Virtual Reality Biofeedback for Postpartum Anxiety and Depression
Phase: NA
Conditions: Anxiety and Depression, Postpartum Depression, Pregnancy Related
Sponsor: Grace Lim, MD, MS

Virtual Reality Biofeedback for Postpartum Anxiety and Depression (VITALISE) 
 
 
 
Protocol Number: 
STUDY21040063 
 
Version Date: 
09/05/2023 
Version Number: 
2 
NCT registration 
NCT04925765 
Principal Investigator: 
Dr. Grace Lim, MD, MSc 
Source of Funding: 
Internal University of Pittsburgh 
History of Protocol Versions: 
 
Version 
Date 
Sections Changed 
Rationale for the Change 
1.0 
September 1, 2021 
N/A 
IRB approval 06/03/2021 
2.0 
September 5, 2023 
Updated for clarity 
ClinicalTrials.gov update 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
v 2.0 9/5/2023 

ii 
v.2.0 9/5/2023 
 
Contents 
1 
Protocol Overview ............................................................................................................ 4 
1.1 
Study Schema ....................................................................................................................... 4 
2 
Background and Rationale .............................................................................................. 4 
2.1 
Background ............................................................................................................................ 4 
2.2 
Rationale ............................................................................................................................... 4 
3 
Hypotheses, Objectives and Endpoints .......................................................................... 5 
3.1 
Hypotheses ............................................................................................................................ 5 
3.1.1 
Primary Hypothesis ......................................................................................................... 5 
3.1.2 
Primary Aim .................................................................................................................... 5 
3.1.3 
Secondary Aim ............................................................................................................... 5 
4 
Research Design: Prospective Observational ................................................................ 5 
5 
Human Subjects ............................................................................................................... 5 
5.1 
Subject Population ................................................................................................................. 5 
5.2 
Inclusion Criteria .................................................................................................................... 5 
5.3 
Exclusion Criteria ................................................................................................................... 5 
5.4 
Recruitment Methods ............................................................................................................. 5 
6 
Research Activities .......................................................................................................... 6 
6.1 
Screening Procedures ............................................................................................................ 6 
6.2 
Research Procedures ............................................................................................................ 6 
7.1 
Reasonably Foreseeable Risks Related to Research ............................................................. 7 
7.2 
Potential Benefits ................................................................................................................... 7 
8 
Protection Against Risks ................................................................................................. 7 
8.1 
Management of research related risks ................................................................................... 7 
9 
Adverse Events and Serious Adverse Events ................................................................ 8 
9.1 
Severity .................................................................................................................................. 8 
9.2 
Relatedness ........................................................................................................................... 8 
9.3 
Expectedness ........................................................................................................................ 9 
9.4 
Reporting Serious Adverse Events ......................................................................................... 9 
10 
Withdrawal of Subjects and Stopping Rules ................................................................ 10 
10.1 
Adverse Events Requiring Discontinuation ........................................................................ 10 
10.2 
Other Criteria Requiring Discontinuation ........................................................................... 10 
11.1 
General Approach ............................................................................................................ 10 
11.2 
Sample Size Determination .............................................................................................. 10 
11.3 
Analysis of Primary Endpoint ............................................................................................ 10 
11.4 
Analysis of Secondary Endpoint ....................................................................................... 11 
12 
Data and Safety Monitoring ........................................................................................... 11 
13 
Regulatory, Ethical, and Study Oversight ..................................................................... 11 
13.1 
IRB Approval .................................................................................................................... 11 
13.2 
Informed Consent Procedures .......................................................................................... 11 
13.3 
Protocol Deviations ........................................................................................................... 12 
14 
References ...................................................................................................................... 12 

iii 
v.2.0 9/5/2023 
 
ABBREIVATIONS AND ACRONYMS 
 
 
 
 
AE 
Adverse Event 
ANX 
Anxiety 
CFR 
Code of Federal Regulations 
CRF 
Case Report Form 
DEP 
Depression 
EPDS 
Edinburgh Postnatal Depression Scale 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act 
HMD 
Head mounted display 
IRB 
Institutional Review Board 
NCT 
National Clinical Trial 
PI 
Principal Investigator 
SAE 
Serious Adverse Event 
STAI 
State-Trait Anxiety Inventory 
UPMC 
University of Pittsburgh Medical Center 
VR 
Virtual Reality 

v.2.0 9/5/2023 
 
Measure of 
current Anxiety 
& Depression 
30-minute VR session 
involved breathing exercises 
Measure of 
Anxiety & 
Depression 
1 
Protocol Overview 
 
Study Description 
This project investigated whether a VR breathing intervention would 
reduce depression and anxiety symptoms in postpartum women with a 
history of depression and anxiety. 
Study Population: 
Six postpartum women with a history of anxiety or depression. All 
women were proficient in English reading and speaking. 
Planned Sample Size: 
10 women were anticipated to participate; 6 completed the study 
protocol 
Participating 
Institutions (if a multi- 
center clinical trial) 
University of Pittsburgh, UPMC Magee Women’s Hospital 
 
1.1 Study Schema 
 
Figure 1. Timeline of all Study Procedures. 
 
 
 
2 
Background and Rationale 
2.1 
Background 
 
Cognitive behavioral therapy is a basic element of treatment for postpartum anxiety (ANX) 
and depression (DEP)1. Exacerbations of existing DEP and ANX are rising in concert with 
the COVID-19 pandemic2, with limited supply of mental health professionals that are trained 
to help these patients. Virtual Reality (VR) offers a potential solution to these care gaps, 
and VR has demonstrated success in treatment of pain, chronic disease, and other mental 
health conditions3-4. However, VR effectiveness for treatment of postpartum ANX or DEP 
has not been investigated. The purpose of this pilot trial is to test patient feasibility and 
acceptability of virtual reality biofeedback program in pregnant and postpartum women for 
ANX and DEP outcomes. 
 
2.2 
Rationale 
This study will assess the feasibility and acceptability of a headset-based virtual reality protocol 
to reduce anxiety and depression within women who have a history of anxiety or depression. 

v.2.0 9/5/2023 
 
3 
Hypotheses, Objectives and Endpoints 
3.1 
Hypotheses 
3.1.1 Primary Hypothesis 
We hypothesized that the headset-based virtual reality system would be feasible as a 
management tool for the treatment of anxiety and depression and that women would find this 
method of treatment acceptable to use. 
3.1.2 Primary Aim: 
To determine the feasibility and acceptability of the use of a virtual reality breathing 
simulation for the treatment of anxiety and depression 
3.1.3 Secondary Aim: 
To identify changes in depression and anxiety from baseline to post treatment. 
 
4 
Research Design: Prospective Observational 
Overview of Visits/Encounters with Participants: 
This is an open label, prospective pilot clinical trial. The individual patient’s active participation 
is approximately two hours. 
5 
Human Subjects 
5.1 
Subject Population 
Six postpartum women with a history of anxiety or depression participated in a single VR 
biofeedback session. 
5.2 
Inclusion Criteria 
• 
Recently postpartum (delivery within 3 months) women 
• 
Diagnosed history of anxiety or depression 
 
5.3 
Exclusion Criteria 
• 
Unable to participate in study procedures. 
• 
English illiterate 
 
5.4 
Recruitment Methods 
In conjunction with clinical teams in the outpatient clinics, Dr. Lim and the study team will 
identify patients eligible for the study, introduce the research to them, and obtain permission 
for the study team to approach them about potential participation. Dr. Lim has direct access to 
potential participants as a clinical at UPMC Magee Women's Hospital; as a consultant 
anesthesiologist Dr. Lim also has direct access to the same patients as a clinical caregiver 
and service administrative leader as the chief of obstetric anesthesia. Dr. Lim and the study 
team will work directly with clinical directors from each community practice to both identify and 
introduce the study to potential participants. 
In addition to that, University of Pittsburgh Pitt+Me Registry will be used as a recruiting tool. 
Once a participant has contacted Pitt+Me with an interest in the study, a Pitt+Me recruitment 
staff will call them for a brief pre-screen. If they pass the pre-screen and agree to be further 
contacted for additional screening, a study coordinator will directly reach out to the interested 
individual for a phone screening. 

v.2.0 9/5/2023 
 
6 
Research Activities 
 
Summary of Experimental Procedures: 
 
Utilizing head mounted display (HMD), smartphone with software rendering stereoscopic images 
to the user and heart rate/respiratory rate sensors connected and displayed. There is a 30- 
minute VR session involved breathing exercises: users saw objects in a virtual world which 
changed movements with their breathing. Measuring pre and post session anxiety and 
depression symptoms were measured by Edinburgh postnatal depression scales (EPDS) and 
State-trait anxiety inventory. Acceptability was assessed by questions, “Would you participate in 
another session?” and “would you participate in regular repeating sessions?”. 
 
6.1 
Screening Procedures 
The screening procedures pertain to specifically women with a history of anxiety and depression. 
Medical record review will be completed to identify eligible participants for this study. Medical 
record review is a minimal risk activity that presents no additional risk beyond standard of care 
procedures. Any information obtained from these medical record reviews on subjects deemed 
ineligible will be immediately destroyed. 
 
In conjunction with Dr. Lim, for patients recruited during the postpartum period, the study team 
will identify patients eligible for the study, introduce the research to them, and obtain permission 
for the study team to approach them about potential participation. As stated above, as a 
consultant anesthesiologist Dr. Lim also has direct access to the same patients as a clinical 
caregiver and service administrative leader as the chief of obstetric anesthesia. Patients will be 
identified through existing recruitment channels from the community OBGYN clinics and through 
prospective review of the OR C-section schedule. 
 
The clinical team will notify the patients of their eligibility for the study; potential participants who 
express interest in learning more about the study will be referred to the study coordinator team. 
The study team will approach and enroll them into this research. The patient will be approached 
by the study team to fully explain the study, answer any questions the patient might have, and 
obtain informed consent postpartum. 
 
6.2 
Research Procedures 
 
Baseline Assessment: 
Once informed consent is obtained subjects will complete baseline measurements which 
include a demographics form, State-Trait Anxiety Inventory (STAI), and Edinburgh Postnatal 
Depression Scale (EPDS). An intrapartum form will also be completed via medical chart review. 
 
VR Assessment: 
The VR intervention consists of three key hardware components required for use. 1) a plastic 
Virtual Reality Headset (also known as HMD: Head Mounted Display), which covers a user’s 
eyes and is secured to their head using elastic straps which can be tightened with Velcro. The 
HMD houses a 2) smartphone which runs the Flowly software and renders stereoscopic 
images which are presented to the user through the HMD. The phone connects to 3) a 
Bluetooth heart rate monitor which gathers heart rate data and clips simultaneously to the 
user’s ear lobe using a spring-loaded clip and to their clothing. 

v.2.0 9/5/2023 
 
The subject will download an app to their smartphone that will transmit data to Amazon Web 
Services managed by Tamade, LLC. Subjects will be lent an iPhone if they do not have an 
iPhone or version that can support the VR sessions. In the case that subjects do have an 
iPhone 6s/6s+ or higher (iPhone 6/6+ not eligible), they will be asked to use it for the 
completion of the study. 
 
Subjects will be given the mobile system VR Shinecon head mounted display (HMD) and 
Bluetooth sensors to provide patients Virtual Reality biofeedback sessions targeted for 
depression/anxiety. While the participant is using the VR intervention, the following outcome 
measure will be gathered: pain level, heart rate, and respiration will be taken via the device and 
smartphone app and stored in a database hosted by Amazon Web Services and managed by 
Tamade, LLC. 
 
Subjects will then complete in a 1-hour VR session. In terms of the experience of the VANISH 
intervention, most exercises focus on breathing. Users will see objects in a 3D virtual world 
which change movements with their breathing and the user will be guided to use these in 
manners that manage body responses. Breathing resonance variation will be collected from the 
subjects during these exercises using the VR device. Training on how to complete these 
breathing exercises will be initiated as a part of the device-training. 
 
Follow-up Assessment: 
To conclude, a post-assessment STAI and EPDS will be repeated, as well as post-assessment 
feasibility questionnaire. 
The subjects will participate in a total of 2-hours to complete all questionnaires and the VR 
session. 
 
7 
Potential Risks and Benefits 
7.1 
Reasonably Foreseeable Risks Related to Research 
Risk associated with collecting and storing PHI. Both common and infrequent risks include a 
loss of confidentiality. 
Risk associated with use of virtual reality devices. No common risks are noted. Infrequent 
risks include the potential for patient to feel frustration, anxiety, or uncomfortable due to the 
device visualizations. 
 
7.2 
Potential Benefits 
There is no direct benefit. 
8 
Protection Against Risks 
8.1 
Management of research related risks 
Risks are associated with screening procedures and risks associated with Breach of 
Confidentiality in the collection and storage of PHI: 
There is a risk of "breach of confidentiality" of the screening procedures. To protect against this 
risk, all screening procedures will be done by study staff who have been completely trained in 
HIPPA/privacy procedures; all information will be kept in a locked and secure location; all data 
associated with the study screening will be stored against a random study ID number; any 
linkages between study ID number and patient identification will be separated, password 

v.2.0 9/5/2023 
 
protected and stored behind UPMC firewall. To protect against the possibility of breach of 
confidentiality, all data collected will be identifiable only by a unique subject ID number, and no 
personal identifiers will be stored with data. Linkage files identifying subjects will be stored only 
in physical records that are kept in locked files accessible only by study staff; electronic data 
will be handled and protected as described above. Only consent forms will have identifiable 
information, and those will be kept in their chart separate from any data. Data will be labeled 
only with participant ID number. We will also conduct research interviews in a private room. We 
will collect only sensitive information limited to the minimum necessary to achieve the aims of 
our research. No sensitivity information will be shared via text-messages or emails. 
9 
Adverse Events and Serious Adverse Events 
The proposed observational study will use the FDA definition of SAE. A serious adverse event 
is any untoward event that is thought by either the investigator to be unexpected and at least 
possibly related to the study and results in any of the following: 
1. Death 
2. A life-threatening adverse event 
3. Inpatient hospitalization or prolongation of an existing hospitalization 
4. A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions. 
5. A congenital anomaly or birth defect 
6. Important medical events that may not result in death, be life threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical 
judgment, they may jeopardize the patient, or subject, and may require medical, or 
surgical intervention to prevent one of the serious outcomes listed above. 
 
9.1 
Severity 
The severity of adverse changes in physical signs or symptoms will be classified as follows: 
• 
Grade 1 (Mild): asymptomatic or mild symptoms; clinical or diagnostic observation only; 
intervention not indicated. 
• 
Grade 2 (Moderate): minimal, local or noninvasive intervention indicated. 
• 
Grade 3 (Severe): medically significant but not immediately life-threatening; hospitalization 
or prolongation of hospitalization indicated; disabling; limiting self-care/ADL. 
• 
Grade 4 (Life-threatening): consequences; urgent intervention indicated. 
• 
Grade 5 (Death): event is a direct cause of death. 
 
9.2 
Relatedness 
• 
Definitely Related – There is clear evidence to suggest a causal relationship, and other 
possible contributing factors can be ruled out. The event cannot be explained by concurrent 
disease or other drugs or chemicals. 
• 
Probably Related – There is evidence to suggest a causal relationship, and the influence of 
other factors is unlikely. The event occurs within a reasonable time after administration of 
the study protocol, is unlikely to be attributed to concurrent disease or other drugs or 
chemicals. 
• 
Possibly Related – There is some evidence to suggest a causal relationship (e.g., the event 
occurred within a reasonable time after administration of study protocol). However, other 
factors may have contributed to the event (e.g., the participant’s clinical condition, other 
concomitant events). Although an AE may rate only as “possibly related” soon after 
discovery, it can be flagged as requiring more information and later be upgraded to 
“probably related” or “definitely related”, as appropriate. 

v.2.0 9/5/2023 
 
• 
Unlikely to be related – An event whose temporal relationship to study protocol 
administration makes a causal relationship improbable (e.g., the event did not occur within a 
reasonable time after administration of the study protocol) and in which drugs, chemicals or 
underlying disease provides plausible explanations (e.g., the participant’s clinical condition, 
other concomitant treatments). 
• 
Not Related – The AE is completely independent of study protocol administration, and/or 
evidence exists that the event is related to another etiology. There must be an alternative, 
definitive etiology documented by the clinician. 
 
9.3 
Expectedness 
The Principal Investigator will be responsible for determining whether an AE is expected or 
unexpected. An AE will be considered unexpected if the nature, severity, or frequency of the 
event is not consistent with the risk information previously described. 
9.4 
Reporting Serious Adverse Events 
Any SAE, which is determined by the PI to be unexpected and at least possibly related to 
study, will be reported to the IRB as soon as possible. The PI report to the IRB will include all 
known details regarding the nature of the SAE. 
 
Life-threatening or fatal unexpected adverse events associated with the study procedures must 
be reported to the IRB within 24 hours of discovery of the incident with subsequent follow-up 
submission of a detailed written report in accordance with the respective policies and 
procedures of the IRB. Outcomes of SAEs will be regularly reported to the IRB. A summary of 
the SAEs that occurred during the previous year will be included in the annual progress report 
as well as in the annual IRB renewal. 
 
9.4.1 Adverse Events Reporting Timeline 
Life-threatening or fatal unexpected adverse events associated with the study must be 
reported to the IRB within 24 hours of discovery of the incident with subsequent follow-up 
submission of a detailed written report. The IRB will be notified by telephone or facsimile 
transmission of a human adverse event that is fatal or life-threatening no later than 7 calendar 
days after receiving the respective human adverse event information, followed by the 
subsequent submission of a written Safety Report. Serious and unexpected adverse events 
associated with the study protocol will be reported to the IRB with subsequent follow-up 
submission of a detailed written report in accordance with the respective policies and 
procedures of the IRB. 
9.4.2 Ensuring necessary medical/professional intervention for adverse events. 
If there is a suggestion that any research procedures have resulted in an injury to subjects, 
there will be immediate contact with the Principal Investigator who is listed on the first page of 
the informed consent documents. Emergency medical treatment for injuries solely and directly 
related to participation in this research study will be provided by the hospitals of UPMC. 
Insurance provider may be billed for the costs of this emergency treatment, but none of those 
costs will be charged directly to patients/subjects. If research-related injury requires medical 
care beyond this emergency treatment, subjects will be responsible for the costs of this follow- 
up care. Currently, there is no plan for any additional financial compensation for these events. 

v.2.0 9/5/2023 
 
10 Withdrawal of Subjects and Stopping Rules 
10.1 Adverse Events Requiring Discontinuation 
For this study, a serious adverse event is any untoward clinical event that is thought by either 
the investigator or the sponsor to be related to the study and results in any of the following 
outcomes: 
 
1. Death 
2. A life-threatening adverse event 
3. Inpatient hospitalization or prolongation of an existing hospitalization 
4. A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions. 
5. A congenital anomaly or birth defect 
6. Important medical events that may not result in death, be life threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical 
judgment, they may jeopardize the patient, or subject, and may require medical, or 
surgical intervention to prevent one of the serious outcomes listed above. 
 
If clinically important and unexpected adverse experiences or clinically important study-related 
adverse experiences occur, they will be recorded on the adverse event case report form. 
 
10.2 Other Criteria Requiring Discontinuation 
Withdrawal of Subjects for reasons other than Non-compliance or Adverse Events: 
• 
Protocol non-adherence: non-adherence at follow-up visits at the judgement of the PI 
• 
Incomplete survey data, defined as missing 20% or more responses 
11 Statistical Analysis 
11.1 General Approach 
Baseline demographic characteristics will be collected and analyzed using descriptive 
statistics. 
Feasibility of the study is measured as the number of patients who report that the study was 
both 1.) easy to use and 2.) The session was worth my time. 
Acceptability was measured as “yes” responses to both questions, “would you participate 
in another session in the future? 2. Based on your experience today, would you participate 
in regular repeating sessions (e.g., daily, or weekly)?” 
Anxiety and depression are measured as continuous variables at baseline and after VR 
intervention. Due to the small sample size, only the number (proportion) of patients whose 
overall anxiety and depression scores changed/decreased from baseline to post- 
intervention will be reported. 
 
11.2 Sample Size Determination 
This is a sample of convenience as a pilot trial. We believe five complete subjects' answers 
will give us adequate information about feasibility and some estimations on measured 
outcomes to perform a sample size calculation for the fully powered trial. 
11.3 Analysis of Primary Endpoint 
To explore the feasibility of use of Virtual Reality as a method to aid in the reduction of 
anxiety and depression in postpartum women. 

v.2.0 9/5/2023 
 
11.4 Analysis of Secondary Endpoint 
To further explore change in anxiety and depression across the trials. 
12 Data and Safety Monitoring 
Dr. Lim will be responsible for data and safety monitoring. She will meet bi-weekly with study 
personnel to review the progress of the research study, including subject recruitment and 
retention and an assessment of the timeliness and quality of the data. Dr. Lim will review all 
data, procedures, and any adverse events that occurred. All adverse events, including breach 
of confidentiality, will be reported to the IRB at minimum at the time of renewal per their policies 
and procedures. 
13 Regulatory, Ethical, and Study Oversight 
13.1 IRB Approval 
The PI obtained IRB approval STUDY21040063, from the University of Pittsburgh IRB, for the 
approval of the clinical protocol and corresponding informed consent form(s); modifications to 
the clinical protocol and corresponding informed consent forms, and advertisements (i.e., 
directed at potential research subjects) for study recruitment. 
 
The only circumstance in which a deviation from the current IRB-approved clinical 
protocol/consent form(s) may be initiated in the absence of prospective IRB approval is to 
eliminate an apparent immediate hazard to the research subject(s). In such circumstances, the 
Investigator will promptly notify the University of Pittsburgh IRB of the deviation. 
 
The IRB will review and approve the Informed Consent Document for the study and provide 
institutional oversight of data and safety issues. The study protocol will be approved prior to 
recruiting or obtaining consent from any participants. Moreover, the study will be reviewed at a 
minimum of annual basis (or more frequently as deemed necessary) by the IRB committee. 
Each participant will sign the approved Informed Consent Form prior to participating in the 
study. 
 
The University of Pittsburgh IRB operates in compliance with FDA regulations at 21 CFR Parts 
50 and 21 CFR 56, and in conformance with applicable ICH Guidelines on GCP. 
 
13.2 Informed Consent Procedures 
Details of Participant Recruitment: 
 
Medical record review will be completed to identify eligible participants for this study. Medical 
record review is a minimal risk activity that presents no additional risk beyond standard of care 
procedures. Any information obtained from these medical record reviews on subjects deemed 
ineligible will be immediately destroyed. 
In conjunction with Dr. Lim, for patients recruited during the postpartum period, the study team 
will identify patients eligible for the study, introduce the research to them, and obtain permission 
for the study team to approach them about potential participation. As stated above, as a 
consultant anesthesiologist Dr. Lim also has direct access to the same patients as a clinical 
caregiver and service administrative leader as the chief of obstetric anesthesia. Patients will be 
identified through existing recruitment channels from the community OBGYN clinics and through 
prospective review of the OR schedule. 
 
The clinical team will notify the patients of their eligibility for the study; potential participants who 

v.2.0 9/5/2023 
 
express interest in learning more about the study will be referred to the study coordinator team. 
The study team will approach and enroll them into this research. The patient will be approached 
by the study team to fully explain the study, answer any questions the patient might have, and 
obtain informed consent postpartum. 
 
In addition to that, University of Pittsburgh Pitt+Me Registry will be used as a recruiting tool. 
Once a participant has contacted Pitt+Me with an interest in the study, a Pitt+Me recruitment 
staff will call them for a brief pre-screen. If they pass the pre-screen and agree to be further 
contacted for additional screening, a study coordinator will directly reach out to the interested 
individual for a phone screening. 
Individuals will be provided with full explanation of study-related goals and procedures. 
Questions will be answered for the patient as well as their support people. Patients will be given 
as much time as they desire to read the consent form and materials and ask questions. If 
desired, patients can take materials home for review and will be consented to participate via 
videoconferencing software and electronic consent via REDCap. 
 
13.3 Protocol Deviations 
Clinical research investigators and staff will be familiarized with the study protocol, GCPs, and 
applicable federal regulations to ensure that the study protocol procedures are followed. When a 
deviation is perceived to have occurred, the procedure completed will be verified against the 
study protocol, applicable regulations and relevant GCP principles. Deviations in the study 
protocol will be identified verbally and in writing to the PI and/or study coordinator as they occur. 
In addition to deviations noticed during completion of study protocol procedures, deviations may 
be identified through routine monitoring visits or audits of the clinical research records, as the 
research team will meet weekly to review the study recruitment, procedures, and retention. All 
deviations will be verified and presented to the PI for timely assessment and IRB reporting, if 
warranted. Any deviation, regardless of severity, will be recorded in the Non- 
compliance/deviation log by the PI or research staff member as they occur. Protocol deviations 
that do not meet the definition of IRB reporting requirements will be subject to yearly review and 
evaluation during the continuing review period. 
Reportable incidence of Non-compliance includes any protocol deviation that: 
 
• 
Significantly adversely affects the safety, rights, or welfare of the research 
participants, OR 
• 
Significantly compromises the quality or integrity of the research data (i.e., negatively 
impacts the ability to draw conclusions from the study data), OR 
• 
Represents Continuing Non-compliance (i.e., has been previously reported or 
represents a pattern of ongoing non-compliance). 
 
Incidents of Non-compliance that do not meet the IRB reporting requirements will be 
documented in a Non-compliance/deviation log and managed as part of the Data and Safety 
Monitoring Plan. The Non-compliance/deviation log will be kept throughout the study and the 
documentation will be made available upon request. 
 
14 References 
1. PMID: 29914574 
2. PMID: 33964789 

v.2.0 9/5/2023 
 
3. PMID: 34036696 
4. PMID: 33952318