Enabling Innovative Respiratory Real World Evidence Generation: Sensor and EHR Integration Pilot Study
Conditions: Pulmonary Disease, Chronic Obstructive
Sponsor: GlaxoSmithKline

.GlaxoSmithKline 
CONFIDENTIAL 
HEALTH OUTCOMES STUDY PROTOCOL 
--
UNIQUE IDENTIFIER 
HO-17-17827 / 207223 
FULL TITLE 
Enabling Innovative Respiratory Real World Evidence 
Generation: Sensor and EHR Integration Pilot Study 
ABBREVIATED TITLE 
Sensor Pilot 
FINAL PROTOCOL APPROVED 
October 16, 2017 
SPONSORSHIP 
Supported 
DIVISION 
Pharma 
BUSINESS UNIT 
Research & Development 
DEPARTMENT 
US VEO 
STUDY ACCOUNTABLE PERSON 
 
CONTRIBUTING AUTHORS 
 
 
I INDICATION 
I Asthma and COPD 
REVISION CHRONOLOGY: 
Version Date 
Document Type 
Change(s) since last version 
10-16-2017 
Original 
n/a 
2-22-2018 
Amendment 01 
Revisions: 
1. 
Added statement 
regarding the data 
captured from devices 
being for research use 
only 
2. 
Updates subject 
identification to include 
study provider referral 
3, 
Added collection of 
height and weight at 
Visit 1 
Copyright 2016 the GlaxoSmithKline group of companies. All rights reserved. 
Unauthorized copying or use of this information is prohibited. 
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I 
2 
4. Added details 
regarding the 2 step 
process for full data 
integration 

Description: 
 sensor pilot 
Unique ldentilier: HO-17-17827 / 207223 
Date 
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Description: 
Sensor Pilot 
Unique Identifier: HO-17-17827 / 207223 
Investigator Protocol Agreement Page 
D 
• 
.. 
I confirm agreement to conduct the study in compliance with the ·protocol. 
I acknowledge that I am responsible for overall study con~uct. I agree to personally 
conduct or supervise the described clinical study. 
I agree to ensure that all associates, colleagues and employees assisting_in the conduct 
of the study are informed about their obligations. Mechanisms are in place to ensure 
that site staff receives the appropriate information throughout the study. 
Investigator Name: Paul Simonelli, MD PhD 
4 
d 
,.. Loi cf 
Date (DD-MMM-YYYY) 
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PROTOCOL SYNOPSIS 
Unique Identifier 
Abbreviated Title 
Rationale 
Objectives 
(Primary, Secondary) 
Study Design 
Study Population and 
Sampling Methods 
HO-17-17827 / 207223 
Sensor Pilot 
This is a pilot study exploring the opportunity for accessing data 
directly from electronic health records (EHR) and integrating with 
data from various sensors and mobile devices. The goal is to assess 
how to scale these methods for use in intervention al trials. 
• 
To assess how the use of EHR may be beneficial in recruiting 
populations for future clinical trials, 
• 
To evaluate how representative the consented, study, 
population is when compared to the eligible population, 
• 
To develop a monitoring dashboard for integration of data 
from various sources, 
• 
To evaluate patient experience, data quality and consistency 
with novel, patient-data collection methods: 
o 
Mobile spirometry 
o 
Sensor for monitoring rescue medication use 
o 
Sensor for monitoring maintenance medication use 
o 
Physical activity monitor 
o 
Electronic patient reported outcomes (ePROs) 
• 
To assess the relationships between EHR-based healthcare 
utilization (ambulatory care visits and hospitalizations for 
COPD or asthma exacerbations) and lcJb measures (specified 
below) with patient data remotely collected via methods 
outlined in previous bullet. 
A prospective study that will include two cohorts of patients (COPD 
and asthma) identified via EHR database analyses recruited from 
sites of usual care. Participants will attend two visits at O and 6 
months and data will be collected via sensors and mobile devices 
between the visits. 
Eligibility Criteria 
Inclusion Criteria 
All patients will be selected based on the following criteria . 
Inclusion Criteria for COPD cohort: 
To be eligible to participate in this study, a subject must meet all of 
the following criteria: 
• 
Provide signed and dated informed consent form. 
• 
Be willing to comply with all study procedures and be 
available for the duration of the study. 
• 
Age;:: 40 
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• 
Diagnosed with COPD, defined as COPD listed on the 
patient's problem list and one of the following: 
o 
At least one inpatient hospitalization with a COPD 
diagnosis listed as the primary or secondary 
diagnosis (J41.x, J42.x, J44.x [chronic bronchitis], 
J43.9 [emphysema] or J44.9 [Chronic obstructive 
pulmonary disease, unspecified]) in the last 12 
months OR 
o 
At least one emergency room encounter with a 
COPD diagnosis (J41.x, J42.x, J44.x, J43.9, J44.9) 
listed as the primary or secondary diagnosis in the 
last 12 months OR 
o 
At least two encounters of any combination of the 
following (each must be a distinctly different event 
with different dates of service): 
• 
an outpatient encounter with a diagnosis 
of COPD exacerbation (J44.1), Acute 
bronchitis (J20.x), or bronchitis (J40) listed 
as the primary or secondary diagnosis in 
the last 12 months, OR 
• 
an urgent care encounter with a COPD 
diagnosis (J41.x, J42.x, J44.x, J43.9, J44.9) 
listed as the primary or secondary 
diagnosis in the last 12 months 
• 
At least one order for an inhaled COPD medication during 
the prior year. 
• 
12+ months of data available in the integrated EHR data 
prior to date of screening. 
Inclusion Criteria for Asthma cohort 
• 
Provide signed and dated informed consent form. 
• 
Be willing to comply with all study procedures and be 
available for the duration of the study. 
• 
Age~ 18 
• 
Diagnosed with asthma, defined as asthma listed on the 
patient's problem list and one of the following: 
o 
At least one inpatient hospitalization with an asthma 
diagnosis (J45.x) listed as the primary or secondary 
diagnosis in the last 12 months OR 
o 
At least one emergency room encounter with an 
asthma diagnosis (J45.x) listed as the primary or 
secondary diagnosis in the last 1? months OR 
o 
At least two urgent care encounters, with different 
dates of service, with an asthma diagnosis (J45.x) 
6 

listed as the primary or secondary diagnosis in the 
last 12 months OR 
0 
At least three or more prescriptions or prescription 
refills in the past 12 months for any combination of 
the following: an inhaled glucocorticoid with or 
without a second controller (Montelukast, 
Theophylline, a long-acting beta agonist [LABA] 
alone), or a combination drug with a LABA and an 
inhaled glucocorticoid 
• 
12+ months of data available in the integrated EHR data 
prior to date of screening 
Exclusion Criteria (screening question) for COPD cohort 
• Inability/Unwillingness to use the required devices, or 
• 
Inability to read and understand English 
Exclusion Criteria (screening question) for Asthma cohort 
• 
Inability/Unwillingness to use the required devices, or 
• 
Inability to read and understand English, or 
• 
Diagnosis of COPD listed on problem list 
--
Data Source 
Integrated EHR records (primary and specialty care) are the key 
source for retrospective analysis and for identifying patients. Digital 
data collection from patient reports, devices, and sensors over six 
months are the key source for the prospective analysis. The full 
data integration will be accomplished in two stages. 
-
-
Data Analysis Methods 
• Spirometry 
0 
Change from baseline in FEV1 
• Activity 
0 
Median/mean steps per day 
0 
Median/mean daily activity level based on vector 
magnitude units (VMUs) 
• PROactive total score and difficulty domain score (C-F7PAC) 
• 
E-RS:COPD symptoms Exacerbations (COPD cohort only) 
0 
EXACT-defined events 
• 
HCRU 
0 
Median/mean number of primary care visits for 
COPD/asthma conditions 
0 
Median/mean number of secondary care visits 
(inpatient, urgent care and ED visits) for 
COPD/asthma conditions 
0 
Median/mean number of all primary care visits 
I 
0 
Median/mean number of all secondary (inpatient, 
urgent care and ED visits) care visits 
7 

o 
Summary of new prescriptions for any COPD/asthma 
treatments 
o 
Number of days in hospital for COPO/asthma 
o 
Number of albuterol inhalers (adjusted to 
equivalence of 200 actuations) prescribed 
• 
ePRO 
o 
Mean change from baseline in CAT (COPO cohort) 
o 
Mean change from baseline in ACT (asthma cohort) 
All PRO data will be collected via electronic platform 
Further details and exploratory analyses describing patterns of 
cohort and individual changes will be described in the full statistical 
and analysis plan. 
All analyses will be performed using SAS v9.4 (SAS Institute, Inc., 
Cary, NC, USA). These will be described in more detail in the full 
statistical analysis plan. 
Sample Size and Power 
This study aims to evaluate the patient experience with new data 
collection methods and the association between new methods and 
the EHR-defined variables regarding disease severity and healthcare 
resource utilization, therefore no comparisons or hypothesis testing 
will be performed. In order to collect adequate information about 
the feasibility of these new data collection methods, approximately 
200 
 patients from the integrated 
delivery network (ION) will participate in the study (100 in each 
group COPO and asthma). If we assume a dropout rate of at most 
25%, we will have complete data on at least 150 patients, which will 
be sufficient to address feasibility of the new collection methods in 
two different cohorts. In addition, since this is a pilot study to 
assess feasibility of an intervention al study that would use the data 
capture methods, a formal power calculation is not required. 
Limitations 
Participants included in this study will be selected from among 
those within the 
 ION, therefore may not be 
representative of a sample of all COPO and asthma patients from 
the US. There will likely be a selection bias based on which 
patients are willing to participate in a study with multiple devices 
and due to established inclusion/exclusion criteria. Medication use 
and activity will be monitored using sensors so there is a risk that 
the patient's behavior may be altered. 
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TABLE OF CONTENTS 
PAGE 
1 
INTRODUCTION/BACKGROUND ...... ............................................ .. ....... .... .... ..... .. ... ..... 11 
2 
OBJECTIVES ........................... .. ........ ......... ........ .... .. ....... ..... .. .. .. .... ..... ..... ... ........ ..... . 11 
2.1 
General Objective .................. ... .. .. .... .. ...... .... .. .. .. ... .. ..... ................ ................ 11 
2.2 
Specific Objectives ................. ... ... .... .. .. ......................... ... ............. .. .......... ... 1 ·1 
2.3 
Information regarding devices ... .............. ......... .. .. .. .... .......... .... ............ .. ...... 11 
3 
RESEARCH METHODOLOGY ..... .. ... ........... .... .... .. ..... .. ....... ..... ....... ....... ......... ........ .... . 12 
3.1 
Study Design ........ ..... .. ............ ... .. .... .. ........................... ...... ......... ............. 12 
3.2 
Study Population ...................................... .. ............. .. .................. .. ...... .... ..... ·12 
3.2.1 
Eligibility Criteria ........................ ........ .... ......... .. ............................. 12 
3.2.1.1 
Inclusion Criteria ...... ............ ........ .......... ..... .... ............ . 12 
3.2.2 
Sampling ................................... ....... .. .. .................... .. .......... .. .. ..... 13 
3.3 
Study Visits .................................................... .... ..... ..... .. ... .......................... 14 
3.3.1 
Recruitment .............................. .... ... ... ..... ... .... ... ... ... .... .. .... .... ...... . 14 
3.3.2 
Baseline Visit ............................. .... ... ... .. ........ ... .......... .. ............ ..... 14 
3.3.3 
Six Month Visit .......................... ........... .. ........... ......... .. ................ . 14 
3.4 
Study Duration ................................................................ ............................ . 14 
3.4.1 
Approximate Duration of Subject Participation .. .... ............................ 14 
3.4.2 
Approximate Duration of Study ....................... ........... .. .............. .. ... 14 
3.5 
Data Source/ Data Collection .................................................. ...... ................. 14 
3.6 
Endpoints ............................................................................ ..... ........ .. .... .... . 15 
3.7 
Sample Size/ Power Calculation ........................................... .... ... ...... .......... .. .. 15 
4 
DATA ANALYSIS CONSIDERATIONS .. .. .... ......... .. ........ ... .... .. ... .. .. .. ......... .... .. .. ... ....... ..... 16 
5 
LIMITATIONS ..... .. ... ..... .............. ...................... ...... ... .... .................... ............. ... .. ..... 16 
6 
STU DY CON DUCT, MANAGEMENT & ETHICS ..... ......... .......... .... .. .. ..... .. ....... ... .. ....... ... ... 17 
6.1 
Ethics Committee/IRS Approval .......... .... .. ... ........ ..... ....................................... 17 
6.2 
Informed Consent ................................ ... .... ....... .. ... ..... .. .... .. ...... .. ... ........... ... 17 
6.3 
Data Protection ...................................... ................ ......... .. .... .... .. ................ . 17 
6.4 
Personally Identifiable Information (PII) .... ...... ....... .............................. .... .. ... .. 17 
6.5 
Adverse Event (AE), Pregnancy Exposure, and Incident Reporting ..... ... .. ... .. .. ... ... 19 
7 
EXTERNAL INVOLVEMENT ....................................................................................... .. 20 
7.1. 
Third Party Suppliers ........................................................................... ... ...... . 20 
7.2 
External Expert/Health Care Professionals (Consultants & Research Pis) ....... .. .. .. 21 
8 
PROTECTION OF HUMAN SUBJECTS ............................. ............ .. ....... ... .... ................... 21 
8.1 
Informed Consent and HIPAA Authorization ..... ... ....... .. .. .. ...... .......................... 21 
8.2 
Protection of Human Subjects Against Risks .... ................ ............. .. .................. 21 
APPENDIX 1. SCHEMATIC OF A PROSPECTIVE STUDY: ....... .. ........ ..... ........... .......... ...... .. .. .... . 22 
9 

ABBREVIATIONS 
ACT 
Asthma Control Test 
AE 
Adverse event 
CAT 
COPD Assessment Test 
COPD 
Chronic obstructive pulmonary disease 
EHR 
Electronic Health Records 
ERS-COPD 
Evaluating Respiratory ?ymptoms Jn COPD 
--
-• 
ePROs 
Electronic patient reported outcomes 
 
 
ION 
Integrated Delivery Network 
IRB 
Institutional Review Board 
PACDC 
Phenomic Analytics Clinical Data Core 
VMUs 
vector magnitude units 
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1 
INTRODUCTION/BACKGROUND 
Flectronic health records (EHR) are becoming more common in clinical practice in the United 
States. This study aims to assess the feasibility of collecting increasing amounts of clinical study 
data from patients (e.g. sensor and web/app based methods) and their EHR to facilitate more 
efficient and meaningful research with acceptable quality. 
2 
OBJECTIVES 
2.1 
General Objective 
To recruit small cohorts (n=lO0 each) of chronic obstructive pulmonary disease (COPD) and 
asthma patients from their usual healthcare environment to gain experience with novel, digital 
data collection methods combined with EHR extraction to explore feasibility of larger real-world 
studies. Overall, we hope to assess how the use of EHR may be beneficial in recruiting 
populations for future clinical trials. 
2.2 
Specific Objectives 
• 
To evaluate how representative the consented, study population is when compared to 
the eligible population. 
• 
To develop a monitoring dashboard for integration of data from various devices 
• 
To evaluate patient experience, data quality and consistency with novel, patient-data 
collection methods: 
o 
Mobile spirometry 
o 
Sensor for monitoring rescue medication use 
o 
Sensor for monitoring maintenance medication use 
o 
Physical activity monitor 
o 
Electronic patient reported outcomes (ePROs) - monthly CAT (COPD cohort), 
ACT (asthma cohort) 
• 
monthly PROactive - using the C-PPAC 
• 
For COPD only: EXACT PRO daily symptoms [ERS-COPD] 
• 
To assess the relationships between EHR-based healthcare utilization (ambulatory care 
visits and hospitalizations for COPD or asthma exacerbations) and lab measures 
(specified below) with patient data remotely collected via methods outlined in previous 
bullet, for example. 
o 
EHR spirometry 
o 
Blood WBC, eosinophils, neutrophils (number and%) 
o 
Other blood biomarker samples if available (e.g. fibrinogen, CRP, periostin, 
sRAGE etc) 
2.3 
Information regarding devices 
All the data collected from the devices in this study listed above (i.e. mobile spirometry and 
actigraphy) are for research use only. This means that the data cannot be used for clinical 
patient management or as a primary clinical outcome measure. 
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3 
RESEARCH METHODOLOGY 
3.1 
Study Design 
This is a prospective study that will include two cohorts of patients (COPD and asthma) 
identified via EHR database analyses, study provider referral (COPD and asthma diagnoses with 
and without specialist confirmation), or recruited from sites of usual care. Participants will 
attend two visits with study team members at O and approximately 6 months, as most data will 
be captured either remotely via sensors and devices provided by GSK to the patients or via a 
data pull of EHR data. At the baseline visit, study team members will obtain written informed 
consent, distribute study devices, and provide instruction for proper use of study devices and 
platforms. Approximately six months later, at the second visit, the patient will return study 
devices. Patients will then be called to complete an exit interview to provide relevant feedback 
on the study. 
3.2 
Study Population 
3.2.1 
Eligibility Criteria 
3.2.1.1 Inclusion Criteria 
All patients will be selected based on the following criteria in EHR. 
Inclusion Criteria for COPD cohort: 
To be eligible to participate in this study, a subject must meet all of the following criteria: 
• 
Provide signed and dated informed consent form. 
• 
Be willing to comply with all study procedures and be available for the duration of 
the study. 
• 
Age~ 40 
• 
Diagnosed with COPD, defined as COPD listed on the patient's problem list and one 
of the following: 
o 
At least one inpatient hospitalization with a COPD diagnosis listed as the 
primary or secondary diagnosis (J41.x, J42.x, J44.x [chronic bronchitis], J43.9 
[emphysema] or J44.9 [Chronic obstructive pulmonary disease, 
unspecified]) in the last 12 months OR 
o 
At least one emergency room encounter with a COPD diagnosis (J41.x, J42.x, 
J44.x, J43.9, J44.9) listed as the primary or secondary diagnosis in the last 12 
months OR 
o 
At least two encounters of any combination of the following (each must be a 
distinctly different event with different dates of service): 
• 
an outpatient encounter with a diagnosis of COPD exacerbation 
(J44.1), Acute bronchitis (J20.x), or bronchitis (J40) listed as the 
primary or secondary diagnosis in the last 12 months, OR 
• 
an urgent care encounter with a COPD diagnosis (J41.x, J42.x, J44.x, 
J43.9, J44.9) listed as the primary or secondary diagnosis in the last 12 
months 
., 
At least one order for an inhaled COPD medication during the prior year 
12 

• 
12+ months of data available in the integrated EHR data prior to date of screening 
Inclusion Criteria for Asthma cohort 
• 
Provide signed and dated informed consent form. 
• 
Be willing to comply with all study procedures and be available for the duration of 
the study. 
• 
Age~ 18 
• 
Diagnosed with asthma, defined as asthma listed on the patient's problem list and 
one of the following: 
o 
At least one inpatient hospitalization with an asthma diagnosis (J45.x) listed 
as the primary or secondary diagnosis in the last 12 months OR 
o 
At least one emergency room encounter with an asthma diagnosis (J45.x) 
listed as the primary or secondary diagnosis in the last 12 months OR 
o 
at least two urgent care encounters, with different dates of service, with an 
asthma diagnosis (J45.x) listed as the primary or secondary diagnosis in the 
last 12 months OR 
o 
At least three or more prescriptions or prescription refills in the past 12 
months for any combination of the following: an inhaled glucocorticoid with 
or without a second controller (Montelukast, Theophylline, a long-acting 
beta agonist [LABA] alone), or a combination drug with a LABA and an 
inhaled glucocorticoid 
• 
12+ months of data available in the integrated EHR data prior to date of screening 
Exclusion Criteria (screening question) for COPD cohort 
• 
Inability/Unwillingness to use the required devices, or · 
• 
Inability to read and understand English 
Exclusion Criteria (screening question) for Asthma cohort 
• 
Inability/Unwillingness to use the required devices 
• 
Inability to read and understand English 
• 
Diagnosis of COPD listed on problem list 
3.2.2 
Sampling 
 located in 
 has a service area that is 
largely rural, mostly Caucasian, remarkably stable population (i.e., a very low out~migration 
rate), and a higher percentage ·of elderly patients (aged 65+) than the national average. 
 catchment area is one of the oldest and sickest in the nation in terms of multiple co-
morbidities. 
Patients will be selected based on the criteria previously described. 
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3.3 
Study Visits 
3.3.1 
Recruitment 
The study team will utilize three recruitment methods. The first method is to have a Phenomic 
Analytics Clinical Data Core (PACDC) data broker identify potential participants through a data 
pull of EHR data or by review of 
 clinical 
dashboard. The second method is for study providers to refer eligible patients to the study 
team. The third method will have a study team member review the pulmonary clinics schedules 
and identify eligible patients. Potential subjects will be invited to participate. 
3.3.2 
Baseline Visit 
A baseline clinic visit will be scheduled with interested patients and a study team member. At 
the visit, the potential participants will be informed of all pertinent details, risks, and benefits of 
the study via the study consent form. A study team member will answer any patient questions 
and patients will be given adequate time to consider participation. Written informed consent 
will be obtained using the study consent form. After consent, the participant will receive study 
devices and training on proper use ofthe devices. Patient vitals including height and weight will 
be collected by study staff. Participants will complete a baseline questionnaire. Data will be 
collected remotely from the devices and platforms for six months. 
3.3.3 
Six Month Visit 
After six months(+/- 2 weeks), a second visit will be scheduled with the participant and a study 
team member. At the second visit, the participant will return the study devices and will 
complete an exit interview to obtain relevant feedback from the patient's perspective on the 
study. Exit interviews will be performed by 
 personnel. 
3.4 
Study Duration 
3.4.1 
Approximate Duration of Subject Participation 
Subjects will participate in the study for approximately 6 months. 
3.4.2 
Approximate Duration of Study 
200 patients will be enrolled over an eight-month period, including 100 in the asthma cohort 
and 100 in the COPD cohort. Each patient will be followed for approximately six months after 
consent and enrollment into the study. 
3.5 
Data Source / Data Collection 
Integrated EHR records (primary and specialty care) are the key source for retrospective 
analysis and for identifying patients. Digital data collection from patient reports, devices, 
sensors, and EHR records over six months are the key sources for the prospective analysis. The 
full data integration will happen in two stages and a summary of variables to be extracted in 
each stage is included in Section 6.4. The study database will be housed on a third-party 
vendor's secure network. In the initial data integration stage and at the baseline visit, the study 
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team member will manually enter patient information (including name, MRN, date of birth, 
gender, ethnicity, date of consent, height, and weight) into the study portal built into the study 
tablet. The information entered into the study portal will calibrate the predictive formulas in 
the study devices and flow to the study database on the third-party vendor's secure network. 
Patients will then take the study devices home and use them as instructed. Data from the study 
devices, including the mobile spirometry device, the sensors for rescue and maintenance 
medications, activity monitors, and the ePRO platform will flow directly to the database on 
Vendor A's network. During stage one of the data integration, no EPIC data will be sentto the 
study database on the third-party vendor's secure network. 
During stage two of the data integration, EHR data will be extracted and combined with device 
data in the database housed on Vendor A's network. Vendor A will de-identify the study 
dat.ibase and send the data set to Vendor 8. 
 staff will administer a study Exit 
Interview at the follow-up visit asking participants to provide feedback on the study, the study 
devices, and ePRO platform. 
 data is part of the mini-sentinel monitoring system which means their 
data set meets standard criteria for data integrity and quality. 
3.6 
Endpoints 
We will be measuring the following: 
• 
Spirometry 
• 
Activity (Steps and daily activity) 
• 
Patient experience of physical activity 
• 
COPD symptoms Exacerbations {COPD cohort only) 
• 
Rescue and maintenance medication use 
• 
Primary care and secondary care visits specific to each cohort and in general, 
• 
Number of days in hospital, new prescriptions, number of albuterol inhalers specific to 
each cohort 
• 
CAT (COPD cohort) and ACT (asthma cohort) 
• 
Exit Interviews 
3.7 
Sample Size/ Power Calculation 
This study aims to evaluate the feasibility of measuring patient experience with new data 
collection methods and the association between new methods and the EHR-defined variables 
regarding disease severity and healthcare resource utilization, therefore no comparisons or 
hypothesis testing will be performed. In order to collect adequate information about the 
feasibility of these new data collection methods, approximately 200 
 
 patients will participate in the study (100 in each group COPD and asthma). If we assume 
a dropout rate of at most 25%, we will have complete data on at least 150 patients, which will 
be sufficient to address feasibility of the new collection methods in two different cohorts. In 
addition, since this is a pilot study to assess feasibility of an interventional study that would use 
the data capture methods, a formal power calculation is not required. 
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4 
DATA ANALYSIS CONSIDERATIONS 
Descriptive statistics will be presented as frequency and percentages, means and standard 
deviations, medians and interquartile range (IQR), and for categorical variables, normally 
distributed and non-normally distributed continuous variables, respectively. Spearman 
correlations will also be assessed between endpoints. The following will be analyzed over the 
study period: 
• 
Spirometry (mobile and clinic) 
o 
Change from baseline irr FEV1 
• 
Activity 
o 
Median/mean steps per day 
o 
Median/mean daily activity level based on vector magnitude units (VMUs) 
• 
PROactive total score and subdomains Symptoms 
• 
E-RS:COPD symptoms Exacerbations (COPD cohort only) 
o 
EXACT-defined events 
• 
HCRU 
o 
Median/mean number of primary care visits for COPD/asthma conditions 
o 
Median/mean number of secondary care visits (inpatient, urgent care and ED 
visits) for COPD/asthma conditions -
o 
Median/mean number of all primary care visits 
o 
Median/mean number of all secondary (inpatient, urgent care and ED visits) care 
visits 
o 
Summary of new prescriptions for any COPD/asthma treatments 
o 
Number of days in hospital for COPD/asthma 
o 
Number of albuterol inhalers (adjusted to equivalence of 200 actuations) 
prescribed 
• 
ePRO 
o 
Mean change from baseline in CAT (COPD cohort) 
o 
Mean change from baseline in ACT (asthma cohort) 
All analyses will be described in more detail in the ful l statistical analysis plan. 
S 
LIMITATIONS 
Participants included in this study will be selected from among those within the 
 
 {ION), therefore may not be representative of a sample of all COPD and asthma 
patients from the US. There will likely be a selection bias based on which patients are willlng to 
participate in a study with multiple devices. Medication use and activity will be monitored 
using sensors so there is a risk that the patient's behavior may be altered. 
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6 
STUDY CONDUCT, MANAGEMENT & ETHICS 
6.1 
Ethics Committee/I RB Approval 
The study will be submitted for Institutional Review Board (IRB) review. 
6.2 
Informed Consent 
All participants will provide signed and dated informed consent prior to initiation of any study 
activities via the study consent form. 
6.3 
Data Protection 
All data collected in this study will be strictly confidential in accordance with all appropriate 
legislation. Data from study devices and ePROs will be encrypted and automatically transmitted 
to Vendor A. The portal that the study staff will enter patient information into during stage one 
of the data integration, including dates, participant names, MRNs, date of birth, gender, and 
ethnicity will be reviewed and approved by 
 EHR data, 
including PHI such as names, dates, and MRNS, will be encrypted and sent to Vendor A via a 
 approved, secure portal. Vendor A's Insight Platform maintains a HITRUST 
certification to protect patient data. Vendor A will integrate the data from study devices, 
ePROs, and 
 on their secure network. Vendor A will de-identify the integrated 
study data set and transfer the de-identified data set to Vendor B. 
Study staff will be instructed to maintain complete confidentiality of all collected data. Patient 
files will be kept on secure servers. The final study report will not contain any patient 
identifying information. Participants will be assigned a unique participant number in the final 
data set to ensure confidentiality and anonymity. Interview transcripts will be identified by this 
unique participant number and will not have any identifiers associated with the individual. 
6.4 
Personally Identifiable Information (PII) 
The final data set will be de-identified and will not contain PHI. However, Vendor A will have 
access to participant names, dates, date of birth, and MRNs to integrate data from multiple data 
sources including study device data, ePRO, EHR data, and Exit Interview transcripts. Vendor A will 
remove PHI elements from the dataset. PHI accessed for recruitment will only be seen by 
 staff. The final data set, housed by Vendor B, will be de-identified. 
The data in the table below, including relevant dates, will be collected. The table also outlines 
who will have access to each type of data during each stage of data integration. 
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Stage One - Data Integration 
 
GSK 
Vendor A 
Vendor B 
Names 
X 
X 
-
Medical record number 
X 
X 
--
Telephone number 
X 
Date of birth/date of death 
X 
X 
Height and weight 
X 
X 
X 
X 
Information relevant to all 
X 
encounters, 
admissions/discharges, clinical 
procedures, medications 
administered, problem list 
entries, and lab values 
--
Baseline demographic variables 
X 
X 
of patients (age, sex, ethnicity, 
tobacco use, comorbidities) 
Clinical outcomes and 
X 
procedural related 
complications 
Information from study devices, 
X 
X 
X 
X 
sensors, and electronic 
platforms 
Information gather from patient 
X 
X I 
X 
X 
interviews at study visits 
I 
I 
Stage Two - Data integration 
 
GSK I 
Vendor A I Vendor B 
Names 
X 
I 
X 
I 
18 
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Medical record number 
X 
X 
Telephone number 
X 
-
---
Date of birth/date of death 
X 
X 
Height/ Weight 
X 
X 
X 
X 
Information relevant to all 
X 
X 
X 
X 
encounters, 
admissions/discharges, clinical 
procedures, medications 
administered, problem list 
entries, and lab values 
Baseline demographic variables 
X 
X 
X 
X 
of patients (age, sex, ethnicity, 
tobacco use, comorbidities) 
Clinical outcomes and 
X 
X 
X 
X 
procedural related 
complications 
Information from study devices, 
I 
X 
X 
X 
X 
sensors, and electronic 
I 
platforms 
Information gather from patient 
X 
X 
X 
X 
interviews. at study visits 
Records of data generated in the course of the study shall be retained for at least 6 years and 
could be used for future research studies submitted and approved by the IRB. 
6.5 
Adverse Event (AE), Pregnancy Exposure, and Incident Reporting 
While this study does not involve the direct solicitation of adverse experience information, it is 
possible that participants could spontaneously describe potential adverse events that occurred 
during the course of their normal clinical care. 
As part of the site orientation process, study team members will be trained in the recognition of 
potentially-reportable adverse events. 
19 

If an AE (serious or non-serious) or product complaint is reported spontaneously by a subject 
during the course of the study and the subject associates the AE with any specifically named GSK 
product, the following AE reporting process will be completed: 
• 
The site staff will complete the AE reporting form (including the patient study ID 
number, their age and sex, the patient's description of the adverse event, and the 
product the patient named). 
The site staff will transmit the report to the GSK study team within 24 hours of being made aware 
of the AE. 
Patients will be asked about adverse events related to the use of the devices provided during the 
study (mobile spirometer, device sensor, activity monitor and tablet) at regular intervals via the 
study provided tablet. These data will not be monitored in real time and patients will be educated 
on the need to contact their physician directly should they have any medical concern. 
7 
EXTERNAL INVOLVEMENT 
7 .1 
Third Party Suppliers 
• 
Accenture (device integration, EHR integration) 
Accenture, LLP 
1160 West Swedesford Road 
Berwyn, PA, 19312 
USA 
• 
Medidata (ePRO, data and visualization platform) 
Medidata Solutions, Inc. 
350 Hudson Street, 9th Floor 
New York, NY 10014 
USA 
• 
ActiGraph (activity monitors) 
49 East Chase Street. 
Pensacola, FL 32502 
USA 
• 
Propeller Health (sensors for MDI and DPI) 
634 West Main Street, Suite 102 
Madison, WI 53703 
USA 
e 
MIR (mobile spirometry) 
20 

5462 S. Westridge Drive 
New Berlin, WI 53151 
USA 
7.2 
External Expert/Health Care Professionals (Consultants & Research Pis) 
 MD, PhD. 
8 
PROTECTION OF HUMAN SUBJECTS 
8.1 
Informed Consent and HIPAA Authorization 
The investigator will provide for the protection of the subjects by following all applicable 
regulations. The informed consent form will be submitted to the IRB for review and approval. 
Before any procedures specified in this protocol are performed, a subject must: 
• 
Be informed of all pertinent aspects of the study and all elements of informed consent. 
• 
Be given time to ask questions and time to consider the decision to participate. 
• 
Voluntarily agree to participate in the study. 
• 
Sign and date an I RB-approved informed consent form. 
We are requesting a partial waiver of HIPAA authorization for pre-screening and contacting 
patients about the study will be requested by the IRB to allow the identification of potentially 
eligible participants from the medical record. 
8.2 
Protection of Human Subjects Against Risks 
There is a risk of loss of confidentiality as PHI will be collected as part of the study. To minimize 
this risk, hard copy data will be stored in a locked environment that is only accessible only to 
the study team members and electronic data will be stored on a secure network (either 
 or Vendor A's HITRUST certified network). The portal into which study staff will 
enter patient information, including PHI, during visit one and stage one ofthe data integration 
will be reviewed and approved by the 
 EHR data, 
including PHI, will be sent to Vendor A through a secure portal approved by 
 
governance during stage two of the data integration process. Vendor A will de-identify the 
dataset before sending the data set to Vendor B. All data transmissions will be encrypted. Only 
aggregate data without personal identifiers will be included when presenting results or 
submitting manuscripts for publication. 
All subjects will be trained on the use of each device - it is important that all instructions be 
followed to minimize potential risks due to misuse. 
21 
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Appendix 1. Schematic of a Prospective Study: 
Clinic Visit 1 
Day l 
During the 6-
month study 
period 
Clinic Visit 2 
Month 6 
• 
Obtain informed consent 
• 
Screen potential participants by inclusion and exclusion criteria 
• 
Demonstrate devices 
• 
Baseline data collection 
• 
Perform mobile spirometry weekly 
• 
Wear the activity monitor daily 
• 
Complete the diary card daily (for COPD subjects) 
• 
Complete the CAT/ACT monthly 
• 
Attach sensors to rescue and maintenance inhalers {where 
appropriate) 
• 
Exit Interview 
• 
Retrieval of devices 
22 

.GlaxoSmithKline 
CONFIDENTIAL 
HEALTH OUTCOMES STUDY PROTOCOL 
UNIQUE IDENTIFIER 
HO-17-17827 / 207223 
FULL TITLE 
Enabling Innovative Respiratory Real World Evidence 
Generation: Sensor and EHR Integration Pilot Study 
ABBREVIATED TITLE 
Sensor Pilot 
FINAL PROTOCOL APPROVED 
DD-MMM-YYYY 
{Enter date of Senior Line Manager approval signature) 
SPONSORSHIP 
Supported 
DIVISION 
Pharma 
BUSINESS UNIT 
Research & Development 
DEPARTMENT 
US VEO 
STUDY ACCOUNTABLE PERSON 
 
CONTRIBUTING AUTHORS 
 
 -
others TBD 
I INDICATION 
I Asthma and COPD 
REVISION CHRONOLOGY: 
Version Date 
Document Type 
Change(s) since last version 
Enter original protocol FPA 
Original 
n/a 
Copyright 2016 the GlaxoSmithKline group of companies. All rights reserved. 
Unauthorized copying or use of this information is prohibited. 
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Description: 
sensor pilot 
Unique Identifier: HO-17-17827 / 207223 
SPONSOR SIGNATORY 
Martin Marcinia
VP CEVEO 
Date 
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Description: 
Sensor Pilot 
Unique Identifier: HO-17-17827 / 207223 
Investigator Protocol Agreement Page 
• 
I confirm agreement to conduct the study in compliance with the protocol. 
• 
I ac;knowledge that I am responsible for overall study conduct. 1. agree to personally 
conduct or supervise the described clinical study. 
• 
I agree to ensure that all associates, colleagues and employees assisting in the conduct 
of the study are informed about their obligations. Mechanisms are in place to ensure 
that site staff receives the appropriate information throughout the study. 
Investigator Name: 
Investigator Signature 
Date (DD-MMM-YYYY} 
3 
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PROTOCOL SYNOPSIS 
Unique Identifier 
Abbreviated Title 
Rationale 
Objectives 
(Primary, Secondary) 
Study Design 
Study Population and 
Sampling Methods 
H0-17-17827 / 207223 
Sensor Pilot 
This is a pilot study exploring the opportunity for accessing data 
directly from electronic health records (EHR) and integrating with 
data from various sensors and mobile devices. The goal is to assess 
how to scale these methods for use in interventional trials. 
• 
To assess how the use of EHR may be beneficial in recruiting 
populations for future clinical trials, 
• 
To evaluate how representative the consented, study population 
is when compared to the eligible population, 
• 
To develop a monitoring dashboard for integration of data from 
various sources, 
• 
To evaluate patient experience, data quality and consistency with 
novel, patient-data collection methods: 
o 
Mobile spirometry 
o 
Sensor for monitoring rescue medication use 
o 
Sensor for monitoring maintenance medication use 
o 
Physical activity monitor 
o 
Electronic patient reported outcomes (ePROs) 
• 
To assess the relationships between EHR-based healthcare 
utilization (ambulatory care visits and hospitalizations for COPD or 
asthma exacerbations) and lab measures (specified below) with 
patient data remotely collected via methods outlined in previous 
bullet. 
A prospective study that will include two cohorts of patients (COPD 
and asthma) identified via EHR database analyses recruited from 
sites of usual care. Participants will attend two visits at O and 6 
months and data will be collected via sensors and mobile devices 
between the visits. 
All patients will be selected based on the following criteria. 
Inclusion Criteria for COPD cohort: 
To be eligible to participate in this study, a subject must meet all of 
the following criteria: 
• 
Provide signed and dated informed consent form. 
• 
Be willing to comply with all study procedures and be 
available for the duration of the study. 
• 
Age~ 40 
• 
Diagnosed with COPD, defined as COPD listed on the 
patient's problem list and one of the following: 
o 
At least one inpatient hospitalization with a COPD 
diagnosis listed as the primary or secondary 
4 
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diagnosis (J41.x, J42.x, J44.x [chronic bronchitis], 
J43.9 [emphysema] or J44.9 [Chronic obstructive 
pulmonary disease, unspecified]) in the last 12 
months OR 
o 
At least two outpatient encounters with a diagnosis 
of COPD exacerbation (J44.1), Acute bronchitis 
(J20.x), or bronchitis (J40) listed as the primary or 
secondary diagnosis, with different dates of service 
in the last 12 months OR 
o 
At least one emergency room encounter with a 
COPD diagnosis (J41.x, J42.x, J44.x, J43.9, J44.9) 
listed as the primary or secondary diagnosis in the 
last 12 months OR 
o 
At least two urgent care encounters with different 
dates of service, with a COPD diagnosis (J41.x, J42.x, 
J44.x, J43.9, J44.9) listed as the primary or secondary 
diagnosis in the last 12 months 
• 
At least one order for an inhaled COPD medication during 
the prior year. 
• 
12+ months of data available in the integrated EHR data 
prior to date of screening. 
Inclusion Criteria for Asthma cohort 
• 
Provide signed and dated informed consent form. 
• 
Be willing to comply with all study procedures and be 
available for the duration of the study. 
• 
Age~ 18 
• 
Diagnosed with asthma, defined as asthma listed on the 
patient's problem list and one of the following: 
o 
At least one inpatient hospitalization with an asthma 
diagnosis (J45.x) listed as the primary or secondary 
diagnosis in the last 12 months OR 
o 
At least one emergency room encounter with an 
asthma diagnosis (J45.x) listed as the primary or 
secondary diagnosis in the last 12 months OR 
o 
At least two urgent care encounters, with different 
dates of service, with an asthma diagnosis (J45.x) 
listed as the primary or secondary diagnosis in the 
last 12 months OR 
o 
At least three or more prescriptions or prescription 
refills in the past 12 months for any combination of 
the following: an inhaled glucocorticoid with or 
without a second controller (Montelukast, 
Theophylline, a long-acting beta agonist [LABA] 
5 

alone), or a combination drug with a LABA and an 
inhaled glucocorticoid 
• 
12+ months of data available in the integrated EHR data 
prior to date of screening 
Exclusion Criteria (screening question) for COPD cohort 
• Inability/Unwillingness to use the required devices, or 
• 
Inability to read and understand English 
Exclusion Criteria (screening question) for Asthma cohort 
• 
Inability/Unwillingness to use the required devices, or 
• Inability to read and understand English, or 
• 
Diagnosis of COPD listed on problem list 
Data Source 
Integrated EHR records (primary and specialty care) are the key 
source for retrospective analysis and for identifying patients. Digital 
data collection from patient reports, devices, and sensors over six 
months are the key source for the prospective analysis 
Data Analysis Methods 
• Spirometry 
0 
Change from baseline in FEV1 
• Activity 
0 
Median/mean steps per day 
0 
Median/mean daily activity level based on vector 
magnitude units {VMUs) 
• PROactive total score and difficulty domain score {C-PPAC) 
• 
E-RS:COPD symptoms Exacerbations {COPD cohort only) 
0 
EXACT-defined events 
• 
HCRU 
0 
Median/mean number of primary care visits for 
COPD/asthma conditions 
0 
Median/mean number of secondary care visits 
(inpatient, urgent care and ED visits) for 
COPD/asthma conditions 
0 
Median/mean number of all primary care visits 
0 
Median/mean number of all secondary (inpatient, 
urgent care and ED visits) care visits 
0 
Summary of new prescriptions for any COPD/asthma 
treatments 
0 
Number of days in hospital for COPD/asthma 
0 
Number of albuterol inhalers (adjusted to 
equivalence of 200 actuations) prescribed 
• ePRO 
0 
Mean change from baseline in CAT {COPD cohort) 
0 
Mean change from baseline in ACT (asthma cohort) 
6 

All PRO data will be collected via electronic platform 
Further details and exploratory analyses describing patterns of 
cohort and individual changes will be described in the full statistical 
and analysis plan. 
All analyses will be performed using SAS v9.4 (SAS Institute, Inc., 
Cary, NC, USA). These will be described in more detail in the full 
statistical analysis plan. 
Sample Size and Power 
This study aims to evaluate the patient experience with new data 
collection methods and the association between new methods and 
the EHR-defined variables regarding disease severity and healthcare. 
resource utilization, therefore no comparisons or hypothesis testing 
will be performed. In order to collect adequate information about 
the feasibility of these new data collection methods, approximately 
200 
 patients from the integrated 
delivery network (IDN) will participate in the study (100 in each 
group COPD and asthma). If we assume a dropout rate of at most 
25%, we will have complete data on at least 150 patients, which will 
be sufficient to address feasibility of the new collection methods in 
two different cohorts. In addition, since this is a pilot study to 
Limitations 
assess feasibility of an interventional study that would use the data 
capture methods, a formal power calculation is not required. 
Participants included in this study will be selected from among 
those within the 
 IDN, therefore may not be 
representative of a sample of all COPD and asthma patients from 
the US. There will likely be a selection bias based on which 
patients are willing to participate in a study with multiple devices 
and due to established inclusion/exclusion criteria. Medication use 
and activity will be monitored using sensors so there is a risk that 
the patient's behavior may be altered. 
7 
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TABLE OF CONTENTS 
1 
INTRODUCTION/BACKGROUND .................................................. ....................... .................... 1.Q9 
2 
OBJECTIVES .... ... ..... .. .... ... ........ ... .................. ... ............... .. ............... .......... ...................... ...... ... ..... 1.Q9 
2.1 
General Objective ............... .. .... ........... ..... ... ... .............. ........ .......................................... .. ..... 1.Q9 
2.2 
Specific Objectives ........... .............................. ..... ...... ................ ........ ..... .. .. .... .... ..... ... .. ...... .... 1.Q9 
3 
RESEARCH METHODOLOGV ..... ..... .......... ..................................... ................. .... .............................. 1.Q9 
3.1 
Study Design .......... ... ....... .... .... ......... ................................................................... ....... ... ....... 1.Q9 
3.2 
Study Population ..... .... ... .... ......... ......... ........ ... ................... ........ ....... .. ........... ..... ...... ...... .... 114-G 
3.2.1 
Eligibility Criteria .. .... .......... ...... .... ........ ............. ........ .. .... ........ ... .. ... ...... .. ............ .... ... ...... 114-G 
3.2.2 
Sampling : .. ... ......... .. ...... ... ....... ... ... ............................ ... ... .... ... ... ...... .... ....... ..... ................ .12.44 
3.3 
Study Visits .... .......... .. .. ......... ...... .... ....... ... ... ... ........... ...... ........... ...... ............. ....... ... ........... 1244 
3.3.1 
Recruitment ............................................................................................................... .12.~-
3.3.2 
Baseline Visit ................. · .................. ........ .................................................................. 1244 
3.3.3 
Six Month Visit. ..................................... ............ ................................ ......................... _Ll_42: 
After six months(+/- 2 weeks), a second visit will be scheduled with the participant and a study 
team member. At the second visit, the participant will return the study devices and will complete 
an exit interview to obtain relevant feedback from the patient's perspective on the study. Exit 
interviews will be performed by 
 personnel. ........................................ ...................... _Ll_42: 
3.4 
Study Duration .............. .................................................................................................... _Ll_42: 
3.4.1 
Approximate Duration of Subject Participation .... ..................................................... _Ll_42: 
3.4.2 
Approximate Duration of Study .............. ............................................. ...................... _Ll_42: 
3.5 
Data Source/ Data Collection .......... ................... ....... ............ .... ...... ..................... .. .............. 1342: 
3.6 
Endpoints .......................................................................................................................... _Ll_42: 
3.7 
Sample Size/ Power Calculation ....................................................................... .. ............ .. 144-d 
4 
DATA ANALYSIS CONSIDERATIONS .................................................. ... ........ .... ... ...... .. .... ............... 144-d 
5 
LIMITATIONS ... ...................... .. ............................... ...... ................ ......... .... ... .......................... .. ... .1§44 
6 
STUDY CONDUCT, MANAGEMENT & ETHICS .............. ............ ..... ............ : ...... .................. ............. .1§44 
6.1 
Ethics Committee/I RB Approval .......... ........... ........... ................... ......................................... .1§44 
6.2 
Informed Consent ..... .. ................ ..................... ................ .................................................... .1§44 
6.3 
Data Protection ... ... ..... .. ....... ... ........ ........................ ............................... .. ........ .. .... ............. .1§44 
6.4 
Personally Identifiable Information (PII) .......... .. ................. ......... ... ......................... ............. . .1§4-a 
6.5 
Adverse Event (AE), Pregnancy Exposure, and Incident Reporting ........... .. ..... ......................... 174-e 
7 
EXTERNAL INVOLVEMENT ................ .. .... .. .. .......... .......... .. .... ...... ....... ..... ...... .. .... .... ...................... 114-e 
7.1 
Third Party Suppliers ........... .. ...... ................ ........ .................................. ........ .............. .... ..... 174-e 
7.2 
External Expert/Health Care Professionals (Consultants & Research Pis) ................................. .1§.4--7 
8 
PROTECTION OF HUMAN SUBJECTS .................................................................................. 184--7 
8.1 
Informed Consent and HIPAA Authorization .................................................................... .1§.4--7 
8 
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8.2 
Protection of Human Subjects Against Risks ................................................................... .1.§.4--7 
Appendix 1. Schematic of a Prospective Study: .................................................................................. .. . 204-9 
ABBREVIATIONS 
ACT 
Asthma Control Test 
AE 
Adverse event 
CAT 
COPD Assessment Test 
COPD 
Chronic obstructive pulmonary disease 
EHR 
Electronic Health Records 
ERS-COPD 
Evaluating Respiratory Symptoms in COPD 
ePROs 
Electronic patient reported outcomes 
 
 
IDN 
Integrated Delivery Network 
IRB 
Institutional Review Board 
PACDC 
Phenomic Analytics Clinical Data Core 
VMUs 
vector magnitude units 
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1 
INTRODUCTION/BACKGROUND 
Electronic health records {EHR) are becoming more common in clinical practice in the United 
States. This study aims to assess the feasibility of collecting increasing amounts of clinical study 
data from patients (e.g. sensor and web/app based methods) and their EHR to facilitate more 
efficient and meaningful research with acceptable quality. 
2 
OBJECTIVES 
2.1 
General Objective 
To recruit small cohorts (n=100 each) of chronic obstructive pulmonary disease {COPD) and 
asthma patients from their usual healthcare environment to gain experience with novel, digital 
data collection methods combined with EHR extraction to explore feasibility of larger real world 
studies. Overall, we hope to assess how the use of EHR may be beneficial in recruiting populations for 
future clinical trials. 
2.2 
Specific Objectives 
• 
To evaluate how representative the consented, study population is when compared to the 
eligible population. 
• 
To develop a monitoring dashboard for integration of data from various devices 
• 
To evaluate patient experience, data quality and consistency with novel, patient-data collection 
methods: 
o 
Mobile spirometry 
o 
Sensor for monitoring rescue medication use 
o 
Sensor for monitoring maintenance medication use 
o 
Physical activity monitor 
o 
Electronic patient reported outcomes {ePROs) - monthly CAT {COPD cohort), ACT 
(asthma cohort) 
• 
monthly PROactive - using the C-PPAC 
• 
For COPD only: EXACT PRO daily symptoms [ERS-COPD] 
• 
To assess the relationships between EHR-based healthcare utilization (ambulatory care visits 
and hospitalizations for COPD or asthma exacerbations) and lab measures (specified below) with 
patient data remotely collected via methods outlined in previous bullet, for example. 
o 
EHR spirometry 
o 
Blood WBC, eosinophils, neutrophils (number and%) 
o 
Other blood biomarker samples if available (e.g. fibrinogen, CRP, periostin, sRAGE etc) 
3 
RESEARCH METHODOLOGY 
3.1 
Study Design 
This is a prospective study that will include two cohorts of patients {COPD and asthma) 
identified via EHR database analyses {COPD and asthma diagnoses with and without specialist 
confirmation), recruited from sites of usual care. Participants will attend two visits with study 
team members at O and approximately 6 months, as most data will be captured either remotely 
via sensors and devices provided by GSK to the patients or via a data pull of EHR data. At the 
baseline visit, study team members will obtain written informed consent, distribute study 
devices, and provide instruction for proper use of study devices and platforms. Approximately 
10 

six months later, at the second visit, the patient will return study devices and complete an exit 
interview to provide relevant feedback on the study. 
3.2 
Study Population 
3.2.1 
Eligibility Criteria 
3.2.1.1 Inclusion Criteria 
All patients will be selected based on the following criteria in EHR. 
Inclusion Criteria for COPD cohort: 
To be eligible to participate in this study, a subject must meet all of the following criteria: 
• 
Provide signed and dated informed consent form. 
• 
Be willing to comply with all study procedures and be available for the duration of 
the study. 
• 
Age 2 40 
• 
Diagnosed with COPD, defined as COPD listed on the patient's problem list and one 
of the following: 
o 
At least one inpatient hospitalization with a COPD diagnosis listed as the 
primary or secondary diagnosis (J41.x, J42.x, J44.x [chronic bronchitis], J43.9 
[emphysema] or J44.9 [Chronic obstructive pulmonary disease, 
unspecified]} in the last 12 months OR 
o 
At least two outpatient encounters with a diagnosis of COPD exacerbation 
(J44.1}, Acute bronchitis (J20.x}, or bronchitis (J40} listed as the primary or 
secondary diagnosis, with different dates of service in the last 12 months OR 
o 
At least one emergency room encounter with a COPD diagnosis (J41.x, J42.x, 
J44.x, J43.9, J44.9} listed as the primary or secondary diagnosis in the last 12 
months OR 
o 
At least two urgent care encounters with different dates of service, with a 
COPD diagnosis (J41.x, J42.x, J44.x, J43.9, J44.9} listed as the primary or 
secondary diagnosis in the last 12 months 
• 
At least one order for an inhaled COPD medication during the prior year 
• 
12+ months of data available in the integrated EHR data prior to date of screening 
Inclusion Criteria for Asthma cohort 
• 
Provide signed and dated informed consent form. 
• 
Be willing to comply with all study procedures and be available for the duration of 
the study. 
• 
Age 2 18 
• 
Diagnosed with asthma, defined as asthma listed on the patient's problem list and 
one of the following: 
o 
At least one inpatient hospitalization with an asthma diagnosis (J45.x} listed 
as the primary or secondary diagnosis in the last 12 months OR 
o 
At least one emergency room encounter with an asthma diagnosis (J45.x} 
listed as the primary or secondary diagnosis in the last 12 months OR 
11 

o 
at least two urgent care encounters, with different dates of service, with an 
asthma diagnosis (J45.x) listed as the primary or secondary diagnosis in the 
last 12 months OR 
o 
At least three or more prescriptions or prescription refills in the past 12 
months for any combination of the following: an inhaled glucocorticoid with 
or without a second controller (Montelukast, Theophylline, a long-acting 
beta agonist [LABA] alone), or a combination drug with a LABA and an 
inhaled glucocorticoid 
• 
12+ months of data available in the integrated EHR data prior to date of screening 
Exclusion Criteria (screening question) for COPD cohort 
• 
Inability/Unwillingness to use the required devices, or 
• 
Inability to read and understand English 
Exclusion Criteria (screening question) for Asthma cohort 
• 
Inability/Unwillingness to use the required devices 
• 
Inability to read and understand English 
• 
Diagnosis of COPD listed on problem list 
3.2.2 
Sampling 
 located in 
 has a service area that is largely 
rural, mostly Caucasian, remarkably stable population (i.e., a very low out-migration rate), and 
a higher percentage of elderly patients (aged 65+) than the national average. 
 
catchment area is one of the oldest and sickest in the nation in terms of multiple co-morbidities. 
Patients will be selected based on the criteria previously described. 
3.3 
Study Visits 
3.3.1 
Recruitment 
Potential participants will be identified by a Phenomic Analytics Clinical Data Core (PACDC) data 
broker through a data pull of EHR data or by review of
 
 clinical dashboard. Potential subjects will be invited to participate. 
3.3.2 
Baseline Visit 
A baseline clinic visit will be scheduled with interested patients and a study team member. At 
the visit, the potential participants will be informed of all pertinent details, risks, and benefits of 
the study via the study consent form. A study team member will answer any patient questions 
and patients will be given adequate time to consider participation. Written informed consent 
will be obtained using the study consent form. After consent, the participant will receive study 
devices and training on proper use of the devices. Participants will complete a baseline 
questionnaire. Data will be collected remotely from the devices and platforms for six months. 
12 
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3.3.3 
Six Month Visit 
After six months(+/- 2 weeks), a second visit will be scheduled with the participant and a study 
team member. At the second visit, the participant will return the study devices and will 
complete an exit interview to obtain relevant feedback from the patient's perspective on the 
study. Exit interviews will be performed by 
 personnel. 
3.4 
Study Duration 
3.4.1 
Approximate Duration of Subject Participation 
Subjects will participate in the study for approximately 6 months. 
3.4.2 
Approximate Duration of Study 
200 patients will be enrolled over an eight-month period, including 100 in the asthma cohort 
and 100 in the COPD cohort. Each patient will be followed for approximately six months after 
consent and enrollment into the study. 
3.5 
Data Source/ Data Collection 
Integrated EHR records (primary and specialty care) are the key source for retrospective 
analysis and for identifying patients. Digital data collection from patient reports, devices, 
sensors, and EHR records over six months are the key sources for the prospective analysis. A 
summary of variables to be extracted is included in Section 6.4. The study database will be 
housed on a third-party vendor's secure network. Data from the study devices, including the 
mobile spirometry device, the sensors for rescue and maintenance medications, activity 
monitors, and the ePRO platform will flow directly to the database on Vendor A's network. EHR 
data will be extracted and combined with device data in the database housed on Vendor A's 
network.' Vendor A will de-identify the study database and send the data set to Vendor B. 
Participants will provide 
 staff with feedback on the study, the study devices, and 
ePRO platform during the study Exit Interview. 
 data is part of the mini-sentinel monitoring system which means their 
data set meets standard criteria for data integrity and quality. 
3.6 
Endpoints 
We will be measuring the following: 
• 
Spirometry 
• 
Activity (Steps and daily activity) 
• 
Patient experience of physical activity 
• 
COPD symptoms Exacerbations (COPD cohort only) 
• 
Rescue and maintenance medication use 
• 
Primary care and secondary care visits specific to each cohort and in general, 
• 
Number of days in hospital, new prescriptions, number of albuterol inhalers specific to 
each cohort 
• 
CAT (COPD cohort) and ACT (asthma cohort) 
• 
Exit Interviews 
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3.7 
Sample Size/ Power Calculation 
This study aims to evaluate the feasibility of measuring patient experience with new data 
collection methods and the association between new methods and the EHR-defined variables 
regarding disease severity and healthcare resource utilization, therefore no comparisons or 
hypothesis testing will be performed. In order to collect adequate information about the 
feasibility of these new data collection methods, approximately 200 
 
 patients will participate in the study (100 in each group COPD and asthma). If we assume 
a dropout rate of at most 25%, we will have complete data on at least 150 patients, which will 
be sufficient to address feasibility of the new collection methods in two different cohorts. In 
addition, since this is a pilot study to assess feasibility of an interventional study that would use 
the data capture methods, a formal power calculation is not required. 
4 
DATA ANALYSIS CONSIDERATIONS 
Descriptive statistics will be presented as frequency and percentages, means and standard 
deviations, medians and interquartile range (IQR), and for categorical variables, normally 
distributed and non-normally distributed continuous variables, respectively. Spearman 
correlations will also be assessed between endpoints. The following will be analyzed over the 
study period: 
• 
Spirometry (mobile and clinic) 
o 
Change from baseline in FEVl 
• 
Activity 
o 
Median/mean steps per day 
o 
Median/mean daily activity level based on vector magnitude units (VMUs) 
• 
PROactive total score and subdomains Symptoms 
• 
E-RS:COPD symptoms Exacerbations (COPD cohort only) 
o 
EXACT-defined events 
• 
HCRU 
o 
Median/mean number of primary care visits for COPD/asthma conditions 
o 
Median/mean number of secondary care visits (inpatient, urgent care and ED 
visits) for COPD/asthma conditions 
o 
Median/mean number of all primary care visits 
o 
Median/mean number of all secondary (inpatient, urgent care and ED visits) care 
visits 
o 
Summary of new prescriptions for any COPD/asthma treatments 
o 
Number of days in hospital for COPD/asthma 
o 
Number of albuterol inhalers (adjusted to equivalence of 200 actuations) 
prescribed 
• 
ePRO 
o 
Mean change from baseline in CAT (COPD cohort) 
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o 
Mean change from baseline in ACT (asthma cohort) 
All analyses will be described in more detail in the full statistical analysis plan. 
5 
LIMITATIONS 
Participants included in this study will be selected from among those within the 
 
 (IDN), therefore may not be representative of a sample of all COPD and asthma 
patients from the US. There will likely be a selection bias based on which patients are willing to 
participate in a study with multiple devices. Medication use and activity will be monitored 
using sensors so there is a risk that the patient's behavior may be altered. 
6 
STUDY CONDUCT, MANAGEMENT & ETHICS 
6.1 
Ethics Committee/lRB Approval 
The study will be submitted for Institutional Review Board (IRB) review. 
6.2 
Informed Consent 
All participants will provide signed and dated informed consent prior to initiation of any study 
activities via the study consent form. 
6.3 
Data Protection 
All data collected in this study will be strictly confidential in accordance with all appropriate 
legislation. Data from study devices and ePROs will be encrypted and automatically transmitted 
to Vendor A. EHR data, including PHI such as names, dates, and MRNS, will also be encrypted 
and sent to Vendor A via a 
 approved, secure portal. Vendor A's Insight Platform 
maintains a HITRUST certification to protect patient data. Vendor A will integrate the data from 
study devices, ePROs, and 
 on their secure network. Vendor A will de-identify 
the integrated study data set and transfer the de-identified data set to Vendor B. 
Study staff will be instructed to maintain complete confidentiality of all collected data. Patient 
files will be kept on secure servers. The final study report will not contain any patient 
identifying information. Participants will be assigned a unique participant number in the final 
data set to ensure confidentiality and anonymity. Interview transcripts will be identified by this 
unique participant number and will not have any identifiers associated with the individual. 
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· 6.4 
Personally Identifiable Information (PII) 
The final data set will be de-identified and will not contain PHI. However, Vendor A will have 
access to participant names, dates, and MRNs to integrate data from multiple data sources 
including study device data, ePRO, EHR data, and Exit Interview transcripts. Vendor A will remove 
PHI elements from the dataset. PHI accessed for recruitment will only be seen by 
 staff. 
The final data set, housed by Vendor B, will be de-identified. 
The data in the table below, including relevant dates, will be collected. The table also outlines 
who will have access to each type of data. 
 
GSI< 
Vendor A 
VendorB 
Names 
X 
X 
Medical record number 
X 
X 
Telephone number 
X 
Date of birth/date of death 
X 
X 
Information relevant to all 
X 
X 
X 
X 
encounters, 
admissions/discharges, clinical 
procedures, medications 
administered, problem list 
entries, and lab values 
Baseline demographic variables 
X 
X 
X 
X 
of patients (age, sex, ethnicity, 
tobacco use, comorbidities) 
Clinical outcomes and 
X 
X 
X 
X 
procedural related 
complications 
Information from study devices, 
X 
X 
X 
X 
sensors, and electronic 
platforms 
Information gather from patient 
X 
X 
X 
X 
interviews at study visits 
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Records of data generated in the course of the study shall be retained for at least 6 years and 
could be used for future research studies submitted and approved by the IRB. 
6.5 
Adverse Event {AE), Pregnancy Exposure, and Incident Reporting 
While this study does not involve the direct solicitation of adverse experience information, it is 
possible that participants could spontaneously describe potential adverse events that occurred 
during the course of their normal clinical care. 
As part of the site orientation process, study team members will be trained in the recognition of 
potentially-reportable adverse events. 
If an AE (serious or non-serious) or product complaint is reported spontaneously by a subject 
during the course of the study and the subject associates the AE with any specifically named GSI< 
product, the following AE reporting process will be completed: 
• 
The site staff will complete the AE reporting form (including the patient study ID 
number, their age and sex, the patient's description of the adverse event, and the 
product the patient named). 
The site staff will transmit the report to the GSI< study team within 24 hours of being made aware 
of the AE. 
Patients will be asked about adverse events related to the use of the devices provided during the 
study (mobile spirometer, device sensor, activity monitor and tablet) at regular intervals via the 
study provided tablet. These data will not be monitored in real time and patients will be educated 
on the need to contact their physician directly should they have any medical concern. 
7 
EXTERNAL INVOLVEMENT 
7.1 
Third Party Suppliers 
• 
Vendor A: Accenture (device integration, EHR integration) 
Accenture, LLP 
1160 West Swedesford Road 
Berwyn, PA, 19312 
USA 
• 
Vendor B: Medidata {ePRO, data and visualization platform) 
Medidata Solutions, Inc. 
350 Hudson Street, 9th Floor 
New York, NY 10014 
USA 
• 
ActiGraph (activity monitors) 
17 

49 East Chase Street. 
Pensacola, FL 32502 
USA 
• 
Propeller Health (sensors for MDI and DPI) 
634 West Main Street, Suite 102 
Madison, WI 53703 
USA 
• 
MIR (mobile spirometry) 
5462 S. Westridge Drive 
New Berlin, WI 53151 
USA 
7.2 
External Expert/Health Care Professionals {Consultants & Research Pis) 
 MD, PhD. 
8 
PROTECTION OF HUMAN SUBJECTS 
8.1 
Informed Consent and HIPAA Authorization 
The investigator will provide for the protection of the subjects by following all applicable 
regulations. The informed consent form will be submitted to the IRB for review and approval. 
Before any procedures specified in this protocol are performed, a subject must: 
• 
Be informed of all pertinent aspects of the study and all elements of informed consent. 
• 
Be given time to ask questions and time to consider the decision to participate. 
• 
Voluntarily agree to participate in the study. 
• 
Sign and date an IRB'-approved informed consent form. 
We are requesting a partial waiver of HIPAA authorization for pre-screening and contacting 
patients about the study will be requested by the IRB to allow the identification of potentially 
eligible participants from the medical record. 
8.2 
Protection of Human Subjects Against Risks 
There is a risk of loss of confidentiality as PHI will be collected as part of the study. To minimize 
this risk, hard copy data will be stored in a locked environment that is only accessible only to 
the study team members and electronic data will be stored on a secure network (either 
 or Vendor A's HITRUST certified network). EHR data, including PHI, will be sent to 
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Vendor A through a secure portal approved by 
 governance. Vendor A will de-
identify the dataset before sending the data set to Vendor B. All data transmissions will be 
encrypted. Only aggregate data without personal identifiers will be included when presenting 
results or submitting manuscripts for publication. 
All subjects will be trained on the use of each device - it is important that all instructions be 
followed to minimize potential risks due to misuse. 
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Appendix 1. Schematic of a Prospective Study: 
Clinic Visit 1 
Day 1 
During the 6-
month study 
period 
Clinic Visit 2 
Month 6 
• 
Obtain informed consent 
• 
Screen potential participants by inclusion and exclusion criteria 
• 
Demonstrate devices 
• 
Baseline data collection 
• 
Perform mobile spirometry weekly 
• 
Wear the activity monitor daily 
• 
Complete the diary card daily (for COPD subjects) 
• 
Complete the CAT/ACT monthly 
• 
Attach sensors to rescue and maintenance inhalers (where 
appropriate) 
• 
Exit Interview 
• 
Retrieval of devices 
20