Woebot for Substance Use Disorders During COVID-19
Phase: PHASE1
Conditions: Substance Use Disorders, Alcohol Use Disorder
Sponsor: Woebot Health

Woebot for Substance Use Disorders During COVID-19 
NCT04460027
April 30, 2022

Title :
Woebot for Substance Use Disorders during COVID-19 (SU sIRB)
Approval Period:
04/30/2022 - 04/30/2023
Continuing Review Form ............................................................................................
2
Personnel Info .............................................................................................................
5
Participant Population .................................................................................................
6
Study Location ............................................................................................................
6
General Checklist ........................................................................................................
7
Funding .......................................................................................................................
9
Resources ....................................................................................................................
9
Purpose, Study Procedures .......................................................................................... 12
Radioisotopes or Radiation Machines ......................................................................... 16
Drugs,Devices,Reagents ............................................................................................. 17
Medical Equipment for Human Subjects and Laboratory Animals ............................ 18
Participant Population(a-g) ......................................................................................... 18
Participant Population(h-m) ........................................................................................ 22
Risks(a-e) .................................................................................................................... 23
Privacy And Confidentiality ....................................................................................... 27
Conflict Of Interest ..................................................................................................... 27
Consent Background ................................................................................................... 31
Assent Background ..................................................................................................... 32
HIPAA Background .................................................................................................... 33
Attachments ................................................................................................................. 34
Obligations .................................................................................................................. 36
eProtocol # 56439 ( Continuing Review )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 1 of 37
Review Type: Regular
Human Subjects Research
Medical
Stanford University

Continuing Review Form
1. Participant Enrollment
a. Number of participants entered (or number of specimens examined or charts reviewed) since the
beginning of study. If this is a combined VA-Stanford study, in addition indicate how many of the
participants (or number of VA specimens examined or VA charts reviewed) enrolled with a VA
consent. If this is a multi-site study, in addition to the number of participants enrolled locally, include
the number of participants enrolled study-wide.
N=180
Study is closed to enrollment and in data analysis in 2021.
b. Number of: males, females, others or individuals whose sex/gender are unknown or not reported.
Male: 63
Female: 117
c. Minority status of participants entered since beginning of study.
American Indian/Alaska Native: 4
Asian: 11
African American: 22
Multiracial: 3
White: 140
d. Number of children (less then 18 years) entered since beginning of study.
0
e. Number of other potentially vulnerable subjects (if applicable) entered since the beginning of study,
including prisoners, pregnant women, economically and educationally disadvantaged, decisionally
impaired and homeless people.
N/A
2. Study Problems/Complications
a. Number of withdrawals of participants from the research (both participant and investigator initiated)
since the beginning of the research study. Provide reasons for the withdrawals.
None
b. Number of participants lost to follow-up since the beginning of the study.
28
c. State if all adverse events have occurred at the expected frequency and level of severity as per study
documents or provide a narrative summary of the adverse events since the last continuing review
indicating whether the adverse events were expected and/or related to the study.
Below is the information reported in the previous continuing review:
One SAE was reported. The event is unrelated, expected, and resolved.
Participant 014 reported in final follow up survey that they went into the hospital on their own to detox
Protocol # 56439 ( Continuing Review )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 2 of 37
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders during COVID-19 (SU sIRB)
Approval Period:
04/30/2022 - 04/30/2023

from alcohol. Participant reported experiencing D.T.'s, severe shaking, visual or auditory hallucinations
after heavy drinking on 10/22/20. They put down the reason or cause of the event as attempting to detox on
their own before deciding to go to a facility for assistance. 10/29/20: After further inquiry regarding what
led to the hospitalization, the participant mentioned they were drinking entirely too much and was on a bad
bender. They are on day 8 of sobriety.
d. Have there been any unanticipated problems involving risks to participants or others (UPs) since the
beginning of the study? A UP must be unexpected (including in severity or frequency), related, AND
harmful. Confirm that all UPs have previously been reported to the IRB (guidance GUI-P13).
N/A
e. Provide a narrative summary of all external (e.g. FDA, OHRP, sponsor) audit reports, monitoring
visits, inspections, and multi-center trial reports received in the past year. Include corrective actions
taken as a result of any audits, inspections, or monitoring visits.
N/A
f.
Complaints about the research in the past year.
N/A
g. Have there been any instances of noncompliance or deviations since the beginning of the study that
have not already been addressed in 2e? Provide a summary and indicate if it has been previously
reported to the IRB. Provide a corrective action plan that includes how you will ensure the
noncompliance does not recur.
No new instances.
Below is the information reported in the previous continuing review:
N=160 was proposed for study enrollment. Final enrollment was N=180. Qualtrics panel recruitment was
the main recruitment method and had resulted in n=160; n=20 were from other recruitment sources
described in the protocol. For the next study, we'll try Qualtrics recruitment before other sources, as the
Qualtrics panel requires a prepaid agreement and results in speedy recruitment.
Below are summaries of responses removed from the study. There's no known effective way of preventing
these types of responses. Future studies will involve quality check of responses.
Four surveys were screened as eligible. These surveys completed the baseline assessment and were
randomized (1 to treatment, 3 to waitlist). Based on the four surveys having identical IP address, common
birth year, and overlap in name/email addresses these surveys were presumed to be a single individual
enrolling at four different time points.
Four survey respondents (screened in and randomized: 1 to treatment, 3 to waitlist) did not provide a valid
email or phone number for follow ups (eligibility criteria).
One survey respondent (screened in and randomized) is confirmed to be a duplicate of another survey
response. The respondent was randomized to the treatment group at both survey completions.
3.Study Assessment
a. Provide a narrative summary of any interim findings from your data in the past year.
Vogel EA, Chieng A, Robinson A, Pajarito S, Prochaska JJ. (2021). Associations between substance use
problems and stress during COVID-19. Journal of Studies on Alcohol and Drugs, 82, 776-781.
Experiencing worsened mental health symptoms during COVID-19 was associated with more substance use
Protocol # 56439 ( Continuing Review )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 3 of 37
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders during COVID-19 (SU sIRB)
Approval Period:
04/30/2022 - 04/30/2023

problems and symptoms of depression and anxiety. Pandemic disruptions may exacerbate preexisting
substance use problems.
Prochaska JJ, Vogel EA, Chieng A, Baiocchi M, Maglalang DD, Pajarito S, Weingardt KR, Darcy A,
Robinson A. (2021). A randomized controlled trial of a therapeutic relational agent for reducing substance
misuse during the COVID-19 pandemic. Drug & Alcohol Dependence, 227, 108986
W-SUDs was associated with significant reductions in substance use occasions. Reduction in substance use
occasions was associated with better outcomes, including improved mental health. W-SUDs satisfaction
was high.
b. Provide a narrative summary of any recent relevant literature.
From Phase 1 (Prochaska JJ, Vogel EA, Chieng A, Kendra M, Baiocchi M, Pajarito S, Robinson A. (2021).
A therapeutic relational agent for reducing problematic substance use (Woebot): Development and usability
study. Journal Medical Internet Research, 23(3): e24850): W-SUDs was feasible to deliver, engaging, and
acceptable and was associated with significant improvements in substance use, confidence, cravings,
depression, and anxiety. Study attrition was high. Future research will evaluate W-SUDs in a randomized
controlled trial with a more diverse sample and with the use of greater study retention strategies.
c. Attach Data Safety Monitoring Reports in section 16 received in the past year which have not
previously been submitted to the IRB.
None. June 2021 meeting minutes attached. We are planning another DSMB meeting in April 2022.
d. Provide a narrative summary of benefits experienced by participants in the past year.
None
e. Provide an assessment of whether the relationship of risks to potential benefits has changed.
None
4. Description of remainder of project:
a.
N
Is the study open to enrollment?
b.
Y
Is the study permanently closed to enrollment of new participants?
c.
Y
Have all participants completed all research-related interventions?
d.
N
Are you still engaged in research-related intervention(s)? If yes, please describe.
e.
N
Do you wish to renew this study only for long term follow-up?
f.
Y
Are you only doing data analysis?
5. Potential Conflict of Interest
N
Is there a change in the conflicting interest status of this protocol?
Protocol # 56439 ( Continuing Review )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 4 of 37
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders during COVID-19 (SU sIRB)
Approval Period:
04/30/2022 - 04/30/2023

6. Protocol Changes
Please note that if these changes involve changes to Radiation Safety or Biosafety, the IRB will hold its
approval until Radiation Safety or Biosafety forwards its approval to the IRB. Use track changes IF revising
consent, assent or HIPAA.
• Summarize all of the proposed changes to the protocol application including consent form changes.
Erin Vogel and Dale Maglalang have been removed from Personnel.
Protocol Information section 8m has been updated to extend the time frame of data analyses and dissemination.
• Indicate Level of Risk
No Change
• Describe any other changes.
None
Protocol Director
Admin Contact
Investigator
Name
Degree (Program/year if
student)
Position, e.g. Assistant Professor,
Resident, etc.
Department
Phone
E-mail
CITI Training current
Protocol # 56439 ( Continuing Review )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 5 of 37
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders during COVID-19 (SU sIRB)
Approval Period:
04/30/2022 - 04/30/2023

Other Contact
Name
Degree (Program/year if
student)
Position, e.g. Assistant Professor,
Resident, etc.
Department
Phone
E-mail
CITI Training current
Academic Sponsor
Name
Degree (Program/year if
student)
Position, e.g. Assistant Professor,
Resident, etc.
Department
Phone
E-mail
CITI Training current
Other Personnel
Department
Phone
Participant Population(s) Checklist
Yes/No
• Children (under 18)
N
• Pregnant Women and Fetuses
N
• Neonates (0 - 28 days)
N
• Abortuses
N
• Impaired Decision Making Capacity
N
• Cancer Subjects
N
• Laboratory Personnel
N
• Healthy Volunteers
N
• Students
N
• Employees
N
• Prisoners
N
• Other (i.e., any population that is not specified above)
Y
• International Participants
N
Please enter the countries separated by comma
Study Location(s) Checklist
Yes/No
• Stanford University
Y
• Clinical & Translational Research Unit (CTRU)
Protocol # 56439 ( Continuing Review )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 6 of 37
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders during COVID-19 (SU sIRB)
Approval Period:
04/30/2022 - 04/30/2023

• Stanford Hospital and Clinics
• Lucile Packard Children's Hospital (LPCH)
• VAPAHCS (Specify PI at VA)
• Other (Click ADD to specify details)
General Checklist
Multi-site
Yes/No
• Is this a multi-site study? A multi-site study is generally a study that involves one or more
medical or research institutions in which one site takes a lead role.(e.g., multi-site clinical
trial)
N
Collaborating Institution(s)
Yes/No
• Are there any collaborating institution(s)? A collaborating institution is generally an
institution that collaborates equally on a research endeavor with one or more institutions.
Y
Institution
Name
Contact Name Contact
Phone
Contact Email
Permission?
Engaged?
Cancer Institute
Yes/No
• Cancer-Related Studies (studies with cancer endpoints), Cancer Subjects (e.g., clinical
trials, behavior/prevention) or Cancer Specimens (e.g., blood, tissue, cells, body fluids with
a scientific hypothesis stated in the protocol).
N
Clinical Trials
Yes/No
• Investigational drugs, biologics, reagents, or chemicals?
N
• Commercially available drugs, reagents, or other chemicals administered to subjects (even
if they are not being studied)?
N
• Investigational Device / Commercial Device used off-label?
Y
• IDE Exempt Device (Commercial Device used according to label, Investigational In Vitro
Device or Assay, or Consumer Preference/Modifications/Combinations of Approved
Devices)
N
• Will this study be registered on# clinicaltrials.gov? ( See Stanford decision tree )
Y
• Who will register for ClinicalTrials.gov?
NCT#
N
Tissues and Specimens
Yes/No
Protocol # 56439 ( Continuing Review )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 7 of 37
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders during COVID-19 (SU sIRB)
Approval Period:
04/30/2022 - 04/30/2023

• Human blood, cells, tissues, or body fluids (tissues)?
N
• Tissues to be stored for future research projects?
N
• Tissues to be sent out of this institution as part of a research agreement? For guidelines,
please see https://sites.stanford.edu/ico/mtas
N
Biosafety (APB)
Yes/No
• Are you submitting a Human Gene Transfer investigation using a biological agent or
recombinant DNA vector? If yes, please complete the Gene Transfer Protocol Application
Supplemental Questions and upload in Attachments section.
N
• Are you submitting a Human study using biohazardous/infectious agents? If yes, refer to
the Administrative Panel on BioSafety website prior to performing studies.
N
• Are you submitting a Human study using samples from subjects that are known or likely to
contain biohazardous/infectious agents? If yes, refer to the Administrative Panel on
BioSafety website prior to performing studies.
N
Human Embryos or Stem Cells
Yes/No
• Human Embryos or Gametes?
N
• Human Stem Cells (including hESC, iPSC, cancer stem cells, progenitor cells)
N
Veterans Affairs (VA)
Yes/No
• The research recruits participants at the Veterans Affairs Palo Alto Health Care
System(VAPAHCS).
N
• The research involves the use of VAPAHCS non-public information to identify or contact
human research participants or prospective subjects or to use such data for research
purposes.
N
• The research is sponsored (i.e., funded) by VAPAHCS.
N
• The research is conducted by or under the direction of any employee or agent of
VAPAHCS (full-time, part-time, intermittent, consultant, without compensation (WOC),
on-station fee-basis, on-station contract, or on-station sharing agreement basis) in
connection with her/his VAPAHCS responsibilities.
N
• The research is conducted using any property or facility of VAPAHCS.
N
Equipment
Yes/No
• Use of Patient related equipment? If Yes, equipment must meet the standards established by
Hospital Instrumentation and Electrical Safety Committee (650-725-5000)
N
• Medical equipment used for human patients/subjects also used on animals?
N
• Radioisotopes/radiation-producing machines, even if standard of care?
http://www.stanford.edu/dept/EHS/prod/researchlab/radlaser/Human_use_guide.pdf More
Info
N
Protocol # 56439 ( Continuing Review )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 8 of 37
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders during COVID-19 (SU sIRB)
Approval Period:
04/30/2022 - 04/30/2023

Payment
Yes/No
• Subjects will be paid/reimbursed for participation? See payment considerations.
Y
Funding
Yes/No
• Training Grant?
N
• Program Project Grant?
N
• Federally Sponsored Project?
Y
• https://doresearch.stanford.edu/policies/research-policy-handbook/definitions-and-types-agreements/specialized-categories-sponsored-p
Industry Sponsored Clinical Trial?
N
Funding
Funding - Grants/Contracts
Funding Administered By :
STANFORD
SPO # (if available) :
138716
Grant # (if available) :
Funded By (include pending) :
NIH Prime
Woebot
Principal Investigator :
Judith Prochaska
Grant/Contract Title if different from Protocol Title :
RCT of Woebot for Treating Substance Use Disorders
Y
For Federal projects, are contents of this protocol consistent with the Federal proposal?
N
Is this a Multiple Project Protocol (MPP)?
N
Is this protocol under a MPP?
Funding - Fellowships
Gift Funding
Dept. Funding
Other Funding
Resources :
a)
Qualified staff.
Please state and justify the number and qualifications of your study staff.
Protocol # 56439 ( Continuing Review )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 9 of 37
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders during COVID-19 (SU sIRB)
Approval Period:
04/30/2022 - 04/30/2023

The staff are well versed in the ethics and rigorous methods of conducting research trials with human
subjects. The staff are responsible for recruitment and consenting, assessments, treatment delivery, and
follow-up activities.
b)
Training.
Describe the training you will provide to ensure that all persons assisting with the research are
informed about the protocol and their research-related duties and functions.
Protocol # 56439 ( Continuing Review )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 10 of 37
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders during COVID-19 (SU sIRB)
Approval Period:
04/30/2022 - 04/30/2023

All study staff maintain up-to-date CITI certification and current knowledge of the research literature on use
of digital health technologies for health behavior change.
c)
Facilities.
Please describe and justify.
Dr. Prochaska has a faculty office at Stanford University in the Medical School Office Building with
full computing resources needed for the trial.
All study data are gathered on a HIPAA compliant web platform that resides behind Stanford security
firewalls and has been tried and tested by the University for several years, thus actual risk from data breach
for study data is low.
d)
Sufficient time.
Explain whether you will have sufficient time to conduct and complete the research. Include how much
time is required.
Dr. Prochaska's faculty time is 100% devoted to research and this is one of her funded projects to
which she dedicates her time.
e)
Access to target population.
Explain and justify whether you will have access to a population that will allow recruitment of the
required number of participants.
This NIDA-funded project (funding pending) is a collaboration with Woebot, a technology start up that is
using artificial intelligence (AI) in a bot to deliver tailored messaging to improve mental health.
Participants will be recruited through a wide variety of strategies including but not limited to paid online
advertising (e.g., sidebar Gmail and Yahoo advertisements); flyers; social media; free online and email
advertising (e.g., Dr Prochaska's laboratory webpage, email listservs of digital health companies and the
Stanford University student, faculty, and staff community); participants from previous studies who have
interest in other studies; and national outpatient clinics with substance abuse programming including
Stanford's Department of Psychiatry and Behavioral Sciences' Dual Diagnosis Clinic.
Dr. Prochaska's team has extensive experience in recruiting research participants who use substances,
including for online studies and has published on best practices.
f)
Access to resources if needed as a consequence of the research.
State whether you have medical or psychological resources available that participants might require as
a consequence of the research when applicable. Please describe these resources.
Study informed consent will state that Woebot (the app being used to deliver the intervention) is not a crisis
program designed to address active suicidal ideation or overdose. Woebot also conversationally informs
first time users that it is not a crisis service. Our current safety net protocol will be adapted for this study.
Woebot detects crisis language and asks to confirm it with the user. If the user confirms, Woebot offers
resources (911, suicide crisis hotlines), carefully curated with expert consultation. Our data indicate that
users do not use Woebot for crisis management; about 6.3% trigger the safety net protocol, with 27%
confirming that it is indeed a crisis when Woebot asks to confirm (i.e., our true positive rate). To make sure
that we do not miss any cases, we over detect, rather than under detect. In addition, we periodically check
the data for true/false positive rates.
Foreseeable risks to subjects include the possibility that some assessment questions and/or treatment
procedures may be upsetting to subjects. Experience at Stanford with similar populations has indicated that
the risk of emotional upset during the assessments is low and if it occurred, the upset would likely not be
Protocol # 56439 ( Continuing Review )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 11 of 37
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders during COVID-19 (SU sIRB)
Approval Period:
04/30/2022 - 04/30/2023

serious in nature and temporary. Such risks will be minimized by the thoughtful selection of questionnaires.
Potential participants will also be informed that they may drop out of the study at any time and if requested,
appropriate treatment referrals would then be given.
g)
Lead Investigator or Coordinating Institution in Multi-site Study.
Please explain (i) your role in coordinating the studies, (ii) procedures for routine communication with
other sites, (iii) documentation of routine communications with other sites, (iv) planned management of
communication of adverse outcomes, unexpected problems involving risk to participants or others,
protocol modifications or interim findings.
1. Purpose
a)
In layperson's language state the purpose of the study in 3-5 sentences.
This study aims to develop a digitally-delivered substance use
disorder program through the Woebot app-based platform to inform a
study that will test the comparative efficacy of the mobile-app based
substance use disorder program to reduce substance use relative to a
wait list control condition, and explore between group differences on
quality of life indices as well as retention and engagement during
COVID-19.
b)
State what the Investigator(s) hope to learn from the study. Include an assessment of the importance of
this new knowledge.
The COVID-19 pandemic introduced significant, unprecedented, and
immediate psychological challenges to all, including individuals with
substance use disorders (SUDs). The impact upon individuals with SUDs
will be multifaceted and far reaching. In terms of physical health,
experts postulate that individuals with SUDs may be at greater risk of
mortality from COVID-19 given the variety of pre-existing physical
health conditions this group has traditionally faced (i.e., COPD,
cardiovascular disease, general poor respiratory health). In addition,
the pandemic will beget significant emotional and psychiatric disruption
from the multifaceted impact of the illness. Such responses may include
large-scale grief, loneliness, fear, loss of life experiences,
constrained or frank inability to work, financial instability, risk of
contagion, overwhelmed hospitals, limited access to recovery programs
and reduced or significantly changed mental health service provision
from clinics.
Woebot, the landmark product released by Woebot Labs Inc. in 2017, is an
automated conversational agent, available through a smartphone
application, that delivers evidence-based psychotherapeutics, empathy,
and emotional health psychoeducation. Woebot for Substance Use Disorders
(W-SUDs) is a 2 phase SBIR industry-academic partnership between Woebot
Labs Inc. and Stanford University that aims to develop and evaluate the
evidence of the novel digital therapeutic, delivered by an artificial
intelligence (AI)-powered, automated conversational agent named Woebot
which is embedded in the therapeutic W-SUDs.
Milestones for Phase I included the development (e.g., content and
engineering) of W-SUDs and piloting its preliminary efficacy,
feasibility and acceptability among n=100 individuals with SUD. Phase I
is well underway presently. At the time of this supplement application,
Protocol # 56439 ( Continuing Review )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 12 of 37
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders during COVID-19 (SU sIRB)
Approval Period:
04/30/2022 - 04/30/2023

W-SUDs had been developed and deployed to pilot phase with N=48
individuals already enrolled into the pilot study.
Phase II is multi-pronged and aims to engage the FDA in collaboration
regarding W-SUDs, test the comparative efficacy of the W-SUDs relative
to a standard control condition (SCC) to reduce substance use, and
explore between group differences on quality of life indices as well as
retention and engagement.
The current supplement proposes an additional study of W-SUDs to obtain
and analyze data on the risks of the COVID-19 pandemic among individuals
experiencing SUDs. The study will not disrupt progress or milestones on
the parent grant. Rather, it offers an opportunity to expand
understanding of W-SUDs' performance among this population whilst
contributing to our overall understanding of COVID-19's impact upon this
population.
Impact
Immediate access to a digital therapeutic in a resource constrained,
social distance healthcare ecosystem amidst growing psychological
challenges in this already vulnerable and underserved population.
When COVID-19 spread, users from around the world came to Woebot to
discuss it and seek help. The company responded by building a Covid-19
specific program for Woebot (W-C19) which is already well underway.
Elements of our W-C19 program have already been integrated into W-SUDs
because we felt that it was timely and appropriate to address users'
concerns about the pandemic and demonstrated that Woebot was
'intelligent' to the current crisis.
c)
Explain why human subjects must be used for this project. (i.e. purpose of study is to test efficacy of
investigational device in individuals with specific condition; purpose of study is to examine specific
behavioral traits in humans in classroom or other environment)
The purpose of this study is to test the efficacy of a mobile-
application delivered substance use disorder intervention in adult
humans in a pandemic, and assess effects due to COVID-19.
2. Study Procedures
a)
Please SUMMARIZE the research procedures, screening through closeout, which the human subject
will undergo. Refer to sections in the protocol attached in section 16, BUT do not copy the clinical
protocol. Be clear on what is to be done for research and what is part of standard of care.
Updated consent forms and HIPAA authorization will be uploaded before
the start of recruitment. Ads, questionnaires, etc. will be uploaded for
review before recruitment begins.
Recruitment will be a joint effort by Stanford University and Woebot
Labs. Woebot will communicate the research opportunity through social
media channels. The Stanford team will recruit through listservs and
contact participants from previous research studies who are interested
in future studies. Working with Dr. Prochaska's research team at
Stanford, the Woebot team will take part in mapping out message
development for the intervention and Woebot's IT team will lead the app
programming (including build and quality control/de-bugging). Woebot
will collect user data via the Woebot app (automatic process), which
Protocol # 56439 ( Continuing Review )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 13 of 37
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders during COVID-19 (SU sIRB)
Approval Period:
04/30/2022 - 04/30/2023

will be provided to the Stanford team. The Woebot team will participate
in disseminating the study findings via publications and presentations.
Participants from recruitment channels will go through and
eligibility screener and if eligible, will be asked to use the W-SUDS
for 8 weeks and answer a couple of questionnaires administered at the
beginning and end of the 8 week period. The data from the
questionnaires and app usage during the 8-week period will be
analyzed to inform the next study. Woebot will rely on Stanford
University IRB for review of this study.
The Stanford team will lead the study evaluations including the study
measures, data collection (baseline and follow-ups at the 4- and 8- week
marks), data analyses, and writing up of study findings for
dissemination. Participants will be randomized to condition after
completion via the online assessment platform, which has the
functionality to allow randomization to one of two webpages. Those
randomized to W-SUDs or WL will see a private, study-only Woebot website
or the WL website, respectively. Only then will participants randomized
to W-SUDs be informed of Woebot in order to avoid contamination. The WL
group has no intervention during the 8-week period and the team will
monitor for any intervention usage.
In order to better understand what specific W-SUDs content the
participants like, Lesson Completion Rates and Content Rating Metrics
will be analyzed. Descriptive statistics will be used for the
following scales: Usage Rating Profile Intervention (UPRI)-
Acceptability, Usage Rating Profile Intervention (UPRI)--Feasibility,
and Client Satisfaction Questionnaire (CSQ-8). Such descriptive
statistics will provide a summary index of how likable the content
and program was overall. Due to the small sample size of this
study, effect sizes, rather than tests involving statistical
significance, will be used to assess the intervention's impact from
baseline to EOT.
Utilizing study results as described above, the research team
will learn the efficacy of a digital substance use therapeutic during a
pandemic. The intent is to utilize and leverage what was
learned in this study to provide an intervention in a time where in
person services are discouraged.
b)
Explain how the above research procedures are the least risky that can be performed consistent with
sound research design.
Given that the research aims to enroll a low-treatment seeking
population, we do not envisage that participation in the study will
be associated with elevated risk.
However, some risk is always present in studies that involve human
participants.
Such risk may include the following:
Risk from breach of protected health information.
Possibly the greatest risk is from a leak of health information. All
study data are gathered on a HIPAA compliant web platform that
resides behind Stanford security firewalls and has been tried and
tested by the University for several years, thus actual risk from
data breach for study data is low. In addition, the Woebot
Protocol # 56439 ( Continuing Review )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 14 of 37
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders during COVID-19 (SU sIRB)
Approval Period:
04/30/2022 - 04/30/2023

application encrypts all message data exchanged between service users
and Woebot, and collects minimal protected health information.
Emails are hashed and not kept along side message data so that they
are not easily associated with each other. In addition, the product
recently became compliant with General Data Protection Regulations
(GDPR) in the European Union which entails a user-ownership model of
data protections.
Risk from answering questions that may be emotionally upsetting.
Experience at Stanford with similar populations has indicated that
the risk of emotional upset during the assessments is low and if it
occurred, the upset would likely not be serious in nature and
temporary. Such risks will be minimized by the thoughtful selection
of questionnaires. Potential participants will also be informed that
they may drop out of the study at any time and if requested,
appropriate treatment referrals would then be given.
Risk of treatment avoidance due to engagement with either of the
randomized interventions. In both interventions it is explicitly
stated that the service should not be used in place of traditional
treatment. In the case of the W-SUDs intervention, Woebot is designed
to hold individuals accountable for pursuing additional options in
conditions of unchanged symptoms for a prolonged amount of time (4
weeks). In addition, Woebot will invite the user to consider what
seeking additional services would look like.
c)
State if deception will be used. If so, provide the rationale and describe debriefing procedures. Since
you will not be fully informing the participant in your consent process and form, complete an
alteration of consent (in section 13). Submit a debriefing script (in section 16).
No deception will be used.
d)
State if audio or video recording will occur. Describe what will become of the recording after use, e.g.,
shown at scientific meetings, erased. Describe the final disposition of the recordings.
No audio or video recordings will occur.
e)
Describe alternative procedures or courses of treatment, if any, that might be advantageous to the
participant. Describe potential risks and benefits associated with these. Any standard treatment that is
being withheld must be disclosed in the consent process and form. (i.e. standard-of-care drug, different
interventional procedure, no procedure or treatment, palliative care, other research studies).
Alternative Treatments for SUDSs include in-person individual and
group forms of psychotherapy as well as Alcoholics Anonymous and
Narcotics Anonymous.
All alternative options will be provided if she/he/they wishes to
engage in an alternative treatment rather than the proposed study.
However, given that previous Woebot study results are promising, the
proposed line of treatments would appear to be appropriate and
acceptable interventions for SUDs.
No standard treatment is being withheld.
f)
Will it be possible to continue the more (most) appropriate therapy for the participant(s) after the
conclusion of the study?
Yes
g)
Study Endpoint. What are the guidelines or end points by which you can evaluate the different
treatments (i.e. study drug, device, procedure) during the study? If one proves to be clearly more
effective than another (or others) during the course of a study, will the study be terminated before the
Protocol # 56439 ( Continuing Review )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 15 of 37
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders during COVID-19 (SU sIRB)
Approval Period:
04/30/2022 - 04/30/2023

projected total participant population has been enrolled? When will the study end if no important
differences are detected?
The endpoint will be the 2-month end-of-treatment survey. This will
end the study and study staff will do analysis.
3. Background
a)
Describe past experimental and/or clinical findings leading to the formulation of the study.
Woebot's app-based platform and user-centered design philosophy makes
it an optimal modality for SUDs treatment delivery; it offers
immediate, evidence-based tailored support in the patient's peak
moment of craving. An RCT demonstrated that Woebot had statistically
and clinically significant reductions in depression compared to a
control group, along with best in class app-engagement rates (mean=12
interactions in 14 days). Woebot does not currently offer a SUDs
program, although 63% of current users expressed interest in said
content. Woebot's current, substantial reach as a consumer app,
preliminary data indicating its high user engagement plus efficacy
to treat a psychological condition, posies it as an ideal platform
for a SUDs-focused, tailored, and immediately scalable digital
therapeutic.
In the Woebot-SUDs phase 1 (pilot) study, there are 2,450+ screening
attempts, indicating interest in a digital therapeutic CA on substance
use both nationally and internationally. 260 were screened out solely
for not residing in the U.S.
COVID-19 offers a unique opportunity for research to consider outbreak
levels and policies in our analyses, and the potential for differential
effects of a treatment for reducing substance use problems during an
infectious disease outbreak.
b)
Describe any animal experimentation and findings leading to the formulation of the study.
N/A
4. Radioisotopes or Radiation Machines
a)
List all standard of care procedures using ionizing radiation (radiation dose received by a subject that
is considered part of their normal medical care). List all research procedures using ionizing radiation
(procedures performed due to participation in this study that is not considered part of their normal
medical care). List each potential procedure in the sequence that it would normally occur during the
entire study. More Info
Identify Week/Month of study
Name of Exam
Identify if SOC or Research
b)
For research radioisotope projects, provide the following radiation-related information:
Identify the radionuclide(s) and chemical form(s).
For the typical subject, provide the total number of times the radioisotope and activity will be
administered (mCi) and the route of administration.
Protocol # 56439 ( Continuing Review )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 16 of 37
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders during COVID-19 (SU sIRB)
Approval Period:
04/30/2022 - 04/30/2023

If not FDA approved provide dosimetry information and reference the source documents (package
insert, MIRD calculation, peer reviewed literature).
c)
For research radiation machine projects, provide the following diagnostic procedures:
For well-established radiographic procedures describe the exam.
For the typical subject, identify the total number of times each will be performed on a single
research subject.
For each radiographic procedure, provide the setup and technique sufficient to permit research
subject dose modeling. The chief technologist can usually provide this information.
For radiographic procedures not well-established, provide FDA status of the machine, and
information sufficient to permit research subject dose modeling.
d)
For research radiation machine projects, provide the following therapeutic procedures:
For a well-established therapeutic procedure, identify the area treated, dose per fraction and
number of fractions. State whether the therapeutic procedure is being performed as a normal part of
clinical management for the research participants's medical condition or whether it is being
performed because the research participant is participating in this project.
For a therapeutic procedure that is not well-established, provide FDA status of the machine, basis
for dosimetry, area treated, dose per fraction and number of fractions.
5. Devices
a) Please list in the table below all Investigational Devices (including Commercial Devices used off-label) to
be used on participants.
5. 1
Device Name :
Woebot
Describe the device to be used.
Woebot, a Conversational Agent (CA)
instantaneously available 24 hours per day, 7
days per week, 'checks in' with users. Using
conversational tones, it encourages mood
tracking and delivers general
psychoeducation as well as tailored empathy,
cognitive behavior therapy (CBT)-based
behavior change tools, and behavioral pattern
insight. Woebot's app-based platform and
user-centered design philosophy makes it an
optimal modality for Substance Use Disorders
(SUD) treatment delivery; it offers immediate,
evidence-based tailored support in the
patient's peak moment of craving.
Manufacturer :
Woebot Labs
Risk :
Non-significant
Y
I confirm the above are true.
Rationale for the device being non-significant risk:
Protocol # 56439 ( Continuing Review )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 17 of 37
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders during COVID-19 (SU sIRB)
Approval Period:
04/30/2022 - 04/30/2023

The research aims to enroll a low-treatment seeking population,
and employ randomization to two low-risk interventions, we do not
envisage that participation in the study will be associated with
elevated risk.
Sponsor of Project
Indicate who is responsible for submitting safety reports to the FDA:
Y
The sponsor is the device manufacturer.
Ordering, Storage and Control
To prevent the device being used by a person other than the investigator, and in someone other than a
research participant: Confirm that the device will be handled according to the SHC/LPCH policy for
Investigational New Devices or as appropriate. If no, please provide an explanation. :
Y
Confirm?
b) Please list in the table below all IDE Exempt Devices (Commercial Device used according to label,
Investigational In Vitro Device or Assay, or Consumer Preference/Modifications/Combinations of
Approved Devices) to be used on participants.
6. Drugs, Reagents, or Chemicals and Devices
a) Please list in the table below all investigational drugs, reagents or chemicals to be administered to
participants.
b) Please list in the table below all commercial drugs, reagents or chemicals to be administered to
participants.
7. Medical Equipment for Human Subjects and Laboratory Animals
If medical equipment used for human patients/participants is also used on animals, describe such
equipment and disinfection procedures.
N/A
8. Participant Population
a)
State the following: (i) the number of participants expected to be enrolled at Stanford-affiliated site(s);
(ii)the total number of participants expected to enroll at all sites; (iii) the type of participants (i.e.
students, patients with certain cancer, patients with certain cardiac condition) and the reasons for
using such participants.
May 2021: N=160 was proposed for study enrollment. Final enrollment was N=180. Qualtrics panel
recruitment was the main recruitment method and had resulted in n=160; n=20 were from other recruitment
sources described in the protocol. For the next study, we'll try Qualtrics recruitment before other sources, as
the Qualtrics panel requires a prepaid agreement and results in speedy recruitment.
N=160 (nationally) will be invited to participate in this study and entered into the study on a rolling basis.
Protocol # 56439 ( Continuing Review )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 18 of 37
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders during COVID-19 (SU sIRB)
Approval Period:
04/30/2022 - 04/30/2023

Recruitment will be a joint effort by Stanford University and Woebot Labs. Neither election or declining to
participate in the study will impact Woebot users ability to continue using the product as they wish.
Inclusion criteria include: all genders aged 18-65 years, access to Woebot on smartphone, be available and
committed to engage with app and complete assessments, be willing to provide email address (to distribute
incentives), and be literate in English (as W-SUDs conversational and video materials will be in English).
Exclusion criteria include: pregnancy (as W-SUDs will not be specifically developed to address the unique
needs of this population), history of severe drug/alcohol use, opioid misuse without medication-assisted
treatment, and suicide attempt or opioid overdose within the past year. Randomization will occur through
the survey program by the time the participant finishes the baseline survey.
Participants and Recruitment: N=160 (nationally) will be invited to participate in this study. Recruitment
channels may include Woebot Labs' social media avenues (e.g., Facebook, Twitter, LinkedIn, Woebot.io,
Nextdoor), Craigslist, Reddit, physical flyers, emailing clinics (with their permission), posting to Stanford
Staffers listserv, and advertising to the WELL cohort. Stanford staff may post in other listservs with
permission, and contact participants from other studies if those participants have interest in other studies.
The team may use Qualtrics panels to recruit. Participants will be entered into the study on a rolling basis.
Neither election or declining to participate in the study will impact Woebot users ability to continue using
the product as they wish. Inclusion criteria include: all genders aged 18-65 years, access to Woebot on
smartphone, be available and committed to engage with app and complete assessments, be willing to
provide email address (as this is how assessment incentives will be distributed), and be literate in English
(as W-SUDs conversational and video materials will be in English).
Exclusion criteria include: pregnancy (as W-SUDs will not be specifically developed to address the unique
needs of this population), history of severe drug/alcohol use, opioid misuse without medication-assisted
treatment, and suicide attempt or opioid overdose within the past year. Participants residing outside the U.S.
will not be included. Participants who have ever used Woebot will also not be recruited. Use of Woebot
(without SUDs program) post randomization, regardless of group assignment, is allowed. Those who elect
to participate will be provided with a specific code to enter into Woebot to cue the SUDs specific content.
Randomization: Randomized controlled trial of W-SUDs vs a wait-list control condition (will get access to
the SUD program at the end of the study; no intervention during the 8 week period)
This supplemental study proposes to randomize individuals to two conditions (estimating n=80 in each
group), W-SUDs or a wait-list control condition, in order to:
(i) compare between group substance use outcomes at end-of-treatment;
(ii) assess and analyze comparative impact of Covid-19 in each group;
(iii) conduct a moderation analysis. Do putative moderators moderate treatment impact upon substance use
outcomes?
Primary aim / outcome: Compare between group treatment outcomes.
Hypothesis: W-SUDs will have significantly improved outcomes compared to the wait-list control group.
Variable of interest: AUDIT/DAST scores across the two groups.
Secondary aim / outcome: Investigate the differential impact of Covid-19 upon psychological functioning
across the two groups (one in W-SUDs, the other without intervention).
Purpose: to understand the impact of Covid-19 under a no intervention vs W-SUDs intervention.
Variables of interest: see list below. These variables will be measured at BL, week 4, and end-of-treatment
at week 8. Total of 3 surveys.
Exploratory aim / outcome: To investigate putative moderators of treatment on outcome (and/or of
treatment engagement).
Variables of interest include:
Mood: depression (PHQ), anxiety (GAD), loneliness, grief
Covid-19 related situational triggers: financial worry, ability to work, essential worker status, safety at
home, children at home, degree of closeness to the illness (know someone who is ill, died),
Protocol # 56439 ( Continuing Review )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 19 of 37
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders during COVID-19 (SU sIRB)
Approval Period:
04/30/2022 - 04/30/2023

Current treatment engagement: level of engagement in other recovery support systems, alliance to Woebot.
Intervention Delivery: W-SUDs will be administered over the course of 8-weeks. Woebot may follow up by
email to encourage participants to open the app and check in. The control group will not have access to the
W-SUDs program till after completion of their EOT survey at the 8-week mark. Additionally, while the
wait-listed group won't have additional surveys (i.e., post app use), we will gather/analyze the info we get
from their use of Woebot.
Survey Administration Plan: Qualtrics or REDCap, HIPAA compliant online data center survey
administration tools (commonly used by Stanford University), will be utilized to administer the assessment
batteries including BL, 4-week, and the EOT questionnaires. During the consent form section, participants
will be asked for their email in order to receive study communications including 1) Their signed consent
form, 2) Instructions for downloading the Woebot app and using the referral code for the Woebot-SUDs
program, and 3) A survey link for follow up assessments. After the baseline is completed, participants will
be emailed their signed consent form and instructions. After the 4-week and 8-week phase, participants will
receive their survey links via email.
Data Analysis: In order to analyze feasibility and acceptability data, descriptive statistics will be used for the
following scales: Usage Rating Profile Intervention (UPRI)-Acceptability, Usage Rating Profile
Intervention (UPRI)--Feasibility, and Client Satisfaction Questionnaire (CSQ-8). Such descriptive statistics
will provide a summary index of how likable the content and program was overall.
In order to better understand what specific W-SUDs content the participants like, Lesson Completion Rates,
and Content Rating Metrics will be analyzed.
Lesson Completion Rates will indicate which of the specific W-SUDs lessons were completed. Content
Rating Metrics are how participants rate each lesson; they are self-reported by the participant, via Woebot,
and are provided on a binary scale: either a thumbs up or thumbs down emoticon. If a lesson receives a
thumbs down, Woebot offers the user a chance to give additional free-text feedback. Thus, both the binary
answers (thumbs up or thumbs down) plus the free-text feedback will be used to pinpoint which lessons are
performing well and which need editing. Effect sizes will surmise mean changes from baseline to
post-treatment on drug use psychopathology. Due to the small sample size of this pilot study, effect sizes,
rather than tests involving statistical significance, will be used to assess the intervention's impact from
baseline to EOT.
Additionally, pain and craving questions will be asked in the Woebot app to monitor change over time.
Subtle changes to wording in these questions may be made for organic conversation.
Refining W-SUDs: Utilizing study results as described above, the research team will learn the efficacy of a
digital substance use therapeutic during a pandemic. The intent is to utilize and leverage what was learned
in this study to provide an intervention in a time where in person services are discouraged.
b)
State the age range, gender, and ethnic background of the participant population being recruited.
Inclusion Criteria:
Eligible participants for this trial must:
1. Have a smartphone
2. Endorse a substance use concern
3. Be between 18 and 65 years of age
4. Be available and committed to engage with the Woebot app
5. Be literate in English.(This is required for inclusion because all materials for app and website will be in
English).
Exclusion Criteria:
1. Pregnancy (as W-SUDs will not be specifically developed to address the unique needs of this population)
2. Suicide attempt within the past year
Protocol # 56439 ( Continuing Review )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 20 of 37
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders during COVID-19 (SU sIRB)
Approval Period:
04/30/2022 - 04/30/2023

3. Symptoms of severe drug/alcohol history: History of delirium tremens; Experiencing seizures or
confusion after stopping alcohol or drugs; Liver trouble (cirrhosis or hepatitis); Convulsions or GI bleeding
due to drug/alcohol use
4. Opioid overdose within the past 12 months
5. Opioid misuse without medication-assisted treatment
6. Ever used Woebot (To avoid sample contamination)
Recruitment efforts will seek to enroll a demographically diverse sample. Substance disorders are prevalent
in individuals of all genders, therefore all genders will be recruited as participants in the proposed study.
c)
State the number and rationale for involvement of potentially vulnerable subjects in the study
(including children, pregnant women, economically and educationally disadvantaged, decisionally
impaired, homeless people, employees and students). Specify the measures being taken to minimize the
risks and the chance of harm to the potentially vulnerable subjects and the additional safeguards that
have been included in the protocol to protect their rights and welfare.
N/A
d)
If women, minorities, or children are not included, a clear compelling rationale must be provided (e.g.,
disease does not occur in children, drug or device would interfere with normal growth and
development, etc.).
Exclusion of Pregnant Women: Pregnancy (as W-SUDs will not be specifically developed to address the
unique needs of this population). Exclusion of Children. The proposed study will include individuals
between 18-65 years of age. Persons younger than 18 will not be included in the study, as the proposed
substance disorder treatments were not designed for nor tested among youth and the characterization of
SUD in youth differs in meaningful ways from that in adults. Given the small sample sizes for this pilot and
that Woebot has not yet been tested among youth, the proposed research is focused on those aged 18 and
older.
e)
State the number, if any, of participants who are laboratory personnel, employees, and/or students.
They should render the same written informed consent. If payment is allowed, they should also receive
it. Please see Stanford University policy.
0
f)
State the number, if any, of participants who are healthy volunteers. Provide rationale for the
inclusion of healthy volunteers in this study. Specify any risks to which participants may possibly be
exposed. Specify the measures being taken to minimize the risks and the chance of harm to the
volunteers and the additional safeguards that have been included in the protocol to protect their rights
and welfare.
0 healthy volunteers. 160 volunteers will have endorsed a substance use concern for problematic use and
screened out if pregnant during recruitment. Other than these health implications, participants will otherwise
be healthy volunteers and will not be exposed to health risks through their participation.
g)
How will you identify and recruit potential participants about the research study? (E.g., by: Honest
Broker or other https://researchcompliance.stanford.edu/participantengagement Research
Participation services; chart review; treating physician; ads). All final or revised recruitment
materials, flyers, etc. must be submitted to the IRB for review and approval before use. You may not
contact potential participants prior to IRB approval. See Advertisements: Appropriate Language for
Recruitment Material.
Recruitment: For this study, Woebot Labs' will post study advertisements and recruit via their already active
internet channels including Twitter (over 2,000 followers), LinkedIn (over 400 followers), and Facebook
(over 16,500 followers). To supplement recruiment, Woebot Labs' may post on Craigslist, Nextdoor, and on
Reddit through relevant subreddits with written permission from the subreddits' moderators. Woebot may
email clinics. Woebot may also post physical flyers and the Stanford team may post on the Stanford Staffers
listserv. The Stanford team may recruit from the WELL cohort, with permission. Stanford staff may post in
other listservs with permission. The Stanford team may recruit participants from other studies who have
Protocol # 56439 ( Continuing Review )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 21 of 37
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders during COVID-19 (SU sIRB)
Approval Period:
04/30/2022 - 04/30/2023

indicated interest in other studies. The team may use Qualtrics panels to recruit. Woebot exchanges an
average of 1-2 million messages per week with its users. Woebot users have indicated interest in substance
use content. Specifically, 63% of current users (surveyed in July 2018) reported interest in content related to
substance use. In regards to their specific substance use behaviors over the previous month, 22% of users
reported having 5 or more alcoholic drinks in a row within a couple of hours (i.e., binge use), and 5%
endorsed using non-prescription drugs. Woebot Labs has used these channels for previous research
participation invitations with success.
Minor editing changes may be made to recruitment materials to enhance clarity.
Participants will be asked for their age during the screener. If ineligible, they will be not be able to
participate in the Woebot for Substance Use Disorders study. We will ask for date of birth in the
questionnaire after the signed consent to confirm that the participant is not underage. This is standard best
practice for use of the program and for other online research studies.
h)
Inclusion and Exclusion Criteria.
Identify inclusion criteria.
Inclusion Criteria:
Eligible participants for this trial must:
1. Have a smartphone
2. Endorse a substance use concern
3. Be between 18 and 65 years of age
4. Be available and committed to engage with the Woebot app
5. Be literate in English.(This is required for inclusion because all materials for app and website will be in
English).
Identify exclusion criteria.
Exclusion Criteria:
1. Pregnancy (as W-SUDs will not be specifically developed to address the unique needs of this population)
2. Suicide attempt within the past year (12 months)
3. Symptoms of severe drug/alcohol history: History of delirium tremens; Experiencing hypertension,
drenching sweats, seizures or confusion after stopping alcohol or drugs; Liver trouble (cirrhosis or
hepatitis); Convulsions or GI bleeding due to drug/alcohol use
4. Opioid overdose within the past year (12 months)
5. Opioid misuse without medication-assisted treatment
6. Not residing in the U.S.
7. Ever used Woebot
i)
Describe your screening procedures, including how qualifying laboratory values will be obtained. If
you are collecting personal health information prior to enrollment (e.g., telephone screening), please
request a waiver of authorization for recruitment (in section 15).
Screening
There will be a brief internet delivered (via Qualtrics or REDCap) screener that will ascertain if individuals
who express interest in participating in the study meet inclusion criteria. The screener-battery will include
the Drug Abuse Screening Test (DAST-10), CAGE Questions Adapted to Include Drug Use (CAGE-AID),
Michigan Alcohol Screening Test (MAST), Psychosis Screening Questionnaire (PSQ), and a few relevant
demographic questions (i.e., age, pregnancy status, suicide or overdose within the past year). Those who do
not meet criteria will be welcomed to begin using the generic (non-SUD focused) Woebot and the website
without restriction but will not be enrolled into the study. In addition, additional substance treatment
resources will be provided.
j)
Describe how you will be cognizant of other protocols in which participants might be enrolled. Please
explain if participants will be enrolled in more than one study.
Consent form will ask whether the participant is currently enrolled in any additional studies.
k)
Payment/reimbursement. Explain the amount and schedule of payment or reimbursement, if any, that
will be paid for participation in the study. Substantiate that proposed payments are reasonable and
commensurate with the expected contributions of participants and that they do not constitute undue
Protocol # 56439 ( Continuing Review )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 22 of 37
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders during COVID-19 (SU sIRB)
Approval Period:
04/30/2022 - 04/30/2023

pressure on participants to volunteer for the research study. Include provisions for prorating payment.
See payment considerations
Supplemental funding pending approval. $25 for an Amazon gift card per assessment (baseline, 4 week, and
8 week) completed for each of the 160 participants. Total potential amount possible per participant: $75
l)
Costs. Please explain any costs that will be charged to the participant.
There will be no cost to participants.
m)
Estimate the probable duration of the entire study. Also estimate the total time per participant for: (i)
screening of participant; (ii) active participation in study; (iii) analysis of participant data.
Total duration estimated to be 3.5 years. Content development is ready. Recruitment for about 2 months.
Participation in the study is estimated to be 2 months. Estimated time for screening is 3 minutes or less;
Each survey estimated to be 15-30min. Active participation is 2 months with a follow up surveys at the 4-
week and 8- week mark. Data analysis and dissemination estimated to be 3 years.
9. Risks
a) For the following categories include a scientific estimate of the frequency, severity, and reversibility of potential
risks. Wherever possible, include statistical incidence of complications and the mortality rate of proposed
procedures. Where there has been insufficient time to accumulate significant data on risk, a statement to this
effect should be included. (In describing these risks in the consent form to the participant it is helpful to use
comparisons which are meaningful to persons unfamiliar with medical terminology.)
The risks of the Investigational devices.
N/A
The risks of the Investigational drugs. Information about risks can often be found in the Investigator's
brochure.
N/A
The risks of the Commercially available drugs, reagents or chemicals. Information about risks can
often be found in the package insert.
N/A
The risks of the Procedures to be performed. Include all investigational, non-investigational and
non-invasive procedures (e.g., surgery, blood draws, treadmill tests).
N/A
The risks of the Radioisotopes/radiation-producing machines (e.g., X-rays, CT scans, fluoroscopy) and
associated risks.
N/A
The risks of the Physical well-being.
N/A
The risks of the Psychological well-being.
Potential Upset due to Survey Questions: Foreseeable risks to subjects include the possibility that some
assessment questions and/or treatment procedures may be upsetting to subjects. Experience at Stanford with
similar populations has indicated that the risk of emotional upset during the assessments is low and if it
occurred, the upset would likely not be serious in nature and temporary. Such risks will be minimized by the
thoughtful selection of questionnaires. Potential participants will also be informed that they may drop out of
the study at any time and if requested, appropriate treatment referrals would then be given.
The risks of the Economic well-being.
N/A
Protocol # 56439 ( Continuing Review )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 23 of 37
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders during COVID-19 (SU sIRB)
Approval Period:
04/30/2022 - 04/30/2023

The risks of the Social well-being.
Potential loss of confidentiality.
Overall evaluation of Risk.
Low - innocuous procedures such as phlebotomy, urine or stool collection, no therapeutic agent, or safe
therapeutic agent such as the use of an FDA approved drug or device.
b)
If you are conducting international research, describe the qualifications/preparations that enable you
to both estimate and minimize risks to participants. Provide an explanation as to why the research
must be completed at this location and complete the
[LINKFORINTERNATIONALREASEARCHFORM] International Research Form. If not applicable,
enter N/A.
N/A
c)
Describe the planned procedures for protecting against and minimizing all potential risks. Include the
means for monitoring to detect hazards to the participant (and/or to a potential fetus if applicable).
Include steps to minimize risks to the confidentiality of identifiable information.
Given that the research aims to enroll a low-treatment seeking population, we do not envisage that
participation in the study will be associated with elevated risk. We are not assessing suicidal ideation in our
questionnaires. During the eligibility screener, those who have had a suicide attempt within the past year
will be excluded from the study. It is not feasible to confirm the responses by participants to the
questionnaires in real time. However, some risk is always present in studies that involve human participants.
Such risk may include the following:
1. Data Protection and Privacy: All study data are gathered on a HIPAA compliant web platform that resides
behind Stanford security firewalls and has been tried and tested by the University for several years, thus
actual risk from data breach for study data is low. All assessments, including the screening, four assessment
batteries, and mediator assessment will be administered via a HIPAA compliant survey administration tool
commonly used by Stanford University in its clinical trials (Qualtrics or REDCap). Given the high data
protection safeguards embedded within Qualtrics or REDCap, there is little risk to the subject associated in
regards to their privacy and/or confidentiality.
Research material obtained from human subjects will involve behavioral and psychological assessments
including self-report questionnaires. All data will be obtained specifically for purposes of this research
project. Data that is obtained from the Qualtrics or REDCap assessments will be stored and protected within
Qualtrics or REDCap. Data that is obtained via Woebot will be encrypted and stored on Amazon Web
Services (AWS); Woebot Labs data gathering and storage procedures are compliant with both the Health
Insurance Portability and Accountability Act (HIPAA) and the European Union's General Data Protection
Regulation (GDPR) compliant. Only members of the research team (PI, Co-PIs, biostatistician, research
assistant) will have access to the data.
2. Potential Upset due to Survey Questions: Foreseeable risks to subjects include the possibility that some
assessment questions and/or treatment procedures may be upsetting to subjects. Experience at Stanford with
similar populations has indicated that the risk of emotional upset during the assessments is low and if it
occurred, the upset would likely not be serious in nature and temporary. Such risks will be minimized by the
thoughtful selection of questionnaires. Potential participants will also be informed that they may drop out of
the study at any time and if requested, appropriate treatment referrals would then be given.
3. Risk of treatment avoidance due to engagement with either of the randomized interventions. In both
interventions it is explicitly stated that the service should not be used in place of traditional treatment. In the
case of the W-SUDs intervention, Woebot is designed to hold individuals accountable for pursuing
additional options in conditions of unchanged symptoms for a prolonged amount of time (4 weeks). In
addition, Woebot will invite the user to consider what seeking additional services would look like.
4. Risk of suicide: Woebot informs the participant that it is not designed for crisis service. Additionally,
Woebot detects crisis language (e.g. "want to kill") and asks to confirm it with the user. If the user confirms,
Protocol # 56439 ( Continuing Review )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 24 of 37
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders during COVID-19 (SU sIRB)
Approval Period:
04/30/2022 - 04/30/2023

Woebot automatically, in real-time offers resources (9-1-1, suicide crisis hotlines, referral to ER). Woebot's
crisis detectors flags around 200 possible harm to self phrases, including about 10 misspellings and 5 slang
phrases. Woebot's data indicate that users do not use Woebot for crisis management; about 6.3% trigger the
safety net protocol, of which 27% confirm that it is indeed a crisis (i.e., for a true crisis rate of 1.7%).
Woebot's algorithm is over-sensitive, designed to over-detect, rather than under-detect to make sure that
cases are not missed. Woebot staff periodically check the data for true/false positive rates. Additionally, if
anyone is developing or indicating serious thoughts about suicide or harming themselves, it is best practice
to call 9-1-1 and/or go to the nearest ER.
d)
Explain the point at which the experiment will terminate. If appropriate, include the standards for the
termination of the participation of the individual participant Also discuss plans for ensuring necessary
medical or professional intervention in the event of adverse effects to the participants.
The study will terminate once the 2-month period with all 150 participants has been completed and the
analyses run and submitted for publication.
Participants can refuse to participate at any time.
When we learn of a participant's adverse event, the team will report the adverse event and may follow up
with the participant for additional information. Resources will be offered. The EOT survey includes
questions that assess for SAEs. More details about adverse events are in section e.
e)
Data Safety and Monitoring Plan (DSMP). See guidance on Data Safety and Monitoring.
A Data and Safety Monitoring Plan (DSMP) is required for studies that present Medium or High risk
to participants. (See Overall Evaluation of Risk above). If Low Risk, a DSMP may not be necessary.
Multi-site Phase III clinical trials funded by NIH require the DSM Plan to have a Data Safety
Monitoring Board or Committee (DSMC or DSMB). The FDA recommends that all multi-site clinical
trials that involve interventions that have potential for greater than minimal risk to study participants
also have a DSMB or DSMC.
The role of the DSMC or DSMB is to ensure the safety of participants by analyzing pooled data from
all sites, and to oversee the validity and integrity of the data. Depending on the degree of risk and the
complexity of the protocol, monitoring may be performed by an independent committee, a board
(DSMC/DSMB), a sponsor's Data Safety Committee (DSC), a Medical Monitor, a sponsor's safety
officer, or by the Protocol Director (PD).
Describe the following:
What type of data and/or events will be reviewed under the monitoring plan, e.g. adverse events,
protocol deviations, aggregate data?
The Data Safety and Monitoring Plan will include Woebot's standard safety net protocol as well as a
Data Safety and Monitoring Board overseen by Stanford University. Woebot's Safety Net Procedures
Study informed consent will state that Woebot is not a crisis program designed to address active suicidal
ideation or overdose. Woebot also conversationally informs first time users that it is not a crisis service.
Our current safety net protocol will be adapted for the proposed study. Woebot's crisis detectors flags
around 200 possible harm to self phrases, including about 10 misspellings and 5 slang phrases. Woebot
detects crisis language (e.g. "want to kill") and asks to confirm it with the user. If the user confirms,
Woebot offers resources (9-1-1, suicide crisis hotlines), carefully curated with expert consultation. Our
data indicate that users do not use Woebot for crisis management; about 6.3% trigger the safety net
protocol, with 27% confirming that it is indeed a crisis when Woebot asks to confirm (i.e., our true
positive rate). To make sure that we do not miss any cases, we over detect, rather than under detect. In
addition, we periodically check the data for true/false positive rates. Adverse Events We do not
anticipate that the use of the interventions will increase risk as outlined above. In addition, there is a
limited capacity to detect adverse events (such as overdose, suicide attempt or hospitalization related to
substance use or other) unless explicitly voluntarily reported by the participant. In the case Stanford
Protocol # 56439 ( Continuing Review )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 25 of 37
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders during COVID-19 (SU sIRB)
Approval Period:
04/30/2022 - 04/30/2023

University and / or Woebot Labs becomes aware of an adverse event, the appropriate protocol, approved
by the DSMB and Stanford University's Institutional Review Board, will be immediately implemented.
This includes immediate notification of the IRB, DSMB, and NIH, and an immediate convening of the
DSMB to discuss requisite follow-up steps.
Identify who will be responsible for Data and Safety Monitoring for this study, e.g. Stanford
Cancer Institute DSMC, an independent monitoring committee, the sponsor, Stanford investigators
independent of the study, the PD, or other person(s).
To ensure the data protection and safety of research participants, Stanford University will serve as the
Data Coordinating Center for the study under the coordination of Drs. Biaocchi and Prochaska. They
will convene a group of three to serve as an oversight board with professional expertise in the area of the
study. Dr. Prochaska is an expert in the field of addiction and substance use, and Dr. Biaocchi has
experience in managing data protections in the context of randomized clinical trials.
Provide the scope and composition of the monitoring board, committee, or safety monitor, e.g.,
information about each member's relevant experience or area of expertise. If the Monitor is the
Stanford Cancer Center DSMC or the PD, enter N/A.
DSMB's specific goals: • Review new or modifications to existing risk management protocols • Review
procedures for maintaining confidentiality, data collection, management, and analyses • Review
progress towards meeting enrollment goals • Recommend continuation, discontinuation, modification,
or termination of a study based on emerging data (from the study and from the literature) and evaluation
of risk/benefit ratios • Conduct annual reviews to determine whether patient safety has been adequately
safeguarded • Review progress reports
Confirm that you will report Serious Adverse Events (SAEs), Suspected Unexpected Serious
Adverse Reactions (SUSARs), or Unanticipated Problems (UPs) to the person or committee
monitoring the study in accordance with Sponsor requirements and FDA regulations.
Yes.
If applicable, how frequently will the Monitoring Committee meet? Will the Monitoring Committee
provide written recommendations about continuing the study to the Sponsor and IRB?
Dr Prochaska will coordinate the meetings by assisting in setting the agenda and ensuring that the
necessary materials are provided for each meeting. The initial meeting of the Board will take place
during the first three months of the study, i.e., before entry into the second Phase of the research, to
allow for the consideration of the protocol from the viewpoint of data safety and participant
confidentiality. Subsequent meetings will be held at 6-month intervals, with the possibility for either an
interim meeting or telephone conversation conference call should the necessity arise. At the first
meeting, Dr Prochaska will brief the board on the study design and procedures. The Board will then
provide feedback on the data that they will wish to review at their subsequent meetings.
Specify triggers or stopping rules that will dictate when the study will end, or when some action is
required. If you specified this in Section 2g [Study Endpoints], earlier in this application enter 'See
2g'.
Endpoints will be indicated by the cessation of W-SUDs intervention delivery at 8-weeks, data analysis
and interpretation, refinement of W-SUDs, and the end of the 4 month period (ending mark of the
study).
Indicate to whom the data and safety monitoring person, board, or committee will disseminate the
outcome of the review(s), e.g., to the IRB, the study sponsor, the investigator, or other officials, as
appropriate.
The proposed study has a dissemination plan that encapsulates two important arenas: 1)
ClinicalTrials.gov compliance and 2) Dissemination. ClinicalTrials.gov Compliance If the proposal is
successfully awarded, the applicant will ensure that the the trial's registration and results reporting
procedures are thoroughly managed. The trial will be registered promptly upon receipt of the award and
before the recruitment of human subjects. All informed consent documents will include specific and
thorough statements referring to the posting on ClinicalTrials.gov. At the conclusion of the study and
Protocol # 56439 ( Continuing Review )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 26 of 37
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders during COVID-19 (SU sIRB)
Approval Period:
04/30/2022 - 04/30/2023

following analysis of the results, results will be reported as well, in compliance with the
ClinicalTrials.gov procedures. Woebot Labs has a protocol in place outlining the importance and details
of ensuring the ClinicalTrials.gov procedures are up to date. Dissemination of Research Both Stanford
University and Woebot Labs will facilitate with the dissemination of research. They will collaborate on
manuscript preparation and submission, as well as abstract submission and presentations at national and
international scientific and technology-oriented conferences.
Select One:
The Protocol Director will be the only monitoring entity for this study.
Y
This protocol will utilize a board, committee, or safety monitor as identified in question #2 above.
10. Benefits
a)
Describe the potential benefit(s) to be gained by the participants or by the acquisition of important
knowledge which may benefit future participants, etc.
When evaluating the risks and benefits of the proposed study, it is
believed that risks are relatively minimal when compared to the
potential therapeutic benefits that subjects are likely to receive. The
benefits of receiving W-SUDs include potentially reducing substance
abuse, acquiring practical psychotherapeutic skills (from cognitive
behavioral therapy, motivational interviewing,
dialectical behavior therapy, and mindfulness), and receiving
psychoeducation about substance abuse. Participants who reduce substance
abuse may derive additional benefits should reduction in substance abuse
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 efficacy, utility, and cost-benefits of a W-SUDs, the first
SUDs-focused digital therapeutic delivered by an artificial intelligence
(AI)-powered conversational agent.
The study allows the opportunity to expand understanding of W-SUDs'
performance among this population whilst contributing to our overall
understanding of Covid-19's impact upon this population. When Covid-19
spread, users from around the world came to Woebot to discuss the
pandemic and seek help. The company responded by building a Covid-19
specific program for Woebot (W-C19) which was initially deployed in
March 2020. Elements of our W-C19 program have already been integrated
into W-SUDs because we felt that it was timely and appropriate to
address users' concerns about the pandemic and demonstrated that Woebot
was 'intelligent' to the current crisis.
The proposed supplement will offer immediate access to a digital
therapeutic in a resource constrained, socially distanced healthcare
ecosystem to an already vulnerable and underserved population, who are
likely faced with readily growing psychological challenges.
11. Privacy and Confidentiality
Protocol # 56439 ( Continuing Review )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 27 of 37
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders during COVID-19 (SU sIRB)
Approval Period:
04/30/2022 - 04/30/2023

Privacy Protections
a)
Describe how the conditions under which interactions will occur are adequate to protect the privacy
interests of participants (e.g., privacy of physical setting for interviews or data collection, protections
for follow-up interactions such as telephone, email and mail communications).
All assessments, including the screening and the two assessment
batteries, will be administered via a HIPAA compliant survey
administration tool commonly used by Stanford University in its
clinical trials (Qualtrics or REDCap). Given the high data protection
safeguards embedded within Qualtrics and REDCap, there is little risk to
the subject associated in regards to their privacy and/or
confidentiality.
Research material obtained from human subjects will involve
behavioral and psychological assessments including self-report
questionnaires. All data will be obtained specifically for purposes of
this research project. Data that is obtained from the Qualtrics or
REDCap assessments will be stored and protected within Qualtrics or
REDCap. Data that is obtained via Woebot will be encrypted and stored on
Amazon Web Services (AWS); Woebot Labs data gathering and storage
procedures are compliant with both the Health Insurance Portability and
Accountability Act (HIPAA) and the European Union's General Data
Protection Regulation (GDPR) compliant. Only members of the research
team (PI, Co-PIs, biostatistician, research assistant) will have access
to the data.
Confidentiality Protections
b)
Specify PHI (Protected Health Information). PHI is health information linked to HIPAA identifiers
(see above). List BOTH health information AND HIPAA identifiers. If you are using STARR, use the
Data Privacy Attestation to ensure that your request will match your IRB-approved protocol. Be
consistent with information entered in section 15a.
Individual names, email addresses, phone numbers, dates of birth,
gender/biological sex, IP addresses (automatically collected through
Qualtrics), geo location (automatically collected through Qualtrics),
and zip codes.
Drug Use Psychopathology
1. The Drug Abuse Screening Test 10 (DAST-10), a brief, 10-item
self-report measure adapted from the 28-item DAST, assesses
consequences related to drug abuse, excluding alcohol and tobacco. A
score of 3 or higher indicates significant problems related to drug
abuse. The DAST-10 demonstrated discriminate validity between
individuals (i) with lifetime drug use disorders and those without and
(ii) who are current abusers and those who are former abusers. It also
has moderate level of test-retest and reliability as well as sensitivity
and specificity.
2. The Alcohol Use Disorders Identification Test-Consumption
(AUDIT-C) is a widely used 3-item self-report screen for hazardous or
harmful alcohol consumption that is based off of the 10-item original
AUDIT. Developed by the World Health Organization, the AUDIT has been
tested extensively in primary-care settings and various outpatient
substance abuse treatment population, supporting the application of this
screener tool. The AUDIT-C has been tested and validated across racial
groups.
6. The Drug Abstinence Self-Efficacy Scale (DASE) is a 12-item
self-report scale, reflecting Bandura's (1986) cognitive-behavioral
Protocol # 56439 ( Continuing Review )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 28 of 37
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders during COVID-19 (SU sIRB)
Approval Period:
04/30/2022 - 04/30/2023

self-efficacy theory, and is a shortened version of the original 20-item
scale. The 20-item scale has shown to be a reliable and valid measure of
self-efficacy for drug use. The scale will be adapted to refer to use of
both drugs and alcohol, by including that language in the item stem.
General Psychopathology
3. The Patient Health Questionnaire (PHQ-9) is a brief 9-item scale
used to determine the severity of depression in medical populations. The
PHQ-9 has high reliability across populations. We will not include item
#9 that assesses suicidal ideation.
4. The Generalized Anxiety Disorder (GAD-7) is a brief self-report
scale that identifies the degree to which an individual may have
generalized anxiety disorder. This scale has good internal consistency,
convergent validity with depression, stress, and anxiety, and is a valid
and efficient tool for GAD screening in clinical and general
populations.
Employee Health
5. The CAGE Adapted to Include Drug USE (CAGE-AID) was developed by
the John Hopkins Dept of Medicine. It's a brief instrument to measure
problematic drug use. The CAGE-AID is designed to be an easy yet
effective way for primary care providers to determine if substance abuse
exists and needs to be addressed.
7. The Michigan Alcohol Screening Test (MAST), revised is a 22
question instrument to measure problematic alcohol use. One of the most
widely used measures for assessing alcohol abuse, the MAST is a
questionnaire designed to provide a rapid and effective screening for
lifetime alcohol-related problems and alcoholism. The MAST has been
productively used in a variety of settings with varied populations.
8.
The Short Inventory of Problems- Alcohol and Drugs (SIP-AD) is a clinically tested 15-item measure
developed by NIH funded research that assesses severity of problematic drinking and drug usage.
c)
You are required to comply with University Policy that states that ALL electronic devices: computers
(laptops and desktops; OFFICE or HOME); smart phones; tablets; external hard disks, USB drives,
etc. that may hold identifiable participant data will be password protected, backed up, and encrypted.
See http://med.stanford.edu/datasecurity/ for more information on the Data Security Policy and links
to encrypt your devices.
Provide any additional information on ALL data security measures you are taking. You must use
secure databases such as https://researchcompliance.stanford.edu/panels/hs/redcap RedCap. If you are
unsure of the security of the system, check with your Department IT representative. Please see
http://med.stanford.edu/irt/security/ for more information on IRT Information Security Services and
http://www.stanford.edu/group/security/securecomputing/mobile_devices.html for more information
for securing mobile computing devices. Additionally,any PHI data on paper must be secured in an
locked environment.
By checking this box, You affirm the aforementioned. Y
All assessments, including the screening and two assessment batteries,
will be administered via a HIPAA compliant survey administration tool
commonly used by Stanford University in its clinical trials (Qualtrics
or REDCap). Given the high data protection safeguards embedded within
Qualtrics, there is little risk to the subject associated in regards to
their privacy and/or confidentiality.
Research material obtained from human subjects will involve behavioral
and psychological assessments including self-report questionnaires. All
data will be obtained specifically for purposes of this research
project. Data that is obtained from the Qualtrics or REDCap assessments
Protocol # 56439 ( Continuing Review )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 29 of 37
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders during COVID-19 (SU sIRB)
Approval Period:
04/30/2022 - 04/30/2023

will be stored and protected within Qualtrics or REDCap, and on Stanford
Medicine Box. Data that is obtained via Woebot will be encrypted and
stored on Amazon Web Services (AWS); Woebot Labs data gathering and
storage procedures are compliant with both the Health Insurance
Portability and Accountability Act (HIPAA) and the European Union's
General Data Protection Regulation (GDPR) compliant. Only members of the
research team (PI, Co-PIs, biostatistician, research assistant) will
have access to the data.
The Stanford research team will use Stanford encrypted, password
protected, and backed up electronic devices (laptops, mobile devices)
for this project.
d)
Describe how data or specimens will be labeled (e.g. name, medical record number, study number,
linked coding system) or de-identified. If you are de-identifying data or specimens, who will be
responsible for the de-identification? If x-rays or other digital images are used, explain how and by
whom the images will be de-identified.
Each participant will be assigned a unique study ID number that will
take the place of any identifying information. Surveys will be done
online with individual survey URLs matched to study ID provided to
participants. All data therefore will be coded for the
large dataset.
No names will be attached to surveys. Study staff is responsible for
the coding.
Woebot user data provided to Stanford will be de-identified and linked
via study ID to the study assessments we collect via RedCap or Qualtrics
and the data will not be shared outside of the Woebot and Stanford
teams.
e)
Indicate who will have access to the data or specimens (e.g., research team, sponsors, consultants) and
describe levels of access control (e.g., restricted access for certain persons or groups, access to linked
data or specimens).
The PD and co-investigator and the research team will have access to
the study data. All data will be locked or password-protected or
both.
f)
If data or specimens will be coded, describe the method in which they will be coded so that study
participants' identities cannot be readily ascertained from the code.
Each participant will be assigned a unique participant ID number,
starting with 001 through 1000, to code data.
g)
If data or specimens will be coded, indicate who will maintain the key to the code and describe how it
will be protected against unauthorized access.
The codes of names and ID numbers will be accessed by the research
team only, stored securely in Qualtrics or REDCap, and/or a password
protected file.
h)
If you will be sharing data with others, describe how data will be transferred (e.g., courier, mail) or
transmitted (e.g., file transfer software, file sharing, email). If transmitted via electronic networks,
describe how you will secure the data while in transit.See
http://www.stanford.edu/group/security/securecomputing/
http://www.stanford.edu/group/security/securecomputing/. Additionally, if you will be using or sharing
PHI see https://uit.stanford.edu/security/hipaa https://uit.stanford.edu/security/hipaa.
Coded data may be sent by secure email settings provided by Stanford.
Protocol # 56439 ( Continuing Review )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 30 of 37
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders during COVID-19 (SU sIRB)
Approval Period:
04/30/2022 - 04/30/2023

Woebot user data provided to Stanford will be coded and linked via study
ID to the study assessments we collect via RedCap or Qualtrics and the
data will not be shared outside of the Woebot and Stanford teams.
i)
How will you educate research staff to ensure they take appropriate measures to protect the privacy of
participants and the confidentiality of data or specimens collected (e.g. conscious of oral and written
communications, conducting insurance billing, and maintaining paper and electronic data)?
The research staff will all be HIPAA and CITI trained and compliant
and supervised by Dr. Prochaska.
12. Potential Conflict of Interest
Investigators are required to disclose any financial interests that "
https://researchcompliance.stanford.edu/eprotocol-coi" target="_blank" reasonably appear to be related/li to this
protocol.
Financial Interest Tasks
Investigators
Role
Potential
COI?
Date
Financial
Interest
Answered
Date OPACS
Disclosure
Submitted
COI Review
Determination
13. Consent Background
13. 1
Consent
W-C19 Consent Form
Check if VA related
a)
Describe the informed consent process. Include the following.
i) Who is obtaining consent? (The person obtaining consent must be knowledgeable about the study.)
ii) When and where will consent be obtained?
iii) How much time will be devoted to consent discussion?
iv) Will these periods provide sufficient opportunity for the participant to consider whether or not to
participate and sign the written consent?
v) What steps are you taking to minimize the possibility of coercion and undue influence?
vi) If consent relates to children and if you have a reason for only one parent signing, provide that
rationale for IRB consideration.
Consent will be received via the mobile application wherever and whenever the participants choose and will
Protocol # 56439 ( Continuing Review )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 31 of 37
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders during COVID-19 (SU sIRB)
Approval Period:
04/30/2022 - 04/30/2023

take approximately 5 minutes. This will provide sufficient opportunity for the participant to consider
whether or not to participate and sign the online consent by mouse, finger, or stylus since there will be no
time limit. The online survey platform can obtain electronic signatures. Study staff will not be with the
potential participant and there will be no possibility of coercion or undue influence. No children will be
recruited.
b)
What is the Procedure to assess understanding of the information contained in the consent? How will
the information be provided to participants if they do not understand English or if they have a hearing
impairment? See HRPP Chapter12.2 for guidance.
Only English speaking participants will be recruited. The consent form will be readable so those with a
hearing impairment will still be able to access it.
c)
What steps are you taking to determine that potential participants are competent to participate in the
decision-making process? If your study may enroll adults who are unable to consent, describe (i) how
you will assess the capacity to consent, (ii) what provisions will be taken if the participant regains the
capacity to consent,(iii) who will be used as a legally authorized representative, and (iv) what
provisions will be made for the assent of the participant.
The consent form will only be accessible to those using a mobile application since that is the investigational
device. Participants will only include those competent to consent in the very low risk study.
13. 2
Consent
W-C19 Screener Consent Form
Check if VA related
a)
Describe the informed consent process. Include the following.
i) Who is obtaining consent? (The person obtaining consent must be knowledgeable about the study.)
ii) When and where will consent be obtained?
iii) How much time will be devoted to consent discussion?
iv) Will these periods provide sufficient opportunity for the participant to consider whether or not to
participate and sign the written consent?
v) What steps are you taking to minimize the possibility of coercion and undue influence?
vi) If consent relates to children and if you have a reason for only one parent signing, provide that
rationale for IRB consideration.
(i)Study staff will be obtaining the consent via online questionnnaire (Qualtrics or REDCap). (ii)This
consent will be at the beginning of the screening questionnaire (Qualtrics or REDCap). Since consent is
obtained online, it can be obtained at any location of the participants choosing. (ii)There is no time limit-
each respondent can take much time as they want to read through the consent. Reading consent is
anticipated to not take more than five minutes. (iv)Since consent is obtained online, the participant may take
as much time as they wish to consider whether or not to participate and proceed with the screener. The
online survey platform can obtain electronic signatures, and participants can sign the online consent by
mouse, finger, or stylus. (v)No incentive for form of coercion is present for the screening process. The study
is voluntary; Participants are informed that they can withdraw or choose not to participate at any time. There
is no payment for going through the screener. (vi)N/A.
b)
What is the Procedure to assess understanding of the information contained in the consent? How will
the information be provided to participants if they do not understand English or if they have a hearing
impairment? See HRPP Chapter12.2 for guidance.
We are not recruiting participants who cannot understand English.
c)
What steps are you taking to determine that potential participants are competent to participate in the
decision-making process? If your study may enroll adults who are unable to consent, describe (i) how
you will assess the capacity to consent, (ii) what provisions will be taken if the participant regains the
capacity to consent,(iii) who will be used as a legally authorized representative, and (iv) what
provisions will be made for the assent of the participant.
Participants will be reading the consent form before beginning the screener. Participants must be English
literate to participate as the questionnaires, consent forms, and Woebot app are only available in English.
The participant will have to select "Agree" to participate in the study. Contact information is also provided
during consent for the participant to use if they have questions about the study.
14. Assent Background (less than 18 years of age)
Protocol # 56439 ( Continuing Review )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 32 of 37
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders during COVID-19 (SU sIRB)
Approval Period:
04/30/2022 - 04/30/2023

15. HIPAA Background
15. 1
Waiver of Authorization for
Recruitment
waiver of authorization for recruitment
a)
Describe the protected health information (PHI) needed to conduct screening or recruitment. PHI is
health information linked to HIPAA identifiers. List BOTH health information AND HIPAA
identifiers. If you are using STARR, use the Data Privacy Attestation to ensure that your request will
match your IRB-approved protocol.
The following PHI will be collected via online screening through REDCap or Qualtrics. PHI collected:
name, phone number, email address, date of birth, gender/biological sex, substance use, health,
demographic information, zipcode, IP address (auto collected by Qualtrics), geographic location (auto
collected by Qualtrics).
b)
Please Answer:
Y
Do you certify that the use or disclosure of protected health information involves no more than a
minimal risk to the privacy of individuals?
Y
Do you certify that the research could not practically be conducted with out the waiver?
Y
Do you certify that you have adequate written assurances that the protected health information will
not be reused or disclosed to any other person or entity, except as required by law, for authorized
oversight of the research project, or for other research for which the use or disclosure of protected
health information would be permitted?
Y
Do you certify that the research could not practically be conducted with out access to and use of the
protected health information?
c)
Please describe an adequate plan to protect any identifiers from improper use and disclosure.
Data that is obtained from the Qualtrics or REDCap assessments will be stored and protected within
Qualtrics or REDcap. Data that is obtained via Woebot will be encrypted and stored on Amazon Web
Services (AWS); Woebot Labs data gathering and storage procedures are compliant with both the Health
Insurance Portability and Accountability Act (HIPAA) and the European Union’s General Data Protection
Regulation (GDPR) compliant. Only members of the research team (PI, Co-PIs, biostatistician, research
assistant) will have access to the data. Each participant will be assigned a unique study ID number that will
take the place of any identifying information. Surveys will be done online with individual survey URLs
matched to study ID provided to participants. All data therefore will be coded for the large dataset. No
names will be attached to surveys. Study staff is responsible for the coding. De-identified data may be sent
by secure email settings provided by Stanford. Woebot user data provided to Stanford will be de-identified
and linked via study ID to the study assessments we collect via REDCap or Qualtrics and the data will not
be shared outside of the Woebot and Stanford teams. The PD and co-investigator and the research team will
have access to the study data. All data will be locked or password-protected or both. The codes of names
and ID numbers will be accessed by the research team only, stored securely in Qualtrics or REDCap. The
research staff will all be HIPAA and CITI trained and compliant and supervised by Dr. Prochaska.
d)
Please describe an adequate plan to destroy the identifiers at the earliest opportunity consistent with
conduct of the research, unless there is a health or research justification for retaining the identifiers
or such retention is otherwise required by law.
The identifiers in the research will be destroyed following publication of the main manuscript.
Protocol # 56439 ( Continuing Review )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 33 of 37
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders during COVID-19 (SU sIRB)
Approval Period:
04/30/2022 - 04/30/2023

16. Attachments
Attachment Name
Attached Date
Attached By
Submitted Date
Woebot Recruitment Flyer
04/27/2020
achieng
Woebot for Substance Use
Disorders - Possible
Subreddits
04/27/2020
achieng
Woebot Branching Logic
04/27/2020
achieng
Referrals for Substance Use
Treatment 12.9.19
04/27/2020
achieng
Directions installing
registering Woebot App
04/27/2020
achieng
Woebot Crisis Language
Response
04/27/2020
achieng
Erin Vogel's CITI Completion
Report
04/27/2020
achieng
Woebot Security Risk
Management Plan
04/27/2020
achieng
Athena Robinson PHRP
Certificate
04/27/2020
achieng
Pain and Craving Questions to
be asked in the bot
04/27/2020
achieng
Stanford Staffers Listserv
Permission
04/27/2020
achieng
DRAFT NIDA Covid 19
Suppl - New Items -
April27_2pm
04/27/2020
achieng
Reddit Posting for NIDA
SUD Phase 1 Study Covid
Supplement for IRB Review
5.14.20
05/14/2020
achieng
Student Wellness Listserv
Permission
05/14/2020
achieng
Covid19 NIDA Application
PHS 398_5.05.20
05/14/2020
achieng
Woebot Listerv Recruitment
05/14/2020
achieng
Screenshots of Woebot
Conversational Pieces
05/14/2020
achieng
Timeline Flow and Woebot
Modules
05/14/2020
achieng
Protocol # 56439 ( Continuing Review )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 34 of 37
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders during COVID-19 (SU sIRB)
Approval Period:
04/30/2022 - 04/30/2023

Woebot EOT Survey Email
Template and Instructions
05/14/2020
achieng
Woebot Terms of Service
05/14/2020
achieng
Woebot Privacy Policy
05/15/2020
achieng
WC19 Scientific Protocol
05/15/2020
achieng
NIDA DSMB Meeting
Welcome Packet- 01.15.20
05/15/2020
achieng
NIDA DSMB Meeting
Agenda 01.15.20
05/15/2020
achieng
NIDA SUD DSMB Meeting
Minutes_01.15.20
05/15/2020
achieng
Woebot Data Protection
05/15/2020
achieng
NIDA SUD Phase I DSMB
Meeting Agenda - 5.6.2020
05/15/2020
achieng
DRA #731 Status
05/15/2020
achieng
WSUDs COVID Screener
Questions
05/15/2020
achieng
Assessment Timeline
05/18/2020
achieng
NIDA SUD DSMB Meeting
Minutes 5.6.20
05/18/2020
achieng
COVID 19 Clinical Research
Review Panel Response
05/18/2020
achieng
Emailing previous
participants
05/19/2020
sfelice
SUsIRB_IAA_Prochaska_564
39_SU signed
05/26/2020
srayate
Email template for Amazon
gift code
05/27/2020
achieng
NIH_NOA_3R44DA048712-
01S1
06/16/2020
achieng
NIDA_SUD_Flyer_COVID
06/16/2020
sfelice
Qualtrics Auto Email
Templates
06/22/2020
achieng
thumbnail_woebot-header-01
06/22/2020
achieng
thumbnail_woebot
06/22/2020
achieng
thumbnail_woebot-header-02
06/22/2020
achieng
thumbnail_woebot-header-04
06/22/2020
achieng
Woebot Phone Script
06/24/2020
achieng
Protocol # 56439 ( Continuing Review )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 35 of 37
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders during COVID-19 (SU sIRB)
Approval Period:
04/30/2022 - 04/30/2023

WC19 Baseline Questions
6.24.20
06/24/2020
achieng
Woebot Reminder email
06/24/2020
achieng
WC19 EOT Questions
7.20.20
07/20/2020
achieng
WC19 4Week Questions
8.12.20
08/12/2020
achieng
NIDA SUD DSMB Meeting
1.27.21_FINAL
03/25/2021
achieng
NIDA SUD DSMB Meeting
Minutes 1.27.21
03/25/2021
achieng
AshleyLee CITI Certifications 06/30/2021
achieng
NIDA SUD DSMB Meeting
6.16.21_FINAL
04/19/2022
gkmurphy
NIDA SUD DSMB Meeting
Minutes_06.16.21
04/19/2022
gkmurphy
Obligations
The Protocol Director agrees to:
•
Adhere to principles of sound scientific research designed to yield valid results
•
Conduct the study according to the protocol approved by the IRB
•
Be appropriately qualified to conduct the research and be trained in Human Research protection, ethical
principles, regulations, policies and procedures
•
Ensure all Stanford research personnel are adequately trained and supervised
•
Ensure that the rights and welfare of participants are protected including privacy and confidentiality of data
•
Ensure that, when de-identified materials are obtained for research purposes, no attempt will be made to
re-identify them.
•
Disclose to the appropriate entities any potential conflict of interest
•
Report promptly any new information, modification, or unanticipated problems that raise risks to
participants or others
•
Apply relevant professional standards.
Any change in the research protocol must be submitted to the IRB for review prior to the implementation of
such change. Any complications in participants or evidence of increase in the original estimate of risk should
be reported at once to the IRB before continuing with the project. Inasmuch as the Institutional Review
Board (IRB) includes faculty, staff, legal counsel, public members, and students, protocols should be written
in language that can be understood by all Panel members. The investigators must inform the participants of
any significant new knowledge obtained during the course of the research.
IRB approval of any project is for a maximum period of one year. For continuing projects and activities, it is
the responsibility of the investigator(s) to resubmit the project to the IRB for review and re-approval prior to
the end of the approval period. A Notice to Renew Protocol is sent to the Protocol Director 7 weeks prior to
Protocol # 56439 ( Continuing Review )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 36 of 37
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders during COVID-19 (SU sIRB)
Approval Period:
04/30/2022 - 04/30/2023

the expiration date of the protocol.
https://stanfordmedicine.box.com/shared/static/qbsi8u8h47qsotxhdpuzz50xlrqa0sgo.pdf Report promptly any
new information, complaints, possibly serious and/or continuing noncompliance, or unanticipated problems
involving risks to participants or others.
All data including signed consent form documents must be retained for a minimum of three years past the
completion of the research. Additional requirements may be imposed by your funding agency, your
department, or other entities. (Policy on Retention of and Access to Research Data, Research Policy
Handbook,
http://doresearch.stanford.edu/policies/research-policy-handbook/conduct-research/retention-and-access-research-data)
APPROVAL LETTER/NOTICE NOTE: List all items (verbatim) that you want to be included in your
approval letter (e.g., Amendment date, Investigator's Brochure version, consent form(s) version(s),
advertisement name, etc.) in the box below.
Y
By checking this box, I verify that I, as the Protocol Director (PD) responsible for this research protocol,
have read and agree to abide by the above obligations, or that I have been delegated authority by the PD to
certify that the PD has read and agrees to abide by the above obligations.
Protocol # 56439 ( Continuing Review )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 37 of 37
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders during COVID-19 (SU sIRB)
Approval Period:
04/30/2022 - 04/30/2023