Upload
others
View
2
Download
0
Embed Size (px)
Citation preview
Outline.
Operational Considerations forDesigning and Setting up a Site-LessDecentralised Clinical Trial (DCT)
Case Study
Bionical Emas are providing full-service CRO support for a Phase 2 study to evaluate
the safety and efficacy of an intranasal antibody in patients with asymptomatic or mild
COVID-19 in the UK.
Challenges.
Study Design
Tactics.
Expertise in Decentralised Trials:Bionical Emas are founding members of the Decentralised Trials and
Research Alliance (DTRA) and are committed to driving decentralised
clinical trials (DCTs) forward and ensuring patient centricity in our
clinical trial strategy. Given the nature of the treatment pathway and
limitations during the COVID-19 pandemic, a site-less DCT was the only
option for this clinical trial. Our experience as leaders in the DCT space
meant that we were well placed to design and implement this novel and
highly decentralised clinical trial.
Home health nursing team:Patients with asymptomatic/mildly symptomatic COVID-19 are required
to self-isolate at home and must not leave the house for any reason other
than to go to a test centre for a PCR test. Without home healthcare, this
patient population would otherwise be inaccessible, therefore, home
health nursing was pivotal to the success of this study. The home health
nursing team are central to navigating the operational complexities of
ensuring that all nurses visits occur per protocol, IP shipments arrive at the
participants house on time, unblinded nurses are available to prepare the
IP at each participants home within 2 hours of administration, and couriers
are available to collect samples.
National Recruitment:The UK COVID-19 landscape is ever changing, and so for COVID-19
studies, it is important to be able to constantly move and adapt to
target areas with high cases numbers. A specialist recruitment team
was a key part of the study strategy and they developed robust and UK
wide digital and community out-reach campaigns. Campaigns were
developed to be instantly adaptable and flexible to move to areas of
high and/or increasing waves of local cases, and they were also tailored
towards the communities within each local area. The specialist
recruitment and home health nursing teams needed a joined-up
strategy, to ensure that nurse teams were available in the areas that
were being targeted for recruitment at each stage of the study.
Sample Collection:With typical UK study start-up timelines, approvals and site level
activities are usually on the critical path. However, due to the
expeditious approval timelines and the Sponsor desire to start the
study rapidly, central laboratory set-up was identified as a potentially
limiting processes on the critical path for this study. It was important
that we identified a central laboratory that could be flexible to this
need, and the selected central laboratory committed to an expedited
4-week set-up process to support same-day collection of samples
from participants homes via a specialist courier, including shipments of
dry ice where frozen samples are required. The nursing team will use
mobile centrifuges to prepare samples for collection as required.
Direct-to-patient IP Distribution:IP labelling and direct-to-patient IP distribution is provided by a
company who are UK experts in this area. As they have an on-site
pharmacist, they were able to obtain a temporary license to act as the
central pharmacy for the study which meant that IP could be
distributed directly to the participants home and did not need to go via
another pharmacy. Following randomisation, the IP distributors
package the appropriate vials into a temperature controlled shipping
container that will arrive at the participants house on the day of
treatment. We also developed a highly complex processes to allow for
same-day IP deliveries where required. This study was the US
Sponsor’s first study in Europe, and we also had to rapidly factor in
audit and qualification steps at their manufacturing sites to ensure
compliance to UK/EU GMP standards. Our project team scheduled
and completed remote audits, responded to findings, completed an
audit report, and turned around a QP declaration within a record time
of 10 business days.
Flexible and Agile Operational Team:To make this study design work, our operational teams had to
constantly think outside of the box and find new ways to work. To
enable this, we empowered our operational teams to act in a way that
facilitates a decentralised design. The team resourced to the study also
had a wealth of experience working on other COVID-19 studies and so
excelled in this type of environment. Highly flexible teams and
processes allowed us to adapt quickly to meet specific needs, without
compromising patient safety or data integrity. Daily scrum calls, which
included the project’s oversight team, were also important to keep the
focus and drive start-up forward.
Industry Leading Electronic Systems:Due to the novel study design, it was important that we identified
systems that met the needs of the study, rather than needing to adapt
systems to fit the study requirements. This was important to ensure
operational activities were streamlined and not overly complicated.
IBM Clinical Development (IBM CD) was chosen as the most
appropriate eDC for the study. As certified IBM CD builders, we build
databases quickly. Utilising our eCRF library of standardised forms
allows an expedited build process for many of the eCRFs needed,
providing time to focus on the study specific forms. Modules available
within IBM CD allowed us to have an eDC, electronic diary (ePRO), and
randomisation all within one system, allowing consistency and ease for
such an innovative study design. Furthermore, the Data Migrator
module allowed easy processes to be set up to enable source data to
be uploaded directly from outputs from our nursing teams system into
the eCRFs, removing the need for transcription, which is critical for a
decentralised study.
Successful Outcome.
Bionical Emas estimated a set-up of less than 6 weeks from final protocol to first patient in, and recruitment of 350 participants in a further 6 weeks. To date, Bionical Emas completed the writing of essential documents (protocol, IB, IMPD), completed early engagement with the MHRA on the study design, and have received full MHRA and REC approvals.
A cost comparison of this site less design vs. a traditional site based model showed a 20% reduction in costs for the site-less design. Cost savings were predominantly due to shorter study timelines, particularly with regards to study start-up and recruitment.
We welcome future opportunities to offer our expertise in the design of novel and decentralised clinical trials.
Develop. Access. Innovate.+44 (0)1462 424 400 | [email protected] | bionicalemas.com
Audit Ready TMF and ISF:Another hurdle to overcome was how to maintain an Investigator Site
File (ISF) in a site-less design when our systems are set up to manage
traditional site-based designs. Although this study is ‘site less’, the
documentation requirements for the study team are the same as for a
site based design, and so we are able to consider the study as having
one ‘virtual’ site. We used Trial Interactives eTMF and eISF solutions
to streamline collection of traditional site facing documents such as
training and delegation of authority logs. Also, we are using a Learning
Management System which will provide training for Investigators and
Nurses working on this study. This solution allowed us to implement a
streamlined solution to the problem, and maintain one ISF for the
entire study.
Virtual Investigator Oversight:Without clinical trial sites, we had to find a way to ensure Investigator
oversight for the study. We identified two Key Opinion Leaders to
support the study; a Chief Investigator to support the protocol design
and ethics submission; and a Principal Investigator to maintain primary
responsibility for the conduct of the study. We also identified a team of
Sub-Investigators who had both clinical trial experience and were
appropriate for the trial, such as GPs. Rather than having site level
Investigators, we have a study level virtual Investigator team, which
has an added benefit of consistency in oversight activities. The team of
Sub-Investigators support the Principal Investigator with the
day-to-day running of the study and complete traditional Investigator
tasks such as reviewing serious adverse events and assessing abnormal
laboratory results for clinical significance. They work on a rostered
shift system, managed by the project team, and provide continuous
cover throughout the trial.
Public Engagement:This study is a relatively new and novel design for the UK, and so it was
important for us to engage with the public to ensure the design would
be acceptable for the target population. We harnessed feedback from
a public group on the participant information sheet, and by carefully
managing timelines and expectations, we collected and responded to
their feedback within 5 business days. In line with their feedback, we
implemented a summary participant information sheet to provide a
simple-to-read document that gave an overview of the study
information considered to be most important to potential participants.
Design a study to expedite the development of potential and much needed COVID-19 treatments.
Working in an evolving and rapidly-changing COVID-19 landscape where cases appear in difficult to predict waves.
Recruiting and treating an outpatient population of COVID-19 positive patients with asymptomatic or mild disease, that are not routinely seen in primary or secondary care in the UK.
Nurse Home VisitsCo-ordinate and complete in-person
visits and administers treatment in
the participant’s home
Participant Support24/7 access to Investigator /
nurse and technical support
call center
Virtual Study VisitsDaily ePRO, regular check-ins
from Investigator
ParticipantIdentification
National recruitment
through digital advertising
and community outreach
Clinical Contact CentrePre-screens, gets participant ‘buy
in’ and books the screening visit
StudyCompletion
Expedited recruitment
Higher retention of
patients
Increased compliance
Trial Aspect Traditional Site-less DCT
Recruitment
In-Person Protocol Visits
Telephone Protocol Visits
ID Dispensing
IP Delivery
Laboratory Assessments
ePRO Completion
Investigator Oversight
Investigator and site team led
On-site
Via telephone
IP distributed to site pharmacy, dispensed by
site pharmacist
Administered at the site
Samples taken on-site and results available
through a local or central laboratory depending
on the same type
Participant completes at home on their own
(or provisioned) device
Site-level on-site Investigator team
Self-referral via advertising
At the participant’s home
Via telephone or virtual call
IP distributed direct-to-participant’s home by
central dispensary
Administered in the participant’s home
Samples taken a visit at the participant’s home,
posted directly to the central laboratory and results
available centrally
Participant completes at home on their on own
(or provisioned) device
Study-level virtual Investigator team