The Utility of "Lollipop" Oral Swabs in the Diagnosis of COVID-19 in an Inpatient Setting
Phase: NA
Conditions: COVID-19, Diagnostic Test
Sponsor: University of Wisconsin, Madison

 
Inpatient COVID-19 Lollipop Study 
 
Last IRB Protocol Approval 4/6/2023 
 
#NCT05801341 

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Inpatient COVID-19 Lollipop Study 
 
 
 
 
Protocol Number: IRB #2023-0290 
Principal Investigator: Ellen Wald, MD 
Co-Principal Investigator: Joseph McBride, MD 
 
 
 
 
 
Protocol Version History 
 
Protocol 
Version 
Version 
Date 
Summary of Revisions Made 
Rationale 
1.0 
03/01/2023 
Initial version 
 
2.0 
04/04/2023 
Study samples may temporarily be 
stored in a designated refrigerator or 
freezer. 
The laboratory suggested 
temporarily storing study samples 
in a refrigerator, so we needed to 
add flexibility in the protocol. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Table of Contents 
 
1.0 
STATEMENT OF COMPLIANCE ............................................................................................................. 1 
2.0 
LIST OF ABBREVIATIONS ...................................................................................................................... 2 
3.0 
STUDY SUMMARY .................................................................................................................................. 2 
 
Synopsis ....................................................................................................................................... 2 
 
Schematic of Study Design ........................................................................................................... 4 
4.0 
KEY ROLES ............................................................................................................................................. 5 
5.0 
INTRODUCTION ...................................................................................................................................... 5 
 
COVID-19 Background .................................................................................................................. 5 
 
Current Standard of Care .............................................................................................................. 5 
 
Oral Lollipop Swabs and COVID-19 PCR Testing ......................................................................... 5 
 
Rationale ....................................................................................................................................... 6 
6.0 
STUDY OBJECTIVES AND ENDPOINTS ................................................................................................ 6 
7.0 
STUDY DESIGN ....................................................................................................................................... 6 
 
General Design ............................................................................................................................. 6 
 
End of Study Definition .................................................................................................................. 7 
8.0 
SUBJECT SELECTION ............................................................................................................................ 7 
 
Inclusion & Exclusion Criteria ........................................................................................................ 7 
 
Vulnerable Populations ................................................................................................................. 7 
 
Lifestyle Considerations ................................................................................................................ 8 
 
Subject Identification ..................................................................................................................... 8 
8.4.1 
Best Practice Alerts ............................................................................................................................................. 8 
8.4.2 
Identification in Clinical Practice .......................................................................................................................... 8 
8.4.3 
Reporting Workbench ......................................................................................................................................... 8 
 
Subject Recruitment ...................................................................................................................... 8 
8.5.1 
Recruitment through Clinical Practice ................................................................................................................. 8 
8.5.2 
Posters/Flyers ..................................................................................................................................................... 8 
 
Remuneration and Retention Strategies ........................................................................................ 9 
 
Early Termination and Withdrawal ................................................................................................. 9 
9.0 
STUDY AGENT (STUDY DRUG, DEVICE, BIOLOGIC, VACCINE, ETC.) AND/OR PROCEDURAL 
INTERVENTION AND/OR BEHAVIORAL/SOCIAL INTERVENTION ...................................................... 9 
 
Study Agent and Control Description ............................................................................................. 9 
9.1.1 
Source ................................................................................................................................................................ 9 
9.1.2 
Packaging and Labeling ...................................................................................................................................... 9 
9.1.3 
Preparation ......................................................................................................................................................... 9 
9.1.4 
Storage and Stability ......................................................................................................................................... 10 
9.1.5 
Accountability .................................................................................................................................................... 10 
9.1.6 
Administration ................................................................................................................................................... 10 
 
Method for Assigning to Treatment Groups ................................................................................. 10 
 
Study Intervention Compliance .................................................................................................... 10 
 
Concomitant Therapy .................................................................................................................. 10 
9.4.1 
Permitted Concomitant Therapy ....................................................................................................................... 10 
9.4.2 
Prohibited Concomitant Therapy ....................................................................................................................... 10 

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10.0 STUDY VISITS AND PROCEDURES ..................................................................................................... 10 
 
Study Calendar ........................................................................................................................... 10 
 
Screening and Enrollment ........................................................................................................... 11 
10.2.1 
Pre-screening .................................................................................................................................................... 11 
10.2.2 
Informed Consent ............................................................................................................................................. 11 
10.2.3 
Enrollment ......................................................................................................................................................... 12 
10.2.4 
Screen Failure and Re-enrollment .................................................................................................................... 12 
 
Study Visit ................................................................................................................................... 12 
10.3.1 
Study Visit ......................................................................................................................................................... 12 
 
Unscheduled Visits ...................................................................................................................... 12 
 
Early Termination/Withdrawal Visit .............................................................................................. 12 
 
Long-Term Follow-up | Re-contacting Subjects ........................................................................... 12 
11.0 DATA HANDLING AND RECORD KEEPING ........................................................................................ 13 
 
Data Collection ............................................................................................................................ 13 
11.1.1 
Data Collection Forms ...................................................................................................................................... 13 
11.1.2 
Data Management Software Systems ............................................................................................................... 13 
 
Confidentiality and Privacy .......................................................................................................... 13 
 
Records Retention ...................................................................................................................... 14 
 
Retention for Future Research: Mandatory Data Banking ........................................................... 14 
11.4.1 
Purpose of Storage ........................................................................................................................................... 14 
11.4.2 
Data and/or Biospecimens Being Stored .......................................................................................................... 14 
11.4.3 
Location of Storage ........................................................................................................................................... 14 
11.4.4 
Duration of Storage ........................................................................................................................................... 14 
11.4.5 
Access to Data and Security Measures ............................................................................................................ 14 
11.4.6 
Procedures to Release Data ............................................................................................................................. 15 
11.4.7 
Process for Returning Results .......................................................................................................................... 15 
11.4.8 
Process for Tracking Subject Consent and Authorization ................................................................................. 15 
11.4.9 
Withdrawal of Permission to Bank Data ............................................................................................................ 15 
 
Protocol Deviations ..................................................................................................................... 15 
 
Publication and Data Sharing Policies ......................................................................................... 15 
12.0 STUDY ANALYSIS ................................................................................................................................ 15 
 
Statistical Hypotheses ................................................................................................................. 15 
 
Sample Size Justification ............................................................................................................ 15 
 
Subject Population(s) for Analysis ............................................................................................... 16 
 
Statistical Methods ...................................................................................................................... 16 
 
Planned Interim Analysis ............................................................................................................. 16 
 
Handling of Missing Data ............................................................................................................ 16 
13.0 RISK/BENEFIT ASSESSMENT ............................................................................................................. 16 
 
Known Potential Benefits to the Subjects .................................................................................... 16 
 
Known Potential Risks ................................................................................................................. 16 
13.2.1 
Known Interventional Risks ............................................................................................................................... 16 
13.2.2 
Other Known Study Risks ................................................................................................................................. 16 
 
Risk/Benefit Analysis ................................................................................................................... 16 
14.0 DATA AND SAFETY MONITORING ...................................................................................................... 17 
 
Adverse Event (AE) Definition ..................................................................................................... 17 
 
Serious Adverse Event (SAE) Definition ...................................................................................... 17 
 
Classification of an Adverse Event .............................................................................................. 17 
14.3.1 
Severity of Event ............................................................................................................................................... 17 
14.3.2 
Relationship to Study, Study Procedure(s) and/or Study Intervention(s) .......................................................... 17 
14.3.3 
Expectedness for Study, Study Procedure(s) and/or Study Intervention(s) ...................................................... 18 
 
Time Period and Frequency for Event Assessment and Follow-Up ............................................. 18 

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Reporting AEs and SAEs ............................................................................................................ 18 
14.5.1 
Reporting AEs ................................................................................................................................................... 18 
14.5.2 
Reporting SAEs ................................................................................................................................................ 18 
 
Reporting of Pregnancy ............................................................................................................... 19 
 
Unanticipated Problems .............................................................................................................. 19 
 
Unanticipated Adverse Device Effect .......................................................................................... 19 
 
Incidental Findings ...................................................................................................................... 20 
 Safety Oversight .......................................................................................................................... 20 
 Study Monitoring ......................................................................................................................... 20 
 Study Stopping Rules .................................................................................................................. 20 
15.0 STUDY FEASIBILITY ............................................................................................................................. 20 
 
Economic Burden to Subjects ..................................................................................................... 20 
 
Facilities and Locations ............................................................................................................... 20 
 
Feasibility of Recruiting the Required Number of Subjects .......................................................... 21 
 
Principal Investigator Considerations .......................................................................................... 21 
15.4.1 
Time Devoted to Conducting the Research ...................................................................................................... 21 
15.4.2 
Process for Informing Study Teams .................................................................................................................. 21 
 
Availability of Medical or Psychological Resources ..................................................................... 21 
16.0 MULTI-SITE RESEARCH ....................................................................................................................... 21 
17.0 REFERENCES ....................................................................................................................................... 21 

Inpatient COVID-19 Lollipop Study 
 
Wald 
 
 
 
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Version Date: 04/04/2023 
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1.0 
STATEMENT OF COMPLIANCE 
I confirm that I have read this protocol. I will comply with the IRB-approved protocol, and applicable 
regulations, guidelines, laws, and institutional policies. 
  
I agree to ensure that all staff members involved in the conduct of this study are informed about their 
obligations in meeting the above commitment. 
 
Name 
Signature 
Date 
 
 
__________________________________ 
_____________________________ 
___________________ 
Principal investigator 
 
 
 
 

Inpatient COVID-19 Lollipop Study 
 
Wald 
 
 
 
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Version Date: 04/04/2023 
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2.0 
LIST OF ABBREVIATIONS 
 
AE 
Adverse Event 
CCC 
Clinical Coordinating Center 
CFR 
Code of Federal Regulations 
COVID-19 
Coronavirus Disease of 2019 
CRF 
Case Report Form 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTMS 
Clinical Trial Management Software 
DHHS 
Department of Health and Human Services 
DMC 
Data Monitoring Committee 
DSMP 
Data & Safety Monitoring Plan 
eCRF 
Electronic Case Report Forms 
EDC 
Electronic Data Capture 
EHR 
Electronic Health Record 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act 
ICTR 
Institute for Clinical and Translational Research 
IRB 
Institutional Review Board 
NP 
Nasal Pharyngeal 
OHRP 
Office for Human Research Protections 
OnCore 
Online Collaborative Research Environment 
PCR 
Polymerase Chain Reaction 
PHI 
Protected Health Information 
PI 
Principal Investigator 
POC 
Point of Contact 
REDCap 
Research Electronic Data Capture 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
UP 
Unanticipated Problem 
 
 
 
3.0 
STUDY SUMMARY 
 Synopsis 
 
Full Title 
The utility of "lollipop" oral swabs in the diagnosis of COVID-19 in an inpatient setting 
Short Title 
Inpatient COVID-19 Lollipop Study 
Protocol Number 
2023-0290 
ClinicalTrials.gov 
Identifier & 
Summary 
NCT ID pending.  
This study is being done to see if collecting saliva samples with a “lollipop” collection method 
works as well as nasal samples for COVID-19 PCR testing.  

Inpatient COVID-19 Lollipop Study 
 
Wald 
 
 
 
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Number of 
Site(s) 
UW-Madison will be the only site enrolling subjects.  
Main Inclusion 
Criteria 
• 
Individuals at least 4 years of age  
• 
Admitted to a hospital 
• 
Verified COVID-19 according to positive NP PCR test criteria 
• 
Enroll within 47 hours of the diagnostic NP swab; lollipop swab collected within 48 hours 
of the diagnostic NP swab 
Main Exclusion 
Criteria 
• 
Unable to suck on a swab 
• 
Previous participation in this study 
• 
Require translation services for medical care 
Objective(s) 
Primary Objective  
• 
To determine the performance characteristics of oral lollipop swabs compared to NP 
swabs for diagnosing COVID-19 via PCR molecular testing. 
Secondary Objectives  
• 
To identify clinical characteristics of patients when there are discordant results for NP and 
oral lollipop test results. 
Endpoints 
Primary Endpoint 
• 
Tabulated results from NP vs. lollipop swab-based PCR COVID-19 tests.  
Secondary Endpoints 
• 
Correlation of clinical characteristics to participants with discordant test results 
Study Design 
This is a prospective quantitative study evaluating the utility of a novel method of saliva 
collection for COVID-19 testing.  
FDA Regulatory 
Overview 
. 
The investigational swab and associated COVID-19 PCR test are FDA regulated and involve 
an IDE-exempt in vitro diagnostic device. 
Study Device 
The lollipop collection swab and the lollipop swab processing procedure are both 
investigational.  
Total Number of 
Subjects 
Up to 225 subjects will be enrolled. 
Study Population COVID-positive patients ages 4 and above admitted to a hospital in the Madison, Wisconsin 
metropolitan area.  
Statistical 
Methodology 
The results of the lollipop swab will be compared to that of the known positive NP PCR to 
estimate the performance of the lollipop test to diagnose COVID-19. Falsely negative lollipop 
samples will be compared with the corresponding NP sample for cycle threshold.  
Estimated 
Subject Duration 
The duration of the study for each subject is a single study visit that will take approximately 
30 minutes.  
Estimated 
Enrollment 
Period & Study 
Duration 
Study enrollment will occur over 6 months with the total expected duration of the trial to be 12 
months. 
 
 
 

Inpatient COVID-19 Lollipop Study 
 
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 Schematic of Study Design 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Prior to Enrollment 
Visit 1 
Time Point 
 
Screen potential participants by inclusion and exclusion criteria. Conduct 
consenting process and obtain informed consent. 
Confirm and document eligibility. Administer verbal questionnaire to collect 
clinical and demographic information. Supervise lollipop method of collecting a 
saliva sample.   
Post-Visit 
Collect information from participant’s electronic medical record and enter into 
the research database.    

Inpatient COVID-19 Lollipop Study 
 
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4.0 
KEY ROLES 
The following is a list of all key personnel and roles: 
 
Principal Investigator 
Ellen Wald, M.D. 
Professor 
UW-Madison Department of Pediatrics 
600 Highland Ave 
Madison, WI 53792-4108 
608-263-8543 
erwald@pediatrics.wisc.edu 
Participating Site(s) 
University of Wisconsin-Madison 
600 Highland Ave 
Madison, WI 53792-4108  
Local Laboratory Services 
Wisconsin Veterinary Diagnostic Lab (WVDL) 
University of Wisconsin – Madison  
445 Easterday Ln 
Madison, WI 53706 
608-262-5432  
Study Regulatory Contact 
 
Department of Pediatrics Regulatory Support 
University of Wisconsin – Madison  
600 Highland Ave 
Madison, WI 53792-4108 
Regulatory@pediatrics.wisc.edu  
5.0 
INTRODUCTION 
 COVID-19 Background 
Coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus is most commonly spread via 
contact with infective respiratory droplets and aerosols produced by coughing, sneezing, talking, and 
singing. 
Common diagnostic methods of COVID-19 infection include amplification of viral nucleic acid via 
polymerase chain reaction (PCR) or identification of viral antigens via rapid antigen detection kits or lateral 
flow assays. PCR techniques are used most frequently on nasopharyngeal (NP) swabs, but PCR 
performed on saliva samples can also identify infection. 
 Current Standard of Care 
Current standard of care in the medical system where this study is being conducted is NP swabs for 
COVID-19 testing.  
 Oral Lollipop Swabs and COVID-19 PCR Testing 
This study will utilize flocked swabs, referred to as “Lollipop” swabs, as a method of sample collection for 
PCR analysis for SARS-CoV-2. An oral lollipop swab will be obtained by placing a flocked swab into the 
mouth and sucking on the swab for 20 seconds as one would suck on a lollipop. Investigators have used 
this technique for sample collection in the diagnosis of Group A Streptococcal pharyngitis by PCR (DeMuri 
GP, Wald ER Detection of Group A Streptococcus in the Saliva of Children Presenting with Pharyngitis 
Using the cobas Liat PCR System Clinical Pediatrics May 19, 2020) and in past COVID-19 lollipop pilot 
studies (McBride JA, DeMuri GP, Wald ER The utility of “lollipop” swabs in the diagnosis of COVID-19 
Pediatric Academic Societies Abstract May 2021). This method of sample collection to test for COVID-19 is 
not typically available as a standard of care outside of this study. 

Inpatient COVID-19 Lollipop Study 
 
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 Rationale 
It has been reported that the ACE2 receptor is a main host cell receptor for SARS-CoV-2 and plays a 
crucial role in the viral entry into human cells. There is high expression of the ACE2 receptor in epithelial 
cells of the oral mucosa and tongue. PCR of saliva samples have been shown to be an alternative to NP 
swabs. 
NP swabs are cumbersome to perform, uncomfortable for the patient, require assistance from health care 
providers, and are not practical for large daycare and school-aged groups that may warrant repeated 
testing. Salivary samples can be challenging due to volume of saliva required to run the test. An oral swab, 
sucked on like a lollipop is a less invasive, quicker, and an easier sample to perform that may also be 
obtained by the individual or parent at home without a medical provider. Therefore, oral lollipop swabs may 
facilitate testing in adults, younger children, greater numbers of children, and when multiple longitudinal 
samples may be required. The oral lollipop swab will be a much more comfortable sample to obtain and will 
allow for the repeated and large-scale testing of populations. 
In addition, PCR is a very sensitive technique that can identify persistent viral nucleic acid following acute 
infection. For this reason, repeat PCR tests are not recommended to determine the end point of COVID-19 
isolation.  Moreover, repeat COVID-19 screening via PCR is not recommended within 90 days of past 
infection. These persistently positive NP PCRs can lead to diagnostic and infection prevention challenges 
as distinguishing which tests represent true, acute, and transmissible infection versus past, non-viable, and 
non-transmissible virus is frequently not possible. 
 
If the oral lollipop swab has a similar performance to the NP swab, then a new testing option, ideal for 
frequent testing of large cohorts of patients, especially young children, will be possible.  In addition, 
identifying differences between NP and oral lollipop swab positivity could determine whether oral lollipop 
swabs have less risk of persistent, post-infectious, positivity. 
6.0 
STUDY OBJECTIVES AND ENDPOINTS 
Objectives 
Endpoints 
Primary 
To determine the performance 
characteristics of oral lollipop swabs 
compared to NP swabs for diagnosing 
COVID-19 via PCR molecular testing. 
 
Tabulated results from NP vs. lollipop swab-
based PCR COVID-19 tests.  
 
Secondary 
To identify clinical characteristics of 
patients when there are discordant results 
for NP and oral lollipop test results. 
Correlation of clinical characteristics to 
participants with discordant test results 
 
7.0 
STUDY DESIGN 
 General Design  
The Inpatient COVID-19 Lollipop Study is a prospective, single-center study to determine if oral lollipop 
swabs provide an adequate/optimum sample for diagnosing COVID-19. A total of up to 225 COVID-positive 
inpatients ages 4 years and older will be enrolled at one study sites. Subject accrual will occur over 6 
months with the total duration of the study expected to be 12 months.    
 

Inpatient COVID-19 Lollipop Study 
 
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Version Date: 04/04/2023 
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Eligible subjects will complete 1 visit that will last approximately 30 minutes. After the study team obtains  
informed consent and assent, if applicable, the study team will provide verbal instructions and supervise 
participants as they suck on a flocked swab for 20 seconds. The sample will be labeled with the study ID 
code and date of sample acquisition, and the result (positive or negative) of the lollipop swab will be 
compared to the NP swab results in the participant’s medical record. Clinical information including 
symptoms, duration of symptoms, known past COVID-19 infections, known COVID-19 household contacts 
within 90 days, and COVID-19 immunization status will be assessed via conversation with the participant 
and review of the electronic medical record. Laboratory information including the cycle threshold of the NP 
sample will be collected. Each participant will be classified as having either symptomatic or asymptomatic 
infection. The electronic medical record will be reviewed for medical record number, birthdate, and the 
above clinical information regarding COVID-19. The sample will be sent to the Wisconsin Veterinary 
Diagnostic Lab (WVDL) for performance of the PCR for SARS-CoV-2. The specimens will be discarded in 
the lab after the sample has been processed.  
 
 End of Study Definition 
The end of the study is defined as the date of completion of any final follow-up activity or data collection 
described in the protocol. 
8.0 
SUBJECT SELECTION 
 Inclusion & Exclusion Criteria  
Eligibility will be determined by inclusion and exclusion criteria below and confirmed by medical record 
review as necessary. 
 
Inclusion Criteria  
1. Ability to understand and the willingness to provide verbal informed consent, if 18 years or 
older. If 4-17 years old, ability to understand and the willingness to provide verbal assent, plus 
have a parent or legal guardian present who can provide verbal informed consent.  
2. Willing to comply with all study procedures and be available for the duration of the study. 
3. Admitted to UW Health University Hospital or UW Health Kids American Family Children’s 
Hospital. 
4. Individuals at least 4 years of age. 
5. Verified COVID-19 according to positive NP PCR test criteria. 
6. Enroll within 47 hours of the diagnostic NP swab; lollipop swab collected within 48 hours of the 
diagnostic NP swab.  
7. Either personally able or have a parent or legal guardian able to verbally answer questions in 
English about clinical symptoms, exposures, and other health and demographic information. 
 
Exclusion Criteria 
1. Unable to suck on a swab.  
2. Previous participation in this study. 
3. Require translation services for medical care.  
4. Not suitable for study participation due to other reasons at the discretion of the investigators or 
their designee. 
 Vulnerable Populations 
This study will enroll children because the research is critical to advance the care of children with COVID-
19. The study presents minimal risk to children, as there are no known or anticipated risks of the lollipop 

Inpatient COVID-19 Lollipop Study 
 
Wald 
 
 
 
Version #: 2 
 
Version Date: 04/04/2023 
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swab collection method. Confidentiality risks are minimal, as this study does not involve collection of 
sensitive data. The research will help inform an important scientific question that may benefit children in the 
future. To further minimize risks to children, permission will be obtained from a single parent/guardian, and 
verbal assent will be obtained using age-appropriate language. Child dissent will always be respected.  
 
This study will enroll pregnant persons because the diagnostic testing method being studied will present no 
more than minimal risk to the fetus, as the study procedures involve the pregnant subject, who is already 
known to be COVID-positive, sucking on a sterile swab and verbally answering questions. This study will 
not seek to identify the pregnancy status of subjects. Pregnant women may be enrolled, but pregnancy 
status will not be identified as part of study procedures or included in research records. 
 Lifestyle Considerations 
During this study, subjects are asked to: 
• 
Always wear a face mask, except when they are collecting the saliva sample.  
• 
Refrain from eating or drinking directly before collecting the saliva sample.  
 Subject Identification 
8.4.1 Best Practice Alerts  
The study team will set up Best Practice Alerts in Health Link so they are notified when a potentially 
eligible patient is admitted for inpatient care at UW Health.  
8.4.2 Identification in Clinical Practice 
Potential subjects may be identified by study team members who provide clinical care to patients with 
COVID-19. A member of the clinical team will inform potential subjects of the research opportunity and 
provide an IRB-approved study flyer. Potential subjects will be pre-screened through medical record 
review. Potential subjects who meet all eligibility criteria will be invited to enroll in the study. 
8.4.3 Reporting Workbench 
Study staff with UW Health electronic health record (Health Link) access may search patient list 
templates made available to them as part of their research access to Health Link to help identify 
potential subjects for study enrollment evaluation. 
 Subject Recruitment 
A total of 225 subjects will be recruited from 1 site in the United States. Individuals from populations who 
are underrepresented in clinical research (e.g., racial and ethnic minorities, women, individuals from rural 
and underserved communities, older individuals, federally recognized nations and tribes) will be enrolled 
with a goal of ensuring that all eligible patients are given the opportunity to participate in novel clinical trials 
and that research findings can be generalizable to the entire population. 
 
Several recruitment strategies will be employed, and the study team will use a combination of methods. 
Specific recruitment strategies are as follows: 
8.5.1 Recruitment through Clinical Practice 
If the potential subject is agreeable, they will be provided a flyer and contact information for the study 
team or the research team will initiate contact. 
8.5.2 Posters/Flyers 
Flyers announcing that volunteers are needed for a study may be posted in UW Health Inpatient 
settings, as well as waiting rooms. Several key details of the study will be included in the flyer (key 
eligibility criteria, number and length of visits, location of study site, type of remuneration) along with a 
call back number for people to call in case they are interested. 

Inpatient COVID-19 Lollipop Study 
 
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 Remuneration and Retention Strategies 
Strategies for retention include:  
• 
Streamline data and sample collection to make the study visit as short as possible, approximately 30 
minutes.  
 Early Termination and Withdrawal 
Subjects are free to withdraw from participation in the study at any time upon request. 
 
The Principal Investigator (PI) may discontinue or withdraw a subject from the study for the following 
reasons at his/her discretion: 
• 
Subject non-compliance with study requirements (e.g., unwilling or unable to suck on swab)  
• 
If any clinical adverse event (AE), laboratory abnormality, or other medical condition or situation occurs 
such that continued participation in the study would not be in the best interest of the subject 
• 
If the subject is no longer an appropriate candidate for participation 
 
Subjects who provide verbal informed consent/assent but do not provide a lollipop swab that can be 
successfully resulted will not be replaced. Subjects who provide verbal informed consent/assent and 
provide a lollipop swab that can be successfully resulted, then subsequently withdraw, or are withdrawn or 
discontinued from the study, will not be replaced. 
 
The study team will attempt to obtain the following information from subjects following early termination or 
withdrawal: self-reported reason for withdrawal.  
9.0 
STUDY AGENT (STUDY DRUG, DEVICE, BIOLOGIC, VACCINE, ETC.) AND/OR PROCEDURAL 
INTERVENTION AND/OR BEHAVIORAL/SOCIAL INTERVENTION 
 Study Agent and Control Description 
Investigational Devices 
Both the “lollipop” collection swab and the lollipop swab processing procedure qualify as an exempt 
diagnostic device/test based on the Code of Federal Regulations device exemption guidelines. The swab 
and test are non-invasive, do not introduce energy to a subject, do not require invasive sampling, and are 
not used as a diagnostic procedure without confirmation of the diagnosis by another medically established 
test. Neither the swab nor the test meet the definition of “significant risk,” which is a device that presents a 
potential for serious risk to health, safety or welfare of subjects.  
 
9.1.1 Source 
The study team is already in possession of a supply of flocked swabs. The swabs are consistent with 
the type of swabs used for standard-of-care NP swabs.  
9.1.2 Packaging and Labeling 
 
The study team will add labels to each packaged swab with the statement "CAUTION - Investigational 
Device. Limited by Federal (or United States) Law to Investigational Use." [§ 812.5(a))]. 
9.1.3 Preparation 
9.1.3.1 
Investigational Swab 
A study team member will open the package of the swab and offer the end of the stick to the 
participant, instructing them to only touch the other end of the stick (i.e., the flocked end of the 
swab) to the inside of their mouth and nowhere else.  

Inpatient COVID-19 Lollipop Study 
 
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9.1.3.2 
Investigational Assay 
The COVID-19 PCR assay will be prepared and performed by the Wisconsin Veterinary Diagnostic 
Lab (WVDL), in the same way that samples are processed for standard of care.  
 
9.1.4 Storage and Stability 
Prior to use, the swabs must be stored separately from normal hospital stocks and must be stored in a 
securely locked area accessible only to authorized study personnel until used. Approved study team 
members will store, handle, and guide administration of the devices. If the package of a swab is 
damaged such that it is no longer sterile, the swab will be discarded.  
9.1.4.1 
Swab Handling After Saliva Collection 
The swab will be taken to the Wisconsin Veterinary Diagnostic Lab as soon as possible. If it cannot 
be delivered to the lab on the same day as collection, then it may be temporarily stored in a 
designated refrigerator or freezer.  
9.1.5 Accountability 
The study team is already in possession of all swabs that will be used for the study. 
 
9.1.6 Administration 
A study team member will instruct the participant to suck on the swab for 20 seconds in the same way 
that they would suck on a lollipop.  
 
 
 Method for Assigning to Treatment Groups 
Not applicable.  
 Study Intervention Compliance 
Immediately after each study visit, the study team member will complete a Reportable Event Form that 
asks about protocol deviations, adverse events, participant complaints, and/or any other potentially 
reportable events that may have occurred. A participant’s data will be included in analyses if their lollipop 
saliva sample is successfully resulted.  
 Concomitant Therapy 
9.4.1 Permitted Concomitant Therapy 
All concomitant therapies are permitted.  
9.4.2 Prohibited Concomitant Therapy 
No concomitant therapies are prohibited.  
10.0 
STUDY VISITS AND PROCEDURES 
 
Study Calendar 
The procedures performed at the single study visit are listed in the table below. 
 

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Procedure 
Study Visit 
Post-Study 
Visit 
End of 
Study/Early 
Withdrawal 
Informed Consent/Assent 
X 
 
 
Demographic and Health Verbal 
Questionnaire 
X 
 
 
Lollipop Swab Saliva Collection  
X 
 
 
Adverse Event Review and Evaluation 
 
 
X 
Collect Information from Medical Record  
 
X 
 
 
Screening and Enrollment 
The single study visit and procedures are described in detail below. 
10.2.1 Pre-screening 
Pre-screening consists of examining a subject’s medical records by research staff who have completed 
HIPAA and human subjects training. 
10.2.2 Informed Consent 
Preliminarily eligible subjects will be approached for informed consent/assent and formal screening. 
The informed consent/assent process will be conducted following all federal and institutional regulations 
relating to informed consent. 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. The 
Consent script will be Institutional Review Board (IRB)-approved. The participant (or legally authorized 
representative) will be asked to read and review the document. A copy of the informed consent 
document will be given to the subjects for their records. Verbal informed consent/assent will be 
obtained prior to conducting any study-related activities. 
 
The informed consent process will be performed as follows: 
• 
A research nurse or study coordinator will review the informed consent form and discuss the study 
in detail with the potential research participant and their parent/legal guardian, if the participant is a 
minor. 
• 
A research nurse or study coordinator will explain the study, its risks and benefits, what would be 
required of the research subject, and alternatives to participation. An oral explanation will be 
provided in terms suited to the participant’s comprehension of the purposes, procedures, and 
potential risks of the study and of their rights as research subjects. 
• 
The research subject will be given the opportunity to review the informed consent form and take 
their time considering, so they may discuss it with family members, friends, clergy or others when 
possible.  
• 
The subject will have the opportunity to ask questions and have all questions answered by the 
research nurse or study coordinator and/or PI. 
• 
A research nurse or study coordinator will obtain oral consent from adult subjects. In the case of 
minor subjects, a parent or legal guardian will provide oral consent and the minor subject will 
provide oral assent. If a minor subject is incapable of reviewing the informed consent form, a 
research nurse or study coordinator will provide a summary of the material in terms that are age-
appropriate and understandable to the subject. 
 
This research involves no greater than minimal risk to adults or children, and it involves no procedures 
for which written documentation of consent is normally required outside of the research context. It may 
not be feasible to obtain written consent and assent from all participants. Hospitalized individuals with 
COVID-19 may be significantly symptomatic and ill. For younger children, writing their names may be 
challenging. COVID-19 is also a contagious infectious disease, so it is safest to minimize the handling 
of paper and pens. For consistency, we would like to have the same consent/assent process for all 

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participants. Therefore, we are requesting a waiver of written documentation of consent, parental 
permission, and assent.  
  
10.2.3 Enrollment 
A research subject will be defined as “enrolled” in the study when they meet the following criteria: 
• 
The subject has been consented/assented by study staff.  
• 
The PI or designee has verified that the subject meets all of the inclusion criteria. 
• 
The PI or designee has verified that subject meets none of the exclusion criteria. 
• 
The subject has provided a saliva sample.  
10.2.4 Screen Failure and Re-enrollment 
Individuals who do not meet the criteria for participation in this trial (screen failure) because of a factor 
that could change over time may be rescreened. Rescreened subjects should be assigned a new 
subject ID number when they are re-screened. 
 
Study Visit 
After subjects have been enrolled, they will complete a single on-study visit, and the procedures performed 
at the visit are described in detail below. 
10.3.1 Study Visit 
Study visits will occur in a private location, such as the participant’s hospital room, during their inpatient 
stay at AFCH or University Hospital. Study team members will adhere to the University Hospital’s 
personal protective equipment (PPE) requirements. After verbal consent/assent is collected and 
documented in REDCap, the study team will collect basic information about participants, including their 
name, date of birth, sex, race and ethnicity. If participants are younger than 18 years old, the study 
team will collect their parent or guardian’s name. The study team will also collect information from 
participants or their parent/legal guardian verbally and from the participant’s medical record. The 
information will be relevant to their COVID-19 symptoms and diagnosis, as well as their vaccination 
status. A detailed list of data points can be found in the Data Collection Sheet. The study team will 
record this information directly in the study’s SMPH REDCap project. Once a study team member has 
collected this information, they will guide the participant through the lollipop swab collection. The 
lollipop swab is obtained by sucking on a swab for 20 seconds in the same way that one would suck on 
a lollipop. The study procedures will take approximately 15-30 minutes to complete.  
 
A study team member will transport the lollipop swab to the WVDL as soon as possible. The WVDL will 
provide the study team with the COVID-19 PCR results.  
 
Unscheduled Visits 
If the single study visit is interrupted by routine clinical care or for another reason, it may be paused and 
restarted when the participant is available to continue.  
 
Early Termination/Withdrawal Visit 
Subjects who are either withdrawn or terminated early from the study may be asked why they chose to 
withdraw.  
 
Long-Term Follow-up | Re-contacting Subjects 
Not applicable.  

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11.0 
DATA HANDLING AND RECORD KEEPING 
 
Data Collection  
11.1.1 Data Collection Forms 
Standardized data collection forms (e.g., source documents, case report forms, standardized 
assessment forms, etc.) are used to ensure data collected are consistent and compliant with the 
protocol and IRB application. 
 
Data collection is the responsibility of study team members under the supervision of the Principal 
Investigator (PI). The PI is responsible for ensuring the accuracy, completeness, legibility, and 
timeliness of the recorded and reported data. 
 
All data collection forms must be completed thoroughly; any missing data will be explained. Data entry 
errors will be corrected within REDCap. 
 
Data collection forms are maintained in the subject files and retained as described in Section 12.3: 
Records Retention. 
11.1.2 Data Management Software Systems 
Clinical data (including AEs, concomitant medications, and solicited events data) and clinical laboratory 
data will be entered into the following data management software system(s) to ensure consistent data 
entry and data quality. Clinical data will be entered directly from the source documents, typically Health 
Link. 
 
OnCore  
The Online Collaborative Research Environment (OnCore) Clinical Trial Management Software (CTMS) 
may be used for this study. 
 
OnCore is a web-based data management system that: a) ensures secure, easy data entry at multiple 
sites; b) integrates multiple data sources; c) provides controlled, secure access to sensitive data using 
role-based access control; and d) provides workflow automation. This software provides protocol and 
subject management functions (e.g., subject scheduling; screening; data organization), maintains 
updated forms, addresses budget development, billing and fiscal management, generates summary 
reports, and provides essential links with research administration and electronic medical records 
systems. The OnCore system eases the burden of the individual researcher and unifies protocol 
management within research programs and across research sites, enhancing protocol integrity and 
regulatory compliance efforts. 
 
REDCap 
The SMPH Research Electronic Data Capture (REDCap) system is used to manage the data for this 
study. 
 
REDCap is a largely self-service, secure, web-based application for building and managing data 
collection forms. REDCap provides data management functionality by allowing the development of 
instrument and surveys to support data capture for research studies. 
 
Confidentiality and Privacy 
Subject confidentiality and privacy are strictly held in trust by the participating investigators, their staff, and 
the sponsor(s) and their agents. This confidentiality is extended to cover testing of biological samples and 
genetic tests in addition to the clinical information relating to subjects. Therefore, the study protocol, 
documentation, data, and all other information generated will be held in strict confidence. No information 

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concerning the study or the data will be released to any unauthorized third party without prior written 
approval. 
 
All research activities will be conducted in as private a setting as possible. 
 
All study staff engaged in the conduct of this project have completed training on the protection of human 
subjects and the Health Insurance Portability and Accountability (HIPAA) Privacy Rule. In addition, all key 
personnel (i.e., Principal Investigator, individuals involved in identifying/recruiting subjects, obtaining 
informed consent, or interacting and intervening with subjects) have undergone Good Clinical Practice 
(GCP) training. 
 
Information about study subjects will be kept confidential and managed according to HIPAA requirements. 
All subjects will receive a combined informed consent and HIPAA authorization script that includes specific 
privacy and confidentiality rights. Study data will be maintained per federal, state, and institutional data 
policies. 
 
The investigator(s) will ensure that the identities of subjects are protected by using coded subject 
information. Data will be maintained securely in REDCap. All paper-based study records will be maintained 
in locked rooms or cabinets, and access will be limited to approved study personnel. Electronic study 
records/files will be stored in SMPH REDCap and on the Department of Pediatrics server. Electronic data 
will be accessed via networked computers that are password-protected with access provided only to 
authorized study personnel. 
 
Authorized representatives of the following groups may need to review this research as part of their 
responsibilities to protect research subjects: representatives of the IRB, and federal oversight agencies, 
such as the Food and Drug Administration (FDA). The clinical study site will permit access to such records. 
 
Records Retention 
At the end of this study, participant names and contact information will be destroyed. All other study data 
will be banked.  
 
Retention for Future Research: Mandatory Data Banking  
11.4.1 Purpose of Storage 
Data is being stored for potential future research uses.  
11.4.2 Data and/or Biospecimens Being Stored 
There is no biospecimen banking in this study, as saliva samples will be exhausted during the PCR 
testing process. Only a coded Limited Data Set will be stored. Names and contact information (i.e., all 
direct identifiers) will be destroyed at study closure. All other data will be banked indefinitely.  
11.4.3 Location of Storage 
Data will be stored on Department of Pediatrics secure server.  
11.4.4 Duration of Storage 
Data will be stored indefinitely.  
11.4.5 Access to Data and Security Measures 
Only UW researchers who have completed the Required Training for Researchers will have access to 
the folder with banked data on the Department of Pediatrics secure server. Only de-identified data will 
be shared with external researchers, using platforms and tools approved by UW Office of 
Cybersecurity.  

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11.4.6 Procedures to Release Data  
Researchers may request data by writing to the Principal Investigator or Co-Principal Investigator. 
Documentation of IRB approval may be required prior to releasing the data.  
11.4.7 Process for Returning Results 
Not applicable.  
11.4.8 Process for Tracking Subject Consent and Authorization 
The study team will document verbal consent from all participants or their parent/legal guardian in the 
study’s REDCap database.  
11.4.9 Withdrawal of Permission to Bank Data 
Data is fully anonymized prior to banking, so participants may not withdraw their banked data from 
future research use after study closure.  
 
Protocol Deviations 
A protocol deviation is any noncompliance with the clinical trial protocol or investigational plan 
requirements. The noncompliance may be either on the part of the subject, the investigator, or the study 
site staff. As a result of deviations, corrective actions are to be developed by the site and implemented 
promptly. 
 
It is the responsibility of the Principal Investigator/site investigator/study staff to use continuous vigilance to 
identify and report deviations. The Principal Investigator is responsible for assessing whether the deviation 
constitutes noncompliance as defined by the reviewing IRB and if so, reporting it within the required time 
frame(s). The site investigator is responsible for knowing and adhering to the reviewing IRB requirements. 
 
Publication and Data Sharing Policies 
Not applicable.  
12.0 
STUDY ANALYSIS 
 
Statistical Hypotheses 
• 
Primary Efficacy Endpoint(s):  
o For participants who have had COVID-19 symptoms for <5 days, the sensitivity of lollipop swab-
based PCR COVID-19 testing is non-inferior to the sensitivity of NP swab-based PCR COVID-
19 testing.  
 
• 
Secondary Efficacy Endpoint(s): 
o For participants who have had COVID-19 symptoms for ≥5 days, the sensitivity of lollipop swab-
based PCR testing is inferior by 50% to the sensitivity of NP swab-based PCR COVID-19 
testing.  
o For participants who are asymptomatic, the sensitivity of lollipop swab-based PCR testing is 
inferior by 50% to the sensitivity of NP swab-based PCR COVID-19 testing.  
 
 
Sample Size Justification 
Based on a small pilot study in 2020-2021, sensitivity of lollipop swabs compared to NP was found to be 
88%. As we will now be including both asymptomatic and symptomatic individuals, we anticipate the 

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sensitivity of the lollipop swab to drop to approximately 80%. With a Type I error rate of 5% and a power of 
90%, our calculated sample size is 206. 
 
Subject Population(s) for Analysis 
Protocol-compliant Population: all participants who provided a lollipop swab that was successfully resulted 
and complied with the protocol sufficiently to ensure that the data would be likely to represent the effects of 
the study intervention according to the underlying scientific model. 
 
Statistical Methods 
Sensitivity and specificity of the lollipop swabs will be calculated. 
 
The primary variable is binary (positive or negative). A separate subgroup analysis of sensitivity/specificity 
of lollipop swabs will be calculated for asymptomatic, symptomatic (<7 days), and symptomatic (>7 days) 
individuals. 
 
Planned Interim Analysis 
An interim analysis will not be performed.  
 
Handling of Missing Data 
Since the analyses of this study won’t involve any formal multivariate or longitudinal statistical modeling, no 
imputation-based analyses will be conducted. 
 
Guidelines promulgated in the National Research Council report on handling of missing data will be 
followed.2,3 
13.0 
RISK/BENEFIT ASSESSMENT 
 
Known Potential Benefits to the Subjects 
There will be no direct health benefit to subjects. 
 
 
Known Potential Risks 
13.2.1 Known Interventional Risks 
There are no known or anticipated risks of the lollipop swab collection method. Our study team 
implemented a similar testing method in a previous study (2017-1425) and it was tolerated well by 
participants.  
There is a risk of breach of confidentiality. 
13.2.2 Other Known Study Risks 
There are no knowns procedural risks potentially related to study participation.  
 
Risk/Benefit Analysis 
The risks are minimal, and the potential benefit to society is significant.  

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14.0 
DATA AND SAFETY MONITORING  
 
Adverse Event (AE) Definition 
Adverse event (AE) means any untoward medical occurrence associated with the use of an intervention in 
humans, whether or not considered intervention-related. 
 
Serious Adverse Event (SAE) Definition 
An adverse event is considered "serious" if, in the view of either the investigator or sponsor, it meets any of 
the following outcomes: 
• 
Death 
• 
A life-threatening adverse event  
• 
Inpatient hospitalization or prolongation of existing hospitalization for ≥ 24 hours 
• 
A persistent or significant incapacity or substantial disruption of the ability to conduct normal life 
functions.  
• 
A congenital anomaly/birth defect. 
• 
Important Medical Events (IME) that may not result in death, be life-threatening, or require 
hospitalization may be considered serious when, based upon medical judgment, they may jeopardize 
the patient or subject and may require medical or surgical intervention to prevent one of the outcomes 
listed in this definition (FDA, 21 CFR 312.32; ICH E2A and ICH E6). 
 
Classification of an Adverse Event 
14.3.1 Severity of Event 
All AEs will be assessed by the clinician using the Common Terminology Criteria for Adverse Events 
(CTCAE), version 5.0. For AEs not included in the protocol-defined grading system, the following 
guidelines will be used to describe severity. 
 
Mild 
(Grade 1) 
Events require minimal or no treatment and do not interfere with the 
subject’s daily activities. 
Moderate 
(Grade 2) 
Events result in a low level of inconvenience or concern with the 
therapeutic measures. Moderate events may cause some interference 
with functioning. 
Severe 
(Grade 3) 
Events interrupt a subject’s usual daily activity and may require 
systemic drug therapy or other treatment. Severe events are usually 
potentially life-threatening or incapacitating. 
Life Threatening 
(Grade 4) 
The subject was at risk of death at the time of the event. 
Fatal 
(Grade 5) 
The event caused death. 
 
14.3.2 Relationship to Study, Study Procedure(s) and/or Study Intervention(s) 
For all collected AEs, the clinician who examines and evaluates the subject will determine the AE’s 
causality based on temporal relationship and his/her clinical judgment. The degree of certainty about 
causality will be graded using the categories below. 
 
Definitely Related 
Clearly related to the study procedures/intervention and other 
possible contributing factors can be ruled out. 

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Probably Related 
Likely related to the study procedures/intervention and the influence 
of other factors is unlikely. 
Possibly Related 
Possibly related to the study procedures/intervention and there are 
other factors that could be equally likely. 
Unlikely to be related Doubtfully related to the study procedures/intervention and there is 
another likely cause. 
Unrelated 
Clearly not related to the study procedures/intervention and/or 
evidence exists that the event is definitely related to another cause. 
 
14.3.3 Expectedness for Study, Study Procedure(s) and/or Study Intervention(s) 
The PI will be responsible for determining whether an AE is expected or unexpected in relation to the 
study procedures and intervention(s) (as applicable).  
 
An AE will be considered unexpected if the nature, severity, or frequency of the event is not consistent 
with the risk information previously described in the clinical protocol, device manual, investigator’s 
brochure, the package insert(s), the IRB application, or the informed consent document. Expectedness 
is recorded for both study procedures and interventions. 
 
 
Time Period and Frequency for Event Assessment and Follow-Up 
The occurrence of an AE or SAE may come to the attention of study personnel during study visits and 
interviews of a study subject presenting for medical care, or upon review by a study monitor. All AEs 
including local and systemic reactions not meeting the criteria for SAEs will be captured on the appropriate 
CRF. Information to be collected includes event description, time of onset, clinician’s assessment of 
severity, relationship to study product (assessed only by those with the training and authority to make a 
diagnosis), and time of resolution/stabilization of the event. All AEs occurring while on study must be 
documented appropriately regardless of relationship. All AEs will be followed to adequate resolution. 
 
Any medical condition that is present at the time that the subject is screened will be considered as baseline 
and not reported as an AE. However, if the study subject’s condition deteriorates at any time during the 
study, it will be recorded as an AE. 
 
Changes in the severity of an AE will be documented to allow an assessment of the duration of the event at 
each level of severity to be performed. AEs characterized as intermittent require documentation of onset 
and duration of each episode. 
 
Events will be followed for outcome information until resolution, stabilization, or completion of study 
participation. 
 
Reporting AEs and SAEs  
14.5.1 Reporting AEs 
• 
AEs will be recorded from enrollment until completing all study activities. 
• 
AEs will be recorded regardless of whether or not they are considered related to the study device. 
• 
All AEs will be recorded on the appropriate study specific REDCap Reportable Event form within 
the study’s REDCap project. 
14.5.2 Reporting SAEs 
The investigator will immediately report to the sponsor any SAE, whether or not considered study 
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assessment of whether there is a reasonable possibility that the study intervention caused the event. 
Study endpoints that are SAEs (e.g., all-cause mortality) must be reported in accordance with the 
protocol unless there is evidence suggesting a causal relationship between the study intervention and 
the event (e.g., death from anaphylaxis). In that case, the investigator must immediately report the 
event to the IRB. 
 
All SAEs will be followed until satisfactory resolution or until the site investigator deems the event to be 
chronic or the subject is stable. 
 
Reporting of Pregnancy 
Not applicable.  
 
Unanticipated Problems 
An unanticipated problem (UP), as defined by the DHHS Office for Human Research Protection (OHRP), is 
any incident, experience, or outcome that meets all of the following criteria:  
• 
The incidence, experience, or outcome is unexpected given the research procedures described in 
protocol-related documents (e.g., the study protocol, the informed consent documents, the 
Investigator’s Drug Brochure) and the characteristics of the subject population being studied. An event 
may be considered unexpected if it exceeds the nature, severity, or frequency described in the study-
related documents, Investigator’s Drug Brochure, product labeling, or package insert. 
• 
The incidence, experience, or outcome is related or probably related to participation in the research 
study. “Probably related” means the incidence, experience, or outcome is more likely than not to be 
caused by the research study procedures. 
• 
The occurrence of the incidence, experience, or outcome suggests that the research places subjects or 
others at a greater risk of harm (physical, psychological, economic, or social) than was previously 
known or recognized. 
 
The investigator will report UPs to the reviewing IRB and to the Data Coordinating Center (DCC)/lead 
Principal Investigator (PI). The UP report will include the following information: 
• 
Protocol identifying information: protocol title and number, PI’s name, and the IRB project 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, informed consent documents, or other corrective actions 
that have been taken or are proposed in response to the UP. 
 
Report UPs within the timeframe(s) specified by the IRB(s) of record. 
 
Unanticipated Adverse Device Effect 
An unanticipated adverse device effect (UADE) means any serious adverse effect on health or safety or 
any life-threatening problem or death caused by, or associated with, a device, if that effect, problem, or 
death was not previously identified in nature, severity, or degree of incidence in the investigational plan or 
application (including a supplementary plan or application), or any other unanticipated serious problem 
associated with a device that relates to the rights, safety, or welfare of subjects (21 CFR 812.3(s)). 
 
An investigator shall submit to the sponsor and to the reviewing Institutional Review Board (IRB) a report of 
any UADE occurring during an investigation as soon as possible, but in no event later than 10 working 
days after the investigator first learns of the effect (21 CFR 812.150(a)(1)). 
 

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A sponsor who conducts an evaluation of an UADE shall report the results of such evaluation to the FDA 
and to all reviewing IRBs and participating investigators within 10 working days after the sponsor first 
receives notice of the effect. Thereafter the sponsor shall submit such additional reports concerning the 
effect as FDA requests (21 CFR 812.150(b)(1).] 
 
Incidental Findings 
Not applicable.  
 
Safety Oversight 
Safety oversight will be under the direction of the Principal Investigator. 
 
Study Monitoring 
Not applicable.  
 
Study Stopping Rules 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable cause. 
Written notification, documenting the reason for study suspension or termination, will be provided by the 
suspending or terminating party to investigator and regulatory authorities. If the study is prematurely 
terminated or suspended, the PI will promptly inform the IRB and will provide the reason(s) for the 
termination or suspension. 
 
Circumstances that may warrant termination or suspension include, but are not limited to: 
• 
Determination of unexpected, significant, or unacceptable risk to subjects 
• 
Demonstration of efficacy that would warrant stopping 
• 
Insufficient compliance to protocol requirements 
• 
Data that are not sufficiently complete and/or evaluable 
• 
Determination of futility 
 
Study may resume once concerns about safety, protocol compliance, and/or data quality are addressed 
and satisfy the applicable federal and institutional regulatory authorities. 
15.0 
STUDY FEASIBILITY  
 
Economic Burden to Subjects 
Subjects will not have to pay for study procedures (such as home blood pressure monitors, 24-hour 
monitoring). The subject will not be billed by the healthcare system or their health insurance company for 
any costs related to a study procedure. 
 
Subjects will be responsible for any costs related to their COVID-19 follow-up as directed by their 
healthcare team, such as clinic visits and medication, including all out-of-pocket costs. 
 
Facilities and Locations 
UW Health Kids American Family Children’s Hospital and UW Health University Hospital inpatient units.  

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Feasibility of Recruiting the Required Number of Subjects 
While COVID levels fluctuate in the community, in 2023 at University Hospital/AFCH there are generally 
10-20 individuals hospitalized with a positive COVID test on any given day. If the COVID rates are 
maintained, then obtaining the sample size is possible over the next few months. 
 
If UW/AFCH stops pre-procedural or COVID admission screening, then the amount of known COVID-
positive individuals will likely decrease and it may take a longer time to identify 225. 
 
Principal Investigator Considerations 
15.4.1 Time Devoted to Conducting the Research 
PI and Co-PI are interested in the results of this study have dedicated academic time to its completion. 
15.4.2 Process for Informing Study Teams 
Not applicable.  
 
Availability of Medical or Psychological Resources 
Not applicable.  
16.0 
MULTI-SITE RESEARCH 
Not applicable.  
17.0 
REFERENCES 
1. National Research Council. The Prevention and Treatment of Missing Data in Clinical Trials. Washington, 
DC: National Academies Press, 2010.  
2. Little RJ, D'Agostino R, Cohen ML, Dickersin K, Emerson SS, Farrar JT, Frangakis C, Hogan JW, 
Molenberghs G, Murphy SA, Neaton JD, Rotnitzky A, Scharfstein D, Shih WJ, Siegel JP, Stern H. The 
prevention and treatment of missing data in clinical trials. N Engl J Med. 2012 Oct 4;367(14):1355-60.