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>> Liz Ness: Welcome to 
Part 2 of Adverse Events, 

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Assessment and Documentation.

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My name is Liz Ness.

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And I'm the director
of the Office of Education

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and Compliance in the 
Center for Cancer Research

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at the 
National Cancer Institute.

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Assessment of adverse events
and timely documentation

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is crucial to research
participant safety

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and a critical component
of good clinical practice.

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At the end of Part 2,

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I hope you'll be able
to describe the components

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of a quality adverse event
assessment and documentation

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as well as the 
common data elements

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that are collected on an 
adverse event case report form.

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When you are assessing safety

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and or toxicity
in a clinical trial,

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you need to first assess

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and document how the 
participant is doing at baseline

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before beginning any 
component of the research.

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So, you want to assess the signs
and symptoms that are present

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when the participant
starts treatment.

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So, for example,
this could be the first day

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immediately pre-dosing
or receiving the intervention.

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It usually doesn't include those
signs and symptoms that occurred

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and resolved between the time
of eligibility screening

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and the starting of dosing.

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Those often are considered
part of medical history

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and are added to a medical
history case report form.

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And you would need to have
some type of a description

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such that you knew how severe
that baseline symptom was.

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Please note though
that some sponsors

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required the research teams
to record adverse events from

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when the patient 
signs the consent

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through the first
study intervention.

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This should be 
defined in the protocol

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or at least in the case
report form instruction manual.

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Assessment of an adverse event

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is done by the 
principal investigator

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or their designee who is
a member of the research team.

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Typically, these are
other licensed individuals.

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And it includes 
determining the severity

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as well as the cause of the event.

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It is this assessment
plus the expectedness

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and outcome of the event
that determine the timelines

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for reporting an adverse 
event to the IRB, sponsor,

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or other regulatory
or oversights groups.

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The reporting will be done
in AE Part 3 and Part 4.

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Using controlled vocabularies
to represent clinical concepts

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is the best way
to describe an adverse event

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or to select an 
adverse event term.

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MedDRA, or the Medical Dictionary

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for Regulatory Activities,
and SNOMED,

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or the Systematized Nomenclature
of Medicine Clinical Terms,

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are two most common sources
for medical terminology.

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MedDRA is widely used
in clinical trials,

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whereas SNOMED Clinical Terms
is used for clinical care data,

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often in your, maybe,
electronic health record.

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In oncology, the clinical --
the common toxicity,

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the CTCAE or the Common
Terminology Criteria

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for Adverse Events

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is used, which is a 
combination of MedDRA terms,

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which we'll talk more 
about in a minute,

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and a severity rating scale,

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which will be described 
later in this session.

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Though the CTCAE
was initiated in oncology,

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other disease specialties do use
this as well for their standard

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in determining
an AE term or severity

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or use it as a model
to create a similar type

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of severity rating scale.

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So, MedDRA is a clinically
validated international

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medical terminology dictionary
with each term

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having a unique code

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and what is referred
to as a concept ID.

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It was initially developed
in 1994 by ICH to facilitate

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the sharing of regulatory
information internationally.

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MedDRA is used by
the biopharmaceutical industry

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and regulatory authorities
for AE classification.

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The structure of MedDRA
is actually very logical.

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There are five levels
to the MedDRA hierarchy,

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arranged from very 
specific to very general,

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or very general
to very specific.

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The first highest level
is called a SOC

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or a System Organ Class

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for which they're
in the version of 26

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that was released
in March of 2023.

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There are 27 SOCs.

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These are the highest 
level of the terminology

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and they're distinguished

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by anatomic or 
physiological systems

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such as infections
or infestations

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or purposes such
as surgical or medical.

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Then there is a 
High-Level Group Term,

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a subordinate to the SOC,
a High-Level Term,

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which is subordinate
to the term above,

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the High-Level Group Term,
a Preferred Term,

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which represents
a single medical concept,

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and then a Lowest Level Term,

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which is related to a 
single preferred term

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as synonyms or quasi-synonyms.

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And here is an example of the
Preferred Term, fatigue,

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which is found in the System
Organ Class of general disorders

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and administrative
site conditions,

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a High-Level Group Term
of general systems disorders NEC

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or not elsewhere classified,

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a High-Level Term
of asthenic conditions,

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Preferred Term of fatigue.

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And then when you look at
the various Lower-Level Terms,

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you can see
that these often represent

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how our research participants

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might express an adverse event
term of fatigue,

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such as,
"I'm feeling washed out."

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"I'm just tired all the time."
"I feel very weary."

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"I'm exhausted."
And that's then how we can take

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what the research 
participant says,

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what we see documented
in a medical record,

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and determine what might be
the most appropriate,

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let's say Preferred Term,
that can be used

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and then shared
across regulatory agencies.

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So, understanding and measuring
severity is also important.

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So, in clinical trials,

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typically there
are rating scales

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that are used
to measure severity.

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The severity of an AE
often determines

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if dosing interruptions,

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modifications, or maybe even
a discontinuation needs to be

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implemented according to
what the protocol says.

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Rating scales can be used
for eligibility criteria.

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They can also include how the
severity of the adverse event

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is to be measured,

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even if only
providing descriptions

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for mild, moderate, or severe.

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And here you can see
some definitions of mild,

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moderate, and severe.

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So, mild, there is an awareness
of a sign, a symptom,

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or an adverse event,
but it's easily tolerated.

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Moderate means
that it's uncomfortable,

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that it's causing
some interference

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with usual activities
of daily living,

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or that it may warrant
some additional investigation.

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And severe is incapacitating
their ability

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to do their usual activities

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or having significant effect
on their clinical status

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that further warrants intervention.

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And sometimes, you know,
my definition of mild

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might be different
than your definition of mild.

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So, it is important to try
to hone in on this in a protocol

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when defining what severity
an adverse event is.

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As I mentioned, in oncology,

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we utilize what
we call the CTCAE.

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The National Cancer Institute
Cancer Therapy Evaluation

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Program actually developed
the original CTC,

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which was Common
Toxicity Criteria, in 1983

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to help aid in recognizing
and assessing the severity,

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or what's referred to as grading
of adverse effects

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on chemotherapy.
The name was changed since,

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as I mentioned in Part 1
of Adverse Events,

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toxicity has an implication
of an association

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with the intervention.

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And as we know, adverse events
do not have that association.

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These became fundamentally
agreed upon terms

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for adverse events
within oncology research.

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But as I mentioned, it has gone
to other disciplines as well.

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And it's organized
by MedDRA terms

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using the System Organ Class

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minus the product issue system
organ classification.

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And the AE term
is a Lowest Level Term,

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which can be rolled up
then to a Preferred Term.

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This is just a brief
evolution of CTCAE.

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Initially, there were categories
and adverse event terms.

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You can see with each version,

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there were an 
increase in categories,

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which with Version 4 in 2010

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was harmonized with MedDRA's
System Organ Class.

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And then the AE terms
have also exponentially grown.

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You'll notice that the 
current Version 5.0

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has 837 adverse event terms.

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And as you saw in a couple
of slides previously,

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the MedDRA Lower-Level Terms,

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there were, you know,
almost 88,000.

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So, these are certainly subsets

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of what is commonly seen
in oncology research.

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I will note as of this taping as
well Version 6 is in the works

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and is waiting
for a finalization

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with the fall release of MedDRA,
which typically is in September.

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They do sort of
a point version --

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point one version release
in the fall

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with their main version
releases in the early spring,

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typically in March.

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If a condition is not listed,
since there's only 837 terms,

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each of the SOCs has what we
refer to as an Other category,

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so that a term
can be applied there.

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And I'll show you
how you would then

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determine what severity rating.

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But let's take a look
of an AE term.

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I selected anemia.

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It falls within the blood and
lymphatic system disorder SOC.

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And the SOCs in general
are located alphabetically.

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And the adverse event terms

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also are listed
alphabetically within a SOC.

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And as I mentioned,
each SOC has an Other AE term.

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All of the AE terms have
a definition that you see here

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as well as different grades.

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So, when you read --
when you're reading CTCAE,

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semicolons are read
as or statements.

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And sometimes you will see
what's called an em-dash

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or a line,
which indicates that that grade

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or that severity rating
is not appropriate.

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For an example of then
how to use this

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in reviewing a lab result,
if you have a hemoglobin of 8.1,

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but the physician feels based on
the symptoms of the participant

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that they need
a blood transfusion.

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At face value, the lab value
itself looks like it would mean

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that that would be
a Grade 2 event.

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However, when a transfusion
is indicated,

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the comma or the semicolon
in Grade 3 reads

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as an or statement.
So, or a transfusion indicated.

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So, a hemoglobin of 8.1
with a participant

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who might be symptomatic
and is in need of a transfusion

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becomes a Grade 3 anemia
as an adverse event.

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Here is another example.

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And I chose this example
of diarrhea

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as an adverse event term

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to indicate how important
baseline assessment really is.

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So, you can see the SOC here
of gastrointestinal disorders.

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And you can see that the grading
or the definitions

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within each grade talk
about an increase over baseline.

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So, it's really critical
to understand

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what the normal bowel pattern
is of a research participant,

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especially when you may
anticipate changes

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in their bowel pattern

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given what you know
about the products

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or the interventions
within that clinical trial.

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You can also notice here
that you have an increase

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or limiting self-care ADLs.

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So, self-care ADLs
are those ADLs

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that you do for yourself
such as bathing, feeding,

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and then there's other ADLs
called instrumental ADLs

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that are part of some
of the definitions.

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And I think of those

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as when you're not able
to do for others,

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such as going
to the grocery store

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or preparing a meal
for your family.

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So, since not all terms are
available that are in MedDRA,

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other is an AE term,
and then you describe that.

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And this is the descriptions
for each of the grades here.

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And again, you would use the
semicolons as an or statement.

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So, if you had a term
that wasn't available

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you would look
to the other grading scale

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and determine which definition
or description it falls in

249
00:16:29,430 --> 00:16:31,630
to select the appropriate grade.

250
00:16:33,690 --> 00:16:37,580
So, for those of you
that do utilize CTCAE.

251
00:16:38,650 --> 00:16:41,580
It is available
on a smartphone or tablet.

252
00:16:41,580 --> 00:16:43,930
It has a great,
easy search feature.

253
00:16:45,140 --> 00:16:48,460
This is just snapshots
from the app from my phone.

254
00:16:48,460 --> 00:16:53,050
This pulls up
the System Organ Class of blood

255
00:16:53,050 --> 00:16:55,100
and lymphatic system disorders.

256
00:16:55,100 --> 00:16:59,040
And when I went and plugged-in
anemia, I can see --

257
00:16:59,040 --> 00:17:02,740
you can see the same grading
scale with the definition here

258
00:17:02,740 --> 00:17:06,240
that I noted
in a few slides previously.

259
00:17:06,240 --> 00:17:09,760
There's also a PDF version
on NCI's website,

260
00:17:10,390 --> 00:17:12,970
and that also, you know,
you can search

261
00:17:12,970 --> 00:17:15,190
using the PDF search feature.

262
00:17:17,440 --> 00:17:20,320
So, the FDA also has a guidance
document

263
00:17:20,320 --> 00:17:24,200
for grading adverse events
in prevention clinical trials.

264
00:17:24,200 --> 00:17:25,940
And so, you can see here

265
00:17:25,940 --> 00:17:30,330
they use a similar system
of Grades 1 through 4,

266
00:17:30,330 --> 00:17:33,490
and that is found
in the guidance document

267
00:17:34,710 --> 00:17:37,270
entitled here on the slide.

268
00:17:37,270 --> 00:17:41,270
But regardless of how an adverse
event is assessed for severity

269
00:17:41,270 --> 00:17:43,830
or which grading scale you use.

270
00:17:43,830 --> 00:17:46,750
The protocol ideally
should help provide you

271
00:17:46,750 --> 00:17:50,130
with that information
to guide you

272
00:17:50,130 --> 00:17:54,040
in having consistent
assessments of severity rating.

273
00:17:55,320 --> 00:17:58,730
Once the severity of an adverse
event is established,

274
00:17:58,730 --> 00:18:00,980
the next step really
is to find the cause

275
00:18:00,980 --> 00:18:03,020
or the attribution of the event.

276
00:18:03,580 --> 00:18:08,090
Is the event related
to the study agents,

277
00:18:08,640 --> 00:18:10,340
the patient's, you know,

278
00:18:10,340 --> 00:18:13,640
underlying condition
that's being studied,

279
00:18:13,640 --> 00:18:17,490
or underlying
pre-existing conditions?

280
00:18:17,490 --> 00:18:20,720
So, determining the attribution
is done by the PI

281
00:18:20,720 --> 00:18:24,750
or a provider designee who's
knowledgeable about the product

282
00:18:24,750 --> 00:18:26,350
and about the protocol.

283
00:18:27,360 --> 00:18:31,180
I always think of determining
an attribution or causality

284
00:18:31,180 --> 00:18:33,190
as not just a science,
but an art.

285
00:18:33,980 --> 00:18:37,540
And here are some following
things that can be --

286
00:18:37,540 --> 00:18:42,140
some questions that you can ask
to help the research team

287
00:18:42,140 --> 00:18:44,120
determine that attribution.

288
00:18:44,820 --> 00:18:48,830
What do you already know
about the drug, the therapy,

289
00:18:48,830 --> 00:18:50,980
or the classification
of the drug?

290
00:18:50,980 --> 00:18:53,030
So, the expectedness.

291
00:18:53,030 --> 00:18:55,970
What is the temporal
relationship of the event

292
00:18:55,970 --> 00:18:58,140
to the study therapy
or intervention?

293
00:18:59,080 --> 00:19:01,770
Does the adverse event
improve or disappear

294
00:19:02,320 --> 00:19:05,710
when the drug
or the therapy is stopped?

295
00:19:06,330 --> 00:19:09,000
If the drug or therapy
is reintroduced,

296
00:19:09,640 --> 00:19:12,660
does the adverse event reappear?

297
00:19:12,660 --> 00:19:14,840
Does it reappear
at the same time point?

298
00:19:14,840 --> 00:19:17,550
Does it reappear
at the same severity rating?

299
00:19:19,030 --> 00:19:21,990
Is the adverse event
a result of signs

300
00:19:21,990 --> 00:19:25,150
or symptoms of the underlying
disease being studied?

301
00:19:25,770 --> 00:19:28,610
Is it a worsening
of baseline symptoms?

302
00:19:29,120 --> 00:19:33,300
Is the adverse event a result
of an underlying concurrent

303
00:19:33,300 --> 00:19:38,110
on medical condition or the use
of a concurrent medication?

304
00:19:40,320 --> 00:19:42,150
So, those are some questions.

305
00:19:42,150 --> 00:19:46,470
And so, what are our options
for then

306
00:19:46,470 --> 00:19:50,200
assigning those attributions
or causalities.

307
00:19:50,200 --> 00:19:52,050
So, there's
sort of two approaches.

308
00:19:52,050 --> 00:19:55,880
This approach one is what I call
the dichotomized approach.

309
00:19:55,880 --> 00:19:58,210
So, you either think
that it's related.

310
00:19:58,210 --> 00:20:01,210
So, there's a reasonable
causal relationship

311
00:20:01,210 --> 00:20:02,810
between the adverse event,

312
00:20:03,760 --> 00:20:06,060
and I'll explain the blanks
in a minute,

313
00:20:06,060 --> 00:20:07,280
or it's not related.

314
00:20:07,280 --> 00:20:09,930
There's no reasonable
causal relationship.

315
00:20:11,530 --> 00:20:15,880
Then there's what I call
the five degrees of separation

316
00:20:15,880 --> 00:20:19,050
or five options
where you have definite,

317
00:20:19,050 --> 00:20:21,300
which means
it's clearly related;

318
00:20:21,300 --> 00:20:23,850
probable, likely related;

319
00:20:23,850 --> 00:20:28,840
possible, maybe related;
unlikely, doubtfully related;

320
00:20:28,840 --> 00:20:31,290
or unrelated, clearly related.

321
00:20:32,310 --> 00:20:35,330
And the trick is really
filling in the blank.

322
00:20:36,250 --> 00:20:41,600
So, if the AE is related
to the investigational product,

323
00:20:41,600 --> 00:20:47,160
the commercial agent,
the underlying comorbid disease,

324
00:20:47,160 --> 00:20:52,620
when you fill in that blank,
that will then help you to know

325
00:20:53,160 --> 00:20:59,030
if you have any reporting
responsibilities to the IRB

326
00:20:59,030 --> 00:21:00,720
or to your sponsor,

327
00:21:00,720 --> 00:21:04,380
who in turn may then need
to report to the IRB --

328
00:21:04,380 --> 00:21:06,450
or to the FDA, my apologies.

329
00:21:07,010 --> 00:21:11,280
The IRB is looking at
the relatedness to the research.

330
00:21:11,280 --> 00:21:14,000
So, all components
of the research,

331
00:21:14,000 --> 00:21:16,600
whereas the sponsor
is often really looking

332
00:21:16,600 --> 00:21:19,720
for the relatedness
to the product.

333
00:21:20,560 --> 00:21:24,470
So, teasing this out
is extremely important.

334
00:21:24,470 --> 00:21:27,160
And we always do want
to tease out

335
00:21:27,160 --> 00:21:32,240
and try to determine how to fill
in that blank and determine,

336
00:21:32,240 --> 00:21:35,340
is there a relatedness or not?

337
00:21:35,340 --> 00:21:38,870
And if the relatedness
is to something else

338
00:21:38,870 --> 00:21:40,450
other than the research,

339
00:21:40,450 --> 00:21:43,980
we do owe it to our participants
to determine that

340
00:21:43,980 --> 00:21:45,770
and to find out that cause.

341
00:21:47,840 --> 00:21:51,310
So, when we start thinking about
assessing of adverse events,

342
00:21:52,200 --> 00:21:55,220
it really comes
from our participants,

343
00:21:55,220 --> 00:21:56,920
you know, review of systems,

344
00:21:56,920 --> 00:22:00,260
physical exam
findings, laboratory

345
00:22:00,260 --> 00:22:02,910
and other radiologic results,

346
00:22:02,910 --> 00:22:07,430
or, you know, EKG results,
things like that.

347
00:22:07,430 --> 00:22:11,880
But again, before starting on
a clinical research study,

348
00:22:11,880 --> 00:22:13,820
especially a clinical trial,

349
00:22:13,820 --> 00:22:17,130
a good baseline assessment
is needed.

350
00:22:17,130 --> 00:22:20,840
And that does include
finding what is abnormal.

351
00:22:20,840 --> 00:22:24,000
So, what laboratory values
are already abnormal?

352
00:22:24,550 --> 00:22:30,100
In a review of systems,
what are the current symptoms

353
00:22:30,100 --> 00:22:33,120
that an individual
may be experiencing?

354
00:22:34,890 --> 00:22:39,550
It's also important to assess
their concomitant

355
00:22:39,550 --> 00:22:41,550
or current medications.

356
00:22:41,550 --> 00:22:44,760
Because sometimes
a change in those,

357
00:22:44,760 --> 00:22:48,340
or if a medication
was recently introduced,

358
00:22:48,340 --> 00:22:53,380
possibly a day before starting
on an intervention,

359
00:22:54,360 --> 00:22:57,720
then the assessment might be
a little bit different.

360
00:22:57,720 --> 00:23:01,280
So, all of
this baseline information

361
00:23:01,280 --> 00:23:03,990
is extremely critical.

362
00:23:06,560 --> 00:23:10,890
So, adverse event information
should be collected really,

363
00:23:11,450 --> 00:23:15,660
as I mentioned, you know,
from either the time of consent,

364
00:23:15,660 --> 00:23:18,130
if that's what
the sponsor wants,

365
00:23:18,130 --> 00:23:22,020
or the initiation
of the study intervention,

366
00:23:22,020 --> 00:23:25,300
or the start of a placebo
lead-in period

367
00:23:25,300 --> 00:23:30,210
or there may be an observational
or washout type of period

368
00:23:31,890 --> 00:23:36,580
to establish what the baseline
condition of the individual is,

369
00:23:36,580 --> 00:23:40,130
which is a little bit different
than the baseline going in.

370
00:23:40,130 --> 00:23:43,270
There could be two baselines,
if you will,

371
00:23:43,270 --> 00:23:45,290
if you have a placebo lead-in

372
00:23:45,290 --> 00:23:47,760
or some type
of an observational period.

373
00:23:49,380 --> 00:23:52,180
So, before documentation
of an adverse event,

374
00:23:52,180 --> 00:23:54,870
the research team really
does need to understand

375
00:23:55,590 --> 00:23:57,590
how AEs should be collected.

376
00:23:58,580 --> 00:24:02,460
In order to prevent bias,
collection of adverse events,

377
00:24:02,460 --> 00:24:06,730
participants should not be
questioned specifically

378
00:24:06,730 --> 00:24:13,030
regarding what we might
anticipate could occur.

379
00:24:13,030 --> 00:24:15,060
So, if we do know, for example,

380
00:24:15,060 --> 00:24:17,720
that there could be a change
in bowel habits,

381
00:24:17,720 --> 00:24:19,920
we wouldn't want
to necessarily say,

382
00:24:19,920 --> 00:24:23,130
"Have you had experienced
any diarrhea?

383
00:24:23,130 --> 00:24:25,450
Have you experienced
constipation?"

384
00:24:25,450 --> 00:24:28,410
But we would want to ask
a general question of,

385
00:24:28,410 --> 00:24:33,740
"Have you had any changes in,
you know, your bowel pattern

386
00:24:33,740 --> 00:24:37,110
or your bowel habits."
So, that's really important.

387
00:24:37,960 --> 00:24:41,990
Ideally, the adverse events
should be spontaneously reported

388
00:24:42,520 --> 00:24:47,560
or elicited from the participant
during open-ended questioning,

389
00:24:47,560 --> 00:24:51,990
during the examination,
or during the evaluation

390
00:24:51,990 --> 00:24:56,970
of the examination review
or review of systems.

391
00:24:59,670 --> 00:25:02,220
Adverse events do need
to be followed

392
00:25:02,220 --> 00:25:05,010
until resolution
or stabilization.

393
00:25:05,600 --> 00:25:09,170
There are some adverse events
that may never resolve.

394
00:25:09,750 --> 00:25:14,140
For example,
with an oncology patient

395
00:25:14,140 --> 00:25:20,550
who has brain metastasis
and receives brain radiation,

396
00:25:20,550 --> 00:25:25,350
the hair on their head
or alopecia may not ever return.

397
00:25:27,100 --> 00:25:33,530
There're also some drugs
that might have a toxicity

398
00:25:33,530 --> 00:25:38,210
of a neuropathy.
That neuropathy may improve,

399
00:25:38,210 --> 00:25:41,830
but it may never be able
to completely go away.

400
00:25:41,830 --> 00:25:43,910
So, those are
a couple of examples

401
00:25:43,910 --> 00:25:46,480
of sort of the stabilization.

402
00:25:47,730 --> 00:25:50,540
So, further decreasing
of severity,

403
00:25:50,540 --> 00:25:52,900
but not a total resolution.

404
00:25:57,120 --> 00:25:59,870
So, all adverse events
should be documented

405
00:25:59,870 --> 00:26:02,230
in a participant's
medical record,

406
00:26:02,230 --> 00:26:06,700
or in some cases
for healthy volunteers,

407
00:26:06,700 --> 00:26:09,310
if a medical record
is not required

408
00:26:09,310 --> 00:26:11,820
for the institution's policy,

409
00:26:11,820 --> 00:26:14,770
it may be documented
in a research record

410
00:26:14,770 --> 00:26:18,560
or potentially
on a case report form

411
00:26:19,670 --> 00:26:24,670
if that has been prearranged
with the sponsor.

412
00:26:24,670 --> 00:26:31,010
The documentation includes, you
know, the adverse event itself,

413
00:26:32,200 --> 00:26:36,650
when it started, any workup
or treatment that is needed.

414
00:26:37,660 --> 00:26:41,720
It is important that
all healthcare providers,

415
00:26:41,720 --> 00:26:44,310
professionals
who are interacting

416
00:26:44,310 --> 00:26:46,020
with the research participant,

417
00:26:46,960 --> 00:26:51,270
understands what is happening
and what the research team,

418
00:26:51,270 --> 00:26:56,990
the PI, thinks the causality
of the adverse event is.

419
00:26:56,990 --> 00:27:00,150
When that information
isn't being shared,

420
00:27:00,150 --> 00:27:07,020
it could lead to the potential,
you know, treatment of the event

421
00:27:07,020 --> 00:27:10,660
with a medication that's
prohibited on the protocol.

422
00:27:10,660 --> 00:27:16,960
Or it could impact, you know,
another provider's ability

423
00:27:16,960 --> 00:27:20,810
to provide an accurate
assessment and plan

424
00:27:21,940 --> 00:27:24,480
if they're not
a member of a research --

425
00:27:24,480 --> 00:27:26,400
of the research team directly.

426
00:27:27,150 --> 00:27:32,030
So, a quality progress note,
documenting an adverse event

427
00:27:32,030 --> 00:27:36,010
does need to include
the date of the adverse event.

428
00:27:36,010 --> 00:27:39,110
It also could be important
to note the time,

429
00:27:39,110 --> 00:27:43,230
especially when dealing
with infusion reactions.

430
00:27:43,230 --> 00:27:45,720
The time from the start
of the infusion

431
00:27:46,430 --> 00:27:51,750
can be extremely helpful
in further developing a product

432
00:27:51,750 --> 00:27:57,950
and the timing of potentially
the rate of infusion

433
00:27:58,680 --> 00:28:00,280
as an example.

434
00:28:00,970 --> 00:28:04,880
Treatment for the event
and indicating if no treatment

435
00:28:04,880 --> 00:28:10,740
is needed or further treatment
or an earlier repeat of a lab.

436
00:28:11,600 --> 00:28:15,410
Those are all examples
of sort of a treatment.

437
00:28:15,410 --> 00:28:17,820
There should be a description
of the adverse event

438
00:28:17,820 --> 00:28:21,570
such that it can be assessed
for severity

439
00:28:21,570 --> 00:28:25,540
or graded depending upon
the rating scale that is used.

440
00:28:25,540 --> 00:28:28,450
As I mentioned,
the adverse event attribution

441
00:28:28,450 --> 00:28:32,640
is important to document, again,
for other health care providers,

442
00:28:33,300 --> 00:28:36,730
and when the adverse event
begins to resolve,

443
00:28:37,240 --> 00:28:39,170
worsen, or improve.

444
00:28:41,360 --> 00:28:46,230
So, recording of adverse events,
also known as data abstraction,

445
00:28:46,230 --> 00:28:48,910
is when we take
what has been documented

446
00:28:48,910 --> 00:28:50,640
in the source document,

447
00:28:50,640 --> 00:28:52,739
the medical record
or the research record,

448
00:28:53,250 --> 00:28:57,110
and we abstract that
onto a case report form.

449
00:28:58,220 --> 00:29:01,030
And that is going to be
dependent on the protocol.

450
00:29:01,640 --> 00:29:07,310
Some protocols may want
all adverse events recorded.

451
00:29:07,310 --> 00:29:11,790
Others may only want
Grade 2 through 5

452
00:29:11,790 --> 00:29:13,790
adverse events recorded.

453
00:29:13,790 --> 00:29:16,370
But the protocol
should clearly outline

454
00:29:16,370 --> 00:29:19,710
what types of adverse events
that have been documented

455
00:29:20,220 --> 00:29:23,230
need to be recorded
on a case report form

456
00:29:23,230 --> 00:29:26,170
and used for further
data analysis.

457
00:29:26,840 --> 00:29:30,450
Though adverse event case
report forms can vary

458
00:29:30,450 --> 00:29:33,160
from institution or sponsor,

459
00:29:33,160 --> 00:29:37,370
most forms contain
similar information.

460
00:29:37,890 --> 00:29:41,070
They contain what is
the adverse event term,

461
00:29:42,340 --> 00:29:47,250
the date of the adverse event,
the severity, the treatment,

462
00:29:47,250 --> 00:29:49,800
the attribution, the treatment,
the attribution,

463
00:29:49,800 --> 00:29:52,860
and when the adverse
event resolves,

464
00:29:52,860 --> 00:29:57,510
or when the grade
of the adverse event ends,

465
00:29:57,510 --> 00:30:00,310
and a new grade begins.

466
00:30:00,310 --> 00:30:04,060
So, always refer to the protocol
for these recording,

467
00:30:04,060 --> 00:30:06,540
what I call recording
exceptions,

468
00:30:06,540 --> 00:30:10,230
and the case report
form instruction manual.

469
00:30:10,840 --> 00:30:13,340
Both of those are going to be
very helpful

470
00:30:13,340 --> 00:30:19,080
when it comes to then
the documentation of the events

471
00:30:19,080 --> 00:30:23,400
in the research database or on
the research case report form.

472
00:30:27,480 --> 00:30:30,810
So, in closing, assessment
of adverse events

473
00:30:30,810 --> 00:30:33,720
is critical for protecting
our research participants

474
00:30:33,720 --> 00:30:38,370
in developing toxicity profiles
for a drug or intervention.

475
00:30:38,370 --> 00:30:41,090
A quality baseline assessment
is the first step

476
00:30:41,090 --> 00:30:43,190
in assessing an adverse event.

477
00:30:43,190 --> 00:30:47,770
Adverse events assessment
includes

478
00:30:47,770 --> 00:30:49,760
asking open-ended questions

479
00:30:49,760 --> 00:30:54,150
as well as reviewing results
from physical exams,

480
00:30:54,150 --> 00:31:00,830
laboratory, imaging reports,
other medical reports.

481
00:31:00,830 --> 00:31:03,130
All adverse events
should be documented

482
00:31:03,130 --> 00:31:05,370
in either the medical
or research record.

483
00:31:05,370 --> 00:31:08,600
So, all health care providers
caring for the participant

484
00:31:08,600 --> 00:31:11,590
can be aware of the event
as well as its cause.

485
00:31:12,110 --> 00:31:15,480
And the attribution of the
adverse event should be assessed

486
00:31:15,480 --> 00:31:20,020
by the PI or provider designee
and shouldn't be taken lightly.

487
00:31:20,590 --> 00:31:22,610
There are several questions
that need to be addressed

488
00:31:22,610 --> 00:31:23,850
to achieve

489
00:31:23,850 --> 00:31:28,240
the most accurate attribution
or causality of the event.

490
00:31:28,240 --> 00:31:30,970
While all adverse events
are documented,

491
00:31:30,970 --> 00:31:32,260
not all adverse events

492
00:31:32,260 --> 00:31:35,270
may need to be recorded
on the case report form.

493
00:31:35,270 --> 00:31:38,790
And even fewer will need
to be reported to sponsors

494
00:31:38,790 --> 00:31:40,700
and regulatory authorities,

495
00:31:40,700 --> 00:31:43,330
which will be discussed
in Parts 3 and 4.

496
00:31:44,640 --> 00:31:46,540
So, let's test your knowledge.

497
00:31:47,270 --> 00:31:50,980
The attribution of an
adverse event can be determined

498
00:31:50,980 --> 00:31:54,230
by the study coordinator
on the research team,

499
00:31:54,230 --> 00:31:55,830
if they are a nurse.

500
00:31:56,690 --> 00:31:57,490
True or false?

500
00:32:00,090 --> 00:32:02:090
And the answer is false.

501
00:32:02,390 --> 00:32:05,360
The severity and 
relationship of an AE

502
00:32:05,360 --> 00:32:10,260
is completed by the PI
or a provider coordinator.

503
00:32:10,260 --> 00:32:15,050
But not the study coordinator
who may be a registered nurse.

504
00:32:15,050 --> 00:32:18,190
No matter how talented
that coordinator is,

505
00:32:18,190 --> 00:32:20,850
the responsibility
lies with the PI.

506
00:32:22,590 --> 00:32:26,440
Thank you for listening
to Part 2 of Adverse Events.