Adverse Event Report Form and Guidelines

Adverse Event Report Form and Guidelines
For Non-serious and Serious Adverse Events
Related to Raltegravir in IMPAACT P1097
The Adverse Event Report (AER) form is used to collect initial and follow-up
information for non-serious and serious adverse events for patients participating in a
Merck-sponsored study anywhere in the world.
All serious adverse events are to be reported to Merck & Co., Inc. within 24 hours of
when first learned by the site (initial and follow up reports). Complete the Clinical Study
Adverse Event form and fax to Merck within 1 business day.
The following guidelines explain how to complete the AER form. Ensure that all relevant
medical information necessary to support the AE term(s) is provided.
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A. General Information
Note: Fields shaded in dark gray in the table below have already been populated in
AER form and clinical sites for IMPAACT P1097 do not need to fill out these
sections of the form.
Field Name
Description
Compound ID
Enter the generic name of the test product, if one is
known, otherwise state the MK#, V#.
Full Name of Primary Enter the full name of the primary investigator.
Investigator
Site #
Enter only the site number designated to the site
Initial
Indicate whether the report is the initial report (first
time SAE is reported), or if it is a follow up.
Follow-Up
Note: see section J for instructions on using the form to
report follow up information
Date Reported to Merck
By Study Site
Protocol #
Enter the date the information included in this report
was reported to Merck by the study site.
Enter the protocol number assigned to the study (3 digit
number + suffix)
The base protocol is indicated with the suffix “-00.”
Extensions and amendments are indicated in 2
additional digits (e.g., “-01” for the first amendment, “10” for the first extension, and “-21” for the first
amendment to the second extension).
E.g., 015-10 (protocol #15, extension #1
Person Reporting Event
Enter the name of the individual from the study site
who is reporting the event.
Complete Study Title
Enter the title of the study, as stated in protocol.
Note: This field will auto-fill, when the form is
completed on-line (based on the compound ID and
protocol # entered above).
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B. Patient Information
Field Name
Description
Allocation #
Enter the allocation number of the patient (postrandomization). For P1097, add the PID# in this
space.
Baseline #
Enter the baseline number assigned to the patient (only
when a randomization number has not been assigned –
pre-treatment period).
Age
Enter the patient’s age at the time of the onset of the
AE.
Sex
Enter Male or female.
Weight
Enter the weight of the subject at the time of study
initiation and circle the unit type (Kg, Lb).
Pregnant
Circle Y if the patient was pregnant at the time of
exposure to the study therapy.
Circle N if the patient was not pregnant at the time of
exposure to the study therapy.
Circle U if it is unknown whether or not the patient was
pregnant at the time of exposure to study therapy.
Note: In IMPAACT P1097, registering the mother's
pregnancy in the Antiretroviral Pregnancy Registry is
encouraged, but not required. If the pregnancy is
registered, please enter the number on the AER form.
Weeks of Gestation
Enter the number of weeks gestation at the time that the
patient initiated study drug therapy.
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C.
Adverse Event(s)
Field Name
Description
Adverse Event(s)
List the verbatim adverse event term(s)
Symptoms (e.g., fever, abdominal pain, etc.) may be all
that is available when the SAE is first reported. If this
is the case, submit the initial report with the signs and
symptoms that met the serious criteria listed as AE
terms; update the form accordingly with the diagnosis,
and submit as a follow up report.
When only the death of the subject is known (no cause
or AE has been yet determined), enter the term “death”
as the AE term. Once the cause is known, the correct
AE term can then be listed.
List all serious as well as non-serious AEs associated
with the event.
Note for P1097: A recurrence of the same AE, an
AE related to the originally reported event, or a new
serious event occurring for the mothers prior to
discharge from the hospital or for the infants
through 14 days after birth should be a follow-up to
the original AE report. These events do not need to
be reported under a new report.
Note: Although an AE can result in hospitalization or
lead to surgery or diagnostic testing, the
hospitalization, surgery or diagnostic procedure is, in
and of itself, not the AE. The event, not the
hospitalization or procedure, should be listed as the AE
term. In addition, hospitalization for elective surgery
for a preexisting condition which has not worsened
while on therapy with study drug is not an AE.
If the patient died, record probable cause(s) of death as
AE(s) OR if the death is unknown, record “death” as
the AE term. Once the cause of death is known,
replace the term “death” with the AE(s) that caused the
death of the patient.
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Enter the date of onset of the signs or symptoms related
to the adverse experience.
AE Onset Date
Note: For hospitalization cases, the onset date of the
SAE may be prior to the date of hospitalization.
Enter the date on which the subject/patient was
determined to have completely recovered or recovered
with sequelae from the reported adverse event
AE Stop Date
Relationship
Drug
to
Study i.e., Causality
Enter Y if the investigator considered that there was a
reasonable possibility that the adverse event may have
been caused by the study drug.
Enter N if the investigator felt that the patient’s
experience was not related to the study drug. NOTE:
If causality = N for raltegravir, do not report the
adverse event to Merck.
Enter U, if the causality is unknown because the
investigator did not report it or because the investigator
has yet to make an assessment.
If the AE report is derived from the CRF, use the
following convention for rating causality on the AER
form:
5 — Definitely drug related: Y
4 — Probably drug related: Y
3 — Possibly drug related: Y
2 — Probably not drug related: N
1 — Definitely not drug related: N
Outcome
Enter the outcome of the adverse experience as:
1 — Recovered
2 — Recovered with Sequelae*
3 — Not Recovered
Sequelae: The signs/symptoms of the reported AE
have not completely resolved and a new baseline for
the subject/ patient is established since full recovery is
not expected
If the AE report is derived from the CRF, use the
following convention for outcome:
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CRF Term
Recovered/Resolved
AER Term
Recovered
Recovered/Resolved
with sequelae
Recovered with
sequelae
Recovered/Not Resolved
Recovering/Resolving
Fatal
Unknown
Not Recovered
Not Recovered
Not Recovered
Not Recovered
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Did the AE Result In (Enter Yes or No for each AE):
Death *
Enter Y, if the AE resulted in the patient’s death.
Enter N if the patient did not die as a result of the AE.
Enter U if it is unknown if the AE resulted in the
patient’s death.
Do not leave blank.
* Additional information is required. See below.
Hospitalization
or Enter Y if the AE resulted in inpatient admission to the
Prolongation of Existing hospital or if the AE prolonged inpatient
hospitalization.
Hospitalization
Enter N if the patient was not hospitalized, or was only
seen in the emergency room.
Enter U if it is unknown whether the SAE resulted in
hospitalization or prolongation of hospitalization.
Do not leave blank.
Note: Hospital discharge diagnoses should be listed
as adverse experiences, as appropriate.
Persistent or Significant Enter Y if the AE resulted in a substantial disruption of
a person’s ability to conduct normal life functions.
Disability
Enter N if the AE did not result in a substantial
disruption of the person’s ability to conduct normal
functions
Enter U if the AE is unknown.
Do not leave blank.
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Is the AE (Enter Yes or No for each AE)
Life-Threatening
Enter Y if the AE placed the patient at immediate risk
of death from the experience as it occurred.
Note: It does not include a reaction that, had it
occurred in a more serious form, might have caused
death. For example, drug-induced hepatitis which
can be fatal would not be considered life threatening
unless the patient almost died from it. It also does
not include a chronic condition that might result in
decreased life expectancy.
Enter N if the AE was not life threatening.
Enter U if the AE is unknown.
Do not leave blank.
Cancer
Enter Y if the AE is a cancer or worsening of a
preexisting cancer.
Enter N if the AE is not a cancer or worsening of a
preexisting cancer.
Enter U if unknown.
Do not leave blank.
Due to an Overdose
Enter Y if the reporter term is the result of an overdose.
Note: If an adverse event is related to an overdose
and related to raltegravir, this event should be
reported to Merck.
Enter N if the AE is not the result of an overdose.
Enter U if unknown
Do not leave blank.
Congenital Anomaly
Enter Y if the AE is a congenital anomaly in the
offspring of the patient (male or female) exposed to the
drug or vaccine.
Enter N if the AE is not a congenital anomaly in the
offspring of the patient (male or female) exposed to the
drug or vaccine.
Enter U if unknown
Do not leave blank.
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Other Medical Event
Other Medical Event is also known as OME.
Enter Y if the AE is determined by the reporter to be an
“other important medical event”
Note: Other Important Medical Event is defined as
an event that may not result in death, be lifethreatening, or require hospitalization but that
based upon appropriate medical judgment, may
jeopardize the subject/patient and may require
medical or surgical intervention to prevent one of
the outcomes listed previously. Examples of other
important medical events include allergic
bronchospasm requiring intensive treatment in an
emergency room or at home; blood dyscrasias;
convulsions that do not result in an in-patient
hospitalization;
the
development
of
drug
dependency; the development of drug abuse. The
term “OME” reflects changes in patient care as a
result of new technology and procedures.
Enter N if the AE term does not meet the definition of
“Other Medical Event”.
Enter U if it is unknown whether or not the AE term
meets the definition of “Other Medical Event”.
Do not leave blank.
* Complete the following fields only when patient dies
Date of Death
Enter the date the patient died.
Autopsy
Indicate whether or not an autopsy was performed.
Autopsy Results
Enter the autopsy results that are relevant to the AE
terms reported, as stated in the autopsy report/death
certificate.
Relevant to the AE
Update the list of AE terms above to include those
stated in the Autopsy report, as appropriate.
Did AE Diminish after Check Yes if the suspect therapy was stopped after the
stopping suspect therapy? onset of the AE and the patient’s symptoms improved.
If Yes, specify which of the AE terms listed diminished
after stopping the suspect therapy.
Check No if the suspect therapy was stopped after the
onset of the AE, and the patient’s symptoms did not
improve.
Check N/A if study therapy was not stopped after the
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onset of the AE or if the AE occurred pre- or posttherapy.
Did AE reappear after re- Check Yes if an AE reappeared after re-starting suspect
therapy.
starting suspect therapy?
If Yes, specify which AE reappeared after re-starting
suspect therapy.
Check No when the AE did not reappear after restarting suspect therapy.
Check N/A when:




The drug is continued.
The patient died while on therapy.
The drug was discontinued before the onset of
the AE.
The drug was not restarted.
NOTE (all fields):
All fields initially answered as “U” for unknown, should be updated with definitive
information prior to closure of the SAE case
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D. Laboratory Results/Diagnostic Tests
List relevant laboratory or diagnostic tests and results which would support the AE
term reported and the outcome (pre-, during, and post- adverse event/study therapy).
List in chronological order when possible. Indicate units, normal ranges and whether
the test result was normal or not.
Field Name
Description
Name of Lab/Diagnostic Enter the name of the lab or diagnostic test.
Test
Date
Enter the date the test was administered.
Value/Results
Enter the value or results of the test.
Units
Enter the units of the test results.
Normal Range
Enter the normal range of the test results.
Comments
(Normal/Abnormal)
Enter results from diagnostic tests, which are not
numerically calculated.
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E. Medical History
Field Name
Description
Concurrent Conditions
List all pertinent medical conditions that developed
either prior to the initiation of drug therapy and that
were still present at the time of the adverse event, or
that represent a chronic condition that developed after
the onset of the study, that was previously reported as
an AE, and that remained unresolved prior to onset of
the SAE being reported (e.g., diabetes mellitus,
carcinoma).
Medical History
List all other medical history relevant to the AEs
reported that occurred prior to the earliest adverse
experience onset date but which would not necessarily
be considered concurrent conditions (e.g., myocardial
infarction, CABG).
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F. Suspect Therapy
Field Name
Description
Primary Suspect Therapy
Note: For P1097, this should be raltegravir.
Secondary Suspect
Therapy or Other Merck
Therapy
Provide the names of any additional therapies which
the investigator felt may have been related to the
adverse event.
For reports originating from non-U.S. sites, provide the
generic name of the secondary suspect drug/other
Merck therapy.
If a Merck product is listed here for a study patient who
experienced a serious adverse experience, provide the
causality for the product in the narrative.
Field Name
Description
Formulation
Provide the appropriate formulation for each drug
listed, e.g., tab, cap, or inj.
Route
Provide the route by which each
administered, e.g., P.O., I.V., or I.M.
Indication for Use
Note: For P1097, this should be HIV infection.
Strength
Provide the dosage strength of the drug including units
(e.g., mg).
Frequency
Provide the frequency of dosing, e.g., b.i.d., q8h.
drug
was
Total Daily Dose at Time Provide the total daily dose that the patient was taking
at the time of the AE. The total daily dose should equal
of AE
the strength times the frequency. For combination
drugs, list the total daily dose of both of the
components of the capsule or tablet separated by a dash
(e.g., for 1 tablet of VYTORIN 10-20, list “10-20”
instead of “1 tablet”).
Start Date
Provide the date that the patient received the first dose
of the medication.
For studies, do not give the start date of the latest phase
of the study, but the actual start date of the study
therapy.
For multiple doses, i.e., vaccines provide the date of
the first dose as the start date.
Stop Date
If the drug was discontinued because of the AE,
provide the date that the patient received the last dose
Page 13 of 20
of the medication.
If the patient continued therapy, list “CONT”. No stop
date should be provided for drugs that are continuing at
the time of the report.
If the drug was interrupted because of an AE, provide
the date that therapy was interrupted as the stop date.
In the event that therapy was continued until death,
provide the date of death as the stop date.
If you are not sure if therapy continued, enter U for
unknown.
Action Taken
If known, provide the action taken (by the treating
physician or by the patient) regarding the suspect drug
relative to the adverse event.
1 = None
2 = Discontinued
3 = Dosage reduced
4 = Dosage interrupted
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G. Concomitant Therapy
Field Name
Description
Concomitant Therapy
Provide all therapies (U.S. reports, enter U.S. trade
name; non-U.S. reports, enter generic name) given
within 14 days prior to the onset of the AE.
Note: Do not include therapies provided to treat the
AE. These therapies should be listed in the
narrative of the AER.
Daily Dose
For each concomitant therapy listed, provide the total
daily dosage of the drug.
Start Date
For each concomitant therapy listed, provide the date
that the patient received the first dose of the
medication. If the start date is an approximate date,
indicate “approx” next to the date. If the start date is
unknown, enter “UNK”.
Stop Date
Provide the date that the patient discontinued therapy.
Enter “CONT” if the patient continued therapy.
PLEASE DO NOT LIST A DASH (-).
Indication for Use
Provide the reason that the patient was taking the
concomitant therapy. Be sure to include the indication
as a concurrent condition as appropriate.
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H. Narrative and Comments
Summarize information that is pertinent to the understanding of the SAE. Pertinent
information includes, but is not limited to: the subjective verbatim information (e.g.,
signs and symptoms) provided by the investigator, the objective information (e.g.,
diagnostic tests and results) gained through clinical evaluation, the treating physician’s
assessment (e.g., physician’s diagnosis, hospital discharge diagnosis, etc.), the
physician’s plan (e.g., action taken as a consequence of each AE including medications
to treat the AE), and the patient’s outcome relative to each SAE as well as the overall
patient outcome (e.g., recovered, died, etc.). If critical data is not obtainable, the
narrative should specifically state this information ie, cardiac enzymes results are not
available
The presence of the following 15 elements in the narrative allows for an independent
assessment of the clinical course of the patient:
1. Concomitant medication (within 14 days of AE)
2. Start date of the study therapy (In P1097, this is raltegravir.)
3. Daily dose
4. Route of Administration
5. Indication for use for each suspect therapy
6. Supporting evaluations, signs and symptoms and/or diagnostic tests and results
to corroborate each AE term reported
7. Stop date of the study therapy
8. Action taken as a result of each AE term reported
9. Dechallenge and/or rechallenge information
10. Information on treatment provided (for each AE term)
11. If the patient was hospitalized, the hospital discharge diagnosis is included in
the narrative
12. If an SAE resulted in death, information on whether or not a post-mortem
evaluation was performed, the cause of death, and its possible relationship to
the study therapy
13. Resolution of each AE term
14. Causal relationship assessment by the investigator
15. Evidence that the SAE was closed (e.g., presence of the statement “no
additional information is expected” in the narrative)
See attached Narrative Template.
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I. Administrative Section
Field Name
Description
Full Address of Primary Enter the address of the Primary Investigator.
Investigator
Reporting
Signature
Study
Staff Section to be completed by Study Site individual
completing the form (when used to report SAE case).
Field Name
Description
Date
Section to be completed by Study Site individual
completing the form (when used to report SAE case).
The following fields are to be completed by the Merck & Co., Inc. contact only:
Received By
(Name/Signature)
Enter the name of the Merck employee who received
the data reported on the AER form from the site.
Include the signature in the hard copy version to be
filed in the Official Regulatory File (ORF).
Date First Learned by
Merck
Enter the appropriate date for this version of the report
(initial or follow up).
Medical Review
Completed By
This is for Merck Personnel Only: Enter the name of
the person who performed the medical review of the
AER and the date of review. Include the signature and
date of review in the hard copy version to be filed in
the Official Regulatory File (ORF). If the approval is
provided electronically (i.e., via e-mail), print a copy of
the e-mail, attach to the AER form and forward to ORF
with the completed AER form.
Date
Enter the date that Medical Review was completed.
Page 17 of 20
J. Follow Up Information
When using this form in hard copy (filling out manually), follow up information may be
provided on a new form such that only new information and/or changes to existing
information is provided. Sections A, B and I need to be completed for every version created.
There is no need to re-enter all other information provided on a previous version(s).
When completing the form electronically, follow up information may be added to the existing
form in the pertinent sections. New information and/or revisions to existing information
should be clearly identified (e.g, bold text in field added/changed, in narrative start statement
with “new information received on XX/XX/XX,” ……)
Page 18 of 20
Please refer to the following template to assist in the preparation of the narrative:
Note: any pertinent information that is specified in this narrative template, but not
available at the time the version is prepared, should be identified as such.
NARRATIVE TEMPLATE
Initial information has been received from ______________________ (the reporting
investigator or coordinator) concerning the following report:
PID# _______, a _____ year old ________ (male /female) with ______________,
______________ and __________________ (concurrent conditions) and (a) history of
______________________________ (medical history) who on _______________ (DDMM-YYYY), entered IMPAACT P1097. On __________________(DD-MM-YYYY),
the patient was placed on raltegravir therapy _______________________ (dosage/usage
e.g. 50 mg tablet, 50 mg daily) for treatment of ___________________ (indications).
Concomitant therapy included ____________________________ (add relevant
concomitant medications).
On
_______________
(DD-MM-YYYY),
the
patient
experienced
_____________________________________________________(SAE symptoms) and
was hospitalized on ___________ (DD-MM – YYYYY) if hospitalized
On _______________ (DD-MM-YYYY) his/her physical examination showed
______________________________________________(pertinent
examination and
related to SAE). On _______________ (DD-MM-YYYY), the lab (lab name) results
revealed ____________________________________(lab examination detailed result).
If applicable: During the hospitalization, the patient developed a _______ (condition)
which the investigator considers to be an NSAE]
On _______________ (DD-MM-YY), the patient was diagnosed with ________
__________________________________.
The condition was treated with
___________(list relevant treatment provided).
On _______________ (DD-MMYYYY), raltegravir was ________________________ (discontinued/ continued/
interrupted).
The patient was recovering (did not recover) from
_____________________ (list AE terms).
If applicable: On _________________
(DD-MM-YYYY), the patient was discharged from the hospital. The discharge
diagnosis was ___________________________. If the pt died: A post-mortem
evaluation <was/was not> done on this patient and the cause of death was determined to
Page 19 of 20
be ______________ _________________ which was assessed to be <related/nonrelated> to treatment (state for each SAE reported)
The reporting investigator considered that the_______________________ (SAE) was
______________________ (definitely, probably, possibly, probably not, definitely not)
related to therapy with _________________________ (any suspected therapy, if
appropriate). Additional information is <expected/no further information is expected>
(choose which statement applies).
For follow up reports – add the following statement to original report:
Follow up information has been received from the investigator on _______________
(DD-MM-YY). _______________ (state any changes about age, gender, dose,
frequency, route of administration, indication, therapy start date, AE onset date, serious
criteria, outcome, dechallenge, rechallenge, concomitant therapy, concurrent condition /
medical history, laboratory / diagnostic tests, reconfirmed causality and outcome in
another attachment if space limited). On _______________ DD-MM-YY,
________________ (labs name) showed __________ (if any new information). At the
time of reporting, the patient was recovering (did not recover) from ______________.
The investigator considered the SAE(s) was/were (definitely, probably, possibly,
probably not, definitely not) related to study therapy.
NOTE:
Consider the following for inclusion in the narrative, when relevant:
1) If hospitalization consisted of observation only, include this fact in the narrative
2) Hospital discharge diagnosis not available at the time of the report.
3) If SAE resulted in death, provide a statement regarding the status of autopsy
results.
4) If subject/patient not on concomitant therapy, state so in the narrative
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