August 2024 SOCRA Source Journal - Journal - Page 28
requires revision. If revision is
required, the SI must make the
corrections, resubmit, and wait
another 30 days for the FDA’s
decision on the revised IND
application.
It took about 1.5 years from
the time the SI submitted the
IND for the safety study for the
clinical hold to end, enabling
the study to begin. The SI went
back and forth quite a bit with
the FDA for revisions, despite
the early conversation with the
FDA. One example of a revision
was that the FDA said that a
Serious Adverse Event was not
clearly de昀椀ned.
After FDA approval, the SI
needs to obtain IRB approval.
In addition, the FDA requires
the SI to submit regular safety
reports to the FDA to ensure
subject safety and study
integrity. The reporting period
may be annual or more often,
depending on the trial. In the
probiotic study, the SI initially
submitted reports annually and
then biannually.
The SI never went on to conduct
the probiotic study in children
as the duration of funding only
allowed the adult safety trial and
the 昀椀ber versus placebo trial
in children with irritable bowel
syndrome to be completed.
Considerations in InvestigatorInitiated Research
There are many considerations
in IIR (Table 3). One example is
that a data safety monitoring
board (DSMB) usually
is required; the SI must
determine who will be part
of the board. For the adult
probiotic safety trial, the DSMB
28
TABLE 3
Considerations in Investigator-Initiated Research
•
•
•
•
•
•
•
Data safety monitoring board
Pharmacy and dispensation
Randomization
Protocol adherence and compliance
Participant compliance
SOP development
Monitoring
had three members: an adult
gastroenterologist, a pediatric
gastroenterologist from another
institution, and a biostatistician.
The FDA wanted to know the
details of the DSMB so the
protocol speci昀椀ed who would
be on the board, how often
they would meet, and what
they would review. The author
submitted the safety and ef昀椀cacy
information to the board twice a
year, with a focus on safety.
During the DSMB meetings, the
SI and study manager would
step out of the room and the
DSMB would deliberate in
private, deciding among other
things, whether the trial could
continue. Reports from the
DSMB were submitted to the
FDA after their meeting.
Pharmacy procedures and
product (e.g., drug, probiotic)
dispensing is another
consideration for the SI. For
the adult probiotic trial, we
went low tech. Since the SI
was employed by a children’s
hospital, we needed to 昀椀nd a
pharmacy we could use that
had licenses to dispense drugs
to adults. It was decided to
use the pharmacy at a local
SOCRA SOURCE © May 2024
hospital located across the
street to handle the storage and
dispensing of the probiotic. The
SI received the probiotic from
the manufacturer and the study
team sent it across the street to
the pharmacy. The pharmacy
was responsible for proper
storage (e.g., temperature) and
dispensing of the probiotic
as well as documenting all
procedures. The SI and his team
were responsible for counting
any probiotic capsules when
the boxes that had contained
the probiotic were returned by
study participants as a measure
of study compliance.
Of note, this was the 昀椀rst time
the pharmacy had worked on an
IIR with FDA oversight so there
was a learning curve. Towards
the end of the trial, some of
the probiotic had expired but
the pharmacy did not notify the
SI. It was discovered months
later when the SI inquired
about how much probiotic
remained in the pharmacy.
Consequently, the SI had to
submit a corrective action plan
to the FDA. Fortunately, the
probiotic manufacturer was able
to test the remaining probiotic
and found that despite the