Reporting Requirements Protocol References Section Title 72 SafetyRelated Data Collection 73 Expedited Adverse Event Reporting Other References and Resources 3 Manual for Expedited Reporting of Adverse Events to DAIDS Version 20 ID: 656926
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Slide1
Expedited
Adverse Event
Reporting RequirementsSlide2
Protocol References
Section
Title
7.2
Safety-Related
Data Collection
7.3
Expedited Adverse Event ReportingSlide3
Other References and Resources
3
Manual for Expedited Reporting of Adverse Events to DAIDS (Version 2.0)
DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events,
Corrected Version 2.1
, dated July 2017
Study drug package insertsDAERS user and reference guidesDAIDS safety training resources https://rsc.tech-res.com/clinical-research-sites/safety-reporting/daidshttps://rsc.tech-res.com/clinical-research-sites/safety-reporting/safety-training-resourcesSlide4
Overview of Presentation
4
Terms and definitions
Protocol specifications for expedited adverse event reporting
Relationship assessment
Case examplesSlide5
Adverse Event
5
Protocol Section 7.2
The definition of the term adverse event provided in Version 2.0 of the DAIDS EAE Manual will be used in this studySlide6
The definition of adverse event provided in
Version 2.0 of the DAIDS EAE Manual will be used in this study.
6
Adverse event
= any untoward medical occurrence in a patient or clinical investigation subject administered a study agent which does not necessarily have a causal relationship with this treatment.
An adverse event can therefore by any unfavorable and unintended sign (including an abnormal
laboratory finding, symptom, or disease) temporally associated with the use of a medicinal (investigational) agent, whether or not related to the medicinal (investigational) agent. (ICH E2A)Slide7
7
The same definition applies to
all
participants
Beginning at the time of enrollment
Regardless of the ARVs the mother takes or does not take
So for each mother-infant pair, we start identifying adverse events immediately after they are randomized in the Subject Enrollment SystemAdverse Event Slide8
8
Pre-existing condition
= untoward medical occurrence identified in a study participant prior to enrollment.
Pre-existing conditions are
not
adverse events.
However, if a pre-existing condition worsens in severity or frequency after enrollment, the worsened condition is an adverse event.Pre-Existing ConditionSlide9
Pre-Existing Conditions
9
Protocol Section 7.2.1
All pre-existing conditions identified among mothers during the 28 days prior to study entry will be entered into maternal medical history eCRFs Slide10
Expedited Adverse Events
10
The following types of adverse events must be reported in an expedited manner in IMPAACT 2010:
Serious adverse events (SAEs)
Suspected unexpected serious adverse reactions (SUSARs)
Pregnancy complications that result in medically indicated and/or elective termination of pregnancy
Spontaneous abortions and fetal deathsHepatic toxicities that result in discontinuation of DTG or EFVSerious ABC hypersensitivity reactions in mothers switching from TDF or TAF to ABCSlide11
Serious Adverse Event
11
Serious adverse event
= an adverse event that ...
Results in death
Is life-threatening
*Requires inpatient hospitalization* or prolongation of existing hospitalizationResults in persistent or significant disability/incapacityIn a congenital anomaly/birth defect*
Is an important medical event that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require intervention to prevent one of the other outcomes listed above
*See helpful clarifications of these terms in the DAIDS EAE ManualSlide12
Congenital anomaly/birth defectSlide13
Do you have any questions
about the definition of SAE for this study?
13Slide14
SUSAR
14
Suspected
= Related to use of study drug
Unexpected
= Nature or severity is not consistent with the study drug’s current package insert
Serious adverse reaction = SAESlide15
Related or Not Related
15
Related
= There is a
reasonable possibility
that the event may be related to study drug.
Not related = There is not a reasonable possibility that the event may be related to study drug.Slide16
Reasonable Possibility
16
Reasonable possibility
is intended to convey that there are facts, evidence, or arguments to suggest a causal relationship between the event and study drugSlide17
Facts, Evidence, or Arguments
to Suggest a Causal Relationship
17
A
temporal relationship
between the event and use of study drug
A plausible biologic mechanism for study drug to cause the eventPrevious reports of similar events associated with study drug (or drugs of the same class)Resolution of the event after de-challenge (hold/discontinuation of study drug)
Recurrence
of the event after re-challenge (resumption of study drug after a hold)Slide18
18
In addition to considering the possibility of a causal relationship with study drug,
consider other potential causes
of the event, e.g.,
Past medical history
Concurrent illness
Concomitant medicationsFor events assessed as not related, document an alternative etiology, diagnosis, or explanation in study recordsRelated or Not RelatedSlide19
19
Reminder of Random AssignmentsSlide20
20
For EAEs reported for participants in
Arm 1
Relationship assessments are required for
DTG, FTC, and TAF
For EAEs reported for participants in
Arm 2Relationship assessments are required for DTG, FTC, and TDFFor EAEs reported for in Arm 3Relationship assessments are required for EFV, FTC, and TDF
Related or Not RelatedSlide21
21
For mothers, assess relationship to each ARV received (ingested)
For infants, assess relationship to each ARV received by the mother to which the infant may have been exposed
in utero
or through breastfeeding
Related or Not RelatedSlide22
EAE Reporting Requirements
for
Infants
Study Entry through Week 14 Postpartum
Week 14 Postpartum through Study Exit
Arm 1
SAEsSUSARsArm 2SAEsSUSARsArm 3SUSARsSUSARsSlide23
EAE Reporting Requirements
for
Mothers
Study Entry through Week 14 Postpartum
Week 14 Postpartum through Study Exit
Arm 1
SAEsSAEsArm 2SAEsSAEsArm 3SUSARsSUSARsSlide24
Additional EAE Reporting Requirements for
Mothers
Event
Arm 1
Arm 2
Arm
3Spontaneous abortions and fetal deathsYesYesNoPregnancy complications that result in medically indicated and/or elective termination of the pregnancy
Yes
Yes
NoSlide25
Additional EAE Reporting Requirements for
Mothers
Event
Arm 1
Arm 2
Arm
3Hepatic toxicities that result in discontinuation of DTG or EFVYesYesYesSerious ABC hypersensitivity reactions in mothers switching from TDF or TAF to ABC
Yes
Yes
YesSlide26
A pregnant woman randomized to Arm 1 at 18 weeks gestation is hospitalized at 20 weeks gestation with a febrile illness.
Yes
No
Maybe
Response Counter
Has a reportable EAE occurred?
26Slide27
A pregnant woman randomized to Arm 2 at 18 weeks gestation is hospitalized at 20 weeks gestation with a febrile illness.
Yes
No
Maybe
Response Counter
Has a reportable EAE occurred?
27Slide28
A pregnant woman randomized to Arm 3 at 18 weeks gestation is hospitalized at 20 weeks gestation with a febrile illness.
Yes
No
Maybe
Response Counter
Has a reportable EAE occurred?
28Slide29
A pregnant woman randomized to Arm 1 at 22 weeks gestation experiences a still birth at 28 weeks gestation.
Yes
No
Maybe
Response Counter
Has a reportable EAE occurred?
29Slide30
A pregnant woman randomized to Arm 2 at 22 weeks gestation experiences a still birth at 28 weeks gestation.
Yes
No
Maybe
Response Counter
Has a reportable EAE occurred?
30Slide31
A pregnant woman randomized to Arm 3 at 22 weeks gestation experiences a still birth at 28 weeks gestation.
Yes
No
Maybe
Response Counter
Has a reportable EAE occurred?
31Slide32
32Slide33
An enrolled pregnant woman reports to the clinic for her antepartum Week 4 visit complaining of severe fatigue, nausea, vomiting, and abdominal pain. Lab testing provides grade 4 ALT and AST results.
Yes
No
Maybe
Response Counter
Has a reportable EAE occurred?
33Slide34
What are your questions
about EAE reporting?
34