Transcript Safety Workshop Part II - Expedited Reporting

Safety Workshop: Part II
Expedited Reporting & Assessment Training
August 19, 2010
Albert Yoyin, M.D.
DAIDS Regulatory Support Center (RSC)
Objectives
• Definitions
• Assessment of Adverse Events
• Expedited Reporting Processes
• Moving from Manual v1.0 to v2.0
2
Expedited Reporting Materials
• Manual for Expedited Reporting to DAIDS v2.0
• SAE Reporting Form 2.0
• SAE Reporting Form
•
•
•
Completion Instructions 2.0
DAIDS AE Grading Table
(Clarification August 2009)
Protocol
3
Manual for Expedited Reporting Version 2.0
• Manual v2.0 (dated Jan 2010) has been issued
and posted on RSC website
• Primary goal is to align expedited reporting to
ICH-SAE definition
• Fulfill DAIDS’ regulatory requirements to FDA
• Fulfill DAIDS’ obligations to industry collaborators
4
Highlights: Major Changes
• Reporting Categories
• Categories of expedited reporting
• Definitions
• Clarifications
• Assessment of Relationship to study agent
• Terms
5
Highlights: Major Changes
• Submission of updates
• Event resolution
• Increase in event severity of ongoing AEs
• Timeframe for expedited adverse event reporting
• Reporting days
• Site investigator assessment and signature timeframe
6
Definitions
Manual v2.0
Expedited Adverse Event Reporting
to DAIDS
Two Reporting Categories:
SAE - All Serious Adverse Events
SUSAR - Only Suspected, Unexpected, Serious
Adverse Reactions
• The protocol will specify which reporting category
will be used
8
Expedited Adverse Event Reporting
to DAIDS
Additional reporting requirements:
• In addition, a protocol may require other AEs to
be reported on an expedited basis
• The protocol will specify the additional AEs to be
reported to DAIDS
9
Expedited Adverse Event Reporting
to DAIDS
• Study agent(s) – drugs, biological agents,
combination of drugs and biological agents or
devices (approved or investigational) defined in
the protocol for which expedited reporting to
DAIDS is required; regardless of who provides
the drugs/products
• The protocol will specify what the study agent(s) are
10
Reporting Period
• Protocol specified reporting period: from enrollment
to end of trial follow-up for that participant
• After the protocol-defined AE reporting period, unless
otherwise noted, only SUSARs will be reported to
DAIDS if the study staff becomes aware of the events on
a passive basis (from publicly available information).
11
SAE Definition (ICH E2A)
A serious adverse event (SAE) is defined as any untoward
medical occurrence that at any dose:
• Results in death
• Is life-threatening
• Requires inpatient hospitalization or prolongation of existing
hospitalization
• Results in persistent or significant disability/incapacity
• Is a congenital anomaly/birth defect
• Is an important medical event that may not be immediately lifethreatening or result in death or hospitalization but may jeopardize the
patient or may require intervention to prevent one of the other
outcomes listed in the definition above
12
Clarification on SAE Definition:
Life-threatening
Life-threatening refers to an event in
which the patient was at risk of death at
the time of the event
• It does not refer to an event which
hypothetically might have caused death if it
were more severe
• E.g. malignancy
13
Clarification on SAE Definition:
Hospitalization
Not an AE, but is an outcome of the AE
The following types of hospitalization do not require
expedited reporting to DAIDS:
• Any admission unrelated to an AE (e.g., for labor/delivery,
cosmetic surgery, administrative or social admission for
temporary placement for lack of a place to sleep)
• Protocol-specified admission (e.g., for a procedure required
by protocol)
14
Clarification on SAE Definition:
Hospitalization cont’d
• Admission for diagnosis or therapy of a condition
that existed before receipt of study agent(s) and
has not increased in severity or frequency as
judged by the clinical investigator.
• A new AIDS-defining event in a subject already known to
be HIV-infected would be considered an increase in
severity of a pre-existing condition [HIV infection] and
would be reportable as an expedited AE
15
Clarification on SAE Definition:
Congenital anomaly/birth defect
Do not report clinically insignificant physical findings
at birth, including those regarded as normal variants
• Report clinically significant anomalies; include all other
findings (even if not individually significant)
• Example: an isolated finding of polydactyly or Mongolian
spot in an infant with no other findings would not be
reported, but polydactyly or Mongolian spot occurring with a
major cardiac defect would be included in the SAE report of
the major cardiac defect
16
Clarification on SAE Definition:
Congenital anomaly/birth defect cont’d
• Information about congenital anomalies can be found on
the Centers for Disease Control and Prevention (CDC)
website: http://www.cdc.gov/ncbddd/bd/monitoring.htm
• Guidelines for Conducting Birth Defects Surveillance,
National Birth Defects Prevention Network (NBDPN),
appendix 3.1. Direct link to document:
www.nbdpn.org/current/resources/sgm/appendix3-1.pdf
• This website listing should not restrict the reporting of
anomalies that the site investigator deems important for
the sponsor to know.
17
Clarification on SAE Definition:
Important Medical Events
• Events considered as important medical events
can meet SAE criteria.
• Examples:
• Intensive treatment in an emergency room or
at home for allergic bronchospasm
• Blood dyscrasias or convulsions that do not
result in hospitalization
• Development of drug dependency or drug
abuse
18
SUSAR Definition
• SUSAR is defined as an adverse event that is a
•
Suspected Unexpected Serious Adverse
Reaction
For the SUSAR reporting category, an SAE will
be reported if it fulfills the following criteria:
• Related and
• Unexpected
•
19
SUSAR Reporting Category
• Used for some non-IND studies/trials
using U.S. FDA-approved agents with
approved dosages for approved
indications in typical populations
• At the discretion of DAIDS
20
Assessment of
Adverse Events
Assessment
• AEs are assessed for:
•
•
• Seriousness
• Severity
• Expectedness
• Relationship
Study physician listed on the
1572 / Investigator of Record
(IoR) Agreement is responsible for the
assessment of AEs
Sponsor Level: DAIDS MOs provide
secondary review
22
Primary Adverse Event
Is there an AE?
If there are associated symptoms, what is the primary AE?
Report only one primary AE per report.
Example: Primary AE:
Myocardial Infraction
Clinically Significant Event
Associated with primary
AE: CHEST PAIN
Clinically Significant Event
Associated with primary AE:
DYSPNEA
23
Primary Adverse Event
How many primary AEs are there?
Events that are not clearly associated with the
primary AE should be reported as separate events.
Example
“Acute Renal Failure and
Gastroesophageal Reflux”
Primary Adverse Event 1
“Acute Renal Failure”
Primary Adverse Event 2
“Gastroesophageal Reflux”
24
Hospitalization
• 61 y.o. HIV-infected, African-American male,
enrolled Feb 15, 09, with Gr. 4 hospitalization
May 8, 09
• Feb 20, 09: subject was started on study agents
ABC and XYZ.
• May 8, 09: subject visited study clinic with
complaints of abdominal pain and non-bloody
diarrhea for the past one week
• Vomited three times on the day of clinic visit
25
Hospitalization
• PE: moderately dehydrated aged man with vague
generalized abdominal tenderness. No guarding or
rebound tenderness. BP: 109/71 mmHg and HR: 69
beats/min
• Given IV Ringers lactate and IM diclofenac, 75 mg
• Sent to hospital for further work up
• Hospital lab results: K+ 2.1 mEq/L (3.5–5.2 mEq/L)
• KCL 20 mmol, was added to each liter of Ringers
lactate
• Results for stool culture pending
• May 9, 2009: stable, awaiting discharge
26
Teaching Points
 Hospitalization in and of itself is not an AE term; it
is an outcome of the AE
• Grading should be on the AE, not the outcome of the AE
 Primary AE: ?
• Abdominal pain, non-bloody diarrhea, vomiting, vague
generalized abdominal tenderness
• Possible AE Term: gastroenteritis, NOT ‘Hospitalization’
 However, if you do not have any information about
the actual AE but the event is reportable you can
report “Hospitalization”
27
Death
• Jan 14, 2009: 40-year-old HIV uninfected, Asian
female enrolled
• Jan 14, 2009: started on the study agent XYZ at
a dose of 32 mg, sublingually, 4 times a week
• May 6, 2009: Took last dose of XYZ; went for
clinic visit
• May 10, 2009: died due to sudden death (AE
term reported as death)
28
Death
• May 11, 2009: subject’s younger brother called to inform
site that subject died on May 10, 2009, at home.
• According to the site, there is a hx of illicit drug use.
[Note: study population is a drug addicted population].
No recent sickness, hospital admission, self-inflicting
injury, violent attack, falls or family history of sudden
death.
• The site has provided a death certificate which gives the
cause of death as “sudden death (cause unknown)”.
• The Site Principal Investigator has assessed the event of
death as not related to the study agent XYZ
29
Teaching Points
• Death in and of itself is not an AE term; it is an
outcome of the AE
• Primary AE:
• Sudden death (per death certificate)
• Possible AE Term: Death unknown cause
• However, if you do not have any information about
the actual AE but the event is reportable you can
report “Death unknown cause.”
30
Seriousness
• Does primary AE meet criteria for an SAE?
• Use ICH-SAE definition provided in Manual v2.0
• Select appropriate SAE criteria
31
Severity
• Severity refers to the intensity of a specific
event
• Events are graded on a severity scale of 1-5:
• 1 = Mild
• 2 = Moderate
• 3 = Severe
• 4 = Potentially Life-threatening
• 5 = Death
32
Seriousness is NOT the same as Severity
Seriousness
Severity
Based on outcome of the
AE and is a factor in
determining reportability
(regulatory definition)
Based on the intensity of the
AE and is not a factor in
determining reportability
(clinical descriptor)
Determined using the
SAE criteria
Determined using the DAIDS
grading table
33
Grading Severity of Events
• All events reported to DAIDS in an
expedited timeframe must be graded for
severity
• Grading does not determine reportability
• Division of AIDS (DAIDS) Table for
Grading the Severity of Adult and Pediatric
Adverse Events Version 1.0 - December
2004 (Clarification dated August 2009)
34
Estimating Severity Grade
Grade 1 – Mild
Symptoms causing no or minimal interference with usual social &
functional activities.
• When a subject experiences a chest pain which does not
interfere with the subjects’ activity of daily living; then it is graded
as 1.
Grade 2 – Moderate
Symptoms causing greater than minimal interference with usual
social and functional activities.
• When the chest pain is such that the subject, is unable to do
some of their activities of daily living.
35
Severity Grade
Grade 3 – Severe
Symptoms causing inability to perform usual social & functional activities.
• When the chest pain is such that the subject is unable to carry out
activities of daily living.
Grade 4 – Potentially Life Threatening
Symptoms causing inability to perform basic self-care functions OR
medical or operative intervention indicated to prevent permanent
impairment, persistent disability, or death.
• When the chest pain makes the subject unable to perform basic
functions and is at risk of permanent impairment/persistent
disability/death if no surgical or medical intervention is done
36
EXAMPLE FROM THE DIVISION OF AIDS
TABLE FOR GRADING THE SEVERITY OF
ADULT AND PEDIATRIC ADVERSE EVENTS
CLINICAL
PARAMETER
GRADE 1
GRADE 2
GRADE 3
GRADE 4
MILD
MODERATE
SEVERE
POTENTIALLY
LIFE-THREATENING
ESTIMATING SEVERITY GRADE
Clinical adverse
event NOT
identified elsewhere
in this DAIDS AE
grading table
Symptoms causing
no or minimal
interference with
usual social &
functional activities
Symptoms causing
greater than minimal
interference with
usual social &
functional activities
Symptoms causing
inability to perform
usual social &
functional activities
Symptoms causing
inability to perform
basic self-care
functions OR Medical
or operative
intervention indicated
to prevent permanent
impairment, persistent
disability, or death
This table is used for estimating the severity grade of a
clinical AE not specifically listed in DAIDS Grading Table
37
EXAMPLE FROM THE DIVISION OF AIDS
TABLE FOR GRADING THE SEVERITY OF
ADULT AND PEDIATRIC ADVERSE EVENTS
SYSTEMIC
PARAMETER
GRADE 1
GRADE 2
GRADE 3
GRADE 4
MILD
MODERATE
SEVERE
POTENTIALLY
LIFE-THREATENING
Chills
Symptoms causing
no or minimal
interference with
usual social &
functional activities
Symptoms causing
greater than minimal
interference with
usual social &
functional activities
Symptoms causing
inability to perform
usual social &
functional activities
N/A
Fever (nonaxillary)
37.7 – 38.6C
38.7 – 39.3C
39.4 – 40.5C
> 40.5C
This table is used for grading a clinical AE specifically listed
in DAIDS Grading Table:
• E.g. grading by symptomatology
• E.g. grading by numerical ranges
38
Severity Grading
Manual Version 1.0
Grade 4 events are
referred to as lifethreatening events
Manual Version 2.0
Grade 4 events are referred to as
potentially life-threatening events
as defined in the DAIDS Grading
Table
Thus a Grade 4 event does not
automatically imply that it meets
SAE criteria, if it is only potentially
and not immediately lifethreatening
39
Issues With Grading
• Death = Grade 5; clarified in DAIDS Grading Table, August 2009
• Potentially life-threatening = Grade 4
•
Potentially life-threatening means at risk of death should the event
occur in a more severe form. This is not the same as immediately lifethreatening.
• Grading abnormal laboratory values associated with a clinical AE:
• Does not correspond to grade provided in the DAIDS toxicity table
• When lab values fall between two grades choose the higher grade
• Grading does not appear to reflect the event:
• Event led to hospitalization, but graded as “Grade 1” or “Grade 2”
• Grade the SAE not the initial AE (initial AE had progressed to level of SAE)
40
Grading: Neonatal Sepsis
Neonatal Sepsis Grade 1
• 27 day-old, male infant, normal delivery, breastfed, nevirapine
• 2-week visit: crying on urination, amoxicillin for 7 days
• 3-week visit: refusing feed, brought back to clinic
• PE: lethargic, HR: 140 bpm, RR: 58 bpm, T: 37.7 0C, WBC: 14.0
with left shift
• Sent to hospital for sepsis workup
• AE term: neonatal sepsis, Severity: Grade 1
• R/O Sepsis is reasonable AE Term
• Basis for severity grade?
41
Grading: Neonatal Sepsis cont’d
CLINICAL
PARAMETER
GRADE 1
GRADE 2
GRADE 3
GRADE 4
MILD
MODERATE
SEVERE
POTENTIALLY
LIFE-THREATENING
ESTIMATING SEVERITY GRADE
Clinical adverse
event NOT
identified elsewhere
in this DAIDS AE
grading table
Symptoms causing
no or minimal
interference with
usual social &
functional activities
Symptoms causing
greater than minimal
interference with
usual social &
functional activities
Symptoms causing
inability to perform
usual social &
functional activities
Symptoms causing
inability to perform
basic self-care
functions OR Medical
or operative
intervention indicated
to prevent permanent
impairment, persistent
disability, or death
• Grading on basis of fever alone: Grade 1
• Grading on clinical basis of possible sepsis:
• at least Grade 3
• Grade 4 reasonable as well
42
Grading: Respiratory Distress
Respiratory Distress Grade 2
• 2 day-old male, delivered at 39 wks GA by C/S, started on oral
zidovudine
• PE: pale, flexed, not crying, given CPAP with improvement, APGAR: 6 at 5
minutes and 9 at 10 minutes, Birth Wt: 3.35 kg, Ht: 47.5, HC: 34 cm, HR:
140 bpm, RR: 62
• 12 hrs after birth: developed tachypnea and fussiness, RR: 62, Pulse Ox on
room air: 70%
• Transferred to NICU, 100% oxyhood, Pulse Ox: 80%, pH: 7.48, pCO2: 27,
pO2: 251, HCO3: 20.
• PE: systolic murmur heard along left sternal border
• Echo: Moderate PDA, ASD, patent foramen, mild TR, trivial MR
• Respiratory Distress is reasonable AE Term
• Basis for severity grade?
43
Grading: Respiratory Distress cont’d
DYSPNEA OR RESPIRATORY DISTRESS
Pediatric < 14 years
Wheezing OR
minimal increase in
respiratory rate for
age
Nasal flaring OR
intercoastal retractions
OR Pulse oximetry 90
- 95%
Dyspnea at rest causing
inability to perform usual
social & functional
activities OR pulse
oximetry < 90%
Respiratory failure with
ventilatory support
indicated
Alkalosis
N/A
pH > 7.5 normal, but ≤
7.5
pH > 7.5 without lifethreatening
consequences
pH > 7.5 with lifethreatening
consequences
PARAMETER
GRADE 1
MILD
GRADE 2
MODERATE
GRADE 3
SEVERE
GRADE 4
POTENTIALLY
LIFE-THREATENING
ESTIMATING SEVERITY GRADE
Clinical adverse
event NOT identified
elsewhere in this
DAIDS AE grading
table
Symptoms causing
no or minimal
interference with
usual social &
functional activities
Symptoms causing
greater than minimal
interference with usual
social & functional
activities
Symptoms causing
inability to perform usual
social & functional
activities
Symptoms causing
inability to perform basic
self-care functions OR
Medical or operative
intervention indicated to
prevent permanent
impairment, persistent
disability, or death
44
Grading: Respiratory Distress cont’d
• Grading on basis of respiratory distress: at least
•
•
Grade 3
• Required CPAP at birth
• 12 hours later: tachypnea and RR:62
• Room air and 100% O2: 70-80%
Grading on basis of respiratory distress: Grade 4
• Need medical intervention beyond 100% O2
• Transferred to NICU
Grading on basis of alkalosis: Grade 2
• Not appropriate because it does not reflect
clinical picture in totality
45
Relationship Assessment
The terms used to assess the relationship of an
event to study agent are:
• Related – There is a reasonable possibility that
the AE may be related to the study agent(s).
• Not Related – There is not a reasonable
possibility that the AE is related to the study
agent(s).
46
Relationship Assessment
• When an SAE is assessed as “not related” to
study agent(s), an alternative etiology,
diagnosis, or explanation for the SAE should be
provided.
• If new information becomes available, the
relationship assessment of any AE should be
reviewed again and updated, as required.
47
Relationship Assessment cont’d
Manual Version 1.0
SAE form allows
assessment of either
combination or by
components
Manual Version 2.0
When the study agent is
a fixed dose combination
agent, an assessment of
attribution will be made
for each component and
the combination agent
48
Expectedness
• Expected AEs are events that have been previously
observed with use of the study agent(s). It is not based
on what might be anticipated from the pharmacological
properties of the study agent
• Listed in the Investigator’s Brochure or Package Insert
• SUSAR Reporting Category:
• Site physician to determine expectedness
• SAE Reporting Category:
• Sponsor to determine expectedness
49
Expedited Reporting
Processes
SAE Reporting Category Flowchart
51
Adverse Events Not Requiring Expedited
Reporting to DAIDS
• An SAE occurring before exposure to a study
agent.
• Immune reconstitution inflammatory syndrome
(IRIS), even if the event otherwise meets the
reporting criteria. IRIS is an intense immune
reaction that may result from a response to HIV
treatment and is an anticipated event for
antiretroviral therapies.
53
Reporting Fetal Loss
Manual Version 1.0
Manual Version 2.0
All congenital
anomalies, birth
defects, or fetal losses
regardless of
relationship to study
agent
SAE criteria: Congenital
anomaly/birth defect.
Clinically insignificant
physical findings at birth,
including those regarded
as normal variants, do not
meet reporting criteria
No fetal loss language
54
New/Initial Reports
AEs that are reportable on New/Initial Reports:
• New AE
• Recurrent AE: only if the first AE has resolved, is
now reoccurring and meets expedited reporting
criteria
• Preexisting condition with increase in severity
55
Updated Information
• Sites must follow each AE until the AE is resolved or stable
• For each AE reported to DAIDS, sites are required to submit
an updated report to DAIDS as soon as significant additional
information becomes available. The following are examples
that must be submitted:
• An updated report documenting the stable or resolved outcome of
the AE, unless the initial report included a final outcome
• Any change in the assessment of the severity grade of the AE or the
relationship between the AE and the study agent
• Additional significant information on a previously reported AE (e.g.,
cause of death, results of re-challenge with the study agent(s)).
56
Reporting Timeframe
• Within 3 reporting days of
site awareness that an
event has occurred at a
reportable level
• “Reporting days” are
those that count toward
the 3-day timeline
provided for reporting of
SAEs to DAIDS
57
Reporting Days
The criteria used to determine reporting days are as follows:
• A reporting day starts at 12:00 AM (midnight) and ends at 11:59 PM
local time.
• A day is counted as a reporting day regardless of the time of day that
awareness occurred. The day a site indicates that site personnel
became aware of an SAE that meets reporting criteria shall count as day
1 if that day occurs on a reporting day (i.e., Monday through Friday). If
that day occurs on a non-reporting day (i.e., Saturday or Sunday), then
the next reporting day shall count as day 1.
• Monday through Friday count as reporting days.
• Saturday and Sunday are not considered reporting days.
• Any holiday (U.S. or in-country/local) that occurs on a Monday through
Friday counts as a reporting day.
58
Site Investigator Signature
• A site physician investigator or sub-investigator
listed on the 1572 or the IoR Agreement must:
• Review and verify the completed report for
accuracy and completeness
• Sign the report
• This physician makes the site’s final
assessment of the relationship to study agent(s)
59
Site Investigator Signature
Manual Version 1.0
Manual Version 2.0
• If necessary to meet timely
reporting requirements,
sites can submit an
expedited adverse event
report without a completed
signature page.
• However, the completed
signature page, and
necessary corrections or
additions, must be
submitted within the next 3
business days.
• In the rare event that such physician(s) are
not available for signature, sites may
submit without signature to meet the
reporting timeframe.
• However, the signature and any necessary
corrections or additions must be submitted
within the next three reporting days
• The IoR or designee is responsible for
designating at least one other physician
who can perform the assessment and
signature so as to provide uninterrupted
coverage of monitoring AEs that will
require expedited reporting
60
Overview of Reporting Timelines
61
DAERS
DAERS: DAIDS Adverse Experience Reporting System:
• An integrated module that is part of the DAIDS Enterprise
•
•
System (DAIDS-ES)
A secure, confidential, web-based system through which sites
are required to submit expedited reports to DAIDS
For sites where DAERS has been implemented, all SAEs and
supporting information will be submitted to DAIDS using the
DAERS, unless the system is unavailable for technical reasons
• Use DAIDS SAE reporting form if DAERS not implemented
62
How to Report SAEs
• Reports must be submitted via DAERS:
• DAERS: via web
•
https://daidses.niaid.nih.gov/Phoenix
• For emergency use only:
• FAX: 1-301-897-1710
or 1-800-275-7619 (USA only)
• Email: [email protected]
• If e-mailing, scan or FAX signature page
63
Confirmation Of Receipt
• DAERS will send a confirmation email for
all SAE reports.
• It is the site’s responsibility to follow-up if
they do not receive a confirmation email.
64
Where to Get Help
• RSC Safety Office:
•
E-mail:
[email protected]
•
Telephone:
+ 1-301-897-1709
or 1-800-537-9979 (US Only)
•
FAX:
+1-301-897-1710
or 1 -800-275-7619 (US Only)
• RSC Web Site:
http://rsc.tech-res.com
• DAIDS-ES Support:
•
E-mail:
[email protected]
•
Telephone:
+1-240-499-2239
or 1-866-337-1605 (US Only)
•
Fax:
+1-301-948-2242
65
Summary of Changes
Major Changes
Reporting Categories
Relationship to study agent
Relationship assessment
for a combination product
Version 1
May 6, 2004
Version 2
Jan 2010
• Levels:
•Standard
• Intensive
•Targeted
• SAEs (Serious Adverse
Events)
•
•
•
•
•
• Related (Reasonable
possibility)
Definitely related
Probably related
Possibly related
Probably not related
Not related
Not specified
• SUSARs (Suspected
Unexpected Serious
Adverse Reactions)
• Not Related (No
reasonable possibility)
Each component
separately as well as the
combination
66
Summary of Changes
Major Changes
(Reportability)
Version 1
May 6, 2004
Version 2
Jan 2010
SAEs
-
Report only if there is exposure to study agent
Life-threatening
events
Only report if
related
SAE level: Report regardless of relationship
SUSAR level: Report if related and unexpected
Hospitalizations
Only report if
related
SAE level: Report regardless of relationship
SUSAR level: Report if related and unexpected
Report only if associated with an AE
Important
medical events
As judged by
site
investigator
Part of ICH-SAE criteria
Report per level of expedited reporting
Fetal Loss
Yes
Not required unless clinically significant, congenital
anomaly detected, or specified by protocol
IRIS events
-
Do not report
67
Summary of Changes
Major
Changes
Version 1
May 6, 2004
Version 2
Jan 2010
Grading
Grade 4 events are referred to
as life threatening events
Grade 4 events are referred to as
potentially life threatening events.
Therefore not all Grade 4 events will
meet SAE reporting criteria
AE
Resolution
Record in source
documentation. Provide only if
requested by DAIDS
Sites must follow each AE until
resolved or stable. Provide as update
New events
vs. Updates
Report as new event if any
ongoing event has a higher
severity grade than previously
reported
Report as an update if any ongoing
event has a change in the severity
grade
68
Questions?