The Accuracy of Digital Assessment of Performance Trial (ADAPT): Walk Test Study
Conditions: Parkinson Disease, COPD
Sponsor: Radboud University Medical Center

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The Accuracy of Digital Assessment of 
Performance Trial (ADAPT): Walk Test Study 
 
 
 
 
 

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PROTOCOL TITLE ‘The Accuracy of Digital Assessment of Performance Trial (ADAPT): 
Walk Test Study’ 
 
Protocol ID 
NL78292.091.21 
Short title 
ADAPT 
EudraCT number  
Not applicable  
Version 
 V4_15-02-2024 
Date 
 February 15, 2024 
Coordinating investigator/project 
leader 
 
N.M. de Vries, PhD 
Center of Expertise for Parkinson & Movement 
Disorders 
Radboud university medical center 
Department of Neurology 
Nijmegen, The Netherlands 
nienke.devries@radboudumc.nl  
 
A.J. (Alex) van ’t Hul, PhD 
Radboud university medical center, Radboud 
Institute for Health Sciences, Department of 
Respiratory Diseases (Route 614),  
Nijmegen, The Netherlands 
 
Principal investigator(s) (in Dutch: 
hoofdonderzoeker/ uitvoerder) 
 
 
Professor Bastiaan R. Bloem, MD, PhD, FRCPE 
Center of Expertise for Parkinson & Movement 
Disorders 
Radboud university medical center 
Department of Neurology 
Nijmegen, The Netherlands 
Sponsor (in Dutch: 
verrichter/opdrachtgever) 
Radboud university medical center 
Department of Neurology (935) 
PO Box 9101, 6500 HB Nijmegen 
The Netherlands 
Subsidising party 
Verily Life Sciences LCC 
269 E. Grand Avenue 
South San Francisco, CA 94080 USA 
Independent expert (s) 
Dr. Bart van de Warrenburg 
Radboudumc 
Reinier Postlaan 4 
6525 GC Nijmegen 
Tel: 024-3613396 

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PROTOCOL SIGNATURE SHEET 
 
Name 
Signature 
Date 
Sponsor or legal representative: 
 
Prof. Dr. C.J.M. Klijn, MD, PhD 
Head of Department of Neurology 
Radboud university medical center 
Nijmegen  
 
 
Principal Investigator  
 
Prof. Dr. B.R. Bloem, MD, PhD, FRCPE 
Department of Neurology 
Radboud university medical center 
Nijmegen 
 
 
 
 
Revision History 
 
Version 
Date 
Comments 
V1.1 
06 AUG 2021 
Original Release 
V1.2 
07 OCT 2021 
Added a new exclusion criteria; Added additional AE 
definitions; Added Device Deficiency section; Updated 
sample size calculation 
V2 
14 March 2022 
Added an optional home measurement with the 
StepWatch for 2 weeks, added one questionnaire/ 
assessment, specified an exclusion criterion, changed 
assessment of medical history from visit one to visit 
one + visit two.  
V3 
20 July 2022 
Added validation of free living passively recorded data 
as a secondary endpoint, added at home StepWatch 
measurement as obligatory, increased number of PD 
patients to be included 
 
 

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TABLE OF CONTENTS 
 
1. 133 
2. 164 
2.1 Primary Objectives 
14 
2.2 Secondary objectives 
14 
2.3 Exploratory objectives 
15 
3. 186 
4. 208 
4.1 Population (base) 
18 
4.2 Inclusion criteria 
18 
4.3  Exclusion criteria 
18 
4.4 Sample size calculation 
19 
5. 241 
6. 252 
6.1 
252 
6.1.1 Verily Study Watch 
22 
6.2 Summary of findings from non-clinical studies 
23 
6.3 Summary of known and potential risks and benefits 
23 
6.4 
274 
7. 27 
7.1 Fitbit Sense 
24 
7.2 Modus StepWatch 4 
25 
8. 296 
8.1 Study endpoints 
26 
8.1.1. Primary study endpoint 
26 
8.1.2 Secondary study endpoints (if applicable) 
26 
8.2 Study procedures 
26 
8.3 Participant recruitment and procedures 
26 
8.4 Assessments – in clinic 
32 
8.5 
362 
8.6 Timeline 
                                                                                                                    33 

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8.7 Withdrawal of individual subjects 
33 
8.8 Specific criteria for withdrawal (if applicable) 
34 
8.9 
384 
8.9 Follow-up of subjects withdrawn from treatment 
34 
8.10 Lost to Follow-up 
34 
8.11 Premature termination of the study 
34 
8.12 Potential factors impacting the data collected 
35 
9. 396 
9.1 Temporary halt for reasons of subject safety 
36 
9.2 
406 
9.2.1 Adverse events (AEs) and Adverse device effect (ADE) 
36 
9.2.2 Serious adverse events (SAEs) and serious adverse device effect (SADEs) 
37 
9.2.3 Device deficiencies, device failures and malfunctions 
38 
9.3 
428 
9.4 
428 
9.5 
429 
10. 
4240 
10.1 Analysis population 
40 
10.2 4340 
10.3 4340 
10.4 4441 
11. 
4442 
11.1 4542 
11.2 4542 
11.3 4542 
11.4  
4542 
11.5 463 
11.6 463 
11.7 463 
11.7.1 
463 
11.7.2 Privacy of Personal Data 
44 
11.7.3 
474 

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11.7.4 Record Keeping 
45 
11.7.5 
485 
 
11.7.6 Record Retention 
46 
11.8 496 
11.8.1 Deviations from clinical investigation plan 
48 
11.8.2 
508 
11.8.3 
509 
11.8.4 
519 
11.9 Amendments 
49 
11.12 
5250 
11.13 Temporary halt and (prematurely) end of study report 
50 
11.14 End of study report 
50 
11.15 
5251 
12 Structured Risk Analysis 
53 
12.1 Potential issues of concern 
53 
12.1.1 Verily Study Watch 
53 
12.1.2 Participant burden and benefits 
53 
12.2 Synthesis                                                                                                                     53 
13. 
5555 
APPENDIX A 
                                                                                                                    57 
 
 
 

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LIST OF ABBREVIATIONS AND RELEVANT DEFINITIONS  
 
6MWT 
6 Minute Walking Test 
ABR 
General Assessment and Registration form (ABR form), the application 
form that is required for submission to the accredited Ethics Committee; in 
Dutch: Algemeen Beoordelings- en Registratieformulier (ABR-formulier) 
AE 
Adverse Event 
ADE 
Adverse Device Effect 
AR 
Adverse Reaction 
ARDS 
Access Restricted Data Store 
CA 
Competent Authority 
CCMO 
Central Committee on Research Involving Human Subjects; in Dutch: 
Centrale Commissie Mensgebonden Onderzoek 
CIP 
Clinical Investigation Plan 
COPD 
Chronic Obstructive Pulmonary Disease 
CV 
Curriculum Vitae 
DSMB 
Data Safety Monitoring Board 
EU 
European Union 
EudraCT European drug regulatory affairs Clinical Trials  
GCP 
Good Clinical Practice 
GDPR 
General Data Protection Regulation; in Dutch: Algemene Verordening 
Gegevensbescherming (AVG) 
IB 
Investigator’s Brochure 
IC 
Informed Consent 
IMP 
Investigational Medicinal Product  
IMPD 
Investigational Medicinal Product Dossier  
METC  
Medical research ethics committee (MREC); in Dutch: medisch-ethische 
toetsingscommissie (METC) 
MCID 
Minimally Clinically Important Difference  
PD 
Parkinson’s Disease  
SAE 
Serious Adverse Event  
SADE 
Serious Adverse Device Effect 
SPC 
Summary of Product Characteristics; in Dutch: officiële productinformatie 
IB1-tekst 

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Sponsor 
The sponsor is the party that commissions the organisation or performance 
of the research, for example a pharmaceutical 
company, academic hospital, scientific organisation or investigator. A party 
that provides funding for a study but does not commission it is not 
regarded as the sponsor, but referred to as a subsidising party. 
SUSAR  
Suspected Unexpected Serious Adverse Reaction 
TUG 
Timed Up & Go Test 
UAVG 
Dutch Act on Implementation of the General Data Protection Regulation; in 
Dutch: Uitvoeringswet AVG 
WMO 
Medical Research Involving Human Subjects Act; in Dutch: Wet Medisch-
wetenschappelijk Onderzoek met Mensen 
 
 

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SUMMARY 
 
Rationale: Physical functioning is an important determinant of quality of life and therefore, a 
relevant issue in people with chronic conditions such as chronic obstructive pulmonary 
disease (COPD) and Parkinson’s disease (PD). Physical capacity and physical activity are 
distinct and relatively independent aspects of physical functioning. With the rise of innovative 
technology, both aspects have become measurable in the free-living environment of people 
with chronic conditions. However, so far, physical capacity and physical activity have mainly 
been assessed in in-clinic settings using standardized performance tests (i.e. Six-Minute 
Walk Test (6MWT)) and questionnaires (i.e. LASA Physical Activity Questionnaire), 
respectively. Here we will examine the validity of a digital solution to remotely measure 
physical capacity and physical activity in two groups of participants: participants with PD and 
participants with COPD. 
 
We aim to develop and validate algorithms to quantify and track physical capacity and 
physical activity to be used as clinical trial endpoints for the development of pharmacological 
and non-pharmacological interventions for participants with COPD and PD. The algorithms 
will be developed from sensor data collected on wrist worn devices (Verily Study Watch and, 
for a subset of participants, the Fitbit Sense). For analytical validation of the step counting 
algorithm, which is the basis of many other algorithms for walking activity and capacity, an 
ankle worn accelerometer (Modus StepWatch) will be used, as a reference device, 
simultaneously with Verily Study Watch at home for all participants. There will be two 
contexts for sensor data collection: 1) during the Virtual Walk Test, which is administered via 
application on a wrist worn device in the home setting, and 2) during the free-living context 
where participants simply wear  the device(s) and the sensor data is passively recorded. In 
addition to the sensor data, each participant’s relevant clinical outcomes, patient-reported 
outcomes, general demographics and medical history information will also be collected. The 
resulting data will be used to develop and/or validate algorithms to estimate participant’s 
physical capacity as well as to quantify physical activity of the participant. By utilizing sensor 
data from wearable devices and their associated algorithms, we will be able to obtain 
frequent assessments of the participant’s functional physical capacity and granular 
measurements of physical activity. Moreover, capturing comprehensive walking behavior 
through passive, continuous monitoring of participants in their own environment provides an 
opportunity for evaluating the possibility of using passive monitoring based measurements to 
be an indicator of one’s functional capacity in the real world. If these digital tools are 
validated, these will support an improved ability to measure a participant's physical 
functioning at baseline and during treatment, and have the potential to capture the treatment-
related change from baseline, more accurately. Ultimately, we expect that this effort will 
contribute to more effective and efficient development of pharmacological and non-
pharmacological interventions for people with COPD and PD.  
 
Objectives: The primary objectives for participants with COPD are: 1) to 
analytically  validate algorithms that utilize free living data to estimate the in-clinic 6-

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Minute-Walk-Test (6MWT) distance (free-living data based 6MWT distance 
estimator); 2) to analytically validate algorithms that utilize virtual 6MWT context-
known data to estimate the in-clinic 6MWT distance (virtual 6MWT distance 
estimator). A subset of pre-selected data will be used to refine algorithms that are 
developed using data from other sources, and 3) to evaluate analytical validity of 
walking measurements based on passively recorded data. Test-retest reliability of 
four types of estimators (two (2) 6MWT distance  and two (2) TUG time estimators) 
and walking measurements will be obtained as well. The primary objectives for 
participants with PD are: 1) to develop algorithms that utilize free living data to 
estimate the in-clinic 6MWT distance;2) to develop algorithms that utilize virtual 
6MWT context-known data to estimate the in-clinic 6MWT distance; and 3) to 
evaluate analytical validity of walking measurements based on passively recorded 
data.   
 
 
The secondary objectives for participants with COPD are: 1) to analytically validate 
algorithms that utilize free living data to estimate the outcome of in-clinic Timed-Up-and-Go 
test (TUG; free-living data based TUG time estimator) and 2) to analytically validate 
algorithms that utilize virtual TUG to estimate the in-clinic TUG (Virtual TUG time estimator). 
A subset of pre-selected data will be used to refine algorithms that are developed using data 
from other sources. Test-retest reliability of four types of estimators (two (2) 6MWT distance 
and two (2) TUG time estimators) will be obtained as well. The secondary objectives for 
participants with PD are, 1) to develop algorithms that utilize free living data to estimate the 
outcome of in-clinic TUG and 2) to develop algorithms that utilize virtual TUG to estimate the 
in-clinic TUG.  
 
The exploratory objectives is  to obtain  datasets that describe clinical and functional 
characteristics of people with COPD and PD for the development of additional digital 
biomarkers based on sensor collected data. The dataset will be used to develop prototype 
algorithms related to disease status or symptoms and test their relationship to clinical 
outcomes of interest.  
 
Study design: We will perform a decentralized, prospective, observational study with a 15 
week follow-up.  
 
In-Clinic Portion: Participants will come to their assigned local physiotherapy practice four 
times (once every five weeks) for in-clinic assessments of walking capacity, and will be 
instrumented with up to three sensor wearable devices (Verily Study Watch, Modus 
StepWatch 4, and the Fitbit Sense) during the assessments. Participants will undergo a 10-
week high intensity exercise training program supervised by a specialized physiotherapist as an 
intervention.    
 
Remote Portion: Participants will be instructed to wear the Verily Study Watch for up to 23 
hours per day for the entire study duration (15 weeks), to enable continuous free-living data 
collection, and will be asked to perform the Six-Minute Walk Test (6MWT) and Timed Up and 
Go test (TUG) once a week using the Verily Study Watch. Verily Study Watch will send out 
notification to perform 6MWT and TUG and guide participants through the remote 
assessments. A subset of participants may also wear the Fitbit Sense concurrently with the 

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Study Watch and will be asked to wear them for the first 5 weeks between first and second 
visits. All COPD and PD participants will  also wear the Modus StepWatch 4 concurrently 
with the Study Watch for 14 days between week 5 and week 15. During these 14 days, 
participants are asked to wear the StepWatch for at least 10 days, which can fall on any 
random day with a minimum of two weekend days. Wear time of four to six hours on these 
days is intended. 
 
Patients who are on a physiotherapist-supervised maintenance program with only low-
frequency sessions (maximum 1 session per week) prior to study entry may continue during 
the first 5 weeks of the study (the baseline period). Newly referred patients will be asked to 
start intensive physiotherapy after the 5 week baseline period. However, if the participant and 
the physiotherapist think it is necessary or needed, it is allowed to start physiotherapy with a 
low frequency (maximum 1 session per week) during the baseline period. Five weeks of 
baseline period will allow to capture variability/fluctuation in symptoms, functional physical 
capacity, and other characteristics in participants activities of daily living based on sensor 
recorded data. Ten weeks of high intensity physiotherapy intervention is expected to induce 
changes in functional physical capacity and we will assess whether we can capture these 
changes using sensor data.  
 
Study populations:  200 participants with COPD and up to 130 with PD (100 complete 
cases with both Study Watch and StepWatch at home) who are referred to a physiotherapist 
will be enrolled at up to 25-30 sites. Both patient groups should have sufficient cognitive 
capacity  to understand and follow study procedures and be able to walk independently (with 
or without an assistive device). People who, in the estimation of their treating physician, are 
not able to perform walking tests safely at home will be excluded as well as those with more 
than one fall in the last three months, or unstable cardiovascular conditions.  
 
Intervention: During this observational study, participants will be treated by a 
physiotherapist for their specific condition and resulting symptoms by undergoing a 
supervised physiotherapy program starting 5th week into the study for 10 weeks. Treatment 
will consist of a personalized approach based on the current clinical guidelines for 
physiotherapy for COPD1 and PD, respectively. This personalized approach will consist of 
multiple treatment modalities, at least one of which has a component of aerobic exercise, 
which is hypothesized to impact walking test scores.2,3  
  
Main study parameters/endpoints: For the analytical validation of algorithms developed 
based on data from people with COPD, the following endpoints will be used.  
Co-Primary Endpoints are 1) Difference between in-clinic 6MWT distance and free-living 
data based 6MWT distance estimate, and 2) Difference between in-clinic 6MWT distance 
and Virtual 6MWT distance estimate. 
Secondary Endpoints are 1) Difference between in-clinic TUG time and free-living data 
based TUG time estimate, 2) Difference between in-clinical TUG time and Virtual TUG time 
estimate, and 3) Difference between Study Watch based at-home walking measurements 
and reference device (StepWatch) based walking measurements, and 4) Test-retest 
agreement across various estimates from each algorithm that is validated.  
Exploratory Endpoints are  1) ICC between free-living data based walking behavior 
measurements by StepWatch and Study Watch obtained from a subset of COPD participants 

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who consented to wear StepWatch as well as Study Watch at home 2) For the PD cohort, we 
will use the entire dataset to develop algorithms to estimate 6MWT distance, and ICC 
between free-living data based walking measurements by StepWatch and Study Watch 
obtained from a subset of PD participants who consented to wear StepWatch as well as 
Study Watch at home, and 3) For both groups, the entire dataset will be also used to develop 
exploratory digital biomarkers related to disease or other functional status and their relation 
with clinical outcomes of interest.     
 
Nature and extent of the burden and risks associated with participation, 
benefit and group relatedness: The burden of participating in this study consists of 
4 visits to the local physiotherapy practice for in-clinic assessments of disease 
status and walking tests. These visits are scheduled in addition to the usual care 
physiotherapy assessments and therefore, can be considered an additional burden. 
Every in-clinic visit will take approximately 120 minutes in total. In addition, 
participants are asked to wear the Study Watch and StepWatch  devices at home 
during waking hours for a minimum of 10 days over the 14 day period between 
second and last visits. The Study Watch will be worn continuously for 15 weeks and 
perform two walking tests once a week. The walking tests are guided and prompted 
by the Study Watch, making it easier to comply with these procedures. 
Simultaneous wear of the StepWatch along with Study Watch on the ankle and 
wrist, respectively, for at least 2 weeks during the study, will be an additional 
burden. However, the StepWatch does not require any form of interaction (i.e., no 
charging / syncing) The Verily Study Watch is being used in another study in 
participants with PD and the participants showed excellent compliance,4 therefore it 
is expected that this will be a realistic approach. Participants will wear three different 
wearable devices in the clinic and max two devices at home. In the clinic, 
participants will wear the Study Watch on one wrist, Fitbit Sense on the other wrist, 
and the Modus StepWatch on the ankle for the duration of clinic visits for all four 
visits. For those who are willing to wear the optional FitBit device  at home 
(minimum 50 people with COPD and 30 people with PD), simultaneous wear of the 
devices on each wrist, for at least the first five weeks of the study duration, will be an 
additional burden. However, participants will only wear a maximum of two  devices 
at home simultaneously, even when the participant chooses to wear optional Fitbit 
device, because the timing of each device wear during study is different (i.e., Fitbit 
will be given for the first five weeks, and StepWatch will be given after the first five 
weeks). It is expected that this would be feasible based on prior studies where 
multiple devices were required to be worn for prolonged periods of time for the 
people with COPD4 and PD.5-7 In addition, wearing FitBit is not an obligatory part of 
the study, and participants can decline wearing multiple devices at the same time at 
home.     
 
The main risks related to the safety of performing an unsupervised (submaximal) aerobic 
exercise test at home are related to falls and cardiovascular events. Falls may be more 
frequent in the PD population, while cardiovascular risk is higher in COPD because of 
(potentially undiagnosed) cardiovascular comorbidity. Risks associated with home 
measurement will be minimized by excluding participants that have fallen more than once in 
the last three months and by asking the treating physician (i.e. general practitioner, 
pulmonologist or neurologist) to assess a person’s ability to participate in this study. Finally, 

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participants will receive 10 weeks of personalized physiotherapy, which they would also 
receive if they would not participate in this study.  
 

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1. INTRODUCTION AND RATIONALE 
Physical functioning is an important determinant of quality of life and therefore a relevant issue 
in people with chronic conditions such as chronic obstructive pulmonary disease (COPD) and 
Parkinson’s disease (PD).3 Physical capacity and physical activity are distinct and relatively 
independent aspects of physical functioning.8 With the rise of innovative technology, both 
aspects have become measurable in the free-living environment of people with chronic 
conditions.9-13 However, so far, in clinical practice, applying wearable technology in at home 
settings is not part of usual care. Physical capacity and physical activity are, for example 
assessed in in-clinic settings using standardized performance tests (i.e. Six-Minute Walk Test 
(6MWT)) and questionnaires (i.e. LASA Physical Activity Questionnaire), respectively.  
 
Relying only on in-clinic standardized tests and surveys is suboptimal for several reasons. 
First, in-clinic tests give limited, or potentially distorted information on how a patient is 
functioning in daily life. For example, patients with PD, experience a phenomenon called 
“kinesia paradoxa,”in which they function unexpectedly well under stressful circumstances, 
including in-clinic observations.14 This problem is compounded by the fact that many patients 
take extra medication prior to the consultation (hoping to make a good impression), and some 
even practice the clinical tests while sitting in the waiting room. Second, the brief in-clinic 
evaluations cannot reliably capture the common and disabling fluctuations in response to 
Parkinson medication (the so-called ON-OFF fluctuations).15 Finally, episodic visits are not well 
suited to detect changes in important lifestyle issues,16,17 such as gradual declines in physical 
activity that can have a devastating impact on both COPD and PD.18 Moreover, measuring 
physical activity with a questionnaire has been shown to be highly unreliable, because of their 
retrospective and subjective nature. Consequently, it is currently impossible to accurately 
assess physical capacity and physical activity in order to tailor treatment decisions to the actual 
needs of patients and to evaluate treatment effects, leading to unnecessary disability, poor 
quality of life, and avoidable medical costs. 
 
Wearable technology, such as inertial sensors (i.e. accelerometers and gyroscopes) may 
offer a solution for the above mentioned challenges. By deploying wearable devices, we are 
able to evaluate how people actually function, for long periods of time (allowing repeated 
measurement), in real-life. Both remote assessments and passive monitoring of mobility 
allow data collection without relying on the patient’s memory or in-clinic functioning. Remote 
assessment will allow us to perform (validated) tests on mobility and physical capacity more 
often and in the person’s own home environment. Passive monitoring data will allow us to 
test the feasibility of developing walking measurements in the real world that reflect a 
comprehensive picture of one’s walking behavior in a real life setting. These are 
hypothesized to be clinically meaningful aspects of health for both PD and COPD. Although 
free-living walking measures may not mimic in-clinic walking capacity measured by in-clinic 
clinical outcome assessments (e.g., 6MWT) in the same manner, some aspects of walking 
behavior in the real world may provide insights in walking capacity (e.g., high end walking 
speed, high end duration of walking during routine activities) and other aspects of 
functionality. Finally, free-living walking measures based on passively recorded data offer a 
few advantages over remote assessment. First, current in-clinic clinical outcome 
assessments of walking capacity require patients to come to the clinic which can be 

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burdensome to patients and their caregivers. Therefore, if sensor based digital tools can 
measure one’s walking capacity at home, that would reduce patient burden. Second, even 
when a test is performed at home, it is still a test, which is not part of the usual daily 
activities. Third, a patient's functioning can fluctuate day-by-day, and even within a day. 
Passively collecting walking measures from sensor data, will provide patients and clinicians a 
fuller picture of these fluctuations. These fluctuations are potentially critical indicators for 
functional status (e.g., variability of walking behavior over days is known to have clinical 
relevance).19,20   
 
Here we will develop digital solutions to remotely measure physical capacity and physical 
activity in two groups of participants-people with COPD and people with PD. Specifically, for 
COPD, we will use the subset of data to refine existing algorithms, and use the majority of 
the data to evaluate the analytical validity for estimation of 6MWT distance and free-living 
walking measurements. For PD, we will use the entire dataset to develop algorithms to 
estimate 6MWT distance. For both groups, the entire dataset will be also used to develop 
exploratory digital biomarkers related to disease or other functional status and their relation 
with clinical outcomes of interest.     
 
 

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2. OBJECTIVES 
 
2.1 Primary Objectives 
We aim to develop digital biomarkers for functional physical capacity and physical activity 
based on data collected both during a virtual walk test, administered on the Verily Study 
Watch, and by using free-living, passively recorded sensor data collected by the watch. More 
specifically, we aim:  
 
For COPD: 
1) To analytically validate algorithms that utilize free living data to estimate the in-clinic 6-
minute-walk-test (6MWT) distance and obtain analytical validation of the algorithms; and 
2) To analytically validate algorithms that utilize virtual 6MWT context-known data to estimate 
the in-clinic 6MWT distance and obtain analytical validation of the algorithms. 
 
A small set of pre-selected data will be used to refine the algorithms that are mainly 
developed using data from other sources. 
 
For PD:  
1) To develop algorithms that utilize free living data to estimate the in-clinic 6-minute-walk-
test (6MWT) distance; and  
2) To develop algorithms that utilize virtual 6MWT context-known data to estimate the in-
clinic 6MWT distance. 
 
2.2 Secondary objectives 
For COPD: 
1) To analytically validate algorithms that utilize free living data to estimate the outcome of in-
clinic Timed-up-and-go test (TUG) and obtain analytical validation of the algorithms; 
2) To analytically validate algorithms that utilize virtual TUG to estimate the outcome of in-
clinic TUG and obtain analytical validation of the algorithms; 
3) To evaluate analytical validity of algorithms capturing various aspects of walking that 
utilize passively recorded sensor data; and   
4) To obtain test-retest reliability of the following algorithms based on weekly Virtual 6MWT 
between first and second visits: 
● Free-living data based 6MWT distance estimator 
● Virtual 6MWT distance estimator 
● Free-living data based TUG time estimator 
● Virtual TUG time estimator. 
● Free-living walking measurements 
 
A small set of pre-selected data will be used to refine the algorithms that are mainly 
developed using data from other sources. 
 
For PD:  
1) To obtain the dataset to develop algorithms that utilize free living data to estimate the 
outcome of in-clinic Timed-up-and-go test (TUG); and 

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2) To obtain the dataset to develop algorithms that utilize virtual 6MWT context-known data 
to estimate the outcome of in-clinic Timed-Up-and-Go test (TUG). 
3) To obtain the dataset to evaluate analytical validity of free-living walking 
measurements utilize passively recorded sensor data.  
 
COPD and PD participants will wear StepWatch and Study Watch at home over two 
weeks. This will provide a dataset to compare free-living data  based walking 
measurements by the two devices. StepWatch will be used as a reference  device to 
evaluate the performance of Study Watch walking measurements to quantify  waking 
activity and walking capacity in at home settings.  
 
2.3 Exploratory objectives 
We aim to obtain datasets to describe clinical and functional characteristics of people with 
COPD and PD for the development of digital biomarkers based on sensor collected data. 
The dataset will be used to develop prototype algorithms related to disease status or 
symptoms and test their relationship to clinical outcomes of interest.  
 
We aim to relate both the virtual 6MWT clinical assessment and free-living based metrics to 
physical capacity and physical activity to patient-centered outcomes (i.e., measures 
something of relevance and importance to the patients, i.e. meaningful aspects of health  in 
activities of daily living). To do that, we will collect Patient Reported Outcomes via well 
established, relevant questionnaires on motor symptoms, non-motor symptoms, activities of 
daily living, physical activity, quality of life and fatigue.  
Additionally, this study aims to assess whether developed algorithms can be 
used/generalized for multiple sensor devices to derive metrics capturing physical capacity of 
patients. To do that Fitbit Sense will be worn in addition to Verily Study Watch to a subset of 
study participants. While being worn in the same individuals simultaneously, common types 
of sensors (i.e., accelerometer and photoplethysmography sensor) in both devices will record 
time-series data with matching timestamps and will be used to derive metrics using the same 
algorithms for assessing the feasibility of device agnostic algorithm development.  
 
 

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3. STUDY DESIGN 
 
This study is a decentralized, prospective, observational study with 15 weeks follow-up 
(Figure 1). The study will be performed in two different populations-participants with COPD 
and participants with PD. Participants will go to their assigned local physiotherapy practice 4 
times (once every 5 weeks) for in-clinic assessments of walking capacity and disease 
symptoms (specific to COPD and PD cohorts), while  wearing three (3) different wearable 
sensor devices-the Verily Study Watch on one wrist, Fitbit Sense on another wrist and 
Modus StepWatch on the ankle. After each visit, participants will also fill out questionnaires 
on motor symptoms, cognition, quality of life, activities of daily living, and fatigue. In addition 
to wearing the Verily Study Watch for 23 hours per day and StepWatch device for two weeks 
of the study, at least 4-6 hours per day, between Visits 2 and 4  (and a Fitbit device for the 
participants who agree to do so, for the first 5 weeks, 23 hours per day of the study 
participation,), participants will be instructed to perform weekly home assessments (i.e. 
6MWT and TUG tests). These assessments will be guided by the graphic user interface on 
the Verily Study Watch. Between week 5, and the end of the study (week 15), participants 
will participate in 10 weeks of physiotherapy treatment including a high-intensity aerobic 
exercise component. The intervention is hypothesized to impact walking capacity and induce 
variation in walking test scores. In the first 5 weeks of the trial, physiotherapy is allowed, only 
when deemed necessary by the patient and physiotherapist. Patients will not receive high-
intensity aerobic exercise training during this period. 
 
Estimated study timelines:  
First Participant enrolled: December , 2021  
Enrolment Period: 18  months  
Follow-up duration: 15 weeks per participant  
Total study duration: 30  months  
Data cleaning/closeout: 3 months  
End of study: July 2024  

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Figure 1. Study Design  
  
COPD arm 
 
 
PD arm 
 
 
 
 

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4. STUDY POPULATION 
4.1 Population (base)  
Two hundred (200) participants with COPD and up to 130  participants with PD who have 
been referred to a physiotherapist will be enrolled. Both cohorts of participants (COPD and 
PD) are expected to have reduced 6MWT distance outcomes that correlate with disease 
severity. However, due to the different underlying mechanisms of the diseases, the reasons 
for changes to the 6MWT distance may be different (i.e., pulmonary obstruction and overall 
limitation of the cardiovascular for people with COPD vs. reduced walking capacity and 
mobility for the people with PD due primarily to neurological impairment). In order to develop 
algorithms that will work across multiple root causes for functional capacity reduction, two 
different populations, COPD and PD, are selected. Different sets of features will be identified 
from each group to assist in developing algorithms with suitable performance for both 
conditions. These conditions are expected to be exemplary for other pulmonary, 
cardiovascular or neurological conditions as we look to expand the usage of developed 
algorithms across more indications. 
 
4.2 Inclusion criteria 
To be eligible to participate in this study, a potential participant must meet all of the following 
criteria:  
● Participant is an adult, at least 18 years of age; 
● Participant can read and understand Dutch; 
● Participant is willing, competent, and able to comply with all aspects of the protocol, 
including follow-up schedule;  
● Participant is willing and able to complete patient-reported outcomes via internet 
through their own devices at home or provided device at assigned physiotherapist’s 
office after each visit; 
● Participant can walk (with or without assistive equipment/oxygen therapy, and the 
circumstances do not completely prevent arm swings for the arm where watch is 
worn); 
● (PD-specific) Participant has PD with Hoehn and Yahr stage 1-2; 
● (COPD-specific) Participant has COPD irrespective of airway obstruction severity and 
has a limited exercise capacity as judged by the physiotherapist 
● (For those who consent to wear optional Fitbit Sense at-home) Participant has a 
smartphone, and is willing to download Fitbit application in the phone to sync Fitbit 
Sense to set up and transfer data from Fitbit Sense to Fitbit database.  
 
4.3  Exclusion criteria 
A potential participant who meets any of the following criteria will be excluded from 
participation in this study: 
● Participant is allergic to nickel used in Study Watch; 
● Participant cannot make an arm swing at all or is in a situation that prevents arm 
swing completely (e.g., rollator);  
● Comorbidity (co-occurrence) of COPD and PD; 
● Participants with cognitive impairment that would prevent them from understanding 
and performing tasks in the study; 

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● Participant is pregnant or plans to become pregnant during the course of the study; 
● Participant is participating in another investigational drug or device study that may 
conflict with the objectives, follow-up, or testing of this study; 
● Participant has recently (within 3 months prior to the start of the study) completed or 
is currently participating in a supervised high-intensity aerobic exercise program. We 
define high-intensity as ≥ 3 sessions per week, for ≥30 minutes at  ≥70% of the 
maximum exercise capacity; 
● Participants with high fall risk or cardiovascular risk profile impacting the safety of 
performing at-home walk tests without supervision (as judged by referring physician’s 
decision, record of unstable cardiac disease, Hoehn and Yahr stage 3 or greater (PD-
specific), >1 fall in the last 3 months); 
● Any disease or condition that prevents understanding or communication of informed 
consent, study demands, and testing protocols, including: 
○ cognitive decline including diagnosed forms of dementia,  
○ psychiatric disease including diagnosed forms of depression.   
 
4.4 Sample size calculation 
The study plans to enroll 200 participants for COPD and 100 for PD. For the COPD cohort, 
the objective is to conduct analytical validation of algorithms that estimate in-clinic 6MWT 
distance based on free-living based data and virtual 6MWT context-known data. The 
algorithms are being developed based on the prior dataset from community-dwelling 
individuals in their usual state of health, including people with COPD.  
 
For COPD 
Sample size calculations were based on our co-primary endpoints of Intra-class correlation 
coefficient (ICC)21 between estimated 6MWT distance from free-living data and virtual 6MWT 
context-known data with in-clinic 6MWT distance. However, since free-living data is known to 
be less structured and may not involve walking for 6 minutes or any prolonged period, we 
expect to see lower performance from the free-living data based model compared to virtual 
context-known data based model. Previous literature22 shows a minimum ICC of 0.75 from 
virtual walk tests. Thus the minimum success criteria for virtual context-known algorithm was 
ICC >0.75. For the IRL model the threshold was lowered to an ICC of >0.70.  
 
All sample size calculations were based on a preliminary COPD and healthy cohorts 
obtained from BHS (NCT03154346) data that predicts 6MWT distance from in-clinic context-
known data and free-living data.  
Based on the preliminary data collected, the following assumptions are made for sample size 
calculations:  
● Each participant will have 2 pairs of data available (a pair consists of one algorithm 
estimated 6MWT distance and one clinician measured 6MWT distance) 
● Model performance based on virtual context-known data will be higher than model 
based on free-living data 
● Minimum target performance based on IRL data is ICC>0.70. Minimum target 
performance based on virtual walk test data is ICC>0.75 
● Since both free-living data based estimate and context-known data based estimate 
algorithms will be validated separately, no multiplicity is being considered, and each 
hypothesis test will be conducted with tolerance of 5% Type I error. 

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● About 75% of participants will have sufficient data for the final algorithm assessment. 
(This takes into consideration participants' drop outs, sensor data of insufficient 
quality to generate reliable algorithm outputs, and failure to obtain the ground truth 
labels (e.g. clinician evaluation of 6MWT distance)) 
● The table below illustrates the power achieved for a given algorithm performance 
assuming N=200 (including 25% drop-out) and a type I error of 0.05.  
 
Table 1: Power Analysis with Various Modeling Assumptions  
Success criteria 
Current Performance 
Power achieved(%) 
ICC from free-living data based model  
>0.70 
0.74 
0.27 
 
0.76 
0.50 
 
0.78 
0.72 
 
0.79 
0.82 
ICC from virtual context-known data based model 
>0.75 
0.78 
0.23 
 
0.80 
0.48 
 
0.82 
0.75 
 
0.83 
0.85 
 
For PD 
. 
 
For our secondary endpoint, we performed a sample size calculation specifically for our PD 
cohort. This is an additional calculation to our primary sample size calculation which aims at 
the analytical validation of 6MWT distance measured with StudyWatch in clinic versus free 
living for COPD patients. This secondary sample size calculation was based on Intra-class 
correlation  coefficient (ICC)19 between estimated walking measurements obtained from 
Study Watch data and StepWatch data in a free-living setting. Sample size calculations were 
derived from a total of 48 walking measurements estimating different aspects of walking 
behavior in an individual such as bouts of walking, bout speed, bout cadence, number of 
bouts, bout durations, and daily step counts.  
Previous literature shows a range of minimum ICC values for walking related metrics in free 
living context.23-25 Not all metrics had known ICC. Generally an ICC ≥0.75 is considered 
excellent, 0.60–0.74 good, 0.40–0.59 fair, and <0.40 poor.26  Minimum success criteria for 
the metrics, based on the literature, are listed in the following table.   
All sample size calculations were based on a preliminary healthy cohort obtained from a 

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prior pilot study data that compared walking measurements obtained from Study watch 
compared with StepWatch in a free-living setting.   
Based on the preliminary data collected, the following assumptions are made for sample 
size calculations:   
● Each participant will have 2 pairs of data available (a pair consists of one 
algorithm estimated free living walking measurements from Study Watch 
and one from StepWatch)  
● Minimum target performance based on free living data is different for 
each metric and thus are specified in the table below 
● Since each of the free living metrics will be validated separately, no 
multiplicity is being considered, and each  hypothesis test will be conducted 
with tolerance of 5% Type I error 
● About 80% of participants will have sufficient data for the final algorithm 
assessment.  (This takes into consideration participants' drop outs (20%), 
sensor data of insufficient  quality to generate reliable algorithm outputs, and 
failure to obtain the ground truth  labels (e.g. step watch errors).  
 
 
The table below illustrates the power achieved by the algorithm for the best 
performing metrics assuming N=100 (including 20% drop-out) and a type I error 
of 0.05. This suggests that N=100 participants with StepWatch at home data will 
provide moderate power with given success criteria and current performance for 
some metrics to assess the analytical validity of these metrics as secondary 
endpoints.   
Table 2: Power Analysis with Various success criteria, for n=100 
Walking Suite Measures 
Success criteria (from 
literature)  
Current Performance  
Power achieved(%) 
Cadence 95 percentile 
>0.82 
0.88 
0.64 
Bout cadence 75 percentile 
> 0.75 
0.82 
0.51 
Cadence 75 percentile 
>0.7 
0.77 
0.4 
Number of Bouts 
>0.66 
0.7 
0.17 
 
For the optional part of the study (i.e. wearing the Fitbit  at home) we only defined minimum 
numbers (for Fitbit, 50 COPD and 30 PD) and have not defined a maximum number of 
participants and aim to include as many participants as possible beyond the minimum 
numbers. 
 
 

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5. TREATMENT OF SUBJECTS 
Participants will be given physiotherapy treatment for 10 weeks, as part of usual care. Both 
participant populations will receive personalized treatment determined by the treating 
physiotherapist according to the most recent physiotherapy guidelines for both COPD and 
PD.27,28 Treatment modalities can vary between participants, but all participants will at least 
have 2 times of aerobic exercise training per week, as part of a multi-modality and 
personalized treatment. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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6. INVESTIGATIONAL PRODUCT 
 
6.1 Name and description of investigational product(s)  
 
 
6.1.1 Verily Study Watch 
The Verily Study Watch is an investigational medical device manufactured by Verily Life 
Sciences LLC.  It  is a wrist-worn wearable device with sensors, band, USB syncing/charging 
hub, and cradle that continuously records physiological, movement, and environmental data. 
The Verily Study Watch is intended to be used for clinical research applications only. As 
such, the device is not CE marked.  
 
As shown in Figure 2, the Study Watch collects physiological and/or environmental 
information through sensors. The sensors collect data that may include movement and 
activity, pulse rate, and electrodermal activity (EDA). The wristband is made of fluoro 
elastomer (similar to other wristwatches). Data from the device is encrypted and securely 
sent to the cloud using a USB syncing/charging cradle and wireless connectivity bridge. The 
USB syncing/charging cradle connects to the Study Watch through 4 contacts on the 
underside of the device. The Study Watch is worn externally on the wrist and does not come 
into contact with any body fluids.  
 
Figure 2. Verily Study Watch 
The Study Watch is a miniaturized data monitoring and data collection device for continuous 
recording of physiological activity and environmental data. The device consists of a wrist 
watch containing sensors, a USB syncing/charging cradle, and a connectivity bridge (Study 
Hub).  
 
The Study Watch is used as a general participant monitor intended for data collection only. 
As a general participant monitor, it provides physiological and environmental information for 
general research and performance measurement purposes. No treatment decisions are 
made with the data collected from the device.  
 
The Study Watch is able to collect data during a set of two Virtual Walk  tests (the 6MWT and 
TUG; see sections 8.4, 8.5 and Figure 3) performed weekly and labels for events (e.g. 
medication intake for the PD cohort) provided by the participant. At the beginning and at the 
end of each test, the participant will press a button on the Study Watch to tag and record the 

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exact time of the test. Participants with PD will also press a button to tag the time when they 
take their medication.  
Except in the case of the Virtual Walk tests, and performance and event tagging, the device 
requires no other user intervention to capture or analyze physiological data and collects data 
passively with minimal information communicated to the user via the device (i.e., date and 
time, charge status, sync status when connected for data transfer). Participants’ button press 
inputs marking the beginning and end of each walk test will be used to determine the onset 
and offset of the test in the sensor data. Medication tagging will be used to understand 
manifestation of medication on and off states in the sensor measurements for PD patients.   
 
The Study Watch has been carefully designed to use current technologies (e.g.virtually 
continuous data collection)) to investigate physiological and environmental variables that 
may shed light on the evaluated disease, its progression, and response to therapy when 
combined with other clinical variables collected during the study.. Since it is intended for 
research only and it is not CE marked, approval from a competent authority in the 
Netherlands will be obtained for use of this investigational device for this Accuracy of Digital 
Assessment of Performance Trial. We have previously obtained approval for using the Study 
Watch in the context of the Personalized Parkinson Project (registered under file 
VGF2002688). 
 
6.2 Summary of findings from non-clinical studies 
A summary of findings from non-clinical studies and clinical studies is provided in the 
Investigator’s Brochure (IB). 
 
 
6.3 Summary of known and potential risks and benefits 
There are limited risks to the participant during the data collection. Potential risks relate to 
the in-clinic assessments and the unsupervised home assessments. Identified risks include 
risk of falls or cardiovascular events which have been mitigated by design (exclusion criteria 
and approval from treating physician). A structured risk and benefit analysis is available in 
section 12.  
 
Potential benefits of use of the Study Watch compared to other monitoring systems may 
include, but are not limited to: 
● The device is portable and easy to use even by participants with tremor or 
dexterity problems; 
● The device is non-invasive and poses no significant safety issues; 
● Data transfer does not require connection to a mobile phone or computer, and 
simply fitting the watch in a cradle / plugging USB is sufficient for both charging 
and data streaming; 
● Device can be used in every situation of daily living (e.g. at home, at the gym, 
or at the office); 
● Faster and more effective data capture than other similar devices; 
● Combines existing sensor and ECG technology for multiparametric 
assessment; 
● Physiological context (motion parameters) associated with detected events; 
● High sampling frequencies (up to 200 Hz), which permits accurate 

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measurements; 
● Long battery life, allowing for continuous data assessment for up to 7 days 
before charging is necessary (in the present study, we ask the participants to 
charge the Study Watch once a day); and 
● Repeated measurements of physical functioning in patients' natural 
environment is permitted. 
 
The following documents are available for detailed information on the device and operating 
instructions: 
● Verily Study Watch and Study Hub Investigator Brochure; 
● Verily Study Watch Instructions for Use; 
● Verily Study Hub User Manual; and 
● Verily Study Watch Virtual Walk Test Instruction Manual. 
 
Participants will be trained by physiotherapists on proper use of devices and will be provided 
Study Watch Instructions for use and Virtual Walk Test participant training guide. 
6.4 Investigational Product Accountability  
The Principal Investigator or an authorized designee shall keep records documenting the 
receipt, use, return and disposal of the investigational devices, which shall include: the date 
of receipt, identification of each investigational device (batch number/serial number or unique 
code), the version and date of the Study Watch firmware, the expiration date (if applicable), 
the date(s) of use, subject identification, and date on which the investigational device was 
returned (if applicable). 
 
The Investigator or authorized designee will record the receipt and disposition of the 
investigational device on the appropriate form. At the end of the clinical investigation, the 
original logs will be returned to the sponsor and copies of the logs kept in the Regulatory 
Binder at the investigational site. 
 
The investigational site, Radboud university medical center, (Radboudumc) is responsible for 
maintaining control over any associated investigational devices that are received and used 
and ensuring all investigational devices are inventoried, and provided only to study staff who 
have been appropriately trained. 
 
7. NON-INVESTIGATIONAL PRODUCT 
 
7.1 Fitbit Sense and Fitabase 
Fitbit Sense is a wrist-worn wearable consumer electronics device (CE marked in EU, made 
by Fitbit). Fitabase is a third party software that allows access to fitbit data for clinical 
research purposes masking sensitive information, and providing de-identification 
(pseudonymization). Fitbit’s on-board sensors collect data that may include movement and 
activity, pulse rate, electrodermal activity (EDA), electrocardiogram (ECG), and on-skin 
temperature. The device also provides a variety of wellness metrics related to activity level, 
pulse rate, heart rate, heart rate variability, oxygen saturation and sleep on the device and 
through mobile application. Fitbit Sense may collect geolocation data if users turn on activity 
labeling features outdoors (like manually selecting a jogging activity on the watch activity 
labeling menu) but this data will not be accessible by site staff nor researchers. The entire 

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data types that are collected and accessible from Fitbit are listed in Appendix A. The Fitbit 
sense device in this investigation is being used within the intended purpose for which CE 
marking was issued.  
 
Data from the device is transferred to Fitbit’s database through Fitbit’s mobile application 
(from the device to the mobile application via bluetooth connectivity and from the mobile 
application to Fitbit’s database via WiFi or cellular connectivity). Researchers and site staff at 
Radboud may access the aggregated data using Fitabase (a third party provider that allows 
access to de-identified Fitbit Data for research purposes) , but to ensure strict adherence to 
current regulations, no data transfer will be made from Radboud to Verily.  Verily must set up 
an appropriate Access Restricted Data Store (ARDS). Verily will be able to access the data 
only through an Access Restricted Data Store (ARDS) that will receive data from Radboud 
via the Fitabase platform.  
 
For the current study, access will be limited to aggregated data and derived metrics (e.g., 
step counts, sleep duration, etc.) based on raw data recorded using Fitbit’s accelerometer, 
gyroscope, and photoplethysmography sensors. These metrics will be used for algorithm 
development and comparison with metrics derived from Study Watch sensor data. Verily will 
not have access to other types of sensor data or participant location data, as these will be 
masked by Fitabase.  
 
 
7.2 Modus StepWatch 4 
StepWatch 4 is an ankle-worn wearable medical device (CE Class 1 medical marked in EU), 
and will be used as a reference device for measuring participants’ ambulation in the 
physiotherapy practice and at-home for a subset of participants who consent to do so. On-
board accelerometer collects motion data, and a companion application installed on an iPad 
at the physiotherapist's office will be used to transfer the data from the StepWatch to Modus 
StepWatch Cloud and to obtain derived metrics (e.g. step counts). The sensor data and 
derived metrics will be transferred from the Modus StepWatch Cloud to Verily Cloud for data 
analysis and algorithm development. The Modus StepWatch 4 device in this investigation is 
being used within the intended purpose for which CE marking was issued. 
 
Both  COPD and PD participants will wear StepWatch at home. Data transfer will occur at the 
physiotherapist's office when they return the device after two weeks of wear. No at-home 
iPad or data transfers are expected from the participants. 
 
Data from the Fitbit Sense and StepWatch 4 are with timestamps which allow the exact 
synchronization of sensor data from the devices with data from Study Watch for analysis to 
achieve study objectives.  
 
The following documents are available for detailed information on the device and operating 
instructions: 
● Fitbit Sense Instructions for Use; and 
● Modus StepWatch Instruction for Use (physiotherapists’ in-clinic use. 
● Modus StepWatch 1 pager for participant’s at home wear 
 

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8. METHODS 
 
8.1 Study endpoints 
8.1.1. Primary study endpoint 
For COPD: 
1) Measurement agreement/Intra-class correlation between in-clinic 6MWT distance and 
free-living data based 6MWT distance estimate; and 
2) Measurement agreement/Intra-class correlation (ICC)  between in-clinical 6MWT distance 
and Virtual 6MWT distance estimate 
For PD: not applicable. 
 
 
8.1.2 Secondary study endpoints (if applicable) 
For COPD: 
1) ICC between in-clinic TUG time and free-living data based TUG time estimate; 
2) ICC between in-clinical TUG time and Virtual TUG time estimate; and 
3) Test-retest agreement across various estimates from each algorithm that is validated. 
 
This is not applicable for PD.   
 
 
 
8.2 Study procedures 
This study will be coordinated by Radboudumc, but executed in 25 - 30 physiotherapy 
practices throughout the Netherlands. In each practice 2 physiotherapists will participate (up 
to 50 in total)- one specializing in COPD, and one specializing in PD. We will recruit 
physiotherapy practices using the nationwide ParkinsonNet infrastructure. Physiotherapists, 
who are part of the national ParkinsonNet, are experts in PD, and in general, have a high 
(>10 participants a year) patient load. Because physiotherapists usually work in a practice 
with more specialized physiotherapists, we aim to recruit physiotherapists with expertise in 
COPD within the same physiotherapy practice as the ParkinsonNet physiotherapists. We will 
select physiotherapists who have completed an additional course that specializes in 
providing physiotherapy in COPD participants. Throughout the study, the Radboudumc 
Helpdesk (already operational as part of the PPP study29) will proactively assist participants, 
physiotherapists, address problems and questions, and solve/communicate issues related to 
the execution of the trial.  
 
 
8.3 Participant recruitment and procedures 
 
The physiotherapist will identify potentially eligible patients and ask if they would be 
interested in the study and if a researcher from Radboudumc can contact them. Further 
information about the study is provided by the research team. When the patient agrees, a 
researcher from Radboudumc will call the potential participant soon after. During this contact 
moment, potential participants can ask questions and the researcher informs the participant 
about the study. When willing to participate, the potential participant is directed to the 
Baseline Platform where he/she is invited to create an account and to electronically sign the 

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screening consent. The researcher subsequently asks the allocated physiotherapist to 
schedule an appointment for the first visit.   , 
 
Before the first visit, potential participants will review and submit a screening consent to 
provide his/her  personal information, information for eligibility, and to give permission to 
contact their treating physician to ask for permission to participate in this study. At the first 
visit, once the potential participant is screened as eligible, a study consent is signed on paper 
by the participant, and physiotherapist. The participant will receive a copy of the signed 
informed consent form. Before signing, participants will review information associated with 
the specific research they are participating in, including objectives, types of data collected, 
study sponsor, study principal investigators, contact method, schedule of visits, and contact 
information for the participant to report issues. After the study consent is signed, participants 
will be asked to wear the Study Watch, Fitbit Sense, and StepWatch during the first visit and 
following visits. Study Watch will be asked to be worn on the non-dominant hand unless 
there are particular reasons preventing the wear. StepWatch  will be worn on the ankle that is 
the same side of Study Watch.  Optional Fitbit will be asked to be worn on the dominant hand 
for those who choose to wear it. Participants will be asked to keep wearing the device(s) on 
the same hand(s) and ankle throughout the study duration/wear duration  and the information 
on wearing hand for each device will be tracked in eCRF.  
 
At the first, and subsequent visits to the clinic, required assessments and measurements are 
performed as described in Table 2. In-clinic assessments are repeated every 5 weeks. After 
each visit, participants are asked to fill out the following questionnaires: FACIT-Fatigue, EQ-
5D-5L, Epworth Sleepiness Scale, HADS, LAPAQ outdoor, MDS-UPDRS part I (PD-only), 
MDS-UPDRS part II (PD-only), PDQ-39 (PD-only), CCQ (COPD-only). All questionnaires will 
be completed once within 14  days after each visit (either digitally in the Baseline platform or 
on paper) except for the FACIT-Fatigue and System Usability Survey, which will be 
completed weekly and only once after Visit 3, respectively. Unless specified as PD-only or 
COPD-only, questionnaires are for both PD and COPD cohorts. Participants will perform the 
virtual 6MWT and TUG at home using the Study Watch one time per week. The day and time 
of the week on which the tests are performed are standardized (i.e. same day + time of the 
week) while they are wearing the watch for up to 23 hours a day. For StepWatch device at 
home, the device will be provided, and  participants will be asked to wear it simultaneously 
with the Study Watch for two weeks, between Visits 2 and 4.For those who are willing and 
consented to wearing a Fitbit device, the device will be provided, and participants will be 
asked to wear it simultaneously with the Study Watch on the opposite wrist for the first five 
weeks between the first and second visits. 
 
 

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Table 2. Overview of study consents, assessments for COPD and PD cohorts 
Exams, Tests and Data 
Collection 
Pre 
Visit 
Visit 1 
(Baseline) 
Visit 2  
(5th wk) 
Visit 3  
(10th wk)  
Visit 4 
(15th wk) 
After each visit 
Weekly at home 
Visit Window 
 
Day 0 
In the 5th 
week 
In the 
10th week 
In the 15th 
week 
 
Within 7 days after 
each visit 
 
Screening consent 
X 
 
 
 
 
 
 
Demographic information 
X 
X 
 
 
 
 
 
Pre-visit platform survey 
X 
 
 
 
 
 
 
Inclusion/Exclusion criteria 
 
X 
 
 
 
 
 
Study consent 
 
X 
 
 
 
 
 
Medical history*  
 
  X 
x 
 
 
 
 
Change in health status 
between visits 
 
 
 
X 
X 
X 
 
 
User experience survey 
 
 
 
 
 
X (at home, post 
visit 3 only) 
 
Post-visit platform survey 
 
 
 
 
X 
 
 

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User feedback on Study 
Watch 
 
 
 
 
X 
 
 
Skin tone (Fitzpatrick Scale) 
 
  X 
 
 
 
 
 
Arm Hair Index  
 
  X 
 
 
 
 
 
  Concomitant Medications  
 
X 
X 
X 
X 
 
 
Physiotherapy 
 
 
 
X  
 
X 
 
X 
 
 
X (self-training at 
home) 
Adverse Events 
 
 
X 
X 
X 
 
 
Exams, Tests and Data 
Collection 
Pre 
Visit 
Visit 1 
(Baseline) 
Visit 2  
(5th wk) 
Visit 3  
(10th wk)  
Visit 4 
(15th wk) 
After each visit 
Weekly at home 
In Clinic Assessments & Surveys 
6MWT with pre & post Borg 
Scale (two times per clinic 
visit) 
 
X 
X 
X 
X 
 
 
TUG 
 
X 
X 
X 
X 
 
 
10MWT with single context 
(three times per clinic visit) 
 
X 
X 
X 
X 
 
 
10MWT with dual context 
(three times per clinic visit) 
 
X 
X 
X 
X 
 
 

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33 
 
Montreal Cognitive 
Assessment (MoCA) 
 
X 
 
 
X 
 
 
MDS-UPDRS Part I Rater 
Questionnaire (PD only) 
 
X 
X 
X 
X 
 
 
MDS-UPDRS Part III (PD 
only) 
 
X 
X 
X 
X 
 
 
MDS-UPDRS Part IV (PD 
only) 
 
X 
X 
X 
X 
 
 
Hoehn and Yahr Scale (PD 
only) 
 
X 
X 
X 
X 
 
 
COPD ABCD categorization 
(mMRC, COPD only) 
 
X 
X 
X 
X 
 
 
In Clinic Vitals & Measurements 
Pre-6MWT (#1&2) Resting 
blood pressure, SpO2, heart 
rate 
 
X 
X 
X 
X 
 
 
Post 0 minute -6MWT 
(#1&2) SpO2, heart rate 
 
X 
X 
X 
X 
 
 
Post 1 minute -6MWT 
(#1&2) SpO2, heart rate 
 
X 
X 
X 
X 
 
 
Post 2 minute -6MWT 
(#1&2) SpO2, heart rate 
 
X 
X 
X 
X 
 
 
Height, weight, leg length 
 
X 
 
 
 
 
 

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Exams, Tests and Data 
Collection 
Pre 
Visit 
Visit 1 
(Baseline) 
Visit 2  
(5th wk) 
Visit 3  
(10th wk)  
Visit 4 
(15th wk) 
After each visit 
Weekly at home 
At-home Clinical Assessments & Surveys** 
Virtual Walk Tests on the 
Study Watch (virtual 6MWT 
& TUG) 
 
 
 
 
 
 
X 
FACIT-Fatigue (13-item) 
 
 
 
 
 
 
X 
EQ-5D-5L 
 
 
 
 
 
X 
 
Epworth Sleepiness Scale 
(ESS) 
 
 
 
 
 
X 
 
Hospital Anxiety and 
Depression Scale (HADS) 
 
 
 
 
 
X 
 
LASA Physical Activity 
Questionnaire (LAPAQ) 
 
 
 
 
 
X 
 
MDS-UPDRS Part I & Part II 
Patient Questionnaires (PD 
only) 
 
 
 
 
 
X 
 
Parkinson's Disease Quality 
of Life Questionnaire (PDQ-
39, PD only) 
 
 
 
 
 
X 
 
Clinical COPD 
Questionnaire (CCQ, COPD 
only) 
 
 
 
 
 
X 
 

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Optional Fitbit at home use 
 
X  
(first 5 
weeks, at 
home, 23 
hours per 
day 
between 
visit 1 and 
visit 2) 
 
 
 
 
 
StepWatch at home use 
 
X 
(for two weeks, at home; within the two weeks wearing the device at least 10 days, which can fall on any 
random day with a minimum of two weekend days. Wear time of four to six hours on these days). 
 
*Medical history will be collected during both visit 1 and visit 2 
** These can be done in-clinic or at-home based on participant’s preference.

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8.4 Assessments – in-clinic 
All study procedures will be performed at the local physiotherapy practices, by the treating 
physiotherapist, with coordination with Radboudumc. Physiotherapists will be extensively trained in 
performing all assessments as part of the study protocol in a highly standardized manner. They will 
also be guided and coached by the research team at Radboudumc to increase engagement and 
data quality. Participants are invited to come to the study site four times over a 15 week duration. 
The in-clinic assessments consist of a number of walking tests: 6MWT (twice), TUG (twice), and 
10MWT with and without cognitive load (three times for each context). In addition, demographics are 
taken during the first visit and participants are asked to fill out some questionnaires on disease 
symptoms and quality of life after each study visit. Questionnaires can be filled out digitally at home 
or at the physiotherapy practice if the participant does not own a computer. The exact assessments 
are described in Table 2 (in-clinic and at-home assessments).  
 
8.5 Assessments – at-home  
After the first study visit to physiotherapists’ clinics, participants will be asked to wear the 
Study Watch (up to 23 hours a day) for passive longitudinal measurements of physiologic 
activity and environmental data. In addition, all participants will be asked to complete the 
virtual 6MWT with pre- and post-6MWT Borg Scales and virtual TUG, once a week (every 
week on the same day) with guidance via graphical user interface on the Study Watch. The 
Verily Study Watch will provide an alert to the participant at 9 am of the preset day of the 
week (preset during the first visit by site coordinator) to remind them to perform the task. 
Participants with PD will be asked to perform the Walk Test 30 minutes to an hour after they 
intake medication and tag the event on the Study Watch. Participants with COPD are asked 
to perform the task any time they prefer during the day that they receive an alert on the Study 
Watch. Participants will have the ability to postpone the task until a later time point in the 
same day, should that suit their schedule better. If a prescribed task is not executed on a 
given day, the reminder alert will be prompted the next day at 9 am. Participants with PD are 
also asked to tag time of medication intake every time they intake PD medication. 
Participants with COPD are not asked to tag time of medication intake. Figure 3 describes the 
in-clinic and at-home sequences of assessments using the Study Watch Participants will also 
wear the Modus StepWatch 4 concurrently with the Study Watch over 14 days, which can fall 
on any random 10 days with a  minimum of two weekend days. At least four to six hours of 
wear on these days is intended.  
 
A subset of participants may also wear the Fitbit Sense concurrently with the Study Watch and will 
be asked to wear them for the first 5 weeks between first and second visits.  
 
 
 

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Figure 3. Study Watch Assessment Sequences in clinic and at home. 
 
 
Each box is a task guided by the Study Watch graphical user interface. Different hues of gray 
represent three different types of walk tasks and 2-minute rest periods. Dotted boxes indicate 
activities required only for the participants with PD. In-clinic: dotted box indicates in-clinic MDS-
UPDRS part III that we will indicate start and finish of the subtests using the Study Watch. At-home: 
during at-home periods, participants with PD will be asked to tag medication intake whenever they 
take medications. For the prescribed day of the week, participants will receive an alert from the 
watch. Participants with PD will be instructed to perform Virtual Walk Test within 30 min to an hour 
relative to a medication intake on that day. Participants with COPD will be instructed to perform the 
task any time they prefer during the prescribed, alerted day.  
 
 
8.6 Timeline 
We aim to include 300 participants within 18  months. We will include  25 – 30 physiotherapy 
practices with both a ParkinsonNet physiotherapist and a physiotherapist specializing in COPD (up 
to 50 physiotherapists). On average each ParkinsonNet physiotherapist30-32 will need to include 4 PD 
participants and each therapist specializing in COPD should include 8 COPD participants. This 
breaks down into 1 participant with PD per physiotherapist per 2 months and 1 participant with 
COPD per physiotherapist per month. Based on our extensive experience in performing large clinical 
trials,5,33-37 we expect this to be highly feasible. After 3 months of inclusion, if we find that enrollment 
rates are too low, we have an alternative, backup scenario in place in which we will recruit 
participants with COPD from hospitals that have a high case load of people with COPD or with PD 
(either pulmonologists or neurologists). In this case, outpatient clinics will refer people with COPD to 
selected COPD specialized physiotherapists and the study activities will be performed as planned. 
With 15 weeks follow-up, all data should be included 13 months after first enrollment.  
 
 
 
8.7 Withdrawal of individual subjects 
Participants can leave the study at any time for any reason if they wish to do so without any 
consequences. The investigator can decide to withdraw a subject from the study for urgent medical 
reasons. If a subject at any time discontinues involvement in the study for any reason (drops-out) 
without explicitly withdrawing consent , the subject will be considered to only have participated in the 
portion of the study with which he/she was eligible and present. The subject will be considered a 
“non-participant” for the portion of the study for which he/she was not eligible or not present. The 
scope of the information covered in the informed consent is limited only to the data collected while 

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the subject is actively participating in study.  
 
 
8.8 Specific criteria for withdrawal (if applicable) 
Participants will only be withdrawn from the study when a medical condition does not allow the 
participant to continue the study procedures, e.g. because of repeated falling or an unstable 
cardiovascular condition. In case of a (serious) adverse event, the sponsor will carefully evaluate 
whether the participant can continue to participate in the study (see section 9.2 on adverse events). 
 
Participants that, during the study, turn out to not have either COPD or PD, but another related 
diagnosed (i.e. Parkinsonism) will be withdrawn from the study.  
 
8.9 Replacement of individual subjects after withdrawal 
 
We have taken into account 25% of data loss due to a drop-out or any other reasons in our sample 
size calculation of the COPD cohort. If the COPD cohort encounters higher than 25% drop-out rates, 
we will include new participants until we reach 150 complete COPD cases. For the PD cohort we 
have considered 10% drop-out. If the PD cohort exceeds the 10%, we will include new participants 
until we reach 90 complete PD cases.  
 
 
8.9 Follow-up of subjects withdrawn from treatment 
If a subject at any time chooses to withdraw from the study, further attempts to collect data will not 
be undertaken.  
 
If a subject at any time discontinues involvement in the study for any reason (drops-out), the subject 
will be considered to only have participated in the portion of the study with which he/she was eligible 
and present. The subject will be considered a “non-participant” for the portion of the study for which 
he/she was not eligible or not present.  
 
8.10 Lost-to- Follow-up 
A subject will be considered lost-to-follow-up and terminated from the study when three unsuccessful 
attempts by the Investigator or his/her designee to contact the subject have been documented.  
 
 
8.11 Premature termination of the study 
If suspicion of an unacceptable risk to subjects arises during the clinical investigation, or when so 
instructed by the Ethics Committee (EC), the sponsor shall suspend the clinical investigation while 
the risk is assessed.  The sponsor shall terminate the clinical investigation if an unacceptable risk is 
confirmed. Moreover, the sponsor will consider terminating or suspending the participation of an 
Investigator if monitoring  and/or auditing identifies major or repeated deviations on the part of an 
Investigator. 
 

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8.12 Potential factors impacting the data collected 
We designed the study to mitigate potential factors affecting data quality and sources of bias. 
The main factors considered were participant compliance (requirement to wear the Study Watch for 
the duration of the study), fatigue bias (when participants repeat tests during sessions), and learning 
bias (associated with surveys). 
Study Watch wear compliance will be monitored and controlled. Physiotherapists will be notified if 
participants are not compliant and will discuss with participants at the following visit. 
Fatigue bias will be monitored by surveys(Facit and Epworth) and assessed by the physiotherapists 
during clinic visits who may offer breaks. 
Learning bias will be mitigated by analyzing the data controlling for the number of repetition of the 
survey. 
 
Factors associated with participant compliance.  
Wearing the Study Watch for the duration of the study is essential for data quality. We will be 
collecting the daily wear of the Study Watch by participants and control the collected data for 
compliance. Physiotherapists will be notified   
  

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9. SAFETY REPORTING 
 
9.1 Temporary halt for reasons of subject safety 
In accordance with section 10, subsection 4, of the WMO (Medical Research Involving Human 
Subjects Act; in Dutch: Wet Medisch-wetenschappelijk Onderzoek met Mensen), the sponsor will 
suspend the study if there is sufficient ground that continuation of the study will jeopardise subject 
health or safety.  The sponsor will notify the accredited METC (Medical research ethics committee 
(MREC); in Dutch: medisch-ethische toetsingscommissie (METC)) without undue delay of a 
temporary halt including the reason for such an action. The study will be suspended pending a 
further positive decision by the accredited METC. The investigator will take care that all subjects are 
kept informed.  
 
9.2 AEs, SAEs, ADEs, SADEs, and device deficiencies 
9.2.1 Adverse events (AEs) and Adverse device effect (ADE) 
Adverse events are defined as any undesirable experience occurring to a subject during the study, 
whether or not considered related to the investigational product or any trial procedures. All adverse 
events reported spontaneously by the subject or observed by the investigator or his/her staff will be 
recorded. Adverse events will be classified according to the definition in Table 3. 
 
An Adverse Device Effect (ADE) is an adverse event related to the use of an investigational medical 
device. Note that this definition includes any adverse event resulting from insufficiencies or 
inadequacies in the instructions for use, the deployment, the implantation, the installation, the 
operation, or any malfunction of the investigational medical device. That also includes any event that 
is a result of a use error or intentional abnormal use of the investigational medical device. 
 
Table 3. Adverse event (AE) classification 
 
ADVERSE EVENTS 
Non-device-related 
Device- or procedure 
related  
Non-Serious 
Adverse Events (AE) 
Adverse Device Effect 
(ADE) 
Serious 
Serious Adverse Event 
(SAE) 
 
 
Serious Adverse Device 
Effect (SADE) 
 
Unanticipated Serious 
Device Effect (USADE) 
 
 
No AEs are expected from the clinical assessments of the self-reported questionnaires.  
 
AEs that may be expected from the Verily Study Watch, include: pruritus, dryness, redness, rash, 
and swelling around the wrist from wearing of the Study Watch. Participants exhibiting anticipated 
adverse events related to Study Watch shall contact the Radboud study team and discuss whether 
they can continue to participate in the study.  

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Any pre-existing medical condition or symptom present in a subject will not be considered an AE in 
this study, unless it worsens as a result of this study. Any mild changes that occur will be monitored 
by the Investigator and data will be recorded appropriately.  
9.2.2 Serious adverse events (SAEs) and serious adverse device effect (SADEs) 
A serious adverse event is any untoward medical occurrence or effect that:  
● Results in death; 
● Is life threatening (at the time of the event); 
● Requires hospitalization or prolongation of existing inpatients’ hospitalization; 
● Results in persistent or significant disability or incapacity; 
● Is a congenital anomaly or birth defect; or  
● Any other important medical event that did not result in any of the outcomes listed above due 
to medical or surgical intervention but could have been based upon appropriate judgment by 
the investigator. 
 
In accordance with section 10, subsection 1, of the WMO, the investigator will inform the subjects 
and the reviewing accredited METC if the frequency and severity of adverse effect suggests that the 
disadvantages of participation may be significantly greater than what was foreseen in the protocol. 
The study will be suspended pending further review by the accredited METC, except insofar as 
suspension would jeopardize the subjects’ health. The investigator will ensure that all subjects are 
kept informed.  
 
The following hospitalizations are not considered to be an SAE:  
● Hospitalizations due to PD or COPD; or 
● Hospital admissions that already were scheduled at the moment of inclusion.  
 
The sponsor will report the SAEs through the web portal, ToetsingOnline, to the accredited METC 
that approved the protocol, within seven (7) days of first knowledge for SAEs that result in death or 
are life threatening followed by a maximum period of 8 days to complete the initial preliminary report. 
All other SAEs will be reported within a maximum period of 15 days after the sponsor has first 
knowledge of the serious adverse events. SAEs will also be reported in the annual progress report to 
the accredited METC, until the end of the study in the Netherlands.  
 
9.2.3 Device deficiencies, device failures and malfunctions 
A device deficiency is defined as an inadequacy of a medical device related to its identity, quality, 
durability, reliability, safety or performance. This may include malfunctions, use errors, or 
inadequacy in the information supplied by the manufacturer. 
An incident is any malfunction or deterioration in the characteristics and/or performance of a device, 
as well as any inadequacy in the labeling or the instructions for use which, directly or indirectly, 

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might lead to or might have led to the death of a patient, or USER or of other persons or to a serious 
deterioration in their state of health. 
Throughout the study, and in conformity with ISO 14155:2020, and Medical device Regulation 
Regulation (EU) 2017/745, all observed device deficiencies are to be documented by the 
Investigator and reported to the Manufacturer on Device Deficiency Forms that are included in the 
study documentation. The investigational device is returned to the Sponsor for analysis if necessary. 
Instructions for returning the investigational device will be provided by Verily. 
The Investigator is responsible for notification of the sponsor within 5 working days. 
Device deficiencies that meet the definition for incidents (i.e. any device deficiency or failures that 
might lead or might have led to a serious adverse event if suitable action had not been taken, or 
intervention had not been made, or if circumstances had been less fortunate) must be reported to 
the Verily immediately without delay. 
 
9.3 Annual safety report 
In addition to the expedited reporting of SUSARs, the sponsor will submit, once a year throughout 
the clinical trial, a safety report to the accredited METC, competent authority, and competent 
authorities of the concerned Member States. 
This safety report consists of: 
● A list of all suspected (unexpected or expected) serious adverse reactions, along with an 
aggregated summary table of all reported serious adverse reactions, ordered by organ 
system, per study; and 
● A report concerning the safety of the subjects, consisting of a complete safety analysis and an 
evaluation of the balance between the efficacy and the harmfulness of the medicine under 
investigation. 
 
9.4 Follow-up of adverse events 
All AEs will be followed until they have abated, or until a stable situation has been reached. 
Depending on the event, follow up may require additional tests or medical procedures as indicated, 
and/or referral to the general physician or a medical specialist. 
SAEs need to be reported until the end of the study within the Netherlands, as defined in the 
protocol  
 
9.5 Data Safety Monitoring Board (DSMB) / Safety Committee 
We will not install a DSMB as this study includes limited risks (see section 12).  
 
 
 

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10. STATISTICAL ANALYSIS 
 
 
10.1 Analysis population 
Full Analysis Set is defined as participants who have at least one available pair of algorithm 
generated output (either 6MWT distance estimator or TUG estimator) and in-clinic collection of 
ground truth (either 6MWT distance or TUG measured by clinicians). Participants from the Full 
Analysis Set will be used in analysis.  
 
10.2 
Primary Analysis 
 
For COPD: 
One of the primary objectives is to assess the validity of the free-living data based 6MWT distance 
estimator. The measurement agreement between the estimates from the free-living 6MWT distance 
Estimator and the in-clinic 6MWT distance measured by the test administrator will be assessed by 
Intra-class correlation (ICC) and is expected to be more than a clinically meaningful threshold. We 
define this clinically meaningful threshold with ICC success criteria and, for COPD population, ICC is 
0.70. A test of equivalence, two one-sided test (TOST), will be used to assess the validity of the free-
living data based 6MWT distance estimator. A Bland Altman plot will also be provided.  
 
The other primary objective is to assess the validity of the virtual 6MWT distance estimator. We 
assume the model performance from virtual 6MWT will be higher than that of the free-living data 
based model, and the ICC threshold is >0.75.  A TOST procedure and a Bland Altman plot will also 
be used to assess the validity of the Virtual 6MWT distance estimator.  
 
Considering that two co-primary endpoints will be validated separately, each TOST will be 
conducted at 5.0 level, without correction for multiplicity. 
 
The algorithms are mainly developed using data collected from other sources, however, a small set 
of pre-selected data will be used to refine these algorithms prior to validation. As such, algorithm 
performance on this subset of data will not be included in the final validation analysis. 
 
For PD: 
The primary objective is to use collected data for future algorithm development. No formal 
performance evaluation will be conducted.  
 
10.3 
Secondary Analysis 
 
For COPD: 
Intraclass correlation coefficent (ICC)  and Bland Altman plots will be used to assess the 
validity of the free-living data based TUG time estimator and the Virtual TUG time estimator. 
ICC will be used to evaluate the agreement in free-living metrics between study watch and 
reference device (Step Watch). 41 

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The test-retest reliability of below algorithms will be assessed by looking at repeated 
estimates from the algorithm (e.g., week-over-week) and compared with the test-retest 
reliability of the in-clinic clinician measured 6MWT distance.  
 
The algorithms are mainly developed using data collected from other sources, however, a 
small set of pre-selected data will be used to refine these algorithms.  
 
For PD:  
ICC will be used to evaluate the agreement in free-living metrics between study watch and 
reference device (Step Watch).   
 
10.4 
Other Statistical Considerations 
Participants’ disposition, device use compliance, and data availability will be summarized for 
participants enrolled in the study. Demographic and baseline characteristics will be 
summarized for participants in the Full Analysis Set.  
 

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11. ETHICAL CONSIDERATIONS 
11.1 
 Regulation statement 
This clinical study involving human subjects are conducted pursuant to the following 
codes:  
● The Declaration of Helsinki 2007-2008 and its subsequent amendments; 
● Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001; 
on the  approximation of the laws, regulations and administrative provisions of the 
Member States  relating to the implementation of good clinical practice (GCP); 
● The Medical Research Involving Human Subjects Act (WMO); 
● ICH E6, International Conference of Harmonization (ICH) guideline for Good Clinical 
Practice; MDR(EU) 2017/745; 
● EN ISO 14155:2020; and 
● General Data Protection Regulation 2018 (GDPR), in Dutch the ‘Algemene 
verordening  gegevensbescherming’ (AVG).   
 
Any additional requirements imposed by the METC or regulatory authority shall be followed. 
 
11.2 
 Recruitment and consent 
The procedure for recruitment and consent is described in paragraph 7.2. Participants are 
recruited by participating physiotherapists; either newly referred people with COPD and PD 
or people who are already treated by the physiotherapist but haven’t received aerobic 
exercise training in the last 6 months are potentially eligible. Potentially eligible participants 
are asked by the physiotherapist if they are interested in participating in this study. If so, they 
receive the information letter. One week after receiving this letter, a researcher from 
Radboudumc calls the person. During this call, the person can ask questions and the 
researcher checks if the person fulfills the inclusion criteria. When eligible and willing to 
participate, an appointment for the first in-clinic assessment is made. Before participants 
come to the first clinic visit, participants will receive an email to create an account in the 
Baseline Platform that they will use for completion of surveys and getting notifications for 
upcoming visits. After creating the account, they will review and sign an electronic screening 
consent form to provide contact information and to give permission to contact their treating 
physician.   
 
At the start of the first in-clinic visit, the IRB approved informed consent form is signed by 
both the participant and the physiotherapist on paper. The participant l receives a copy of the 
form.  
 
11.3 
 Objection by minors or incapacitated subjects (if applicable) 
Not applicable (study only includes adults able to provide informed consent). 
 
 
11.4  
Benefits and risks assessment, group relatedness 
There are limited risks to the participant during the data collection. Potential risks relate to 
the in-clinic assessments and the unsupervised home assessments. A structured risk and 
benefit analysis is available in section 12. The participant will not directly benefit the study. 
However, they do receive 10 weeks of personalized physiotherapy as part of this protocol. 

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Because they have an indication for physiotherapy, they will also receive a physiotherapeutic 
intervention if they choose not to participate in this study.  
 
Importantly, participants will indirectly benefit from the study. The remote 
measurement of physical capacity, physical activity and potentially disease status are 
novel insights being derived and measured by the data generated by the participants 
wearing the sensors. This may, in the future, have a positive impact on remote 
disease monitoring and  more precise and personalized disease  management. In 
turn, this  potentially provides future benefits for all people affected by the disease. 
Prospectively, measurements from the Verily Study Watch could supplement and 
enhance the  information available to the physician, providing continuous 
measurement and quantitative (rather  than subjective) data. The device detects 
important physiologic parameters that are expected to  change with disease 
conditions or behavioral patterns (e.g. electrodermal activity, physical  movement of 
the body in three dimensions [acceleration], skin temperature, heart rhythm, etc.). In 
addition to collecting data, the  device also functions as a wristwatch.  
 
11.5 
 Compensation for injury 
The sponsor/investigator has liability insurance in accordance with article 7 of the WMO.  
Additionally, the sponsor has insurance in accordance with the legal requirements in the 
Netherlands (see Article 7 WMO). This insurance provides coverage in the event of damage 
to research subjects as a result of the study.This coverage applies to damage that becomes 
apparent during the study, up to and within, 4 years after the end of the study. 
 
11.6 
 Incentives (if applicable) 
The only potential incentive that participants receive as part of this study is enhancement of 
the treatment already being provided as part of their physiotherapy that is covered by the 
participant’s health insurance.    
11.7 
 Handling and storage of data and documents 
11.7.1 Data Protection 
Radboudumc will use Verily’s proprietary online platform (i.e. Baseline Platform) to collect 
clinical, behavioral, psychological, self-reported, other health-related data and demographic 
information. The Baseline Platform includes a proprietary Electronic Data Capture system, 
referred to as EDC, or eSource. Participants will be assigned a unique identifier (code) by the 
Baseline Platform.  
The participant must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant. All data used in the analysis and reporting of this evaluation will 
be pseudonymized and used without identifiable reference to the study participant.  
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB members, and by inspectors from regulatory authorities. Sponsor may provide 
access to study data to its scientific collaborators to perform further explorative analysis. 
 

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11.7.2 Privacy of Personal Data 
The collection and processing of personal data from participants enrolled in this study will be 
limited to the data that are necessary to fulfill the objectives of the study. This data will be 
collected and processed with adequate precautions to ensure confidentiality and compliance 
with applicable data privacy protection laws and regulations. Appropriate technical and 
organizational measures to protect the personal data against unauthorized disclosures or 
access, accidental or unlawful destruction, or accidental loss or alteration must be put in place. 
Study personnel whose responsibilities require access to personal data agree to keep the 
identity of participants confidential. 
 
The informed consent obtained from the participant describes the legal basis for the processing 
of personal data, i.e. the legal basis for collecting and processing data for this study is for 
research purposes as the legitimate interest.  This is the lawful basis for the 
Investigator/institution to have direct access to participant’s original source data for study-
related monitoring, audit, IRB review, and regulatory inspection.  We must also describe the 
technical and organizational measures we are using to protect the privacy, security, and 
confidentiality of this data as part of processing this data for research purposes. 
 
The informed consent also addresses the transfer of the data to other entities and to other 
countries, both within and outside of the EU. 
 
The participant has the right to request through the Investigator access to his or her personal 
data and with some limitations related to research, the right to request rectification of any data 
that are not correct or complete. Reasonable steps will be taken to respond to such a request, 
taking into consideration the nature of the request, the conditions of the study, and the 
applicable laws and regulations. 
 
11.7.3 Data Quality Assurance 
All participant data relating to the study will be recorded on printed or electronic CRF or 
ePRO, unless transmitted to the sponsor or designee electronically (e.g., device data). Verily 
uses a proprietary online portal (“Baseline Platform”) for collecting clinical, behavioral, 
psychological, self-reported, and other health-related data from participants. Additionally, 
Verily utilizes a proprietary Electronic Data Capture system, referred to as EDC, or eSource. 
Verily is responsible for the data management activities of this study, including data quality 
review. The sponsor assumes accountability for actions delegated to other individuals. The 
sponsor will review data to ensure key elements are collected, as it concerns the study. In 
case it should become necessary, additional monitoring instructions can apply. 
 
 
 
11.7.4 Record Keeping 
It is the responsibility of the Investigator and research staff to maintain a comprehensive and 
centralized filing system of all study-related documentation. This filing system must be 
suitable for inspection at any time by the sponsor, a CRO (Clinical Research Organization), 
an auditor, and/or the site EC. The study records should include: 
● Participant Files, which include (but not limited to):  

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○ Signed and dated Informed Consent Form and supporting documentation of 
the Informed Consent process; and 
○ Participant eCRFs and supporting source documentation/medical records. 
● Regulatory Binder, which contains the following (but not limited to):  
○ Clinical Investigation Plan/amendments/signature pages; 
○ EC submissions/approvals/communications; 
○ EC approved Informed Consent Forms (current and previous); 
○ Clinical Study Agreement(s)/Investigator Agreements; 
○ Investigator Brochure; 
○ Instructions For Use, if required; 
○ Electronic Case Report Forms; 
○ Signature and Delegation of Authority Logs; 
○ Site Screening and Enrolment Logs; 
○ Device Accountability Logs; 
○ CVs/Medical/Professional Licenses/Financial Disclosure Form; 
○ Training Logs; 
○ Laboratory documents (e.g., certification, norms/ ranges, etc.), if required; and 
○ Correspondence between the Site and the sponsor. 
 
The PI (Principal Investigator) will ensure that the records are maintained for a period of 15 
years after the investigation is terminated or completed, according to “Medical Device 
Regulations (EU) 2017/745”. 
 
11.7.5 Investigator Records and Reports 
Records may be audited by regulatory authorities, and must be retained for the appropriate 
period (according to the regulatory requirements). The Investigator is responsible for the 
following: 
● Records of all persons authorized to conduct the clinical study; 
● Records of receipt, use or disposition of the devices, as applicable; 
● Participant completed electronic Case Report Forms and any supporting 
documentation; and 
● Informed Consent documentation (including copy of an approved, blank consent 
form). 
● Records of all Adverse Events, Serious Adverse Events (SAE), Adverse Device 
Effects, Serious Adverse Device Effect (SADE)  and Unanticipated Adverse Device 
Effects (UADE) 
● Clinical Investigational Plan (including certification of approval) and reasons for 
deviations from the CIP; 
● Signed Investigator Agreement and CVs for all Investigators participating in the study; 
and 
● All correspondence which pertains to the clinical study. 
 
 
 
11.7.6 Record Retention 
In compliance with the ICH/GCP guidelines, the Investigator/institution will maintain all 
(e)CRFs/ source documents that support the data collected from each participant, as well as 

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all study documents as specified in ICH/GCP Section 8, Essential Documents for the 
Conduct of a Clinical Trial, and all study documents as specified by the applicable regulatory 
requirement(s). 
 
The participating physiotherapy practices will maintain records related to the study and 
excluding treatment records during the study. After the study, the records are archived at 
Radboudumc for an additional 13 years (total storage of 15 years, as required by law). The 
informed consents are stored at a different location than the investigator records and reports 
(separated locked cabinets at the Expertise Center for Parkinson and Movement disorders, 
route 914).  
  
In order to constitute evidence with respect to product safety or regulatory or legal 
compliance, the Investigator agrees to retain study-related documents in a location that is 
secure and to which access can be gained if required. The following documents must be 
archived-the Regulatory Binder containing all regulatory required documents as well as the 
Participant Files, which include the signed participant Informed Consent Forms, eCRFs, and 
source documents, if necessary. Records must be retained for the 15 years (according to 
“Medical Device Regulations (EU) 2017/745”).  
 
11.8 Monitoring and Quality Assurance  
Monitoring of the clinical investigation will be a continuous process to ensure that high-quality 
data are obtained through compliance with the study protocol and will be conducted in 
accordance with Good Clinical Practice guidelines (ICH E6).  Electronic Case Report Forms 
(eCRFs) will be reviewed for completeness, conformity with requirements, and safety 
monitoring of adverse events. A detailed monitoring plan will be submitted to the designated 
Authority at the Radboudumc for approval.  
 
On-site monitoring will be frequent enough to assure continued acceptability of the data by 
assessing compliance of the center to the protocol, adherence to the data collection 
procedures, and maintenance of clinical investigation records. Accuracy of data reported on 
the forms will be verified by comparison to the subject’s source documents/medical records, 
when applicable. If necessary, appropriate corrective action will be taken to ensure 
adherence to the CIP. 
 
The Investigator guarantees direct access to source documents/medical and hospital records 
by sponsor personnel or their designee and appropriate regulatory authorities. The clinical 
investigation may also be subject to a quality assurance audit by the sponsor or their 
designee, as well as inspection by appropriate regulatory authorities. 
 
All monitors will be qualified to perform their assigned responsibilities. Monitors are qualified 
by training and experience to monitor the progress of clinical trials and will not be involved in 
the study beyond their activities required to ensure adherence to the protocol.  
11.8.1 Deviations from clinical investigation plan 
Investigators must follow the study protocol as defined in this document. Under emergency 
circumstances, deviations from the CIP to protect the rights, safety and well-being of human 

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subjects may proceed without prior approval of the principal investigator and the METC. 
Such deviations shall be documented and reported to the sponsor and the METC 
immediately. 
Any other protocol deviations should be avoided and they should be first discussed with the 
principal investigator and, for medical issues, the Independent Expert may be consulted prior 
to implementation. 
Any deviation from the protocol will be recorded together with an explanation for the 
deviation and reported within 30 working days to the principal investigator, who is 
responsible for analysing them and assessing their significance in terms of impact of the 
deviation on the scientific value of the trial as well as the impact on the subject’s safety and 
rights. Deviations will be reviewed by the principal investigator and corrective actions taken. 
These may imply the need to amend the protocol or to terminate the investigation. In most 
cases, corrective actions will consist of additional training of investigators and support staff 
on the protocol and study procedures, and to conduct ongoing training with regard to protocol 
amendments, in order to prevent further deviations. In the event of repetitive, significant 
deviations at a particular study site, which jeopardize subject safety and/or quality of data, 
the principal investigator may consider to terminate the investigation at that particular site.  
All amendments to the protocol shall be approved by the Principal Investigator(s) and be 
recorded with a justification for the Amendments. Protocol amendments shall be submitted to 
the METC as applicable. 
 
11.8.2 Site Initiation Visit 
Site Initiation Visits (SIV) will be conducted by the Radboudumc to train the Investigator and 
supporting clinical investigation staff on the CIP objectives, subject timelines, device 
operation, electronic Case Report Form completion, Informed Consent procedures, subject 
screening and enrollment, study documentation and administration, device accountability, 
record-keeping requirements, Investigator and sponsor responsibilities, role of the Ethics 
Committee (EC)/Competent Authority (CA), adverse event and protocol deviation reporting, 
monitoring requirements and any applicable regulatory documents prior to enrolling the first 
participant. The site may not enroll study subjects into the clinical investigation until all 
applicable EC and regulatory approvals have been received by the sponsor and the site 
initiation visit is completed. SIV training will be documented and the documentation filed at 
the investigational site and at the sponsor. 
11.8.3 Interim Site Monitoring and/or Audits 
On-site monitoring visits (performed by Radboudumc or designee) and/or audits (performed 
by an independent party, commonly a Regulatory Agency) will assess the progress of the 
clinical investigation and identify any concerns that result from device performance or review 
of the Investigator’s study records, study management documents and subject Informed 

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Consent documentation. The study monitor will also ensure the Investigator adheres to the 
CIP and all applicable regulations. 
 
To assure the integrity of key data collected in the clinical investigation, the study monitor will 
compare individual subject medical records/source documentation and reports prepared by 
the Investigator or designee to the electronic Case Report Forms (eCRFs).  
 
In some instances, Site Monitoring Visits can be performed remotely as long as key data 
provided on eCRFs is properly monitored against source documents. 
Investigators found not complying with the CIP and regulations will be terminated from the 
clinical investigation and shall be required to return all unused devices and/or associated 
clinical investigation materials and procedure manuals to the sponsor. 
 
11.8.4 Site Close-out Visit 
A Site Close-out Visit will be conducted at the completion of the clinical study. During the 
close-out visit, Radboudumc or designee will ensure that all eCRFs and data queries are 
signed and dated and have been transmitted to the sponsor, the device accountability log 
has been reconciled and any remaining study devices have been shipped back to Verily. 
Additionally, Radboudumc will review the Investigator’s ongoing study responsibilities, 
including to report any unexpected or device related adverse events, to submit a final study 
report and a notification of study close to the EC and to maintain study files per regulations. 
In some instances, the Site Close-out Visit may be conducted over the phone. 
 
Completed eCRFs will be verified against source data/medical records by the designated 
study monitor for completeness and consistency. If corrections/modifications are needed 
during the monitoring visit, the Investigator or designee will correct the data directly on the 
eCRF. Corrections will be listed in the audit trail of the eCRF/EDC system. All data 
corrections will comply with the International Conference of Harmonization (ICH) and Good 
Clinical Practice (GCP) guidelines.  
 
 
11.9 Amendments  
Amendments are changes made to the research after a favourable opinion by the accredited 
METC has been given. A ‘substantial amendment’ is defined as an amendment to the terms 
of the METC application, or to the protocol or any other supporting documentation, that is 
likely to affect to a significant degree: 
● the safety or physical or mental integrity of the subjects of the trial; 
● the scientific value of the trial; 
● the conduct or management of the trial; or 
● the quality or safety of any intervention used in the trial. 
 
 All substantial amendments will be notified to the METC and to the competent authority.  
Non-substantial amendments will not be notified to the accredited METC and the competent 
authority, but will be recorded and filed by the sponsor.  
 

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11.12 
 Annual progress report 
The sponsor/investigator will submit a summary of the progress of the trial to the accredited 
METC once a year. Information will be provided on the date of inclusion of the first subject, 
numbers of subjects included and numbers of subjects that have completed the trial, serious 
adverse events/ serious adverse reactions, other problems, and amendments.  
 
 
11.13 Temporary halt and (prematurely) end of study report 
The end of the study is defined as the last participant’s last visit. The sponsor or the safety 
committee can decide to terminate the study at any time. While the study may be terminated 
early due to safety or adverse event concerns, there is no plan for early termination based on 
outcomes. 
 
The investigator/sponsor will notify the accredited METC of the end of the study within a 
period of 15 days. The sponsor will notify the METC immediately of a temporary halt of the 
study, including the reason for such an action.  
    
In case the study is ended prematurely, the sponsor will notify the accredited METC within 15 
days, including the reasons for the premature termination. 
 
Within one year after the end of the study, the investigator/sponsor will submit a final study 
report with the results of the study, including any publications/abstracts of the study, to the 
accredited METC.  
 
 
11.14 End of study report 
The sponsor will notify the accredited EC and the Competent Authority of the end of the 
study within three (3) months of completion or termination of the study. Study completion is 
defined as the last participant’s last visit.  
 
Within one year after the end of the study, the sponsor will submit a final Clinical Report with 
the results of the study, including any publications/abstracts of the study, to the accredited 
EC and the Competent Authority.  
 
The investigator/sponsor will notify the accredited METC of the end of the study within a 
period of 8 weeks. The end of the study is defined as the last participant’s last visit.  
 
Within one year after the end of the study, the investigator/sponsor will submit a final study 
report with the results of the study, including any publications/abstracts of the study, to the 
accredited METC.  
 
11.15 
 Public disclosure and publication policy 
Any publication or presentation by the Investigator, Research Collaborators, or any other 
collaborative center(s) based on data or results resulting from this study shall only be done in 
strict accordance with the Publication Policy specified in the respective Collaboration 
Agreements with Radboudumc. 
 

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The Party proposing a Publication shall provide the other Party with a copy of the proposed 
Publication at least thirty (30) business days prior to its intended submission for publication. 
The non-publishing Party will review the Publication to: (1) determine whether any of such 
Party’s Confidential Information is disclosed in the Publication; (2) identify potentially 
patentable inventions; and (3) with respect to Partner as the publishing Party, determine 
whether the Publication in any way may disclose details relating to the performance of the 
Verily Technology itself, its derivatives, or the methods or technology by which it was 
collected or generated. The non-publishing Party shall provide comments within thirty (30) 
days of receipt of any proposed Publication by the publishing Party. Upon the request of the 
non-publishing Party, the publishing Party will delete the non-publishing Party’s Confidential 
Information (other than as expressly and mutually agreed by the Parties under the applicable 
Work Plan) from any form of Publication. If the non-publishing Party notifies the publishing 
Party that the Publication reveals a potentially patentable invention of the non-publishing 
Party, then the publishing Party will delay submission of the Publication for publication to 
enable the preparation and filing of a patent application with respect to such invention; 
provided, however, that such delay shall not exceed ninety (90) days.  If Verily notifies 
Partner that the Publication is reasonably likely to disclose details relating to the performance 
of the Verily Technology itself, its derivatives, or the methods or technology by which it was 
collected or generated, Partner will delete that portion of the Publication so implicated.

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12. STRUCTURED RISK ANALYSIS  
 
12.1 Potential issues of concern 
 
There are limited risks to the participant during the data collection. Potential risks relate to 
the in-clinic assessments and the unsupervised home assessments with the TUG and 
6MWT. Considering the in-clinic assessments, all tests are supervised by a trained 
physiotherapist who will monitor participant safety continuously. As these tests that are 
performed as part of this project are also part of usual care, we expect the risks during 
clinical assessment to be minimal. For the home assessments, there may be a risk of falling 
or cardiovascular events. We have tried to minimize these risks by including a population that 
is expected to perform these tests safely at home (i.e. exclusion criteria; not fallen more than 
once in the last 3 months, no unstable cardiovascular diseases, permission of treating 
physician to participate). Moreover, the first walking tests are performed under direct 
supervision of the physiotherapist who can judge and discuss potential safety issues with the 
participant.  
 
 
 
12.1.1 Verily Study Watch 
The structured risk analysis of the Verily Study Watch is included in the Investigator Brochure      
(D1. Investigator Brochure.2020-6969.v3.11-JUN-2019). 
 
 
 
12.1.2 Participant burden and benefits  
The burden of participating in this study consists of 4 visits to the local physiotherapy practice 
for in-clinic assessments of disease status and walking tests. Every in-clinic visit will take 
approximately 120 minutes. In addition, participants are asked to wear the Study Watch 
continuously for 15 weeks and perform two walking tests once a week. Participants may 
benefit directly from participating in this study because they will receive 10 weeks of 
physiotherapy by a specialized physiotherapist.  
 
 
12.2 Synthesis 
 
The risks associated with participation in this study can be considered negligible in terms of 
participants getting serious harm. Even though the potential damage is serious (i.e fractures 
after a fall incident or cardiovascular events), the chances of this to occur is minimal because 
we have taken a number of actions to minimize the risk. These actions include: 
● Including a population with low fall risk (i.e. patients that have fallen more than once in the 
last six months will be excluded); 
● Excluding participants with an unstable cardiovascular condition;  
● Asking the treating physician permission for participation; and/or 
● Performing the first walking tests in-clinic, and under direct supervision of the 
physiotherapist. The physiotherapist will be able to make a reliable judgement of the potential 
risk of performing the tests unsupervised at home.  
 
 
 

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Table 5. Risk classification schedule 
Extent of additional 
risk/ 
Degree of damage 
Minimal damage 
Moderate damage 
Serious damage 
Minimal chance 
Negligible risk 
Negligible risk 
Moderate risk 
Moderate chance 
Negligible risk 
Moderate risk 
High risk 
High chance 
Moderate risk 
High risk 
High risk 
 
 
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Disease: A Review. Journal of Parkinson's disease 2016; 6(4): 685-98. 
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Variability of Walking Performance Measures in Individuals Poststroke and Individuals With 
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Ummels D, Beekman E, Theunissen K, Braun S, Beurskens AJ. Counting Steps in 
Activities of Daily Living in People With a Chronic Disease Using Nine Commercially 
Available Fitness Trackers: Cross-Sectional Validity Study. JMIR mHealth and uHealth 2018; 
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Parkinson's Disease The Netherlands: KNGF/ ParkinsonNet, 2014. 
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KNGF richtlijn COPD: Koninklijn Nederlands Genootschap voor Fysiotherapie (KNGF), 2020. 
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Project: examining disease progression through broad biomarkers in early Parkinson's 
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ParkinsonNet approach. BMJ (Clinical research ed) 2014; 348: g1838. 
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a low cost health care innovation with a systems approach from the Netherlands Health 
Affairs 2017; In press. 
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Interventions for Parkinson Patients. Journal of Parkinson's disease 2018; 8(1): 45-58. 
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34. 
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patients with Parkinson's disease: a randomised controlled trial. The Lancet Neurology 2014; 
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van der Marck MA, Munneke M, Mulleners W, et al. Integrated multidisciplinary care 
in Parkinson's disease: a non-randomised, controlled trial (IMPACT). The Lancet Neurology 
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van der Kolk NM, de Vries NM, Kessels RPC, et al. Effectiveness of home-based and 
remotely supervised aerobic exercise in Parkinson's disease: a double-blind, randomised 
controlled trial. Lancet Neurol 2019; 18(11): 998-1008. 
37. 
Radder DLM, Lennaerts HH, Vermeulen H, et al. The cost-effectiveness of 
specialized nursing interventions for people with Parkinson's disease: the NICE-PD study 
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APPENDIX A 
Researchers and/or study staff at Radboud will access and download the following data 
gathered from your de-identified Fitbit account: 
 
● Daily steps total 
● Measured steps per minutes 
● Estimated energy expenditure per minutes 
● Distance moved per minutes 
● Minutes of vigorous activity per minutes 
● Minutes of moderate activity per minutes 
● Minutes of light activity per minutes 
● Minutes of sedentary time per minutes 
● Sleep length, quality, and movement per minutes 
● Heart rate per second 
● Manually entered and automatically detected physical activities, such as walking or 
running 
● Manually entered information in your Fitbit study account (such as height, weight, 
gender, and age; information that you elected to share with the Fitbit account (for 
example linking a smart scale), and information about other accounts that you may 
link with your Fitbit study account. This information will be ignored by the study staff. 
 
Note that geolocation data collection is not accessible by researchers and study staff. No 
data will be transferred to Verily or available for Verily employees until Verily sets up 
appropriate Access Controlled Data Store (ARDS).