***[Phase 2 Single Agent Template]{.underline}***

***X.* ADVERSE EVENTS: LIST AND REPORTING REQUIREMENTS**

> Adverse event (AE) monitoring and reporting is a routine part of every
> clinical trial. The following list of AEs *(Section X.1)* and the
> characteristics of an observed AE *(Section X.2)* will determine
> whether the event requires expedited (via AdEERS) reporting **in
> addition** to routine (via CTMS or CDUS) reporting.
>
> ***X.1* Comprehensive Adverse Events and Potential Risks List
> (CAEPR)**
>
> The Comprehensive Adverse Event and Potential Risks list (CAEPR)
> provides a single, complete list of reported and/or potential adverse
> events (AE) associated with an agent using a uniform presentation of
> events by body system.
>
> In addition to the comprehensive list, a [subset,]{.underline} the
> Agent Specific Adverse Event List (ASAEL), appears in a separate
> column and is identified with ***bold*** and ***italicized*** text.
> This [subset]{.underline} of AEs (the ASAEL) contains events that are
> considered 'expected' for expedited reporting purposes only. Refer to
> the "CTEP, NCI Guidelines: Adverse Event Reporting Requirements"
> (<http://ctep.cancer.gov/reporting/adeers.html>) for further
> clarification. The CAEPR does not provide frequency data; refer to the
> Investigator's Brochure for this information.

The Comprehensive Adverse Events and Potential Risks (CAEPR) list will
be provided with the LOI approval letter. Please insert the CAEPR here.

> ***X.2* Adverse Event Characteristics**

-   **CTCAE term (AE description) and grade:** The descriptions and
    grading scales found in the revised NCI Common Terminology Criteria
    for Adverse Events (CTCAE) version 3.0 will be utilized for AE
    reporting. All appropriate treatment areas should have access to a
    copy of the CTCAE version 3.0. A copy of the CTCAE version 3.0 can
    be downloaded from the CTEP web site
    ([http://ctep.cancer.gov](http://ctep.cancer.gov/)).

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-   **"Expectedness"**: AEs can be 'Unexpected' or 'Expected' (*see
    Section X.1 above*) for expedited reporting purposes only.
    'Expected' AEs (the ASAEL) are ***bold and italicized*** in the
    CAEPR (*Section X.1.1*).

-   **Attribution** of the AE:

    -   Definite -- The AE *is clearly related* to the study treatment.

    -   Probable -- The AE *is likely related* to the study treatment.

    -   Possible -- The AE *may be related* to the study treatment.

    -   Unlikely -- The AE *is doubtfully related* to the study
        treatment.

    -   Unrelated -- The AE *is clearly NOT related* to the study
        treatment.

> ***X.3* Expedited Adverse Event Reporting**
>
> *X.3.1* Expedited AE reporting for this study must use AdEERS (Adverse
> Event Expedited Reporting System), accessed via the CTEP home page
> ([http://ctep.cancer.gov](http://ctep.cancer.gov/)). The reporting
> procedures to be followed are presented in the "CTEP, NCI Guidelines:
> Adverse Event Reporting Requirements" which can be downloaded from the
> CTEP home page
> ([[http://ctep.cancer.gov]{.underline}](http://ctep.cancer.gov/reporting/adeers.html)).
> These requirements are briefly outlined in the table below (*Section
> X.3.3*).
>
> In the rare occurrence when Internet connectivity is lost, an AE
> report may be submitted using CTEP\'s Adverse Event Expedited
> Report-Single Agent or Multiple Agent paper template (available at
> [http://ctep.cancer.gov](http://ctep.cancer.gov/)) and faxed to
> 301-230-0159. A 24-hour notification is to be made to CTEP by
> telephone at 301-897-7497, only when Internet connectivity is
> disrupted. Once Internet connectivity is restored, an AE report
> submitted on a paper template or a 24-hour notification phoned in must
> be entered electronically into AdEERS by the original submitter at the
> site.
>
> *X.3.2 The following text is required for multi-institutional studies
> only and may be deleted for single institution studies.*
>
> AdEERS is programmed for automatic electronic distribution of reports
> to the following individuals: Study Coordinator of the Lead
> Organization, Principal Investigator, and the local treating
> physician. AdEERS provides a copy feature for other e-mail recipients.
>
> *X.3.3* **[Expedited Reporting Guidelines]{.underline}** -- AdEERS
> Reporting Requirements for Adverse Events that occur within 30 Days^1^
> of the Last Dose of the Investigational Agent on Phase 2 and 3 Trials

<table style="width:100%;">
<colgroup>
<col style="width: 9%" />
<col style="width: 11%" />
<col style="width: 9%" />
<col style="width: 9%" />
<col style="width: 9%" />
<col style="width: 10%" />
<col style="width: 9%" />
<col style="width: 10%" />
<col style="width: 10%" />
<col style="width: 10%" />
</colgroup>
<tbody>
<tr class="odd">
<td colspan="10"><strong>Phase 2 and 3 Trials</strong></td>
</tr>
<tr class="even">
<td rowspan="3"></td>
<td><strong>Grade 1</strong></td>
<td><strong>Grade 2</strong></td>
<td><strong>Grade 2</strong></td>
<td colspan="2"><strong>Grade 3</strong></td>
<td colspan="2"><strong>Grade 3</strong></td>
<td><p><strong>Grades</strong></p>
<p><strong>4 &amp; 5<sup>2</sup></strong></p></td>
<td><p><strong>Grades</strong></p>
<p><strong>4 &amp; 5<sup>2</sup></strong></p></td>
</tr>
<tr class="odd">
<td rowspan="2"><p><strong>Unexpected</strong></p>
<p><strong>and Expected</strong></p></td>
<td rowspan="2"><strong>Unex-pected</strong></td>
<td rowspan="2"><strong>Expected</strong></td>
<td colspan="2"><strong>Unexpected</strong></td>
<td colspan="2"><strong>Expected</strong></td>
<td rowspan="2"><p><strong>Unex-</strong></p>
<p><strong>pected</strong></p></td>
<td rowspan="2"><strong>Expected</strong></td>
</tr>
<tr class="even">
<td><p><strong>with</strong></p>
<p><strong>Hospitali-zation</strong></p></td>
<td><strong>without Hospitali- zation</strong></td>
<td><p><strong>with</strong></p>
<p><strong>Hospitali-</strong></p>
<p><strong>zation</strong></p></td>
<td><p><strong>without Hospitali-</strong></p>
<p><strong>zation</strong></p></td>
</tr>
<tr class="odd">
<td><p><strong>Unrelated</strong></p>
<p><strong>Unlikely</strong></p></td>
<td><p>Not</p>
<p>Required</p></td>
<td><p>Not</p>
<p>Required</p></td>
<td><p>Not</p>
<p>Required</p></td>
<td><p>10 Calendar</p>
<p>Days</p></td>
<td><p>Not</p>
<p>Required</p></td>
<td><p>10 Calendar</p>
<p>Days</p></td>
<td><p>Not</p>
<p>Required</p></td>
<td><p>10</p>
<p>Calendar</p>
<p>Days</p></td>
<td><p>10</p>
<p>Calendar</p>
<p>Days</p></td>
</tr>
<tr class="even">
<td><p><strong>Possible</strong></p>
<p><strong>Probable</strong></p>
<p><strong>Definite</strong></p></td>
<td><p>Not</p>
<p>Required</p></td>
<td><p>10 Calendar</p>
<p>Days</p></td>
<td><p>Not</p>
<p>Required</p></td>
<td><p>10 Calendar</p>
<p>Days</p></td>
<td><p>10 Calendar</p>
<p>Days</p></td>
<td><p>10 Calendar</p>
<p>Days</p></td>
<td><p>Not</p>
<p>Required</p></td>
<td><p>24-Hour;</p>
<p>5 Calendar</p>
<p>Days</p></td>
<td><p>10</p>
<p>Calendar</p>
<p>Days</p></td>
</tr>
<tr class="odd">
<td colspan="10"><p><strong><sup>1</sup> Adverse events with attribution
of possible, probable, or definite that occur <u>greater</u> than 30
days after the last dose of treatment with an agent under a CTEP IND
require reporting as follows:</strong></p>
<blockquote>
<p>AdEERS 24-hour notification followed by complete report within 5
calendar days for:</p>
</blockquote>
<ul>
<li><p>Grade 4 and Grade 5 unexpected events</p></li>
</ul>
<p>AdEERS 10 calendar day report:</p>
<ul>
<li><p>Grade 3 unexpected events with hospitalization or prolongation of
hospitalization</p></li>
<li><p>Grade 5 expected events</p></li>
</ul>
<p><sup>2</sup> Although an AdEERS 24-hour notification is not required
for death clearly related to progressive disease, a full report is
required as outlined in the table.</p>
<p>December 15, 2004</p></td>
</tr>
</tbody>
</table>

**Note:  All deaths on study require both routine and expedited
reporting regardless of causality.  Attribution to treatment or other
cause must be provided.**

-   Expedited AE reporting timelines defined:

    -   "24 hours; 5 calendar days" -- The investigator must initially
        report the AE via AdEERS within [24 hours]{.underline} of
        learning of the event followed by a complete AdEERS report
        within [5 calendar days]{.underline} of the initial 24-hour
        report.

    -   "10 calendar days" - A complete AdEERS report on the AE must be
        submitted within [10 calendar days]{.underline} of the
        investigator learning of the event.

-   Any medical event equivalent to CTCAE grade 3, 4, or 5 that
    precipitates hospitalization (or prolongation of existing
    hospitalization) must be reported regardless of attribution and
    designation as expected or unexpected with the exception of any
    events identified as protocol-specific expedited adverse event
    reporting exclusions.

-   Any event that results in persistent or significant
    disabilities/incapacities, congenital anomalies, or birth defects
    must be reported via AdEERS if the event occurs following treatment
    with an agent under a CTEP IND.

-   Use the NCI protocol number and the protocol-specific patient ID
    assigned during trial registration on all reports.

> *X.3.4* [Protocol-Specific Expedited Adverse Event Reporting
> Exclusions]{.underline}

-   [For this protocol only]{.underline}, certain AEs/grades are
    exceptions to the Expedited Reporting Guidelines and [do not require
    expedited reporting ( *i.e*., AdEERS)]{.underline}. The following
    AEs must be reported through the routine reporting mechanism
    (*Section X.4*):

  ------------ --------------- ----------- -------------------- ----------------- ------------------
  **CTCAE      **Adverse       **Grade**   **Hospitalization/   **Attribution**   **Comments**
  Category**   Event**                     Prolongation of                        
                                           Hospitalization**                      

                                                                                  

                                                                                  

                                                                                  

                                                                                  

                                                                                  
  ------------ --------------- ----------- -------------------- ----------------- ------------------

> ***X.4* Routine Adverse Event Reporting**
>
> All Adverse Events **must** be reported in routine (CTMS or CDUS)
> study data submissions. **AEs reported through AdEERS must
> [also]{.underline} be reported in routine study data submissions.**
>
> ***X.5* Secondary AML/MDS**
>
> Investigators are required to report cases of secondary AML/MDS
> occurring on or following treatment on NCI-sponsored chemotherapy
> protocols using the [NCI/CTEP Secondary AML/MDS Report
> Form.]{.underline} This form can be downloaded from the CTEP web site
> ([http://ctep.cancer.gov](http://ctep.cancer.gov/reporting/index.html)).
> Refer to the "CTEP, NCI Guidelines: Adverse Event Reporting
> Requirements" (available at
> [[http://ctep.cancer.gov]{.underline}](http://ctep.cancer.gov/reporting/adeers.html))
> for additional information about secondary AML/MDS reporting.