An Exploratory Open-Label Potency and Precision Investigation of a Relational Agent Intervention
Phase: NA
Conditions: Depression, Anxiety
Sponsor: Woebot Health

An Exploratory Open-Label Potency and Precision Investigation of a Relational 
Agent Intervention
NCT06240091
March 18, 2024

Protocol Number:
W-DISC-002
NCT Number:
NCT06240091
Date
18/MAR/2024
W-DISC-002
An Exploratory Open-Label Potency and Precision Investigation of a Relational Agent Intervention
Document Type: Clinical Trial Protocol
Clinical Trial Phase: Phase I/II
Version Number: 1.1
Property of Woebot Health
Confidential
May not be used, divulged, published, or otherwise disclosed
without the consent of Woebot Health

Woebot Health
Version 1.1
W-DISC-002
18/MAR/2024
CLINICAL STUDY PROTOCOL
An Exploratory Open-Label Potency and Precision Investigation of a Relational Agent
Intervention
Protocol Number
W-DISC-002
Investigational Product
DISC-MA
Sponsor
Woebot Health
535 Mission Street, 14th Floor
San Francisco, CA 94105
Principal Investigator
Tim Campellone, PhD
tim_campellone@woebothealth.com
Version
1.1
Date
18/MAR/2024
This study will be performed in compliance with the principles of Good Clinical Practice.
CONFIDENTIAL
2

Woebot Health
Version 1.1
W-DISC-002
18/MAR/2024
Protocol Version and Amendment Tracking
Version
Date
Brief Summary of Changes
1.0
21/DEC/2023
Original Protocol
1.1
18/MAR/2024
Updated administration timeline for the NIH Toolbox
Social Relationship scales (i.e., removed Week 2
assessment point), added in details for an optional
post trial user experience interview, and added
clarifying language around safety monitoring
procedures.
Confidentiality Statement
The information in this protocol is confidential and proprietary information of Woebot Health. It is
provided to you as a site, Investigator or consultant for review by you, your staff, and other applicable
regulatory bodies. Acceptance of this document constitutes agreement that you will not disclose the
information contained herein to others without written authorization from the Sponsor or in a way that
is inconsistent with contractual language.
CONFIDENTIAL
3

Woebot Health
Version 1.1
W-DISC-002
18/MAR/2024
Protocol Signature Page | Sponsor
This protocol has been reviewed and approved by the representative(s) listed below. Any modification of
the protocol must be agreed upon by the Sponsor and the investigator and must be documented in
writing.
Woebot Health Representative(s):
_______________________________________________________
_________________________
[Principal Investigator or Sponsor Signature]
[Signatory Date]
______________________________________________________
[Name and Title of Signatory]
CONFIDENTIAL
4

Woebot Health
Version 1.1
W-DISC-002
18/MAR/2024
Protocol Signature Page | Principal Investigator
I have read this protocol, which has been agreed by Woebot Health, and given approval/favorable
opinion by the institutional review board, and I agree that it contains all necessary details for my staff
and I to conduct this study as described. I will provide copies of the protocol and any amendments to all
study personnel under my supervision and provide access to all information provided by Woebot Health
or their specified designees. I will discuss the material with the study personnel to ensure that they are
fully informed about the study.
I understand that information contained in or pertaining to this protocol is confidential and should not
be disclosed, other than to those directly involved in the execution or the ethical review of the study,
without written authorization from Woebot Health. It is, however, permissible to provide information to
a participant in order to obtain consent.
I agree to conduct this study according to this protocol and to comply with its requirements, participant
to ethical and safety considerations and guidelines, and to conduct the study in accordance with the
Declaration of Helsinki, International Council for Harmonisation guidelines on Good Clinical Practice, and
applicable regional regulatory requirements.
I agree to comply with the procedures described for data recording and reporting and to permit
monitoring and auditing by Woebot Health and inspection by the appropriate regulatory authorities.
I agree to make my participants’ study records available to Woebot Health personnel, their
representatives, and relevant regulatory authorities in order to verify data that I have entered in the case
report forms. I will retain the study-related essential documents until Woebot Health indicates that they
are no longer needed. I am aware of my responsibilities as an investigator as provided by Woebot Health.
I understand that Woebot Health may decide to suspend or prematurely terminate the study at any time
for whatever reason; such a decision will be communicated to me in writing. Conversely, should I decide
to withdraw from execution of the study, I will communicate my intention immediately in writing to
Woebot Health.
_____________________________________________________
_________________________
[Principal Investigator Signature]
[Date]
_____________________________________________________
_________________________
[Name and Title]
[Site]
CONFIDENTIAL
5

Woebot Health
Version 1.1
W-DISC-002
18/MAR/2024
Protocol Synopsis
Protocol Number:
W-DISC-002
Full Title:
An Exploratory Open-Label Potency and Precision Investigation
of a Relational Agent Intervention
Abbreviated Title:
PAPI: Potency and Precision Investigation
Sponsor:
Woebot Health
Study Type:
Product learning
Number of Participants:
200
Number of Sites:
1
Study Objective:
The overarching goal of this study is to establish initial proof of
mechanism for precision interventions in an adult population.
Primary Aim and Endpoint:
Aim: Describe therapeutic alliance with Woebot at week 1 and
week 4 of the intervention.
Endpoints:
●
Working Alliance Inventory (WAI) total score at week 1
and WAI total score at week 4.
Secondary Aims and Endpoints:
N/A
CONFIDENTIAL
6

Woebot Health
Version 1.1
W-DISC-002
18/MAR/2024
CONFIDENTIAL
7

Woebot Health
Version 1.1
W-DISC-002
18/MAR/2024
Study Design:
Single arm pilot study
Study Duration:
4 week intervention period
Target Population:
Adults between the ages of 18 and 75 years experiencing at
least mild depression or anxiety symptoms.
Key Inclusion Criteria:
1.
Adults 18 - 75
2.
Has regular access to a smartphone (Android or iOS
smartphone with a recent supported operating system)
with reliable WiFi access or sufficient data to engage
with assigned study arm for the duration of the study
3.
Available and committed to engage with the program
and complete assessments for study duration
4.
Able to read and write in English
5.
U.S. resident
6.
PHQ-8 > 4 and/or GAD-7 > 4, assessed at
Screening/Baseline
Key Exclusion Criteria:
1.
Current suicidal ideation with a plan and/or intent or a
suicide attempt within the past 12 months
2.
Previous Woebot use
3.
Involuntary inpatient psychiatric hospitalization any
time within the past 30 days
4.
Lifetime diagnosis of bipolar disorder
5.
Lifetime diagnosis of a psychotic disorder
Study Condition:
DISC-MA
CONFIDENTIAL
8

Woebot Health
Version 1.1
W-DISC-002
18/MAR/2024
Test Device:
DISC-MA
Control Device:
N/A
Statistical Methods:
Descriptive statistics will be reported for study measures.
Summary reports will be presented for all time periods
independently.
Bivariate analyses will use chi-squared tests, Fisher exact test,
t-tests, one-way ANOVA, Person’s correlation, and Spearman’s
correlation, where applicable. No hypothesis testing will be
completed, and only effect sizes and 95% confidence intervals
will be provided where applicable. For departures from
normality, the appropriate non-parametric method will be
applied.
Protocol Version and Date:
1.1
(18
/MAR
/2024
)
Keywords:
digital mental health intervention, chatbot, conversational
agent, relational agent, natural language processing, artificial
intelligence
CONFIDENTIAL
9

Woebot Health
Version 1.1
W-DISC-002
18/MAR/2024
Table of Contents
Table 1. Schedule of Events
13
1. Introduction
14
1.1 Background
14
1.2 Study Rationale
14
1.3 Investigational Device
14
2. Objectives
15
2.1 Primary Aim
15
3. Study Design
16
3.1 Description of Trial Design
16
Figure 2: Participant Journey Flowchart
17
3.2 Rationale for Trial Design
17
4. Trial Intervention
17
4.1 Study Condition
17
4.3 Trial Intervention Compliance
18
5. Study Population
18
5.1 Selection of Study Population
19
5.1.1 Inclusion Criteria
19
5.1.2 Exclusion Criteria
19
5.2 Screen Failures
19
5.3 Withdrawal of Participants from the Study
20
6. Study Assessments and Procedures
20
6.1 Pre-Screening Procedures
21
6.2 Screening Assessments and Procedures
21
6.2.1 Identity Verification Call
21
6.2.2 Demographic Questions
21
6.2.3 Medical History
21
Prior and Concomitant Medication and Therapy
21
Psychiatric History
21
6.3 Primary Endpoint
21
Working Alliance Inventory (WAI-SR)
21
CONFIDENTIAL
10

Woebot Health
Version 1.1
W-DISC-002
18/MAR/2024
​
7. Study Stopping Rules
24
7.1 Early Study Termination
24
8. Data and Safety Monitoring
25
8.1 Risk and Benefit Assessment
25
8.1.1 Risks
25
8.1.2 Procedures for minimizing risk
25
Misunderstanding the Capabilities of the Application
25
Data Breach
25
Potential Upset due to Study Procedures
25
8.1.3 Benefits
26
8.2 Adverse Events
26
8.2.1 Definitions
26
8.2.2 Previously Noted Adverse Device Effects
28
8.3 Assessment of Adverse Events
28
8.3.1 Time Frame
28
8.3.2 AE Severity
28
8.3.3 AE Causality
29
8.3.3 AE Outcomes
29
8.4 Documenting and Reporting AE and SAEs
29
8.5 Safety Monitoring
29
8.5.1 Safety Procedures At Screening
29
8.5.2 Unscheduled Visits
30
8.5.3 Safety Event Solicited Self-Report Survey
30
8.5.4 Language Detection Protocol (LDP)
30
CONFIDENTIAL
11

Woebot Health
Version 1.1
W-DISC-002
18/MAR/2024
8.6 Safety Assessment Committee (SAC)
32
8.6.1 Risk and Quality Tolerance Limits
33
8.7 Quality Control and Quality Assurance
33
9. Statistical Analysis
33
9.1 General Methodology
33
9.2 Analysis Sets
33
9.3 Sample Size Determination
34
10. Statistical Methods
34
10.1 Primary Endpoint
34
10.1.1 Aim
34
10.1.2 Hypothesis
34
10.1.3 Endpoints
34
10.1.4 Analysis Plan
34
10.3 Safety Endpoints
35
10.3.1 Aims and Endpoints
35
10.3.2 Analysis of Safety
35
10.4 Demographic and Baseline Characteristics
35
10.5 Handling of Missing Values
35
11. Ethics and Responsibilities
36
11.1 Good Clinical Practice
36
11.2 Institutional Review Board
36
11.3 Informed Consent
36
12. Records Management
37
12.1 Source Documentation
37
12.2 Case Report Form Completion and Data Management
38
12.3 Study Files and Record Retention
38
13. Auditing and Monitoring
39
13.1 Protocol Adherence and Deviations
39
14. Amendments
40
15. Study Start and Termination
40
16. Confidentiality
40
17. References
42
CONFIDENTIAL
12

Woebot Health
Version 1.1
W-DISC-002
18/MAR/2024
Table 1. Schedule of Events
Visit Weeks/Days
Screening Period
Intervention Period
Screening / Baseline
Day -14 to Day 1
Week 1
Day 7 (+6)
Week 2
Day 14 (+6)
Week 4
Day 28 (+6)
Informed Consent (asynchronous e-Consent
via Citrus)
X
Participant Identity Verification a
X
Eligibility Confirmation (inc/exc) b
X
Demographics b
X
Medical History | Prior & Concomitant
Medications/Therapy b
X
Medical History | Psychiatric History b
X
The Accountable Health Communities
Health-Related Social Needs Screening Tool b
X
App Download / Registration c
X
Working Alliance Inventory (WAI-SR) b
X
X
Safety Survey b
X
X
Assessment of AE/SAEs
X
Enactment c
X
App Engagement Metrics c
X
Termination of App Access c
X
Estimated Time to Complete
45 minutes
15 minutes
30 minutes
30 minutes
a Live video call with Lindus Health trial team b Self-report through Citrus platform c Study app
Participants will have up to two weeks from the time of providing informed consent to complete all screening and
baseline tasks including registering for the study application. Participants will be considered a screen fail and removed
from the study for failing to register for the app by Day 3.
CONFIDENTIAL
13

Woebot Health
Version 1.1
W-DISC-002
18/MAR/2024
1. Introduction
1.1 Background
Precision medicine is defined by the Food and Drug Administration as “...to target the right treatments to
the right patients at the right time”1. In the context of mental health, the goal of a precision medicine
approach is to use the various tools and data to develop more effective and safe treatments2. Digital
mental health interventions are uniquely positioned to create and deliver precision interventions that
follow this FDA definition by being able to deliver in a standardized way fit for purpose interventions that
target mechanisms for specific users at specific moments of the user journey.
1.2 Study Rationale
The overarching goal of this study is to inform the development of precision interventions within the
Woebot for Mood and Anxiety investigational product. This study will provide initial learning on the
current implementation of precision interventions and generate data and hypotheses to inform the
exploration of future interventions by identifying mechanisms and moments in the user journey to
target.
1.3 Investigational Device
DISC-MA is a discovery version (3.2) of the investigational product Woebot for Mood and Anxiety and is a
non-prescription digital software device, accessible via iOS and Android smartphone operating systems.
CONFIDENTIAL
14

Woebot Health
Version 1.1
W-DISC-002
18/MAR/2024
2. Objectives
2.1 Primary Aim
●
Describe therapeutic alliance with Woebot at week 1 and week 4 of the intervention.
●
Primary Endpoints:
○
Working Alliance Inventory (WAI) total score at week 1 and WAI total score at week 4.
CONFIDENTIAL
15

Woebot Health
Version 1.1
W-DISC-002
18/MAR/2024
3. Study Design
3.1 Description of Trial Design
This study is a single arm pilot trial aimed at exploring and informing precision interventions within the
Woebot for Mood and Anxiety investigational device. Study participation is up to 7 weeks in total,
including a 2 week screening/baseline phase, followed by a 4 week active intervention phase, and 1
week to complete the final study survey.
Participants will be recruited and enrolled into the study by Lindus Health. All remaining data collection
and study monitoring will be managed through the Citrus decentralized trial platform managed by Lindus
Health and by designated Woebot Health study personnel.
Self-report survey assessments will be administered to all participants at Screening/Baseline, Week 1,
Week 2, and Week 4. Members of the study team may contact participants through the Citrus platform
via phone/sms and/or email to remind participants to complete study activities.
CONFIDENTIAL
16

Woebot Health
Version 1.1
W-DISC-002
18/MAR/2024
Figure 2: Participant Journey Flowchart
3.2 Rationale for Trial Design
This trial design will allow for characterization of participants at baseline in order to better understand
and generate hypotheses about how these characteristics interact with patterns of engagement within
the Woebot for Mood and Anxiety investigational product.
4. Trial Intervention
4.1 Study Condition
All participants will have access to the same trial intervention, DISC-MA, for 4 weeks. The trial
intervention will be accessed through a mobile app and will be made available exclusively for study
participants through unique access codes.
CONFIDENTIAL
17

Woebot Health
Version 1.1
W-DISC-002
18/MAR/2024
4.3 Trial Intervention Compliance
Participants will be removed from the study and considered a “screen failure” for failing to register for
the app by Day 3. Trial intervention compliance will not be monitored during the live trial and
participants will not be withdrawn for not regularly engaging with their assigned treatment. Instead,
intervention compliance will be assessed post study during analysis. Compliance may be defined as
opening the app at least once per week for a minimum of 50% of weeks (2 of 4) during the intervention
period.
5. Study Population
Participants will be recruited through the Lindus Health CitrusRecruit network which utilizes a
combination of participant sources including but not limited to existing patient databases, primary care
networks, and targeted social media campaigns. Those interested in participating will be invited to
complete a survey to confirm they meet the pre-screening criteria and be presented with the
opportunity to independently review and electronically sign the study consent form. Upon signing the
consent form, participants will be asked to schedule a video call during which a designated member of
the Lindus Health trial team will verify the participants identity. After successful completion of the
verification call, participants will be provided with a secure link to complete the screening/baseline
survey. In order to further assess eligibility, participants will be asked questions about their medical
history including self-report of (1) any involuntary inpatient psychiatric hospitalizations within the past
30 days, (2) a lifetime diagnosis of bipolar disorder, (3) a life time diagnosis of a psychotic disorder, and
CONFIDENTIAL
18

Woebot Health
Version 1.1
W-DISC-002
18/MAR/2024
(4) current suicidal ideation with plan and/or intent or an attempt in the past 12 months. People who do
not meet study criteria based on these additional exclusionary criteria will be notified that they may
benefit from a level of care beyond the scope of the study and that if they feel they are in need of
immediate medical care they should contact 911 or go to their nearest emergency room and reach out
to someone they trust and that can help them stay safe. Additional resources will also be provided
electronically. If a participant endorses presence of current suicidal plan and/or intent, the study PI will
attempt to follow-up with the participant (up to three times). See Section 8.5.1 of this protocol for more
details.
5.1 Selection of Study Population
The study aims to enroll approximately 200 adults between the ages of 18 and 75 years experiencing at
least mild depression or anxiety symptoms into the study. An enrolled participant is defined as a
participant that meets all eligibility criteria as described below and registers in the app by Day 3 of the
study.
5.1.1 Inclusion Criteria
In order to be eligible to participate in this study, an individual must meet all of the following criteria:
1.
Adults between the ages of 18 and 75 years
2.
Own or have regular access to a smartphone with a recent operating system installed (Android:
0S 8.0 or higher, Apple: iOS 13.0 or higher) with reliable Wi-Fi access or sufficient data plan to
engage with assigned treatment condition for the duration of the study
3.
Available and committed to engage with the program and complete assessments for a 4-week
duration
4.
Able to read and write in English
5.
U.S. resident
6.
PHQ-8 > 4 and/or GAD-7 > 4, assessed at screening/baseline
5.1.2 Exclusion Criteria
An individual who meets any of the following criteria will be excluded from participation in this study:
1.
Current suicidal ideation with a plan and/or intent or a suicide attempt within the past 12
months
2.
Previous Woebot use
3.
Involuntary inpatient psychiatric hospitalization any time within the past 30 days
4.
Lifetime diagnosis of bipolar disorder
5.
Lifetime diagnosis of a psychotic disorder
5.2 Screen Failures
Participants who sign study consent and (1) do not meet inclusion/exclusion criteria or (2) fail to register
in the app by Day 3, will be considered a Screen Failure. Participants will be notified that they did not
meet eligibility criteria and provided with a set of resources. Re-screens will not be permitted in this
study. De-identified participant ID numbers assigned to participants who screen fail will not be reused.
CONFIDENTIAL
19

Woebot Health
Version 1.1
W-DISC-002
18/MAR/2024
5.3 Withdrawal of Participants from the Study
If a participant decides to withdraw consent from the study, they will be removed from future study
activities and any data collected before withdrawal may be retained and used in study analyses. In
addition, a participant may be withdrawn by the investigator if the participant violates the study plan, or
for administrative and/or other safety reasons.
Discontinuation of study treatment for a participant occurs when study treatment is stopped earlier than
the protocol planned duration and can be initiated by either the participant or the investigator. The
investigator must discontinue study treatment for a given participant if he/she believes that continuation
would negatively impact the participant’s well-being. Involvement in the study is strictly voluntary.
Participants have the right to withdraw from the study at any time for any reason, without any reprisal.
Participants should be discontinued from the study if any of the following occur:
1.
It is discovered that the participant shared app images/screenshots publicly
2.
The participant withdraws consent to participate in the study
3.
The participant develops an illness that would interfere with their continued participation in the
study
4.
The participant has an SAE rated as Grade 3 (severe) or higher (see Section 8.3.2)
5.
The participant is noncompliant with treatment schedule, study procedures, in the opinion of
the investigator and per the protocol, where applicable
6.
The PI, Sponsor, IRB, or regulatory agency requests withdrawal of the participant
7.
Any other reason relating to the participant's safety or integrity of the study data as determined
by the Safety Assessment Committee (SAC)
Participants who withdraw or are withdrawn from the study may be replaced. Participants who withdraw
or are withdrawn from the study cannot subsequently rejoin the study.
If a participant withdraws or is withdrawn from the study for reasons related to safety, the study
Sponsor-Investigator and SAC will be informed immediately.
If the participant withdraws consent for disclosure of further information, the Sponsor-Investigator may
retain and continue to use any collected data before such a withdrawal of consent.
Although a participant is not obliged to give a reason for withdrawing from a study, the investigator
should make a reasonable effort to ascertain the reason, while fully respecting the participant's rights.
6. Study Assessments and Procedures
All assessments, and their corresponding administration points, are listed in Table 1.
CONFIDENTIAL
20

Woebot Health
Version 1.1
W-DISC-002
18/MAR/2024
6.1 Pre-Screening Procedures
Participants will have the opportunity to learn about the study through digital recruitment efforts.
Interested participants will complete a pre-screening survey to determine preliminary eligibility ahead of
consent. Eligible participants at this stage will then proceed to review and sign the eICF.
6.2 Screening Assessments and Procedures
6.2.1 Identity Verification Call
After passing pre-screening criteria and signing the study eICF, participants will be asked to schedule an
identity verification video call with a member of the Lindus Health study team. During this call the
designated member of the study team will ask the participant to verify their identity (e.g., show a
government issued ID) as well as confirm their contact information and DOB.
6.2.2 Demographic Questions
In an effort to ensure equitable access and representation as well as assess clinical efficacy in diverse
populations, Woebot Health has researched current best practices and language around demographic
data collection, and developed a health equity demographic battery. The demographic battery consists
of age, biological sex, gender identity, sexual orientation, race, ethnicity, education, marital status,
employment status, living situation, able bodiedness, physical health conditions, and health insurance
status.
6.2.3 Medical History
Prior and Concomitant Medication and Therapy
Participants will be asked to complete questions evaluating whether they are currently seeing a mental
health professional (i.e., therapist, social worker), whether they are currently taking any psychotropic
medications, as well as satisfaction with concurrent mental health treatment.
Psychiatric History
Participants will be asked to complete questions about their history of diagnosed mental health
disorders including self-report of a lifetime diagnosis of bipolar disorder and/or a psychotic disorder as
well as whether they have current suicidal ideations with plan and/or intent or if they have had a suicide
attempt in the past 12 months. Participants will also be asked to endorse whether they have experienced
any involuntary inpatient psychiatric hospitalizations within the past 30 days.
6.3 Primary Endpoint
Working Alliance Inventory (WAI-SR)
The WAI-SR5 is a measure of therapeutic bond and consists of a composite score and three subscales;
Bond, Goal, and Task. Bond measures the strength of the therapeutic relationship between the client
and therapist. Goal measures agreement on the goal of the overall therapeutic program between the
client and therapist. Task measures agreement between the client and therapist, regarding the specific
activities needed for a therapeutic change to occur such as doing an exercise to ameliorate a specific
CONFIDENTIAL
21

Woebot Health
Version 1.1
W-DISC-002
18/MAR/2024
symptom3. The present study utilized the validated 12-item Short Revised version (WAI-SR) with minor
changes to language, replacing “therapist” with the name of the assigned treatment group.
CONFIDENTIAL
22

Woebot Health
Version 1.1
W-DISC-002
18/MAR/2024
CONFIDENTIAL
23

Woebot Health
Version 1.1
W-DISC-002
18/MAR/2024
7. Study Stopping Rules
Study procedures will be stopped if the Sponsor-Investigator, in discussion with the SAC and/or IRB as
applicable, determines that the number and/or severity of AEs justify putting the study on hold.
The study may resume following the safety review, if the Sponsor-Investigator agrees it is safe to
proceed.
The Sponsor-Investigator may initiate study closure at any time, provided there is reasonable cause and
sufficient notice is given in advance of the intended termination.
7.1 Early Study Termination
The study can be terminated by the Sponsor-Investigator at any time. Reasons for early termination
include:
●
Study recruitment or retention is too low for the study to provide meaningful results
●
Unanticipated, significant, or unacceptable safety risk to participants enrolled in the study
●
Decision based on recommendations from Sponsor-Investigator and SAC after review of safety
and efficacy data
●
Discontinuation of study if Sponsor-Investigator, in collaboration with study team members and
SAC, determine from planned analyses that the app is not efficacious or if there are safety
concerns.
CONFIDENTIAL
24

Woebot Health
Version 1.1
W-DISC-002
18/MAR/2024
In making the decision to terminate, the Sponsor-Investigator and SAC will always consider the
participants’ welfare and safety. Should early termination be necessary, participants must be contacted
as soon as possible to conduct EOS assessments, if willing, and treated as a prematurely withdrawn
participant. Additional procedures may be provided to ensure that adequate consideration is given to
the protection of the participant’s interests. The Sponsor-Investigator will be responsible for informing
IRB of the early termination of the trial.
8. Data and Safety Monitoring
8.1 Risk and Benefit Assessment
8.1.1 Risks to Participants
Given that the research aims to enroll participants into a low-risk intervention, we do not anticipate that
participation in the study will be associated with elevated risk.
The overall
evaluation of risk is that it is low.
8.1.2 Procedures for minimizing risk
Misunderstanding the Capabilities of the Application
DISC-MA is not intended to be a crisis service, however there is the potential that participants may
misunderstand the limitations of the app. To mitigate this risk, the study will provide clear information
on the capabilities of the app, intended use, and limitations of the app at consent, treatment
assignment, and key points throughout. Resources are also accessible within the app as well and will be
sent to the participant in the event that they are requested.
Data Breach
All study data are gathered on either a HIPAA-compliant web platform that resides behind Woebot
Health security firewalls or via HIPAA-compliant online platforms, thus actual risk from data breach for
study data is low. Research material obtained from human subjects will include self-report
questionnaires and conversations and engagement data within the mobile app. All data obtained via
Woebot will be encrypted and stored on Amazon Web Services (AWS) and/or Google Cloud Platform;
Woebot Health data gathering and storage procedures are compliant with both HIPAA and the European
Union's General Data Protection Regulation. Only members of the research team will have access to
identifiable study data. De-identified data will be accessible to the product development team
(designers, user researchers, and product managers) as well as the research team.
Potential Upset due to Study Procedures
Foreseeable risks to participants include the possibility that some assessment questions and/or
treatment procedures may be upsetting to participants. Experience with similar populations has
indicated that the risk of emotional upset during the assessments is low and if it occurred, the upset
would likely be temporary and not be serious in nature. Such risks will be minimized by the thoughtful
selection of questionnaires. Participants will also be informed that they may withdraw from the study at
any time and if requested, appropriate resources will be provided.
CONFIDENTIAL
25

Woebot Health
Version 1.1
W-DISC-002
18/MAR/2024
There is also a potential risk for upset upon discontinued access to the study intervention at end of
treatment/study (Week 4). Participants are informed during the consent process and are reminded at
onboarding of how long they will have access to the intervention for. Return to care and other resources
are provided upon removing access to DISC-MA. 
Participants can refuse and withdraw from participation at any time. If they withdraw consent from the
study, they will no longer have access to the study treatment.
8.1.3 Benefits
When evaluating the risks and benefits of the proposed study, it is believed that risks are relatively
minimal when compared to the potential
benefits that subjects are likely to receive. The
benefits of engaging with DISC-MA include potentially improving mood (anxiety, stress, and/or
depression), acquiring practical psychotherapeutic skills (from cognitive behavioral therapy, dialectical
behavior therapy, and mindfulness), and receiving psychoeducation about mental health.
Participants who improve mood may derive additional benefits should said mood improvements be
associated with other psychological improvements such as interpersonal or occupational functioning.
Study of the effectiveness of this intervention will also benefit society more generally by providing data
on the utility of Woebot.
8.2 Adverse Events
8.2.1 Definitions
Adverse Event (AE): An AE is any unanticipated medical occurrence in a clinical study participant using an
investigational product or from study procedures that does not necessarily have a causal relationship
with this product. An AE can therefore be any unfavorable and unintended sign (including an abnormal
laboratory finding), symptom, or disease temporally associated with the use of an investigational
product, whether or not related to the investigational product.
Serious Adverse Event (SAE): An SAE is any AE that meets any of the following criteria:
●
Results in death
●
Is life-threatening
●
Requires inpatient hospitalization or prolongation of existing hospitalization
●
Results in persistent or significant disability/incapacity
●
Is a congenital anomaly/birth defect
●
Is an important medical event that may not result in death, be life-threatening, or require
hospitalization may be considered a serious adverse event 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 outcomes listed above.
Unanticipated Problem (UAP): A UAP is an incident, experience, or outcome that meets all of the
following criteria:
CONFIDENTIAL
26

Woebot Health
Version 1.1
W-DISC-002
18/MAR/2024
●
Unexpected in nature, severity, or frequency (i.e., not described in study-related documents such
as the IRB- or IEC-approved protocol or consent form)
●
Related or possibly related to participation in the research (i.e., possibly related means there is a
reasonable possibility that the incident experience or outcome may have been caused by the
procedures involved in the research)
●
Suggests that the research places subjects or others at greater risk of harm (including physical,
psychological, economic, or social harm)
An individual AE observed during the conduct of a study may be considered an unanticipated study
problem involving risk to human subjects, and reported to the IRB, only if it is unexpected, serious, and
would have implications for the conduct of the study (e.g., requiring a significant and, usually,
safety-related change in the protocol such as revising the inclusion/exclusion criteria or including a new
monitoring requirement or informed consent). Investigators should report possible UAP to the Sponsor
and the Sponsor will make a determination for the UAP in the context of the study and any change to the
study.
Adverse Device Effect (ADE): Any adverse event related to the use of an investigational medical device.
This includes any adverse event resulting from insufficiencies or inadequacies in the instructions for use,
the deployment, the implantation, the installation, the operation, or any malfunction of the
investigational medical device. This also includes any event that is a result of a use error or intentional
misuse.
Unanticipated Adverse Device Effect (UADE): Any serious adverse effect on the health or safety, or any
life-threatening problem or death caused by or associated with a device which was not previously
identified in nature, severity or degree of incidence in the protocol, Instructions for Use, Summary of
Previous Studies Document, or other sources of information for the investigational product. Additionally,
a UADE is any other unanticipated serious problem associated with the investigational device that relates
to the rights, safety, or welfare of subjects.
UADEs will include events meeting either A or B as stated below:
A. Events meeting ALL of the following criteria:
●
Not included in the list of Anticipated Events (refer to protocol section 8.2.2)
●
Related (possibly, probably, or definitely) to the investigational device per the site
principal investigator
●
Serious (meets any of the SAE criteria)
B. Any other unanticipated serious problem associated with the investigational device that
relates to the rights, safety, or welfare of participants.
Device Deficiencies: Inadequacy of a medical device related to its identity, quality, durability, reliability,
safety or performance, such as malfunction, misuse or use error and inadequate labeling. The reporting
of a Device Deficiency is a Product Complaint.
CONFIDENTIAL
27

Woebot Health
Version 1.1
W-DISC-002
18/MAR/2024
Product Complaints: Any written, electronic, or oral communication that alleges deficiencies related to
the identity, quality, durability, reliability, safety, effectiveness, or performance of a device after it is
released for distribution.
8.2.2 Previously Noted Adverse Device Effects
Any ADE that is not identified in nature, severity, or is not listed below is considered unanticipated:
●
Temporary upset may occur as a result of discontinued access to DISC-MA at the end of the
study.
●
Given that the study involves use of a smartphone application, there is the small possibility of
unintended application outages.
8.3 Assessment of Adverse Events
The investigator will be alert to any complaints or adverse reactions that arise and will take appropriate
steps to Reduce the impact of any event
. Existing disclaimers that DISC-MA is not intended for crisis
management will be presented in the ICF and at onboarding. AEs may be received/identified
via:
1)
Spontaneous participant self reports communicated outside of the app
2)
Solicited participant self reports collected via the Week 2 and Week 4 survey
3)
Upon review of select conversations/transcripts with Woebot
Upon learning of a potential safety event, all relevant trial data will be compiled by a designated
member of the study team and shared with the investigator. All events which meet criteria for an
AE/SAE/UAP/UADE/Device Deficiency will be recorded by the PI or designee on the appropriate
electronic Case Report Form (eCRF) and will follow a predetermined safety protocol as outlined in a
Safety Management Plan (SMP).
8.3.1 Time Frame
Collection of AEs and SAEs will begin at ICF signature, and will continue through EOS at Week 4.
Identification of any collected AEs/SAEs from transcript or LDP reviews is anticipated to be completed no
earlier than 1 month following the last patient visit and no longer than 4 months from the last patient
visit or until all data has been monitored and query cleaned.
8.3.2 AE Severity
If possible, investigators should report event terms that reflect a single, unifying diagnosis rather than
individual signs or symptoms (e.g., “influenza” instead of “coughing, body aches, fever;” and “anemia”
rather than “low hemoglobin”). A corresponding severity grading is to be performed by the investigator
based on his/her best medical judgment as follows:
●
Mild (Grade 1): asymptomatic or mild symptoms; clinical or diagnostic observations only;
intervention not indicated
●
Moderate (Grade 2): minimal, local, or noninvasive intervention indicated; limited
age-appropriate instrumental activities of daily living (ADL)
CONFIDENTIAL
28

Woebot Health
Version 1.1
W-DISC-002
18/MAR/2024
●
Severe (Grade 3): medically significant but not immediately life-threatening; hospitalization or
prolongation of hospitalization indicated; disabling; or limiting self-care ADL
●
Life-threatening (Grade 4): life-threatening consequences; urgent intervention indicated
●
Fatal (Grade 5): death related to an AE
8.3.3 AE Causality
An event’s relatedness to the investigational device will be determined by the Principal Investigator and
classified under the following causality ratings:
●
Non-related: There is no evidence of any causal relationship.
●
Related: There is clear evidence of a casual relationship between the device and event; all other
explanations have been ruled out.
8.3.3 AE Outcomes
The Investigator should document the outcome of AE and SAEs as:
●
Resolved
●
Resolved with sequelae / chronic condition, no resolution expected
●
Ongoing
●
Death
●
Ongoing at time of death
●
Unknown
8.4 Documenting and Reporting AE and SAEs
Designated members of the study team will report any identified potential safety events to the
investigator within one business day from awareness. The investigator should seek
to obtain
information required to make a determination of causality
and must assess the relationship of the
event to the study device and complete the AE/SAE eCRF. Relevant follow up information
should be
updated as collected.
Any event that the Sponsor-Investigator determines is/are reportable to the IRB will be reported
within 5 working days from making that determination. If it should be determined that an event presents
an unreasonable risk to all participants, the study or parts of the study presenting that risk will be
terminated as soon as possible.
8.5 Safety Monitoring
8.5.1 Safety Procedures At Screening
At screening, s
tudy participants will be asked to self-report on recent suicidal thoughts including
current suicidal ideation with plan and/or intent as well as attempts in the past 12 months. Responses
are not monitored in real time. Participants who endorse having a current suicidal plan or intent or an
attempt in the past 12 months will be excluded from the study. Participants will be notified that:
CONFIDENTIAL
29

Woebot Health
Version 1.1
W-DISC-002
18/MAR/2024
●
They may benefit from a level of care beyond the scope of the study and investigational
treatment.
●
They should call 9-1-1 or go to their local emergency room and reach out to someone they trust
and can help them stay safe if they feel they are in crisis or in need of medical attention.
●
Will be electronically provided with a list of resources.
Participants who endorse current suicidal ideation with a plan or intent will also be notified that a
member of the study team will attempt to follow-up with them. Three attempts will be made by the
Study PI to contact participants by phone and/or email. The study team will make every effort to
follow-up with the participant as soon as possible and no more than 3 business days following
the
initial report.
8.5.2 Unscheduled Visits
Study participants are able
to initiate contact with the study team at anytime throughout the duration
of the study. If the contact is attributable to safety reasons or if the study team learns about a suspected
safety event at any time, then an Unscheduled Visit would ensue, wherein the qualified study personnel
would attempt to follow-up with the participant, and if it is determined that they are in immediate risk
for hurting themselves or others, appropriate steps would be taken as outlined in the study specific
Safety Management Plan (SMP).
8.5.3 Safety Event Solicited Self-Report Survey
Study participants will be asked to self-report on potential safety events at the Week 2 and Week 4
timepoints. Questions will explicitly ask about changes in the past two weeks to their (1)medication
and/or therapy, (2) mental and/or physical health, and (3) any new thoughts about ending their life
including new intent/plan/or attempts. Information gathered through this survey will be used to inform
the need for follow-up, AEs/SAEs/UAPs/UADEs/Device Deficiencies/UADE determination, and resolution.
8.5.4 Language Detection Protocol (LDP)
In addition to the onboarding screens re-stating that Woebot is not a crisis service, DISC-MA has a
Language Detection Protocol (LDP), developed by Woebot Health.
The purpose of the LDP is to detect
potentially concerning topics within participant-input free-text and will be enacted for all participants in
the study
. Upon detection of any concerning topics, LDP initiates a conversation to remind the
participant of the application's limitations of services and offer a resource list which includes readily
accessible support channels. If a possible mention of concerning topics is detected, the participant is
reminded of the limitations of services (which they will have already seen in both the informed consent
and well as Woebot’s onboarding screens) as well as offered a list of external-to-application resources,
specifically contact information, that have been curated in consultation with suicide prevention experts.
This resource list includes emergency contact phone numbers, and suicide ideation and domestic
violence hotline information. 
CONFIDENTIAL
30

Woebot Health
Version 1.1
W-DISC-002
18/MAR/2024
 
CONFIDENTIAL
31

Woebot Health
Version 1.1
W-DISC-002
18/MAR/2024
8.6 Safety Assessment Committee (SAC)
The SAC is the formal WH committee charged with responsibility for the review and evaluation of
previous as well as accumulating data from clinical studies of WH devices, to assess safety, perform
signal confirmation and risk assessment, assess the risk-benefit associated with study continuation,
efficacy and other trial conduct issues such as scientific merit, and to develop recommendations so as to
ensure safety across studies and minimize risk for subjects.The SAC members will include the following
individuals:
1.
Independent Medical Safety Expert, who will serve as the SAC Chair;
2.
A Clinical Development Lead;
3.
a Medical Lead;
4.
a Regulatory Lead;
5.
a Device Vigilance Lead
Validated, accurate and interpretable data are to be provided to the SAC, as requested. Data files to be
used for SAC analyses will undergo established data review/QC procedures to the extent possible and
critical fields will be identified. The Sponsor must ensure that data is of sufficient quality to support the
performance of safety surveillance and confirm the assessment of causality associated with the event(s),
the associated WH application and confirmation of reportability.
The SAC will determine whether any missing data will significantly impact the safety assessment and will
direct the necessary actions to address missing data.
CONFIDENTIAL
32

Woebot Health
Version 1.1
W-DISC-002
18/MAR/2024
8.7 Quality Control and Quality Assurance
The Sponsor maintains a robust Quality Management System (QMS) that includes all activities involved
in quality assurance and quality control per 21 CFR 820, to ensure compliance with written SOPs as well
as applicable global/local GCP regulations and ICH Guidelines.
Audits of investigator sites, vendors, and Sponsor systems are performed by auditors, independent from
those involved in conducting, monitoring, or performing quality control of the clinical trial. The clinical
audit process uses a knowledge/risk-based approach.
Audits are conducted to assess 21 CFR 820 and GCP compliance with global and local regulatory
requirements, protocols and internal SOPs and are performed according to specified Sponsor processes.
9. Statistical Analysis
9.1 General Methodology
Given the exploratory nature of this study, and its hypothesis-generating purpose, analyses will be
descriptive in nature and will not include significance testing. Descriptive statistics for all endpoints will
be reported for the full sample. All continuous variables will be tested for normality using a skewness
cutoff of 1.00. For continuous variables, means and standard deviations will be reported if the data are
normally distributed; for non-normal data, medians and interquartile ranges will be reported.
Frequencies and percentages will be reported for categorical variables. The amount of missing data will
be summarized. Where applicable, bivariate comparisons will be conducted using chi-squared tests,
Fisher exact test, t-tests, one-way ANOVA, Person’s correlation, and Spearman’s correlation. However, no
hypothesis testing will be completed, and only effect sizes and 95% confidence intervals will be provided
where applicable. For departures from normality, the appropriate non-parametric method will be
applied.
9.2 Analysis Sets
Primary analyses will be completed on two sets of data - the full intent-to-treat (ITT) sample of anyone
randomized with available survey data, as well as a per-protocol (PP) sample (i.e., registered for app,
completed all assessment timepoints, no protocol deviations, etc).
9.3 Sample Size Determination
No formal sample size calculations were performed due to the exploratory nature of this study; however,
N=200 was targeted to allow for a large enough sample to sufficiently explore potency and precision
patterns, and certain health equity outcomes (depending on sample diversity and attrition).
CONFIDENTIAL
33

Woebot Health
Version 1.1
W-DISC-002
18/MAR/2024
10. Statistical Methods
10.1 Primary Endpoint
10.1.1 Aim
Describe therapeutic alliance with Woebot at week 1 and week 4 of the intervention.
10.1.2 Hypothesis
Understanding aspects of the working alliance between users and Woebot at both the beginning and
end of treatment will provide hypotheses for the future development of precision interventions.
10.1.3 Endpoints
Therapeutic alliance will be measured by the Working Alliance Inventory (WAI) total scale score at week
1 and WAI total scale score at week 4.
10.1.4 Analysis Plan
Descriptive statistics will be used to describe therapeutic alliance at week 1 and week 4 of the
intervention. Descriptive statistics will also summarize socio-demographic characteristics of the sample.
CONFIDENTIAL
34

Woebot Health
Version 1.1
W-DISC-002
18/MAR/2024
10.3 Safety Endpoints
10.3.1 Aims and Endpoints
The safety profile of DISC-MA will be investigated as an exploratory aim and measured through:
●
Frequency of AE/SAE/UADEs
○
Spontaneous participant report of safety events that are determined to be an
AE/SAE/UADE
○
Direct participant self-report of safety events at the Week 2 and Week 4 survey that are
determined to be an AE/SAE/UADE
○
Transcript reviews that detect safety events and are determined to be an AE/SAE/UADE
10.3.2 Analysis of Safety
To observe and describe upon the utilization and outcomes of the safety procedures utilized within this
study (e.g.,
AE/SAEs and device relatedness). For each safety endpoint, n(%) will be
reported.
10.4 Demographic and Baseline Characteristics
Demographic and baseline characteristics will be summarized for the full sample. Continuous variables
will be summarized using tables of descriptive statistics, with normally distributed variables summarized
by mean and standard deviation and non-normal data summarized by median and interquartile range
(IQR). Categorical and ordinal variables will be described using frequencies and percentages.
10.5 Handling of Missing Values
Frequencies of missing values will be indicated in all descriptive tables, and no imputation or other
statistical manipulation will be used for missing values.
11. Ethics and Responsibilities
11.1 Good Clinical Practice
This study will be conducted in accordance with the Note for Guidance on GCP ICH Harmonised Tripartite
Guideline E6 (R1)/Integrated Addendum E6 (R2); US FDA Code of Federal Regulation (CFR) (Title 21 Parts
50, 56, 312); the general guidelines indicated in the Declaration of Helsinki; and all applicable regulatory
requirements.
CONFIDENTIAL
35

Woebot Health
Version 1.1
W-DISC-002
18/MAR/2024
11.2 Institutional Review Board
The final study protocol, including the final version of the ICF, must be approved, or given a favorable
opinion in writing from the IRBs as appropriate. A written approval from the IRB is required for any study
protocol amendment(s), ICF updates, participant recruitment procedures (e.g., advertisements), and any
written information to be provided to participants and a statement from IRB to ensure compliance with
GCP requirements (if applicable). The investigator is required to sign a protocol signature page
confirming their agreement to conduct the study in accordance with the document and all of the
instructions and procedures found in this protocol and to give access to all relevant data and records to
Sponsor monitors, auditors, Sponsor Quality assurance representatives, designated agents of Sponsor,
IRBs, and regulatory authorities as required.
The IRB approval must identify the protocol version as well as the documents reviewed. Any
amendments to the protocol will require IRB approval before the implementation of the changes made
to the study, except for changes necessary to eliminate an immediate hazard to the study participants.
The investigator will be responsible for the following:
●
Providing written summaries of the status of the study to the IRB annually or more frequently in
accordance with the requirements, policies, and procedures established by the IRB
●
Notifying the IRB of SAEs or other significant safety findings as required by IRB procedures
●
Providing oversight of the conduct of the study at the site and adherence to the requirements of
all applicable regulations
●
Promptly reporting deviations from, or changes to, the protocol to eliminate immediate hazards
to the study participants
11.3 Informed Consent
In obtaining and documenting consent via an Electronic Informed Consent Form (eICF), the investigator
should comply with the applicable regulatory requirement(s) and should adhere to GCP and to the
ethical principles that have their origin in the Declaration of Helsinki. Prior to the beginning of the study,
the investigator should have the IRB’s written approval/favorable opinion of the eICF and any other
pertinent information to be provided to participants.
●
Following completion of pre-screening, participants will be provided with a link to the eICF
where they will have the opportunity to independently review and determine whether they are
interested in participating.
●
Participants will be provided with contact information for the study team whom they can reach
out to with any questions prior to signing the eICF.
●
Participants are informed that their participation is voluntary, and consent can be withdrawn at
any point.
●
Participants will be required to sign a statement of informed consent that meets the
requirements of US FDA CFR Title 21 Part 50, local regulations, ICH guidelines, HIPAA
requirements in the US, and the IRB or study site.
CONFIDENTIAL
36

Woebot Health
Version 1.1
W-DISC-002
18/MAR/2024
●
Prior to a participant’s participation in the study, the eICF should be signed and personally dated
by the participant.
●
An electronic copy of the signed eICF will be retained by the study team.
●
A copy of the eICF and any other pertinent information must be provided to the participant.
●
If the eICF is revised, the revised eICF must have received the IRB's approval/favorable opinion in
advance of its use. Participants must be informed of the changes to the eICF and must
re-consent to the most current version during their participation in the study if the IRB confirms
the change requires re-consent. The participant should be informed in a timely manner if new
information becomes available that may be relevant to the participant’s willingness to continue
participation in the study. The communication of this information should be documented.
12. Records Management
All clinical study information should be recorded, handled, and stored in a way that allows its accurate
reporting, interpretation, and verification. This principle applies to all records referenced in this protocol,
irrespective of the type of media used. All records will be collected and maintained via secure and
approved online platforms.
Details regarding eCRF access and handling are detailed in the “Electronic Case Report Form Completion
and Data Management” section.
Any contact with the participant via telephone or other means that provides significant clinical
information is to be documented and maintained as part of the study record. Information from the study
records and other source documents is to be promptly entered into the appropriate section of the eCRF.
Changes to information in the study record and other source documents will be electronically tracked. If
the reason for the change is not apparent, a brief explanation for the change is to be written adjacent to
the change.
The lead biostatician will write a data management plan, which will be finalized prior to performing any
data validation.
12.1 Source Documentation
Source documents will be collected electronically. Source documents contain the results of original
observations and activities of this research study. They are the original records in which raw data are first
recorded. Source documents include, but are not limited to screening logs, consent forms, and recorded
data from automated instruments.
The investigator/study personnel should maintain adequate and accurate source documents and study
records that include all pertinent observations on each of the study participants. Source data should be
attributable, legible, contemporaneous, original, accurate, and complete. Changes to source data should
be traceable, should not obscure the original entry, and should be explained if necessary (e.g., via an
audit trail).
CONFIDENTIAL
37

Woebot Health
Version 1.1
W-DISC-002
18/MAR/2024
All source documents from this study are to be maintained by the investigator and made available for
inspection by authorized persons. The investigator will provide direct access to source documents/data
for study-related monitoring, audits, IRB review, and regulatory inspections. The Sponsor-Investigator
should verify that each participant has consented, in writing, to direct access to his/her original study
records for study-related monitoring, audit, IRB review, and regulatory inspection.
12.2 Case Report Form Completion and Data Management
Access to the eCRF will be strictly password protected and limited to personnel directly participating in
the study. Data should be entered into the eCRF completely by authorized site personnel (e.g.,
investigators and the study coordinator). The eCRF must be completed as soon as possible (no later than
5 business days) after any participant evaluation or communication. Changes to the eCRF will be
electronically tracked.
Data will be entered/loaded into a validated online platform. Computerized data cleaning checks will be
used in addition to manual review to check for discrepancies and to ensure consistency of the data.
12.3 Study Files and Record Retention
All data derived from the study will remain the property of the Sponsor-Investigator. The
Sponsor-Investigator assumes accountability for actions delegated to other individuals (e.g., CRO, other
study personnel).
Records must be retained in accordance with the current ICH Guidelines on GCP. All essential study
documents, including records of participants, source documents, and eCRFs must be kept on file.
Essential documents should be retained until at least 2 years after the last approval of a marketing
application in an ICH region and until there are no pending or contemplated marketing applications in an
ICH region, or until at least 2 years have elapsed since the formal discontinuation of clinical development
of the investigational product. However, essential documents may be retained for a longer period if
required by the applicable regulatory requirements or by agreement with the Sponsor. The Sponsor is
responsible for informing the investigator when these documents need no longer be retained.
The investigator is not to dispose of any records relevant to this study without written permission from
the Sponsor and is to provide the Sponsor the opportunity to collect such records. The investigator shall
take responsibility for maintaining adequate and accurate hard copy source documents, if utilized, of all
observations and data generated during this study. Such documentation is subject to inspection by the
Sponsor, its representatives, and regulatory authorities.
If an investigator moves, withdraws from a study, or retires, the responsibility for maintaining the records
may be transferred to another person who will accept responsibility. Notice of transfer must be made to
and agreed by the Sponsor.
13. Auditing and Monitoring
Quality control will occur at each stage of data handling to ensure that all data are reliable and have
been processed correctly. The Sponsor-Investigator should ensure oversight of any study-related duties
CONFIDENTIAL
38

Woebot Health
Version 1.1
W-DISC-002
18/MAR/2024
and functions carried out on its behalf, including study-related duties and functions that are
subcontracted to another party by the Sponsor’s contracted vendors or other study personnel.
The eCRFs should be completed in a timely manner and on an ongoing basis to allow regular review by
the study monitor or designee.
Details describing the strategy, responsibilities, and requirements of the study monitoring are provided
in the study monitoring plan.
The purpose of an audit is to assess whether ethics, regulatory, and quality requirements are being
fulfilled. The Sponsor or its representative may conduct audits including, but not limited to, presence of
required documents, the informed consent process, and comparison of eCRFs with source documents.
Government regulatory authorities may also conduct an inspection during or after the study. All study
records must be available for audit. The Sponsor-Investigator must agree to participate with audits
conducted at a convenient time in a reasonable manner.
13.1 Protocol Adherence and Deviations
The investigator and study personnel should conduct the study in compliance with the protocol and
should use continuous vigilance to identify and report protocol deviations.
A protocol deviation is any change, divergence, or departure from the study design or procedures
defined in the protocol that may be on the part of the investigator, site personnel, or the participant.
Protocol violations are a subset of protocol deviations that may significantly impact the completeness,
accuracy, and/or reliability of the study data or that may significantly affect a participant's rights, safety,
or well-being. For example, important protocol deviations may include enrolling participants in violation
of key eligibility criteria designed to ensure a specific participant population or failing to collect data
necessary to interpret primary endpoints, as this may compromise the scientific value of the study.
The investigator should not implement any deviation from the protocol without agreement from the
Sponsor and prior review and approval from the IRB of an amendment, except where necessary to
eliminate an immediate hazard to a study participant, or when the change involves only logistical or
administrative aspects of the study, such as a change in a monitor or telephone number.
In the event of an important protocol deviation, the investigator will report the deviation to the SAC, as
described in the SMP, and will come to an agreement as to whether the participant should be withdrawn
from the study due to the important protocol deviation.
14. Amendments
Protocol modifications, except those intended to reduce immediate risk to study participants, may be
made only by the Sponsor. A protocol change intended to eliminate an apparent immediate hazard to
participants should be implemented immediately.
Any permanent change to the protocol must be handled as a protocol amendment. The written
amendment must be submitted to the IRB, and the investigator must await approval before
CONFIDENTIAL
39

Woebot Health
Version 1.1
W-DISC-002
18/MAR/2024
implementing the changes. The Sponsor will submit protocol amendments to the appropriate regulatory
authorities for approval.
The current version of the ICF will require similar modification if the IRB, investigator, and/or Sponsor,
judge the amendment to the protocol to substantially change the study design and/or increase the
potential risk to the participant and/or impact the participant's involvement as a study participant. In
such cases, the ICF will be renewed for enrolled participants before their continued participation in the
study.
15. Study Start and Termination
The study start date is the date on which the first participant provides informed consent.
The end of the study is defined as the last participant’s last assessment.
Both the Sponsor and the investigator reserve the right to terminate the study or the participation in the
study at an investigator’s site at any time. In terminating the study, the Sponsor and the investigator will
assure that adequate consideration is given to the protection of the participants’ interests.
If the study is prematurely terminated or suspended for any reason, the Sponsor-Investigator or
designated study personnel should promptly inform the study participants and should assure
appropriate therapy and follow-up for the participants. Where required by the applicable regulatory
requirements, the IRB, and other entities involved in the study should be informed promptly and be
provided with a detailed written explanation of the termination or suspension.
16. Confidentiality
All information generated in this study is considered highly confidential and must not be disclosed to any
person or entity not directly involved with the study unless prior written consent is gained from the
Sponsor. However, authorized regulatory officials, IRB personnel, the Sponsor and its authorized
representatives are allowed full access to the records.
All study participants must be informed that their personal study-related data will be used by the
Sponsor in accordance with local data protection law. The level of disclosure must also be explained to
the participant, who will be required to give consent for their data to be used as described in the ICF.
Participants must be informed that their medical records may be examined by auditors or other
authorized personnel appointed by the Sponsor, by appropriate IRB members, and by inspectors from
regulatory authorities.
Identification of participants and eCRFs shall be by unique participant identification numbers (such as
screening or randomization number) only. All personal identifiers according to applicable regulations
(e.g., name, phone number) must be redacted permanently by the site personnel and replaced with the
participant ’s unique identification number in all records and data before transfer to the Sponsor (or
designee).
All personal details will be treated as confidential by the investigator and study team members.
CONFIDENTIAL
40

Woebot Health
Version 1.1
W-DISC-002
18/MAR/2024
CONFIDENTIAL
41

Woebot Health
Version 1.1
W-DISC-002
18/MAR/2024
17. References
1. Center for Devices and Radiological Health. Precision Medicine. U.S. Food & Drug Administration
(FDA). Published August 18, 2023. Accessed December 21, 2023.
https://www.fda.gov/medical-devices/in-vitro-diagnostics/precision-medicine
2. Fernandes BS, Williams LM, Steiner J, Leboyer M, Carvalho AF, Berk M. The new field of ‘precision
psychiatry.’ BMC Med. 2017;15(1):80. doi:10.1186/s12916-017-0849-x
3. Kroenke K, Strine TW, Spitzer RL, Williams JBW, Berry JT, Mokdad AH. The PHQ-8 as a measure of
current depression in the general population. J Affect Disord. 2009;114(1-3):163-173.
doi:10.1016/j.jad.2008.06.026
4. Spitzer RL, Kroenke K, Williams JBW, Löwe B. A brief measure for assessing generalized anxiety
disorder: the GAD-7. Arch Intern Med. 2006;166(10):1092-1097. doi:10.1001/archinte.166.10.1092
5. Munder T, Wilmers F, Leonhart R, Linster HW, Barth J. Working Alliance Inventory-Short Revised
(WAI-SR): psychometric properties in outpatients and inpatients. Clin Psychol Psychother.
2010;17(3):231-239. doi:10.1002/cpp.658
6. Dennis J, Vander Wal J. The Cognitive Flexibility Inventory: Instrument Development and Estimates of
Reliability and Validity. Cogn Ther Res. 2010;34:241-253. doi:10.1007/s10608-009-9276-4
7. Kaufman E, Xia M, Fosco G, Yaptangco M, Skidmore C, Crowell S. The Difficulties in Emotion
Regulation Scale Short Form (DERS-SF): Validation and Replication in Adolescent and Adult Samples. J
Psychopathol Behav Assess. 2016;38. doi:10.1007/s10862-015-9529-3
8. Gard D, Germans Gard M, Kring A, John O. Anticipatory and consummatory components of the
experience of pleasure: a scale development study. J Res Personal. 2006;40:1086-1102.
doi:10.1016/j.jrp.2005.11.001
9. Cyranowski JM, Zill N, Bode R, et al. Assessing social support, companionship, and distress: National
Institute of Health (NIH) Toolbox Adult Social Relationship Scales. Health Psychol. 2013;32(3):293-301.
doi:10.1037/a0028586
10. Terides MD, Dear BF, Karin E, et al. The frequency of actions and thoughts scale: development and
psychometric validation of a measure of adaptive behaviours and cognitions. Cogn Behav Ther.
2016;45(3):196-216. doi:10.1080/16506073.2016.1149876
11. Centers for Medicare and Medicaid Services, Billioux A, Verlander K, et al. Standardized Screening for
Health-Related Social Needs in Clinical Settings: The Accountable Health Communities Screening Tool.
NAM Perspect. 2017;7(5). doi:10.31478/201705b
CONFIDENTIAL
42