This was presented at the Panagora Pharma Clinical Trials Patient Experience Summit. In Learning Health Systems (LHSs), practice influences research and research influences practice. This makes LHSs the new frontier for adaptive clinical trials and the harbinger of what's to come in a patient-centered clinical development world. Many organizations still struggle with sufficient understanding and experience with digital medicine. Few commercial examples exist where a product has gone through the entire clinical development life cycle - a life cycle which is rampart with barriers to innovation. By leveraging the rise of LHSs and Adaptive Learning Studies, both biopharmaceutical companies and academic research centers can cross the chasm and accomplish what patient engagement can do for clinical development: faster, cheaper, and more efficacious outcomes. For researchers, it is a dream come true. For traditional CROs, it is a challenge.

1. Digital Medicine
Acceleration!
T h e P r o m i s e o f L e a r n i n g
H e a l t h S y s t e m s
Ahmed Albaiti
Founder and CEO

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We’re Digital Health Experts. !
• 100% Healthcare since 2005
• Steeped in Lean & Learning Development
• Geared for complex collaborations
• Focused on iteratively driving Outcomes

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3!page© Medullan Inc.
Today’s Discussion
1
Why
Now?!
What
Matters?!
Where
To?!2
3

4. Why Now?
Because it’s already been thousands of years.

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5!page© Medullan Inc.
First, let’s start with a couple of fundamental truisms…!
We have many more
questions in medicine than
we have randomized
clinical trials
?
?
?
?
?
?
?
If we want the cost of
medicine to drop, the
cost of clinical trials
must come down
$$$

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6!page© Medullan Inc.
6!page© Medullan Inc.
Then, let’s add a healthy dose of bold hypotheses!
The single biggest
contributor to better
cost and outcomes is
successful use of
patient experiences
and measurement
The rise of patient-
centered design and
Health IoT will make
adaptive clinical
studies the new
gold standard over
conventional RCTs
Disruption in clinical
development to
digitally-enabled,
adaptive studies will
destroy current
operations and
out-sourcing models

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7!page© Medullan Inc.
Lastly, let’s not forget how long the gold standard took!
From Legumes &
Lemons to James
Lind took
thousands of years!
Study Zero:
Legumes &
Lemons
Arrival"
of the
Placebo
The First
Double blind
Controlled Trial
The First
Randomized
Controlled Trial
FDA issues draft
guidance on
Adaptive Trials
FDA acknowledges
need for “larger,
simpler” trials
Scurvy
Trial
1943! 1946!500 BC! 2010!1747-1811! 2012!

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8!page© Medullan Inc.
Which brings us to Learning Health Systems…!
“… where progress in science, informatics,
and care culture align to generate new
knowledge as an ongoing, natural by-product
of the care experience …”
- Institute of Medicine

9. What Matters?
Patient experience isn’t all it’s worked up to be.

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10!page© Medullan Inc.
What’s this all got to do with patient experience?!
Patient experience
Care experience
Patient recruiting
Patient subscribing
Patient journeys
Patient mental models
From: To:
Patient data
Patient measurement
Patient retention
Patient relationships

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11!page© Medullan Inc.
How does it line up with evolution in digital medicine?!
App computing
Cloud computing
Biosensors
Smart, connected devices
Predictive analytics
Prescriptive analytics
From: To:
Randomized Control Trials
Adaptive Learning Trials
Prescription-based clinical practice
Shared-decision-based clinical practice

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12!page© Medullan Inc.
While the cost of low technology adoption is well documented…!
75%of trial patients are
using digital
channels to
coordinate their
health
41Kconsented
participants for
MyHeart Counts
study
80online patient stories
kicked off SCAD
research study and re-
classified the disease
as “frequently
undiagnosed”
$18B"in recruiting costs
in the US alone
30%"of clinical trials cost is
associated with data
management
80%"of clinical trials still
conducted with paper
services

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13!page© Medullan Inc.
The care experience factors have to be discovered …!
Patient lack of
expression and
inconsistent physician
background contributed
to over 70% of time
required for effective
therapy selection
The majority of non-
responsive, newly
diagnosed patients
had a mental model
of antibiotics when
considering adhering
to their medication
75% of CMPA care
givers preferred an
app from a nutrition
manufacturer versus
8% for other infant
allergy caregivers
Psoriasis Therapy
Consultation
Schizophrenia
Self-Management
Infant CMPA

14. Where To?
Learning Health Systems and Adaptive Studies

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Big Data analytics enables Scalable Adaptive Design!
“in context” prediction that
includes evidence, and
interpretation and
recommended actions for
each predicted outcome
Predictive analytics
linked to clinical priorities
and measurable events,
such as cost effectiveness,
clinical protocols, or patient
satisfaction and outcomes
Prescriptive analytics

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16!page© Medullan Inc.
Adaptive Design enables true Patient-Centered Research!
Conventional Clinical Trials
Phase 1! Phase 2! Phase 3! Phase n!
IND
POC
Filing Decision
IND
Transition time
Patient Centered Clinical Studies
Discovery! Learn! Confirm!
Transition zone Transition zone

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17!page© Medullan Inc.
Patient-Centered Research underpins Learning Systems!
“Market” Studies
Pilot &
Point-of-Care
Studies
HEOR Studies
Adaptive"
Learning Studies
Adaptive!
Design!
PROMs!
Health IoT!
Big Data!
Analytics!
Experience Factors
Technology Factors
• Progressive learning and
investment
• Increased
randomizations
• Early “surprise”
detection and correction
• Deeper understanding of
unmet patient needs
• Higher retention rates for
patients and physicians
• “Real world” data
variation and validity

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18!page© Medullan Inc.
Adaptive!
Design!
PROMs!
Health IoT!
Big Data!
Analytics!
Integrate care experience
and adaptive protocol into trial
design to create the ideal
framework for research
Adopt a “market to
outcomes” rather than a “lab
to market” approach to deliver
earlier and cheaper learning
Start with a cultural shift to a
“learning health system” and
find – sometimes novel –
partners to execute
Research stakeholders will
increasingly engage directly
with each other and with
patients – HIPAA be damned!
New players will fill the
demand for digitally-driven
clinical research capabilities
Digitally-enabled adaptive
studies will destroy current
operations and out-sourcing
models
Learning Systems align science, informatics, care culture!

19. Ahmed Albaiti
Thank You
Founder and CEO
ahmed@medullan.com
@ahmedullan