November 2024 SOCRA Source Journal - Journal - Page 55
treatment (Table 7). Relatedness
is an assessment regarding the
causal relationship between the
study intervention and/or IP
and an AE. When determining
relatedness or causality, a
quali昀椀ed, delegated and
trained clinician should ask the
following questions:
•
•
•
•
•
Was the condition present
at baseline and can it be
explained by the underlying
disease?
Is the event a known
reaction documented in the
Investigator Brochure (IB),
protocol, or ICF?
Has the event occurred
before in the study?
Did the event happen
contemporaneously with the
intervention and does it go
away when the intervention
is stopped?
Can any other potential
causes explain the
condition?
It is also helpful to refer to
the Bradford Hill Criteria for
Causation.
The most common
‘Relationship’ categories are:
•
•
•
•
•
De昀椀nitely (clearly) related
Probably (likely) related
Possibly (may be) related
Unlikely (doubtfully) related
Unrelated (not) related
Choices for ‘Action Taken’
regarding study intervention,
depending on the log used,
include:
•
•
•
•
•
No change/None
Regimen increased/
decreased
Regimen held
Drug/Device discontinued
and re-introduced
Drug/Device stopped
permanently
TABLE 7
Relationship of AEs to Study Treatment
•
Relationship and causality: “Relatedness is a term intended to
indicate that a determination has been made that event had
a reasonable possibility of being related to exposure to the
product.”
o
•
Questions to ask when assessing causality:
- Was the AE present at baseline assessment or in recent
medical history?
- Can the AE be reasonably explained by subject’s clinical
disease status?
- Is the AE a known reaction of the intervention?
- Is the AE similar to others listed in protocol, consent,
or safety documents?
- Has the AE occurred before in this study?
- Is the AE reasonably temporally related to the
intervention?
- Does the AE improve or disappear when intervention is
discontinued; re-tested?
- Are there other potential causes for the AE?
Relationship categories:
o De昀椀nitely Related:
- The AE is clearly related to study treatment
- Onset occurs in a plausible time relationship to study
treatment and other contributing factors can be ruled out
o Probably Related:
- The AE is likely related to study treatment
- Onset occurs in a plausible time relationship to study
treatment and the in昀氀uence of other contributing
factors is unlikely
o Possibly Related:
- The AE may be related to study treatment
- Onset occurs in a plausible time relationship to study
treatment; though, other factors may have contributed
to it
o Unlikely Related:
- The AE is doubtfully related to study treatment
- Onset does not occur in a plausible time relationship to
study treatment, and other contributing factors are likely
o Unrelated:
- The AE is clearly NOT related to study treatment
- There is no causal relationship between the AE and
the study treatment
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