AAHRPP Update

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AAHRPP Update

• Marisue Cody, PhD
• Director, COACH
• Los Angeles
• January 29, 2008

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Objectives

• Understand the AAHRPP accreditation process
• Be able to prepare a self-evaluation
• Be ready for the AAHRPP site-visit
• Understand the response process to the AAHRPP
  report

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Why accreditation???
VA HRPP
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Background

• 1999 Kiser testimony to Congress
• VA would become the driving force to establish an
  accreditation program
• 2000 5-year 5.8 million contract to NCQA
• 72 VA facilities accredited
• 2005 5-year 4.9 million contract to AAHRPP
• 3 VA facilities accredited

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AAHRPP Accreditation Update

• 64 applications (81 FWAs)
• 51 site visits (59 FWAs)
• 43 applications reviewed by AAHRPP Council (51
  FWAs)
• 29 HRPPs accredited (34 FWAs)

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What does AAHRPP accredit?

• Organization
• Research Review Unit
• Investigator

Human Research Protection Program
A shared responsibility
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AAHRPP Accreditation Standards Domains

• Organization
• Research Review Unit
• Investigator
• Sponsored Research
• Participant Outreach

Obligations of
Obligations to
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How does accreditation work?
Application
Self Evaluation
Expert site visitors Tailored to setting
Site Visit
Determines Accreditation category
Council on Accreditation
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Self-evaluation

• 77 elements
• Review of all HRPP policies and procedures
• Overview of HRPP program
• Range of pages in a completed self-evaluation
  application 350 to 1500

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Site Visit Process

• 2 6 site visitors
• 2 4 days
• Records review
• Interviews
• Front-line
• Management
• Senior Management
• Exit briefing
• Draft report sent in 30 days

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Categories of Accreditation

• Full AAHRPP accreditation
• Qualified AAHRPP accreditation
• Accreditation-pending
• Accreditation withheld

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Application process

• Do not underestimate the time commitment begin
  early
• Organization and communication are key
• Be familiar with policies and procedures, and
  practices

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Gap analysis

• Evaluate your policies and procedures against the
  AAHRPP standards and elements
• Identify gaps where you dont have policies and
  procedures
• Create new policies
• Identify policies that are incomplete,
  inconsistent, or unclear
• Update these according to the AAHRPP guidance

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Element-by-element review

• This is the core of the application
• Describes where in your policies and procedures
  the elements can be found

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Section C Element by Element DOMAIN I Element
I.1 .A The Organization has a written plan for
its Human Research Protection Program appropriate
for the volume and nature of the research
involving human participants conducted under its
auspices. Document 1 (Section 3. Part A)
States and defines VA BHHCS HRPP Mission
(Section 3. Part B) States and defines VA BHHCS
HRRP Vision (Section 3. Part D) Describes the
Authorization and Oversight within the HRPP at
the VA BHHCS (Section 3. Part C) Describes
ethical principals that govern the HRPP Document
2 (Section 3, Part A) Describes types of
activities subject to review (RD) Document 5
(Section 2) Describes the QA/QI programs
intention of heightening awareness of regulatory
and ethical conduct of research
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Site Visit Interview Questions
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General Tips

• Be honest
• If you dont know something, say who you would go
  to for the answer
• This is not the place to pick or air battles

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Clarify your policies and procedures

• Questions are often individualized based on your
  application
• Focus on how you do things in practice
• Interested in communication among all the
  components of the HRPP

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Sample questions

• Tell me about how your VA coordinates review and
  oversight of human subject research with the
  smaller VAs in your system
• How do you assure the independence of the IRB
  process?
• How does an investigator in your facility know
  what needs to be submitted to the IRB?
• How do you assure that research is not started
  until all approvals are given?

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Records review

• Protocol files
• IRB records
• Contracts
• Training records
• Site agreements

• Site records
• Non-compliance
• Conflict of interest
• Scientific review

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Records review

• Representative sample
• Chosen in advance
• Requested one week before visit
• Can be modified on-site

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Lead contact review

• Site visitors will go over findings on every
  element
• There is little time for questions or arguments
• Take thorough notes and plan on a follow-up call
  to the AAHRPP Accreditation Director

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Post AAHRPP site visit

• Begin communicating with the AAHRPP Accreditation
  Director
• Review notes from site-visit
• Meet with team and discuss strategies to address
  deficiencies

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Receipt of draft report

• Review carefully
• Compare to your site visit notes
• Electronically communicate with AAHRPP
• Element number in the message line
• One element per message
• Include observation from draft report
• Anticipate several communications per element

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Draft report format

• Observations
• Both positive and negative
• Only respond to the negative
• Recommendations
• General
• Restate the element goals

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Communication is key

• Institutional official response and timeline
• Discuss with the IRB the institutions response,
  implications, and timeline
• Distribute policies and procedures to PIs and
  their research teams

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AAHRPP Council

• Review draft report and your response
• Presented by Accreditation Director
• Decision communicated within a couple of days
• Set new timeline if put in pending category

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Key Areas in Accreditation
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Conflict of interest

• Whose conflict?
• Definitions
• Disclosures
• Evaluation
• Management

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Whose conflict?

• RD Members
• IRB Members
• Investigators and study staff
• Institution

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Conflicts Ethics

• Federal Employees hold the public trust.
• Two core concepts - -
• Employees shall not use public office for private
  gain, and
• Employees shall act impartially and not give
  preferential treatment to any private
  organization or individual.
• Also cant create the appearance of a violation
  of the ethics rules.
• (5 CFR 2635.101)

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FDA additions

• Any financial arrangement entered into between
  the sponsor of the covered study and the clinical
  investigator involved in the conduct of a covered
  clinical trial, whereby the value of the
  compensation could be influenced by the outcome
  of the study
• Any significant equity interest in the sponsor of
  the covered study

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Disclosures

• May be annual or as new reportable significant
  financial interests are obtained
• Must be reviewed per protocol

34
Evaluation

• Can be triaged (e.g., COI administrator or the
  like) written record must be maintained
• RD Committee resolve prior to approval
• IRB appropriately managed, disclosures to
  subjects

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Management

• Public disclosure
• Monitoring of research by independent reviewers
• Modification of the research plan
• Disqualification from participation in all or a
  portion of the research
• Divestiture of significant financial interests
• Severance of relationships that create COI

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Unanticipated problems involving risks

• Definitions
• Reporting by PIs to the IRB
• IRB Evaluation
• Reporting by IRB to the federal authorities

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Non-compliance

• Definitions
• Evaluation
• Reporting

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Definitions

• Non-compliance not following the rules
• Serious non-compliance increased risk of harm
  to subjects
• Continuing non-compliance intentionally and
  repeatedly not following the rules

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false
Allegation
Investigate allegation
true
Confirmed non-compliance
IRB decides
Is it serious or continuing?
Yes
No
Corrective actions
Corrective actions
Report
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Allegations or other forms of discovery

• Study personnel
• Routine audits
• IRB or RD review for cause audits
• Participant complaints
• Protocol deviation reports

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Range of corrective actions

• No action
• Modification of research protocol
• Modification of consent
• Additional information to be given to past
  participants
• Notification of current participants
• Re-consent current participants

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Corrective actions (cont)

• Modification of continuing review schedule
• Monitoring of the research
• Monitoring of the consent process
• Require additional training
• Suspension or termination
• Refer to other organizational entities (e.g.,
  legal counsel, risk management, institutional
  official)

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IRB report to Federal authorities

• Who drafts the report
• Content of the report
• Who approves the report
• The distribution of the report
• The maximum time allowed between the recognition
  of a reportable event and fulfilling the
  reporting requirements

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FDA-regulated studies

• When is an IND or IDE required?
• Is the IND or IDE valid?
• Investigator-sponsor oversight
• Emergency use of a test-article

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When is an IND or IDE required?

• An IND is required when an unapproved drug or
  biologic is used in a clinical investigation
• An IDE is required if the investigational device
  represents a significant risk and the clinical
  trial is to obtain safety and effectiveness day
  about the investigational device

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Validation of the IND or IDE

• More than making sure a number is on an IRB
  application
• Source document
• Industry-sponsored clinical trials
• Clinical Protocol
• Investigators Brochure (for investigational
  drugs)
• Sponsor correspondence or e-mail
• FDA correspondence
• Investigator-initiated
• FDA correspondence
• AAHRPP does not define who or what entity must
  conduct the validation

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Investigator-sponsor oversight

• When the organization or an individual assumes
  the sponsor function, policies and procedures
  should describe the organizations evaluation
  whether the investigator is knowledgeable about
  the additional regulatory requirements of
  sponsors and followed them.

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Emergency use of a Test Article Regulations

• Use of a test article on a human subject
• in a life-threatening situation
• no standard treatment is available
• there is not sufficient time to obtain IRB
  approval
• 21 CFR 56.102(d)

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Emergency IND

• Intended subject does not meet the criteria of an
  existing study protocol
• Approved study protocol does not exist
• Manufacturer cannot make the unapproved
  investigational drug or biologic available under
  the companys IND
• FDA request by telephone or other rapid
  communication means

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IRB Issues

• What is the IRB s role in emergency use of a
  test article?
• FDA regulations only require retrospective IRB
  notification
• Did the use meet the criteria for an emergency
  exemption from prospective IRB approval?
• If informed consent was not obtained, did the
  investigator meet the requirements for exception
  from informed consent requirements?

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Continuing review

• What should be reviewed
• Regulatory criteria for approval
• Lapse of approval

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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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Criteria for IRB Approval

• 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
• Vulnerable subjects are protected
• 9. Conflict of interest is appropriately
  managed
• 10. Ensure Investigator educational requirements
  and certifications

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Lapse of approval

• All research activities must stop
• 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
• IRB to notify investigator to submit immediately
  to the IRB Chair, a list of participants for whom
  stopping research activities would cause harm
• Report expiration to the sponsor
• Re-approval must occur prior to re-initiation

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