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Wearables and
Patient Reported
Outcomes in
Research and Post-
Market Surveillance
CRT Plenary Meeting 2019
Tallin
04.10.2019 / Dr. Christian Müller
MA-M_VEN-DE-0004-1
Agenda
Digital (Health) Transformation
Real World Evidence
Breelib, BreeConnect, Ventavis®
Ventastep study
Evidence Matrix
ePRO collection
/// CRT Plenary Meeting /// Dr. Christian Müller /// Tallin 4
th
of October 20192
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/// CRT Plenary Meeting /// Dr. Christian Müller /// Tallin 4
th
of October 2019
Disruption -
Letterpress
• Self referring on written words
creates own reality
• Radical reduction on character
shape
• Social need
• Development of additional
technology skill: reading
• Data doubling the world
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• Identifies probabilistic patterns in
datasets
• Infinity, ubiquitious, loss of control
• Binary coded functional systems in
society
• Economy (payment/ no payment)
• Politics (power/ no power)
• Medicine (ill/ healthy)
• Binary code enables endless
operational opportunities
• For which problem digitalization is a
solution?
/// CRT Plenary Meeting /// Dr. Christian Müller /// Tallin 4
th
of October 2019
Disruption -
Digitalization
Digitalization assesses social complexity
Real World
Data
/// CRT Plenary Meeting /// Dr. Christian Müller /// Tallin 4
th
of October 2019 www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM513027.pdf5
electronic health records (EHRs),
claims and billing data,
data from product and disease
registries,
patient-generated data including in
home-use settings,
data gathered from other sources that
can inform on health status, such as
mobile devices
clinical evidence regarding the usage and
potential benefits or risks of a medical
product derived from analysis of real world
data
Real World
Evidence
/// CRT Plenary Meeting /// Dr. Christian Müller /// Tallin 4
th
of October 2019 Corrigan-Curay J, Sacks L, Woodcock J. Real-World Evidence and Real-World Data for Evaluating Drug Safety and effectiveness. Jama. 2018;320(9):867-8.6
Digitalization leverages
box-stop medicine
to
Real World Evidence
/// CRT Plenary Meeting /// Dr. Christian Müller /// Tallin 4
th
of October 20198
Characterized by endothelial cell proliferation,
pulmonary vascular remodeling, culminating in right
heart failure and death
Symptoms include: shortness of breath, fatigue,
chest pain, syncope, swelling (legs/ankles)
Dual combination therapy : endothelin receptor
antagonists (ERA`s) and phosphodiesterase-5
inhibitors (PDE5-i`s) or stimulators of soluble
guanylate cyclase (sGC)
synthetic analogue of prostacyclin PGI2
dilates systemic and pulmonary arterial vascular
beds
approval in Sept 2003 for the treatment of PAH
NYHA/World Health Organization (WHO) FC III,
may be added to dual combination therapy
/// CRT Plenary Meeting /// Dr. Christian Müller /// Tallin 4
th
of October 20199
Date of inhalation, inhalation time, inhalation
frequency, inhalation complete/incomplete
Data is stored for about 9 months of
inhalations
BreeConnect™ app can be actively
connected to Breelib via Bluetooth
10:37 AM
Date, time and duration of iloprost inhalations are captured
continously and displayed to the patient
/// CRT Plenary Meeting /// Dr. Christian Müller /// Tallin 4
th
of October 201910
Detection of micromovemet & translation into real life activities
by xbird GmbH
Identification of micromovements during real life activities and transfer into study variables
/// CRT Plenary Meeting /// Dr. Christian Müller /// Tallin 4
th
of October 201911
https://www.researchprotocols.org/2019/4/e12144/pdf
Local, German, prospective, uncontrolled, non-
interventional, digital cohort study
31 Ventavis® treatment naïve patients recruited at 9
sites
2 observation periods per patient (baseline period;
before start of Ventavis® treatment &
observational period; 3 months after start of
Ventavis® treatment)
Ventavis® (Iloprost): Evaluation of inhaled iloprost effects
using the Breelib™ nebulizer, clinical outcomes and
physical activity of patients with advanced pulmonary
arterial hypertension.
Fusion of classical and digital biomarkers out of 4 data sources
/// CRT Plenary Meeting /// Dr. Christian Müller /// Tallin 4
th
of October 201912
Using wearables in a digital research ecosystems enables
identification of relevant digital biomarkers
/// CRT Plenary Meeting /// Dr. Christian Müller /// Tallin 4
th
of October 201913
25 MB per
patient per day
/// CRT Plenary Meeting /// Dr. Christian Müller /// Tallin 4
th
of October 2019 Source: Mueller et al. 201914
Study visits & data collection
/// CRT Plenary Meeting /// Dr. Christian Müller /// Tallin 4
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of October 201915
to evaluate the potential use of device-based measures as outcome-surrogates for clinical assessments. This
is done by assessing patient-wise correlations between of 3-month/ baseline differences of clinical measures
(i.e. 6MWD, QoL, WHO FC and proBNP species) and wearable-based measures (physical activity)
VENTASTEP objectives
From correlation to pattern identification
/// CRT Plenary Meeting /// Dr. Christian Müller /// Tallin 4
th
of October 201916
From correlation to pattern identification
/// CRT Plenary Meeting /// Dr. Christian Müller /// Tallin 4
th
of October 201917
Pearson Correlation Statistics (Fisher-Z-Transformation)
Variables
6MWD (
investigator)
Borg Dyspnea Scale
(investigator)
EQ
-5D
WHO
-FC
Borg
Dyspnea Scale
(investigator
)
EQ
-5D
WHO
-FC
NT
-proBNP/BNP
EQ
-5D
WHO
-FC
NT
-proBNP/BP
Distance walked
(device based)
WHO
-FC
NT
-proBNP/BNP
Distance
walked
(device
based)
Number of steps
(device based)
…
/// CRT Plenary Meeting /// Dr. Christian Müller /// Tallin 4
th
of October 201918
Endpoint
Biomarker
Validity
Sensor/Device
Indication
Patient
Real world evidence generation in a digital world - using an
evidence matrix for primary data collection
Outer package is our hardware in the household of patients – just deliver software to collect data
Falsified medicines directives 2D Matrix Code can work as patient
authentification in remote, patient centric real-world data collection
/// CRT Plenary Meeting /// Dr. Christian Müller /// Tallin 4
th
of October 201919
Primer
Country Code
Product Code (PZN)
Serial number
Expiry date
Charge
my ePRO app in a nutshell
Download - Scan - Consent - Answer - Compensation
BAYathlon • February 2018 • Dr. Christian Müller • Dr. Ulf HengstmannPage 20
Download
my ePRO app from
public app store
Scan 2D Matrix Code
for authentification as
BAYER drug taking patient
Consent
to PIIC electronically
Answer PRO
using validated PROs &
additional data sources
Compensation
based on time needed
for answering PROs
With my ePRO app we help patients to report their outcomes – PRO – with a compensation for their time required
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Take home
message
• need for RWE research with
digital features
• digital support to identify patterns
• overcome box-stop medicine
• implementation into routine care
Forward-Looking Statements
This website/release/presentation may contain forward-looking statements based on current assumptions
and forecasts made by Bayer management.
Various known and unknown risks, uncertainties and other factors could lead to material differences
between the actual future results, financial situation, development or performance of the company and the
estimates given here. These factors include those discussed in Bayer’s public reports which are available
on the Bayer website at http://www.bayer.com/.
The company assumes no liability whatsoever to update these forward-looking statements or to conform
them to future events or developments.
/// CRT Plenary Meeting /// Dr. Christian Müller /// Tallin 4
th
of October 201922
