Tele-health Outcomes as Digital Biomarkers of Parkinson's Disease Progression During Extended Follow up of STEADY-PD3 and SURE-PD3 Trial Participants
Conditions: Parkinson Disease
Sponsor: Massachusetts General Hospital

   Protocol Title: AT-HOME PD [Assessing Tele-Health Outcomes in Multiyear Extensions of PD trials] 
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CLINICAL STUDY PROTOCOL 
 
Title: 
 
Tele-health outcomes as digital biomarkers of 
Parkinson’s disease progression during extended 
follow-up of STEADY-PD III and SURE-PD3 trial 
participants. 
 
Acronym: 
 
AT-HOME PD [Assessing Tele-Health Outcomes in 
Multiyear Extensions of PD trials] 
 
Sub-Study Title: 
AHPD – SUPER-PD Tele-visit Validation 
 
Protocol No.: 
 
AHPD-U01NS107009 
 
Clinical Phase:  
 
Observational 
 
Sponsor: 
 
National Institute of Neurological Disorders and Stroke 
(NINDS) 
 
Principal Investigators: E. Ray Dorsey, MD MBA 
 
 
 
Larsson Omberg, PhD 
 
 
 
Michael Schwarzschild, MD PhD 
 
 
 
Tanya Simuni, MD 
 
Co-Principal  
 
 
Elise Kayson, MS, ANP 
Investigators:  
 
Mike Kellen, PhD  
 
 
 
 
 
Clinical Coordination 
University of Rochester  
Center: 
 
 
Center for Health & Technology (CHeT) 
 
 
 
Clinical Trials Coordination Center (CTCC) 
 
 
 
265 Crittenden Boulevard 
 
 
 
Rochester, New York 14620 
 
 
 
 
Biostatistics Center: 
Eric Macklin, PhD 
 
 
 
Massachusetts General Hospital  
 
 
 
MGH Biostatistics Center 
 
 
 
50 Staniford St., Suite 560 
 
 
 
Boston, MA 02114 
 
CONFIDENTIAL 
This document is a confidential communication of the Parkinson Study Group (PSG). The 
recipient agrees that no information contained herein will be published or disclosed without 
written approval by a study PI. This document may be disclosed to appropriate institutional 
review boards, independent ethics committees, or duly authorized representatives of the U.S. 
Food & Drug Administration or other regulatory authorities as appropriate; with the 
understanding that confidentiality is requested 
 
NCT03538262

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PROTOCOL APPROVAL 
 
STUDY TITLE: 
Tele-health outcomes as digital biomarkers of 
Parkinson’s disease progression during extended 
follow-up of STEADY-PD III  and SURE-PD3 trial 
participants.  
  
STUDY ACRONYM:  
AT-HOME PD [Assessing Tele-Health Outcomes in 
Multiyear Extensions of PD trials]  
SUB-STUDY TITLE: 
AHPD – SUPER-PD Tele-visit Validation 
 
E. Ray Dorsey, MD MBA  
             
 
 
Date 
Principal Investigator 
 
Larsson Omberg, PhD 
             
 
 
Date 
Principal Investigator 
 
Michael Schwarzschild, MD PhD 
             
 
 
Date 
Principal Investigator 
 
Tanya Simuni, MD 
             
 
 
Date 
Principal Investigator 
 
Eric Macklin, PhD 
 
 
 
 
Date 
Biostatistician 
 
Codrin Lungu, MD 
 
 
 
 
Date 
Program Director, NINDS [Sponsor] 
 
Lindsey Riley 
 
 
 
 
Date 
Senior Associate Director, Research Partnerships, MJFF [Collaborator]  
 

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INVESTIGATOR AGREEMENT 
CHeT Site 
I have carefully read this protocol, including all appendices, and agree that it contains 
all the necessary information for conducting the study safely. 
 
I will conduct this study in strict accordance with this protocol and according to the 
current Good Clinical Practice (GCP) regulations and guidelines [21 CFR (Code of 
Federal Regulations) Parts 11, 50, 54 and 56 and ICH (International Conference on 
Harmonization of Technical Requirements for Registration of Pharmaceuticals for 
Human Use) Topic E6 (R2)], and local regulatory requirements. Any changes in 
procedure will only be made if necessary to eliminate immediate hazards and/or to 
protect the safety, rights or welfare of participants.  
 
I will provide copies of the protocol and all other information relating to the study, which 
were furnished to me, to all physicians and other study personnel responsible to me 
who participate in this study. I will discuss this information with them to assure that 
they are adequately informed regarding the conduct of the study. 
 
I will ensure that the supplies/equipment supplied to me for this study will be used only 
for administration to participants enrolled in this study protocol and for no other 
purpose. 
 
I agree to keep records on all participant information (electronic case report forms, 
electronic informed consent forms, and all other information collected during the study) 
in accordance with the current GCP, local and national regulations. 
 
 
Printed Site Name  
 
 
 
 
 
 
 
Printed CTCC Site Investigator Name* 
 
 
 
 
 
 
CHeT  Site Investigator Signature 
 
Date 
 
*NOTE: E. Ray Dorsey, MD MBA, is the Site Investigator of record with Rochester’s Research 
Subjects Review Board (RSRB). Dr. Dorsey is delegating responsibilities for the actual tele-visits 
to other UR clinicians and documented on the study Delegation Log. 
 

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DOCUMENT HISTORY 
Version 
Date of Issue 
Summary of Changes 
1.0 
17 Sep 2018 
Initial Version 
2.0 
21 Nov 2018 
Investigator agreement page and 
throughout protocol: Replaced 
CTCC with CHeT when describing 
study site 
2.0 
21 Nov 2018 
List of Abbreviations – added VC 
(video conference) and API 
(application program interface) 
2.0 
21 Nov 2018 
Protocol Synopsis, Sections 4.2 and 
5.1 – Added language to allow 
subjects from STEADY PDIII and 
SURE PD3 who declined consenting 
to future contact the ability to 
directly contact UR to request 
information about participating in 
AT-HOME PD 
2.0 
21 Nov 2018 
Schedule of Activities and Section 
5.5.2 – replaced tele-visit with video 
conference to describe the screening 
visit 
2.0 
21 Nov 2018 
Schedule of Activities and Section 
5.5.3 – Removed smartphone app 
registration from the list of activities 
performed at the baseline visit and 
added language to allow for 
registration in Synapse web portal 
to occur just prior to the visit date 
2.0 
21 Nov 2018 
Section 1.1 – Updated the length of 
time DAT scan follow-up that will be 
conducted in SURE-PD3 to over a 
length of 1 to 2 years.   
2.0 
21 Nov 2018 
Section 5.1 – Revised language 
regarding contacting SURE-PD3 
subjects to allow contact after 
completion of SURE-PD3 study 
2.0 
21 Nov 2018 
Sections 5.1 and 8 – Replaced 
subject payment method from debit 
card to check and added language 
offering additional standard internet 
and/or smartphone/data plan 
reimbursement for minorities. 

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Version 
Date of Issue 
Summary of Changes 
2.0 
21 Nov 2018 
Sections 5.1, 5.5.1, 5.5.2, and 5.5.3 
– Revised the window of timing for 
contacting SURE-PD3 participants 
and completing the prescreen call, 
screening video conference, and 
baseline tele-visit and replaced the 
description of the last in-person 
SURE-PD3 study visit from “on-
drug” to “final visit (or equivalent) in 
the planned treatment period” 
2.0 
21 Nov 2018 
Section 5.2 – Removed language 
stating CTCC team member will 
email reminders to participants to 
eConsent, revised language to 
specify screening visit will be 
scheduled during prescreen call, 
and added language to state AHPD 
staff may email participant the 
current UR IRB approved consent 
form, if requested during the 
prescreen call  
2.0 
21 Nov 2018 
Section 5.4 – Revised to reflect 
REDCap entries will be created on 
all participants AHPD study team 
establishes direct contact with 
2.0 
21 Nov 2018 
Section 5.5.1 – Clarified delivery 
method and timing of eConsent and 
technology survey 
2.0 
21 Nov 2018 
Section 5.5.2 – Modified duration of 
screening visit to approximately 30 
minutes 
2.0 
21 Nov 2018 
Section 5.5.2 – Modified the list of 
information required for creating a 
participant’s FI account and 
updated the description of events 
occurring if a participant is already 
enrolled in FI  
2.0 
21 Nov 2018 
Section 5.5.4 – Removed SMS as the 
means of notification method for 
mPower reminders 

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Version 
Date of Issue 
Summary of Changes 
2.0 
21 Nov 2018 
Section 6.1.3 – Removed sentences 
from MDS-UPDRS Part III stating 
that subjects on symptomatic 
dopaminergic therapy will be asked 
to (optionally) hold their morning 
dose during visit days 
2.0 
21 Nov 2018 
Section 12 – Removed “enactment of 
Medical Safety Escalation Plan” 
from the list of reportable events 
and added a statement below that it 
should be reported to the CTCC PM 
2.0 
21 Nov 2018 
Section 15.5 – Replaced “de-
identified” with “transformed” to 
describe the transferred dataset 
2.0 
21 Nov 2018 
Section 15.5 – Updated the 
description of tele-visit REDCap 
data access to state Sage 
Bionetwork access via API 
2.0 
21 Nov 2018 
Section 17.2 – Added process of 
entering data during REDCap 
downtime via collection on paper 
CRFs 
2.0 
21 Nov 2018 
Administrative changes throughout 
3.0 
06 Nov 2019 
Replacement of Lara Mangravite 
with Larsson Omberg as a principal 
investigator 
3.0 
06 Nov 2019 
Replacement of Lauren Bataille with 
Lindsey Riley as listed collaborator 
from MJFF 
3.0 
06 Nov 2019 
Updated Steering Committee List 
3.0 
06 Nov 2019 
Updated Acronyms List with 
addition of PD-PROP and SUPER-
PD 
3.0 
06 Nov 2019 
Protocol Synopsis and Section 13.4 
– updated sample size 
determination and true 
concordance for SURE-PD3 and 
combined SURE-PD3 and SUPER-
PD participants expected to 
complete at least one TV close in 
time to their in-person clinic visit.  
3.0 
06 Nov 2019 
Updated Figures 1 and 2 with 
added data flow description from 
DMR to Qualified Researchers and 
added Figure 1a 

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Version 
Date of Issue 
Summary of Changes 
3.0 
06 Nov 2019 
Addition of SUPER-PD sub-study 
throughout 
3.0 
06 Nov 2019 
Administrative Changes Throughout  
 
 
 

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Table 1. List of abbreviations and definition of terms 
 
Abbreviation or 
specialist term 
Definition 
ADAGIO  
Attenuation of Disease Progression with Azilect Given Once-daily 
AE 
Adverse Event  
AHPD 
AT-HOME Parkinson's Disease  
API 
Application Program Interface 
AUC 
Area under the concentration-time curve  
CAPA 
Corrective and Preventive Action Plans  
CDEs  
Common Data Elements  
CFR 
Code of Federal Regulations 
CGI-S 
Clinician Global Impression – Severity   
CHeT 
University of Rochester Center for Health + Technology 
CNS 
Central Nervous System 
Co-I 
Co-Investigator 
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
CTCC 
Clinical Trials Coordination Center 
DAT  
Dopamine transporter  
DATATOP 
Deprenyl And Tocopherol Antioxidative Therapy Of Parkinsonism 
DM 
Data Management 
DMR 
Data Management Resource 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
EDL 
Experiences of Daily Living 
ET 
Early Termination  
FDA 
Food and Drug Administration 
FI 
FoxInsight 
GCP 
Good Clinical Practice 
GPS 
Global Positioning System 
GUID 
Global Unique Identifier 
HIPAA 
Health Insurance Portability and Accountability Act 
HSPP 
Human Participant Protection Program 

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Abbreviation or 
specialist term 
Definition 
ICC 
Intra-class correlation  
ICD 
International Classification of Diseases 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
ICJME 
International Committee of Medical Journal Editors 
ID 
Identification Number 
IR 
Immediate Release 
IRB 
Institutional Review Board 
ITT 
Intent-to-treat 
IV/WRS 
Interactive Voice/Web Response System 
LONI 
Laboratory of Neuro Imaging 
MDS-UPDRS 
Movement Disorders Society-Unified Parkinson’s Disease Rating 
Scale  
MedDRA 
Medical dictionary for Regulatory Activities 
MGH 
Massachusetts General Hospital 
MJFF 
Michael J Fox Foundation for Parkinson’s Research 
MMSE 
Mini-Mental State Exam  
MoCA 
Montreal Cognitive Assessment 
NINDS 
National Institute of Neurological Disorders and Stroke  
NW 
Northwestern University 
ORPA 
Office of Research and Project Administration 
PD 
Parkinson’s Disease  
PD-PROP 
Parkinson Disease Patient Reported Outcome of Problems 
PDBP 
Parkinson’s Disease Biomarkers Program 
PDF 
Portable Document Format 
PGI 
Patient Global Impression 
PI 
Principal Investigator 
PM 
Project Management 
PP 
Per Protocol 
PPMI 
Parkinson’s Progression Markers Initiative 
PRO 
Patient Reported Outcomes 
PSC 
Protocol Steering Committee 
PSG 
Parkinson Study Group  

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Abbreviation or 
specialist term 
Definition 
PT 
Preferred Term 
PW 
Premature Withdrawal 
QA 
Quality Assurance 
QC 
Quality Control 
RE 
Reportable Events 
REDCap 
Research Electronic Data Capture 
ROC 
Receiver Operating Characteristic Curve 
RSRB 
Research Subjects Review Board 
SA 
Specific Aim 
SAE 
Serious Adverse Event  
SAP 
Statistical Analysis Plan 
SC 
Steering Committee 
SD 
Standard Deviation 
SE 
Standard Error 
SEADL 
Schwab & England Activities of Daily Living Scale 
SMC 
Safety Monitoring Committee 
SOA 
Schedule of Activity 
SOC 
System Order Class 
SOP 
Standard Operating Procedure 
SP 
Smartphone 
ST 
Symptomatic Dopaminergic Therapy 
SUPER-PD 
Sensor Use to Monitor Progression and Evaluate Symptoms 
Remotely in Parkinson’s Disease 
TBI 
Traumatic Brain Injury 
TV 
Tele-visit  
UPDRS 
Unified Parkinson’s Disease Rating Scale 
UR 
University of Rochester 
URMC 
University of Rochester Medical Center 
USC 
University of Southern California 
 VC 
Video Conference 
 
 
 

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AT-HOME PD PROTOCOL SYNOPSIS 
Protocol Title 
Tele-health outcomes as digital biomarkers of Parkinson’s 
disease progression during extended follow-up of STEADY-
PD III and SURE-PD3 trial participants 
Acronym 
AT-HOME PD  
(Assessing Tele-Health Outcomes in Multiyear Extensions of 
PD trials) 
Protocol No. 
AHPD-U01NS107009 
Sponsor 
NINDS  
Investigators 
Principal Investigators 
E. Ray Dorsey, MD MBA 
Larsson Omberg, PhD 
Michael Schwarzschild, MD PhD  
Tanya Simuni, MD 
Institutions 
Primary project performance  
Massachusetts General Hospital 
Northwestern University 
Sage Bionetworks 
University of Rochester 
Collaborating 
Michael J. Fox Foundation for Parkinson’s Research 
Parkinson Study Group (PSG) 
Steering Committee 
Alberto Ascherio, MD DrPH  
James Beck, PhD 
Kevin Biglan, MD, MPH 
E. Ray Dorsey, MD MBA 
Alberto Espay, MD 
Robert Holloway, MD MPH 
Elise Kayson, MS ANP 
Caroline Tanner, MD PhD 
Eric Macklin, PhD 
Larsson Omberg, PhD 
David Oakes, PhD 
Michael Schwarzschild, MD PhD (SC Co-chair [initial]) 
Ira Shoulson, MD 
Tanya Simuni, MD (SC Chair [initial]) 
Dan Novak, PhD (Parkinson’s Foundation PAIR program 
patient advocate) 
Codrin Lungu, MD (NINDS Scientific Program Director) 

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No. Study Centers 
One: University of Rochester, Center for Health + 
Technology (CHeT)/Clinical Trials Coordination Center 
(CTCC) 
Objectives 
 
 
1. To establish and implement an infrastructure for 
longitudinal remote follow-up of phase 3 trial cohorts: 
a. Transition from site-based to a centralized site and 
coordination center to manage all participant 
activity in virtual extensions of SURE-PD3, with 
projected enrollment of ≥70% of final trial cohorts, 
and core data collection in accordance with 
Parkinson’s Disease Biomarkers Program (PDBP) 
schedule of activities. 
b. Conduct an annual research visit (tele-visit) 
program and establish the feasibility and cross-
sectional reliability of tele-visit versus in-person 
visit assessments in a subset of STEADY-PD III and 
SURE-PD3 participants. 
c. Deploy a smartphone application, based on the 
mPower study, for remote data collection in a 
clinical trial cohort as preliminarily characterized 
in the Smart4SURE sub-study of SURE-PD3. 
d. Establish a mechanism for linking STEADY-PD III 
and SURE-PD3 study data with data collected 
through smartphone-based assessments, tele-
visits, and Fox Insight (FI), a separate longitudinal 
patient-reported outcomes (PROs) online research 
study. 
2. To compare patient-driven (smartphone, web-based 
surveys) vs clinician-driven (tele-visit) outcomes by:  
a. Correlating 
the 
smartphone 
and 
tele-visit 
platforms’ component and composite features, and 
their changes over years. 
b. Comparing 
the 
smartphone 
and 
tele-visit 
platforms’ abilities to: i) measure PD progression 
and predict clinical events and changes in PROs; ii) 
distinguish rapid vs slow progressors based on 
baseline 
Movement 
Disorders 
Society-Unified 
Parkinson’s Disease Rating Scale (MDS-UPDRS) 
scores, dopamine transporter (DAT) deficit (in 
SURE-PD3) or serum urate levels (in STEADY-PD 
III); iii) demonstrate persistence of any effects of 
isradipine or inosine in their respective trials. 
c. Comparing completion status and performance on 
FI and tele-visit PROs. 
3. To explore novel smartphone-based real-life mobility 
biomarkers of PD disability and its progression that 
are 
normally 
inaccessible 
with 
traditional 
office 
measures. We will investigate the ability of passively 
collected smartphone data on ambulation and location 
to enable assessments of physical 
activity and 

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socialization that correlate with motor and non-motor 
functions.  
Study/Observation 
Period 
24 months (with rolling enrollment), after completion of the 
interventional phases of STEADY-PD III and SURE-PD3 
Study Population 
All individuals with early idiopathic PD enrolled in the 
STEADY-PD 
III 
(NCT02168842) 
and 
SURE-PD3 
(NCT02642393) studies (N≈600) who have consented to be 
contacted for future research will be asked to participate or 
if a subject from these two studies directly contacts the 
University of Rochester (UR) to request information about 
study participation. 
We expect approximately 70% of STEADY-PD III and SURE-
PD3 participants (N≈420) are expected to consent and 
participate in at least the tele-visit portion of the study. 
We expect approximately 80% of individuals who enroll in 
this study (N≈340) to participate in the smartphone portion 
(and thus the smartphone vs tele-visit comparison) of the 
study. 
We expect approximately 70% of individuals who participate 
in the smartphone portion of the study (N≈240) to consent 
to passive collection of motor and mobility data. 
We expect approximately 80% of individuals who enroll in 
this study (N≈340) to participate in the FI portion of the 
study. 
Study Design 
Observational study to characterize and compare long-term 
clinical outcomes data collected remotely through annual 
tele-visits, quarterly interactive smartphone app sessions, 
and web-based surveys in individuals with PD who have 
completed the interventional phases of STEADY-PD III and 
SURE-PD3 clinical trials. 
Number of 
Participants 
Approximately 420 
Main Inclusion 
Criteria 
 
1. Enrollment in STEADY-PD III or SURE-PD3 studies  
2. Prior consent to be contacted by the University of 
Rochester (UR) or if  a subject from STEADY-PD III or 
SURE-PD3 studies directly contacts UR to request 
information about study participation  
3. Internet-enabled device that will support participation in 
tele-visits  
4. Have created or willing to create a Global Unique 
Identifier (GUID) 
5. Willing and able to provide informed consent 
6. English fluency 
7. For participants opting to participate in the smartphone 
component, possession of a suitable smartphone (iPhone 

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or Android) with adequate data plan and cellular network 
access/signal or Wi-Fi access 
Main Exclusionary 
Criteria 
1. Inability to carry out study activities as determined by 
study staff 
Study background 
and Rationale 
At the launch of AT-HOME PD the STEADY-PD III and 
SURE-PD3 trials were active NINDS-funded phase 3 studies 
of potential disease-modifying interventions in PD. The long-
term observation of participants from these trials, while 
challenging to implement, was deemed a valuable research 
opportunity. The reliance on in-person visits and snapshot 
assessments in a condition characterized by variable 
symptoms is an important limitation. Tele-visit, web-based 
surveys, and smartphone-based remote sensor assessments 
represent particularly promising methods for streamlining 
study conduct, reducing participant burden, and enabling 
the collection of data beyond the usual episodic, in-clinic 
assessments. The objective of this study is to leverage 
modern technology to develop, pilot and implement a 100% 
virtual model for long-term follow-up utilizing tele-visit and 
smartphone platforms for quantitative monitoring of 
clinician- and patient-reported outcomes (PROs).  
Study Platforms and 
Outcome Measures  
Tele-visit platform – Participants will complete a total of 
three tele-visits, which will occur at baseline, month 12, and 
month 24. Some activities will be completed either prior to 
or post tele-visit by the participant. Assessments will 
include: 
x 
Review of reportable events 
x 
Review of concomitant medications 
x 
MDS-UPDRS parts 1a, 3, and 4 (where applicable) 
x 
Montreal Cognitive Assessment (MoCA) 
x 
Schwab & England Activities of Daily Living Scale 
(SEADL) 
x 
Clinician Global Impression and Patient Global 
Impression – Severity and Change  
x 
Determination of Falls 
x 
Performance of one complete set of active motor and 
cognitive 
smartphone 
application 
tasks 
(when 
applicable) 
x 
Review of completion of MDS-UPDRS parts 1b and 2, 
self-reported falls, and patient global impression – 
severity and change (with direct link to survey sent 
ahead of visit) 
x 
Review of compliance with smartphone tasks and FI 
assessments where applicable 
x 
Preference and Burden Survey 

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Investigators administering MDS-UPDRS part 3 (motor 
examination) will be neurologists or nurse practitioners who 
have obtained formal MDS-UPDRS certification and will 
have additionally undergone joint training to reconcile 
scoring differences and minimize inter-rater variability. 
Tele-visits will be scheduled in either the morning or 
afternoon according to participant preference and, for 
participants on symptomatic dopaminergic therapy, the 
MDS-UPDRS will be preferably performed in the usual ON 
state. 
 
FI web-based survey platform – Participants will be asked 
to complete a set of standard questionnaires every 3 months 
through an online observational companion study called FI. 
Study participants will be encouraged but not required to 
participate in FI. Standard assessments include: 
x 
The Parkinson’s Disease Questionnaire, short-form 8 
item version (PDQ-8) 
x 
MDS-UPDRS part 2  
x 
Physical Activity Scale for the Elderly (PASE) 
x 
Your Cognition and Daily Activities (PDAQ-15) 
x 
Euroqol Five (EQ-5D)  
x 
Non-motor symptoms questionnaire (NMS-QUEST) 
x 
Geriatric Depression Scale, short form (GDS) 
x 
Parkinson’s Disease-Patient Reported Outcomes of 
Problems (PD-PROP) 
Participants are invited to complete additional PRO surveys 
about, but not limited to, symptoms, disease progression, 
quality of life, patient preference or general health. 
Smartphone session platform (mPower-based app) – We 
will use mPower 2.0 developed by Sage Bionetworks on both 
iOS and Android. mPower will include active tasks to be 
completed (Scientific Aim (SA) 2) and allow passive collection 
of motor and mobility data with participant permission (for 
SA3). 14-day smartphone sessions will occur every 3 
months. During these sessions, participants will complete 
smartphone-based motor tasks daily on at least 10 days and  
cognitive assessments on at least 3 days. Given diurnal 
variation in active task performance, participants will be 
asked to select morning or afternoon as their preferred 
window for completion and to consistently complete the 
active tasks according to their selected preference. 
Motor Tasks: 
x 
Gait task - a 30 second walk   
x 
Finger tapping task - 30 seconds of rapid finger 
tapping in each hand 

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x 
Resting tremor task - 30 seconds of holding phone in 
each hand 
x 
Balance task - 30 seconds of standing still  
  Cognitive Assessments: 
x 
Digit span 
x 
Digit symbol substitution 
x 
Spatial working memory 
Enrolled participants will also use the application to track 
their medication adherence relative to tasks and, optionally, 
self-reported symptoms and triggers. For those participants 
who optionally consent to passive data collection, the 
smartphone application will collect multiple streams of 
passive data including: movement patterns captured by 
location services on phone and walking patterns captured 
by accelerometer gyroscope, and pedometer.  
Study Compliance 
Compliance with all three study platforms will be monitored.  
CHeT/CTCC will monitor compliance through tele-visits and 
patient interview during the visit. Sage Bionetworks will 
utilize push notifications and Short Message Service (SMS) 
reminders to encourage compliance with smartphone-based 
assessments. MJFF will send automated e-mail reminders 
to complete the quarterly assessments after approximately 
45 days and again after approximately 88 days. CHeT/CTCC 
will receive quarterly compliance reports from Sage 
Bionetworks and from MJFF (until a publicly-accessible 
research dashboard becomes available through University of 
Southern California’s Laboratory of Neuro Imaging (LONI)). 
Data Management 
1) Data collected during tele-visits will be entered and 
maintained in REDCap (a secure web-based survey and 
data management system) and transferred to Synapse (an 
open source collaborative platform, for analysis).  
2) Survey data collected by FI will be exported to LONI (a 
secure online neuroscience dataset sharing system of 
USC’s) and then to Synapse.  
3) Data collected from smartphones will be transferred to 
the Sage Bionetworks maintained Bridge server and then 
to Synapse. 
4) All platform data will be transferred from Synapse to 
PDBP-DMR All data will be identified by the GUID, the 
date, time of the visit, and then transferred to the Sage 
Bionetworks managed Synapse. From Synapse the 
cleaned, processed, and event date and time transformed 
dataset will be transferred to the PDBP’s Data 
Management Resource (DMR) for further distribution to 
PDBP investigators and will be made available to the wider 
research community through their qualified researchers 
program [See Resource Sharing Plan]. 

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All the data being shared will be detailed in the data user 
agreement (DUA). 
Statistical Analysis 
(by Specific Aim) 
SA 1: We will use results from the REACT-PD study to 
establish a calibration of tele-visit (TV) assessments to 
predict in-clinic MDS-UPDRS scores (Aim 1b). Lin's 
concordance correlation coefficient, rc, will be used to 
summarize accuracy of the calibrated TV estimates vs. 
scores collected from in-person SURE-PD3 visits conducted 
close in time, accepting TV estimates as sufficiently accurate 
if rc > 0.8. If we observe insufficient concordance, we will re-
calibrate using all available data from both REACT-PD and 
the current study. 
SA 2: The study sample will be randomly split 2:1 into 
calibration and validation subsets. The calibration sample 
will be used to derive smartphone (SP) measures that best 
match the TV assessed composite scores of motor function 
(MDS-UPDRS part 3), non-motor function (MoCA total 
score), 
subjective 
function 
(including 
clinical 
global 
impression [CGI] scores, patient global impression scores, 
modified Schwab and England ADL scores, and MDS-
UPDRS parts 1b and 2 scores), and estimates of MDS-
UPDRS part 1-3 total scores (Aim 2a). The accuracy of 
calibrated SP measures will be tested in the reserved 
validation sample using Lin's concordance correlation 
coefficient, rc. If we observe insufficient concordance, we will 
recalibrate using all available data from both the calibration 
and validation samples.  
TV assessments and calibrated SP measures of disease 
progression will be compared generally and between specific 
subsets of participants expected to progress at different 
rates (Aim 2b). Each measure will be standardized to 30% of 
the observed mean change over 2 years based on a random-
slopes linear mixed model of the full sample such that a one-
unit change of all standardized, calibrated measures would 
reflect an equivalent magnitude of change relative to natural 
rates of progression. Estimated measure-specific variance 
components will be used to estimate the standard error for 
a treatment group comparison from a two-arm trial 
assuming an assessment schedule appropriate for a given 
measure, e.g., annual for TV measures and quarterly for SP 
measures. The ratio of squared standard errors will be used 
to estimate the relative sample size required using one or 
another measure for designs with equivalent power. The 
same approach will be used to identify measures that are 
sensitive to biological subgroups (e.g., among participants 
stratified by their rate of MDS-UPDRS progression over the 
first 2 years of in-clinic follow-up in the parent trials) or 
treatment-based subgroups (e.g., participants randomized 
to isradipine or serum urate elevation). TV assessments and 
SP measures will also be compared with respect to their 
accuracy in predicting future clinical events and changes in 

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PROs, e.g., dropping below 80% on the modified Schwab and 
England ADL, experiencing a fall and other PROs as 
captured by FI application including PD-PROP measures. 
SA 3: We will derive novel measures that best predict disease 
progression using passively collected SP data. We will split 
the sample 2:1 into discovery and validation subsets, like 
active tasks. A range of SP measures will be derived from 
passive data. For walking data (Aim 3a) these include but 
are not limited to time and frequency domain statistics, 
energy and entropy of frequency spectrum from the tri-axial 
accelerometer, 
along 
with 
absolute 
displacement 
measurements. For displacement information (Aim 3b) data 
will be summarized into variables such as furthest distance 
traveled, frequency of trips, average daily distance etc. 
Resulting summary metric will then be matched with the TV 
assessed composite scores of motor function (MDS-UPDRS 
part 3), Schwab and England ADL scores, MDS-UPDRS 
(parts 1b and 2 scores), and estimates of MDS-UPDRS part 
1-3 total scores. The accuracy of the associations will then 
be tested in the validation data subset using Lin's 
concordance correlation coefficient, rc.  
Passive measures will be assessed for progression using the 
same methods as described in SA 2b. 
Power Calculations 
SA 1b. With a sample size of ~10 SURE-PD3 participants 
expected to complete at least one TV close in time to their 
in-person clinic visit, the study will have 80% power to 
conclude that the REACT-PD calibrated tele-visit estimates 
are sufficiently accurate (rc > 0.8 at alpha = 0.05) if the true 
concordance is at least 0.89. 
SA 2a. With a 2:1 split of ~340 AT-HOME PD participants, 
yielding ~115 participants contributing to validation tests, 
the study will have 80% power to declare a given SP measure 
sufficiently accurate (rc > 0.80 at alpha = 0.05) if the true 
concordance is at least 0. 87. 
SA 2b. With approximately 80% of participants participating 
in the SP portion of the study, yielding ~340 participants 
contributing to the smartphone vs tele-visit comparison, the 
study would have an 80% probability of selecting the true 
preferred measure from a pair of TV or SP if the preferred 
measure had lower standard error by an effect size of at least 
0.065. 
SA 3. With a 2:1 split of ~240 participants, yielding ~80 in 
the validation sample and at least 25% experiencing at least 
an 8-point progression in MDS-UPDRS parts 1-3 total score, 
the study would have 80% power to declare a novel measure 
derived from passive SP monitoring to have a ROC AUC 
significantly greater than 0.80 if the true AUC were at least 
0.95. 

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AHPD – SUPER-PD TELE-VISIT VALIDATION SUB-STUDY SYNOPSIS 
 
Study Center 
University of Rochester 
Objectives 
To establish the cross-sectional reliability of tele-visit versus in-
person research visit assessments of participants with PD 
Study 
Population 
Individuals with PD enrolled in the University of Rochester’s on-
going Sensor Use to Monitor Progression and Evaluate Symptoms 
Remotely in Parkinson’s Disease (SUPER-PD) study 
Study Design 
Individuals with PD from SUPER-PD will complete a single tele-
visit within ±2 weeks of their SUPER-PD baseline or month 12 in-
person study visit. 
Number of 
Participants 
Approximately 50 
Main Inclusion 
Criteria 
1. Enrollment in SUPER-PD 
2. Diagnosis of idiopathic PD (as determined by UK Parkinson’s 
Disease Brain Bank Criteria in SUPER-PD) 
3. Have consented to future contact by the University of 
Rochester 
4. Internet-enabled device that will support participation in tele-
visits 
5. Willing and able to provide informed consent 
Main Exclusion 
Criteria 
1. Inability to carry out study activities 
Study 
Rationale 
Tele-visits offer the promise of streamlining study conduct and 
reducing the burden on study participants. The objective of this 
sub-study is to establish the cross-sectional reliability of tele-visit 
assessments. 
Study Outcome 
Measures 
x 
MDS-UPDRS part 3 
x 
Montreal Cognitive Assessment 
Data 
Management 
Data collected during tele-visits will be entered and maintained in 
REDCap (a secure web-based survey and data management 
system).  Each participant’s baseline demographic information, 
concomitant medications, and health history as well as clinical 
data including PD-PROP from the corresponding SUPER-PD visit, 
will be transferred from the SUPER-PD REDCap project to the 
AHPD sub-study REDCap project.  All data will ultimately be 
transferred to Synapse (an open source collaborative platform) for 
analysis. For any sub-study participants who are participating in 
the mPower 2.0 component of SUPER-PD, their smartphone data 
from the corresponding SUPER-PD visit and associated remote 2-
week burst will be linked with AT-HOME PD data within Synapse.  
 
From Synapse, the cleaned, processed, and event date- and time- 
transformed dataset will be transferred to the PDBP’s Data 
Management Resource for further distribution to PDBP 
investigators and will be made available to the wider research 
community through their qualified researchers program. 
Statistical 
Analysis 
Paired MDS-UPDRS and MoCA scores from in-person and TV 
assessments of SUPER-PD participants will be pooled with data 
from SURE-PD3. The accuracy of predicted in-clinic scores based 

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on TV assessments using calibrations from REACT-PD will be 
summarized by Lin's concordance correlation coefficient, rc, 
equivalent to an intra-class correlation (ICC). The REACT-PD 
calibrations will be judged sufficiently accurate if rc > 0.8. If we 
observe insufficient concordance, we will re-calibrate using all 
available data from REACT-PD, SURE-PD3, and SUPER-PD. 
Sample Size 
With a combined sample size of ~60 SURE-PD3 and SUPER-PD 
participants expected to complete at least one TV close in time to 
their in-person clinic visit, the study will have 80% power to 
conclude that the REACT-PD calibrated tele-visit estimates are 
sufficiently accurate (rc > 0.8 at alpha = 0.05) if the true 
concordance is at least 0.89. 

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Table 1: AT-HOME PD Schedule of Activities (SOA) 
 
Pre-screen 
TC 
Screen 
VC(within 
30 days of 
eConsent) 
Visit 1 BL 
Day 0*** 
TV 
Month 3 
SP 
Month 6 
SP 
Month 9 
SP 
Visit 2 
Month 12 
(±28 days) 
TV 
Month 15 
SP 
Month 18 
SP 
Month 21 
SP 
Visit 3 
Month 24  
(±28 days) 
TV 
Unscheduled/PW 
TV 
Study/Visit Setup 
Verify Consent 
 
X 
 
 
 
 
 
 
 
 
 
 
Verify eligibility 
X 
X 
 
 
 
 
 
 
 
 
 
 
Pre-Screening Questionnaire 
X 
 
 
 
 
 
 
 
 
 
 
 
eConsent 
X 
 
 
 
 
 
 
 
 
 
 
 
Technology Survey 
X 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
 
X 
 
 
 
 
 
 
 
 
 
 
Tele-visit Test connection 
 
X 
 
 
 
 
 
 
 
 
 
 
Fox Insight Account Creation 
 
X 
 
 
 
 
 
 
 
 
 
 
GUID Creation1 
 
X 
 
 
 
 
 
 
 
 
 
 
SimplyBook.me Orientation 
 
X 
 
 
 
 
 
 
 
 
 
 
Smartphone app orientation 
 
 
X 
 
 
 
 
 
 
 
 
 
Tele-visits 
Reportable Events 
 
 
X 
 
 
 
X 
 
 
 
X 
 
Concomitant Medications 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
MDS-UPDRS part 1a, 3, 4 (if 
applicable) 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
Self-Reported Falls2 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
MDS-UPDRS part 1b, 22 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
MoCA 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
Schwab & England 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
CGI* and PGI**2– Severity 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
CGI* and PGI**2– Change 
 
 
 
 
 
 
X 
 
 
 
X 
X 
Determination of Falls 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
Performance of complete set 
of active smartphone tasks 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
Preference & Burden survey3 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
Review study compliance 
 
 
X 
 
 
 
X 
 
 
 
X 
 
Early termination survey 
 
 
 
 
 
 
 
 
 
 
 
X 
Smartphone Sessions 
Motor tasks  
 
 
X (x10) 
X (x10) 
X (x10) 
X (x10) 
X (x10) 
X (x10) 
X (x10) 
X (x10) 
X (x10) 
 
Cognitive tasks 
 
 
X (x3) 
X (x3) 
X (x3) 
X (x3) 
X (x3) 
X (x3) 
X (x3) 
X (x3) 
X (x3) 
 
Fox Insight Surveys  
See Table 2 
1If not already existing; 2 Completed pre-tele-visit; 3 Completed post tele-visit 
*Completed by the investigator; ** Completed by the patients; *** Within 60 days of Screening/TV 
 

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Table 3: AHPD - SUPER-PD Cohort Schedule of Activities (SOA) 
 
Pre-Screen Contact (TC or in-person)* 
Baseline Tele-Visit  
(±14 days of SUPER-PD baseline or month 12 visit) 
Pre-Screening Questionnaire 
X 
 
eConsent 
X 
 
Verify Eligibility 
 
X 
Verify Consent 
 
X 
Reportable Events 
 
X 
MoCA 
 
X 
MDS-UPDRS part 3 
 
X 
*May occur either in-person (at time of their SUPER-PD visit) or by phone

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Table of Contents 
AT-HOME PD PROTOCOL SYNOPSIS ...................................................................... 11 
AHPD – SUPER-PD TELE-VISIT VALIDATION SUB-STUDY SYNOPSIS ................... 19 
1. 
INTRODUCTION .................................................................................. 26 
1.1 
Background 
26 
1.2 
Tele-visit and Smartphone Experience 
31 
2. 
STUDY OBJECTIVE ............................................................................ 32 
2.1 
Specific Aims: 
32 
3. 
STUDY DESIGN .................................................................................. 33 
3.1 
Overview 
33 
3.2 
Discussion of Study Design 
37 
4. 
STUDY POPULATION .......................................................................... 38 
4.1 
Participant Numbers 
38 
4.2 
Inclusion Criteria 
39 
4.3 
Exclusion Criteria 
39 
4.4 
Discussion of Participant Characteristics 
39 
5. 
STUDY PROCEDURES ........................................................................ 40 
5.1 
Recruitment 
40 
5.2 
Process of Consent 
41 
5.3 
Schedule of Activities 
42 
5.4 
Participant Identification Numbers (ID) Number 
42 
5.5 
Study Visits 
43 
6. 
ASSESSMENTS ................................................................................... 50 
6.1 
Primary Assessments 
50 
6.2 
Smartphone Assessments 
52 
6.3 
Fox Insight (FI) Assessments 
53 
6.4 
Safety Assessments (see Section 9 Reportable Events) 
53 
6.5 
Assessment of Participant Compliance 
53 
7. 
COSTS TO THE SUBJECT ................................................................... 54 
8. 
PAYMENT FOR PARTICIPATION .......................................................... 54 
9. 
RISK/BENEFIT ASSESSMENT ............................................................ 54 
9.1 
Potential Risks 
54 
9.2 
Protection Against Risks 
55 

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9.3 
Potential Benefits to Subjects 
56 
9.4 
Alternatives to Participation 
56 
10. 
CONCOMITANT MEDICATIONS ........................................................... 56 
10.1 
Required Therapy 
56 
11. 
PARTICIPANT WITHDRAWALS/DROPOUTS ........................................ 56 
12. 
REPORTABLE EVENTS ....................................................................... 57 
12.1 
Recording of Reportable Events 
58 
12.2 
Emergency Actions 
58 
13. 
STATISTICAL ANALYSIS ...................................................................... 58 
13.1 
Data Processing and Quality Control (QC) for Smartphone (SP) Based 
Measures: 
58 
13.2 
Statistical Analysis Plan 
59 
13.3 
Go/No-go Milestones, Challenges and Opportunities 
61 
13.4 
Sample Size Determination 
62 
13.5 
Non-Compliance, and Withdrawals 
63 
13.6 
Safety Analysis 
63 
14. 
REGULATORY/ETHICS ....................................................................... 63 
14.1 
Compliance Statement 
63 
14.2 
Informed Consent 
63 
14.3 
Institutional Review Board/Independent Ethics Committee 
64 
14.4 
Protocol Amendments 
64 
14.5 
Participant Confidentiality 
65 
15. 
DOCUMENTATION .............................................................................. 65 
15.1 
Investigator Site File 
65 
15.2 
Maintenance and Retention of Records 
66 
15.3 
QA Review 
67 
15.4 
Regulatory Inspections 
67 
15.5 
Data Management 
67 
16. 
INVESTIGATOR/SITE .......................................................................... 70 
17. 
SAFETY MONITORING ........................................................................ 71 
17.1 
Study Committees 
71 
17.2 
Case Report Forms 
71 
17.3 
Primary Source Documents 
72 
17.4 
Closeout Visit 
72 
17.5 
Closeout Plan 
72 

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18. 
PUBLICATION OF RESEARCH FINDINGS ............................................ 72 
19. 
RESOURCE SHARING PLAN................................................................ 73 
20. 
REFERENCES ..................................................................................... 74 
21. 
APPENDIX ........................................................................................... 78 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1. INTRODUCTION 
1.1 
Background 
 
 
 
 
 
Disease modification is the primary unmet need in Parkinson’s disease 
(PD) therapeutics. To aid in achievement of this goal, as recognized by 

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NINDS, validated PD biomarkers that improve the efficiency of clinical 
trials are urgently needed. While discovery of biological signatures of the 
disease has been a central focus of PD biomarker research, a similarly 
important priority is the application of novel technologies to provide 
digital biomarkers of disease progression. 
Clinical trials of therapies aiming to slow PD progression have been 
hindered by the need for study participants to repeatedly visit a research 
clinic for in-person testing. Tele-visits, web-based surveys and 
smartphone-based remote sensor assessments represent particularly 
promising opportunities to streamline study conduct, reduce participant 
burden, and allow for the collection of data beyond the usual episodic, 
in-clinic assessments. Demonstrating the accuracy of these relatively 
inexpensive and accessible platforms for the measurement of PD 
progression would facilitate long-term follow-up of participants after 
completion of interventional studies. New infrastructure will be required 
to 
implement 
tele-visit 
and 
smartphone-based 
remote 
sensor 
assessments. 
This project will investigate novel strategies for measuring the 
progressive disability of PD using tele-visits from participants' homes 
and smartphone technology in order to overcome limitations of 
traditional clinical trials and thereby accelerate development of improved 
treatments for people with PD. 
1. Tele-health alternatives to traditional in-clinic outcomes data 
collection 
a. 
Advantage of telemedicine (tele-visit) versus in-office research 
visits and current state of the field  
Telemedicine, the use of real-time synchronous videoconferencing with 
patients, could revolutionize clinical trial design. Telemedicine-based 
virtual 
research 
encounters 
between 
participants 
and 
clinical 
investigators (tele-visits) can be conducted on readily available internet-
enabled devices and in any location where privacy can be established. 
Numerous studies have shown that telemedicine is feasible for patients 
with PD (1,2). In the largest randomized controlled trial of telemedicine 
in PD to date, 91% of 388 scheduled telemedicine visits were completed 
(3). With some modifications, the Unified Parkinson’s Disease Rating 
Scale (UPDRS) motor component can be administered remotely and 
demonstrates good test-retest reliability and good overall agreement with 
in-person UPDRS motor assessment (1,4). A modified version of the 
UPDRS, with rigidity and postural instability items removed, has been 
shown to be reliable and valid (5). There have not been any published 
studies examining the remote administration of the MDS-UPDRS and 
evaluation is needed to determine if this is a valid and reliable tool when 
administered remotely. Non-motor assessments, including the Montreal 
Cognitive Assessment (MoCA), can also be feasibly administered 
remotely (6). The majority of patients are satisfied or more than satisfied 
with telemedicine visits (1, 3). Individuals are interested in participating 
in studies of telemedicine (3) and may be more interested in participating 
in trials that incorporate tele-visits delivered outside of the home (7). 
Telemedicine visits result in a reduction in distance travelled, time 

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associated with the visit, and cost (8). The incorporation of tele-visits into 
clinical trials could reduce the burden on participants, enable 
individuals with greater disability or other (e.g., geographic or economic) 
travel barriers to participate, allow for long-term clinical trial follow up, 
enable a shift towards centralized raters (9), and allow for remote 
obtainment of informed consent (10,11).  
b. 
Value of smartphone-based data acquisition – PD is readily 
monitored using remote sensors embedded in smartphones or wearables 
(12-14) due to the outward manifestations of the disease. While 
wearables have gained popularity for measuring gait within the context 
of clinical trials, smartphones provide a more flexible, less invasive 
approach for long-term at-home evaluation. Motor symptoms can be 
captured using smartphones using built-in accelerometers, pressure 
sensor in screens and microphones for assessment of phonation, and 
non-motor symptoms can be tracked by electronic patient-reported 
outcomes (PROs) or other activities. Smartphones have the potential to 
provide objective, frequent, and sensitive assessments of PD. 
In the mPower study (NCT02696603), participants have been tracked 
longitudinally as they perform daily active tasks and PROs. The 
smartphone application associated with the mPower study was adopted 
by over 12,000 individuals in the first 6 months who together performed 
over 200,000 active tasks. Modifications of the application have been 
deployed in several sub studies, including in Smart4SURE in a 
collaboration between PIs Mangravite, Dorsey and Schwarzschild, and in 
the PDBP-sponsored Harvard Biomarker Study. Preliminary evaluation 
of mPower features relative to in-clinic disease assessments – initiated 
through collaboration between Co-I Omberg and Dorsey – demonstrated 
that motor metrics captured by mPower corresponded well with in-clinic 
assessment of MDS-UPDRS motor exam (R=0.89, p<10-5 for tapping) and 
were able to identify daily fluctuations in disease burden associated with 
L-dopa administration or natural diurnal variations (15).  In addition to 
the ability for remote, self-administered monitoring of proxy for standard 
disease measures, smartphone assessments also provide multiple 
opportunities to extend understanding of disease beyond in-clinic 
measures including 1) the ability to evaluate the impact of disease on 
quality of life (see Aim 3), and 2) the ability to observe natural 
fluctuations in disease symptoms over time and in relation to 
environmental or lifestyle choices (16). 
In addition to their utility for remote administration of active disease 
evaluations, smartphones possess the capacity for passively monitoring 
the impact of PD on daily life over time. Novel measures of ambulatory 
and social behaviors may be extracted from smartphone (e.g., GPS map) 
systems to shed light on PD disability inaccessible with traditional in-
office measures. Smartphones are generally carried around throughout 
the day and can provide a low burden approach to collect a continuous 
stream of passive data including movement patterns (travel distances 
and location displacements throughout the day), daily activity and 
exercise patterns, and communication patterns.  In contrast to the 
episodic nature of standard disease assessments, these patterns provide 

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a continuous measure that has been successfully used to monitor 
disease in neuropsychiatric and cognitive disorders, where changes in 
daily activity patterns are markers for changes in disease status. In 
conjunction with collection of active measures as described in SA 1 and 
SA 2, SA 3 will evaluate the ability to collect passive data over long 
periods of time and use these data to identify markers of relative and 
absolute changes in disease severity.  
 
2. 
Importance of long-term follow up of participants completing 
interventional studies 
Even if an intervention appears effective early in the course of the 
disease, it remains to be proven that the benefit will persist. This has 
proven problematic in studies of other potentially neuroprotective drugs. 
For example, the initial data from the DATATOP trial (17-19) conducted 
by the Parkinson Study Group (PSG) pointed to a disease-modifying 
effect of selegiline that was not supported by the long-term data at least 
in regard to the primary outcome (20). A more recent example is the 
inconclusive result of the ADAGIO study of rasagiline (21). Promptly 
initiated long-term follow up of the cohort would have been highly 
valuable for further data interpretation. Such an effort was undertaken 
but unfortunately with a gap of two years post completion of ADAGIO, 
accounting for a 42% dropout rate from the original cohort, which made 
data interpretation much less meaningful (22). Nevertheless, a number 
of important observations on major milestones of PD progression were 
made by extending the follow up of the DATATOP and ADAGIO cohorts 
(20-24). Similarly, follow-up studies evaluating the impact of initiating 
therapy with dopamine agonists versus levodopa have found that early 
differences do not necessarily result in longer duration benefits (25,26). 
Thus, the interpretation of multiple studies of several different 
potentially disease-modifying therapies has been obscured by the lack of 
long-term follow up. Unplanned longer-term follow up of participants in 
these studies has generated valuable observations though conclusions 
have been limited by delays in extension phase initiation with 
substantial participant dropout and by post-hoc analysis.  
AT-HOME PD is a 24-month observational study that will seamlessly 
transition from two parent trials to enroll the majority of their 
participants. This additional observation may not be sufficiently long to 
see emergence of long-term disability like postural instability and 
cognitive impairment, but most of the participants will be approaching 
the 6-7 year-mark from PD onset when the dopaminergic therapy (DT) 
‘honeymoon’ has ended (27) and such events begin to manifest in 
earnest. Thus, the follow up of these merged phase 3 trial cohorts, 
comprising one of the longest observational studies of a baseline de novo 
PD population, is likely long and large enough to provide insight into: 1) 
any persistent or delayed effect of isradipine or inosine on relevant motor 
and non-motor outcomes, and 2) milestones of disease progression in 
the current era of PD therapeutics. The cohort will be especially valuable 
as it is enriched by DNA and other biologics data (with sequentially 
collected plasma samples +/- DAT imaging), which will be fully integrated 
into the PDBP database, and the dataset will be open to the public. The 
only other baseline de novo cohort of similar size is the Parkinson’s 

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Progression Markers Initiative (PPMI; clintrials.gov NCT01141023). 
While PPMI has a tremendously rich biologics dataset, it is an 
observational study that never had an interventional arm and currently 
does not incorporate telemedicine or smartphone assessments. The 
novelty of AT-HOME PD stems not only from long-term follow up of 
combined PD trial cohorts but also from accomplishing it by virtual 
assessment tools. 
 
The AHPD – SUPER-PD Tele-visit Validation sub-study is a single tele-
visit occurring in close proximity to in-clinic assessments that will help 
evaluate the accuracy of tele-visit assessments. 
 
a. 
Overview of STEADY-PD III (clintrial.gov NCT02168842), Phase 
3 Double-blind Placebo-controlled Parallel Group Study of Isradipine as 
a Disease Modifying Agent in Participants with Early Parkinson Disease. 
The study is based on preclinical studies that demonstrated a 
neuroprotective effect of isradipine via antagonism of calcium channels 
(28), as well as a number of epidemiological studies suggesting reduced 
incidence of PD in users of calcium channel antagonist antihypertensive 
agents (29-33). The Phase 3 study was also supported by our open-label 
and Phase 2 multicenter safety, tolerability and dose selection studies 
(34,35). The primary hypothesis of the study is that patients with early 
PD treated with isradipine IR will have slower progression of PD disability 
as determined by the change in the total UPDRS (36) score between 
baseline and 36 months in 336 participants with early PD not yet 
requiring dopaminergic therapy (DT). The STEADY-PD III study design 
and methodology have been published (37). 
b. 
Overview 
of 
SURE-PD3 
(clintrial.gov 
NCT02642393), 
A 
Randomized, Double-blind, Placebo-controlled Trial of Urate-elevating 
Inosine Treatment to Slow Clinical Decline in Early PD.  
The primary objective of SURE-PD3 is to determine whether the urate 
precursor inosine dosed to moderately elevate serum urate over 2 years 
slows clinical decline in early PD. Urate elevation is targeted based on 
preclinical evidence of its neuroprotective antioxidant properties, 
together with epidemiological and clinical biomarker studies showing 
that higher levels of urate predict a reduced risk of PD and a slower rate 
of progression. Our phase 2 trial demonstrated our ability to produce 
long-term CSF and serum urate elevation with adequate safety and 
tolerability (38). SURE-PD3 has been conducted at ~60 US PSG clinical 
sites.  
Unique features of SURE-PD3 include its enrichment for participants 
with lower serum urate (predictive of faster clinical decline) and its 
exclusion of subjects without a striatal dopamine transporter (DAT) 
deficit demonstrated on a screening DAT scan, which can increase the 
likelihood of an accurate diagnosis of PD, in early, untreated disease. 
SURE-PD3, like STEADY-PD III, includes a biomarker sub-study with 
blood collected for DNA (e.g., for whole genome sequencing) and serial 
plasma sample storage. In addition, a follow-up DAT scan will be 
conducted in SURE-PD3 to estimate rates of striatal DAT binding site 

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loss over one to two years as a neuroimaging biomarker of PD 
progression. 
 
c. Overview of SUPER-PD 
SUPER-PD is a 24-month single-center observational study to develop 
and validate novel PD measures using sensor-based technologies.  The 
study is enrolling individuals with PD and controls in order to evaluate 
ability of various technologies to differentiate those with PD from those 
without, to detect disease progression, to assess response to current 
medications, and to produce novel insights into PD that cannot currently 
be ascertained from in-clinic measurements. 
 
 
1.2 
Tele-visit and Smartphone Experience 
 
 
 
 
 
Preliminary data 
1. 
REACT-PD, a recent observational study of 40 individuals 
concurrently enrolled in STEADY-PD III, aimed to establish the 
feasibility, reliability, and value of web-based tele-visits in the conduct 
of a clinical trial in PD. Participants were scheduled for a tele-visit within 
2-4 weeks of a corresponding in-person STEADY-PD III visit over 12 
months, with visit frequency dependent on the participant’s STEADY-PD 
III visit schedule. All clinical trial assessments performed at the 
preceding in-person visit were performed remotely during the tele-visit, 
including motor assessments, non-motor assessments, and orthostatic 
vital signs. Visits were performed on smartphones that were provided to 
participants. 
Study results:  
1) Feasibility:  
Preliminary data suggests that tele-visits are feasible. The study 
started recruitment in April 2016 and successfully completed 
recruitment of 40 participants within ~4 months. 38/40 participants 
completed all three tele-visits and 84% of tele-visits were completed 
within window. 
2) Reliability:  
There was excellent correlation between in-person visits and tele-
visits for non-motor outcome measures. Intra-class correlation (ICC) 
coefficients for the Montreal Cognitive Assessment (MoCA), MDS-
UPDRS 1A, MDS-UPDRS 1B, and MDS-UPDRS II were 0.78, 0.83, 
0.88, and 0.90 respectively.  There was good correlation for the MDS-
UPDRS Part III (ICC 0.53). 
3) Value: 
Participant satisfaction has been positive with >90% of participants 
being satisfied or very satisfied with the convenience, connection, 
and comfort of the tele-visit. More than 75% of participants agreed or 
strongly agreed that they would be more interested in participating 
in future clinical trials if some visits could be conducted virtually. 

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Final longitudinal analysis will be completed once STEADY-PD III 
database is locked  
2. 
Smart4SURE is an ongoing remote observational study embedding 
technology from mPower into the SURE-PD3 trial. Designed as a 
feasibility study, the primary aim is to determine the ability to track 
disease progression using remote assessment via a smartphone. 
Smart4SURE longitudinally collects measures of parkinsonian motor 
(speeded tapping, phonation, gait, balance, and resting/postural/action 
tremor) and non-motor (short-term memory) deficits via scheduled 
activity tasks and of PROs via periodic surveys. The sub-study and 
planned analyses are described in the SURE-PD3 protocol.  
3. 
Readiness of both cohorts to transition to a virtual extension 
study and centralized coordination 
Both cohorts are prepared to efficiently transition to long term remote 
participant’s ascertainment and have necessary ethical and logistical 
provisions in place: 1) both studies have a consent clause asking for 
permission to be contacted for future research, which may be obtained 
by a centralized coordination center; 2) both studies have agreed with 
the NINDS to use DMR to upload clinical datasets: 3) both studies are 
currently putting provisions in place to generate global unique identifiers 
(GUID) to link participants in study datasets; 4) both studies have met 
with all involved stakeholders to create a flow diagram and timeline for 
data and sample transfers; 5) both studies are conducted under the 
auspices of the Parkinson Study Group (PSG) and as such function 
under common PSG by-laws ensuring uniform governance and 
publication policy; and 6) both studies use the CTCC data coordination 
center, streamlining the current database development and transition 
plan. CTCC will be responsible for the project and data management of 
AT-HOME PD.  
 
 
 a. Readiness to recruit a new sub-study cohort  
The study team is well-positioned to efficiently recruit participants 
from  SUPER-PD, which has the following necessary ethical and 
logistical provisions in place: 1) the study has a consent clause 
asking for permission to be contacted for future research; 2) the 
study currently generates global unique identifiers (GUID) to link 
participants in study datasets; 3) the study team is currently 
working on creating a flow diagram and timeline for data and 
sample transfers; and 4) the study uses the same data management 
system 
as 
AHPD 
(REDCap), 
streamlining 
new 
database 
development and transition planning. CTCC will be responsible for 
the project and data management of the AHPD – SUPER-PD Tele-
visit Validation sub-study.  
 
 
 
2. STUDY OBJECTIVE 
 
 
2.1 
Specific Aims:  
 
 
 
 
 

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1. To establish and implement an infrastructure for longitudinal 
remote follow-up of phase 3 trial cohorts: 
a. Transition from site-based to a centralized site and coordination center 
to manage all participant activity in virtual extensions of STEADY-PD 
III and SURE-PD3, with projected enrollment of ≥70% of final trial 
cohorts, and core data collection in accordance with Parkinson’s 
Disease Biomarkers Program (PDBP) schedule of activities. 
b. Conduct an annual research visit (tele-visit) program and establish the 
feasibility and cross-sectional reliability of tele-visit versus in-person 
visit assessments in a subset of SURE-PD3 and SUPER-PD 
participants. 
c. Deploy a smartphone application, based on the mPower study, for 
remote data collection in a clinical trial cohort as preliminarily 
characterized in the Smart4SURE sub-study of SURE-PD3. 
d. Establish a mechanism for linking STEADY-PD III and SURE-PD3 
study data with study data collected through smartphone-based 
assessments, tele-visits, and Fox Insight (FI), a separate longitudinal 
patient-reported outcomes (PROs) online research study. 
2. To compare patient-driven (smartphone, web-based surveys) vs 
clinician-driven (tele-visit) outcomes by:  
a. Correlating the smartphone and tele-visit platforms’ component and 
composite features, and their changes over years. 
b. Comparing the smartphone and tele-visit platforms’ abilities to: i) 
measure PD progression and predict clinical events and changes in 
PROs; ii) distinguish rapid vs slow progressors based on baseline 
Movement Disorders Society-Unified Parkinson’s Disease Rating Scale 
(MDS-UPDRS) scores, dopamine transporter (DAT) deficit (in SURE PD-
3) or serum urate levels (in STEADY-PD III); iii) demonstrate 
persistence of any effects of isradipine or inosine in their respective 
trials. 
c. Comparing completion status and performance on FI and tele-visit 
participant-reported outcome measures. 
 
3. To explore novel smartphone-based real-life mobility biomarkers of 
PD disability and its progression that are normally inaccessible with 
traditional office measures. We will investigate the ability of passively 
collected smartphone data on ambulation and location to enable 
assessments of physical activity and socialization that correlate with 
motor and non-motor functions. 
 
3. STUDY DESIGN 
 
 
 
 
 
3.1 
Overview 
 
 
 
In this 24-month observational study, we will enroll STEADY-PD III and 
SURE-PD3 participants in order to prospectively and remotely 
characterize long-term clinical outcomes through the use of tele-visits, 
smartphone assessments, and web-based surveys. The overall study 
design is conceptualized below in Figure1.  
As schematized in Figure 1, our objectives will be pursued by first 
developing a study infrastructure, which will establish tele-visit and 

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smartphone assessment platforms while sequentially transitioning the 
parent study cohorts from site-based to centralized coordination. The 
data collected over 2 years of serial (annual) tele-visits and (quarterly 
clusters of) smartphone assessments of the combined cohort will be 
characterized and compared to gauge their clinicometric properties and 
relative potential for monitoring clinical progression in future PD 
studies. Lastly, data collected passively (with participant permission) 
from the smartphone sensors will be explored as a novel strategy for 
mobility and socialization correlates of PD progression.

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Figure 1. Aims of the AT-HOME PD study in context of data flow.  
Each participant (depicted upper left) will contribute data (blue arrow) in annual tele-visits and may contribute data in more frequent 
smartphone sessions and FI sessions. Cleaned data are transferred (red arrow) and aggregated in Synapse and then the DMR for 
distribution (green arrow) to the Biostats Core and the broader research community.

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Figure 1a. Aims of the AHPD – SUPER-PD Tele-visit Validation sub-study in context 
of data flow.  
Each SUPER-PD participant (depicted top), once enrolled in AHPD sub-study, will contribute 
data (blue arrow) in one tele-visit. Cleaned data are transferred (red arrow) and aggregated in 
Synapse and then the DMR for distribution (green arrow) to the Biostats Core and the broader 
research community.

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Study Platforms 
• Tele-visit platform – Participants will participate (from home or other preferred 
private environment) in three approximately one hour-long tele-visits using a web-
based video platform with accessibility on any internet-enabled device. The first tele-
visit will occur shortly after screening and then annually for two subsequent visits. 
Each visit will include a series of PROs, which will be completed by the participant 
in REDCap, a cognitive test (MoCA), and clinician-conducted assessments including 
a modified MDS-UPDRS part 3, SEADL and CGI; see SOA.  
• FI web-based survey platform – AT-HOME PD participants will be asked to 
complete a set of standard questionnaires every 3 months through a companion 
study called Fox Insight (FI). This online observational study, sponsored by The 
Michael J. Fox Foundation (MJFF), seeks to better understand experiences of daily 
living (EDL) in PD and how they change with disease progression. Over 22,000 FI 
participants have enrolled to complete web-based surveys (on a quarterly basis for 
up to 5 years) (https://foxinsight.michaeljfox.org).  The PRO data collected via FI 
are largely complementary and more extensive than those collected through the 
smartphone and tele-visit components, allowing for a comparison of motor and 
cognitive tasks. The modest overlap between a few surveys (e.g., MDS-UPDRS part 
2 on EDL) is by design as comparison of these results will allow assessment of 
whether state-of-art web-based PRO data collection by FI can still be enhanced (with 
respect to completion rates, variability and predictive power) by investigator 
oversight, even if provided remotely via tele-visits. FI data, linked to a participant’s 
GUID, will be made available to the research team as well as PDBP and the broader 
research community through FI’s data repository (LONI). 
• Smartphone platform (mPower-based app) – The mPower application captures 
sensor data within the context of self-administered activity tasks (motor and 
cognitive). Processed sensor data is converted into multiple features that are 
evaluated individually and in aggregate as digital biomarkers for disease severity. 
Building on experience gained in the mPower and Smart4SURE studies, a new 
application will be deployed to assess motor and cognitive functions sensitive to PD 
progression (see SOA; Table 2). The mPower 2.0 app is compatible with Android as 
well as iPhone devices, and has been modified to allow passive collection of gait and 
mobility data with participant permission (for SA3). The application will include a 
defined set of tasks; described below under Study Procedures. As per the SOA, 
participants will be asked to complete a four to six-minute battery of motor tasks 
daily for at least 10 days and an eight-minute battery of cognitive tasks daily for at 
least 3 days within a two-week period every quarter. The two-week burst will be 
considered successful if we are able to collect at least 10 daily activities and can be 
extended by 5 days if this minimum is not met. 
 
3.1.1 Sub-Study Overview 
Individuals with PD from SUPER-PD will complete a single tele-visit 
within ±14 days of their SUPER-PD baseline or month 12 in-person study 
visit. 
 
3.2 
Discussion of Study Design 
 
 
 
 
 
a. 
Rationale for Study  
 
 
 
 

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Disease modification is the primary unmet need in PD therapeutics. To 
aid in achievement of this goal, validated PD biomarkers that improve 
the efficiency and thereby the results of clinical trials are urgently 
needed. While discovery of biological signatures of the disease has been 
a central focus of PD biomarker research, a similarly important priority 
is the application of novel technologies to provide digital biomarkers of 
disease progression. Telemedicine and smartphone-based remote sensor 
assessments 
represent 
particularly 
promising 
opportunities 
to 
streamline study conduct, reduce participant burden, and allow for the 
collection of data beyond the usual episodic, in-clinic assessments. 
Demonstrating the utility of these relatively inexpensive accessible 
platforms for the measurement of PD progression would also establish 
the infrastructure for long-term follow up of participants after completion 
of interventional studies.  
 
Long-term observation of participants from STEADY-PD III and SURE-
PD3, together comprising ~600 early PD participants, would be 
invaluable not only in characterizing any persistent or delayed benefits 
of either treatment but also in the development of tele-health outcomes 
to facilitate future interventional trials in PD and of neurotherapeutics 
more broadly.  
 
The objective of this study is to leverage modern technology to develop, 
pilot and implement a 100% virtual model for long-term follow up 
utilizing telemedicine and smartphone platforms for quantitative 
monitoring of clinician- and patient-reported outcomes (PROs).  
 
The objective of the sub-study is to improve our estimates of the accuracy 
of tele-visit assessments relative to in-clinic assessments. 
 
 
 
 
 
4. STUDY POPULATION 
 
 
 
 
 
4.1 
Participant Numbers  
 
 
 
4.1.1 AT-HOME PD Participants 
 
Approximately 420 
 
All individuals with early idiopathic PD enrolled in the STEADY-PD III 
(NCT02168842) and SURE-PD3 (NCT02642393) studies (N≈600) who have 
consented to be contacted for future research will be asked to participate. 
We expect approximately 70% of them (N≈420) to consent and participate 
in at least the tele-visit portion of the study. We expect approximately 80% 
of enrolled individuals (N≈340) to participate in the smartphone portion 
(and thus the smartphone vs tele-visit comparison) of the study. We expect 
approximately 70% of participants in the smartphone portion (N≈240) to 
consent to passive data collection (and thus contribute to Aim 3). We 
expect approximately 80% of enrolled individuals (N≈340) to participate in 
the FI portion of the study. 
 
4.1.2 AHPD – SUPER-PD Tele-visit Validation Sub-study Participants 
 

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Approximately 50 individuals with PD enrolled in the University of 
Rochester’s on-going Sensor Use to Monitor Progression and Evaluate 
Symptoms Remotely in Parkinson’s Disease (SUPER-PD) study (N≈160) 
who have consented to be contacted for future research will be asked to 
participate. Participants will complete a single tele-visit and will not be 
asked to participate in the smartphone or Fox Insight portions of the AT-
HOME PD study. 
 
4.2 
Inclusion Criteria 
 
 
 
 
 
1. Enrollment in STEADY-PD III or SURE-PD3 studies 
2. Prior consent to be contacted by the UR unless a subject from 
STEADY-PD III or SURE-PD3 studies directly contacts UR to request 
information about study participation  
3. Internet-enabled device that will support participation in tele-visits 
4. Have created or willing to create a Global Unique Identifier (GUID) 
5. Willing and able to provide informed consent 
6. English fluency 
7. [For participants opting to participate in the smartphone component] 
possession of a suitable smartphone (iPhone or Android) with 
adequate data plan and cellular network access/signal or Wi-Fi 
access. 
 
 
 
Sub-Study Inclusion Criteria 
1. Enrollment in SUPER-PD 
2. Diagnosis of idiopathic PD (as determined by UK Parkinson’s Disease 
Brain Bank Criteria in SUPER-PD) 
3. Have consented to future contact by the University of Rochester 
4. Internet-enabled device that will support participation in tele-visits 
5. Willing and able to provide informed consent 
 
 
 
 
 
4.3 
Exclusion Criteria 
 
 
 
 
 
1. Inability to carry out study activities as determined by study staff.  
 
 
 
 
 
4.4 
Discussion of Participant Characteristics 
 
Only individuals who are currently enrolled or completed participation in 
STEADY-PD III or SURE-PD3 will be eligible for participation in this study. 
Only individuals currently enrolled in the SUPER-PD study will be eligible 
for participation in the sub-study.  Because of the nature of the study, an 
internet-enabled device with web-camera capacity or compatibility is 
necessary to participate. Participants without a camera will be provided 
with a suitable external camera.   
 
 
 
 
 
 
 
 
 

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5. STUDY PROCEDURES 
 
 
 
 
5.1 
Recruitment 
 
Cohort Recruitment and Retention (SA1) 
 
The study will recruit solely from STEADY-PD III and SURE-PD3. The sub-
study will recruit solely from SUPER-PD.  All STEADY-PD III and SURE-
PD3 participants who have consented to be contacted by the University of 
Rochester (UR) for future research or independently contacts the UR will 
have their personal contact information, study-specific unique identifier, 
CTCC unique identifier, and GUID (where available) entered into a secure 
HIPAA-compliant database at the UR. These individuals will be contacted 
by an AT-HOME PD study team member during or following their 
completion of the parent study. The AT-HOME PD study team member will 
provide an overview of the study, assess interest, and pre-screen for 
eligibility. Participants who have not already created a GUID will be 
required to create a GUID for this study.  Recruitment for the sub-study 
will occur either via telephone or during a SUPER-PD study visit by an AT-
HOME PD study team member. 
 
AT-HOME PD study participants from STEADY-PD III cohort: 
A majority of STEADY-PD III participants (who consent to being contacted 
for future research by the UR) will have already completed their STEADY-
PD III participation when this study commences and will be approached 
post-study completion. The remainder will be contacted either while still 
actively participating or shortly after completion of the study.  
 
AT-HOME PD study participants from SURE-PD3 cohort: 
All SURE-PD3 participants will be contacted following completion of their 
last SURE-PD3 visit in the planned treatment period. 
 
AHPD – SUPER-PD Tele-visit Validation sub-study participants from SUPER-
PD: 
SUPER-PD participants with PD (who consented to being contacted for 
future research by the UR) will be contacted during their participation in 
the SUPER-PD study. 
 
We have developed a proactive plan for recruitment and retention, relying 
on our experience with the parent studies. The STEADY-PD III and SURE-
PD3 parent studies have had excellent retention, with both having enrolled 
ahead of schedule. We expect recruitment will be facilitated by the PD 
research community that has been cultivated in both parent cohorts and 
by conveying the value of the AT-HOME PD study to which these parent 
study participants are uniquely able to contribute. We project that 
approximately 420 participants, or 70% of the original parent cohorts, will 
enroll in AT-HOME PD. We expect that essentially everyone will have 
access to an internet-enabled device that will support participation in tele-
visits. According to the Pew Research Center, 88% of adults use the 
internet, 
including 
87% 
of 
those 
aged 
50-64 
(http://www.pewinternet.org/fact-sheet/internet-broadband/) and 77% 
of adults own a smartphone, including 74% of those aged 50-64 

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(http://www.pewinternet.org/fact-sheet/mobile/).  Moreover, the study 
procedures were reviewed by patient advocates and considered feasible. 
 
In addition, although the pre-specified recruitment pool provides minimal 
opportunity to enhance racial and ethnic diversity of the study, we intend 
to maximize the proportion of minority participants who enroll by 
earmarking resources to assist any minority participant currently enrolled 
in STEADY-PD III or SURE-PD3 who is interested and otherwise eligible to 
enroll but does not have the requisite technical resources. For these 
participants 
the 
costs 
of 
standard 
internet 
access 
and/or 
a 
smartphone/data plan (above the reimbursement payment) would be 
reimbursed. We anticipate enrolling a relatively high proportion of women 
given their enrichment in SURE-PD3 (due to a screening process that 
targets people with lower serum urate, and given women, on average, have 
a substantially lower serum urate than men). 
 
If AT-HOME PD study participants will be considered for any future follow 
up research their contact information will be obtained from the University 
of Rochester (UR) secure HIPAA compliant database based on original 
consent. If the subject declined contact in the original study, the subject 
will be allowed to contact the UR AHPD study team directly with an interest 
in study participation. 
 
Considering the low participant burden of remote data collection, an 
inherent advantage of the outcome measures under investigation, we 
anticipate a modest dropout rate of ~15% from the tele-visit component 
over the two-year extension study. In addition, recruitment and retention 
will be motivated by multiple tested strategies ranging from reasonable 
reimbursement payments (to be paid in three installments following each 
tele-visit via check) to regular communication with participants. 
Formative research through patient interviews indicates that long-term 
data collection in a remote setting will only be sustainable with a 
smartphone application that is specifically designed to meet the needs and 
interests of the participant population. Based on initial interviews, 
engagement strategies will focus on altruism, self-exploration, education, 
and community. These are implemented through the application using 
news feeds, infographics, participation dashboards, and notifications. 
Importantly, participants will be provided with the option to view the 
outcomes of their assessments in a manner that was highly effective at 
promoting engagement within mPower but was not feasible during the 
smartphone sub-study (Smart4SURE) of SURE-PD3. 
 
5.2 
Process of Consent 
 
Interested and eligible potential participants who possess the necessary 
technology, as determined by phone pre-screening, will be emailed a direct 
link to an IRB-approved eConsent document in REDCap. Potential 
participants will be asked to review this document and indicate their 
consent electronically if they are willing to participate. As this is a minimal 
risk study and electronic signature is not recognized by the Research 
Subjects Review Board (RSRB) and the Office of Research and Project 

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Administration (ORPA), a waiver of documentation of informed consent will 
be requested. As part of the eConsent document, potential participants 
will be provided with the contact information for a study team member in 
the event that they have study-related questions. If there is no response to 
the emailed eConsent link, the participant will be sent follow-up 
reminder(s). 
 
In order to ensure that passive data collection does not have a major 
negative impact on overall enrollment, participants will be asked to opt 
into passive data collection as an optional sub-study in the mPower 
application.   
 
The participant’s screening visit will be scheduled during their prescreen 
phone call with an AT-HOME PD team member. If requested during the 
initial contact, an AHPD study team member will email the current UR IRB 
approved informed consent form to the participant and schedule a follow-
up phone call to complete the prescreening visit and/or schedule the 
participant’s screening visit.  At the screening visit, via video conference 
(VC), which is described in detail below, a study team member trained in 
human participant’s protection in accordance with UR IRB procedures will 
verify that the participant understands why the study is being done, what 
will happen during the study, possible risks and benefits, how personal 
information will be protected, and what to do if there is a problem or 
question. The study team will ensure that prospective participants have 
sufficient knowledge and understanding of the details of the study to allow 
them to make an informed decision whether or not to participate. 
Prospective participants will be provided with an opportunity to ask 
questions.  The study team member will verify the identity of the 
participant (via photo ID or by asking verification questions) and 
electronically record in REDCap that informed consent has been 
confirmed. 
 
 
5.3 
Schedule of Activities 
 
See Schedule of Activities (SOA) for AT-HOME PD study and sub-study 
activities. 
 
 
 
5.4 
Participant Identification Numbers (ID) Number 
  
 
For all prospective participants with whom the study team has been able 
to establish contact, the study team will create a new record in REDCap 
assigning the potential participant a prescreening unique participant 
identifier. This record will be used to complete the pre-screening process 
and eConsent process. If the participant appears eligible on the basis of 
pre-screening questions and provides eConsent, the study team will create 
a new record in REDCap assigning the potential participant their Global 
Unique Identifier (GUID) as their unique ID.  
 
 
Within REDCap, the participant’s contact information will be stored for UR 
staff to email the assessments and surveys to be completed by the 
participants before and after their tele-visits. This contact information will 

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remain within REDCap database and will NOT be transferred. Once the 
GUID is assigned, the GUID will be the only identifier used.   
 
a. 
Global Unique Identifier (GUID)  
Participants may have already been assigned a Global Unique Identifier 
(GUID) as part of their participation in STEADY-PD III or SURE-PD3. For 
those participants who have not already created a GUID, a study team 
member will create a GUID for them.  Sub-study participants will have 
already been assigned a GUID as part of their participation in SUPER-PD. 
 
The GUID is a universal participant ID that enables researchers to share 
and track participant data across multiple studies without exposing any 
personally identifiable information. The GUID Tool uses multiple pieces of 
personal information (first name at birth, presence of middle name, middle 
name, last name at birth, data of birth, city of birth, country of birth, and 
sex at birth) to generate a unique 10 (14 if created manually)-character ID. 
 
5.5 
Study Visits 
a. 
Pre-Screening Call 
The Pre-Screening Call will be conducted via telephone by an AT-HOME 
PD team member.  For SURE-PD3 participants it should generally occur 
within approximately 90 days after the participant’s last SURE-PD3 visit 
in the planned treatment period.  It is expected to take approximately 10-
15 minutes to complete. 
 
The following activities will be completed: 
x Overview of the study and assessment of interest 
 
If the individual is interested in participating: 
 
x Pre-screen questionnaire for eligibility 
x eConsent (link to REDCap emailed) 
x Technology survey (automatically follows eConsent in REDCap) 
b. 
Screening Visit (within 30 days following eConsent) 
The Screening Visit will be conducted remotely using a web-based video 
platform (VC). For SURE-PD3 participants it should occur after the final 
SURE-PD3 visit in the planned treatment period. It is expected to take 
approximately 30 minutes to complete. 
 
The following activities will be completed:  
x 
Verify consent (see 5.2 Process of Consent) 
x 
Verify participant’s identity (photo ID or answering verification 
questions) 
x 
Verify eligibility (see below) 
x 
Demographics 
x 
Test connection 
x 
Creation of FI Account (see below) 
x 
Creation of GUID (if not already created) 

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x 
Simplybook.me orientation 
 
Eligibility Verification: 
The study team member will verify eligibility.  All of the inclusion criteria 
and none of the exclusion criteria must be met unless a study PI or 
designee provides a waiver for certain criteria. More detail regarding this 
process and instructions for the requirements for waivers can be found in 
the Operations Manual.  
 
Eligibility Identification: 
The study team member will verify the participant’s identity at the time of 
eConsenting.  The study participant will be asked to verify their identity 
by showing the study team member their photo ID. The identity 
verification will be done by only viewing the ID during the tele-visit and 
this information will not be collected. If a photo ID is not available, every 
effort will be made to verify the participant’s identify by asking the 
questions below: 
i. 
ask the participant to repeat their name 
ii. 
ask the participant to state their year of birth 
iii. 
ask the participant to provide their address of record  
If for any unforeseen reason the study team member is unable to verify 
the identity of the participant by photo ID or verification questions, the 
study team member will document the reason and continue with 
completing the eConsenting process and enrolling the eligible participant 
in to the study. This will ensure that the study is able to meet the 
recruitment numbers (from a limited patient population), as well as 
ensure that the study is able to enroll all - otherwise eligible - 
participants. 
FI Account Creation:  
A study team member will create a FI account for the participant using 
email address and GUID. If the participant is already enrolled in FI, the 
participant will receive an email notifying them that their FI profile has 
been linked to the AT-HOME PD study. If the participant is not already 
enrolled in FI, he/she will receive an email from FI with instructions 
regarding how to verify their new account.  Once this has been done, the 
participant will be prompted to complete the registration and consent 
process for FI. 
 
 
SimplyBook.me Orientation: 
A study team member will introduce the participant to the 
SimplyBook.me HIPAA-compliant scheduling software, which will be used 
to schedule tele-visits and send tele-visit reminders. The participant will 
be asked to choose whether they would like to schedule tele-visits in the 
morning or afternoon and all tele-visits will be scheduled according to 
their preference. Follow-up tele-visits will preferentially be scheduled with 
the same provider, unless that is logistically impossible (due to staffing 
schedules or the like). In order to reduce variability related to diurnal 
fluctuation, participants should select the same time window (morning or 
afternoon) for performance of smartphone tasks. 
 

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c.  Tele-Visits (Baseline (Day 0; within 60 days of Screening/VC), 
Month 12 (+/- 28 days), Month 24 (+/- 28 days) 
STEADY-PD III  
STEADY-PD III participants will undergo visits per the SOA. The baseline 
tele-visit will occur within 0-60 days of the screening visit.  
 
SURE-PD3 
All SURE-PD3 participants who have not yet (or have recently) completed 
their participation in SURE-PD3 should have their baseline tele-visit  after 
their final in-person study visit (or equivalent) in the planned treatment 
period. Ideally, this baseline tele-visit will occur within 28 days of the final 
in-person study visit (or equivalent) in the planned wash-out period to 
allow validation of tele-visit data acquisition versus that of the standard 
in-office visits. The baseline visit will occur within 0-60 days of the 
screening visit. 
 
¾ All of the tele-visits will be conducted remotely using a web-based video 
platform and are expected to take approximately 60-90 minutes to 
complete. 
¾ All of the tele-visits will consistently be attempted to be conducted in 
either the morning or the afternoon, according to participant preference, 
to reduce the effect of diurnal symptom variation. For participants on 
symptomatic dopaminergic therapy, the Movement Disorder Society – 
Unified Parkinson Disease Rating Scale (MDS-UPDRS) part 3 will be 
obtained in the usual ON state. The timing of last dopaminergic 
medication intake will be recorded.   
¾ A +/- 28-day window (from baseline TV) will be used for the Month 12 and 
Month 24 visits, however, visits should ideally be scheduled such that 
they are conducted during the corresponding 14-day smartphone session. 
 
Pre-tele-visit – Up to one week prior to each visit, participants will be 
emailed the direct links to the following REDCap surveys, which will need 
to be completed before the tele-visit. 
x 
MDS-UPDRS parts 1b and 2.  
x 
Self-Reported Fall Questionnaire 
x 
Patient Global Impression (PGI)-Severity.  PGI-Change will be 
completed during month 12 and month 24 visits only. 
 
The following assessments will be completed during the tele-visit: 
x 
Review Reportable Events 
x 
Review Concomitant Medications 
x 
MDS-UPDRS parts 1a, 3 and 4 (where applicable).  Part 4 will only 
be completed for individuals who are receiving dopaminergic 
therapy. 
x 
Montreal Cognitive Assessment (MoCA) 
x 
Modified Schwab & England Activities of Daily Living Scale 
(SEADL) 

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x 
Clinical Global Impression (CGI)-Severity. CGI-Change will be 
completed during month 12 and month 24 visits only. 
x 
Determination of Falls 
x 
Confirmation of participant completion of MDS-UPDRS parts 1b 
and 2, self-reported falls assessment, and PGI-severity and change 
x 
Review of participant compliance with smartphone tasks and FI 
patient-reported outcome measures where applicable 
x 
Where applicable, smartphone application registration will occur 
shortly prior to the baseline visit and orientation will occur during 
the baseline tele-visit (see below).  
x 
Completion of a complete set of smartphone active motor and 
cognitive tasks (where applicable)  
 
 
 
Post-tele-visit 
x 
Participant Preference and Burden Survey. Following completion 
of the visit, participants will be emailed a direct link to REDCap to 
complete this survey. 
 
Smartphone Application Registration:  
The study team member will initiate the registration process by inputting 
the participant’s GUID, smartphone number and visit date into Sage 
Bionetworks Synapse web portal a couple of days before the participants 
orientation visit. This will create a mPower account for the participants in 
the Sage Bionetworks Bridge service. During the baseline tele-visit the 
study team member will help the participants to download and install the 
application. After installation, the study team member will review proper 
performance of each task and direct the participant towards helpful 
resources in the event that they have any further questions about the 
tasks. A study team member will remotely supervise the participant while 
he/she completes a complete set of smartphone tasks. 
d. Smartphone Sessions (Baseline, Month 3, 6, 9, 12, 15, 18, 21, 24) 
x 
14-day smartphone sessions will occur on a quarterly basis. 
x 
Given diurnal variation in active task performance, participants 
will be asked to select morning or afternoon as their preferred 
window for completion and to consistently attempt to complete the 
active tasks according to their selected preference. 
x 
Participants will be notified one day before the start of each 14-day 
session 
 
During these 14-day sessions, participants will be asked to complete daily 
4 to 6-minute smartphone-based motor tasks. If they fall behind and are 
not able to complete at least 10 daily activity sets they can optionally 
continue for up to 5 additional days. 
The following motor activities will be completed by the participant: 
● Gait Task  
● Finger Tapping Task  
● Resting Tremor Task  

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● Balance task  
 
During these 14-day sessions, participants will be asked to complete an 
approximately 8-minute set of smartphone-based cognitive assessments 
on at least 3 of the days. 
 
The following activities will be completed by the participant: 
x 
Digit Span 
x 
Digit Symbol Substitution Tests 
x 
Spatial Working Memory 
 
Participants will be asked to provide basic demographic information 
through the application once. Participants will also use the application to 
track their medication adherence relative to tasks and, optionally, self-
reported symptoms and triggers. Additionally, participants may perform 
the active tasks at any time outside of the 14-day smartphone sessions if 
desired. 
 
Compliance will be actively monitored.   
x 
Participants will receive reminders if they do not perform the 
activities for two consecutive days and/or after not performing the 
activities for four days of the 14-day session. 
x 
Participants who enable notifications will receive daily notifications 
during each 14-day session 
x 
Sage Bionetworks will make quarterly reports available to 
CHeT/CTCC that will include each participant’s compliance 
status. 
 
e. FI Sessions (Baseline, Month 3, 6, 9, 12, 15, 21, 24) 
x 
AT-HOME PD participants will be asked to complete a set of 
standard questionnaires through a companion study called FI, 
(https://foxinsight.michaeljfox.org). 
x 
Participants will be asked to complete the questionnaires in the SOA 
every 90 days. [Refer to SOA] The baseline visit takes approximately 
one hour to complete; subsequent visits take only 10-15 minutes to 
complete. 
x 
Participants will have a 90-day window in which to complete the 
questionnaires.  However, they will be encouraged to complete the 
Baseline, Month 12, and Month 24 FI questionnaires within 28 days 
of the corresponding tele-visit. 
Compliance will be actively monitored. 
x 
Those participants that fail to complete all of the assessments will 
be sent an email reminder by FI after approximately 45 days. 
x 
FI will send another email reminder after approximately 88 days if 
all of the assessments still have not been completed. 
x 
FI will send quarterly reports to CHeT/CTCC that will include each 
participant’s compliance status. This will continue until a publicly-
accessible FI research database is available through LONI. 

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f. Premature Withdrawal Visit 
 
Premature withdrawal will be defined as withdrawal from the tele-visit 
component (or the full study) prior to completion of the month 24 tele-visit. 
Participants have the right to withdraw from the study, or any individual 
component of the study, at any time without prejudice. Although not 
anticipated, an investigator may withdraw a participant from the study if 
participation places the participant at undue risk or if the participant dies 
or experiences another reportable event that precludes further study 
participation. In all other circumstances, all participants should be 
retained in the study regardless of compliance to limit bias from 
informative drop-out. 
 
In the event of premature withdrawal from the study, the Premature 
Withdrawal (PW) Visit procedures and evaluations should be completed 
whenever possible whether or not the withdrawal is determined at a 
regularly scheduled study visit or at an unscheduled visit. 
 
Reasons for withdrawal of the participant prior to completion of the study 
must be stated in the eCRF for all study participants who were enrolled in 
the study. 
 
The premature withdrawal tele-visit is expected to take approximately 60 
minutes to complete. 
 
Pre-tele-visit – up to one week prior to each visit, participants will be 
emailed the direct links to the following REDCap surveys, which will need 
to be completed before the tele-visit. 
x 
MDS-UPDRS parts 1b and 2.  
x 
Self-Reported Fall Questionnaire 
x 
Patient Global Impression (PGI)-Severity. PGI-Change will be 
completed during month 12 and month 24 visits only. 
 
The following assessments will be completed during the tele-visit: 
x 
Review Reportable Events 
x 
Review Concomitant Medications 
x 
MDS-UPDRS parts 1a, 3 and 4 (where applicable). Part 4 will only 
be completed for individuals who are receiving dopaminergic 
therapy. 
x 
Montreal Cognitive Assessment (MoCA) 
x 
Modified Schwab & England Activities of Daily Living Scale 
(SEADL) 
x 
Clinical Global Impression (CGI)-Severity. CGI-Change will be 
completed during month 12 and month 24 visits only. 
x 
Determination of Falls 
x 
Confirmation of participant completion of MDS-UPDRS parts 1b 
and 2, self-reported falls assessment, and PGI-severity and change 

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x 
Review of participant compliance with smartphone tasks and FI 
patient-reported outcome measures where applicable 
x 
Smartphone application registration and orientation, where 
applicable, will occur during the baseline tele-visit (see below).  
x 
Completion of a complete set of smartphone active motor and 
cognitive tasks (where applicable)  
x 
Early termination survey 
 
 
 
Post tele-visit 
x 
Participant Preference and Burden Survey. Following completion 
of the visit, participants will be emailed a direct link to REDCap to 
complete this survey. 
 
g. Passive Data Collection 
For participants that optionally consent to passive data collection, the 
smartphone application will collect multiple streams of passive data: 
movement patterns captured by location services (including GPS) and 
motor activity patterns captured by accelerometers and gyroscopes. To 
reduce issues relating to patient privacy concerns, movement patterns will 
be collected using displacement vectors without storing actual GPS 
coordinates. To reduce burden relating to use of data plans for data 
transfer, the application will transfer data on a daily basis and preferably 
using a Wi-Fi connection. In order to ensure that monitoring is 
naturalistic, participants will not be given any instructions regarding how 
or when to carry their smartphone. 
5.5.1 Sub-study Study Visits 
a. Pre-Screen  
The Pre-Screen will be conducted via telephone or during a 
potential participant’s SUPER-PD study visit by an AT-HOME PD 
team member. It is expected to take approximately 10-15 minutes 
to complete. 
 
The following activities will be completed: 
x Overview of the study and assessment of interest 
 
If the individual is interested in participating: 
 
x Pre-screen questionnaire for eligibility 
x eConsent (link to REDCap emailed) 
 
b. 
Tele-Visit (within 14 days of SUPER-PD baseline or month 
12 study visit) 
¾ The tele-visit will be conducted remotely using a web-
based video platform and is expected to take approximately 
30 minutes to complete. 

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¾ For participants on symptomatic dopaminergic therapy, the 
Movement Disorder Society – Unified Parkinson Disease 
Rating Scale (MDS-UPDRS) part 3 will be obtained in the 
usual ON state. The timing of last dopaminergic medication 
intake will be recorded.   
The following assessments will be completed during the tele-visit: 
x 
Verify eligibility and eConsent  
x 
MDS-UPDRS part 3  
x 
Montreal Cognitive Assessment (MoCA) 
x 
Reportable Events 
 
 
6. ASSESSMENTS 
 
 
 
 
 
6.1 
Primary Assessments 
 
a. 
Pre-Screening Questionnaire 
 
The pre-screening questionnaire includes questions regarding access to 
an internet-enabled device that will support participation in tele-visits, 
possession of a web-camera, and possession of a suitable smartphone. 
 
b. 
Technology Survey 
 
 
 
Survey questions were originally adapted from the Pew Internet & 
American Life Project Question database. The survey includes questions 
regarding access and use of specific technology and prior experience with 
tele-visits.  
 
 
c. 
Movement Disorders Society Unified PD Rating Scale (MDS-
UPDRS) 
The MDS-UPDRS will be conducted per the Schedule of Activities. The 
MDS-UPDRS was designed by movement disorders experts to address 
weaknesses of the original UPDRS (e.g., by adding questions on 
constipation and sialorrhea) while preserving its overall format. The 
MDS-UPDRS has four parts: 
x 
Part I (non-motor experiences of daily living), comprising 
 
Part Ia concerning behaviors that are assessed by the CHeT  Site 
Investigator with all pertinent information from patients and 
caregivers 
 
Part Ib that is completed by the patient with or without the aid of 
the caregiver, but independently of the Investigator. 
x 
Part II (motor experiences of daily living), designed to be a self-
administered questionnaire like Part Ib, but similarly can be 
reviewed by the study team to ensure completeness and clarity. 

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x 
Part III (motor examination) has instructions for the rater to give 
or demonstrate to the patient; it is completed by the clinician rater. 
Given the remote nature of our evaluations, we will administer a 
modified version of part III that does not include assessment of 
rigidity or postural instability. 
x 
Part IV (motor complications) with instructions for the rater and 
also instructions to be read to the patient. This part integrates 
patient-derived information with the rater's clinical observations 
and judgments and is completed by the rater. Complete Part IV 
only if ST has been initiated.  
Participants will self-administer Parts Ib and II, through completion 
of REDCap surveys, but the study team member will review 
responses for completion and ask the participant to complete it 
during the tele-visit if incomplete. Use of MDS-UPDRS is responsive 
to core instrument recommendations for the Quality of Life 
subdomain of the National Institute of Neurological Disorders and 
Stroke (NINDS) Common Data Elements (CDEs) for PD, and to the 
Food and Drug Administration (FDA) guidance encouraging use of 
PROs as a substantial portion of the responses are patient-reported.  
The investigators are neurologists 
or board-certified nurse 
practitioners who have received formal MDS-UPDRS certification (by 
the MDS) and will have additionally undergone joint training to 
reconcile scoring differences and minimize inter-rater variability. 
Ideally, the same Site Investigator should assess all participants on 
parts Ia, III, and IV (when applicable) of the MDS-UPDRS at all study 
visits. 
 
D. 
Montreal Cognitive Assessment (MoCA) 
In early PD, when cognitive deficits occur, they are subtle and mild, 
and the participants usually perform in the normal range of the 
widely used Mini-Mental State Exam (MMSE). The MoCA is a rapid 
screening instrument like the MMSE but was developed to be more 
sensitive to patients presenting mild cognitive complaints. It is 
designated an NINDS CDE for PD. The MoCA assesses short-term and 
working 
memory, 
visual-spatial 
abilities, 
executive 
function, 
attention, concentration, language and orientation. As completion of 
the MoCA requires performance of some tasks on paper, the 
participant will be sent a copy of the relevant portions of the MoCA 
(trail-making, cube copying) prior to the tele-visit. Ideally, this will be 
sent in a sealed envelope and the participant will be asked to open 
the envelope only during their tele-visit.  However, it may alternatively 
be sent via email with instructions to print immediately prior to the 
tele-visit. During the tele-visit, the participant will be instructed on 
how to complete these tasks and will be asked to display their 
responses such that they can be visualized and evaluated by the 
study team member. The total score ranges from 0 to 30 (highest 
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E. 
Modified Schwab and England Activities of Daily Living Scale 
(SEADL) 
The SEADL is an Investigator and participant assessment of the 
participant’s level of independence. The participant will be scored on 
a percentage scale reflective of his/her ability to perform acts of daily 
living. Printed scores with associated descriptors range from 100% to 
0% in increments of 10%, where 100% is “participant has full ability 
and is completely independent; essentially normal” and 0% is 
“vegetative functions such as swallowing, bladder and bowel 
functions are not functioning; bedridden”. Scores should be coded in 
increments of 10, (i.e. 090, 080, 070). This assessment will be 
completed jointly by the participant and Investigator.  
F. 
Clinical Global Impression and Patient Global Impression 
Scales (CGI) 
The CGI is an observer-rated scale that measures illness severity 
(CGIS) and global improvement of change (CGIC). Each component 
of the CGI is rated separately; the instrument does not yield a global 
score.  
The CGIS is rated on a 7-point scale, with the severity of illness scale 
using a range of responses from 1 (normal) through to 7 (amongst the 
most severely ill patients). CGIC scores range from 1 (very much 
improved) to 7 (very much worse). 
Similarly, the PGI is a patient-rated scale that measures illness 
severity (PGIS) and global improvement of change (PGIC).   
 
g. 
Falls Assessment 
Falls will be assessed using two questionnaires, which have been 
incorporated into an on-going large prospective study (PPMI). The 
self-reported falls assessment is a 1-item questionnaire that will be 
completed by the participant. The determination of falls assessment, 
which will be completed by the investigator, includes questions about 
freezing of gait and falls over two time periods (the past week and the 
past 12 months). 
 
6.2 
Smartphone Assessments 
 
The following motor activities will be completed by the participant: 
● Gait Task - A 30 second walking task where the participant will 
walk with their phone in their pocket to measure gait using the 
phone accelerometer and gyroscope.  
● Finger Tapping Task - A 30 second speeded tapping task in each 
hand where screen presses are captured.  
● Resting Tremor Task - A 30 second task in each hand where the 
participants hold the phone with their hand in their lap while the 
phone records accelerometer and gyroscope readings. 

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● Balance task - A standing task where the participant tries to stand 
still while the phone measures accelerometer and gyroscope 
readings. 
 
The participant will be asked to complete cognitive tasks, which may 
include the following: 
 
x 
Digit Span - A short term memory test in which the participant 
reports back a series of numbers that were displayed rapidly to 
them. 
x 
Digit Symbol Substitution Tests - A neuropsychological test 
sensitive to brain damage, dementia, age and depression. It 
consists of (e.g. nine) digit-symbol pairs followed by a list of digits. 
Under each digit the subject should write down the corresponding 
symbol as fast as possible. 
x 
Spatial Working Memory - A neuropsychological test that tests 
memory and manipulation visuospatial information. 
 
6.3 
Fox Insight (FI) Assessments 
 
FI is a separate online research study with a separate consent process. 
As such, the assessments will not be described in detail. The following 
validated assessments are included in FI:  
 
 
The Parkinson’s Disease Questionnaire, short-form 8 item version 
(PDQ-8) 
 
MDS-UPDRS part 2  
 
Physical Activity Scale for the Elderly (PASE) 
 
Your Cognition and Daily Activities (PDAQ-15) 
 
Euroqol Five (EQ-5D)  
 
Non-motor symptoms questionnaire (NMS-QUEST) 
 
Geriatric Depression Scale, short form (GDS) 
 
Parkinson’s disease-Patient Reported Outcomes of Problems (PD-
PROP) 
The complete list of assessments can be found in the SOA. Participants 
are also invited to complete additional PRO surveys about, but not 
limited to, symptoms, disease progression, quality of life, patient 
preference and general health. 
6.4 
Safety Assessments (see Section 9 Reportable Events) 
 
 
 
As this is a minimal risk observational study that does not involve a drug 
or device intervention, adverse events are not anticipated and will not be 
assessed. Safety assessments will be limited to the collection of 
reportable events either spontaneously offered by the participant or 
observed by a study team member during a tele-visit. 
 
 
 
 
6.5 
Assessment of Participant Compliance 
 
At each tele-visit, the Investigator and/or study team member will 
assess the participant’s compliance with the study requirements. This 

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will include checks of protocol compliance, including completion of 
surveys for tele-visits, smartphone tasks (where applicable), and FI 
survey completion (where applicable). More detail regarding the 
monitoring of compliance can be found in Section 5.5. 
 
While we will strive to retain all participants, we will consider successful 
participants to be those who complete at least six of nine smartphone-
based test batteries over 24 months- including two of the three sets that 
coincide with the tele-visits. 
 
7. COSTS TO THE SUBJECT 
 
There is no direct cost to the participants to participate in this study. If they 
participate in the smartphone component of this study, data collected through 
the app may count against their existing mobile data plan. The internet 
connection can be configured within the app to only use Wi-Fi connections to 
limit the impact running this app has on the data costs. Subjects will not have 
to pay for research procedures. 
 
8. PAYMENT FOR PARTICIPATION 
 
Participants will be compensated $50 for each tele-visit completed, as applicable 
(baseline, month 12 and month 24) for a total of up to $150 for expenses incurred 
to participate in the AHPD study via a check. They will not be paid for tele-visits 
that they do not complete. If a web camera is provided to the participants, they will 
be allowed to keep it after completion of the study for their own use.  
 
The costs of standard internet access and/or a smartphone/data plan (above the 
compensation amount) will be reimbursed for minority participants currently 
enrolled in STEADY-PD III or SURE-PD3 who are interested and otherwise eligible 
to enroll but do not have the requisite technical resources. 
 
 
9. RISK/BENEFIT ASSESSMENT 
 
9.1 
Potential Risks 
The risks of participating in this study are very low.  
x 
The most common risk is discomfort with some of the questions 
or assessments. 
x 
Some of the questions in the questionnaires may be upsetting or 
make the participant feel uncomfortable. They may feel frustrated 
while taking a test used to evaluate the memory or thinking: it is 
meant to be challenging. 
x 
During the tele-visits the study team will watch the participant 
walk, and there is a possibility that they could fall.  
x 
Another risk is breach of confidentiality if someone were to access 
the study information without authorization. Because this study 
involves collecting personal, identifiable information, there is a 
potential for invasion of privacy or breach in confidentiality. 
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unintended data breaches. In such an event, that the data may 
be misused or used for unauthorized purposes. 
 
Smartphone Application 
There are a few additional risks to participating in the smartphone 
assessments: 
x 
Other people may glimpse the study notifications and/or 
reminders on the smartphone and may become privy to the 
information that the participant is enrolled in this study. This can 
make some people feel self-conscious. 
x 
There is a potential for invasion of privacy or breach of 
confidentiality. The data collected through the  mPower app will 
be encrypted on the smartphone, transferred electronically and 
stored securely in Synapse. Sage team will separate the 
participant 
account 
information 
(name, 
email, 
contact 
information, etc.) from the study. 
x 
Sage will not access the personal contacts, other apps, text or 
email message content, or websites visited.  
 
9.2 
Protection Against Risks 
x 
Participants are free to stop a test at any time. Participants can 
take breaks as needed.   
x 
If they typically walk with an assistive device (such as a cane or 
walker) or with the help of a caregiver, they will only be asked to 
walk under their usual conditions. Participants will not be asked 
to try to walk if they typically use a wheelchair or if they or the 
investigator has concerns about the risk of falling. If a participant 
does fall during the visit, or have another medical event during 
the tele-visit that requires emergent evaluation, the study 
investigator or a team member will assist in contacting emergency 
services if needed. 
x 
Every effort will be made to maintain confidentiality and protect 
personal information obtained as a result of this study. 
x 
Study team will assign a GUID number instead of labeling the 
information collected from the participant with their name (or 
medical record number). Study team will use GUID instead of the 
name on all the study data. Information about the GUID number 
will be kept in a secure system. Only the study investigators and 
some technical staff for AHPD, STEADY-PD III or SURE-PD3 
studies and some FI clinical operations staff will have the key to 
link the coded study data to the participant name and account 
information.  
x 
Study will use a HIPAA compliant, secure video-conferencing 
system for the tele-visits. Note: real time video conferencing will 
be used to complete the assessments which will not be recorded. 
x 
The software that will be used for the surveys and to store the 
information from the tele-visits has been specifically designed to 
protect the privacy of research subjects and access to the 
database is restricted. 

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x 
Data obtained through Fox Insight questionnaires are stored in a 
secure databank. Only the Fox Insight study team will have access 
to this information before any parts that could identify the 
participants will be removed. 
x 
The study combined data will be stored securely in Sage 
Bionetworks’ databank Synapse (synapse.org), using Amazon-
Web Cloud Services.  
 
9.3 
Potential Benefits to Subjects 
Participants will not benefit directly from being in this research study. 
Benefits may include contributing to the future research advances and 
experiencing new ways of tracking and measuring the disease. 
 
9.4 
Alternatives to Participation 
If the participant elects not to participate in the study, there are no 
alternatives available.  
10. 
CONCOMITANT MEDICATIONS 
 
10.1 
Required Therapy  
There is no restriction on medications in this study. All concomitant 
medications will be recorded. 
 
11. 
PARTICIPANT WITHDRAWALS/DROPOUTS 
 
 
Participants will be advised in the written informed consent forms that they have 
the right to withdraw from the study at any time without prejudice and may be 
withdrawn at the Investigator’s or sponsor’s discretion at any time. 
 
Premature withdrawal will be defined as withdrawal from the tele-visit component 
(or the full study) prior to completion of the month 24 tele-visit. If a participant 
who has started the study terminates the study prematurely, every effort should 
be made to complete the premature withdrawal visit. Reasonable effort should be 
made to contact any participant lost to follow-up during the course of the study 
in order to complete study related assessments and retrieve any outstanding 
data. Participants may be deemed lost to follow-up after 15 months without 
contact. Contact attempts may include phone calls, emails, and physical mail. 
Such efforts should be documented in the source documents. 
A participant may withdraw or be withdrawn from the study for the following 
reasons: 
 
• 
Administrative 
 
1. Withdrawal of consent 
2. Participant deemed lost to follow-up 
3. Premature withdrawal of study 
 

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• 
Medical Events 
 
1. Death 
2. Other reportable event that precludes further study participation 
 
Participant premature withdrawal should be reported to the CTCC Project 
Manager within 5 business days of site’s knowledge of the event. 
The Demographic form must be completed for all study participants who provide 
informed consent. This includes participants who completed the study or 
withdrew/were withdrawn from the study or were screened and provided consent 
but did not start the study.  
 
The Conclusion of Study Participation form should be completed for all 
participants who have been enrolled. If a participant withdraws due to a 
reportable event, the site must ensure that the event is captured on the reportable 
event form. 
 
12. 
REPORTABLE EVENTS  
 
Based on the nature of the study, routine adverse events will not be collected. In 
this study, the following pre-specified events that are thought to be relevant to 
the safety and feasibility of the study population will be considered Reportable 
Events (RE). REs will be assessed at the tele-visits and reported on the RE log 
within 72 hours of the event, or the CHeT Site Investigator’s knowledge of the 
event.  
x 
Compromise of confidentiality 
x 
Loss of competence to consent 
x 
Withdrawal from the study 
x 
Severe depression and suicidal ideation 
x 
Suicide attempt 
x 
Hospitalization for serious (non-elective) medical issues (including 
childbirth) 
x 
Any psychiatric hospitalization 
x 
Participant intends to or has participated in another research 
study involving experimental interventions 
x 
Any neurologic event (e.g., TBI, Seizure, etc.) 
x 
Identification of a safety concern warranting referral for medical 
evaluation 
x 
Identification of a safety concern warranting referral for 
psychiatric evaluation 
x 
Death 
 
Although not a reportable event the enactment of the Medical Safety Escalation Plan 
should be reported to the CTCC PM  
Enactment of the Medical Safety Escalation Plan (see section 9.2) 
 
 

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12.1 Recording of Reportable Events  
 
At each tele-visit the study team member will assess REs by recording 
all voluntary complaints of the participant and by assessment of clinical 
features. 
 
All REs, whether observed by the Investigator or volunteered by the 
participant, should be recorded on the eCRF RE Log. This will include 
the type and description of the event, the date of onset, investigator 
opinion of relatedness to study participation, and any action taken. 
This recording will commence with the institution of protocol-specific 
procedures and continue until either withdrawal or study completion. 
 
The CHeT Site Investigator will comply with the UR Institutional Review 
Board (IRB) regulations regarding the reporting of reportable events.  
 
 
 
12.2 Emergency Actions  
 
 
 
A Medical Safety Escalation Plan has been created for urgent and non-
urgent medical situations (see Operations Manual). The purpose of the 
Medical Safety Escalation Plan is to responsibly manage complex or 
acutely escalating medical issues that may arise during a tele-visit to 
ensure participant safety. 
 
13. STATISTICAL ANALYSIS 
 
Planned analyses are summarized here. Additional details will be included in a 
separate Statistical Analysis Plan (SAP). In the event of a conflict between the 
protocol and the SAP, the SAP will take precedence. 
13.1 
Data Processing and Quality Control (QC) for Smartphone (SP) 
Based Measures: 
Data QC and cleaning: As data from the SP are deposited on a daily basis into 
Synapse, we will have a clear measure of compliance and engagement.  
Additionally, data streams can be monitored for quality. Data scientists and 
statisticians at Sage Bionetworks have developed an extensive pipeline to 
monitor and QC active task measurements from smartphone applications (e.g., 
https://github.com/Sage-Bionetworks/mpowertools). These tools will be 
adopted and expanded to monitor and QC passive data streams. During the 
development stage of the application we will run small scale internal 
experiments where user use Android and iOS devices concurrently to establish 
bounds on differences between devices. 
Data processing/feature extraction: Quality processed data will be summarized 
into features using extensions of our feature extraction pipelines for active 
tasks. These include but are not limited to time and frequency domain 
statistics, energy and entropy of frequency spectrum from the tri-axial 
accelerometer, 
along 
with 
absolute 
displacement 
measurements. 
For 
displacement information (Aim 3b) data will be summarized into variables such 
as furthest distance traveled, frequency of trips, average daily distance etc. Also, 
additional specific features will be selected based on previously published 

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studies using passive data and expert knowledge of behavioral patterns of PD 
patients. These measures will be summarized to a single measure by training a 
n-fold cross-validated machine learning model using the discovery data subset. 
Additionally, features will be evaluated by test-retest reliability across time. 
Data analysis will be performed as described in SA 3.B and 3.C below. 
 
13.2 Statistical Analysis Plan 
 
Aim 1: To evaluate concordance between in-clinic and tele-visit MDS-
UPDRS assessments (Aim 1b), we will use results from the REACT-PD 
study to calibrate tele-visit assessments to in-clinic MDS-UPDRS scores, 
matching means and standard deviations cross-sectionally. We will use 
Lin's concordance correlation coefficient, rc, to summarize accuracy of the 
calibrated tele-visit estimates vs. scores collected from in-person SURE-
PD3 and SUPER-PD visits conducted close in time, accepting tele-visit 
estimates as sufficiently accurate if rc > 0.8. If we observe insufficient 
concordance, we will investigate contributions of bias, scale difference, 
and imprecision and re-calibrate using all available data from both 
REACT-PD and the current study. 
Aim 2: We will assess the calibration and correlation between tele-visit 
(TV) and SP metrics both cross-sectionally and longitudinally (Aim 2a). 
We will generate SP-derived metrics that best match composite scores of 
motor function (MDS-UPDRS part 3), non-motor function (MoCA total 
score), subjective function (including global impression (CGI) scores, 
Schwab and England ADL scores, MDS-UPDRS parts 1b and 2 scores, 
and estimates of MDS-UPDRS part 1-3 total scores. We will randomly split 
our sample 2:1 into calibration and validation subsets. For each measure, 
we will use the calibration sample to develop a transformation of SP data 
that best matches the TV measurement machine learning models using a 
variety of machine learning techniques with a final selection based on 
overall accuracy by 10-fold cross-validation. We will test the accuracy of 
calibrated SP measures in the reserved validation sample using Lin's 
concordance correlation coefficient, rc. If we observe insufficient 
concordance, we will investigate contributions of bias, scale difference, 
and imprecision and re-calibrate using all available data from both the 
calibration and validation samples.  
We will compare TV vs. calibrated SP measures of disease progression 
generally, as predictors of future clinical events and changes in patient 
reported outcomes, and between specific subsets of participants expected 
to progress at different rates (Aim 2b) due to biology or treatment. After 
calibration, we will estimate the standard error for a treatment-group 
comparison from a two-arm trial using measure-specific variance 
components from a bivariate random-slopes linear mixed model for each 
pair of TV and SP measures and assuming an assessment schedule 
appropriate for each measure, e.g., annual for TV measures and quarterly 
for SP measures. Preferred measures would have smaller standard errors, 
and specifically, the ratio of squared standard errors provides an estimate 
of the relative sample size required. We will use the same approach to 
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subgroups (e.g., among participants stratified by their rate of MDS-
UPDRS progression over the first 2 years of in-clinic follow-up in the 
parent 
trials) 
or 
treatment-based 
subgroups 
(e.g., 
participants 
randomized to Isradipine or serum urate elevation). To compare TV 
assessments and SP measures with respect to their accuracy in predicting 
future clinical events and changes in patient reported outcomes, we will 
use the same 2:1 training: validation split and train separate models 
using TV and SP metrics collected over the first year of follow-up to predict 
clinical events and changes in PROs over the second year of follow-up. 
Clinical events will include dropping below 80% on the modified Schwab 
and England ADL and experiencing a fall. PROs of interest will include 
summary scores from the PDQ-8, EQ-5D, and PDAQ-15 and measures 
derived from the PD-PROP. Selection of the best training models will be 
based on 10-fold cross-validated accuracy for binary outcomes and 
residual sum of squares for continuous measures. Positive and negative 
predictive values of TV and SP-derived predictions will be estimated from 
the validation sample for binary outcomes and compared by logistic 
regression. For continuous outcomes, RSS estimates will be compared 
between TV and SP-derived predictions. As an exploratory analysis, 
additional models that combine TV and SP measures will be constructed 
and tested for accuracy relative to models derived from TV or SP measures 
alone. 
Completion rates of PROs collected during TVs vs. those collected online 
via FI will be compared by mixed effect logistic regression with 
participant-specific and participant x form random effects (Aim 2c). 
Concordance between PROs assessed during TVs vs. those obtained 
online via FI will be estimated using Lin's concordance correlation 
coefficient (Aim 2c). 
Aim 3:  
We will evaluate the feasibility to collect and use passive data to track 
disease progression.  Passive data collection will come in two flavors - 
displacement tracking that captures a participant’s life space, i.e. their 
mobility patterns and collection of accelerometer and gyroscope readings 
when the participants are walking throughout the day. The walking data 
will be analyzed exactly the same as the actively collected data as 
described in Aim 2. The displacement tracking requires more care and 
will require us to first determine feasibility of data collection (Aim 3a) and 
extensive norming before assessing ability to track progression (Aim 3b).  
Evaluation of Data Collection: 
The first component of this Aim will focus on evaluating the feasibility of 
collecting passive data from individuals over a 2- year time period. This 
includes addressing two potential barriers to data collection: (1) 
Participant willingness to provide permission for passive monitoring and 
(2) the ability to collect passive data continuously over a 2-year period 
despite infrastructure changes caused by smartphone hardware and 
software upgrades. 
Hypothesis: 70% of AT-HOME PD participants who participate in the 
smartphone component will consent to collection of passive data. 

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This will be evaluated by observing the number of active participants 
willing to enroll in this sub-study. 
 
Hypothesis: Passive data will be collected in a persistent manner for the 
full 2-year study in at least 75% of consented individuals. Data collection 
will be monitored on a continuous basis. 
 
We will evaluate the ability to use passive motor measures to predict 
relative changes in disease severity within a participant. Due to the highly 
individualized nature of activity patterns, it is unknown whether passive 
data can be used to derive absolute measures of disease severity. 
However, we expect that relative changes in activity patterns over time 
will provide a mechanism to track disease progression on an 
individualized basis.  Features from displacement data such as total daily 
movement, number of daily trips, etc. will be generated and normed per 
individual before evaluation of disease progression using the same 
methods as described in SA 2b. 
 
We will evaluate the use of passive measures to directly assess disease 
severity. The longitudinal nature of the displacement data provides the 
ability to identify personalized changes in disease burden over time and 
to evaluate whether changes in activity patterns over time are comparable 
to changes in disease severity as evaluated within the other components 
of this study. By focusing on changes in app active task performance and 
changes in tele-visit evaluations we can test the ability to track disease 
severity. Daily displacement will be evaluated per individual relative to: 
finger tapping, gait assessment, and overall composite score for 
smartphone-based motor evaluation using passive data collected during 
the burst periods using Lin's concordance correlation coefficient, rc 
Likewise we will perform the same analysis on the tele-visit assessments.  
Anticipated outcomes and alternatives:  
The overarching goal of Aim 3 is to evaluate whether and how passive 
data collection can be used for long-term monitoring of PD symptoms in 
clinical research cohorts. If we can observe relative changes in disease 
state, it could be used to trigger standard assessments – providing a way 
to reduce clinic burden and cost by deploying expensive clinic visits only 
when necessary rather than at regular time intervals. The use of these 
data also provides a mechanism to augment existing severity measures 
by directly evaluating the impact of disease on daily life. While not 
explicitly described in this proposal, the data collected within the program 
can be used to evaluate additional approaches to passive monitoring. For 
example, collection of accelerometer data provides the opportunity to 
develop an algorithm to monitor gait and balance from daily activities 
rather than formal assessments. Such assessments are exploratory for 
PD assessment but have demonstrated utility in the context of other 
neurological disorders. 
 
13.3 
Go/No-go Milestones, Challenges and Opportunities   
 

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Our systematic approach to building the study’s main tele-health 
assessment platforms and then sequentially recruiting its sub-cohorts 
suggests realistic prospects of meeting our project timeline and of 
reaching pivotal Go/No-go milestones set at 75% of recruitment and 
retention goals to ensure a reasonable likelihood of accomplishing our 
SAs. However, in the event that a milestone was not achieved then NINDS 
program staff would determine in discussion with the SC whether the 
study should be continued and/or adapted. 
 
Just as our infrastructure plans (under SA1) rely on logistical capabilities, 
our experimental hypotheses (under SAs 2 and 3) depend on scientific 
assumptions, which if challenged would lead us to consider contingencies 
accordingly. For example, the ability to compare disability progression 
measured by tele-health platforms relies on true disease progression 
during two years of cohort follow up. However, this period coincides with 
the so-called ‘honeymoon’ phase of treatment after DT initiation when 
observable motor progression may be modest due to early, uncomplicated 
medication titration (40). Anticipating this possible pitfall, we will 
incorporate an adjustment for levodopa dose equivalents in our motor 
score-based progression analysis. We will also explore dopa-resistant 
cognitive outcomes and would proactively consider options to further 
extend the cohort into subsequent phases of non-motor and dopa-
resistant disability accumulation. In addition, we will remain open to new 
opportunities to leverage the project’s resources; for example, adopting 
potentially more sensitive wearable technologies in this rapidly evolving 
mobile health field, or assessing events to which the study cohort may be 
uniquely suited such as the impact of parent trial results, which should 
be announced during the follow-up period. 
 
 
 
 
 
13.4 
Sample Size Determination 
 
SA 1b. With a sample size of ~10 SURE-PD3 and ~50 SUPER-PD 
participants expected to complete at least one TV close in time to their in-
person clinic visit, the study will have 80% power to conclude that the 
REACT-PD calibrated tele-visit estimates are sufficiently accurate (rc > 0.8 
at alpha = 0.05) if the true concordance is at least 0.89. 
SA 2a. With a 2:1 split of ~340 AT-HOME PD participants, yielding ~115 
participants contributing to validation tests, the study will have 80% 
power to declare a given SP measure sufficiently accurate (rc > 0.80 at 
alpha = 0.05) if the true concordance is at least 0. 87. 
SA 2b. With approximately 80% of participants participating in the SP 
portion of the study, yielding ~340 participants contributing to the 
smartphone vs tele-visit comparison, the study would have an 80% 
probability of selecting the true preferred measure from a pair of TV or SP 
if the preferred measure had lower standard error by an effect size of at 
least 0.065. 
SA 3. With a 2:1 split of ~240 participants, yielding ~80 in the validation 
sample and at least 25% experiencing at least an 8-point progression in 
MDS-UPDS parts 1-3 total score, the study would have 80% power to 

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declare a novel measure derived from passive SP monitoring to have a 
ROC AUC significantly greater than 0.80 if the true AUC were at least 
0.95.  
13.5 
Non-Compliance, and Withdrawals 
 
All available data will be included in the primary analyses regardless of 
protocol compliance. Secondary analyses may restrict the sample to 
participants meeting pre-specified compliance criteria. 
We will summarize the proportion of eligible participants in the parent 
trials who enroll in AT-HOME PD and the proportion of those enrolled 
who (1) complete each tele-visit, (2) complete each FI quarterly 
assessment, (3) download and install the AT-HOME PD app, (4) complete 
periodic AT-HOME PD tasks, and (5) consent to passive data collection. 
13.6 
Safety Analysis  
RE information collected at study tele-visits will be summarized. All 
participants will be included in the safety analysis. At a minimum, 
individual report information will be displayed, and RE rates tabulated. 
 
PART B - GOOD CLINICAL PRACTICE/ADMINISTRATION 
 
 
 
 
 
14. 
REGULATORY/ETHICS 
 
14.1 
Compliance Statement 
 
This study will be conducted in accordance with the Good Clinical 
Practice (GCP) guidelines promulgated by the International Conference 
on Harmonization (ICH) and the FDA, and any applicable national and 
local regulations including FDA regulations under 21 CFR Parts 11, 50, 
54, 56, 312 and 314. 
 
All procedures not described in this protocol will be performed according 
to the study Operations Guide/Manual unless otherwise stated.   
 
14.2 
Informed Consent  
 
 
 
 
 
This study will be conducted in accordance with the provisions of 21 
Code of Federal Regulations (CFR) Part 50. NINDS and the CHeT/CTCC 
must be given an opportunity to review the consent form prior to site IRB 
submission and before it is used in the study. 
 
In accordance with relevant regulations, an informed consent agreement 
explaining the procedures and requirements of the study, together with 
any potential hazards/risks must be provided to each participant. Each 
participant will electronically sign such an informed consent form. 
 

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The proposed research poses minimal risk to participants. Waiver of 
documentation of consent will be sought as eConsenting is not 
recognized by the Office of Research and Project Administration. 
 
The participant must be assured of the freedom to withdraw from 
participation in the study at any time. 
 
It is the study team’s responsibility to make sure that the participant 
understands what she/he is agreeing to and that informed consent is 
obtained before the participant is involved in any protocol-defined with 
the exception of those pre-screening questions. It is also the study team’s 
responsibility to verify participant identity, verify completion of the 
eConsent form and participant understanding of the study. 
 
The consent process for each participant who provides consent will be 
documented in the participant’s electronic source record and should 
include the date eConsent was provided, the date participant 
understanding was verified by the study team, and the date of the 
screening visit. 
 
14.3 
Institutional Review Board/Independent Ethics Committee      
 
The study team will supply the CHeT/CTCC with all necessary 
information for submission of the protocol and consent form to the IRB 
for review and approval. The CHeT Site Investigator agrees to provide the 
IRB with all appropriate material. The study will not begin until the 
Investigator has obtained appropriate IRB approval. A copy of the 
approval letter listing all documents and versions that were approved 
and the approved electronic consent form must be placed on file at the 
CHeT/CTCC. 
 
The CHeT Site Investigator will request from the IRB a composition of the 
IRB members reviewing the protocol and informed consent. Appropriate 
reports on the progress of this study by the Investigator will be made to 
the IRB and NINDS in accordance with institutional and government 
regulations. It is the CHeT Site Investigator’s responsibility to notify the 
IRB when the study ends. This includes study discontinuation, whether 
it is permanent or temporary. A copy of the site IRB’s acknowledgement 
of study completion must be filed at the CHeT/CTCC. 
 
The CHeT Site Investigator will discuss any proposed protocol changes 
with the CTCC Project Manager and no modifications will be made 
without prior written approval by NINDS, except where clinical judgment 
requires an immediate change for reasons of participant welfare. The IRB 
will be informed of any amendments to the protocol or electronic consent 
form, and approval, where and when appropriate, will be obtained before 
implementation. 
 
14.4 
Protocol Amendments  
 
Changes to the protocol should only be made via an approved protocol 
amendment. Protocol amendments must be approved by the Sponsor, 

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the study’s Steering Committee and the respective site’s IRB prior to 
implementation, except when necessary to eliminate hazards and/or to 
protect the safety, rights or welfare of participants. (See Investigator’s 
Agreement.) 
 
14.5 
Participant Confidentiality 
 
The CHeT Site Investigator must assure that the privacy of participants, 
including their personal identity and personal medical information, will 
be maintained at all times. In the U.S. there are additional privacy 
obligations to study participants under the Health Insurance Portability 
and Accountability Act (HIPAA). Participants will be identified by code 
numbers on case report forms and other documents. 
 
After a participant agrees to study participation via an eConsent form, it 
is required that the CHeT  Site Investigator permit the study monitor, 
independent auditor or regulatory agency personnel to review the 
completed informed consent(s) and that portion of the participant’s 
medical record that is directly related to the study. 
 
The participant’s authorization allows the Sponsor and CHeT/CTCC to 
receive and review the participants’ protected health information that 
may be re-disclosed to any authorized representative of the Sponsor, 
CHeT/CTCC for review of participant medical records in the context of 
the study. 
 
 
15. DOCUMENTATION 
 
15.1 
Investigator Site File  
 
As part of the Trial Master File, the CHeT Site Investigator should have 
the following study documents accessible for review during the study. 
i. 
Curriculum vitae for investigator and staff signed and dated 
within 2 years of initiation of involvement in study 
ii. 
The signed IRB/IEC form/letter stating IRB/IEC approval of 
protocol, eConsent forms, and advertisement notices, 
documentation of the IRB/IEC composition, and all IRB/IEC 
correspondence including notification/approval of protocol 
amendments, notification of reportable events to the 
IRB/IEC per local reporting requirements, and IRB/IEC 
notification of study termination 
iii. 
IRB/IEC approved electronic consent form (sample) and 
advertisement materials 
iv. 
Signed protocol (and amendments, where applicable) 
v. 
Electronically consented and dated participant electronic 
consent forms will reside in the REDCap database. 
vi. 
Access to eCRF source records 

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vii. 
Delegation Log with names, signatures, initials, and 
functional 
role 
of 
all 
persons 
completing 
protocol 
assessments, 
providing 
back-up 
to 
the 
CHeT 
Site 
Investigator and Coordinator, if applicable, as well as staff 
entering data to the REDCap system. 
viii. 
Any source data not kept within the participant’s REDCap 
database. 
ix. 
Signed and dated receipt of equipment if required for the 
study. 
x. 
Record of all monitoring visits made by NINDS personnel  
xi. 
Copies of correspondence to and from NINDS, including all 
other platforms and CHeT/CTCC. 
xii. 
Record of any Corrective and Preventive Action Plans (CAPA) 
as required by the NINDS 
xiii. 
Certificate for Human Participant Protection Program (HSPP) 
training for each individual named on the Delegation Log 
who have direct participant contact 
xiv. 
Copy of professional licensure/registration, as applicable, for 
each individual named on the Delegation Log, who has direct 
participant contact ensuring licensure is in the state in 
which the study will be conducted 
xv. 
A Note to File indicating the assessments that will be 
considered source documents, if applicable 
xvi. 
Any other documentation as required by the CHeT/CTCC 
(e.g., Conflict-of-Interest/Financial Disclosure)  
 
The CHeT Site Investigator must also retain all printouts/reports, which 
are not recorded in REDCap.  
 
15.2 
Maintenance and Retention of Records  
 
It is the responsibility of the CHeT Site Investigator to maintain a 
comprehensive 
and 
centralized 
filing 
system 
of 
all 
relevant 
documentation. Investigators will be instructed to retain all study 
records required by NINDS and the federal regulations in a secure and 
safe facility with limited access for one of the following time periods based 
on notification from NINDS and/or CHeT/CTCC. 
 
The CHeT Site Investigator will be instructed to consult with NINDS 
and/or CHeT/CTCC before disposal of any study records and to notify 
NINDS and/or CHeT/CTCC of any change in the location, disposition, or 
custody of the study files. 
 
Electronic Records:  
An electronic case report form (eCRF) utilizing an Electronic Data 
Capture (EDC) application will be used for this study (see Sections 15.5 
and 17.3).  

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At the conclusion of the study a PDF (portable document format) file 
depicting the eCRFs for each site will be prepared by CTCC Data 
Management. In the event of an audit or regulatory authority inspection, 
the eCRFs can be printed out. 
 
15.3 
QA Review  
 
During the course of the study and after it has been completed, QA 
review may be undertaken by authorized representatives of the Sponsor 
or CHeT/CTCC. 
 
The purpose of the review is to determine whether or not the study is 
being, or has been, conducted and monitored in compliance with the 
protocol as well as recognized GCP guidelines and regulations. This 
review will also increase the likelihood that the study data and all other 
study documentation can withstand a subsequent regulatory authority 
inspection. 
 
If such reviews are to occur, they will be arranged for a reasonable and 
agreed time.  
 
15.4 
Regulatory Inspections 
 
The study may be inspected by regulatory agencies. These inspections 
may take place at any time during or after the study and are based on 
the local regulations as well as ICH guidelines. 
 
15.5 
Data Management 
 
All outcomes, demographics and other data originating from participants 
will flow through the 3 study platforms for data collection before 
converging for analysis in the Sage Bionetworks-managed Synapse 
platform for project analysis. From Synapse the fully transformed 
dataset will be transferred to the PDBP’s Data Management Resource 
(DMR) and further distributed to the wider research community. See 
Resource Sharing Plan for more detail.  
Specifically, 1) data collected during tele-visits will be entered and 
maintained in REDCap (a secure web-based survey and data 
management system routinely employed by CHeT/CTCC) with GUIDs, 
date and time of visit as identifiers, where it will be accesses via an 
application program interface (API) by Sage Bionetworks. 2) Survey data 
collected by FI will be, stored, and accessed from a FI researcher portal 
developed by LONI (USC’s Laboratory of Neuro Imaging which specializes 
in secure archival and sharing of neuroscience data) with GUIDs, date 
and time of visit as identifiers from which automated data transfer to 
Synapse will be configured 3) Data collected from participant 
smartphones will be transferred from users’ phones in real time on 
completion to the Sage Bionetworks-maintained Bridge server, where 
data will be aggregated, coded, and transferred to Synapse with GUIDs, 

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date and time of visit as identifiers on a daily basis where it will be in 
real time accessible to all research partners involved in this study. For 
any sub-study participants who are participating in the mPower 2.0 
component of SUPER-PD, their smartphone data from the corresponding 
SUPER-PD visit and associated remote 2-week burst will be linked with 
AT-HOME PD data within Synapse.  
The Bridge server is actively maintained by a team of engineers at Sage 
Bionetworks and has been effectively used to manage  smartphone-based 
research studies including Smart4SURE and mPower. Synapse is a 
scientific data management and research collaboration platform 
designed 
and 
actively 
maintained 
by 
Sage 
Bionetworks 
(http://synapse.org).  
All the SP and FI data will be aggregated and cleaned within Synapse 
prior to combination with the tele-visit data using GUIDs, date and time 
of visit as key identifiers. Data combined from all three platforms is 
further transformed in Synapse using a random number of days that will 
be added to all dates for that subject, to obscure actual dates but 
maintain durations and relative dates. Standard pipelines developed at 
Sage Bionetworks provide tools for data cleaning and feature extraction 
that will automatically be run on the raw data streams. Accelerometer 
readings, click streams etc. are converted into hundreds of distinct 
measures of disease severity capturing different aspects of the PD that 
correspond to multiple phenotypic subtypes of behavior. Sage 
Bionetworks will continue to monitor and update both quality control 
methodology and features being extracted as new devices and technology 
are used by study cohort. Once cleaned and processed compatible data 
will be deposited in the PDBP’s DMR (see Data Sharing Plan).

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Figure 2. Data Flow Details  
 
 

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Utilizing Electronic Data Capture (EDC). Research Electronic Data 
Capture (REDCap), an Internet accessible Electronic Data Capture (EDC) 
system for data management will be utilized for this study. The REDCap 
system is designed to ensure timeliness and accuracy of data as well as 
the prompt reporting of data from the study on an ongoing basis to the 
study principal and co-investigators. REDCap is a free, secure, HIPAA-
compliant, web-based application used for electronic capture and 
management of research and clinical study data. The REDCap system, 
developed by Vanderbilt University, provides an intuitive user interface 
to enter, audit, monitor, and export data. It also helps users create web-
based surveys. 
Data review and query processing will be done through interaction with 
the CHeT/CTCC and site personnel. Once the data are entered into 
REDCap, it is immediately stored in the central study database located 
at the URMC Data Center and is accessible for review by data 
management staff.  Any changes to the data will be fully captured in an 
electronic audit trail. 
 
The cycle of electronic data entry, review, query identification/resolution, 
and correction occurs over the course of the study period until all 
participants have completed the study. 
   
Aggregated data, where event dates and times are transformed, will be 
made available through Synapse using version data snapshots to the 
Biostatistics Center. Once the Biostatistics Center and the CHeT/CTCC, 
in conjunction with the Sponsor and the principal investigator, agree 
that all queries have been adequately resolved and the database has been 
deemed “clean”, the database will be officially signed off and deemed 
locked. All permissions to make changes (append, delete, modify or 
update) to the database are removed at this time.  
 
The Massachusetts General Hospital (MGH) Biostatistics Center will be 
responsible for creation of analytical databases and the statistical 
analysis plan. Data management staff at the CHeT/CTCC will facilitate 
creating the data management plan, however, each collaborator will be 
individually responsible for data collection specific to their platform as 
well as providing documentation to be added to the overall data 
management plan. 
 
There will be a data user agreement put in place for the use and transfer 
of data between CTCC and Sage Bionetworks. The University of 
Rochester Information Security Office has reviewed and approved 
methods of data transfer and storage with entities outside the University 
[including Sage Bionetworks]. 
 
16. 
INVESTIGATOR/SITE 
 
The protocol, informed consent form, and advertisement notices will be 
approved by the UR IRB (RSRB). 
The CHeT Site Investigator is responsible for providing copies of the 
protocol and all other information relating to the prior clinical experience, 

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P a g e  71 | 103 
which were furnished to him/her, to all physicians and other study 
personnel responsible to them who participate in this study. The CHeT 
Site Investigator will discuss this information with them to assure that 
they are adequately informed regarding the study drug and conduct of 
the study. The CHeT Site Investigator must assure that all study staff 
members are qualified by education, experience and training to perform 
their specific responsibilities. 
 
17. 
SAFETY MONITORING 
 
All aspects of the study will be monitored by the CHeT Site Investigator 
and designees in compliance with Good Clinical Practice (GCP) and 
applicable regulations. There is no clinical monitor or safety monitoring 
committee for this study. The Steering Committee will review collected 
reportable events on a quarterly basis. 
 
17.1 
Study Committees  
 
a. 
Steering Committee 
 
The Steering Committee (SC) is composed of the 4 project Principal 
Investigators (PIs), study biostatistician, and independent investigator 
members of the Parkinson Study Group with expertise in PD and allied 
fields of study, a patient advocate, and scientific or programmatic officers 
of partner institutions. The roles of SC Chair and Co-chair are filled by 
rotating pairs of its PI members according to the project’s Multiple PI 
Leadership Plan as approved by NINDS. The SC is responsible, along 
with the Sponsor, for the design of the study protocol and analysis plan 
and oversees the clinical trial from conception to analysis and 
publication. 
 
17.2 
Case Report Forms 
 
 
 
 
 
Utilizing Electronic Data Capture (EDC). Site will enter participant 
information and data into an electronic case report form (eCRF) in the 
Electronic Data Capture (EDC) application - REDCap. The eCRFs are 
used to record study data and are an integral part of the study and 
subsequent reports. Authorized study personnel will each be granted 
access to the EDC tool via provision of a unique password-protected 
user-ID that will limit access to enter and view data. Data should be 
directly entered into the EDC system at the time of the 
participant’s tele-visit. 
 
Data will be directly entered into eCRFs via computer stations connected 
remotely to the central server through an Internet browser. In the event 
of REDCap unavailability paper CRFs will be used and the data will be 
entered when REDCap is available.   
 
 
CHeT Site Investigator approval of eCRFs: 

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An approval from the CTCC Site Investigator is required on the following 
eCRFs: 
 
x 
Signature Form 
 
A form with the Investigator signature, either wet or electronic signature, 
will be uploaded into the database.  
 
It is the CHeT Site Investigator’s responsibility to ensure that entries are 
proper and complete. Error checks will be implemented in the EDC based 
upon specifications defined in the data management plan. 
 
At the conclusion of the study, the CTCC Data Management Team will 
create a PDF file depicting eCRFs for each participant. The PDF file 
should be printed for each participant in the study and filed in the 
participant’s binder. 
 
17.3 
Primary Source Documents 
 
The Investigator will maintain primary source documents supporting 
significant data for each participant in REDCap. Any relevant telephone 
conversations with the participant regarding the study or possible 
adverse events and attempts to reach participants by telephone or mail 
regarding medical events and/or compliance will also reside in REDCap. 
 
17.4 
Closeout Visit  
 
Following the completion of the study, the study team will ensure all the 
data is entered and queries are resolved, any protocol deviations are 
documented appropriately, all relevant study data has been retrieved, 
and that the Investigator has copies of all study-related data/information 
on file. 
 
17.5 
Closeout Plan 
 
A study closeout plan will be developed that provides information about 
study close-out procedures and timelines internally as well as externally. 
Full details will be documented in the operations manual. 
 
18. 
PUBLICATION OF RESEARCH FINDINGS 
 
Publication of the results of this trial will be governed by the policies and 
procedures developed by the Parkinson Study Group, Steering 
Committee and in accordance with the International Committee of 
Medical Journal Editors (ICJME) Uniform Requirements for Manuscripts 
Submitted 
to 
Biomedical 
Journals 
(http://www.icmje.org/urm_main.html).  Any presentation, abstract, or 
manuscript will be made available for review by the Sponsor NINDS prior 
to submission. 
 

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19. 
RESOURCE SHARING PLAN 
 
Data will be collected across individual sites (U. Rochester for tele-visit 
data; Sage Bionetworks for smartphone data; MJFF-sponsored portal in 
LONI for FI data). Data from all three sites will be aggregated in a 
centralized location using Synapse. Synapse is a cloud based scientific 
data management and research collaboration platform designed and 
actively maintained by Sage Bionetworks (https://www.synapse.org/) 
that is used to coordinate data across dozens of consortia and 
collaborations. All data will be aggregated within Synapse using GUIDs, 
event dates and times as unique identifiers. Following aggregation, event 
dates and times are transformed by transferring them to duration since 
a random first visit for analysis and for distribution to the PDBP Data 
Management Resource (DMR) on a recurring, regular basis that complies 
with NINDS program requirements. Data is cleaned on an on-going basis, 
however, until the database is locked changes in data may occur. 
Deposition will use standard DMR protocols for clinical and PRO data. 
Because the DMR is not yet set up to receive sensor data, the appropriate 
deposition protocols will be developed in collaboration with the DMR. As 
these are developed, we have the alternative of working with NINDS to 
develop a system that provides PDBP and DMR-approved investigators 
with access to sensor data directly through the Synapse platform. 
 
Data sharing will be performed in two additional ways. The smartphone 
data, tele-visit data, and FI data will be distributed for secondary use 
through the mobile health data repository that Sage Bionetworks has 
developed and that is also housed in Synapse. The shared study dataset 
will be made available to qualified researchers who are registered users 
of Synapse and who have agreed to use the data in an ethical manner, 
to do no harm and not attempt to re-identify or re-contact participants. 
No name or contact information will be included in this shared study 
dataset. Researchers will have access to the shared study data but will 
be unable to map any particular data to the identities of the participants. 
The qualified researcher program is operated through an IRB-approved 
Synapse data governance plan. For more information about the data 
practices in the context of the Synapse research platform, see the 
Synapse 
Governance 
Overview 
(http://docs.synapse.org/articles/governance.html). In addition, data 
will be collected as part of FI, an IRB-approved web-based study.  All data 
collected through FI will be automatically deposited into a research 
portal hosted at LONI (http://www.loni.usc.edu/) for use by the research 
community. 
 
The code used to run the smartphone application developed for this 
study will be made public through github (https://github.com/) and 
made available to the research community for reuse under an open 
license. The study will be registered at clinicaltrials.gov.  
 

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21. 
APPENDIX 
AHPD study - Patient Facing CRFs continued in next page…………… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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BaselinePreferenceAndBurden_13SEP2018 (cont.) 
  

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P a g e  81 | 103 
  

   Protocol Title: AT-HOME PD [Assessing Tele-Health Outcomes in Multiyear Extensions of PD trials]  
AHPD PROTOCOL_V3; Version date: 11/06/2019 
 
 
P a g e  82 | 103 
  

   Protocol Title: AT-HOME PD [Assessing Tele-Health Outcomes in Multiyear Extensions of PD trials]  
AHPD PROTOCOL_V3; Version date: 11/06/2019 
 
 
P a g e  83 | 103 
  

   Protocol Title: AT-HOME PD [Assessing Tele-Health Outcomes in Multiyear Extensions of PD trials]  
AHPD PROTOCOL_V3; Version date: 11/06/2019 
 
 
P a g e  84 | 103 
PreAnnualVisitSurvey_27JUL2018 
(cont.) 
 

   Protocol Title: AT-HOME PD [Assessing Tele-Health Outcomes in Multiyear Extensions of PD trials]  
AHPD PROTOCOL_V3; Version date: 11/06/2019 
 
 
P a g e  85 | 103 
 

   Protocol Title: AT-HOME PD [Assessing Tele-Health Outcomes in Multiyear Extensions of PD trials]  
AHPD PROTOCOL_V3; Version date: 11/06/2019 
 
 
P a g e  86 | 103 
 

   Protocol Title: AT-HOME PD [Assessing Tele-Health Outcomes in Multiyear Extensions of PD trials]  
AHPD PROTOCOL_V3; Version date: 11/06/2019 
 
 
P a g e  87 | 103 
 

   Protocol Title: AT-HOME PD [Assessing Tele-Health Outcomes in Multiyear Extensions of PD trials]  
AHPD PROTOCOL_V3; Version date: 11/06/2019 
 
 
P a g e  88 | 103 
 

   Protocol Title: AT-HOME PD [Assessing Tele-Health Outcomes in Multiyear Extensions of PD trials]  
AHPD PROTOCOL_V3; Version date: 11/06/2019 
 
 
P a g e  89 | 103 
 

   Protocol Title: AT-HOME PD [Assessing Tele-Health Outcomes in Multiyear Extensions of PD trials]  
AHPD PROTOCOL_V3; Version date: 11/06/2019 
 
 
P a g e  90 | 103 
PreBaselineVisitSurvey_27JUL2018                 (cont.)  
 

   Protocol Title: AT-HOME PD [Assessing Tele-Health Outcomes in Multiyear Extensions of PD trials]  
AHPD PROTOCOL_V3; Version date: 11/06/2019 
 
 
P a g e  91 | 103 
 

   Protocol Title: AT-HOME PD [Assessing Tele-Health Outcomes in Multiyear Extensions of PD trials]  
AHPD PROTOCOL_V3; Version date: 11/06/2019 
 
 
P a g e  92 | 103 
 

   Protocol Title: AT-HOME PD [Assessing Tele-Health Outcomes in Multiyear Extensions of PD trials]  
AHPD PROTOCOL_V3; Version date: 11/06/2019 
 
 
P a g e  93 | 103 
 

   Protocol Title: AT-HOME PD [Assessing Tele-Health Outcomes in Multiyear Extensions of PD trials]  
AHPD PROTOCOL_V3; Version date: 11/06/2019 
 
 
P a g e  94 | 103 
 

   Protocol Title: AT-HOME PD [Assessing Tele-Health Outcomes in Multiyear Extensions of PD trials]  
AHPD PROTOCOL_V3; Version date: 11/06/2019 
 
 
P a g e  95 | 103 
 

   Protocol Title: AT-HOME PD [Assessing Tele-Health Outcomes in Multiyear Extensions of PD trials]  
AHPD PROTOCOL_V3; Version date: 11/06/2019 
 
 
P a g e  96 | 103 
PreferenceAndBurdenSurveyVisit_13SEP2018 (cont.)   
 

   Protocol Title: AT-HOME PD [Assessing Tele-Health Outcomes in Multiyear Extensions of PD trials]  
AHPD PROTOCOL_V3; Version date: 11/06/2019 
 
 
P a g e  97 | 103 
  

   Protocol Title: AT-HOME PD [Assessing Tele-Health Outcomes in Multiyear Extensions of PD trials]  
AHPD PROTOCOL_V3; Version date: 11/06/2019 
 
 
P a g e  98 | 103 
  

   Protocol Title: AT-HOME PD [Assessing Tele-Health Outcomes in Multiyear Extensions of PD trials]  
AHPD PROTOCOL_V3; Version date: 11/06/2019 
 
 
P a g e  99 | 103 
  

   Protocol Title: AT-HOME PD [Assessing Tele-Health Outcomes in Multiyear Extensions of PD trials]  
AHPD PROTOCOL_V3; Version date: 11/06/2019 
 
 
P a g e  100 | 103 
  

   Protocol Title: AT-HOME PD [Assessing Tele-Health Outcomes in Multiyear Extensions of PD trials]  
AHPD PROTOCOL_V3; Version date: 11/06/2019 
 
 
P a g e  101 | 103 
 

   Protocol Title: AT-HOME PD [Assessing Tele-Health Outcomes in Multiyear Extensions of PD trials]  
AHPD PROTOCOL_V3; Version date: 11/06/2019 
 
 
P a g e  102 | 103 
TechnologySurvey_27JUL2018                     (contd.) 
 

   Protocol Title: AT-HOME PD [Assessing Tele-Health Outcomes in Multiyear Extensions of PD trials]  
AHPD PROTOCOL_V3; Version date: 11/06/2019 
 
 
P a g e  103 | 103