November 2024 SOCRA Source Journal - Journal - Page 56
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•
•
•
Concomitant medication
treatment
Medical intervention
Hospitalization
Other
Similarly, ‘Outcome’ categories
also depend on the log used,
including:
•
•
•
•
•
Subject recovered and the
event resolved with minor,
major, or no aftereffects
Event is ongoing or
recovering (based on
severity)
Subject did not recover
Event resulted in death
Outcome is unknown
Expected AEs are those
that may be anticipated as
documented in Reference
Safety Information (RSI) such as
the protocol, ICF, IB, package
insert, or device manual.
Expectedness is not determined
by what could happen in the
regular course of the treated
disease. For example, in
an oncology study, nausea,
vomiting, and diarrhea may be
expected as side effects from
the chemotherapy but should
not be labeled as “expected”
AEs unless these symptoms
are thought to be IP-related.
Unexpected events would not
have been documented in
RSI or their nature, speci昀椀city,
severity, or outcome is not
consistent with RSI. Unless the
event is mentioned in the RSI,
it is most likely to be classi昀椀ed
as unexpected. Bottom line
in determining expectedness:
Focus on the treatment, not
the disease.
UAMS requires study teams
to use AE Logs that allow
for clinical investigator
oversight to be con昀椀rmed with
signature and/or initial. The
56
clinical investigator should be
periodically reviewing the log
for trends over time to look
for systemic problems with the
study and/or IP.
The Deviation Log
A written protocol is at the heart
of every scienti昀椀c investigation,
especially in the context of
clinical trials. The importance
of following the protocol can
be seen by referring to the
outcome of FDA Bioresearch
Monitoring (BIMO) program
inspections, in which lack
of protocol compliance is
consistently the number one
昀椀nding. It is important to note,
although “protocol deviation”
is common terminology,
deviations can involve events
that fall outside the con昀椀nes of
the protocol.
Deviations, whether intentional
or unintentional, big or small,
affect the strength of the
results, the data integrity (e.g.,
completeness and accuracy)
and possibly the safety of the
subjects. It is therefore natural
that tracking, recording and
reporting deviations is a major
concern in clinical development.
Ongoing and repeated
deviations could signify the
need for protocol updates,
logistical / work昀氀ow changes or
additional staff training.
Deviations are mentioned in
FDA regulations, guidance
documents and GCP guidelines.
See FDA Guidance for Industry
E3 Structure and Content
of Clinical Study Reports
Questions and Answers (R1):
Deviation: “Any change,
divergence, or departure from
the study design or procedures
de昀椀ned in the approved
protocol.”
Violations (aka “Important
Protocol Deviation”) may be
SOCRA SOURCE © November 2024
considered a subset of protocol
deviations that might signi昀椀cantly
affect the completeness, accuracy,
and/or reliability of the study data
or that might signi昀椀cantly affect
a subject’s rights, safety, or wellbeing.
The content of the Deviation
Log (see Diagrams 18 and 19
on next page) depends upon
who is providing the document.
Most often, logs include 昀椀elds for
subject ID, dates the deviation
occurred and was identi昀椀ed, a
description and reporting (to
whom and when). Another 昀椀eld
commonly seen is “Description
of Corrective Action”. The author
encourages the inclusion of a
number 昀椀eld, which can then be
cross-referenced on AE Logs,
IRB submissions, monitoring
reports, and other study-related
documentation.
Less common contents for
Deviations Logs may be 昀椀elds for
protocol version (helpful when
determining whether a missed lab or
test was indeed required at that time
point) and whether the deviation
resulted in an AE or subject dropout (helpful when tracking safety,
outcomes and Unanticipated
Problems Involving Risks to Subjects
or Others [UPIRTSOs]).
Often, codes are used to record
the type of deviation, with
provided logs having built-in
legends, allowing space for
additional codes speci昀椀c to the
clinical research site or study.
Table 8 (on page 58) provides an
overview of the Deviation Log.
Common types of deviations are:
• Informed consent/
Randomization
• Eligibility
• Study procedures/Visit
schedules
• Safety
• Prohibited medications or
therapy
