CORE WEST 2021

Changing Business Model

of Clinical Trials
Ed Seguine – CEO Clinical Ink
 Agenda

• Expertise = Perspective
• Buzzwords
• Lessons Learned: 4 Case Studies
• BYOD
• Covid – Remote
• Covid – Pivot
• DCT by Design

• Core Operational Consideration

© 2021 Clinical Ink | Confidential
Clinical Ink Experience
Global Experience Study Growth by Year
• 325 Studies 350
Phase IV
Phase I
• 70+ Countries 300
• 80+ Languages
250
• 8,000+ Sites
• 500+ Scales/Instruments 200

150
2021 Study Overview 100 Phase III Phase II
• 173 Active Studies
• 7,300+ Live Sites 50
• 13,500+ Live Devices 0
201320142015201620172018201920202021
• 85,500+ Active Users
Studies

Founded: 2007 | FTEs : 275

Regulatory Acceptance
Customers: 120+ (sponsors and CROs)
Locations: Horsham, PA; Winston-Salem, NC 35 Submissions
Ownership: GI Partners 9 Approvals

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Global Experience

132 PHASE
3 STUDIES

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 eSource Direct Data eCOA/Rater Scales ePRO/Engagement
• Simple-High Complexity • BYOD / Provisioned
Capture • Virtual Visit support • Virtual Visit Support
• Site/Virtual workflow • TA Specific Applications • Enablement model
• eSource/eCRF

Complex eSource Ecosystem Simple

eConsent Remote Review

• Simplifies startup • Data, Documents,
• Improves patient Audio, Video, Photo
• Structured Workflows
experience

© 2021 Clinical Ink

 Regulatory Expertise
Major regulatory contributions: Ad-Hoc contributions:
• July 2021 – DTRA • FDA Guidance July 2021 (pending)
Regulatory co-lead for Decentralized Trial Alliance • DCTs; Remote Data Acquisition

• July 2019 – EMA Other Relevant Guidance:

Qualification Opinion: eSource Direct Data Capture;
• Clinical Systems – EMA Jun ‘21
Clinical Ink experience cited in 15 studies

• September 2013 – FDA • DCT Guideline – Denmark Sep

Guidance: Electronic Source Data ‘21
“Please note that we expect to update
• August 2010 – EMA this guidance frequently. DCT is an
Reflection paper: Electronic Source Data area undergoing significant and rapid
development…”
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Industry Influence

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Business Model Evolution
2000s Electronic Data Capture; paper CRF to eCRF
Acceptability of Patient Reported Outcomes as an endpoint
Increased emphasis on CROs and outsourcing

2010s EDC standardized processes

eCOA migration from paper; BYOD hopes unrealized
Data Integration (IWR, CTMS, eTMF, RBM, Labs)
EHR data access (recruitment, site selection, clinical data

2020s COVID was/is imminent mortal threat; overnight

‘Anything Goes’ approach initially; sort it out later
Remote ‘everything’
© 2021 Clinical Ink 8
 Current Buzzwords
• Virtual • BYOD • Televisits
• Hybrid • Engagement • AI/ML
• Decentralized • Sensors • eConsent
• Adaptive • eCOA (in • Remote
• Master Protocols all its Monitoring
forms)

What’s it all Mean?

At the end of the day, it’s all about options and
flexibility for sponsors, sites and especially patients.
© 2021 Clinical Ink | Confidential
Execution Optionality

Flexible Options for Sites/Patients

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Hypotheses
1. BYOD device usage for eCOA will increase
2. Remote, “Hybrid” trials will increase
3. Build timelines will decrease; more self-service options
4. Core operations will grow more complex (Project Management,
Help Desk, Training, Hardware Expertise)

5. ‘Instrumented’ data will increase and drive platform choice

© 2021 Clinical Ink 11

Study 1: BYOD
The Study
APPROVED - Phase III sleep disorder
275 patients, 56 sites, US/Europe
• 1-3 daily diaries for 3 months
• 16 dynamic timepoint measurements
• Patient Education content

The Result
90% BYOD; 10% Provisioned
Work phone, Older model, Bad battery life
>92% diary compliance for 30% of patients and sites
100% timepoint compliance for 86% of patients
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 BYOD Insights: 70+ Global Studies
BYOD – Increases Compliance
BYOD – Increases Engagement
• Twice as often
• Twice as long

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 BYOD Equivalence: Study Design

Period 1 Period 2 Period 3

BYOD BYOD BYOD

Paper Paper Paper
Provisioned Device Provisioned Device Provisioned Device
Washout Washout
Distraction Task Distraction Task

156 Subjects SF-20

• 19 to 69 years old (48.6  13.1) • VRS
• Female: 83 (54%) • Y>3, Y<3, N
• Male: 72 (46%) • Likert
• Conditions resulting in chronic pain • VAS and NRS-11 (pain)
• Broad range of educational
backgrounds https://www.sciencedirect.com/science/article/pii/S109830151733615X
© 2021 Clinical Ink https://acrpnet.org/2021/05/18/what-makes-a-successful-byod-strategy-in-clinical-trials/
BYOD Equivalence: Study Results
Association Measured by Intraclass Correlation Coefficients

Very High Correlation Between the Three Modes of Administration:

•ICCs: 0.816 to 0.974
•Lower bound of the 95% confidence interval > 0.70

Very High Correlation Between Paper and BYOD

•ICCs: 0.806 to 0.974
•Lower bound of the 95% confidence interval > 0.70

Very High Correlation Between Site Device and BYOD

•ICCs: 0.791 to 0.966
•Lower bound of the 95% confidence interval > 0.70

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BYOD Equivalence: Patient Experience

79% 94%

68% 92%

Age
41%
48%
47%

46% 42% 12%

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 BYOD Insights
BYOD Design Regulatory Viewpoint
Keep It Simple • 2017 21CFR11 Q&A doesn’t
• No fancy font formatting differentiate between BYOD &
provisioned
Single Item per Screen • Difference between ‘Regulators’
• Standardization and ‘Regulatory’
• ‘Whisper’ concerns related to:
Standard Widgets • Data Privacy
• Technical Feasibility
• NRS (equidistant)
• Inclusivity – no patient excluded due
• VRS (same box size/height) to lack of adequate device
• VAS (101 data points, NOT 100 mm)

© 2021 Clinical Ink 17

Study 2: COVID Remote
The Study
Phase III COVID vaccine
1100 patients, 82 sites, Europe
Long-term care facility residents 60+ yrs
Televisits not possible; bandwidth, usability

The Approach
Tablet-based hardware for traveling nurse coordinators
Real-time data capture; Online/Offline flexibility
Real-time monitoring, including ad-hoc written notes

© 2021 Clinical Ink 18

Study 2: eSource DDC
Clinical Ink Pioneered the DDC concept beginning in 2012

COVID accelerated adoption

• Lack of access to sites; inability to travel; remote monitoring of SOURCE
• Criticality of real-time data; speed to insights
• Combination of ‘EDC’ data and ‘eCOA’ in same platform

© 2020 Clinical Ink | Confidential 19

Study 2: Optional Designs
• Previously used during Ebola outbreak (6000
patients in West Africa)
• Originally designed for ‘mobile’ site locations;
offline/online workflow with satellite uplink
• Tablets optimize data quality with real-time edit
checks and immediate remote monitoring
• Minimize ‘keyboard’ usage (hard with gloves) by
using stylus and scanner
• Easily sterilize devices between patients to
reduce contagion
• IRT and eConsent integration

© 2021 Clinical Ink | Confidential 20

Study 3: COVID Pivot
The Study
4 Study Program: 2 Phase II, 2 Phase III
2500 patients, 275 Sites, US/Europe/Asia
10 Site-Based ePRO with clinician oversight

The Approach
10 Day Build/Deploy time; use existing library (SF36, HADS, LEC5)
Agile build – ‘self-defined specs’ based on as-built functionality
Remote UAT; Real-time decisions, Live iteration
Simultaneous copyright approval and translations

© 2021 Clinical Ink 21

Additional Implications
• Allow for flexible use of televisit solutions
• Sites will, most likely, already have a solution
• Ensure an integrated helpdesk
• Can patients call the helpdesk? Text? Chat?
• Helpdesk must understand protocol; AE SOPs “Our patients are experiencing tremendous
distress at a time when the traditional counseling
• Embrace a BYOD approach and therapy options are not possible. We
appreciate the commitment Clinical Ink has
• BUT - Have a backup device plan made to help us provide these devices to our
patients who are extremely grateful.”
• Device qualification/testing; know what works Brianne Hahn, CEO, Thrive Behavioral Health

• ‘Random Acts’ initiative

• Donated gently-used devices to needy
community mental health providers
© 2021 Clinical Ink
Study 4: DCT by Design
The Study
20,000 Screened; 3,300 Enrolled + Caregivers; 200+ sites
First-Ever DCT in complex CNS
Primary efficacy: TICS, MOCA, C-SSRS, CDR, MMSE

The Approach
5 Week Build/Deploy time
Zoom-Health for usability, control; Recorded
Patients draw images remotely (clock, 3D Box, trail making test)
50+ Remote Assessors
5 year duration; Continuous followup
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Purposeful DCT Design
PI PI PI

At Site At Site At Home At Home At Site At Home

Baseline Year 1 Year 2-3 End of Study Follow Up

Screening Visit Assessments
Assessments Assessments Assessments Assessments

• How can tasks be done differently but yield same result?

• Can Single Platform support multiple data collection mechanisms?
• Does provider have experience, maturity, capability to pivot?
© 2021 Clinical Ink
Cognitive Assessment Using eCOA:
MoCA

For virtual visits, can be performed remotely via

video link using a handoff to participant for
completion of the trial and drawing tasks on device

Recording of audio and video, on-site and remotely,

for central review or monitor access
Item administration & scoring instructions on-
screen

© 2021 Clinical Ink

Cognitive Assessment Using eCOA:
CDR

Record form built within the eCOA platform

Minimizes administration & scoring errors

Highlighting prevents missing data

Automatically tabulates scores

Photo capabilities to capture images

(e.g., CDR Global Score, calculated via the
Washington University website)

© 2021 Clinical Ink

Cognitive Assessment Using eCOA:
MMSE

On-screen instructions & verbatim text content

Expected answers account for miscalculations

by the participant
Photo capabilities to capture images
(e.g., participant’s written sentence or figure
drawing)

Handwritten clinical notes

Automatically tabulates scores

© 2021 Clinical Ink

 Beyond Technology - Operational Maturity
Word Cloud from Customer Survey 2021

OPERATIONAL EXPERTISE!!!!
© 2021 Clinical Ink
 Project Management
Weekly Traffic Light Snapshot
• CSAT + 10 key success criteria
• ‘Live’ Dashboard for Management
• Full weekly history
• Automated escalation paths
Project Manager subjectively assigns ranking and
provides commentary on each Yellow or Red issue.
AGENDA for weekly Project Leadership meetings
PM compliance monitored; 100% compliance
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 Translation Timelines

Saves 2-3 weeks

Depends on a final build AND copyright holder approval

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Key Operational Bottlenecks
License Holders
• Engage early and get early buy-in and agreement
• Constantly changing landscape
• EORTC now charges 40.000€ PER STUDY for quality of life scales

IRB Approval
• ‘Study Build’ timeline is not FPFV or Investigator Meeting – earlier
• Late changes impact approval
• BYOD potentially complicates screenshot generation

Hardware
• Minimum Expertise: Provisioning, Deployment, Imaging, MDM
• Complications: Kitting, Sensor Interactions, OS Updates, chargers
international customs 95% On-Time

© 2021 Clinical Ink

 Dynamic, Adaptive, Context-Based

Support for Traveling Coordinators Support for televisit at Home

Long term care facilities | Home
Remote locations

BYOD diary and questionnaires Reminders and tasks Medication compliance

© 2021 Clinical Ink
 Beyond the Platform

Experience Operational Maturity Innovation

Not all experience is good
With over 320 studies Experience & Maturity are
experience! Clinical Ink
deployed Clinical Ink has not enough. New problems
has evolved processes,
the practice and familiarity and better outputs require
services, and products for
required. new ways of thinking.
reliability.

© 2021 Clinical Ink

Hypotheses
1. BYOD device usage for eCOA will increase
2. Remote, Hybrid trials will increase
3. Build timelines will decrease; more self-service options
4. Core operations will grow more complex (Project Management,
Help Desk, Training, Hardware Expertise)
5. ‘Instrumented’ data will increase and drive platform choice
Innovation

Experience Operational Maturity

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