The Common Rule and VHA 1200'5: One and the Same

1
The Common Rule and VHA 1200.5 One and the Same?
Presented by John C. Hudson Research
Compliance Officer Wm. S. Middleton Memorial
Veterans Hospital Madison, WI
2
Objectives

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

3
What are the Common Rule and VHA 1200.5?

• The 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 now DHHS
• Adopted in 1991 by 17 agencies

4
17 Federal Agencies that Signed the Common Rule

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

• 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

5
Code of Federal Regulations or the Common
Rule

• 45 CFR 46 refers to DHHS
• 38 CFR 16 refers to the VA
• Also FDA adds 21 CFR 56 (IRB)
• 21 CFR 50 (informed consent)
• Big VA difference
• Subparts B, C, D not included

6
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

7
(No Transcript)
8
Common Rule and VHA 1200.5

• Common Rule
• Describes Types of Research subject to regulation
• Defines Key Terms research, human subject,
• minimal risk
• Requires Written Assurance of compliance with
  Common Rule
• Describes Requirements for IRB membership,
  authority, review procedures, records, and
  approval criteria
• Lists basic Requirements for Informed Consent

9
Common Rule and VHA 1200.5

• VHA Handbook 1200.5
• Issued July 2003 same regulatory weight as Fed.
  Regs
• Describes VA procedures for protection of Human
  Subjects
• ? interprets Common Rule for every-day
  field use in
• VA facilities engaged in research
• SO THEN COMBINING COMMON RULE 1200.5 IS ALL
  YOU NEED TO RUN YOUR HRPP EFFECTIVELY AND MEET
  THE REGS?
• NO!
• Together act as major guide, but also need
• Common Rule subparts, HIPAA, 1200.1, FDA Regs,
• plus various and sundry other VA, federal,
  state, local regulations, directives, guidance,
  etc., etc.

10
Common Rule and VHA 1200.5

• VHA Handbook 1200.5
• Describes Roles/Responsibilities
• Medical Center Director
• IRB
• Investigators
• Details Duties of IRB
• Membership, functions, research review, record
  keeping
• Addresses Special VA Issues
• Surrogate consent, subject payment, use of VA
  records, investigational drugs and devices,
  non-vets in VA research

11
IRB Composition Responsibilities
12
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

13
IRB Composition VHA 1200.5

• Licensed Physician for FDA regulated products
• ACOS/AO/RCO
• As non-voting ex officio members only
• 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
• Two VA IRB voting members per IRB
• One VA IRB voting member must have scientific
  expertise

14
IRB Functions Operations (.108)

• Follow written procedures
• NOTE This implies you HAVE
• written instructions!
• Review must take place at a convened meeting with
  a majority present, including a non-scientist.
  Approval must be by majority of those present

15
VHA 1200.5 Written procedures for operation

• Other stuff
• Communication with RD Committee
• Reporting requirements
• Conducting audits
• Education requirements
• Reporting to Privacy Officer
• Reporting to VHA Information Security Officer
• Major focus document, document, document!
• 1200.5 give the hows, whens and whos
• (sometimes implies a bit of the whys)

16
IRB Review of Research (.109)

• Authority to approve, require modifications, or
  disapprove to observe consent process
• Informed Consent must follow Common Rule
  requirements (detailed in .116!)
• Documentation of informed consent
• (or of waiver of documentation)
• Notify investigators of decision in writing
• Continuing review at least annually

17
VHA 1200.5 adds

• Prior to initiation
• Research must be reviewed and approved by both
  IRB and RD!
• Substantive modifications subsequent review must
  be by the convened IRB
• Specific, minor modifications IRB chair or
  designee may approve on behalf of IRB

18
Continuing Review in VHA 1200.5

• Requires a written progress report
• Brief summary
• Number of subjects (entered/withdrawn)
• Gender minority status
• How many from vulnerable populations
• Proposal approved amendments
• Current consent document
• Current HIPAA Authorization document

19
Continuing Review in VHA 1200.5

• Written Progress Report (cont.)
• Info that may impact on risk benefit ratio
• Research findings to date
• Summary of DSMB/DMC info
• All SAEs and UAEs reported as required
• New scientific or other relevant findings

20
Continuing Review in 1200.5 But wait,
theres more!
Automatic suspension if Continuing Review
not Completed w/in IRB-specified time

• Local research office notifies PI
• Continue research interventions?
• ONLY in consultation with COS
• ?if in best interest of individual
  subjects
• Inform other agencies as appropriate (e.g., FDA)
• Re-review/re-approval must occur
• prior to re-initiation

21
Expedited Review (.110)

• Must fit list of categories in Fed. Register
• (see 1200.5, Appendix B, Para 2)
• No more than minimal risk,
• or minor change in approved protocol
• Carried out by IRB Chair or designee
• (cannot disapprove the research)
• Have a process to inform the IRB members
• VHA 1200.5? ? No difference other than
• Appendix B category descriptions

22
A Tribute to All Our Dedicated Researchers The
Regs are for them, too
23
Criteria for IRB Approval (.111)

• The Big Kahuna One-Eleven
• ? Describes what IRB must review in a protocol
• ? .111 .116 is the meat and potatoes of IRB
  function (or meat substitute, if you prefer)

• Risks to subjects are minimized
• Risks reasonable in relation to benefits
• Selection of subjects equitable

24
.111 continued

• Prospective consent (i.e., meeting .116)
• Informed consent appropriately documented
• Adequate provisions for safety monitoring
• Adequate provisions to protect privacy and
  confidentiality
• Also Protections for Vulnerable Subjects
• Safeguards if children, prisoners, pregnant
  women, mentally disabled, or other vuln. pop.
  subjects included

25
VHA 1200.5 adds a bit more

• Conflict of interest
• IRB ensures that the institution has COI
  procedures and policies in place
• Includes investigators, institution, and
  committees
• Investigator education
• IRB assures that investigators meet educational
  requirements
• As mandated by facility, VA ORD, OHRP, and other
  groups

26
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
• Rule of thumb
• Disapprovals can override approvals
• Approvals cannot override disapprovals

27
Suspension/termination (.113) Cooperative
research (.114)

• IRB has authority to suspend/terminate a project
  not being conducted in accordance with IRB
  requirements or associated with unexpected
  harm to subjects
• Such actions must be reported
• An institution participating in a cooperative
  project may (w/ proper approval) enter into a
  joint review arrangement, rely upon the review of
  another qualified IRB, or make similar
  arrangements for avoiding duplication
• 1200.5 has nothing to add
• except who to report to

28
IRB records (.115)

• Proposals reviewed, scientific evaluations,
  consent docs, progress reports, injury reports
• IRB meeting minutes IRB membership lists
• Continuing review activities
• Relevant correspondence
• Written IRB procedures
• Statements of significant new findings

29
1200.5 Adjustments Additions

• Minutes written reviewable in 3 weeks
• Additional vulnerable subject safeguards
• Determination of risk level
• Correspondence with RD Committee
• Retain records for 5 years (CR 3 years)
• Records are the property of the VA
• Also
• RD Comm. must receive review
• non-redacted IRB minutes (VA or affiliate)

30
Informed Consent .116 .117
31
General requirements for informed consent (.116)

• a. Basic Elements of Consent
• Study involves research
• Description of risks
• Description of benefits
• Alternative procedures
• Confidentiality identifiably
• Compensation for injury (MinRisk )
• Who to contact (subjects rights injury
  questions)
• Statement participation voluntary

32
General requirements for informed consent (.116)

• b. Additional elements
• Unforeseeable risks
• Anticipated circumstances participation
  terminated
• Additional costs to subjects
• Consequences of withdrawal from research
• Reporting of significant new findings
• Approximate number of subjects

33
General requirements for informed consent (.116)

• c. Alteration or waiver of elements of consent
  Govt. Study
• Research conducted by/subject to approval of
  state/local govt. designed to study, evaluate or
  otherwise examine public benefit program, AND
• Research could not practicably be carried out
  without the waiver or alteration
• d. Alteration or waiver of elements of consent
  Min. Risk
• No more than minimal risk
• Not adversely affect the rights and welfare of
  subjects
• Could not be practicably done without waiver
• AND
• When appropriate subjects provided pertinent
  information

34
Documentation of informed consent (.117)

• Documenting written consent
• Approved by the IRB
• Signed by the subject or LAR
• Copy given to person signing the form
• Consent process
• May be read to subject or LAR
• Given adequate opportunity to read before it
  is signed OR
• Given a short form (documenting oral presentation
  of elements of consent)

35
Documentation of informed consent (.117)

• Waiver of requirements
• If only record linking subject with research and
  breach of confidentiality would be harmful,
• OR
• Research presents no more than minimal risk AND
  involves no procedures for which written consent
  is normally required outside of research

36
VHA 1200.5 Additions to .116 .117 Appendix C

• VA form 10-1086 must be used
• Signed, dated by
• Subject or LAR
• Person obtaining consent
• Witness (to signature only)
• File original ICF in subjects case history
• Flag medical record
• Progress note document consent process
• Consent criteria
• Entry and termination dates

37
Subparts B-D Vulnerable Pops
38
Subpart B - Protections for Pregnant Women, Human
Fetuses and Neonates

• ?Definitions ?Duties of the IRB
• ?Risks and benefits ?Consent process
• VHA 1200.5? Appendix D, Para 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 consistent with Common Rule Sub-part B

39
Subpart C- Additional Protections for Research
Involving Prisoners as Subjects

• ?Definitions ?Duties of the IRB
• ?Permitted Research
• VHA 1200.5? Appendix D, Para 5
• Prisoner research allowed BUT
• ? Requires a waiver from the CRADO
• IF waiver granted
• ? rules consistent with Common Rule Sub-part C

40
Subpart D-Additional Protections for Children as
Subjects in Research

• Definitions
• Duties of the IRB
• Risks of Research
• Of special note when research involving children
  
• may be greater than minimum risk
• Requirements for permission by parents or
  guardians and for assent by children

41
1200.5 Research Involving Children

• Appendix D, Paragraph 7
• Requires a waiver from the CRADO
• IF waiver is granted
• ? rules consistent with Common Rule Sub-part D

• For details VHA Directive 2001-028
• Guidance for waiver process
• Requires IRB to have specific policies and
  procedures regarding children in research
• IRB must have expertise

42
Research Involving Human Subjects with Surrogate
Consent

• Common Rule
• Section 117 subjects legally authorized
  representative
• VHA Handbook 1200.5
• Paragraph 11
• Under appropriate conditions
• 1. Research subject unique to population
• 2. Priority of who can give consent
• 3. How determine decision-making capacity
• Research must meet conditions in Appendix D

43
Research with Surrogate Consent (cont.)

• VHA Handbook 1200.5 Appendix D, Para. 6
• 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
• Decision making ability may fluctuate
• Resistance to participation must be honored!

44
Investigational Drugs Devices
45
Investigational Drugs

• 1200.5, Para 14
• Mostly follow FDA regs
• ? especially 21 CFR 312
• Also VHA Handbook 1108.04
• Caution definition of investigational drugs for
  VA not same as for FDA
• Yields to FDA on investigational drug regulatory
  jurisdiction when there is conflict

46
Investigational Devices

• 1200.5, Para 15
• Mostly follow FDA regs
• ? especially 21 CFR 812
• Particular note Significant Risk (SR)
• v. Nonsignificant Risk (NSR)
• Also facility must have procedures for receipt,
  control, custody, and dispensing of
  investigational devices
• ? of particular interest to AAHRPP

47
Investigators Responsibilities

• There is NOTHING regarding investigators in the
• Common Rule except that they must get consent
• BUT in VHA 1200.5 Paragraph 10
• Training and credentialing
• Research plan
• Consent process
• Reporting of SAEs and/or AEs
• Amendments
• IRB Review
• Record retention
• HIPAA

48
QUESTIONS