August 2024 SOCRA Source Journal - Journal - Page 29
expiration, the probiotic
organisms were still viable.
Carrying out the randomization
was lowtech for this IIR given
limitations in funding. The study
was an open-label trial in which
participants were randomized
to take the probiotic for either
four or eight weeks. The study
team wrote numbers on pieces
of paper; placed the numbers
in envelopes; mixed up the
envelopes like a deck of cards;
then wrote the participant
identi昀椀cation numbers on the
outside of the envelope. Once
subject #1 was enrolled, we
would choose the corresponding
envelope and whatever number
was inside (four or eight), is the
number of weeks the participant
took the probiotic.
Participant compliance
focused on ensuring that they
took the probiotics daily as
prescribed (two packets, once
a day for either four or eight
weeks depending on their
randomization). As noted above,
the study team was responsible
for determining participant
compliance based on the
number of remaining probiotic
capsules. The team would then
notify the pharmacy so they
also could record compliance.
One participant, for example,
only took half of the prescribed
probiotics as required by the
study.
One thing we learned is that it
is important when doing an IIR
to hire an external monitor. This
can help not only a research
team that may be inexperienced
but also provides an objective
second set of eyes to review
the study to ensure all records
are in order. The FDA sent
an investigator to investigate
the study. When some minor
de昀椀ciencies were noted by the
investigator, they emphasized the
need for an external monitor. It is
important to build this cost into
the study budget. If the SI does
not hire an external monitor, the
SI must decide whether someone
at the clinical research site has
suf昀椀cient monitoring experience
to be delegated this task.
The FDA inspection of the
probiotic study was random and
not for-cause (i.e., there was
an identi昀椀ed issue that needed
to be investigated). The FDA
provided two weeks’ notice and
spent three days at our site. The
author offered the investigator
a conference room, with only
the requested 昀椀les. Once an
investigator sees something of
concern, they can proceed to
investigate it. The investigator
is not a “friend”—they are there
only to ensure the safety and
compliance of the clinical trial
involving experimental drugs
or devices. It is best not to offer
more information than what
is requested.
An FDA inspection is not as
intimidating as it sounds as long
as the SI has all of the necessary
昀椀les and documentation. Less
experienced clinical research
coordinators working on an
IIR should reach out to more
experienced clinical research
coordinators to learn how to
conduct compliant research.
As noted above, external
monitors are a valuable asset,
if available, who can work with
the research team to ensure
appropriate documentation
and compliance—making an
FDA inspection much less
intimidating. Both the SI and
research team can learn a great
deal from external monitors.
Electronic Study Experience
The author has spent most of her
career in IIR. One investigatorinitiated observational study
the author manages is a U grant
from the National Institute for
Dental and Craniofacial Research
of the NIH. This study has 14
sites, of which 12 are clinical
sites enrolling participants, while
two sites are solely data analysis
sites. As an observational
pediatric study, it did not require
FDA oversight. Key elements of
the study that were electronically
created/stored:
•
•
•
•
•
The protocol
The manual of procedures
The electronic database with
e-consent using REDCap
The essential documents
binder on SharePoint/
OneDrive
Quality management
activities
The SI must design the
protocol for an IIR. The overall
template for the protocol varies
depending on institution,
funding source, and type of
study (e.g., interventional
versus observational). The NIH
has several templates based
on ICH GCP E6 requirements
that can be used for protocol
development. The website also
has educational materials about
conducting research and other
templates (e.g., for monitoring).
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