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New Adverse Event Reporting Policy


Local adverse events are those experienced by subjects enrolled by the ... Individual non-local adverse events should only be reported to SCRIHS when a ... – PowerPoint PPT presentation

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Title: New Adverse Event Reporting Policy

New Adverse Event Reporting Policy
  • Effective September 1, 2007

Local adverse event reporting
  • Local adverse events are those experienced by
    subjects enrolled by the investigator(s) at this
    institution or in the local community area
  • Local investigator typically becomes aware of the
    event directly from the subject, another
    collaborating investigator at the same site, the
    subjects healthcare provider, or an affiliated
    hospital (MMC, SJH, etc.)

  • Serious adverse event is any adverse event
  • results in death
  • is life-threatening (places the subject at
    immediate risk of death from the event as it
  • results in inpatient hospitalization or
    prolongation of existing hospitalization
    results in a persistent or significant
  • results in a congenital anomaly/birth defect or
  • based upon appropriate medical judgment, may
    jeopardize the subjects health and may require
    medical or surgical intervention to prevent one
    of the other outcomes listed in this definition.

  • Unexpected adverse event - any adverse
    experience, the nature, severity, or frequency of
    which is not consistent with the current
    investigator's brochure, risk information
    described in the investigational plan, or consent
    form. Expected Adverse Event- any adverse
    experience, the nature, severity or frequency of
    which is consistent with the current
    investigator's brochure, risk information
    described in the general investigational plan, or
    consent form.

Keep in mind, the SCRIHS reporting schedule does
not relieve investigators of sponsor requirements
to report earlier.
NIH funded cooperative group studies
  • Often include lifetime or long-term follow-up for
    enrolled subjects.
  • A subject who has completed on-study therapy can
    be a subject that completed the protocol
    required therapy, a subject that was removed from
    active treatment, a subject that chose to stop
  • New SCRIHS reporting guidelines for long-term
    adverse event reporting as it relates to subjects
    that are no longer receiving active study therapy
    but continue to have long-term follow-up
    completed as per NIH protocol guidelines and

  • Subject must be gt30 days from the last dose of
    any protocol therapy.
  • Adverse event reporting should be consistent with
    the protocol guidelines. Individual protocol
    guidelines will mandate the required expedited
    reporting requirements.
  • Expedited Report Special reporting of an
    adverse event or events directly to CTEP/NCI/NIH
    within a shorter/specified time frame, usually
    ranging from 24 hours up to 10 calendar days
    based on the severity of the event(s). This does
    NOT include routine follow-up or reporting to the
    cooperative group, although the cooperative group
    will receive copies of the expedited reports.

  • If expedited reporting is required for any
    subject in long-term follow-up- a report to
    SCRIHS must be submitted within 5 working days of
    the completion of the expedited report along with
    a copy of the submitted expedited report.
  • Deaths of subjects in long-term follow-up if
    unrelated to prior protocol therapy no report
    to SCRIHS required.
  • All deaths deemed at least possibly related to
    prior protocol therapy require reporting under
    Serious, Unexpected guidelines regardless of
    length of time from last protocol therapy

Minimal Risk studies
  • For studies involving no risk or minimal risk,
    report adverse event only if the event is
    directly related to the study.
  • Minimal risk studies exempt and expedited
    studies that do not involve an invasive
    procedures, drug or device.

Non-local Adverse Event Reporting Policy
  • Those adverse events experienced by subjects
    enrolled by investigators at other institutions
    engaged in a multi-center clinical trial.
  • Investigators at all participating institutions
    learn of such events via reports that are
    distributed by the sponsor or coordinating center
    of the multi-center clinical trials. 
  • Reports of non-local adverse events represent the
    majority of adverse event reports currently being
    submitted by investigators to SCRIHS.

Individual non-local adverse events should only
be reported to SCRIHS when a determination has
been made that the adverse event meets the
criteria for an unanticipated problem.
Ideally, these AEs should be submitted for review
and analysis to a monitoring entity such as a
Data Safety Monitoring Board or Committee
(DSMB/DMC), a coordinating statistical center or
the research sponsor in accordance with a
monitoring plan described in the SCRIHS-approved
protocol. In cases when there is no monitoring
entity charged with this responsibility, it will
be the responsibility of the local PI to review
all of the non-local adverse events and determine
which ones meet the criteria of an unanticipated
problem (UP) and subsequently report that UP to
Okay, so what is an Unanticipated Problem (UP)?
  • Any incident, experience, or outcome that meets
    all of the following criteria
  • unexpected (in terms of nature, severity, or
    frequency) given (a) the research procedures that
    are described in the protocol-related documents,
    such as the IRB-approved research protocol, IB
    and ICF and (b) the characteristics of the
    subject population being studied
  • related or possibly related to participation in
    the research (possibly related there is a
    reasonable possibility that the incident,
    experience, or outcome may have been caused by
    the procedures involved in the research)
  • suggests that the research places subjects or
    others at a greater risk of harm (including
    physical, psychological, economic, or social
    harm) than was previously known or recognized

A UP will likely warrant consideration of
substantive changes in the research protocol
and/or informed consent process/document or other
corrective actions in order to protect the
safety, welfare and rights of subjects or others
  • changes to the protocol initiated by the
    investigator prior to obtaining SCRIHS approval
    to eliminate apparent immediate hazards to
  • modification of inclusion or exclusion criteria
    to mitigate the newly identified risks
  • implementation of additional procedures for
    monitoring subjects
  • suspension of enrollment of new subjects
  • suspension of research procedures in currently
    enrolled subjects
  • modification of ICF to include a description of
    newly recognized risks
  • re-consenting

Some UPs involve social or economic harm instead
of the physical or psychological harm associated
with adverse events Some UPs place subjects or
others at increased risk of harm, but no harm
Unexpected adverse event
  • the nature, severity, or frequency of which is
    not consistent with either  
  • the known or foreseeable risk of adverse events
    associated with the procedures involved in the
    research that are described in (a) protocol,
    applicable IB, and the current ICF, and (b) other
    relevant sources of information, such as product
    labeling and package inserts or 
  • the expected natural progression of any
    underlying disease, disorder, or condition of the
    subject(s) experiencing the adverse event and the
    subjects predisposing risk factor profile for
    the adverse event.

Majority of AEs are expected and thus--do not
meet criteria of unexpected--are not UPs--are
not reportable
Does the event suggest that the research places
subjects or others at a greater risk of harm than
was previously known or recognized ?
  • Is it serious?
  • If event is unexpected, related or possibly
    related to participation in research, and serious
  • always suggests that the research places
    subjects or others at a greater risk of physical
    or psychological harm than was previously known
    or recognized

  • UPs should be reported to SCRIHS within 5
    working days of the investigator becoming aware
    of the event.

What if sponsor says they require reporting?
  • What if AE does not meet the criteria for a UP
    and is non-reportable, per SCRIHS, but the
    sponsor requirements are inconsistent with our
    reporting policy? It would be acceptable for the
    PI/Study Coordinator to refer the company to the
    SIU policy located on the SCRIHS website. It
    would also be acceptable for the PI/Study
    Coordinator to indicate in the Case Report Form
    and AE log "...that the AE was not reported to
    the IRB per institutional policy."

Consequences of reporting out of timeframe or
incomplete reporting
  • PI and research staff will receive an email from
    SCRIHS staff reminding them of the reporting
    time-frame requirements (mainly for local AEs of
    less serious nature)
  • PI receive a letter from the SCRIHS Chairman
  • Review by the full SCRIHS committee who will
    decide on the course of action which can include
    but is not limited to requesting written
    response from the PI, requesting presence of PI
    at next SCRIHS meeting to address the issue with
    the committee, scheduling an audit of the PIs
    research, suspension of enrollment into one or
    more of the PIs ongoing studies, and report of
    non-compliance to OHRP and/or the FDA

What needs to be on a UP report?
  • protocol title, PI name, and the SCRIHS protocol
  • a detailed description of the adverse event,
    incident, or experience, and the outcome
  • an explanation of the basis for determining that
    the adverse event, incident, or experience
    represents an UP and
  • a description of any changes to the protocol, ICF
    or other corrective actions that have been taken
    or are proposed in response to the UP (these
    changes must be submitted on an Amendment Summary
    Form with all of the necessary documents)

  • What happens if a local PI independently
    proposes changes to the protocol or informed
    consent document in response to an unanticipated
  • SCRIHS requires that the local PI provide
    documentation of the communication with the
    sponsor and the outcome of such communication to

SCRIHS review process
  • Chairman will review all UP reports
  • Is this indeed a UP?
  • Further review by SCRIHS subcommittee or full
    SCRIHS committee at convened meeting
  • Does research still meet requirements for IRB
  • Are risks to subjects still minimized and
    reasonable in relation to the anticipated
  • As a condition of continued approval of the
    research study, does SCRIHS need more detailed
    information from the investigator(s), the
    sponsor, the study coordinating center, or
  • Are we satisfied with the corrective action taken?

Changes to protocol and/or consent as a result of
a UP
  • Most likely will require full-board approval
  • If SCRIHS requires additional changes in a
    multi-center trial, SCRIHS will request in
    writing that the local PI discuss the proposed
    modifications with the study sponsor or
    coordinating center and submit a response or
    necessary modifications for review by SCRIHS

For multi-center studies, only the institution at
which the subject(s) experienced an adverse event
determined to be an UP (or the institution at
which any other type of UP occurred) must report
the event to OHRP and/or the FDA.
Requirements for initial SCRIHS approval
  • Sufficient information regarding the risk
    profile of the proposed study, including the
    type, probability, and expected level of severity
    of the adverse events that may be caused by the
    procedures involved in the research, and how the
    risks of the research will be minimized
  • The IRB is responsible for determining if a
    study needs formal ongoing monitoring of data to
    ensure that research subjects will be protected.
    If the study presents greater than minimal risks
    to subjects or risks that are unforeseeable,
    SCRIHS will likely require adequate provisions
    for monitoring the adverse event data collected
    to ensure the safety of subjects

Adequate monitoring provisions for research
involving greater than minimal risk must include
  • The type of data or events that are to be
    captured under the monitoring provisions.
  • The entity responsible for monitoring the data
    collected, including data related to
    unanticipated problems and adverse events, and
    their respective roles (e.g., the investigators,
    the research sponsor, a coordinating or
    statistical center, an independent medical
    monitor, a DSMB/DMC, and/or some other entity). 
  • The required time frames in which investigators
    must report adverse events and unanticipated
    problems to the monitoring entity.

  • The frequency of assessments (e.g., how often the
    sponsor, DSMB/DMC, etc. will meet to review the
    information) of data or events captured by the
    monitoring provisions.
  • Definition of specific triggers or stopping rules
    that will dictate when some action is required by
    the monitoring entity to ensure patient safety.
  • As appropriate, procedures for communicating to
    the IRB(s), the study sponsor, the
    investigator(s), and other appropriate officials
    the outcome of the reviews by the monitoring
  • Added to the Application

Requirements for continuing review approval
  • Confirm that any provisions under the previously
    approved protocol for monitoring study data to
    ensure safety of subjects have been implemented
    and are working as intended
  • A report from the monitoring entity described in
    the approved protocol including 
  • 1) A statement indicating what information
    (e.g., study- wide AEs, interim findings, and any
    recent literature that may be relevant to the
    the research) was reviewed by the monitoring
  • 2) The date of the review(s)
  • 3) The monitoring entitys assessment of the
    information reviewed

What if there is no monitoring entity?
  • The local PI is responsible for reviewing and
    assessing all adverse events (local and
    non-local) and he/she is required to document all
    adverse events, whether reportable to SCRIHS or

What does the local PI need to submit with the
continuing review?
  • Two spreadsheets (one for local AEs and one for
    non-local AEs) with the following information
    about each event
  • Description of the AE
  • Date the event occurred
  • Outcome of the event
  • Determination of serious vs non-serious
  • Determination of causality (relatedness to the
    research procedures)

Since, prior to this policy, SCRIHS did not
review data monitoring plans for any of the
currently approved SCRIHS studies, a review of
such plans will be done at the time of CR for all
studies. Therefore, it will be the
responsibility of the PI to obtain the data
monitoring plan (including all of the required
elements) from the monitoring entity, along with
the most current report, and include these items
in the continuing review submission