Pilot: Randomized Controlled Trial of an Digital Therapeutic Versus Education for the Management of Problematic Substance Use
Phase: NA
Conditions: Alcohol Use Disorder (AUD), Substance Use Disorders
Sponsor: Woebot Health

Pilot: Digital Therapeutic vs Education for the Management of Problematic Substance Use
NCT04974645

Title :
Woebot for Substance Use Disorders Phase 2 RCT: Digitally Delivered Intervention for
Reducing Problematic Substance Use (SU sIRB)
Approval Period:
04/13/2022 - 05/12/2022
Modification Form ......................................................................................................
2
Personnel Info .............................................................................................................
3
Participant Population .................................................................................................
4
Study Location ............................................................................................................
5
General Checklist ........................................................................................................
5
Funding .......................................................................................................................
7
Resources ....................................................................................................................
8
Purpose, Study Procedures .......................................................................................... 10
Radioisotopes or Radiation Machines ......................................................................... 15
Drugs,Devices,Reagents ............................................................................................. 16
Medical Equipment for Human Subjects and Laboratory Animals ............................ 17
Participant Population(a-g) ......................................................................................... 17
Participant Population(h-m) ........................................................................................ 19
Risks(a-e) .................................................................................................................... 20
Privacy And Confidentiality ....................................................................................... 24
Conflict Of Interest ..................................................................................................... 25
Consent Background ................................................................................................... 28
Assent Background ..................................................................................................... 30
HIPAA Background .................................................................................................... 30
Attachments ................................................................................................................. 31
Obligations .................................................................................................................. 34
eProtocol # 58725 ( Modification )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 1 of 35
Review Type: Regular
Human Subjects Research
Medical
Stanford University

Modification
1. Summarize your proposed changes.
0 participants enrolled to date. We intend to incorporate the knowledge gained from the pilot study (IRB
62053) for this study prior to starting recruitment.
Proposed changes below.
Resources: Section a has been updated. Ken Weingardt, Amer Raheemullah, and Ashley Lee have been
removed.
Main Protocol Adjustments:
1) Removing PEth tests (biomarker of alcohol use)from the project . This affects General Checklist (#5),
Resources section c on PO Box, Protocol Information sections 2a, 8, 9, 11, ICF.
2) Removing MINI interviews from the project. This affects section 2a, 8, 11, ICF.
3) Section 2a: Added potential recruitment sources (also affects Resources e, and section 8g). Added Data
Flow wording from IRB 62053 (pilot study).
4) Section 3a background: Updated background info with preliminary data from pilot study (IRB 62053).
5) Sample size proposed for this study has been updated from 268 to 400. Sections 8a, 8k, 9d, ICF have been
updated. Justification for increase in sample size: The team has decided not to use the data for the FDA as a
pivotal trial. This decision simplifies the study consenting process (Part 11 and Adobe Sign) and the
assessment schedule (i.e., dropping the PEth and MINI). These changes greatly reduce personnel time and
research costs and enable us to direct resources to increasing the sample size to permit greater diversity in our
sample and testing of subsample effects of interest (i.e., differences in treatment outcomes by gender, alcohol
as the primary substance, and by race/ethnicity).
6) Section 8c updated with wording from IRB 62053 (pilot study).
7) Sections 8k, 13, 15, and 16 have been updated.
Section 16 attachment updates:
1) Updated documents to the version in IRB 62053: EdOnly Week 6 document, Debrief doc 7.21.21, DSMB
Minutes and Slides from 6.16.21, Email template for Education Only Group Intervention Content
2) Removed documents related to the MINI and PEth test collection.
3) Updated questionnaires based on approved questionnaires (modified 7.22.21) from IRB 62053. Changes
tracked.
4) Updated group instructions based on version in IRB 62053. Changes tracked.
5) Updated and added templates.
6) Attached additional recruitment materials.
7) Attached Woebot letter regarding 21 CFR Part 11 Compliance.
Consent form:
1) The ICF has been updated based on the approved ICF for IRB 62053 (pilot study).
2) Protocol Information Section 11a) Added line "Informed consent will utilize Stanford's Adobe Sign
platform and procedures for part 11 compliance."
2. Indicate Level of Risk
No Change
Protocol # 58725 ( Modification )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 2 of 35
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders Phase 2 RCT: Digitally Delivered Intervention for Reducing Problematic Substance Use (SU sIRB)
Approval Period:
04/13/2022 - 05/12/2022

3. Update the Conflict of Interest (COI) section if any changes in COI have been made since the last
protocol submission.
N
Is there a change in the conflicting interest status for any existing personnel on this protocol?
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
Other Contact
Name
Academic Sponsor
Name
Degree (Program/year if
student)
Position, e.g. Assistant Professor,
Resident, etc.
Protocol # 58725 ( Modification )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 3 of 35
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders Phase 2 RCT: Digitally Delivered Intervention for Reducing Problematic Substance Use (SU sIRB)
Approval Period:
04/13/2022 - 05/12/2022

Department
Phone
E-mail
CITI Training current
Other Personnel
Participant Population(s) Checklist
Yes/No
Protocol # 58725 ( Modification )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 4 of 35
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders Phase 2 RCT: Digitally Delivered Intervention for Reducing Problematic Substance Use (SU sIRB)
Approval Period:
04/13/2022 - 05/12/2022

• 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)
• 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?
Protocol # 58725 ( Modification )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 5 of 35
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders Phase 2 RCT: Digitally Delivered Intervention for Reducing Problematic Substance Use (SU sIRB)
Approval Period:
04/13/2022 - 05/12/2022

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
• 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? Please review the Administrative Panel on BioSafety website
form more information.
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
Protocol # 58725 ( Modification )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 6 of 35
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders Phase 2 RCT: Digitally Delivered Intervention for Reducing Problematic Substance Use (SU sIRB)
Approval Period:
04/13/2022 - 05/12/2022

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
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
Protocol # 58725 ( Modification )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 7 of 35
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders Phase 2 RCT: Digitally Delivered Intervention for Reducing Problematic Substance Use (SU sIRB)
Approval Period:
04/13/2022 - 05/12/2022

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 # 58725 ( Modification )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 8 of 35
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders Phase 2 RCT: Digitally Delivered Intervention for Reducing Problematic Substance Use (SU sIRB)
Approval Period:
04/13/2022 - 05/12/2022

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.
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 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); third party vendors such as Qualtrics panels,
Clara Health, Map & Story, Splash Clinical; 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.
Protocol # 58725 ( Modification )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 9 of 35
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders Phase 2 RCT: Digitally Delivered Intervention for Reducing Problematic Substance Use (SU sIRB)
Approval Period:
04/13/2022 - 05/12/2022

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
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 validate W-SUDs as a digitally-delivered substance use disorder program through a
fully-powered randomized control trial that will test the comparative efficacy of the mobile-app based
substance use disorder program to reduce substance use relative to an education-only control condition,
which has no cognitive behavioral therapy and the content is not delivered through a conversational user
interface.
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
Protocol # 58725 ( Modification )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 10 of 35
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders Phase 2 RCT: Digitally Delivered Intervention for Reducing Problematic Substance Use (SU sIRB)
Approval Period:
04/13/2022 - 05/12/2022

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=101 individuals with SUD.
Phase I (N=101) has concluded and a manuscript is in submission. In this study, W-SUDs was feasible to
deliver, engaging, and acceptable; and associated with significant improvements in substance use,
confidence, cravings, depression, and anxiety. Study attrition was high.
The supplemental study (W-C19) is a randomized control trial with a wait-list control condition. This study
aimed to expand understanding of W-SUDs' performance among users experiencing SUDs whilst
contributing to our overall understanding of COVID-19's impact upon this population. The intervention had
concluded with N=180 participants enrolled. Experiencing worsened mental health symptoms during
COVID-19 was associated with more substance use problems and depression and anxiety symptoms.
Pandemic disruptions may exacerbate preexisting substance use problems.
Phase II will evaluate the efficacy of W-SUDs in a large scale RCT relative to an education-only control
condition. Primary outcomes will be measures of the quantity and frequency of substance use including,
number of substance use occasions, heavy drinking days (if applicable), percent days abstinent.
Additionally, phase II will evaluate whether W-SUDs results in a greater reduction in substance-related
problems than Education Only control and explore: Does engagement with W-SUDs, relative to
education-only control (a) improve symptoms of depression and anxiety (b) improve work productivity (i.e.
reduce presenteeism/absenteeism), (c) reduce cravings, (d) improve situational confidence. Phase II will
also allow the team to learn more about the population interested in digitally delivered interventions.
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.
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 compared to an education only control group.
Protocol # 58725 ( Modification )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 11 of 35
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders Phase 2 RCT: Digitally Delivered Intervention for Reducing Problematic Substance Use (SU sIRB)
Approval Period:
04/13/2022 - 05/12/2022

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 may communicate the research opportunity through social
media channels, and third party recruitment groups (e.g. Splash Clinical, Map & Story, Clara Health). The
Stanford team may recruit through Qualtrics panels, ResearchMatch, 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 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
screening consent and eligibility screener, and if eligible, will be asked to participate in their randomized
group for 8 weeks and answer questionnaires administered at the beginning, mid-intervention (4-week), end
of intervention (8-week), and post intervention (12-week). Informed consent form will appear after
screening eligible, and must be signed before the baseline survey can be accessed. Computer randomization
will occur after the baseline survey, and instructions for their group will be sent out. 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-week, 8-week, and 12-week/30 days post
treatment marks), data analyses, and writing up of study findings for dissemination. Participants will be
randomized to condition via the online assessment platform, which has the functionality to allow
randomization to one of two groups. Those randomized to W-SUDs (group 1) or education control (group 2)
will see a private, email or study-only page pertaining to their group. To minimize bias and maximize study
validity, group blinding will be in place; Participants should not know what the other intervention involves.
Instructions will be provided for each group. A study debrief regarding group blinding will be provided to
participants after the final survey. If the final survey is not completed, the debrief will be provided a month
after the final survey was due.
Woebot is responsible for app management, study payments (e.g. purchasing Amazon e-gift cards for
participant compensation). Participant management is on the Stanford side, including sending out the
compensation, kits, etc. If the participant ends up contacting Woebot about the app or for a study related
question, that message is passed on to the Stanford team or answered by the Woebot team if they have the
answers.
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. 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 compared to an education only control group.
Protocol # 58725 ( Modification )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 12 of 35
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders Phase 2 RCT: Digitally Delivered Intervention for Reducing Problematic Substance Use (SU sIRB)
Approval Period:
04/13/2022 - 05/12/2022

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 and to see if the intervention is more beneficial than a nonactive
treatment condition.
Data flow:
Participants provide data by completing surveys. The Stanford team is the recipient of this data. Emails are
shared with the Woebot team for the interventions, payment, and cross-checking for intervention
contamination (i.e. commercial Woebot app use, WSUDs program use but are supposed to be in Education
only group). Intervention contamination information will be shared by Woebot to Stanford. Participants also
provide data by interacting with the Woebot app. Woebot Labs will share user data with the Stanford team,
who will link the data to survey responses. The Stanford team will analyze the data and then share analyzed
data with the Woebot team.
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
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 in the consent form 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
Protocol # 58725 ( Modification )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 13 of 35
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders Phase 2 RCT: Digitally Delivered Intervention for Reducing Problematic Substance Use (SU sIRB)
Approval Period:
04/13/2022 - 05/12/2022

alteration of consent (in section 13). Submit a debriefing script (in section 16).
There will be intervention group blinding to maximize validity and minimize bias (i.e. reducing factors may
affect the study outcomes). The research team does not know if W-SUDs is more effective than an
education only control group. Group blinding minimizes preconceived expectations for each group and
behaviors as a result of those expectations. To keep the group blinding effective, the groups are not fully
described in the consent form, the company involved is not named (will be obvious which is the new
intervention since the company makes a digital therapeutic mobile app with a chat bot), and full details of
the group intervention a participant is randomized to will be provided after randomization.
A debrief document is attached in Section 16 and will be provided to participants after their study period.
For those who complete the final survey, it'll be provided by email soon after. For those who do not
complete the final survey, the information will be provided by email a month after the final survey (at
12-weeks) is due. This is to allow sufficient opportunity for the final survey to be completed before the
timing of the final survey is considered "late". No participant will be given the debrief after the intervention
period at 8-weeks since the study will also be observing sustained change post-intervention (between
8-weeks and 12-weeks).
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
projected total participant population has been enrolled? When will the study end if no important
differences are detected?
The endpoint will be the follow-up 30 days after end-of-treatment. This will end their study participation
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
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PD: Judith Prochaska
APPLICATION FORM
Page 14 of 35
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders Phase 2 RCT: Digitally Delivered Intervention for Reducing Problematic Substance Use (SU sIRB)
Approval Period:
04/13/2022 - 05/12/2022

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. W-SUDs was feasible to deliver, engaging, and acceptable; and associated with
significant improvements in substance use, confidence, cravings, depression, and anxiety. Study attrition
was high (50%). Future research will evaluate W-SUDs in a randomized controlled trial with a more diverse
sample and with use of greater strategies for study retention.
W-C19 study: COVID-19 offered 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. There were 2468+ screening attempts, and 180 participants
randomized to a condition. Follow up retention rates have fared better than phase 1. Final retention rate for
4-week assessments is at 79.4% (143/180). EOT retention rate is 84.4% (152/180). Experiencing worsened
mental health symptoms during COVID-19 was associated with more substance use problems and
depression and anxiety symptoms. Pandemic disruptions may exacerbate preexisting substance use
problems.
W-SUDs Pilot for the phase II RCT (IRB 62053): Preliminary data from this study shows that there are
feasibility issues with the study including time demand on personnel, complications introduced with the
Adobe Sign process (multiple emails to each participant, difficulty with the secure email process, varying
delays between screening to consent to baseline survey), MINI interviewing scheduling challenges, and
delays between baseline completion and randomization. Based on recruitment data so far, over 1574
screening attempts were made (responses at 0% do not get recorded in Qualtrics), with 128 respondents
passing the screening. Of those that have passed, 23 (18% of the 128) have signed informed consent, and 18
have completed the baseline survey. 1 respondent was removed due to no use of substances in the past 30
days. 12 (71% of the 17 completing baseline survey) have completed the MINI interview.
The W-SUDs phase II study will evaluate the efficacy of W-SUDs in a large scale RCT relative to an
education-only control condition, where there is no active treatment. To diversify the sample, we will utilize
Qualtrics panels and set quotas. We'll utilize retention strategies in the W-C19 study to improve retention.
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
Protocol # 58725 ( Modification )
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PD: Judith Prochaska
APPLICATION FORM
Page 15 of 35
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders Phase 2 RCT: Digitally Delivered Intervention for Reducing Problematic Substance Use (SU sIRB)
Approval Period:
04/13/2022 - 05/12/2022

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.
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
Protocol # 58725 ( Modification )
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PD: Judith Prochaska
APPLICATION FORM
Page 16 of 35
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders Phase 2 RCT: Digitally Delivered Intervention for Reducing Problematic Substance Use (SU sIRB)
Approval Period:
04/13/2022 - 05/12/2022

(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:
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);
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PD: Judith Prochaska
APPLICATION FORM
Page 17 of 35
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders Phase 2 RCT: Digitally Delivered Intervention for Reducing Problematic Substance Use (SU sIRB)
Approval Period:
04/13/2022 - 05/12/2022

(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.
N=400 (nationally) will be invited to participate in this study and entered into the study on a rolling basis.
Inclusion criteria include: all genders aged 18-65 years, meet CAGEAID score of 2+ (WSUDs is designed
for substance use); access to the apps on smartphone, be available and committed to engage with app and
complete assessments, be willing to provide working email address (to distribute incentives), working
telephone number (for interview portion and follow ups), and be literate in English (as educational materials
and 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.
b)
State the age range, gender, and ethnic background of the participant population being recruited.
Recruitment efforts will seek to enroll a demographically diverse sample age 18-65. 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.
These populations are not being targeted but are also not excluded from the study. Exception: Pregnant
women and children will be screened out.
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. 268 volunteers for the main trial 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
Protocol # 58725 ( Modification )
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PD: Judith Prochaska
APPLICATION FORM
Page 18 of 35
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders Phase 2 RCT: Digitally Delivered Intervention for Reducing Problematic Substance Use (SU sIRB)
Approval Period:
04/13/2022 - 05/12/2022

contact potential participants prior to IRB approval. See Advertisements: Appropriate Language for
Recruitment Material.
Recruitment: For this study, Woebot Labs' may 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, Google Ads, 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 via
newsletter, with permission. Stanford staff may post in other listservs with permission. The Stanford team
may recruit participants from other studies who have indicated interest in other studies. The team may use
Qualtrics panels, ResearchMatch (online health research tool funded by NIH to match volunteers with
studies), the Stanford COVID-19 directory to recruit, and other third party recruitment vendors (e.g. Splash
Clinical, Map & Story, Clara Health). 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 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 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),
Protocol # 58725 ( Modification )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 19 of 35
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders Phase 2 RCT: Digitally Delivered Intervention for Reducing Problematic Substance Use (SU sIRB)
Approval Period:
04/13/2022 - 05/12/2022

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
pressure on participants to volunteer for the research study. Include provisions for prorating payment.
See payment considerations
Phase II funding approved. For each of the 400 participants: $25 for completing the baseline survey; $25 for
4-week survey completion; $25 for EOT (8-week) assessment completion; $25 for the 12-week (30 days
post EOT) assessment completion. Total amount possible per participant is $100.
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 for the research team is estimated to be 11 months. Content development is ready.
Recruitment for about 5 months. Participation in the study is estimated to be 3 months. Estimated time for
screening is around 5 minutes; Each survey estimated to be 15-30min. Study intervention is 8-weeks/2
months. Active participation is 3 months with follow up surveys at the 4- week, 8- week, and 12-week
marks.
Data analysis is estimated to be 3 months.
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
Protocol # 58725 ( Modification )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 20 of 35
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders Phase 2 RCT: Digitally Delivered Intervention for Reducing Problematic Substance Use (SU sIRB)
Approval Period:
04/13/2022 - 05/12/2022

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.
Possible risks of Woebot: Woebot is not intended to replace standard of care and should not be used in place
of standard treatment.
Neither of the intervention groups are crisis services.
The risks of the Economic well-being.
N/A
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
Protocol # 58725 ( Modification )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 21 of 35
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders Phase 2 RCT: Digitally Delivered Intervention for Reducing Problematic Substance Use (SU sIRB)
Approval Period:
04/13/2022 - 05/12/2022

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,
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 3-month period with all 400 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 and 12-week surveys
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).
Protocol # 58725 ( Modification )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 22 of 35
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders Phase 2 RCT: Digitally Delivered Intervention for Reducing Problematic Substance Use (SU sIRB)
Approval Period:
04/13/2022 - 05/12/2022

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
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
Protocol # 58725 ( Modification )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 23 of 35
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders Phase 2 RCT: Digitally Delivered Intervention for Reducing Problematic Substance Use (SU sIRB)
Approval Period:
04/13/2022 - 05/12/2022

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 and educational intervention delivery at
8-weeks, the 12-week mark for WSUDs group (content will no longer be accessible), data analysis and
interpretation, refinement of W-SUDs, and the end of the 3 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
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
and will offer those in the WSUDs group 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.
Protocol # 58725 ( Modification )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 24 of 35
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders Phase 2 RCT: Digitally Delivered Intervention for Reducing Problematic Substance Use (SU sIRB)
Approval Period:
04/13/2022 - 05/12/2022

11. Privacy and Confidentiality
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 four 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.
Informed consent will utilize Stanford's Adobe Sign platform and procedures for part 11 compliance.
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, mailing addresses, phone numbers, dates of birth, demographic
information (gender, biological sex,race/ethnicity, disability status), IP addresses, geo location, survey, drug
use.
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 Drug Abstinence Self-Efficacy Scale (DASE) is a 12-item
self-report scale, reflecting Bandura's (1986) cognitive-behavioral
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.
Protocol # 58725 ( Modification )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 25 of 35
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders Phase 2 RCT: Digitally Delivered Intervention for Reducing Problematic Substance Use (SU sIRB)
Approval Period:
04/13/2022 - 05/12/2022

3. 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.
4. 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.
5.
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.
6.
The Quick Drinking Screen (QDS) by Sobell & Sobell (2003), is a brief and reliable measure of
drinking. Compared with the Timeline Followback (TLFB), the QDS collected similar aggregate drinking
data for four drinking variables in a clinical sample of alcohol abusers.
General Psychopathology
9. The Patient Health Questionnaire (PHQ-8) is a brief 8-item scale used to determine the severity of
depression in medical populations. The PHQ-8 has high reliability across populations.
10. 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
11.
The Stanford Presenteeism Scale is (SPS-6) a six item measure derived from a 34 item measure of
workforce productivity impacted by health status. The 6-item scale has excellent psychometric properties
and has been validated.
12.
The CAIR Pandemic Impact Questionnaire (C-PIQ) and the International COVID-19 Awareness
and Evaluation Study questions were developed for measuring the impact of COVID-19. These include
questions about COVID-19 in relation to their health, work, and lifestyle changes.
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 three assessment batteries, will be administered via a HIPAA
compliant survey administration tool commonly used by Stanford University in its clinical trials (Qualtrics
Protocol # 58725 ( Modification )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 26 of 35
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders Phase 2 RCT: Digitally Delivered Intervention for Reducing Problematic Substance Use (SU sIRB)
Approval Period:
04/13/2022 - 05/12/2022

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 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 or biomarker tests. 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.
Protocol # 58725 ( Modification )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 27 of 35
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders Phase 2 RCT: Digitally Delivered Intervention for Reducing Problematic Substance Use (SU sIRB)
Approval Period:
04/13/2022 - 05/12/2022

Coded data may be sent by secure email settings provided by Stanford, or through Stanford Medicine Box.
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
Screening Consent
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
Protocol # 58725 ( Modification )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 28 of 35
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders Phase 2 RCT: Digitally Delivered Intervention for Reducing Problematic Substance Use (SU sIRB)
Approval Period:
04/13/2022 - 05/12/2022

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. (v)No
incentive or 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.
13. 2
Alteration of Consent
Phase 2 ICF - Alteration of Consent
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) Consent will be obtained via Adobe Sign platform. (ii) The online consent can be obtained at anytime
and place the potential participant would like. (iii) Potential participants may take as long as they like to
read through the consent form. Estimated time is 5min. Contact information is available on the consent form
if any questions come up. Potential participants will be informed of what to expect on the survey platform.
Informed consent form will be accessed on Adobe Sign. Passwords will be provided via secure email or by
phone. The Adobe Sign email template will also include the study team's contact information if any
questions come up. Fully signed consent forms will be provided via secure email or as a password protected
document in an email. (iv) Yes. (v) Study staff will not be with the potential participant and there will be no
possibility of coercion or undue influence. (vi) If under 18 years of age, the respondent is screened out
before the consent form appears.
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 fluent participants will be recruited. The Consent form will be readable and those with a
hearing impairment will still be able to access the consent form.
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 who can meet screening criteria. Participation will only
include those competent to consent in the low risk study.
Address the following four regulatory criteria for an alteration of consent and provide protocol-specific
justification for each:
Protocol # 58725 ( Modification )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 29 of 35
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders Phase 2 RCT: Digitally Delivered Intervention for Reducing Problematic Substance Use (SU sIRB)
Approval Period:
04/13/2022 - 05/12/2022

1)
Y
The research involves no more than minimal risk to the participants.
The study is a RCT with group blinding to test whether WSUDs is more effective in reducing
problematic substance use than an education only control. The study will involve four questionnaires
about physical and mental health, and substance use. Participation information will be coded and
stored on compliant platforms (Stanford Medicine Box) and on encrypted, password protected
computers. App data is protected with Woebot's security measures.
2)
Y
The waiver or alteration will not adversely affect the rights and welfare of the participants.
Confidentiality and HIPAA practices will still be in place. Data is stored on compliant platforms (e.g.
Qualtrics, Stanford Medicine Box) and on encrypted password protected computers.
3a)
Y
The research could not practicably be carried out with out the requested waiver or alteration.
3b)
Y
For research using identifiable private information or identifiable biospecimens, the research
could not practicably be carried out without using such information or biospecimens in an
identifiable format.
There will be intervention group blinding to maximize validity and minimize bias. To keep the group
blinding effective, the groups are not fully described in the consent form, and full details of the group
intervention a participant is randomized to will be provided after randomization. A debrief will be
provided to participants after the 12-week assessment period.
4)
Y
Whenever appropriate, the participants or legally authorized representatives will be provided
with additional pertinent information after participation.
Participants will be provided with a debrief of group blinding at the end of their study participation.
This will be provided by email either be after completion of the final survey or a month after the final
survey was due (for those who don't complete the final survey).
14. Assent Background (less than 18 years of age)
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.
Those who are interested in screening to participate in the study are asked to sign and print name in the
online screening consent as the screening questionnaire involves questions on drug use. PHI collected
during screening will include demographics, age, drug use, health history (including mental health), email,
IP address (upon entering survey), and name + signature (consent). If a respondent meets eligibility
requirements, email and phone number asked for in the screening consent. This is to verify a working email
prior to proceeding to next steps (Adobe Sign for informed consent).
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?
Protocol # 58725 ( Modification )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 30 of 35
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders Phase 2 RCT: Digitally Delivered Intervention for Reducing Problematic Substance Use (SU sIRB)
Approval Period:
04/13/2022 - 05/12/2022

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.
The screening survey 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. 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, and on Stanford Medicine Box. 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.
The research staff will all be HIPAA and CITI trained, 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.
Authorization for use and disclosure of the respondent's health information ends on December 31, 2045 or
when the research project ends, whichever is earlier. When the authorization expires, the identifiers will
manually be destroyed by the study team.
16. Attachments
Attachment Name
Attached Date
Attached By
Submitted Date
NIH_NOA_4R44DA048712-
02
02/08/2021
achieng
Resources for Substance Use
Treatment 12.9.19
02/08/2021
achieng
Woebot Scope of Work
02/08/2021
achieng
Woebot_Security_Risk_Mana
gement_Plan_20190812
02/08/2021
achieng
Woebot_Findings_And_Reco
mmendations (1)
02/08/2021
achieng
Woebot Privacy Policy
02/08/2021
achieng
Woebot Data Protection
02/08/2021
achieng
Woebot_SBIR_Application
02/08/2021
achieng
Woebot Branching Logic
02/08/2021
achieng
Directions installing
registering Woebot App
02/08/2021
achieng
Screenshots of Woebot
Conversational Pieces
02/08/2021
achieng
Protocol # 58725 ( Modification )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 31 of 35
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders Phase 2 RCT: Digitally Delivered Intervention for Reducing Problematic Substance Use (SU sIRB)
Approval Period:
04/13/2022 - 05/12/2022

Woebot Terms of Service
02/08/2021
achieng
Athena Robinson PHRP
Certificate
02/08/2021
achieng
Student Wellness Listserv
Permission
02/08/2021
achieng
Stanford Staffers Listserv
Permission
02/08/2021
achieng
Woebot Crisis Language
Response
02/08/2021
achieng
Woebot Listerv Recruitment
02/08/2021
achieng
Woebot for Substance Use
Disorders - Possible
Subreddits
02/08/2021
achieng
thumbnail_woebot-header-01
02/08/2021
achieng
thumbnail_woebot
02/08/2021
achieng
thumbnail_woebot-header-02
02/08/2021
achieng
thumbnail_woebot-header-04
02/08/2021
achieng
Study Design
02/08/2021
achieng
NIDA SUD DSMB Meeting
Minutes 1.27.21
02/23/2021
achieng
DSMB NIDA SUD Meeting
Powerpoint 1.27.21
02/23/2021
achieng
WSUDs Upcoming Survey
Email Template
03/26/2021
achieng
Phase II Education Only
Content
03/26/2021
achieng
DRA #1085 Intake Form
04/07/2021
achieng
DRA 1085 Third Part Portion
of the Intake Form
04/07/2021
achieng
Lauren Haruno CITI
Certification
04/22/2021
achieng
NIDA_SUD_Flyer_colorful
04/22/2021
achieng
WSUDs Phase 2 Advertising
Language v2
04/22/2021
achieng
WSUDs Phase 2 Emailing
previous participants v.2
04/22/2021
achieng
LittleDove CITI Completion
Look Up
04/22/2021
achieng
Protocol # 58725 ( Modification )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 32 of 35
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders Phase 2 RCT: Digitally Delivered Intervention for Reducing Problematic Substance Use (SU sIRB)
Approval Period:
04/13/2022 - 05/12/2022

Phase 1 Protocol: IRB-50953
04/26/2021
achieng
WC19 Supplement Study
Protocol: IRB-56439
04/26/2021
achieng
WCovid19 trial (For
reference; Not IRB 56439)
04/27/2021
achieng
WSUDs Phase 2 CRRP
Review Sub Form
04/27/2021
achieng
WSUDs Phase 2 Scientific
Protocol in Relation to
COVID-19
04/27/2021
achieng
2021-JMIR Woebot Phase I
Manuscript
05/09/2021
achieng
ICO Contract
05/09/2021
achieng
DRA 1085 Review Email
05/19/2021
achieng
AshleyLee CITI Certifications 06/07/2021
achieng
EdOnly_Week1_Understandi
ng Alcohol Use Disorder
06/16/2021
achieng
EdOnly_Week2_What is
binge drinking
06/16/2021
achieng
EdOnly_Week3_Addiction
and Health
06/16/2021
achieng
EdOnly_Week4_Is Addiction
a Disease
06/16/2021
achieng
EdOnly_Week5_Drugs and
the Brain
06/16/2021
achieng
EdOnly_Week7_Alcohol
Facts and Stat
06/16/2021
achieng
EdOnly_Week8_Fast Facts
about Addiction
06/16/2021
achieng
Woebot Statement on 21 CFR
Part 11 1.25.22
01/25/2022
achieng
NIDA Phase II RCT
Recruitment
Language_Images 1.25.22
01/25/2022
achieng
EdOnly_Week6_Drugs that
People Misuse Updated Ver
01/25/2022
achieng
NIDA SUD DSMB Meeting
6.16.21_FINAL
01/26/2022
achieng
NIDA SUD DSMB Meeting
Minutes_06.16.21
01/26/2022
achieng
Protocol # 58725 ( Modification )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 33 of 35
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders Phase 2 RCT: Digitally Delivered Intervention for Reducing Problematic Substance Use (SU sIRB)
Approval Period:
04/13/2022 - 05/12/2022

Woebot Phase 2 BL Survey
1.26.22
01/26/2022
achieng
Woebot Phase 2 Survey 4wk
1.26.22
01/26/2022
achieng
Woebot Phase 2 EOT Survey
1.26.22
01/26/2022
achieng
Woebot Phase 2 Survey 3m
1.26.22
01/26/2022
achieng
WSUDs Debrief Doc 7.21.21
01/26/2022
achieng
Email template for sending
out signed consent forms for
the study 1.26.22
01/26/2022
achieng
Email Template for Education
Only Group Intervention
Content
01/26/2022
achieng
NIDA Phase II Participant
Facing Materials and
Additional Wording 3.8.22
03/08/2022
achieng
Message Templates Related to
Adobe Sign 3.8.22
03/08/2022
achieng
WSUDS Phase 2 Instructions
for Groups 2.3.22 ver3
03/08/2022
achieng
Secure Email Template 3.8.22 03/08/2022
achieng
WSUDs Phase 2 Manual
Email Templates 3.8.22
03/08/2022
achieng
WSUDs Qualtrics Auto Email
Templates 3.8.22
03/08/2022
achieng
Woebot Phase 2 Screening
Questionnaire 3.8.22
03/08/2022
achieng
WSUDs Phone Script 3.8.22
03/08/2022
achieng
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
Protocol # 58725 ( Modification )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 34 of 35
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders Phase 2 RCT: Digitally Delivered Intervention for Reducing Problematic Substance Use (SU sIRB)
Approval Period:
04/13/2022 - 05/12/2022

•
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
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 # 58725 ( Modification )
PROTOCOL
PD: Judith Prochaska
APPLICATION FORM
Page 35 of 35
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Woebot for Substance Use Disorders Phase 2 RCT: Digitally Delivered Intervention for Reducing Problematic Substance Use (SU sIRB)
Approval Period:
04/13/2022 - 05/12/2022