Digital Scholar Webinar: Breaking Down (Brick) Walls: Switching to Remote, Virtual, & Decentralized Clinical Trials

1. Breaking Down (Brick) Walls:
Switching to Decentralized Clinical Trials
Pamela Tenaerts, MD, MBA
Executive Director Clinical Trials Transformation Initiative
@pamelatenaerts pamela.tenaerts@duke.edu
3 Feb 2021

2. Employee of Duke University
 Salary support comes from pooled membership fees of
the Clinical Trials Transformation Initiative and from FDA
Cooperative agreement (U19)
Independent director on the board of TRxADE, inc

3. Multi-stakeholder,
public-private partnership
co-founded by Duke University & FDA
Participation of 500+ more orgs and
+ 80 member organizations
MISSION: To develop and drive
adoption of practices that will
increase the quality and efficiency
of clinical trials

4. Includes pharma,
bio, device, CRO,
health data/tech
Better
Streamlined
Fit for purpose
Clinical Trials
Everyone
must have an
equal seat at
the table
Investigators
& Sites
Industry Academia
IRBs Trade &
Prof. Orgs
Gov’t
&
Regulators
Patients,
Caregivers
& Patient
Advocacy
Groups
All Stakeholders Have an Equal Voice

5. CTTI Recommendations & Resources
Quality Patient Engagement Investigators & Sites
▶ Create better protocols with
Quality by Design (QbD)
▶ Move Recruitment planning
upstream
▶ Create Pregnancy Testing
plans for improved clinical trials
▶ Involve Patient Groups as
equal partners
▶ Strengthen the Investigator
Site Community
▶ Improve Investigator
Qualification & reduce
GCP Training inefficiencies
Digital Health Trials
Novel Clinical Trial
Designs
Ethics & Human
Research Protection
▶ Pathways for developing Novel
Endpoints and running trials
using Digital Health
Technologies
▶ Overcome Decentralized
Clinical Trials hurdles
▶ Engaging Sites and Patients
when incorporating digital health
technologies
▶ Design and conduct Master
Protocol studies
▶ Use Real-World Data to plan
eligibility criteria and enhance
recruitment
▶ Use Registries to conduct more
efficient clinical trials
▶ Streamline Antibacterial
Pediatric and HABP/VABP
Studies
▶ Improve ethics review process
via use of Single IRB
▶ Organize DMCs to ensure
patients’ safety
▶ Perform higher quality
Informed Consent process
▶ Develop a better IND Safety
Reporting system

6. Decentralized Clinical Trials
https://www.ctti-clinicaltrials.org/projects/decentralized-clinical-trials

7. CTTI DCT Recommendations (Fall 2018)
Decentralized Clinical Trials defined as those executed through
telemedicine and mobile/local healthcare providers (HCPs), using
procedures that vary from the traditional clinical trial model (e.g., the
investigational medical product [IMP] is shipped directly to the trial
participant)

8. Not All-or-Nothing Approach
Certain activities can be done remotely by mobile or HCP
 E.g., blood draws, vital sign measurements, trial drug
injections
Some visits may still be needed to determine eligibility,
discuss trial progress, or review participant’s questions
Visits to facility when requiring major medical equipment
 E.g. x-rays, magnetic imaging, tomography scans
In single trial, can enroll some patients at traditional trial
sites, while others managed in decentralized or remote
manner

9. Limitations of Technology
ACCESS
DISPARITY
CANNOT FULLY
REPLACE AN
IN-PERSON
VISIT/HUMAN
CONNECTION
NOT ALL ENDPOINTS
CAN BE MEASURED
REMOTELY

10. Sections of DCT Recommendations
1. Approaches and Protocol Design
2. Telemedicine State Licensing Laws
3. Mobile Healthcare Providers
4. Drug Supply Chain
5. Investigator Delegation and Oversight
6. Safety Monitoring

11. 1) Engaging Key Stakeholders in
Protocol Design
Incorporate SOPs that describe processes that are unique to
DCT elements
Meet with regulatory bodies early in the process
 Numerous examples of specific meeting types and
relevant FDA offices are provided
Engage and learn from experienced vendors
 DCT trial executors with telemedicine
and/or mobile HCP experience
Protocol design: Focus on what matters
 to safety of trial participants
 credibility of the results

12. 2) Telemedicine State Licensing
DCTs operating across numerous states can:
 Maintain an investigator in each active trial state
 Utilize investigators licensed in multiple states
 Contract with vendors providing mobile HCP services across U.S.
Keep abreast of complex and varying state-by-state legal
landscape
 Use online policy
resource centers
 Dedicate internal legal
staff or seek external
legal consultants

13. 3) Mobile Healthcare Providers
Consult or partner mobile HCP vendor with experience
conducting clinical trial activities
 Specific credentials, experiences, and training are included in
recommendations
Possible mobile HCP protocol contributions:
 Blood draws and biological sampling
 Investigational medical product (IMP)
administration
 Trial participant training (e.g. IMP self-
administration)
 Clinical assessments
 In-home compliance checks (e.g.
timely completion of trial participant
diary, proper storage of IMP)

14. 4) Drug Supply Chain
Review state laws regarding direct-to-patient
shipment
Describe direct-to-patient shipment procedures in
protocol: Provides necessary clarity to
investigators, IRBs, and regulatory agencies
Consider engaging IMP vendor management
vendor with experience shipping IMP directly to
patients
Formalize SOPs for the IMP accountability
chain

15. 5) Investigator Delegation and Oversight
Highly protocol specific
Routine care / practice of medicine vs.
clinical trial related activities
Delegation of authority considerations
and responsibilities
Determine who belongs on the Form
FDA 1572

16. 6) Safety Monitoring
Highly protocol specific
Clearly articulate procedures and train investigative staff on
processes that are unique to DCTs
 Ensure trial participants knows procedures related to
possible AEs (e.g. list of approved local facilities)
 Pre-coordination efforts between investigators and
approved facilities/clinicians
Develop protocol-specific safety monitoring
and communication escalation plans

17. Then there was

18. COVID-19 Impact on Ongoing Trials?
https://www.oracle.com/oce/dc/assets/CONT2CC43C146CD14B52A0A103ABD34D70BB/native/oracle-report-11-17-
20.pdf?elqTrackId=9416c79188ad4c50a7bd8beb10c9837b&elqaid=103092&elqat=2

19. https://www.oracle.com/oce/dc/assets/CONT2CC43C146CD14B52A0A103ABD34D70BB/native/oracle-report-11-
17-20.pdf?elqTrackId=9416c79188ad4c50a7bd8beb10c9837b&elqaid=103092&elqat=2
COVID-19 Impact on Ongoing Trials? Cont’d

20. COVID-19 Impact on Ongoing Trials? Cont’d
https://www.oracle.com/oce/dc/assets/CONT2CC43C146CD14B52A0A103ABD34D70BB/native/oracle-report-11-17-
20.pdf?elqTrackId=9416c79188ad4c50a7bd8beb10c9837b&elqaid=103092&elqat=2

21. Imagining a ‘New Normal’ for Clinical Trial Visits
Pre-COVID-19:
Site based visits & care
Possibilities:
Home based visits & care
Adapting clinical trials during COVID 19: solutions Laura Cooke, Amgen

22. Switching to Remote & Virtual Visits (n=62)
Pharma,
10
Patient
Group,
3
Academia,
14
Technology,
7
Device/
Diagnostics,
3
Gov,
1
Investigator/Site,
11 Other,
2
CRO,
9
Biotech,
2
collected 29April/7May20

23. The Parts of Pre-Pandemic Site Visits that
Transitioned to Remote/Virtual
• Informed consent
• Study visits/ use of Mobile Healthcare Providers (MCPs)
• Safety collection: blood draws, local labs
• Endpoint collection: wearable sensors, clinician reported
outcomes, PROs, online cognitive tests
• IP shipment
Site - Participant interactions
• Site initiation visits (SIVs)
• Monitoring
Sponsor/CRO - Site interactions

24. Mid-Pandemic Hurdles in Switching to Remote/Virtual
Protocol Simplification:
What & How?
Platform
Supplement (Local Labs &
HealthCare Providers)
Investigational Medical
Product
Monitoring Visits:
What & How?
As conveyed by 57% of respondents
• Assessments
• Statistics implication
• Choice (licenses & contracts, no best standard)
• Ease of use & Adoption (participants & sites)
• Limited access to telehealth platforms pre-pandemic
• Reimbursement for remote/virtual visits
• Local: Laws & regulations, licensing, contracts
• Quality (unknown) & availability (clinical care)
• Cannot do every assessment
• How to get to participants
• How to administer if IV
• Sites = short staffed & working from home,
scheduling
• Risk based monitoring

25. Best Practices & Words of Wisdom
Site
Think ahead & create a plan
Test run the telehealth
platforms
Be flexible
Maintain clear & on-going
communication
Industry
Evaluate which assessments
can be done remotely
Use mobile HCPs & Local
Labs (match to assessments)
Follow regulations:
privacy/OCR, local,
Ethics/IRB
Be respectful of sites: this is
not their only priority
Run a stats analysis to
determine validity of remote
data
Tech
Deploy privacy compliant
tech platforms
Train pts/caregivers & sites
on platform
Create an appropriate
environment
Know how to handle system
failures
As conveyed by 50% of respondents

26. CTTI Members’ Experience

27. Lessons Learned from CTTI Members
(n=27)
between Sep 25- Oct 12

28. Survey Findings:
Digital Health and Decentralized Trials
Change Selected Lessons Learned
Switched to e-consent
Need to be sure of identity
Compliance is better, it is recorded
Protocol Simplification Preplanning is beneficial
Virtual & Remote Visits
Demonstrated feasibility of telemedicine trials
Right incentives were in place
Facilitate research, more widespread participation
Supplement (Local Labs &
HealthCare Providers)
Participants could stay locally
Some labs/imaging were easier set up than others
Logical extension of where we were going
Investigational Medical Product
IP needs to be appropriate for shipping & self
administration
Geographic differences drive site receptiveness
Monitoring
Increased appreciation of what could be done off-site
Setting up pro-actively would help

29. DCT 2.0 Recommendations Refresh
Timeline 1 year
Updating sections on
 DCT approaches and protocol design
 Drug supply chain
Document lessons-learned related to DCT elements during
the COVID-19 pandemic and identify opportunities to
enhance recommendations & resources

30. Conclusion
Real
momentum
towards DHT
&
decentralized
clinical trials
60% of respondents
express changes
will continued to be
implemented in
trials going forward
About 60% of those
implementing changes
going forward are
evaluating the
changes they are
implementing

31. Academic Example:

32. November: results published
Nice…BUT must be confirmed
(burnt by hydroxychloroquine).
Ps: better do it quickly!
Scientific community response
Courtesy Eric Lenze, MD Wash U

33. STOP COVID 2 was designed
Fluvoxamine 100mg
twice daily (x15d)
Placebo
Outcomes:
Primary:
clinical deterioration over 15
days (definition: SOB and/or
hosp, plus O2 <92%)
Secondary:
-15-day and 3 month function
(Global Health Scale)
* one or more of: African-Am, Latinx, Native-Am,
age >40, obesity, diabetes, HTN, heart disease
(CAD/MI/CHF), lung disease, or immune condition
Participants:
n=1100
enriched sample*
SARS-CoV-2+
community-dwelling
symptomatic (<7d)
Courtesy Eric Lenze, MD Wash U

34. Decentralized Clinical Trial elements
National recruitment
Telemedicine intervention
and remote monitoring
One site randomizing 10 participants per day
Ship study supplies
and medication
Courtesy Eric Lenze, MD Wash U

35. STOP COVID 2: enrolled 200/1100
start: 12/23/2020
Recruit
from here
Lead site
Partner sites:
FredHutch (Seattle)
University of Utah
Northwestern
McGill
Enroll at stopcovidtrial.wustl.edu Courtesy Eric Lenze, MD Wash U

36. Breaking down
(Brick) Walls
Switching to
decentralized clinical trials

37. www.ctti-clinicaltrials.org
THANK YOU.
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