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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1

2

3

4

6

7

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


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


Case Study #1 ContinuedRemote Site Selection, Initiation, Monitoring, Closeout

6

Continuity Solution



closeout

Related Continuity

Solutions Deployed

Remote source data

verification & review







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 #2Remote Monitoring & Sponsor

Visits to Study Sites Remote Source Data Review and Verification


Case Study #2Remote Source Data Verification & Review

8

Continuity Solution

Remote Source Data Verification & Review

Related Continuity

Solutions Deployed



closeout







way of working. To

maintain oversight, data

integrity and protect

subject safety


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.


Remote SDR/SDV is not an approach that is currently adopted by many other sponsors.


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 experience? No



Case Study #2 ContinuedRemote Source Data Verification & Review

9


• 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.


• 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



closeout







way of working. To

maintain oversight, data

integrity and protect

subject safety


Case Study #3Direct to Patient Shipping


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,


close out, Remote

SDV/SDR/eMR






blueprint for a future way

of working


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 continued Direct to Patient Shipping (DtP)

12

Continuity Solution


Related Continuity

Solutions Deployed








close out, Remote

SDV/SDR/eMR







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.


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 continued Direct to Patient Shipping (DtP)

13

Continuity Solution


Related Continuity

Solutions Deployed








close out, Remote

SDV/SDR/eMR







of working


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 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.


Continued on next page


Case Study #3 continuedDirect to Patient Shipping (DtP)

14


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.


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


Related Continuity

Solutions Deployed








close out, Remote

SDV/SDR/eMR







of working


Case Study #4Home Health Visits


Case Study #4Home Health Visits

16

Continuity Solution

Home Health Visits

Related Continuity

Solutions Deployed

Telemedicine







way of working.


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.


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.


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 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.


Related Continuity

Solutions Deployed

Telemedicine







way of working.



Case Study #4 ContinuedHome Health Visits

18


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.


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.


Continuity Solution

Home Health Visits

Related Continuity

Solutions Deployed

Telemedicine







way of working.

Case Study #5Telemedicine


Case Study #5Telemedicine

20

Continuity Solution

Telemedicine

Related Continuity

Solutions Deployed

Digital Data Collection

tools


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.


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.


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 continuedTelemedicine

21


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 patient experience? Not yet measured



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.


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


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.

modernizing clinical trial conduct continuity solution ... · case study #3 direct to patient...

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