A PATIENT-CENTRIC OUTCOMES REGISTRY OF PATIENTS WITH KNOWN OR SUSPECTED NOVEL CORONAVIRUS INFECTION SARS-COV-2 (COVID-19)
Conditions: Coronavirus
Sponsor: xCures

 
A PATIENT-CENTRIC OUTCOMES REGISTRY OF PATIENTS WITH 
KNOWN OR SUSPECTED NOVEL CORONAVIRUS INFECTION SARS-
COV-2 (COVID-19) 
 
Protocol Number: 
XC-PCOR-COVID19 
Version Number:  
V1.0 
Version Date: 
March 20, 2020 
IND Number: 
N/A 
NCT Identified 
Number: 
TBD 
Sponsor: 
 
 
Funded by: 
xCures 
Central IRB: 
Genetics Alliance IRB 
IORG Number: 
IORG0003508 
Principal 
Investigator: 
Mark Shapiro 
VP, Clinical Development 
xCures, Inc. 
 
 
 
 
 

 
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Summary of Changes from Previous Version: 
Affected 
Section(s) 
Summary of Revisions Made 
Rationale 
N/A 
N/A 
N/A – Initial Draft 
 
 
 
 
 

 
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Table of Contents 
Contents 
STATEMENT OF COMPLIANCE 
5 
1 
PROTOCOL SUMMARY 
6 
1.1 
Synopsis ...................................................................................................................................................................... 6 
2 
STUDY RATIONALE 
8 
2.1 
Disease Setting and Trial Context ............................................................................................................................... 8 
2.2 
Objectives and Aims ................................................................................................................................................... 8 
2.3 
Risk/Benefit Assessment ............................................................................................................................................ 8 
2.3.1 
Known Potential Risks ............................................................................................................................................ 8 
2.3.2 
Known Potential Benefits ....................................................................................................................................... 8 
2.3.3 
Assessment of Potential Risks and Benefits ........................................................................................................... 8 
3 
OBJECTIVES 
9 
4 
STUDY DESIGN 
10 
4.1 
Overall Design .......................................................................................................................................................... 10 
4.2 
Scientific Rationale for Study Design ........................................................................................................................ 10 
4.3 
End of Study Definition ............................................................................................................................................ 10 
5 
Study Procedures 
11 
5.1 
Registration and Consent of Participants ................................................................................................................. 11 
5.1.1 
Selection of Patients ............................................................................................................................................ 11 
5.1.2 
Inclusion Criteria .................................................................................................................................................. 11 
5.1.3 
Exclusion Criteria.................................................................................................................................................. 11 
6 
Data Management 
12 
6.1 
Data Handling and Record Keeping .......................................................................................................................... 12 
6.1.1 
Data Management ............................................................................................................................................... 12 
6.1.2 
Study Records Retention...................................................................................................................................... 12 
6.1.3 
Source Documents ............................................................................................................................................... 12 
6.2 
Discontinuation of Participation .............................................................................................................................. 13 
6.3 
Unanticipated Problems ........................................................................................................................................... 13 
6.3.1 
Definition of Unanticipated Problems (UP) ......................................................................................................... 13 
6.3.2 
Unanticipated Problem Reporting ....................................................................................................................... 13 
6.3.3 
Reporting Unanticipated Problems to Participants ............................................................................................. 14 
7 
ANALYTIC METHODS AND STATISTICAL CONSIDERATIONS 
15 
7.1 
Overview of Analytic Methods ................................................................................................................................. 15 
8 
SUPPORTING DOCUMENTATION AND CONSIDERATIONS 
16 
8.1 
Regulatory and Ethical Considerations..................................................................................................................... 16 
8.1.1 
Regulatory Considerations ................................................................................................................................... 16 
8.1.2 
Confidentiality, Privacy, and Data Security .......................................................................................................... 16 
8.1.3 
Schema and Overview of Services Data Versus Research Data in XCELSIOR .......... Error! Bookmark not defined. 
8.1.4 
Future Use of Stored Data ................................................................................................................................... 17 
8.1.5 
Publication and Data Sharing Policy..................................................................................................................... 17 
8.1.6 
Conflict of Interest Policy ..................................................................................................................................... 17 
8.1.7 
Ethical Considerations .......................................................................................................................................... 18 
8.2 
Study Oversight and Other Considerations .............................................................................................................. 18 
8.2.1 
Financial Considerations ...................................................................................................................................... 18 
8.2.2 
Study Discontinuation and Closure ...................................................................................................................... 18 
8.2.3 
Quality Assurance and Quality Control ................................................................................................................ 18 
8.2.4 
Key Roles and Study Governance......................................................................................................................... 18 
8.3 
Protocol Amendment History .................................................................................................................................. 20 
9 
REFERENCES 
21 
Appendix 1: Informed Consent and Assent Text 
22 

 
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Appendix 2: Web Site Content 
24 
Appendix 3: Planned Data Elements 
26 
 
 
 
 

 
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STATEMENT OF COMPLIANCE 
 
This registry study will be carried out in accordance with applicable guidelines and regulations.  The protocol, 
informed consent form(s), recruitment materials, and all participant materials will be submitted for Institutional 
Review Board (IRB) for review and approval.  Approval of both the protocol and the consent form will be obtained 
before any participant is enrolled.  Any amendment to the protocol will require review and approval by the IRB 
before the changes are implemented to the study.  In addition, all changes to the consent form will be IRB-
approved; a determination will be made regarding whether a new consent needs to be obtained from participants 
who provided consent, using a previously approved consent form. 
 
 

 
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1 
 
PROTOCOL SUMMARY 
1.1 
SYNOPSIS  
Study Sponsor: 
xCures, Inc. 
Study Title: 
A Patient-Centric Outcomes Registry of Patients with Known or Suspected Novel 
Coronavirus Infection SARS-CoV-2 (COVID-19) 
Study Acronym: 
TBD 
Study Description: 
This study is a patient-centric outcomes registry enrolling patient with known or 
suspected COVID-19 infection.  This study includes enrollment via on-line informed 
consent to participate in a data registry, including remote collection of symptoms, 
treatments, and outcomes.  
Study Number: 
XC-COVID19-2020 
IND Number: 
N/A 
NCT Identified Number: 
TBD 
General Study Design: 
Patient-centric outcomes registry 
Objectives: 
 
To collect demographic and medical history information from patients with known 
or suspected COVID-19 infection with a daily e-diary that includes symptoms, 
treatments.  
Secondary Objectives: 
 
● 
Define natural history of COVID-19 infection among different demographic 
and medical subgroups 
● 
Assess the impact of different comorbid conditions and treatment regimens 
on the duration and severity of COVID-19 infection. 
Endpoints: 
The purpose of this study is to understand at the population level the symptomatic 
course of known or suspected COVID-19 patients while sheltering-in-place or under 
quarantine.  Symptoms will be measured using a daily report derived from the 
CTCAE-PRO as well as free response.  Outcomes will be assessed based on the 
duration and severity of infection, hospitalization, lost-to-follow-up, or death.  As a 
patient-centric registry, patients themselves may propose, suggest, and/or submit 
evidence or ideas for relevant collection. 
 
The registry should provide real-world data on the course of COVID-19 among 
patients under quarantine or sheltering-in-place and will supplement information 
collected by others in formal clinical trials, which are currently focused on the 
inpatient population. 
 
Study Population: 
This study will initially include up to 100,000 adults with known or suspected 
COVID-19 infection or others who are present in the United States.   
Key Inclusion Criteria: 
Adult men and women currently in the United States and willing to provide written 
informed consent and: 
• 
who are feeling sick but have not tested positive for COVID-19 
• 
who are feeling sick and have tested positive for COVID-19 
• 
People who are not feeling sick but want to participate 
 

 
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Key Exclusion Criteria: 
Patients unwilling or unable to provide informed consent. 
Phase: 
Not applicable. 
Sites Enrolling 
Participants: 
This is a patient-centric, real-world data registry.  Patients will be enrolled over 
the Web at a dedicated web site (URL to be determined) using electronic 
informed consent.   
Study Duration: 
The longitudinal, observational study will run for an initial period of one year for 
patient recruitment with up to one year of observation of enrolled patients or until 
community transmission of COVID-19 has ended.  If community transmission 
continues, the duration of enrollment and data collection may be extended. 
Participant Duration: 
Patients will be asked to complete a baseline information questionnaire at 
registration and will be sent daily diary questionnaires until the COVID-19 outbreak 
has resolved.  Patients will be asked to provide authorization for future follow-up 
contacts related to outcomes confirmation and medical record access under HIPAA. 
 
 
 

 
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2 
STUDY RATIONALE 
 
2.1 
DISEASE SETTING AND TRIAL CONTEXT 
The COVID-19 pandemic is an urgent, global public health crisis.  In addition to non-treatment interventions 
underway, there is urgent need for detailed information about the natural history and course of the disease in 
non-hospitalized patients, in particular to develop an understanding of the nature, duration, and severity of 
symptoms in various demographic and medical subgroups. 
 
2.2 
OBJECTIVES AND AIMS 
The objective of this project is to develop a patient-centric registry for participants from before the 
development of symptoms through the course of the illness by tracking symptoms, treatments, and outcomes of 
patients with known or suspected novel coronavirus-19 (COVID-19) through the prospective collection of 
symptoms information from non-hospitalized participants who are or may become infected with COVID-19 
infection.  This dataset will provide valuable information for researchers trying to understand the natural history 
of COVID-19 in different population in the community setting.  Additional aims include understanding 
differences between subgroups and obtaining authorization for future collection of medical records information 
for inclusion in the disease registry and obtaining the permission of registry participants to be contacted in the 
future for follow-up information related to their COVID-19 diagnosis and/or treatments. 
 
2.3 
RISK/BENEFIT ASSESSMENT  
 
2.3.1 
KNOWN POTENTIAL RISKS  
 
This is a non-interventional study.  The purpose is to develop case-histories for patients with known or 
suspected COVID-19 infection while they are sheltering-in-place or under quarantine.   
 
 
2.3.2 
KNOWN POTENTIAL BENEFITS  
Ongoing insights and findings from this registry will be made available to participants and their medical 
providers, as well as to the wider public health community.  Such information may be helpful to COVID-19 
patients directly, or to patients with medical conditions who may be at increased risk.  Through participation in 
this registry patients, healthcare providers and public health officials may receive information that supports 
management of COVID-19.  
 
2.3.3 
ASSESSMENT OF POTENTIAL RISKS AND BENEFITS  
The only risk of this project is potential loss of participant confidentiality.  To mitigate this risk, xCures uses a 
secure data architecture that follows commercially reasonable and customary procedures to secure participant 
confidentiality.   The risks minimal in accordance with the definition of Minimal Risk in 21 CFR 50 and 56 and 
outweighed by the potential benefits to individuals and society. 
 

 
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3 
OBJECTIVES  
During the current COVID-19 pandemic there is urgent need for information about the natural history of the 
infection in non-hospitalized patients, including the severity and duration of symptoms, and outcome from early 
in the infection, among different subgroups of patients.  In addition, a large, real-world data registry can provide 
information about how different concomitant medications may differentially affect symptoms among patient 
subgroups.  Such information can be invaluable for clinicians managing chronic diseases during this pandemic, as 
well as identify interventions undertaken in a naturalistic setting that have differential effects.  Such factors may 
include patient diet, over the counter or prescription medications, and herbal and alternative treatments, 
among others.  Identifying the natural disease history in patients from different demographic and disease 
subgroups will be important for identifying at-risk patients and effectiveness of interventions undertaken in the 
community. 
 
 

 
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4 
STUDY DESIGN  
4.1 
OVERALL DESIGN 
 
This is a patient-centric outcomes registry prospectively enrolling healthy volunteers and those who know or 
suspect they may have the COVID-19 infection.  This study includes enrollment and consent through a secure 
Web page and completion of on-line surveys for inclusion into a data registry, including remote collection of 
symptoms, treatments, and outcomes.  Additional retrospective data collection, including chart review of 
medical records for select cases is included.  Cases selected for additional records collection will be contacted 
and their authorization for records collection will be conducted under HIPAA.   
 
4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
 
The purpose of a patient-centered registry is to serve one or more predetermined scientific or clinical purposes.  
In this case, the purpose is to develop a longitudinal, observational dataset of people before, during, and after 
infection with COVID-19 in the community.  Such data is currently lacking and will provide useful information 
about the natural history of the disease, treatments administered in the community, and outcomes, particularly 
among demographic and medical subgroups.  This data may provide useful prognostic regarding characteristics 
of people at greater risk for more severe infection as well as comparative analysis of the effects of treatments or 
concomitant medications used in the general population.   Registries are valuable for providing information 
about the safety and effectiveness of treatments in patients that are not part of clinical trials, for example by 
evaluating the effectiveness of off-label therapies used during routine clinical practice and dietary interventions.   
 
4.3 
END OF STUDY DEFINITION 
 
This is a longitudinal, observational study that will run for an initial period through the end of the current 
pandemic, which is anticipated to be approximately one year from initial approval, but may be extended should 
the outbreak continue or for long term follow with infected patients.  
 
 
 

 
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5 
STUDY PROCEDURES 
5.1 
REGISTRATION AND CONSENT OF PARTICIPANTS 
 
Patients will be registered for through the study Web site, covid19-registry.org (or the redirect site, beat19.org).  
Following Web site registration, patients will receive an electronic informed consent form (Appendix A).  
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in the study and 
continues throughout the individual’s study participation. Consent forms will be Institutional Review Board 
(IRB)-approved and the participant will read and review the document electronically.  A FAQ page will be on the 
Web site (Appendix C) and an email address will be available for additional questions.  Participants must sign the 
informed consent document prior to participating in the registry. Participants will be informed that participation 
is voluntary and that they may withdraw from the study at any time, without prejudice by emailing the study 
team or simply unsubscribing from study emails.   
5.1.1 
SELECTION OF PATIENTS 
5.1.2 
INCLUSION CRITERIA 
 
As a real-world data registry, any adult men and women currently in the United States and willing to provide 
written informed consent and: 
 
• 
who are feeling sick but have not tested positive for COVID-19, or? 
• 
who are feeling sick and have tested positive for COVID-19, or? 
• 
who are not feeling sick but want to participate can enroll? 
 
5.1.3 
EXCLUSION CRITERIA 
 
Patients unwilling or unable to provide informed consent will be excluded. 
 
 
 

 
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6 
DATA MANAGEMENT 
6.1 
DATA HANDLING AND RECORD KEEPING  
  
6.1.1 
DATA MANAGEMENT 
A registry database will be maintained with identified registry data elements captured into the REDCap Cloud 
EDC system, a commercial eClinical Platform that is 21 CFR Part 11 Validated, HIPAA & FISMA compliant, and 
WHODrug and MedDRA certified.  All access and activity in the system is tracked and can easily be monitored by 
the Administrator. The system has a login audit feature that tracks who has logged into the system, the date and 
time of login, and the IP address of the connection. The system also tracks failed logins and automatically locks a 
user’s account after several failed attempts. The REDCap Cloud system has a robust audit trail that shows all 
changes to any records within the system including who made the change, the date and time of the change, the 
field that was changed, the old value of the field and the new value of the field. Access can be monitored via a 
dashboard or email alerts.  Data management activities will follow standard operating procedures. 
6.1.2 
STUDY RECORDS RETENTION  
In the event that patient authorize the collection of additional medical records, those records will be maintained 
in xCures’ HIPAA compliant box storage platform hosted on Amazon’s HIPAA-compliant cloud servers.  Source 
information, including medical records will be abstracted into a study database and not made available in their 
original format outside the study team.  Study data including source records and case reports forms will be 
maintained in electronic format indefinitely. De-identified databases derived from the study records may be 
made available to other researchers and may be retained by those organizations indefinitely based on the terms 
of the agreement under which the data was provided. 
6.1.3 
SOURCE DOCUMENTS 
Source data can include clinical findings and observations, or other information incorporated into the registry 
database to support analysis of data.  Source data is all information from which information in the registry 
database is derived in original form (or certified copies of an original record).  Examples of these original 
documents and records include but are not limited to the following: electronic medical records, clinical and 
office charts, laboratory notes, memoranda, correspondence, subjects’ diaries or patient-reported 
questionnaires, data from automated instruments, such as ECG machines, photographs and other imaging 
(DICOM) files, slides, pharmacy records, and the reports documenting medical interpretation of those files. 
Data may be entered into the eCRF either manually by the study team performing data abstraction from the 
EMR or electronically using direct entry of data into the or from an electronic import of data. Patients may also 
enter information directly into the eCRF using a patient-facing survey functionality either over the Web or using 
a smartphone app.  Data elements originating in EMR may be automatically transmitted directly into the eCRF 
using a suitable API. Source data derived in that manner may have an intervening process, such as abstraction by 
third-party including software including processing using machine learning algorithms prior to transferring to the 
eCRF. xCures will retain source records in a secure that will be maintained separately and securely from the 

 
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eCRF.  However, metadata tagging may be employed to electronically map source data back from the eCRF to 
the source data record to create an audit trail.   
 
6.2 
DISCONTINUATION OF PARTICIPATION 
 
Participants can withdraw from the registry at any time by sending a written request to xCures.  Withdrawal 
from the study means that no additional data will be collected from the patient and does not constitute 
revocation of the right to use the data collected prior to withdrawal for the purposes described herein.  xCures 
may discontinue the study at any time for any reason.  In the event the registry is discontinued enrolled 
participants may receive an email notification and a public posting on the study Web site will be made, if 
possible. 
 
 
6.3 
UNANTICIPATED PROBLEMS 
 
6.3.1 
DEFINITION OF UNANTICIPATED PROBLEMS (UP) 
 
Unanticipated problems involving risks to participants or others to include, in general, any incident, experience, 
or outcome that meets all the following criteria: 
 
• 
Unexpected in terms of nature, severity, or frequency given (a) the research procedures that are 
described in the protocol-related documents, such as the Institutional Review Board (IRB)-approved 
research protocol and informed consent document; and (b) the characteristics of the participant 
population being studied; 
• 
Related or possibly related to participation in the research (“possibly related” means there is a 
reasonable possibility that the incident, experience, or outcome may have been caused by the 
procedures involved in the research); and 
• 
Suggests that the research places participants or others at a greater risk of harm (including physical, 
psychological, economic, or social harm) than was previously known or recognized. 
 
6.3.2 
 UNANTICIPATED PROBLEM REPORTING  
 
xCures will report unanticipated problems (UPs) to the Genetic Alliance Institutional Review Board (GAIRB) in 
accordance with the IRB’s policies and procedures. The UP report will include the following information: 
 
• 
Study identifying information: protocol title and number; 
• 
A detailed description of the event, incident, experience, or outcome;  
• 
An explanation of the basis for determining that the event, incident, experience, or outcome represents 
an UP;  
• 
A description of any changes to the protocol or other corrective actions that have been taken or are 
proposed in response to the UP. 
 

 
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To satisfy the requirement for prompt reporting, UPs will be reported within 10 working days of xCures 
identifying or learning of the event. 
 
6.3.3 
REPORTING UNANTICIPATED PROBLEMS TO PARTICIPANTS  
 
Unanticipated problems will be reported to registry participants that are affected by the UP within 30 days of 
xCures becoming aware of the problem. 
 
 
 

 
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7 
ANALYTIC METHODS AND STATISTICAL CONSIDERATIONS 
7.1 
OVERVIEW OF ANALYTIC METHODS 
 
The patient-focused outcomes research outlined in this registry protocol is focused on generating a large dataset 
for hypothesis identification and testing using machine learning or other analytic models.  Participants and 
external researchers may suggest hypotheses for testing and qualified researchers may receive a de-identified 
dataset. 
 
The analysis of the registry data should lead to new information about emerging signals from treatments used in 
the community, as well as the role of comorbid conditions and concomitant medications as risk factors for 
COVID-19 infection.   
 
 

 
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8 
SUPPORTING DOCUMENTATION AND CONSIDERATIONS 
8.1 
REGULATORY AND ETHICAL CONSIDERATIONS 
8.1.1 
REGULATORY CONSIDERATIONS 
 
As a patient-centric, non-interventional prospective, observational study, the proposed research program meets 
the regulatory criteria under 21 CFR 312.2(b)(1) for an exemption from the requirement for the submission and 
FDA-acceptance, of an IND application.  Specifically: 
 
1. The investigation is not intended to be reported to the FDA as a well-controlled study in support of a new 
indication for the use of an FDA-regulated product, nor intended to be used to support any other significant 
change in the labeling of an FDA-regulated product.   
 
2. The investigation is not intended to support a significant change in the advertising for an FDA-regulated 
product.  The purpose of this study is to use machine learning to identify factors which may be predictive of 
treatment response at the level of individual patients and disseminate that information to patients, 
physicians, and public health officials. 
 
3. The investigation does not involve a route of administration or dosage level or use in a patient population or 
other factor that significantly increases the risks (or decreases the acceptability of the risks) associated with 
the use of an FDA regulated product.  Specifically, this is a data-collection registry, treatment of patients will 
continue at the discretion of their physician.  xCures may provide information to the public based on public 
information related to therapeutic options and/or clinical trials for which the participant may be eligible.   
 
4. The investigation is subject to prior approval by the Genetic Alliance IRB, based in, which operates in 
compliance with the FDA regulations including 21 CFR Parts 50 and 56 and is registered with OHRP as IRB 
Organization number IORG0003358. 
 
5. Neither the participants in this clinical investigation, nor their insurance providers, will be charged for the 
procedures associated with participation in the study.  Patients in this registry will be treated according to 
their institution’s normal standards of practice and at their oncologist’s discretion. 
 
xCures maintains strong data security procedures has procedures in place to comply with the FTC Health Breach 
Notification Rule (16 CFR 318) in the event of an unauthorized breach of confidentiality of patient information.  
Such an incident would be reported to the Genetic Alliance IRB in accordance with the procedures for UP 
reporting.   As a patient-centric outcomes registry, we encourage patients to communicate publicly about their 
conditions and to share information.  Disclosures are made by patients and are not considered unauthorized 
disclosure. 
 
This registry study will comply with sections 402(i) and 402(j) of the Public Health Service Act (PHS Act) (42 U.S.C. 
§§ 282(i) and (j)), which was amended by Title VIII of the Food and Drug Administration Amendments Act of 
2007 (FDAAA) (Public Law No. 110-85, 121 Stat. 904) by registering and reporting results in the Clinicaltrials.gov 
database. 
   
8.1.2 
CONFIDENTIALITY, PRIVACY, AND DATA SECURITY 
 

 
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Participant confidentiality and privacy is strictly held in trust by xCures, their staff, partners, and affiliates.  
xCures maintains the confidentiality of records and that confidentiality extends to cover test results of biological 
samples and genetic tests in addition to the clinical information relating to participants. Therefore, the study 
data will be stored in secure electronic format and personally identifiable information will not be disclosed 
without the express permission of the participant, however authorized representatives of xCures and 
representatives of the Genetic Alliance IRB, as well as regulatory agencies may inspect records in certain 
circumstances without prior approval. 
 
Research data, which is for purposes of statistical analysis and scientific reporting, will be transmitted to and 
stored by xCures in a research study database within the REDCap EDC system. REDCap is a secure, cloud-based 
system that is HIPAA, FISMA, GDPR, Annex 11, and 21 CFR 11 compliance system for the collection and storage 
of clinical research and survey information. Services Data related to the provision of information services or 
management of the study Web site will not be considered Research Data under this protocol and will be 
maintained separately.   
 
For both Research Data and Services Data, sensitive personal information will be stored in a secure database 
using a role and permission-based system for access.  Sensitive data elements, including PHI or other sensitive or 
identifiable information will be stored in encrypted-at-rest format.  Research Data will identify participants only 
by a unique study identification number. The decode list for this information will be maintained securely and not 
disclosed to recipients of the Research Data.   Research Data may be disclosed outside of xCures and their 
agents and affiliates for the purposes of research and education, public health, or to further the development of 
treatments for COVID-19. 
 
8.1.3 
FUTURE USE OF STORED DATA  
 
Data collected for this study will be analyzed and stored by xCures and their designated data/technology 
provider(s).  In the event the study is terminated for any reason, the de-identified, archived data will be retained 
for future use by other researchers possibly including those outside of the study.  Access to the study data will 
require agreement to comply with the privacy policies herein. 
 
8.1.4 
PUBLICATION AND DATA SHARING POLICY 
 
This study will be conducted in accordance with the ICMJE publication and data sharing policies. xCures and 
their partners are responsible for submitting manuscripts for publication.  Every attempt will be made to publish 
results in a suitable, peer-reviewed journal.  External researchers may publish articles based on access to the de-
identified or limited study data following agreement to comply with applicable regulations. 
 
8.1.5 
CONFLICT OF INTEREST POLICY 
 
The independence of this study from any actual or perceived influence, is critical.  Therefore, any actual conflict 
of interest of persons who have a role in the design, conduct, analysis, publication, or any aspect of this trial will 
be disclosed and managed. Furthermore, persons who have a perceived conflict of interest will be required to 
have such conflicts managed in a way that is appropriate to their participation in the design and conduct of this 
trial.  The study leadership at xCures has established policies and procedures for all study group members to 
disclose all conflicts of interest and will establish a mechanism for the management of all reported dualities of 
interest. 
 

 
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8.1.6 
ETHICAL CONSIDERATIONS 
The research protocol and consent form will be provided to the Genetic Alliance IRB for review and approval 
prior to implementation. 
All patients must provide informed consent.  The process will be conducted electronically using the secure e-
consent process.  Documentation of the consent will be maintained.  Participants will receive an electronic copy 
of their consent.  Further, participants may discontinue participation at any time in accordance with the 
procedures outlined in the consent form.  All data collected up to the point of withdrawal will remain in the 
Research Database and may be included in de-identified data for future analyses. 
8.2 
STUDY OVERSIGHT AND OTHER CONSIDERATIONS 
8.2.1 
FINANCIAL CONSIDERATIONS 
xCures is a for-profit organization and will be responsible for the costs associated with implementing and 
maintaining the registry.   
8.2.2 
STUDY DISCONTINUATION AND CLOSURE 
This study may be suspended or prematurely terminated at any time for any reason, at the discretion xCures.  
Written notification, documenting the reason for study suspension or termination, will be provided by the 
suspending or terminating party to study participants at their provided contact email and via public notice on 
the study Web site, if possible, as well to  the IRB, and regulatory authorities, if required.   
8.2.3 
QUALITY ASSURANCE AND QUALITY CONTROL 
 
xCures will perform internal quality management of study conduct, including collection, handling and analysis of 
data.  A quality management system will be implemented and written Standard Operating Procedures (SOPs) 
will be followed. 
 
Quality control (QC) procedures will be implemented within the data collection and storage systems with quality 
control procedures.  Any missing data or data anomalies will be investigated. 
 
Noncompliance events that meet the IRB’s reporting requirements must be reported to the IRB office within 10 
working days of xCures becoming aware of the event. 
 
 
8.2.4 
KEY ROLES AND STUDY GOVERNANCE 
 
VP, Clinical Development 
Lead Data Scientist 
Legal and Compliance 
Mark Shapiro, MA, MBA 
Asher Wasserman, PhD 
Christopher Porter, JD, MBA 
xCures, Inc.  
xCures, Inc. 
Porter Advisory Services 
308 W Rosemary St. Suite 308 
Chapel Hill, NC 27516 
5050 El Camino Real, Suite 215, 
Los Altos, CA  94022 
5050 El Camino Real, Suite 215, 
Los Altos, CA  94022 

 
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Mobile: (919) 306-3675 
 Fax: (919) 883-4400   
 
Mobile: (919) 306-3006 
 
mshapiro@xcures.com 
awasserman@xcures.com 
cporter@xcures.com 
 
Director of Research 
VP, Clinical Operations 
CTO 
Jeff Schrager, PhD 
Bryan Federowicz 
Glenn Kramer, PhD 
xCures, Inc.  
xCures, Inc.  
xCures, Inc.  
5050 El Camino Real, Suite 215, 
Los Altos, CA  94022 
308 W Rosemary St. Suite 308 
Chapel Hill, NC 27516 
5050 El Camino Real, Suite 215, 
Los Altos, CA  94022 
Office Main: (650)530-3636 
Office: (919) 277-9903 
Mobile: (919) 812-1288  
 
jschrager@xcures.com 
bfederowicz@xcures.com 
gkramer@xcures.com 
 
 
 

 
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8.3 
PROTOCOL AMENDMENT HISTORY 
The table below is intended to capture changes of IRB-approved versions of the protocol, including a description 
of the change and rationale. A Summary of Changes table for the current amendment is located in the Protocol 
Title Page.  
 
Version 
Date 
Description of Change  
Brief Rationale 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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9 
REFERENCES  
 
 
Gliklich RE, Dreyer NA, eds. Registries for Evaluating Patient Outcomes: A User’s Guide. 2nd ed. (Prepared by 
Outcome DEcIDE Center [Outcome Sciences, Inc. d/b/a Outcome] under Contract No. HHSA29020050035I TO3.) 
AHRQ Publication No.10-EHC049. Rockville, MD: Agency for Healthcare Research and Quality. September 2010 
 
Lim L, Pullenayegum E, Moineddin R, Gladman D, Silverman D, Feldman B. Methods for analyzing observational 
longitudinal prognosis studies for rheumatic diseases: a review & worked example using a clinic-based cohort of 
juvenile dermatomyositis patients. Pediatric Rheumatology 2017; 15:18 
 
Sherman R, Anderson S, Dal Pan G, Gray G, Gross T, Hunter N, LaVange L, Marinac-Dabic D, Marks P, Robb M, 
Shuren J, Temple R, Woodcock J, Yue L, Califf R.  Real-World Evidence: What Is It and What Can It Tell Us? NEJM 
2016 Dec; 375(23):2293-7. 
 
 
 

 
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APPENDIX 1: INFORMED CONSENT AND ASSENT TEXT 
xCures COVID-19 Registry Informed Consent 
xCures is conducting a research study of people who may have the novel coronavirus COVID-
19.  This study involves many thousands of people.  To be in the study you must be in the 
United States or US territories. If you sign up on the Web site, you can participate. 
By signing up for this study, you will receive a series of emails with questions about your 
health.  These are focused on symptoms thought to be caused by COVID-19 as well as any 
treatments or actions that you take to manage your health.  You can share information that you 
think is important.  We will collect the data and present summaries of how the COVID-19 virus 
affects people differently.  No one will be individually identified, but reports may be created on 
how groups of people of different ages or with different health conditions experience the 
infection.  We will also ask for geographic location (Zip Code) to understand how changing 
weather may alter the transmission of COVID-19.    
Being in the study should not put you at risk, but because we collect some of your information, 
there is a risk of breach of confidentiality.  To reduce this risk, your research information is 
stored in a secure and encrypted database.  Information may be shared with other researchers 
in the future, but your identifying information will not be shared or disclosed outside of study 
team.  
If you on longer want to be contacted or change your mind about being in the study, you can 
stop participating at any time by contact xCures via email or through an opt out on the study 
Web site.  If you ask to stop, we will no longer contact information about you, but they will keep 
the information that has been collected for research purposes.  
If you have questions about the study, you can ask COVID19-Registry@xcures.com. For 
questions about your rights as a participant in research, you can contact the Genetic Alliance 
IRB at 202.966.5557 or by email at info@geneticalliance.org. 
By entering your information, clicking "I Agree" below and signing you are agreeing to the 
electronic consent form and to get important information about the study online. This process 
takes the place of traditional paper forms. 
xCures is responsible for the study and for giving you notices, forms, and other information 
about your participation in the study. That information is already in this consent document 
(collectively, the "required information"). By electronically initialing this document, you are 
confirming that you agree:  
(1) to receive online the required information, notices and other disclosures related to taking 
part in this research study;  

 
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(2) to continue to receive online any records, documents or other notices regarding the study 
until and unless you change your mind and withdraw your agreement by notifying xCures in 
writing; and  
(3) to use an electronic signature in place of a handwritten signature to sign the form agreeing 
to participate in the study.  
By entering your information and clicking on the "I agree" button, you confirm and agree to the 
above terms and conditions and agree that your electronic consent is the same as signing a 
paper consent form. 
 
Agree to Participate? Make one selection 
 
 
I have read the consent document and I wish to participate in the study 
 
 
 
I have read the consent document and I DO NOT wish to participate in the study 
 
I am the legally authorized representative for the participant listed below and have reviewed the study 
with them and they have verbally assented to be in the study 
 
 
Participant First Name:  
 
 
 
Participant Last Name: 
Legally Authorized Representative First Name (if applicable): 
 
Legally Authorized Representative Last Name (if applicable): 
Signature of Participant or Legally Authorized Representative: 
 
Date of Signature: 
 
 
 

 
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APPENDIX 2: WEB SITE CONTENT 
What is the COVID-19 Registry? 
The COVID-19 Registry is a patient-centric research study designed to help us all of learn about how 
people experience the COVID-19 infection, including characteristics associated with risk and severity of 
infection.  
What is xCures? 
 
xCures is a precision medicine company based in Los Altos, California and Chapel Hill, North Carolina.  
We are a team of data scientists, software engineers, and biomedical scientists working to find out what 
treatments work for individual patients.  Our team supports many non-profit patient advocacy organizations 
with their efforts to encourage and find treatments for the patients that they represent.   
Why is xCures doing this? 
 
There are a number of urgent and unanswered questions about COVID-19.  While many small clinical 
trials are happening in hospitalized patients, there is an urgent need to understand the natural history and look 
for signals in a large dataset.  We are all in this together and we need a large de-identified dataset made publicly 
available for qualified researchers and data scientists in real time. 
How does xCures’ COVID-19 Registry Work? 
The COVID-19 Registry works by asking people to register online, contribute data about themselves, their 
health and any symptoms, and provide consent for the use of their data in this research study.  People in 
the study will complete a daily survey by email.  The information that is collected will be analyzed and 
shared with all study participants through updates at the Web site.  Findings from the study will be 
submitted for peer review in medical or scientific journals. 
Who can be in this study? 
1.) People who are feeling sick but have not tested positive for COVID-19 
2.) People who are feeling sick and have tested positive for COVID-19 
3.) People who are not feeling sick but want to participate 
What information will participants receive during the COVID-19 Registry? 
We will present daily summary information at our Web site on where and how different groups 
experience symptoms, as well as treatments they are using to manage symptoms, other health 
conditions, and any interaction between symptoms and treatments.  If sufficient information is available, 
we will present heat maps of symptoms at a geographic level that does not risk identifying individuals 
(First three numbers of Zip code). 
How Participants provide data to the COVID-19 Registry? 

 
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Questions will be emailed to patients daily.  In some cases, the research team may contact patients for 
additional information or to request permission to collect medical records associated with COVID-19 
treatment or to contact their medical care provider to ask questions related to their treatment.  Such 
requests will utilize a separate patient agreement providing legal authorization under HIPAA to access 
such records. 
How will your data be kept secure? 
All your personal information will be kept private and stored in encrypted form.  Extensive efforts are 
undertaken to ensure data security including the use of validated systems that are HIPAA, FISMA, and 21 
CFR 11 compliant.   Analysis of data will be at the aggregate and/or group level and individually 
identifying information will be removed from analysis dataset. 
What do I get from joining the COVID-19 Registry? 
When you join the COVID-19 Registry you will get access to: 
1.) A curated fact sheet that details current evidence potential treatments under study for COVID-19. This 
will be updated and available at the study website as knowledge emerges. 
2.) Access to the combined data from all the study participants shared on an online dashboard 
3.) An opportunity to collaborate to help us all learn quickly about what to do about COVID-19 
 
 

 
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APPENDIX 3: PLANNED DATA ELEMENTS 
1. Demographics  
a. Name: First, MI, Last 
b. Current age and Year of Birth (parity check (+/- 1-year accuracy) Or, 18 – 20, 21 – 29, 30 
– 39, etc.… 
c. Gender M, F, Other  
i. If F, are you pregnant?   
ii. If F, are you nursing? 
d. Ethnicity: Are you Hispanic or Latino, Not Hispanic or Latino, Not Reported/Not Known 
e. Race: American Indian or Alaska Native, Asian, Black or African American, Native 
Hawaiian or Other Pacific Islander, White or Caucasian, Other, Decline to answer 
f. Participant Contact 
i. Email address for surveys: 
ii. Phone number 
iii. May we contact you by phone or email for follow-up questions? Y/N 
g. Would you like to provide an alternate contact: Y/N, If Y: 
i. Name 
ii. Email 
iii. Phone 
iv. Relation: parent, guardian, other 
 
2. Environment 
a. Are you currently in an area with under shelter-in-place recommendation? Y/N 
i. Do you leave the home regularly for work? 
ii. Do you work in any of the following settings?  [List Clinic, Hospital, Nursing 
Home, Senior Care Facility, Other health or medical facility] 
b. In what city and state are you currently residing?  (This may not be your home address 
but is the location where you are staying during the outbreak.) 
c. What is the Zip code where you currently reside? 
d. With how many people do you currently reside (not counting yourself)?  
i. Are any people in your household under age 18? 
e. Have you had contact with anyone known or suspected to have COVID-19 within the last 
two weeks? 
f. NEW Question: Are you feeling sick today?  Y/N 
i. IF Y, when did you start feeling sick?  Calendar widget.  Note: we will start 
sending you surveys about your symptoms once you complete this intake form. 
 
3. Health status 
a. Height and weight 

 
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b. For your age, how healthy are you 1-5 (much less than average, less than average, 
average, better than average, much better than average) 
c. Do you smoke?  
d. Do you exercise regularly? 
e. Do you have or have you ever had any of the following problems with your: 
 
i. (let’s do a two-column table with a check box for things that they have in the 
med hx, and another column for currently taking medication for this condition). 
 
ii. Lungs:   
iii. Asthma 
iv. COPD 
v. Emphysema 
vi. Lung disease or tuberculosis 
 
vii. Immune system: 
viii. Allergies 
ix. HIV/AIDS 
x. Transplant 
 
xi. Heart and blood: 
xii. Bleeding 
xiii. High blood pressure 
xiv. Heart disease 
xv. Arrythmia or pacemaker 
xvi. Stroke 
 
xvii. Other medical conditions: 
xviii. Alzheimer’s Disease 
xix. Cancer 
xx. Kidney disease 
xxi. Diabetes (T1 or T2) 
xxii. Arthritis 
xxiii. Liver disease or hepatitis 
xxiv. Other medical conditions:  free text 
 
4. Do you take any prescription medications? 
5. List (free text OK, we’ll do NLP) 

 
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6. Daily Survey Questions: 
 
 
7. Activity: Are you in an area under a shelter-in-place recommendation?   
 
8. Travel: Did you go to work or school outside the house today?  IF Y, how did you travel, walk, 
bicycle, bus, taxi/rideshare service, personal vehicle, subway/rail/train, air travel? 
 
9. With how many people outside your immediate family did you interact today? 0, 1-3, 4-10, 10-
20, 20+ 
 
10. Is anyone in your household sick with known or suspected COVID-19? Y/N 
 
11. Physically, how have you been feeling today on a scale of 0-10? 
 
12. What is your stress right now level on a scale from 0-10? (0 = no stress, 10 = as stressed as you 
can possibly imagine). 
 
13. Are you concerned that you may be getting sick? 
 
14. Have you sought care for or been tested for COVID-19? Y/N 
 
15. If yes, did you have a rapid flu test?  Was the flu test positive or negative? (not known) 
 
16. Did you have a COVID-19 test?  Result positive or negative? (not known) 
 
17. Have you had any problems with the following (draw terms and rubric from validated scales 
CTCAE-PRO, TCS): 

 
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Your head, eyes, ears, nose and throat: Y/N, if Y: 
 
a. Headache  0-3 scale (none, mild, moderate, severe) 
b. Sore throat 
c. Runny 
d. stuffy nose 
e. gritty/itchy eyes 
f. watery eyes 
g. Other problem:  
Problems with your stomach, like nausea, vomiting, or diarrhea? Y/N if y: 
 
h. Nausea 
i. Vomiting 
j. Diarrhea 
k. Other:  
 
Problems with your chest or lungs? Y/N, if Y 
 
l. Sneezing: 
m. Coughing: If mild+ symptoms then ask: wet or dry cough, if wet: blood in phlegm? 
n. Shortness of breath 
o. difficulty breathing: 
p. Pain or pressure in your chest 
 
q. Other problems:  
 
r. Have you had other problems like fever, chills, aches and pains, or feeling tired/fatigued: 
Y/N, if Y: 
 
s. Fever y/n if y: what was your temperature _ _ _. _ 
t. Chills 
u. Body aches  
v. Fatigue 
w. Other issues: Free text___________ (NLP) 
 

 
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18.  
no symptoms 
= 0 
mild  
symptoms = 1 
moderate  
symptoms = 2 
severe      
symptoms = 3 
19. runny nose 
 
 
 
 
20. stuffy nose 
 
 
 
 
21. sneezing 
 
 
 
 
22. itchy nose 
 
 
 
 
23. gritty/itchy 
eyes 
 
 
 
 
24. watery 
eyes 
 
 
 
 
 
25. Note: any serious scores should prompt them to contact medical assistance immediately.   
 
26. Have you taken any of the following medications today?   
 
No 
Yes  
Did you use an oral antihistamine (e.g., Zyrtec, 
Allegra, Claritin, Benadryl, etc.) today? 
Dis you use eye drops (Visine, Clear Eyes, etc.) 
today? 
Did you use a nasal corticosteroid (Flonase) 
today? 

 
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Did you use an over-the-counter multi-symptom 
cold/cough medication (Dayquil, Nyquil, 
Robitussin, etc.) 
 
 
Did you use a fever reducing medication (Advil, 
Tylenol, Aleve, or similar)? 
 
 
 
27. Are you taking other medications?  Free text 
 
28. Has a doctor prescribed any medications for your symptoms? Y/N if Y, type or upload photo of 
the label. 
 
29. Are you using any nutritional supplements or other remedies? Y/N If Y: free text 
 
30. Is there other information that you think is important to share? Y/N if Y free text for NLP. 
 
 

 
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