From SAE, AE, and Deviations To UPIRTSO and NonUPIRTSO

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From SAE, AE, and Deviations To UPIRTSO and
Non-UPIRTSO

• Mayo Clinic - Office for Human Research
  Protection Institutional Review Board (IRB)
• March 19, 2007

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Federal Regulations

• Investigators must report any unanticipated
  problems/events involving risk to subjects or
  others (UPIRTSO).
• 45 CFR 46,103(b)(5) and 21 CFR
  56.108(b)(1)

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Why A Change in the SAE Policy?

• Clarify responsibilities
• What needs to be reported
• to the IRB
• Existing terms are confusing
• Reduce the burden
• Focus on the important

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New Mayo Terminology

• UPIRTSO
• Unanticipated Problems Involving Risk to Subjects
  or Others
• Non-UPIRTSO
• Problems/Events that do not meet the IRBs
  definition

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UPIRTSOUnanticipated Problems Involving Risk
to Subjects or Others

• UPIRTSO is any problem/event that was
• 1) serious AND
• 2) unanticipated AND
• 3) at least possibly related to the research
  procedures.
• The problem/event must meet all three criteria in
  the IRBs definition.

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Two Definitions of Serious
Well-defined

• 1. Serious problems/events
• Death
• Life-threatening adverse experience
• Hospitalization inpatient, new or prolonged.
• Disability/ incapacity persistent or significant
  
• Birth defect/anomaly
• Per-protocol

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Two Definitions of Serious
Subjective

• 2. A problem/event that
• in the opinion of the investigator may have
  adversely affected the rights, safety or welfare
  of the subjects or others, or substantially
  compromised the research data.

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UPIRTSOAdversely affected.
Subjective

• Rights
• Safety
• Welfare
• Data integrity

• Confidentiality breached
• Monitoring equipment failed
• Info on new treatment alternative not shared
• Data lost

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Definitions Unanticipated problem/event

• Unforeseeable
• Occurred at an increased frequency or increased
  severity than expected.
• not already described in the consent form
• not listed in the Investigators Brochure
• not part of the underlying disease

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Definitions Related

• Possibly
• Probably
• Definitely
• occurred due to participation in the research
  study.

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UPIRTSO Needs to meet all 3 criteria in the
definition

• Mayo Clinics IRB defines unanticipated
  problems/events involving risk to subjects or
  others
• Serious
• Unanticipated AND
• Related

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Reporting UPIRTSOs

• The Mayo Clinic IRB requires that Investigators
  promptly report any unanticipated problems
  involving risk to subjects or others (UPIRTSO).
• 45CFR46,103(b)(5) 21CFR56.108(b)(1).
• At the investigators study site

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Reporting UPIRTSOs

• Submit Mayo UPIRTSO within 5 working days
• http//www.hhs.gov/ohrp/policy/AdvEvntGuid.htm
• Submit non-Mayo UPIRTSO at next continuing
  progress report (sooner if required by sponsor)
• When applicable, also submit a Protocol
  Modification
• Note Reports of deaths within 24hrs to Mayo IRB
  no longer required

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Non-UPIRTSO

• In the opinion of the investigator, no
  substantial effect on rights, safety, welfare of
  subjects or others, and no substantial compromise
  of the research data

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Non-UPIRTSO Examples

• Different study date
• Different blood draw volume
• Different study medication dose
• if no substantial effect on rights, safety,
  welfare of subjects or others, and no substantial
  compromise of the research data

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Reporting Non-UPIRTSO

• In the next continuing progress report
• Sooner, if required by the sponsor
• The Investigator is reminded that while a
  problem/event may not initially meet the
  definition of a UPIRTSO, it can transform (based
  on severity and frequency) to a UPIRTSO.

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Name Changes
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Implications for Researchers

• Fewer separate reports to Mayo Clinic IRB
• The Investigator needs to have defined Standard
  Operating Procedures (SOP) that explicate how
  problems/events will be assessed and monitored
• The Investigator is reminded that while a
  problem/event may not initially meet the
  definition of a UPIRTSO, it can transform (based
  on severity and frequency) to a UPIRTSO.

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Implications for Researchers

• Submit Mayo Clinic UPIRTSOs individually
• Submit non-Mayo Clinic UPIRTSOs and all
  Non-UPIRTSOs at the time of IRB continuing review
• Narrative summary / synthesis
• Details addressed in your SOPs

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Implications for the IRB

• Clarification on reporting responsibilities is
  essential to protect research participants
• Study safety monitoring systems have primary
  responsibility for receiving, interpreting, and
  proposing or taking action on expected adverse
  events
• Mayos IRB has primary responsibility for
  receiving, interpreting and taking action on
  unanticipated problems/event that cause risk to
  study subjects or others.
• Reporting is based on this division of
  responsibility

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Implication for the IRB

• A procedural mechanism is in place to triage
  reporting forms. This system will have an
  inherent ongoing quality review.
• IRB review will focus on unanticipated problems
  involving risk to subjects or others that may
  require it to act.

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Additional Questions??

• Contact the IRB Service Center at
• (77) 6-4000 or off campus at [phone].
• Email IRB Service Center