Modernizing Clinical Trial Conduct Continuity Solution ... · Case Study #3 Direct to Patient...
Transcript of Modernizing Clinical Trial Conduct Continuity Solution ... · Case Study #3 Direct to Patient...
Published July 2020
Modernizing Clinical Trial ConductContinuity Solution Case Studies
Copyright ©2020 TransCelerate BioPharma Inc., All rights reserved. 2
TABLE OF CONTENTS
Case Study #1 |Remote Site Selection,
Initiation, Monitoring, Closeout
Case Study #2 |Remote Source Data
Verification & Review
Case Study #3 |Direct to Patient Shipping
Case Study #4 |Home Health Visits
Case Study #5 |Telemedicine
4 – 6
SLIDE #
7 – 9
10 – 14
15 – 18
19 – 21
Copyright ©2020 TransCelerate BioPharma Inc., All rights reserved.
Introduction
3
TransCelerate has actively begun collecting case studies of continuity solutions implemented during the COVID-19 pandemic. The five case studies presented in this document are selected examples from a larger set of 55 collected cases.
As additional case studies and information become available, the data will be provided to health authorities to grow the body of knowledge needed to support their prolonged use within modernized clinical trials.
Please note: The graphic shown (right) represents the volume of case studies collected, organized by a variety of continuity solution topics. Collection numbers by topic should not be interpreted as a statement on the most commonly utilized or valuable continuity solutions. Data collection is ongoing.
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3
4
6
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13
18
0 5 10 15 20
Continuity Solution Case Studies| By Topic
Use Cases Collected
Remote Monitoring/Sponsor Visits to Study Sites
Direct to Patient Shipping
Home Health Visits
Telemedicine
Electronic Informed Consent
Local Community-Based Laboratory Utilization
Other
Electronic Health Record & Electronic Data Capture
Digital Data Collection Tools
N=55 as of July 13, 2020
Case Study #1Remote Monitoring & Sponsor
Visits to Study Sites Site Selection, Initiation, Monitoring, Closeout
Copyright ©2020 TransCelerate BioPharma Inc., All rights reserved.
Case Study #1Remote Site Selection, Initiation, Monitoring, Closeout
5
Continuity Solution
Remote site selection,
initiation, monitoring,
closeout
Related Continuity
Solutions Deployed
Remote source data
verification & review
Implementation Intent
To provide a short term
solution (based on the
COVID-19 crisis) with
potential for it to serve as
a blueprint for a future
way of working. To
maintain oversight, ensure
quality and continue
engagement with the site
Description of continuity solution
Site selection is already done remotely in most instances. We implemented a deviation from existing
process to consider remote site initiation where it is critical to do so. Globally, all onsite monitoring was
stopped relatively early (late March) and replaced with remote monitoring. Remote monitoring
(excluding source data review [SDR] and verification [SDV]) is already part of the Risk Based Monitoring
model, so it’s easily implemented. Decision to allow onsite monitoring on a country-by-country basis
considering staff safety and a consistent decrease in the number of new cases. Close-out visits are being
delayed until onsite monitoring is permitted and close-out activities can be performed. Database locks
are not delayed. We were largely able to maintain the prescribed frequency at which the sites needed
to be visited (engaged) per the monitoring plan.
Difference to traditional models
All visits were remote whereas in the current model it is a mixture of remote and onsite. There were
limitations in that some activities were not possible (e.g., IP reconciliation, Investigator site file review and
SDR/SDV). Focus was on critical elements due to availability of site staff.
▪ Did changes in global regulatory policy during COVID-19 enable, accelerate, or help expand use of
the continuity solution? No
▪ Has the continuity solution impacted patient safety? Not yet measured
▪ Has the continuity solution impacted data integrity? Not yet measured
▪ Has the continuity solution impacted patient experience? No
Case Study #1 | Slide 1 of 2
Copyright ©2020 TransCelerate BioPharma Inc., All rights reserved.
Case Study #1 ContinuedRemote Site Selection, Initiation, Monitoring, Closeout
6
Continuity Solution
Remote site selection,
initiation, monitoring,
closeout
Related Continuity
Solutions Deployed
Remote source data
verification & review
Implementation Intent
To provide a short term
solution (based on the
COVID-19 crisis) with
potential for it to serve as
a blueprint for a future
way of working. To
maintain oversight, ensure
quality and continue
engagement with the site
Challenges of continuity solution implementation
• Staff availability for monitoring generally was problematic and not the process itself.
Success factors of continuity solution implementation
• Model was already set up to allow remote monitoring visits and site staff are accustomed
to the remote visit approach. The current model also allows for triggered visits that allowed
for flexibility to the site staff availability.
Case Study #1 | Slide 2 of 2
Case Study #2Remote Monitoring & Sponsor
Visits to Study Sites Remote Source Data Review and Verification
Copyright ©2020 TransCelerate BioPharma Inc., All rights reserved.
Case Study #2Remote Source Data Verification & Review
8
Continuity Solution
Remote Source Data Verification & Review
Related Continuity
Solutions Deployed
Remote site selection,
initiation, monitoring,
closeout
Implementation Intent
To provide a short term
solution (based on the
COVID-19 crisis) with
potential for it to serve as
a blueprint for a future
way of working. To
maintain oversight, data
integrity and protect
subject safety
Description of continuity solution
The solution created a framework which remote source data review (SDR) and source data verification
(SDV) could be performed. The framework allowed for flexibility to accommodate the various methods
in which data can be reviewed / verified remotely (i.e., electronic medical records, virtual meeting,
secure portals, e-mail), the local ethics / regulatory requirements around remote SDR/SDV and informed
consent considerations. The global landscape was quite varied so the solution needed to provide
flexibility. Even though most of the late phase studies adopt a reduced SDR/SDV approach it is still an
important activity that supports the risk-based monitoring model. Therefore it was critical to enable it
where-ever possible.
Difference to traditional models
Remote SDR/SDV is not an approach that is currently adopted by many other sponsors.
▪ Did changes in global regulatory policy during COVID-19 enable, accelerate, or help expand use of
the continuity solution? Yes; Many local regulatory authorities issued guidance specific to the
conditions under which remote SDR/SDV could be implemented during the COVID-19 pandemic.
▪ Has the continuity solution impacted patient safety? Not yet measured
▪ Has the continuity solution impacted data integrity? Not yet measured
▪ Has the continuity solution impacted patient experience? No
Case Study #2 | Slide 1 of 2
Copyright ©2020 TransCelerate BioPharma Inc., All rights reserved.
Case Study #2 ContinuedRemote Source Data Verification & Review
9
Challenges of continuity solution implementation
• Differences between sites in terms of the types of source data - electronic, paper or a
mixture of both.
• Country to country differences in the data privacy regulations and COVID-19 specific
regulatory guidance issued related to remote SDR/SDV.
• Differences in country data privacy requirements also created complexity in the need for
additional subject consent for remote SDR/SDV to be implemented.
• Some of the remote SDR/SDV methods placed additional burden on site staff that were
already stretched. To limit the amount of burden to the site the solution focused on critical
data but there were challenges in defining what the critical data was.
Success factors of continuity solution implementation
• The issuing of regulatory guidance helped define the scenarios under which the solution
could be implemented.
Continuity Solution
Remote Source Data Verification & Review
Related Continuity
Solutions Deployed
Remote site selection,
initiation, monitoring,
closeout
Implementation Intent
To provide a short term
solution (based on the
COVID-19 crisis) with
potential for it to serve as
a blueprint for a future
way of working. To
maintain oversight, data
integrity and protect
subject safety
Case Study #2 | Slide 2 of 2
Case Study #3Direct to Patient Shipping
Copyright ©2020 TransCelerate BioPharma Inc., All rights reserved.
Case Study #3Direct to Patient Shipping (DtP)
11
Continuity Solution
Direct to patient shipping
Related Continuity
Solutions Deployed
Telemedicine, Electronic
Informed Consent , Data
Collection/EHR/EDC, Use
of Local Laboratories,
Home/Mobile Nursing,
Remote Site selection,
initiation, monitoring,
close out, Remote
SDV/SDR/eMR
Implementation Intent
To provide a short term
solution (based on the
COVID-19 crisis) with
potential for it to serve as
blueprint for a future way
of working
Description of continuity solution
In order to sustain dosing for patients in ongoing trials, Direct to Patient (DtP) shipping strategies were
implemented. Our existing SOP pertaining to the management of investigational products (IP) does
allow for direct shipments of IP to a subject in exceptional circumstances. While the existing SOP allows
for these direct shipments on an exception basis, no dedicated procedures, forms, or training for DtP are
part of our standard practices; therefore, this DtP process is not positioned for incorporation in the design
of a new trial and is purely a mitigation to support ongoing studies. Due to the volume of DtP requests
over a sustained period of time, we developed a more sustainable approach for these exceptions by
creating a Guidance Document, Request Forms, virtual training, and a team of subject matter experts
to assist with execution. The evaluation for utilizing DtP focuses on various aspects of the demand for
ongoing clinical trials in specific countries based on the country Health Authority (HA) requirements,
medical need, alternatives to maintain protocol-specified treatment schedule, IP storage, administration
requirements, and other factors. The Guidance Document and all associated request forms were
developed by a cross-functional team comprised of Clinical Supply Chain, Global Development /
Global Clinical Operations, Regulatory, GMP Quality, GCP Quality, and various other subject matter
experts in an iterative approach as each version of the procedure and corresponding documentation
are continually improved and expanded. To date, we have successfully completed more than 750 DtP
shipments in more than 40 countries.
Implementation intent continued
The primary intent of the DtP process is to ensure safe continuity of clinical trials and to maintain dosing
for patients while minimizing risk of exposure during the pandemic. Many clinical sites were unsafe or not
accessible for patients which required us to develop new approaches for supplying the needed
medicinal products.
Case Study #3 | Slide 1 of 4
Copyright ©2020 TransCelerate BioPharma Inc., All rights reserved.
Case Study #3 continued Direct to Patient Shipping (DtP)
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Continuity Solution
Direct to patient shipping
Related Continuity
Solutions Deployed
Telemedicine, Electronic
Informed Consent , Data
Collection/EHR/EDC, Use
of Local Laboratories,
Home/Mobile Nursing,
Remote Site selection,
initiation, monitoring,
close out, Remote
SDV/SDR/eMR
Implementation Intent
To provide a short term
solution (based on the
COVID-19 crisis) with
potential for it to serve as
blueprint for a future way
of working
Implementation intent continued
The DtP shipment process is not applicable to all products, trials, and regions, but focuses on
Investigational Medicinal Product (IMP)/ Non Investigational Medicinal Product (NIMP) that is released
by the company and is distributed from the clinical site to the patient via courier. To summarize, this DtP
process is positioned for:
• Shipments from site to patient within the same country.
• Shipment via company contracted courier.
• Shipment via site-contracted courier.
• Non temperature-controlled products (e.g. ambient non temperature-controlled) and temperature-
controlled products (e.g. ambient controlled 15-30°C, refrigerated 2-8°C).
• Products that patients can self-administer per the protocol.
• Products which are not defined as self-administered per the protocol but can be self-administered
based on the clinical study team evaluation, patient safety, and required training.
Difference to traditional models
Traditional dosing and/or dispensing is conducted at the clinical site; however, the DtP model allows for
products to be shipped to a patient’s home for administration. The targeted scope of our DtP
procedures is for self-administered products, although home healthcare services can be contracted
through a vendor in combination with DtP logistics if required. As noted previously, the current DtP
process is not positioned for incorporation in the design of a new trial and is purely a mitigation to
support ongoing studies during the COVID-19 pandemic.
Case Study #3 | Slide 2 of 4
Copyright ©2020 TransCelerate BioPharma Inc., All rights reserved.
Case Study #3 continued Direct to Patient Shipping (DtP)
13
Continuity Solution
Direct to patient shipping
Related Continuity
Solutions Deployed
Telemedicine, Electronic
Informed Consent , Data
Collection/EHR/EDC, Use
of Local Laboratories,
Home/Mobile Nursing,
Remote Site selection,
initiation, monitoring,
close out, Remote
SDV/SDR/eMR
Implementation Intent
To provide a short term
solution (based on the
COVID-19 crisis) with
potential for it to serve as
blueprint for a future way
of working
▪ Did changes in global regulatory policy during COVID-19 enable, accelerate, or help expand use of
the continuity solution? Yes; Many country Health Authority / regulatory bodies have adjusted their
policies to allow for direct to patient shipping. These procedures may only be applicable during the
pandemic and the environment is changing constantly so it is crucial that we stay apprised of local
regulatory requirements. These current exceptions have offered the ability to support our patients
while minimizing their requirement to travel and pick-up supplies.
▪ Has the continuity solution impacted patient safety? Not yet measured
▪ Has the continuity solution impacted data integrity? Not yet measured
▪ Has the continuity solution impacted patient experience? Not yet measured
▪ Do you have data comparing traditional approaches with the implemented continuity solution? In
progress; We have not performed any direct data evaluations; however, we are monitoring supply
levels, scrap rates, patient satisfaction, compliance, in-transit excursions, costs, and many other
factors which will contribute to our long-term DTP approach.
Case Study #3 | Slide 3 of 4
Continued on next page
Copyright ©2020 TransCelerate BioPharma Inc., All rights reserved.
Case Study #3 continuedDirect to Patient Shipping (DtP)
14
Challenges of continuity solution implementation
There have been many challenges with implementation which is why we have chosen to follow
an iterative approach to creating our procedures. Our first DtP logistics efforts were performed
in China only on a case-by-case basis, but quickly expanded to include additional countries. As
the demand grew, our processes became more formalized and structured. Some of the major
challenges included:
• vendor interactions under COVID restrictions,
• temperature monitoring during transit,
• maintaining patient privacy,
• keeping apprised of the local HA / regulatory landscape,
• and ensuring a safe and compliant chain of custody.
Success factors of continuity solution implementation
Our biggest success factor has been the focus on patient safety and centricity. While ensuring
full compliance in the regulatory requirements, it was critical to continually consider the
patient’s needs and how we can support them during the pandemic to ensure continued
dosing while minimizing the risk of exposure to COVID-19. A hyper-focused team was quickly
assembled to develop a process that abides by all GCP, GMP, and GDP requirements while
simultaneously providing flexibility to operate globally with various types of products and
patient populations. The current process is still designed for mitigation use in ongoing studies
only, but our experiences and lessons learned will be directly applied to a more conventional
and planned approach for utilizing DtP logistics in future trials.
Continuity Solution
Direct to patient shipping
Related Continuity
Solutions Deployed
Telemedicine, Electronic
Informed Consent , Data
Collection/EHR/EDC, Use
of Local Laboratories,
Home/Mobile Nursing,
Remote Site selection,
initiation, monitoring,
close out, Remote
SDV/SDR/eMR
Implementation Intent
To provide a short term
solution (based on the
COVID-19 crisis) with
potential for it to serve as
blueprint for a future way
of working
Case Study #3 | Slide 4 of 4
Case Study #4Home Health Visits
Copyright ©2020 TransCelerate BioPharma Inc., All rights reserved.
Case Study #4Home Health Visits
16
Continuity Solution
Home Health Visits
Related Continuity
Solutions Deployed
Telemedicine
Implementation Intent
To provide a short term
solution (based on the
COVID-19 crisis) with
potential for it to serve as
a blueprint for a future
way of working.
Description of continuity solution
The COVID pandemic has resulted in some sites running studies becoming focused on dealing with
patients with the virus. Therefore, they may be finding it difficult to run study visits due to staff shortages
and restrictions in place at both the hospitals and travel to the hospitals. Patients may also be reluctant
to attend sites due to the possibility of picking up an infection either on their way to or at site. To mitigate
these issues a home nursing solution has been put in place so that, where possible, the visits can be
conducted from the patients’ home. This can be done either by the healthcare practitioner at the
home with or without support from the site via a telemedicine platform.
Difference to traditional models
Traditionally all the visits would have been run at site. The use of home health visits by healthcare
practitioners (e.g., nurses) has been ‘superimposed’ over the top of studies that were to run in a
traditional model rather than being built in up front as a model for running some of the visits. However,
for future studies we will be looking for ways to make as many visits as possible home/virtual visits.
▪ Did changes in global regulatory policy during COVID-19 enable, accelerate, or help expand use of
the continuity solution? Yes; there has been COVID specific advice released that has helped pave
the way for using non-traditional ways of working. In addition there has been a rapid acceptance of
new ways to work that support studies during the pandemic. There has also been the ability to
introduce some solutions like home nursing without changing the protocol or getting formal ethics
approval if introduced as a mitigation for COVID to keep patients in the study and ensure safety. For
work out of COVID mitigation full approval will then be required.
Case Study #4 | Slide 1 of 3
Copyright ©2020 TransCelerate BioPharma Inc., All rights reserved.
Case Study #4 ContinuedHome Health Visits
17
Continuity Solution
Home Health Visits
▪ Has the continuity solution impacted patient safety? Yes; using Home nursing has improved patient
safety by ensuring they are monitored and treated just as they would if they had come to site. It has
enabled subjects to comply with study procedures and has prevent many protocol violations that
missed visits and procedure would have otherwise inevitably occurred.
▪ Has the continuity solution impacted data integrity? Yes; it has prevented protocol violations and
missing data that missed visits would have brought and enabled sites and patients to comply with
care, oversight and procedures done as planned.
▪ Has the continuity solution impacted patient experience? Yes; the patients have been positively
impacted. Home nursing has allowed options that can alleviate concerns patients have about their
participation in the study and need to visit sites during the pandemic.
Case Study #4 | Slide 2 of 3
Related Continuity
Solutions Deployed
Telemedicine
Implementation Intent
To provide a short term
solution (based on the
COVID-19 crisis) with
potential for it to serve as
a blueprint for a future
way of working.
Continued on next page
Copyright ©2020 TransCelerate BioPharma Inc., All rights reserved.
Case Study #4 ContinuedHome Health Visits
18
Challenges of continuity solution implementation
The challenges to introduction of the home nursing solution has necessitated the needs to
quickly conduct due diligence on providers and to put in place contracts so study teams can
quickly contract with the vendors. The teams need to understand how the solution works and in
particular we came upon issues with the data capture with what will be regarded as source
and how will it get into the database. The time it takes to agree the data flows and understand
if nurses will enter data directly in the EDC Telemedicine platform or complete source
documents the site will enter. The varying acceptance of the home nursing across countries and
sites means that implementation may not be consistent for all countries or sites within a study.
Tracking the changes to studies and ensuring that communication works effectively (e.g., where
new vendors are suddenly working with lots of teams all at once) has needed careful project
management. Additionally, there needed to be careful consideration of how data will be
monitored, what constitutes source data and whether that is actually eSource.
Success factors of continuity solution implementation
We are still in the process of implementation, however what we are implementing in this rapid
COVID mitigation response will form the basis for future ways of working. Combining home
nursing with Telemedicine platforms and DtP supplies will mean as many visits as possible in the
future can be done at home and indeed paves the way to running suitable studies in a fully
decentralised model.
Case Study #4 | Slide 3 of 3
Continuity Solution
Home Health Visits
Related Continuity
Solutions Deployed
Telemedicine
Implementation Intent
To provide a short term
solution (based on the
COVID-19 crisis) with
potential for it to serve as
a blueprint for a future
way of working.
Case Study #5Telemedicine
Copyright ©2020 TransCelerate BioPharma Inc., All rights reserved.
Case Study #5Telemedicine
20
Continuity Solution
Telemedicine
Related Continuity
Solutions Deployed
Digital Data Collection
tools
Implementation Intent
To be a blueprint for a
new way of working that
was developed
independently from
COVID-19, but was
accelerated or expanded
as a result. Needed to find
ways to stay in contact
with patients despite
patient mobility restrictions
due to local situation.
Description of continuity solution
In studies where study visits using telemedicine are implemented; these visits include an investigator or
research nurse calling the patient to discuss health status/adverse events and is mainly used for safety
and follow up visits that do not involve drug administration. The use of vendors varied between studies,
most sites just use phone calls. In addition, some studies allow for patient reported outcome (PRO) and
other secondary endpoints to be conducted over the phone. For some protocols, where follow up visits
over the phone were not prohibited by protocol language, sites did a follow up call to check on
patients when patients missed visits due to COVID-19. Two examples on the use of telemedicine for
endpoint-related data collection are: Movement Disorder rate scale in Parkinson's (two parts) and data
collection of clinical outcome assessments (primary and co-primary endpoints) in some Alzheimer's
studies.
Difference to traditional models
Level of adoption increased but the approach was largely as before. In a couple of cases,
Telemedicine visits were implemented in an unstructured way by site staff. A more formal approach
(with approved vendors and technology) may be preferable.
Case Study #5 | Slide 1 of 2
Continued on next page
Copyright ©2020 TransCelerate BioPharma Inc., All rights reserved.
Case Study #5 continuedTelemedicine
21
▪ Did changes in global regulatory policy during COVID-19 enable, accelerate, or help expand use of
the continuity solution? No
▪ Has the continuity solution impacted patient safety? Yes; allowed for ongoing monitoring of patient
well-being and follow up during the trial without putting patient at risk by insisting on in-person visits.
▪ Has the continuity solution impacted data integrity? Not yet measured
▪ Has the continuity solution impacted patient experience? Not yet measured
Case Study #5 | Slide 2 of 2
Challenges of continuity solution implementation
Variable levels of site adoption and readiness to implement. In some cases (individual project
teams), "approval" from the project team was required. Because many of our products are
administered via IV infusion, telemedicine or remote visits were limited to non-administration
visits.
Success factors of continuity solution implementation
Site motivation to ensure patient continuity and safety. Team willingness to be flexible to
accommodate local situations.
Continuity Solution
Telemedicine
Related Continuity
Solutions Deployed
Digital Data Collection
tools
Implementation Intent
To be a blueprint for a
new way of working that
was developed
independently from
COVID-19, but was
accelerated or expanded
as a result. Needed to find
ways to stay in contact
with patients despite
patient mobility restrictions
due to local situation.