S5-2_Jessica Liu

Tigermed Consulting Co. Ltc
www.tigermedgrp.com
Ethic protection of Oncology
patients in clinical trials
during COVID19
Jessica Liu MD
Senior Consultant
Tokyo, Japan 20231201
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Case studies on Ethic Challenges of
the operational BCP
Lessons to be learned
Challenges to clinical trial
during COVID19
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Table of
Content
1 COVID19 Human Challenges Study in China
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Operational Challenges for HCT in China
• Ethical consideration(debate) on HCT via a publication
• No experience in conducting HCT in China, ig. Genetically Modified Organism
(GMO), lab for viral load titration
• Novo Study Design by hVIVO but no business partner in China
➢ Model development
➢ Overall clinical trial design
➢ Endpoint
➢ Operational procedures
• Chinese vaccine companies already initiated traditional vaccine clinical trials,
hoping to conclude in 12-18 months, at that time, hence no patience for this
debate
Hot Debate on Human Challenge Study in China
Title: Ethical Challenges in Human Challenge Studies for a COVID-19 Vaccine
DOI:10.19524/j.cnki.10-1009/g3.2020.02.001
Authors: Wen Huang & Xiaomei Zhai
Institution: Center for Bioethics, Chinese Academy of Medical Sciences
Topic: Global Public Health Crisis due to COVID-19 Pandemic
Purpose: Exploring Ethical Issues in COVID-19 Vaccine Human Challenge Studies
Urgency: Need to Accelerate Vaccine Development amidst High Infection and
Death Rates
Ethical Challenges to HCT
1.Assessment of Benefits and Risks
• Balancing Social Benefits with Participant Risks
• Categorizing into those benefiting only society and those benefiting
both society and participants (4300+GB compensation fee!?).
2.Acceptable Level of Risk
• Suggests setting thresholds for acceptable risks
• Highest risk when exposing volunteers to potential risks with active
COVID19 virus
3. Absence of Effective Treatment to COVID-19 Pandemic
Conclusion
• Human Challenge Studies Can Significantly Expedite Vaccine Development
• Present Substantial Ethical Dilemmas that Require In-depth Evaluation and
Prudent Decision-Making
• Scientific Assessment and Ethical Judgments Should Not be Compromised by
Political, Social, and Economic Pressures
Recommendations and Future Outlook
• Emphasize the Importance of Ethical Review
• Enhance Public Understanding and Trust in Human Challenge Studies
• Conducting research under high standards
• Future Research Direction: Balancing Accelerated Vaccine Development with
Ensuring Participant Safety
The Pandemic has Challenged the Viability of
Traditional Clinical Trials Across the World
Of patients will be
less likely to enroll in
new clinical research
trials due to COVID-19
Of sites anticipate
patients enrolled in
trials to be less willing to
keep participating
Of biotech and
pharma companies
reported an impact to
their ongoing trials due
to COVID-19
66%
50% 78%
Sources:
BioCentury Report, S. Koch (2020)
The Wall Street Journal, J. Hopkins (27March2020)
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The Pandemic has Challenged the Viability of
Traditional Clinical Trials Across the World
Of respondents
identified
that the pandemic has
had a permanent impact
on their clinical trials
53%
Reported
substantial or
transformational
impact
to Clinical Trials
78%
Source:
PPD Decentralized Clinical Trials Survey Report (2020) with industry KOLs
Life threatened
Oncology
patients as
vulnerable
Population
• Some solid tumor, especially at late stage, could progress
fast if without treatment
More IPs are IV administrated
• Protocol specific IP storage and administration in proper
clinical settings/investigational sites
• Drug supply management plan in place
Disease progress monitored by
medical imaging exam
• Protocol specific exam and measures
• Established data transfer and review/adjudication
procedure。
Safety monitored by lab tests
• Protocol specific exam and measures
• Established data transfer and review procedure。
CCHRPP consensus document highlights the patients
safety and wellbeing during COVID19
区域差异 受试者选择 剂量选择 终点选择
样本量
+ 1st draft on 2020-1-30
+ Finalized on 2020-2-2
+ English version published
on DIA Global Forum
+ This is not a government
regulation or other type
of official government
document: adherence is
voluntary. Guidelines
subsequently issued in
the Us (by FDA) in March
2020, in the European
Union (by EMA) in April
2020and in China (by
NMPA, formerly CFDA)
concur with many of the
experiences and opinions
expressed herein.
CCHRPP Consensus Document Highlights The Patients
Safety And Wellbeing During Covid19
区域差异 受试者选择 剂量选择 终点选择
样本量
+ Key principle: patient protection>>PV&Risk Managemnet>>GCP
+ DCT and remote monitoring to be implemented/piloted in COVID19 treatment
clinical trials
+ Central monitoring via EDC and Risk Based Quality Monitoring (RBQM)to ensure
data completion and quality
+ Patient privacy should be ensured during remote monitoring while with access to
source data such as Electronic Medical Record (EMR)
+ Patient-centric clinical trial model could be enabled by digital technologies.
Coming together the Digital Elements:
Tools, Resources and Systems
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eCOA
Electronic clinical outcomes
assessments replace the
need for paper-based
outcomes data collection
Devices and
Wearables
Collect real-time data
and biometrics from
patients anywhere
TeleVisits
A visual communication
tool used to facilitate
investigator and patient
engagement
Home Health
Care + Nursing
Qualified medical personnel
can conduct required
protocol procedures at the
patient’s home
eConsent
A fit-for-purpose tool to
capture digital signatures on
consent forms
DTP/DFP
Delivery and collection of
clinical trial materials
directly to/from the
patient
Communication
gateway
Patient engagement and
communication including
reminders, notes,
appointments, etc.
eSource
Data extraction from the
patient’s electronic health
record
Remote
monitoring
Ability to perform
monitoring activities
remotely, as part of the
monitoring process
Strategy
Challenge
+ Ethic Committee office and
members being lockdown,
irregularly,
+ Too many protocol deviations
being reported, along with
specific BCP proposals, to be
reviewed and responded
urgently
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Flexible working schedule
+ Virtual meetings and Electronic document
submission
+ Careful approval of new trials , with
balance of the unmet medical need and
potential protocol compliance issue during
the pandemic
+ Accelerated review/meeting on critical
safety issue in the ongoing trials
Ethic Committee Functionality During COVID19
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eSource & eConsent
+ All the sites used the DCT platform for any eSource
documentation（mandatory site selection criteria)
+ eSource forms are not the same as CRF pages in EDC
system.
+ Data from the DCT platform will be migrated into the EDC
+ All queries and SAEs were entered and followed directly in
the EDC system
+ eConsent: mobile phone or web-based
Challenges
+ Regulatory compliance issue by
generating SD in a platform
outside hospital in China?
+ SD quality: better consistency
across sites; less missing SD?
Investigators‘ better GCP
compliance in documenting
source data timely?
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IP management: DTP/DFP for Oral IP
Best practice/ to be improved：
+ Central IP management team supplied COVID-trial-in-a-box no IP
shipment from sites;
+ IP accountability: Site staff worked with the subjects to
document IP compliance (take photo via TeleVisit)
✓ Sponsor and PI actively look for
solution, then put in written as
protocol amendment for EC
review
 No IP tablets counting was
conducted in this study, to be
improved
 How to make sure patients did
take the IPs?
Challenge
+ Only feasible for oral IP
+ Limited delivery
companies involved in
clinical trial before
+ Route delivery process
required very detailed
personal information
posing the ethic concern
on patient privacy
protection
Strategy
+ Couple of largest delivery
companies jump to join
clinical trial business, with
commitment to new SOP and
compliance
+ Comprehensive training on
the study subject
information formal
+ Combine delivery company
technology and smartphone
function to ensure subject ID
in the study and IP delivery
accuracy
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TeleVisit+Site Transfer in lieu of DTP
Challenges：
+ The subjects were well informed of the TeleVisit via ICF
+ All the visits including screening can be performed using the
DCT platform telemedicine capabilities
+ COVID-19(+) participant population
+ Participants will hold up the thermometer and the oximeter
during TeleVisit to be observed and recorded by the study
staff in the DCT platform.
+ During TeleVisits, the participants will be provided guidance
about how to perform nasal swabs correctly. Then the
participants shipped nasal swab to central lab after collection;
+ Qualification of new sites to receive transferred patients:
same study or same city
+ Additional local lab/Medical Imagine central for critical visit
+ Subjects’ acceptance in China
+ Hospital’s acceptance?
+ Any specific approval in China:
any regulator? HGRAC?
+ Secure, HIPAA compliant
videoconferencing solution?
+ Participant-centric scheduling in
the chaos of COVID19 lockdown?
Strategy
Challenge
Significantly increased
protocol deviations
including:
+ missing visit schedule
+ out-of-window visit
+ Non-investigational site
data
Posing ethic concerns on
data quality and integrity
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+ Sponsor and investigator submit to
EC the protocol amendment,
Statistical Analysis Plan update, in
order to reduce the impact of these
PDs.
+ EC and Investigators make
risk/benefit assessment on
concerned patient, balancing
individual patient treatment
outcome vs. overall study result, to
decide his continuity in clinical trial.
Protocol Deviation Handling: Missing Data
Page 19
© 2021 DIA, Inc. All rights reserved.
DTC evolvement
call for:
Additional Stakeholders
to Clinical Trial Operations
Detailed Regulation & Guidelines
New Patient Engagement Model
More Training for PI team
on DCT process
Reflection and Lessons Learned
from COVID19 experiences
© 2021 DIA, Inc. All rights reserved.
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Facility
Technology
Patient safety
Data
integrity
Accountability
Oncology Clinical Trials during and post COVID19
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