carried out without the
  waiver, AND
• Whenever appropriate the subjects will be
  provided pertinent information

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Documentation of informed consent (.117)

• Written consent
• Approved by the IRB
• Signed by the subject or LAR
• Copy given to person signing the form
• Must be read to the subject or LAR, who is given
  adequate opportunity to read it before it is
  signed, or given a short form

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Documentation of informed consent (.117)

• Waiver of requirements (c)
• Only record linking the subject with the research
  and breach of confidentiality would be harmful,
  OR
• Research presents no more than minimal risks and
  involves no procedures for which written consent
  is normally required outside of the research
  context

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VHA 1200.5 Appendix C

• 10-1086 must be used
• Signed, dated by
• Subject or LAR
• Witness (to signature only)
• Person obtaining consent
• Progress note
• Consent
• Entry
• Termination
• Flag medical record
• Filed in Case History

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Subparts B-D
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Subpart B-Additional Protections for Pregnant
Women, Human Fetuses and Neonates

• Definitions
• Duties of the IRB
• Risks and benefits
• Consent

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VHA Handbook 1200.5 Appendix D

• Paragraph 4
• Forbids research with a fetus, in-utero or
  ex-utero (including human fetal tissue)
• Forbids research related to in vitro
  fertilization
• Allows participation of pregnant women, rules are
  consistent with Sub-part B section 204

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Subpart C-Additional Protections Pertaining to
Biomedical and Behavioral Research Involving
Prisoners as Subjects

• Definitions
• Duties of the IRB
• Permitted Research

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VHA Handbook 1200.5 Appendix D

• Paragraph 5
• Requires a waiver from the CRADO
• If waiver is granted, must follow Subpart C
  regulations

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Subpart D-Additional Protections for Children
Involved as Subjects in Research

• Definitions
• Duties of the IRB
• Risks of Research
• Requirements for permission by parents or
  guardians and for assent by children

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VHA Handbook 1200.5 Appendix D

• Paragraph 7
• Requires a waiver from the CRADO
• VHA Directive 2001-028
• Guidance for waiver process
• Requires IRB to have specific policies and
  procedures regarding children in research
• IRB must have expertise
• If waiver is granted, must follow Subpart D
  regulations

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Research Involving Human Subjects with Surrogate
Consent

• Common Rule
• Section 117 subjects legally authorized
  representative
• VHA Handbook 1200.5
• Paragraph 11
• Appendix D Paragraph 6

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Paragraph 11

• Under appropriate conditions
• Research problem must be unique
• Priority of who can sign consent
• How determination is made regarding capacity
  (turn to page 21)
• IRB must find that the research meets the
  conditions in Appendix D

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Appendix D, Paragraph 6

• c. Conditions for approval
• Only persons with impaired decision making
  capacity are suitable as research subjects
• Research entails no significant risks or if
  possibility of harm, there must be at least a
  greater probability of direct benefit
• Procedures assure participants representatives
  are well informed about their roles and
  obligations

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Investigational Drugs Devices
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Investigational Drugs

• VHA Handbook 1108.04
• VA differs from FDA on how it defines
  investigational drugs
• Yields to FDA on investigational drug regulatory
  jurisdiction when there is conflict

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Investigational Devices

• Conducted according to FDA regulations at 21 CFR
  Part 812
• Significant risks (SR) vs. Nonsignificant risk
  (NSR)
• Receipt, control, custody and dispensing

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Investigator Responsibilities
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Investigators Responsibilities

• There is NOTHING regarding investigators in the
  Common Rule
• 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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QUESTIONS