Electronically Collecting Data from
Participants in Clinical Trials
June 1, 2015
Ben Baumann
bbaumann@openclincia.com
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Trajectory
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Terminology
Benefits & Promises
Barriers & Reality
Technology
Regulatory
Content
Data Management
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eCOA
(electronic clinical outcomes assessment)
Definition: an electronic assessment that may be influenced by human
choices, judgment, or motivation and may support either direct or indirect
evidence of treatment benefit.
Patient Driven eData
Assessment = instrument = questionnaire = form…
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eCOA Modalities
Modality
Definition
Use When
Examples
ePRO
Data reported electronically
directly verbatim by subjects.
Self report, or interview.
• Trained health professional
not needed + self-report
feasible and appropriate.
• Unobservable concepts
(feelings, sensations)
• Pain intensity
• Mood/feelings
• Eating habits
Report from a health-care
professional observing
subject’s condition. Involves
clinical
judgement/interpretation.
Trained health professional
needed
• tumor size
• Parkinson’s patient who
cannot comment
• palpating a spleen
Measurement based on an
observation by someone
other than the patient or a
health professional. Does not
include medical
judgment/interpretation.
Trained health professional
not needed and self-report
NOT feasible/appropriate.
• parent/infant
• caregiver/elderly person
Performance of a task by
subject based on instructions
administered by a HC
professional
The specific task is required
by protocol
• 6 minute walk test
• Memory recall
(Patient-reported
outcomes)
ClinRO
(Clinician-reported
outcome)
ObsRO
(Observer-reported
outcome)
PerfO
(Performance outcome)
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Why do it?
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Quality
Productivity
• Better data
• Faster, less labor
•
Engage
patients
in
Enablement
new ways
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May Clinic Study
 3,704 cancer patients
How would you describe your overall quality of life today?
0
1
2
3
4
5
6
As bad as
can be
7
8
9
10
As good
as can be
 Score of 5 or less, 15 months survival
 Sore of 5+, 52 months survival
 Cannot ignore decrease of 2
This is a prognostic factor for cancer patient survival
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 Incorporated QOL assessment into daily clinical
oncology practice
 Initiated conversations with patients
 Insomnia
 Stupid thoughts
 Reduced emergent care
 Improved survival
 Improved quality of life
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Paper vs. Electronic
Paper
eCOA
 Piles of paper can be confusing
 Don’t need to worry about the
internet
 Chance of getting lost/destroyed
 Slow access to actionable
 More controlled experience
 System prompts user automatically
 Increased compliance (regulatory,
information
 Parking lot syndrome
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patient)
 Requires secure login/password
 Date/Time Stamped in Audit Trail
 E-Source recorded in Audit Trail
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Drivers of eCOA
 Quality & Efficiency
 Increased data quality (edit checks, data
types, show/hides, required fields)
 More efficient data collection (reduce
need for data entry)
 Improved patient compliance1,2
 Auto-reminders
 Electronically monitor
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Cost savings
Know exactly when something happens
Report deviations to sites immediately
Get data earlier to prevent problems
Better patient care
1
ePRO often produces compliance rates over 90%. See Meltzer EO, Kelley N, Hovell MF (2008). "Randomized,
Cross-Over Evaluation of Mobile Phone vs Paper Diary in Subjects with Mild to Moderate Persistent Asthma".
2
Friedberg F, Sohl SJ (2008). "Memory for Fatigue in Chronic Fatigue Syndrome: The Relation Between Weekly
Recall
and Momentary Ratings". International Journal of Behavioral Medicine 15 (1): 29–33
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Drivers of eCOA (cont.)
 Technology trends
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Ubiquity of internet access
Mobile devices
Responsive design
Sensory devices
Apple ResearchKit
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Drivers of eCOA (cont.)
 Patient engagement
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Integrate into subjects’ lives, especially if BYOD
Fewer dropouts
More events
Feedback
 Improvement over time
 Comparison vs. the field
Increased
Compliance
Engaged
Patients
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eCOA in an ALCOA World
Attributable
Login / access code
Legible
It’s digital, structured
Contemporaneous
Can control when things happen
Original
ePRO captured directly from subject
Accurate
Edit checks, rules logic
Complete
Consistent
Enduring
Available
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Barriers to Adopting eCOA
 Expense (or, at least perceived expense)
 Devices / Logistical complexity
 Usability
 Fit with study population
 Integrating with existing EDC/CDM Systems
 “Translating” existing PROs to electronic form
 Others? What has stopped you?
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Adoption of eCOA
 2009 FDA PRO guidance1
 More trials are collecting COA data
 Use of BYOD increasing, but mostly in post-approval
studies
 Scientific evidence growing to broaden use
 Technology farther ahead of the regulations and adoption
1
http://www.fda.gov/downloads/Drugs/Guidances/UCM193282.pdf
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Formula for Success
Success = Planning + Implementation
So, let’s break it down:
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Patient experience
Content
Regulations
Technology
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Patient Experience
How will you engage your patients?
 Motivation
 Incentive
 Feedback
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Usability
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Number of forms/instruments
Items per page
Scolling
“Simple can be harder than complex:
You have to work hard to get your
Edit
checks
thinking clean to make it simple. But it’s
worth it in the
end because once you
Required
fields
get there, you can move mountains.”
Skip logic
- Steve Jobs
Accommodating disabilities
Offline
Support: patients, devices, logistics
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Language
press
click
mouse
select
choose
enter
 Will instrument be translated?
 Avoid idiomatic expressions
 Allowing for text length
 Left Right, Right Left
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Item Stems & Recall
 Making questions self contained
 During the last week, how has the pain interfered with:
 Going to work
 Sleeping at night
 During the last week, how has the pain interfered with
going to work?
 During the last week, how has the pain interfered with
sleeping at night?
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Usability Testing
 Field-test involving patients (ePRO) and/or clinicians
(ClinRO) -- use the real thing
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Electrifying Existing COAs
 Must show eCOA version yields data which are
equivalent or superior to paper version.
 eCOA version must measure the same thing as paper
 Need to show evidence of evidence of equivalence1
 Level of evidence depends on severity of change
1 FDA
PRO Guidance 2009: http://www.fda.gov/downloads/Drugs/Guidances/UCM193282.pdf
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Evidence of Equivalence
Table from ISPOR ePRO Task Force Paper: http://www.ispor.org/workpaper/patient_reported_outcomes/Coons.pdf
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Content: Leveraging Others’ Work
 C-Path PRO and ePRO Consortia (www.c-path.org)
 Pre-competitive, FDA + industry
 Collaborate to generate measurement equivalence data
 Best practices
 PROMIS (www.nihpromis.org/)
 Freely distributes instruments
 Tested, multiple languages
 ISPOR (http://www.ispor.org/)
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Regulations: Available Guidance
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2009 FDA PRO Guidance
How FDA reviews and evaluates existing, modified, or newly created
patient-reported outcome (PRO) instruments used to support
claims in approved medical product labeling.
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2013 FDA E-Source Guidance
 Assure reliability, quality, integrity, and traceability of data from electronic source
to electronic regulatory submission.
 Promotes capturing source data in electronic form
 Retention of electronic source data in FDA-regulated clinical investigations.
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2013 Mobile Medical Applications
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Mobile Medical Applications
 Mobile App: A software application that can be run on a mobile
platform, or a web-based software application that is tailored to a mobile
platform but runs on a server.
 Mobile Medical App: A mobile app that meets the definition of a
device and is intended:
 To be used as an accessory to a regulated medical device
 To transform a mobile platform into a regulated medical device (e.g., via a
sensor or electrode)
 FDA intends to apply its regulatory oversight to only those mobile apps
that are medical devices and whose functionality could pose a risk to a
patient’s safety if the mobile app were to not function as intended.
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Technology
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Choices, choices…
Choice
Considerations
Smart Phone
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Typically used for ePRO
Well-integrated messaging (SMS, phone, email)
Smaller screens may present issues for certain
instruments
Logistics if provisioning
Tablets
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Typically used in ClinRO settings
More readily emulate paper
Logistics if provisioning
Less validation burden
Digital Pen
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Special pen, special paper
Still have paper
Legibility
Technology support
IVR
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Limited types of questions
Recall time
Patients get frustrated
Web-based
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App vs. Web
 Limitations and Liberties
 Pushing updates
 Validation
 Data stored on device
 Responsive design
 What actually is the app?
Web?
App?
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Device Provisioning vs. BYOD
Device
BYOD
User may forget
Already in habit of using
Greater control
Unknown device configurations
Connectivity issues
Already connected
Simpler validation
Device checks
Responsive design
Connectivity issues
Participate already connected
Lots of logistics and
support
Little to none
Hybrid BYOD /
Provisioning an option
BYOD?
Provide
device?
…or both?
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Role of Data Management
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Edit checks/controls at entry
Required fields: complete data vs. accurate data
Frequency of data collection
EDC/CDMS integration
Reviewing data
How to handle data received too early / too late
Clear policy with sites around changing ePRO data (e.g. visit dates,
basic demographics)
 Under control of investigator at all times
 Paper as back-up; how to handle
 Site Support, FAQ
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Putting it All Together
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Thinking About ROI
Paper
Vs.
Costs you are incurring:
 Printing
 Mailing
 Data Entry
 Data Cleaning
Electronic
Costs you are incurring:
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Some estimates as high as $20 per page
Electronic system
Costs you are saving:
 Less data entry
 Less data cleaning
 Printing and mailing
 Fewer site payments
Quality benefits:
 Increased accuracy
 Removing interpretation
 More time for patients
Faster study closeout
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We Can Do This!
Technology has advanced and we have the power to use
that technology to improve patient care.
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Thank You!
Ben Baumann
OpenClinica, LLC
bbaumann@openclincia.com
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