Evaluating Signs of Safety: A Deaf-Accessible Therapy Toolkit for AUD and Trauma
Phase: NA
Conditions: PTSD, Alcohol; Use, Problem
Sponsor: University of Massachusetts, Worcester

Evaluating Signs of Safety: A Deaf-Accessible Therapy Toolkit for AUD and Trauma 
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Evaluating Signs of Safety: A Deaf-Accessible Therapy 
Toolkit for AUD and Trauma 
This title should include, where possible, information on the participants, condition being evaluated, and 
intervention(s) studied. 
Unique Protocol Identification Number: STUDY00001149 
National Clinical Trial (NCT) Identified Number: TBD 
Principal Investigator: Melissa L. Anderson 
Sponsor:  
"Sponsor" indicates an institution, foundation, or individual who takes responsibility for and initiates a 
clinical investigation; often times this is the university with which the Principal Investigator is affiliated. 
Grant Title: Evaluating Signs of Safety: A Deaf-Accessible Therapy Toolkit for 
AUD and Trauma 
Grant Number: R01AA031010 
Funded by: NIAAA 
Version Number: v.1.016 
16 February 2024 
All versions should have a version number and a date. Use an international date format (e.g.,YYYY-MM-
DD [2017-12-21] or write out the month (e.g., 21 December 2017). 
For the initial submission of a protocol to the IRB, indicate "Not applicable; this is the first version of the 
protocol." in the table below. For any subsequent amendment being submitted to the IRB, add details of 
the specific changes that are being implemented in the amendment. Please note that Section 10.4 is a 
high-level summary of all formal protocol versions/amendments. 
 
 
Summary of Changes from Previous Version: 
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Section(s)  
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Table of Contents 
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STATEMENT OF COMPLIANCE 
Provide a statement that the trial will be conducted in compliance with the protocol, International 
Council on Harmonisation Good Clinical Practice (ICH GCP) and applicable state, local and federal 
regulatory requirements. Each engaged institution must have a current Federal-Wide Assurance (FWA) 
issued by the Office for Human Research Protections (OHRP) and must provide this protocol and the 
associated informed consent documents and recruitment materials for review and approval by an 
appropriate Institutional Review Board (IRB) or Ethics Committee (EC) registered with OHRP. Any 
amendments to the protocol or consent materials must also be approved before implementation. Select 
one of the two statements below. If the study is an intramural NIH study, use the second statement 
below: 
1. The trial will be carried out in accordance with International Council on Harmonisation Good 
Clinical Practice (ICH GCP) and the following: 
o 
United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 CFR Part 
46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 812). 
National Institutes of Health (NIH)-funded investigators and clinical trial site staff who are 
responsible for the conduct, management, or oversight of NIH-funded clinical trials have 
completed Human Subjects Protection and ICH GCP Training. 
OR 
2. The trial will be conducted in accordance with International Council on Harmonisation Good 
Clinical Practice (ICH GCP), applicable United States (US) Code of Federal Regulations (CFR), and 
the [specify NIH Institute or Center (IC) [ Terms and Conditions of Award. The Principal 
Investigator will assure that no deviation from, or changes to the protocol will take place 
without prior agreement from the funding agency and documented approval from the 
Institutional Review Board (IRB), and the Investigational New Drug (IND) or Investigational 
Device Exemption (IDE) sponsor, if applicable, except where necessary to eliminate an 
immediate hazard(s) to the trial participants. All personnel involved in the conduct of this study 
have completed Human Subjects Protection and ICH GCP Training. 
For either option above, the following paragraph would be included: 
The protocol, informed consent form(s), recruitment materials, and all participant materials will 
be submitted to the IRB for review and approval. Approval of both the protocol and the consent 
form(s) must be obtained before any participant is consented. Any amendment to the protocol 
will require review and approval by the IRB before the changes are implemented to the study. 
All changes to the consent form(s) will be IRB approved; a determination will be made regarding 
whether a new consent needs to be obtained from participants who provided consent, using a 
previously approved consent form. 
INVESTIGATOR'S SIGNATURE 
Principal Investigator or Clinical Site Investigator: 

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Signed: 
Melissa L. Anderson, PhD 
Date: 
2/12/2024 
Name*:  
Melissa L. Anderson, PhD 
Title*:  
Associate Professor of Psychiatry and PQHS 
 
 
Investigator Contact Information: 
Affiliation*:  UMass Chan Medical School 
Address:  
222 Maple Ave., Chang Building, Shrewsbury, MA 01545 
Telephone:  508-856-5820 
Email:  
melissa.anderson@umassmed.edu 
 
For multi-site studies, the protocol should be signed by the clinical site investigator who is responsible  
for the day to day study implementation at his/her specific clinical site:  
Signed: 
  
Date: 
  
Name:  
  
Title:  
  
Affiliation:    
 
 

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1 PROTOCOL SUMMARY 
1.1 SYNOPSIS 
Title: 
Evaluating Signs of Safety: A Deaf-Accessible Therapy Toolkit 
for AUD and Trauma 
Grant Number: 
R01AA031010 
Study Description: 
The U.S. Deaf community – a group of more than 500,000 Americans 
who communicate using American Sign Language (ASL) – experiences 
nearly triple the rate of lifetime problem drinking and twice the rate of 
trauma exposure compared to the general population. Although there 
are several treatments for alcohol use disorder (AUD) and 
posttraumatic stress disorder (PTSD) in hearing populations, none have 
been developed for or tested with Deaf clients. To address these 
barriers, our team developed Signs of Safety, a Deaf-accessible therapy 
toolkit for treating AUD and PTSD. We propose a nationwide, virtual 
clinical trial to compare (1) Signs of Safety with (2) treatment as usual 
and (3) a no treatment control, to collect data on clinical outcomes, and 
to explore potential mediators and moderators of outcome. 
  
Objectives*: 
Primary Objective: Conduct a nationwide, full-scale, virtual clinical 
trial of Signs of Safety. Leveraging the existing 
infrastructure and robust referral network of 
National Deaf Therapy, we will enroll 144 Deaf 
adults with past-month PTSD and problem 
drinking into our study protocol. Primary clinical 
outcomes at immediate post-treatment and 
post-treatment follow-up are alcohol use 
frequency/quantity (Alcohol Timeline 
Followback) and PTSD severity (PTSD Checklist 
for DSM-5) since the last assessment timepoint. 
Assessment will occur at baseline, mid-
treatment, immediate post-treatment, three-
month post-treatment follow-up, and six-month 
post-treatment follow-up. 
  
Secondary 
Objectives: 
Explore potential moderators and mediators 
that lead to positive outcome. Identified from 
the literatures on Seeking Safety, alcohol 
treatment research, and Deaf mental health 
research, potential mechanisms of change are 
coping self-efficacy, self-compassion, motivation 
for treatment, and access to health information. 
  
 

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Endpoints*: 
Primary Endpoint: Alcohol use frequency/quantity (Alcohol 
Timeline Followback) and PTSD severity (PTSD 
Checklist for DSM-5) 
  
Secondary 
Endpoints: 
DSM-5 Alcohol Use Disorder diagnostic criteria 
  
Drug use frequency/quantity 
  
Substance-related problems 
  
Drug and alcohol craving 
  
Mental health symptoms 
 
Study Population: 
Deaf adults 
Phase* or Stage: 
Stage II/III 
  
Description of 
Sites/Facilities Enrolling 
Participants: 
National Deaf Therapy (NDT) is a Deaf-female-owned agency that is by 
far the nation’s largest provider of Deaf mental health services. NDT 
specializes in personalized telemental health care for Deaf individuals. 
NDT reaches 400+ persons served annually across 24 U.S. states. 
  
Description of Study 
Intervention/Experimental 
Manipulation: 
Signs of Safety is a Deaf-accessible toolkit to be used with the Seeking 
Safety treatment protocol. Seeking Safety is a manualized, non-
exposure-based, cognitive behavioral therapy for trauma and 
addiction. Experimental participants will be offered 12 one-hour, 
weekly individual therapy sessions of Seeking Safety delivered with the 
Signs of Safety toolkit. Sessions will occur virtually via NDT’s secure 
HIPAA-compliant video chat platform. The length of treatment is 
limited to six months; the number of completed sessions will be tracked 
as a measure of participant adherence. 
  
Study Duration*: 
48 months 
  
Participant Duration: 
9 months to 1 year 
 
 

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1.2 SCHEMA 
 
 
 

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1.3 SCHEDULE OF ACTIVITIES 
 

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2 INTRODUCTION 
2.1 STUDY RATIONALE 
In partnership with Deaf-owned agency National Deaf Therapy, we will conduct the first-ever full-scale 
psychotherapy trial conducted in the Deaf community - “Evaluating Signs of Safety: A Deaf-Accessible 
Therapy Toolkit for AUD and Trauma.” The U.S. Deaf community – more than 500,000 Americans who 
communicate using American Sign Language (ASL)2 – experiences nearly triple the rate of lifetime 
problem drinking compared to the general population (33.0% vs. 12.3%)3,4,5,6 and twice the rate of 
trauma exposure.7,8,9,10,11 Among Deaf people in treatment for alcohol use disorder (AUD), 74% report 
lifetime physical, emotional, or sexual abuse and 44% report past-year abuse.4 Comorbid AUD/PTSD 
impairs multiple domains of functioning,12 especially for Deaf individuals, who show poorer functional 
outcomes than hearing individuals in socialization,13 employment,13 and physical health.14 
Hearing individuals have access to several validated treatments for comorbid AUD/PTSD;15,16,17,18,19 yet 
there are no evidence-based treatments to treat any behavioral health condition with Deaf clients.20,21 
Available treatments fail to meet Deaf clients’ unique language access needs.20 Deaf people’s median 
English literacy level falls at the fourth grade22 and health-related vocabulary among Deaf sign language 
users parallels non-English-speaking U.S. immigrants.23 Available treatment resources, therefore, require 
plain text revisions, filmed ASL translations, or education through storytelling to better match Deaf 
clients’ language needs.24,25,26 
Leveraging extensive community engagement to address these barriers, the PI’s team of Deaf and 
hearing researchers, clinicians, filmmakers, actors, artists, and Deaf people with AUD/PTSD developed 
and pilot tested Signs of Safety, a Deaf-accessible toolkit to be used with the Seeking Safety treatment 
protocol.19 Seeking Safety is a manualized, non-exposure-based, cognitive behavioral therapy for trauma 
and addiction. Among evidence-based treatments for AUD/PTSD, Seeking Safety is the optimal choice 
for Deaf clients – its focus on psychoeducation and simple coping skills is an ideal match for Deaf 
people’s language and literacy disparities, which prohibit the use of narrative, verbal problem-solving, 
and cognitive processing strategies that other AUD/PTSD therapies require.27 Yet, Seeking Safety’s client 
materials rely on written English and are, therefore, not well understood by Deaf clients. As such, the 
Signs of Safety toolkit provides a supplemental therapist guide and population-specific client materials 
(e.g., visual handouts, filmed ASL teaching stories). 
Preliminary data from the Signs of Safety single-arm pilot and randomized feasibility pilot showed 
reductions in alcohol use frequency and PTSD severity from baseline to follow-up on the Reliable 
Change Index.28 The delivery of the experimental intervention was deemed feasible by study therapists 
and was well-received by participants,28 especially when moved to a virtual platform. In response to the 
COVID-19 pandemic, we overhauled in-person study methods to implement a virtual clinical trial – an 
acceleration of the inevitable development needed to scale Signs of Safety to a national level. This 
adaptation also established a crucial collaboration with National Deaf Therapy (NDT), by far the nation’s 
largest provider of Deaf mental health services, currently serving clients across 21 states. This 
collaboration, paired with comprehensive feasibility data we collected by testing a variety of virtual 
methods, serves as the foundation of our proposed aims: 

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Aim 1: Conduct a nationwide, full-scale, virtual clinical trial of Signs of Safety. Leveraging the existing 
infrastructure and robust referral network of NDT, we will enroll 144 Deaf adults with past-month PTSD 
and problem drinking into our study protocol. Primary clinical outcomes at immediate post-treatment 
and post-treatment follow-up are past 30-day alcohol use frequency/quantity (Alcohol Timeline 
Followback)29 and past 30-day PTSD severity (PTSD Checklist for DSM-5).30 Assessment will occur at 
baseline, mid-treatment, immediate post-treatment, three-month post-treatment follow-up, and six-
month post-treatment follow-up. 
Aim 1a: Participants residing in the 21 states served by NDT (n = 96) will be randomized to receive either 
(1) a 12-session protocol of Seeking Safety + Signs of Safety, or (2) 12 sessions of therapy as usual (TAU; 
general, open-ended, non-manualized supportive counseling provided by an NDT therapist). 
Aim 1b: Augmenting the Aim 1a RCT, we will enroll an additional 48 Deaf adults into a 
contemporaneous no-treatment control arm. These individuals will be recruited from the existing NDT 
waitlist, comprised of Deaf individuals residing in the 29 states not yet served by NDT but voluntarily 
awaiting NDT services. 
Aim 2: Analyze potential moderators and mediators that lead to positive outcome. Identified from the 
literatures on Seeking Safety, alcohol treatment research, and Deaf mental health research, mechanisms 
of change are coping self-efficacy, self-compassion, motivation for treatment, and access to health 
information. 
Our proposed aims build on eight years of KL2 and R34 empirical work, moving this program of research 
from Stage IB (two-arm feasibility and pilot testing) to Stage II/III (real world efficacy). The proposed R01 
will potentially validate the first-ever evidence-based therapy for Deaf people, as well as provide future 
behavioral health researchers with a vital roadmap for conducting community-engaged clinical trials 
with Deaf people. 
 
 
2.2 BACKGROUND 
SIGNIFICANCE 
A1. Deaf people experience triple the rate of lifetime problem drinking and double the rate of trauma 
exposure compared to the general population.3,4,5,6,7,8,9,10,11 The U.S. Deaf community – a group of 
500,000+ Americans who communicate using American Sign Language (ASL)2 – reports nearly three 
times the rate of lifetime problem drinking compared to the general population (33.0% vs. 12.3%; 
adjusted OR = 2.5, p = 0.0004).3 An estimated 15% of Deaf Americans meet criteria for current alcohol 
use disorder (AUD),31 with high rates of comorbid posttraumatic stress disorder (PTSD) complicating 
their recovery.12 Deaf individuals report double the rate of interpersonal trauma compared to hearing 
peers,7,8,9,10,11 with the PI’s research finding that 61% of Deaf college women experienced past-year 
sexual coercion (hearing = 28%) and 52% past-year physical assault (hearing = 28%).7,32 Among Deaf 
people in AUD treatment, 74% report lifetime physical, emotional, or sexual abuse and 44% report past-
year abuse.4 

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Comorbid AUD/PTSD complicates treatment and affects multiple domains of functioning.12 Hearing 
individuals with this comorbidity have greater physical and social impairment, higher rates of mood, 
anxiety, and personality disorders, and increased trauma-related craving (i.e., craving substances in 
response to PTSD symptoms) compared to those with AUD alone.17,33,34 Deaf people show even greater 
impairment than hearing peers, with poorer outcomes in socialization,13 employment,13 and physical 
health.14 These pervasive disparities stress the critical need for accessible, validated AUD/PTSD 
treatments for Deaf clients. 
A2. Although hearing clients have access to several validated treatments for comorbid AUD/PTSD, 
there are no evidence-based treatments for any behavioral health condition that have been 
developed for or formally evaluated with Deaf clients.20,21,28 Currently available treatments fail to meet 
the unique language needs of Deaf clients.20 Deaf people’s median reading level falls at the fourth 
grade.22 Health-related vocabulary parallels non-English-speaking U.S. immigrants.23 Many have minimal 
understanding of basic recovery concepts (e.g., substance, relapse, trigger)35 and are unaware that being 
hit, choked, or coerced into sex is considered abuse.32 Such health literacy gaps are caused by a lifetime 
of impoverished communication access to health education materials, healthcare professionals, and 
one’s own parents.36,37 Written treatment materials, therefore, require plain text revisions, ASL 
translations, or education through storytelling.24,25,26 
Moreover, due to lack of early language exposure, poor educational experiences, and resulting long-
term language dysfluency, many Deaf adults enter treatment unable to construct a narrative or a 
coherent timeline of events.24,38 Therefore, the narrative, verbal problem-solving, and cognitive 
processing strategies required by most evidence-based AUD/PTSD therapies are contraindicated in the 
treatment of many Deaf clients.27 
A3. Leveraging extensive community engagement to address these barriers, our team created Signs of 
Safety,28 a Deaf-accessible therapy toolkit to be used with an existing treatment for trauma and 
addiction – Seeking Safety.19 Seeking Safety is a manualized, non-exposure-based, cognitive behavioral 
therapy that focuses on psychoeducation and development of simple coping skills that simultaneously 
target AUD and PTSD (or either alone). Seeking Safety is the most widely implemented model for PTSD 
and substance use disorder, with a 2016 meta-analysis indicating positive outcomes on both PTSD and 
substance use disorder among 1000+ patients across studies.1,39,40,41,42,43,44 Although there is preliminary-
to-promising evidence for other manualized treatments for comorbid AUD/PTSD,16,18,33,45 these 
treatments rely on the client’s ability to formulate a trauma narrative,55 which, as described above in 
section A2, is contraindicated for many Deaf clients.7,35 Such models also have limitations for Deaf clients 
from a public health standpoint (e.g., more costly, exclude more complex clients).56 
Given these contraindications, our team selected Seeking Safety as our base intervention due to its 
present-focus (i.e., no need to retell the trauma narrative) and reliance on simple coping skills. Notably, 
among women with disabilities,57 those treated with Seeking Safety experienced sustained reductions in 
PTSD symptoms while women in the comparison condition experienced experienced full PTSD 
recurrence by 12-month follow-up.57 Changes in AUD over time could not be investigated in this 
secondary analysis, as the majority of participants with disabilities reported no alcohol use at baseline. 
Despite this floor effect, this study provided preliminary support that Seeking Safety would be an 
engaging and effective approach among individuals with disabilities, including Deaf individuals.57 Indeed, 
Seeking Safety has been used successfully with highly diverse populations, translated into 14 foreign 

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languages, and aligns with most strategies for Deaf-friendly treatment – skill-building and 
psychoeducation, structured sessions, case management, present focus, and strength-based work.27,58 
Yet, similar to other manualized treatments, Seeking Safety ’s client materials rely on written English, 
failing to meet the linguistic needs of Deaf clients.20,35 
To address this barrier, the PI assembled an impressive team of Deaf and hearing researchers, clinicians, 
filmmakers, actors, artists, and Deaf people with AUD/PTSD to develop and pilot test Signs of Safety, a 
Deaf-accessible toolkit to be used with Seeking Safety. A similar toolkit approach has been used to 
augment Seeking Safety for adolescents59 and individuals with HIV.60 To develop Signs of Safety, our 
team followed NIDA behavioral therapy development approaches61 and recommended principles for 
creating Deaf-accessible interventions: language adaptations and simplification of English-based 
materials; use of teaching stories and examples; inclusion of visual aids; active treatment strategies and 
role-playing; attention to health literacy gaps; leveraging of technology; and, drawing on Deaf 
community members’ desire to help and teach each other.27,58 For future generalizability and public 
health impact, Signs of Safety is designed for use by both Deaf/signing clinicians and non-signing 
clinicians who communicate with Deaf clients through ASL interpreters. 
Signs of Safety includes two primary components: 
The therapist companion guide teaches clinicians how to effectively implement Seeking Safety with 
Deaf clients by providing recommended ASL translations of common Seeking Safety concepts and 
vocabulary, exploring how issues raised by each Seeking Safety topic interact with common Deaf 
experiences, and discussing helpful tips for working with Deaf clients with addiction and PTSD. 
Client materials include: (1) ASL teaching stories on digital video for 12 core Seeking Safety topics, which 
present critical learning points portrayed by Deaf actors; and (2) visual handouts, which present key 
information using plain text and visual aids created by a Deaf artist.  
To design the main component of Signs of Safety – the ASL teaching stories described above – we 
leveraged the cultural tradition of storytelling in the Deaf community.62 Additionally, we drew on the 
Slater Model of Narrative Communication,25,26 in which a compelling storyline, the level of similarity 
between the characters and the audience, and high production quality coalesce to produce changes in 
attitudes, skills, and behaviors. 
To formally test the efficacy of Signs of Safety, we will partner with National Deaf Therapy to conduct a 
nationwide, full-scale virtual clinical trial. The proposed R01 builds on eight years of KL2 and R34 
research, moving this program from Stage IB (two-arm feasibility and pilot testing) to Stage II/III (real 
world efficacy). 
  
INNOVATION 
This program of research is infused with innovation, from study start-up through end-of-study 
dissemination: 
• 
We will conduct the first-ever full-scale psychotherapy clinical trial in the Deaf community. 
• 
We will formally translate validated, commonly used, open access behavioral health measures from 
written English to ASL. None of our proposed measures are currently available in ASL in the public 
domain; we will make the resulting ASL translations publicly available for behavioral health researchers 
and clinicians who work with Deaf people to further increase the public health impact of our research. 

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• 
We will apply an exceptional level of community engagement throughout the research process:  
o 
The team is co-led by a Deaf co-investigator, a significant feat given that only 1% of science and 
engineering doctorates are earned by Deaf or hard-of-hearing individuals.63 
o 
We will hire four Deaf Community Advisors onto the team – Deaf laypeople with lived 
experience of AUD and/or PTSD who will help guide online survey development, study methods 
and recruitment, interpretation of findings, and dissemination back to the Deaf community. 
We are partnering with National Deaf Therapy, a Deaf-female-owned company that specializes in 
personalized tele mental health care for Deaf individuals. Given the agency’s reach of 400+ persons 
served annually across 21 U.S. states, this partnership will also serve as an essential mechanism for end-
of-study dissemination of Signs of Safety into the larger Deaf community. 
 
 
2.3 RISK/BENEFIT ASSESSMENT 
2.3.1 KNOWN POTENTIAL RISKS 
There is a potential risk of loss of confidentiality. There is a potential risk of discomfort or increased 
mental health symptoms associated with completing study interventions and assessments. There is also 
a potential risk of experiencing alcohol withdrawal symptoms. We address each below: 
Risks associated with potential loss of confidentiality. There is a slight risk that research records (e.g., 
assessment data, video recordings) might be obtained by unauthorized persons. There is a slight risk 
that research data files might be compromised and obtained or viewed by unauthorized persons.  
Risks associated with study interventions and assessments. Potential risks to participants include an 
increase in mental health symptoms while participating in Seeking Safety/Signs of Safety therapy, a 
known risk of participating in treatment in general. Additionally, completing study-related assessments 
may cause potential risk to participants, including discomfort, embarrassment, triggers of PTSD 
symptoms, or triggers of substance cravings.  
Risks associated with reductions in alcohol use. Another potential risk to participants with severe AUD 
is symptoms of alcohol withdrawal. 
2.3.2 KNOWN POTENTIAL BENEFITS 
The following potential benefits cannot be guaranteed. Potential benefits to participants include:  
• Access to an evidence-based intervention (Seeking Safety) and treatment materials that they may not 
otherwise be able to access. 
• Decrease in mental health symptoms and addiction severity. 
• Increase in safe coping skills and ability to manage their trauma symptoms. 
2.3.3 ASSESSMENT OF POTENTIAL RISKS AND BENEFITS 
Risks associated with potential loss of confidentiality. Comprehensive procedures to protect 
participants' confidentiality are described in Section 10.1.3 - Confidentiality and Privacy. 

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Risks associated with study interventions and assessments. Potential risks to participants include an 
increase in mental health symptoms while participating in Seeking Safety/Signs of Safety therapy, a 
known risk of participating in treatment in general, but not a pattern that has previously been identified 
with Seeking Safety or in the Signs of Safety preliminary studies. Rather, participants in Seeking Safety 
are instructed not to delve deeply into trauma details, with the purpose of minimizing exposure and 
adverse responses to trauma triggers. Additionally, completing study-related assessments may cause 
potential risk to participants, including discomfort, embarrassment, triggers of PTSD symptoms, or 
triggers of substance cravings. Our procedures for protecting against and managing such risks are 
described in the attached “NIAAA Data and Safety Monitoring Plan.” 
Risks associated with reductions in alcohol use. Another potential risk to participants with severe AUD 
is symptoms of alcohol withdrawal. Study therapists will be trained to have a low threshold for alcohol 
withdrawal risk. For any participants reporting alcohol discontinuation, study therapists will ask 
participants if they are experiencing any significant symptoms of withdrawal - tremors, sweating, 
flushing, nausea, vomiting, hallucinations, or seizures. If a participant endorses any of these symptoms, 
the therapist will briefly pause the session to consult with Co-I Jefee-Bahloul, Addiction Psychiatrist, who 
will be available for on-call phone consultation. Given the potential lethality of alcohol withdrawal, Dr. 
Jefee-Bahloul will likely recommend voluntarily sending the participant to detox or the Emergency 
Department for evaluation (Note: Prior to study initiation, our team will work with National Deaf 
Therapy to identify detox programs in each state where study intervention will be provided). Following 
the therapy session, the therapist will report the event to PI Anderson. 
Any serious adverse events, unanticipated problems, or breaches of confidentiality that occur during the 
intervention period and/or the one-month follow-up period will be reported to the UMass Chan 
Institutional Review Board and the NIAAA project officer within 48 hours. Additionally, an annual report 
will be submitted to the NIAAA project officer summarizing all adverse events. 
 
 

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3 OBJECTIVES AND ENDPOINTS 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
PUTATIVE 
MECHANISMS OF 
ACTION 
Primary 
Conduct a 
nationwide, full-
scale, virtual clinical 
trial of Signs of 
Safety. Leveraging 
the existing 
infrastructure and 
robust referral 
network of National 
Deaf Therapy, we 
will enroll 144 Deaf 
adults with past-
month PTSD and 
problem drinking into 
our study protocol. 
Primary clinical 
outcomes at 
immediate post-
treatment and post-
treatment follow-up 
are alcohol use 
frequency/quantity 
(Alcohol Timeline 
Followback) and 
PTSD severity (PTSD 
Checklist for DSM-5) 
to the last assessment 
timepoint. 
Assessments will 
occur at baseline, 
mid-treatment, 
immediate post-
treatment, three-
month post-treatment 
follow-up, and six-
month post-treatment 
follow-up. 
Alcohol use 
frequency/quantity 
(Alcohol Timeline 
Followback); 
PTSD severity (PTSD 
Checklist for DSM-5) 
Measures of primary clinical 
outcome are: the Alcohol 
Timeline Followback,28 to 
assess daily drinking 
frequency and quantity for a 
selected time range (we will 
use “past 30 days” at 
baseline and “time since to 
assessment” for all other 
timepoints); and the PTSD 
Checklist for DSM-5,29 a 
measure of DSM-5 PTSD 
symptoms that is reliably 
used to monitor symptom 
change.70 
TBD: See 
Tertiary/Exploratory 
Below. 
Secondary 

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OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
PUTATIVE 
MECHANISMS OF 
ACTION 
Same as above. 
DSM-5 Alcohol Use 
Disorder diagnostic 
criteria; 
Drug use 
frequency/quantity; 
Substance-related 
problems; 
Drug and alcohol 
craving; 
Mental health 
symptoms. 
Measures of secondary 
clinical outcome are the 
Timeline Followback – Drugs, 
Cigarettes, and Marijuana, 
which we will use to assess 
frequency and quantity of 
drug use for the same 
referent time period; the 
DSM-5 AUD Assessment 
Tool to track AUD symptoms 
over time; the Short 
Inventory of Problems 
Revised, to assess alcohol-
related consequences; two 
items querying alcohol and 
drug craving from the Brief 
Addiction Monitor – Revised; 
and the Outcome 
Questionnaire (OQ-30.2) for 
Adults, to assess changes in 
psychosocial functioning over 
time. 
TBD: See 
Tertiary/Exploratory 
Below. 
Tertiary/Exploratory 
Explore potential 
moderators and 
mediators that lead to 
positive outcome. 
Identified from the 
literatures on Seeking 
Safety, alcohol 
treatment research, 
and Deaf mental health 
research, potential 
mechanisms of change 
are coping self-efficacy, 
self-compassion, 
motivation for 
treatment, and access 
to health information. 
Coping self-efficacy; 
Self-compassion; 
Motivation for 
treatment; access to 
health information. 
We identified potential 
mechanisms of change from 
the Seeking Safety literature, 
alcohol treatment literature, 
and Deaf mental health 
literature. One key 
moderator is motivation for 
treatment.74,75,76 Potential 
mediators are participants’ 
reported ability to use coping 
skills,39,72,77,78 practice self-
compassion,72,79,80,81 and 
understand health 
information.23,34,35,36,58 These 
constructs will be measured 
by the Contemplation 
Ladder,82,83 a single-choice, 
visual analogue scale whose 
higher rungs represent 
greater levels of readiness to 
N/A 

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OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
PUTATIVE 
MECHANISMS OF 
ACTION 
change; the Brief Resilient 
Coping Scale,84,85 a measure 
of perceived ability to 
effectively use coping 
strategies in flexible, 
committed ways to actively 
solve problems despite 
stressful circumstances; the 
Self-Compassion Scale – 
Short Form,86 a measure of 
self-compassion in instances 
of perceived failure, 
inadequacy, or suffering; 
and, the Ask, Understand, 
Remember Assessment 
(AURA),87 a measure of one’s 
ability to obtain, understand, 
and remember health 
information communicated 
by a provider. 

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4 STUDY DESIGN 
4.1 OVERALL DESIGN 
In partnership with National Deaf Therapy (NDT) and informed by feasibility data generated during the 
Signs of Safety single-arm pilot and randomized feasibility pilot (see preliminary data in section 4.2), we 
will conduct a nationwide, full-scale, virtual clinical trial of Signs of Safety. To prepare, we will fine-tune 
our therapist training program and certify eight study therapists from NDT in Seeking Safety + Signs of 
Safety. Additionally, to streamline study outcome assessment, we will formally translate study measures 
from written English to ASL, professionally film the final translations, and design a Deaf-accessible online 
REDCap survey platform. 
Across three years of rolling recruitment, we will recruit 144 Deaf adults with past-month PTSD and 
problem drinking into our study protocol (Aim 1). Primary clinical outcomes at immediate post-
treatment and follow-up are alcohol use frequency/quantity (Alcohol Timeline Followback)29 and PTSD 
severity (PTSD Checklist for DSM-5)30 since the last assessment timepoint. Assessments will occur at 
baseline, mid-treatment (week 6), immediate post-treatment (week 12), three-month post-treatment 
follow-up, and six-month post-treatment follow-up. 
Participants residing in the 21 states served by NDT (n = 96) will be randomized to receive either (1) a 
12-session protocol of Seeking Safety + Signs of Safety, or (2) 12 sessions of therapy as usual (Aim 1a). 
Augmenting the Aim 1a RCT, we will enroll an additional 48 Deaf adults into a contemporaneous no-
treatment control arm. These individuals will be recruited from the existing NDT waitlist, comprised of 
Deaf individuals residing in the 29 states not yet served by NDT but voluntarily awaiting NDT services 
(Aim 1b). 
We will also explore potential moderators and mediators that may lead to positive outcomes, including 
participants’ coping self-efficacy, self-compassion, motivation for treatment, and perceived access to 
health information (Aim 2). 
 
 
4.2 SCIENTIFIC RATIONALE FOR STUDY DESIGN 
This Signs of Safety clinical trial is informed by two foundational studies – a single-arm open pilot study 
(2014 – 2019) and a pilot feasibility randomized controlled trial (2018 – 2022). 
Open Pilot Study (2014 – 2019) 
PI Anderson’s single-arm open pilot study resulted in the successful creation of the Signs of Safety 
toolkit prototype, the demonstration of recruitment feasibility and acceptability of the study 
intervention, and evidence of preliminary efficacy. Participants (n = 13) reported high levels of 
satisfaction with the Seeking Safety + Signs of Safety intervention. This finding was supported by a 23% 
attrition rate (3/13), lower than the average rate of 27% observed in longitudinal addiction studies.64 
Our attrition rate was especially noteworthy given that retained participants completed a lengthy 25-
session treatment protocol and end-of-treatment assessment. 

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Clinically meaningful reductions in alcohol use frequency and PTSD severity were observed from 
baseline to immediate post-treatment.28 Participants who received the minimum dose of Seeking Safety 
+ Signs of Safety (at least six sessions; n = 10) exhibited a 9.9 point mean reduction on the PTSD Checklist 
for DSM-5 (PCL-5),28 aligning with the 10 point clinically meaningful improvement on this measure.65 
Alcohol use frequency decreased by an average of 4.7 days per month across the course of the study. 
Eight participants (80.0%) were abstinent or evidenced clinically meaningful reduction in past-month 
alcohol use by the end of treatment (Reliable Change Index > 1.96), one remained unchanged, and one 
increased their drinking.28 
Randomized Feasibility Pilot (2018 – 2022) 
The Signs of Safety randomized feasibility pilot resulted in the professional production of a final version 
of the Signs of Safety toolkit, the development and successful implementation of a prototype therapist 
training program, and the mid-2019 launch of an in-person, two-arm pilot feasibility randomized 
controlled trial. Just as enrollment ramped up, our trial was disrupted by the onset of the COVID-19 
pandemic. In response, we paused the study to overhaul our in-person research methods and instead 
implement a virtual clinical trial – an acceleration of the inevitable development needed to scale Signs of 
Safety to a national level. This adaptation made possible our crucial collaboration with National Deaf 
Therapy, as well as provided comprehensive feasibility data from testing a variety of virtual clinical trial 
methods. These data informed our proposed methods and are interspersed throughout the Approach in 
sections labeled Feasibility Findings.  
Despite significant COVID-related disruptions, the delivery of the experimental intervention was deemed 
feasible by study therapists and was well-received by participants,28 especially after we moved to a 
virtual platform. Initial outcome data reinforce the preliminary efficacy observed during the Signs of 
Safety open pilot. Using intent-to-treat analyses, participants assigned to the active treatment arm (n = 
8) exhibited a 22% decrease in PTSD symptom severity from baseline to follow-up, compared to a 9% 
decrease among those assigned to waitlist control (n = 7). Active treatment participants exhibited an 8-
point mean reduction on the PCL-5, especially notable considering the intervention protocol reduced 
from 25 treatment sessions in the open pilot to 12 sessions in the pilot feasibility RCT. Active treatment 
participants reduced binge drinking by 1.75 days per month, as compared to 0.14 days per month in the 
waitlist control arm. Two participants in active treatment became fully abstinent from alcohol by follow-
up, as compared to none of the waitlist participants. 
 
 
4.3 JUSTIFICATION FOR INTERVENTION 
Seeking Safety is a manualized, non-exposure-based, cognitive behavioral therapy that focuses on 
psychoeducation and development of simple coping skills that simultaneously target AUD and PTSD (or 
either alone). Seeking Safety is the most widely implemented model for PTSD and substance use 
disorder, with a 2016 meta-analysis indicating positive outcomes on both PTSD and substance use 
disorder among 1000+ patients across studies.1,39,40,41,42,43,44 Although there is preliminary-to-promising 
evidence for other manualized treatments for comorbid AUD/PTSD,16,18,33,45 these treatments rely on the 

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client’s ability to formulate a trauma narrative,55 which, as described above in section 2.1, is 
contraindicated for many Deaf clients.7,35 Such models also have limitations for Deaf clients from a 
public health standpoint (e.g., more costly, exclude more complex clients).56 
Given these contraindications, our team selected Seeking Safety as our base intervention due to its 
present-focus (i.e., no need to retell the trauma narrative) and reliance on simple coping skills. Notably, 
among women with disabilities,57 those treated with Seeking Safety experienced sustained reductions in 
PTSD symptoms while women in the comparison condition experienced experienced full PTSD 
recurrence by 12-month follow-up.57 Changes in AUD over time could not be investigated in this 
secondary analysis, as the majority of participants with disabilities reported no alcohol use at baseline. 
Despite this floor effect, this study provided preliminary support that Seeking Safety would be an 
engaging and effective approach among individuals with disabilities, including Deaf individuals.57 Indeed, 
Seeking Safety has been used successfully with highly diverse populations, translated into 14 foreign 
languages, and aligns with most strategies for Deaf-friendly treatment – skill-building and 
psychoeducation, structured sessions, case management, present focus, and strength-based work.27,58 
Yet, similar to other manualized treatments, Seeking Safety ’s client materials rely on written English, 
failing to meet the linguistic needs of Deaf clients.20,35 
To address this barrier, the PI assembled an impressive team of Deaf and hearing researchers, clinicians, 
filmmakers, actors, artists, and Deaf people with AUD/PTSD to develop and pilot test Signs of Safety, a 
Deaf-accessible toolkit to be used with Seeking Safety. A similar toolkit approach has been used to 
augment Seeking Safety for adolescents59 and individuals with HIV.60 To develop Signs of Safety, our 
team followed NIDA behavioral therapy development approaches61 and recommended principles for 
creating Deaf-accessible interventions: language adaptations and simplification of English-based 
materials; use of teaching stories and examples; inclusion of visual aids; active treatment strategies and 
role-playing; attention to health literacy gaps; leveraging of technology; and, drawing on Deaf 
community members’ desire to help and teach each other.27,58 For future generalizability and public 
health impact, Signs of Safety is designed for use by both Deaf/signing clinicians and non-signing 
clinicians who communicate with Deaf clients through ASL interpreters. 
Signs of Safety includes two primary components: 
The therapist companion guide teaches clinicians how to effectively implement Seeking Safety with 
Deaf clients by providing recommended ASL translations of common Seeking Safety concepts and 
vocabulary, exploring how issues raised by each Seeking Safety topic interact with common Deaf 
experiences, and discussing helpful tips for working with Deaf clients with addiction and PTSD. 
Client materials include: (1) ASL teaching stories on digital video for 12 core Seeking Safety topics, which 
present critical learning points portrayed by Deaf actors; and (2) visual handouts, which present key 
information using plain text and visual aids created by a Deaf artist.  
To design the main component of Signs of Safety – the ASL teaching stories described above – we 
leveraged the cultural tradition of storytelling in the Deaf community.62 Additionally, we drew on the 
Slater Model of Narrative Communication,25,26 in which a compelling storyline, the level of similarity 
between the characters and the audience, and high production quality coalesce to produce changes in 
attitudes, skills, and behaviors. 

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4.4 END-OF-STUDY DEFINITION 
An active treatment participant is considered to have completed the study if they have completed all 12 
intervention sessions, as well as all assessment time points (baseline, mid-treatment/week 6, immediate 
post-treatment/week 12, three-month post-treatment follow-up/week 25, and six-month post-
treatment follow-up/week 38.) 
  
A no-treatment control participant is considered to have completed the study if they have completed all 
assessment time points (baseline, mid-treatment/week 6, immediate post-treatment/week 12, three-
month post-treatment follow-up/week 25, and six-month post-treatment follow-up/week 38.) 
  
The end of the study is defined as completion of the 6-month follow-up assessment shown in the 
Schedule of Activities (SoA), Section 1.3. 
 
 

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5 STUDY POPULATION 
5.1 INCLUSION CRITERIA 
• Self-identification as Deaf or hard-of-hearing  
• Proficiency in American Sign Language (ASL) 
• Age 18 years or older 
• Access to videoconferencing technology for informed consent and, if applicable, study therapy 
sessions  
• Access to online survey technology for study assessments 
• “Problematic alcohol consumption, drinking behaviors, and alcohol-related problems” on the AUD 
Identification Test (AUDIT),71 a 10-item screening measure developed by the World Health Organization 
that demonstrates good sensitivity and specificity in many populations72,73,74 (past-month referent time 
period; score ≥ 8 for men or ≥ 6 for women) 
• “Subthreshold or full PTSD,” on the PTSD Checklist for DSM-5 (PCL-5),30 a 20-item measure of PTSD 
symptoms reliably used to monitor symptom change75 (past-month referent time period; 
“subthreshold” = meets at least two DSM-5 diagnostic categories (B, C, D, and/or E) at moderate or high 
severity76) 
 
Baseline AUDIT scores of 8 to 19 are appropriate for brief research interventions77 such as our 12-
session protocol, and subthreshold PTSD is associated with levels of impairment comparable to full PTSD 
(i.e., social/work functioning, suicide attempts).78 Moreover, we intentionally include individuals across 
the full range of severity of both AUD and PTSD for the broadest possible public health relevance.79 
 
 
5.2 EXCLUSION CRITERIA 
• Participation in concurrent formal psychotherapy (Note: Participants in all study conditions will be 
asked to refrain from concurrent formal psychotherapy. Participants who engage in formal 
psychotherapy outside of the research will be removed from the study at the point of treatment 
initiation. Outside treatment engagement will be queried at each assessment timepoint. If endorsed, the 
participant will be removed from the study at that timepoint, but data collected prior to treatment 
initiation will remain in the dataset. Aligning with the Seeking Safety model, AA/NA/DRA attendance will 
be encouraged; attendance will be tracked as a potential outcome mediator.) 
• Members of the following special populations: Adults unable to consent; Individuals younger than 18 
years; Prisoners; Pregnant women (Note: We will not knowingly include pregnant women as 
participants; however, we will not assess participants’ pregnancy status.) 
  

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Exclusion criteria are intentionally minimal to recruit a diverse sample. Other behavioral health 
comorbidities (e.g., mood/anxiety disorders, substance use disorders other than AUD) will not be 
excluded, given high rates of comorbidity.72 
 
 
5.3 LIFESTYLE CONSIDERATIONS 
N/A 
 
 
5.4 SCREEN FAILURES 
Screen failures are defined as participants who consent to participate in this study but are not 
subsequently assigned to the study intervention or entered in the study. Individuals who do not meet 
the criteria for participation in this trial (screen failure) because of meeting one or more exclusion 
criteria that are likely to change over time may be rescreened. Examples include increases in alcohol use 
or PTSD symptoms that would then meet the threshold for study participation. Rescreened participants 
will be assigned the same participant number as for the initial screening. 
 
 
5.5 STRATEGIES FOR RECRUITMENT AND RETENTION 
Study recruitment will leverage the existing infrastructure and robust referral network of National Deaf 
Therapy (NDT). NDT receives more than 600 new client referrals per year; this projects to approximately 
1,800 referrals across the course of our three-year rolling recruitment phase. During open recruitment, 
new clients who present to NDT to address issues of trauma and/or alcohol use will be asked if they are 
potentially interested in participating in the Signs of Safety clinical trial. Interested individuals will be 
sent a link to our eligibility screening survey via email or text. Those who are eligible will be promptly 
contacted by our research team for informed consent procedures, described in more detail in section 
10.1. 
Our research team will further support study advertisement by disseminating ASL recruitment videos 
and plain English flyers to Deaf-related organizations, Facebook groups, and listservs across the US. The 
PI has used such methods successfully in six previous studies involving Deaf research 
participants.6,31,93,94,95 Recruitment materials will direct interested individuals to contact NDT for 
eligibility screening. 
To evaluate feasibility of recruitment, we analyzed one year of NDT’s diagnostic billing data (5/1/2021 – 
4/30/2022). In this period, 21.8% of clients presented with PTSD or a trauma-related disorder; NDT 
therapists estimate that approximately half of those with PTSD also reported alcohol-related problems 

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(10.9% of NDT clientele). Projected onto 1,800 new referrals during our rolling recruitment period, we 
anticipate that approximately 196 individuals will meet study eligibility criteria across our three-year 
recruitment period. In the Signs of Safety randomized feasibility pilot, 83% of eligible individuals chose 
to enroll in the study protocol. Applying a more conservative enrollment rate of 75% to the proposed 
trial, we estimate that, of the 196 projected positive eligibility screens, at least 144 individuals will 
enroll. 
To evaluate anticipated sample diversity, we analyzed deidentified demographic data for the 10.9% of 
NDT clientele who would likely meet eligibility criteria for the proposed study. Assuming stable 
demographic characteristics over time, data suggests a median participant age of 34 years (range = 26 to 
66 years). Approximately 63% of the sample will be non-Hispanic White, 20% Hispanic/Latino, 3% 
Black/African American, and 14% other race/ethnicity. Approximately 77% of the sample will be female, 
10% male, and 13% other gender identity (e.g., non-binary, transgender).  
 
 

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6 STUDY INTERVENTION(S) OR EXPERIMENTAL MANIPULATION(S) 
6.1 STUDY INTERVENTION(S) OR EXPERIMENTAL MANIPULATION(S) ADMINISTRATION 
6.1.1 STUDY INTERVENTION OR EXPERIMENTAL MANIPULATION DESCRIPTION 
Assignment to condition. After baseline assessment is complete, study staff will assign participants to 
study condition. The PI and all Co-Is will be masked to study condition. Assignment will adhere to ethical 
and legal obligations to match participants with therapists licensed to practice in the participant’s 
state of residence. Study therapists will be compensated at their normal National Deaf Therapy (NDT) 
reimbursement rate and will take on professional liability for their cases. 
• 
Participants residing in a state served by NDT will be randomly assigned to receive the experimental 
Seeking Safety + Signs of Safety intervention or therapy as usual (TAU). During study start-up, our team 
will support and fund NDT therapists to seek additional state licensures to ensure that each NDT state has 
at least one therapist available to provide Seeking Safety + Signs of Safety and one therapist available to 
provide TAU. Therapists will not cross over between study conditions. 
• 
Participants in states with no NDT therapists and who prefer to be placed on NDT’s waitlist instead of 
being referred outside of NDT (currently comprised of 200 individuals) will be automatically assigned to 
the no-treatment control. Additional detail about this condition is located below. 
Experimental condition: Seeking Safety + Signs of Safety toolkit. Experimental participants will be 
offered 12 one-hour, weekly individual therapy sessions of Seeking Safety delivered with the Signs of 
Safety toolkit. Sessions will occur virtually via NDT’s secure HIPAA-compliant video chat platform. Length 
of treatment is limited to six months; number of completed sessions will be tracked as a measure of 
participant adherence. 
Feasibility Findings: Prior to the Signs of Safety pilot feasibility RCT, we reduced our experimental 
intervention from 25 to 12 core sessions to fit within a feasible timeframe for clinical research and for 
practicality of future implementation in community-based practice. This decision was made in 
consultation with Seeking Safety’s developer, Dr. Najavits, and is further supported by a NIAAA-funded 
RCT that showed efficacy of a 12-session, partial-dose Seeking Safety for reducing alcohol use 
frequency.1 
Active comparison condition: Treatment as usual. Participants assigned to the active comparison 
condition will receive therapy as usual - i.e., general, open-ended, non-manualized supportive 
counseling provided by an NDT therapist. In the absence of any evidence-based therapies available for 
Deaf clients, this unstructured therapy approach is the current standard of care in the field of Deaf 
mental health. All NDT therapists are Deaf, fluent in ASL, and specialize in issues common to Deaf 
individuals seeking mental health care. NDT therapists come from a wide variety of training 
backgrounds, but each works with their clients to build on their existing strengths and provide support 
as clients develop new strategies and behaviors for overcoming adversity. Like the experimental 
condition, participants will receive 12 one-hour, weekly individual therapy sessions via NDT’s secure 
virtual therapy platform. Length of treatment is limited to six months; number of completed sessions 
will be tracked as a measure of participant adherence. 

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Control condition: No treatment. Participants in states with no NDT therapists and who prefer to be 
placed on NDT’s waitlist instead of being referred outside of NDT for therapy will be automatically 
assigned to the no-treatment control condition. At the time of this submission, there are approximately 
200 individuals on the NDT waitlist; individuals remain on the waitlist until a licensed therapist from 
their state joins the NDT team. 
Participants in the control condition will be prompted to complete assessments at baseline, week 6, 
week 12 (to approximate immediate post-treatment), week 25 (to approximate three-month follow-up), 
and week 38 (to approximate six-month follow-up). Such repeated assessment in the control arm will 
allow us to quantify and control for participants’ natural change over time and any potential assessment 
reactivity. 
Feasibility Findings/Alternate Designs Considered: In the Signs of Safety randomized feasibility pilot, we 
tested an artificial waitlist as our control condition. Seventeen percent of eligible participants chose not 
to enroll in the study because they were motivated for treatment at the time of screening, needed 
immediate treatment, and would not risk the chance of being placed on a four-month waitlist. Of 
enrolled participants who were assigned to the waitlist condition, only 57% took advantage of the 12 
free sessions of treatment after the four-months waiting period, suggesting that we missed the critical 
opportunity to intervene at a transitory moment of readiness for change. Given that the proposed study 
protocol is one year in length (maximum 6-month treatment period + 6-month post-treatment follow-up 
period), it is ethically unfathomable to create an artificial waitlist and ask that participants refrain from 
much-needed treatment during this extended period of time. As such, we will use NDT’s natural waitlist 
to feed the proposed control condition. Control participants who gain access to treatment during the 
study protocol (i.e., come off of NDT’s waitlist or gain access to formal psychotherapy elsewhere) will be 
removed from the study at the point of treatment initiation (see Section 6.5 Concomitant Therapy for 
additional detail). 
6.1.2 ADMINISTRATION AND/OR DOSING 
Experimental condition: Seeking Safety + Signs of Safety toolkit. 12 one-hour, weekly individual 
therapy sessions of Seeking Safety delivered with the Signs of Safety toolkit.  
Active comparison condition: Treatment as usual. Like the experimental condition, participants will 
receive 12 one-hour, weekly individual therapy sessions. 
Control condition: No treatment. N/A - no treatment, assessment only. 
 
 
6.2 FIDELITY 
6.2.1 INTERVENTIONIST TRAINING AND TRACKING 
We will train eight study therapists from National Deaf Therapy in how to provide Seeking Safety + 
Signs of Safety. In the second half of Year 1, consultant Najavits or one of her Treatment Innovations 
associates will provide a full-day training seminar on how to conduct Seeking Safety. Subsequently, PI 
Anderson and consultant Butland will train therapists in how to add on the Signs of Safety toolkit to the 

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Seeking Safety protocol using a formal didactic training seminar and supervision program. The 
culmination of the training program will be Seeking Safety certification, overseen by Treatment 
Innovations. Study therapists will be paid their hourly therapy rate and will be provided with CEUs to 
compensate for time spent in training. 
Study therapist credentials include independent licensure in mental health counseling, psychology, or 
clinical social work; ASL fluency; and experience with addiction and trauma treatment. Of the 15 
therapists currently employed by National Deaf Therapy, all meet these criteria. Eight of these 15 
therapists are interested in becoming Seeking Safety + Signs of Safety certified for the proposed trial. 
Therapist performance will be evaluated via a structured program of fidelity monitoring, including 
ongoing ratings of experimental session videos and a data-driven supervision group. For each 
experimental participant, two out of 12 sessions (approximately 96 sessions; 16.7%) will be randomly 
selected for screen recording. We will capture fidelity throughout the treatment course by randomly 
selecting one session from sessions 1 - 6 and one session from sessions 7 - 12. Study therapists will be 
compensated for the time required for video processing and uploading to UMass Chan’s secure MoveIt 
file transfer system. 
Session videos will be rated for fidelity on an ongoing basis by consultant Butland, who will be trained 
and certified as a Seeking Safety fidelity rater and supervisor during Year 1 (Table 1). Sessions will be 
rated with the Seeking Safety Adherence Scale.84 Fidelity results will be reviewed on an ongoing basis to 
identify common challenges to implementation across study therapists; these results will drive 
discussion topics for a monthly supervision group, which will be co-facilitated by PI Anderson and 
consultant Butland.  
 
 
6.3 MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
Participants residing in one of the 21 states served by NDT will be randomly assigned to receive the 
experimental Seeking Safety + Signs of Safety intervention or therapy as usual (TAU). During study start-
up, our team will support and fund NDT therapists to seek additional state licensures to ensure that 
each NDT state has at least one therapist available to provide Seeking Safety + Signs of Safety and one 
therapist available to provide TAU. Therapists will not cross over between study conditions. 
The PI and all Co-Is will be masked to study condition. 
 
 
6.4 STUDY INTERVENTION/EXPERIMENTAL MANIPULATION ADHERENCE 
For both active treatment conditions, length of treatment is limited to six months; number of completed 
sessions (out of a possible total of 12 sessions) will be tracked as a measure of participant adherence. 
 
 

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6.5 CONCOMITANT THERAPY 
Participants in all study conditions will be asked to refrain from concurrent formal psychotherapy. 
Participants who engage in formal psychotherapy outside of the research will be removed from the 
study at the point of treatment initiation. Outside treatment engagement will be queried at each 
assessment timepoint. If endorsed, the participant will be removed from the study at that timepoint, 
but data collected prior to treatment initiation will remain in the dataset. Aligning with the Seeking 
Safety model, AA/NA/DRA attendance will be encouraged; attendance will be tracked as a potential 
outcome mediator. Additionally, medication use for psychiatric conditions and substance use will be 
tracked as a potential outcome mediator. 
6.5.1 RESCUE THERAPY 
If at any time a participant is identified as having a serious psychiatric or substance use problem that 
requires a higher level of care than our study can provide, this concern will be immediately reported to 
the PI, who will provide referral and bridging to appropriate treatment options for stabilization. Once 
stabilized, the participant has the option to return to our study. Additional detail is located in Section 7. 
 
 

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7 STUDY INTERVENTION/EXPERIMENTAL MANIPULATION DISCONTINUATION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1 DISCONTINUATION OF STUDY INTERVENTION/EXPERIMENTAL MANIPULATION 
Given the proposed study’s classification as an NIH-defined Stage III clinical trial, this project will involve 
oversight from a Data Safety and Monitoring Board (DSMB). UMass Chan Medical School (UMass Chan) 
has a Population & Quantitative Health Sciences Department that provides DSMB services to University 
investigators, and we will utilize these services for the proposed trial. Specifically, Co-I Barton, 
Biostatistician, will oversee the preparation of the DSM report, and he will present that report at DSMB 
meetings held every year until the end of data collection. The DSMB will be composed of three UMass 
Chan faculty unaffiliated with the project (e.g., a psychiatrist, an internal medicine physician, and a 
statistician/epidemiologist). The DSM report will include 1)participants’ sociodemographic 
characteristics; 2) expected versus actual recruitment rates; 3)any quality assurance or regulatory issues 
that occurred during the past year; 4) a summary of adverse events; and 5) any actions or changes with 
respect to the protocol. The DSM report will also include, when available, the results of any data 
analyses. The DSMB Reports will present data from blinded treatment groups. No interim analyses are 
planned for this study unless the DSMB requests an interim analysis assessment of study efficacy or 
futility. An independent statistician will prepare any interim analyses requested by the DSMB. The DSMB 
can request other data in the form of tables, listings, and figures as it determines the necessity to review 
other information. The DSMB will provide recommendations to NIAAA for the continuation or cessation 
of the study based on their review of the data. 
In addition to the oversight of the DSMB, the PI, a licensed clinical psychologist, will be responsible for 
monitoring the safety of this trial, executing the NIAAA-approved Data and Safety Monitoring Plan 
(DSMP), and complying with all reporting requirements. Diligent safety monitoring will be conducted 
throughout the study as follows: 
• 
Individual data will be monitored by the PI, Co-I Wilkins, and the study therapists over the course of the 
study to identify any participants who may need additional intervention. Data sources include (1) 
frequency and quantity of weekly alcohol and drug use collected at the beginning of each therapy session 
during a structured check-in process; (2) suicidal thoughts, plans, or intent assessed during the structured 
check-in if the participant reports feelings of depression; (3) check-out process at the end of each therapy 
session that asks participants if any problems arose for them during the session; (4) PTSD symptoms and 
alcohol use data collected at five outcome assessment timepoints across the study. 
• 
After each assessment time point, the PI and/or Co-I Wilkins will review data to determine if any 
particular participants are reporting significant clinical deterioration (i.e., “clinically meaningful” increase 
of 10+ points on the PTSD Checklist for DSM-5, increase in AUD category of severity based on DSM-5 
criteria). Should a participant be identified as experiencing significantly worsening distress over the course 
of the study, the PI will determine the appropriate course of action (e.g., withdrawal from the study and 
referral to outside treatment). Once stabilized, the participant would have the option to return to our 
study. 

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• 
If at any time a participant is identified as having a serious psychiatric or substance use problem that 
requires a higher level of care than our study can provide, this concern will be immediately reported to 
the PI, who will provide referral and bridging to appropriate treatment options for stabilization. Once 
stabilized, the participant has the option to return to our study. 
• 
Should a participant communicate distress and intent to withdraw from the study, the PI will provide 
referral and bridging to appropriate treatment options. 
• 
Study therapists will assess withdrawal symptoms on an as-needed basis (e.g., if participants report 
abrupt alcohol discontinuation) using the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar). 
Therapists will be instructed to discuss any concerns regarding withdrawal immediately with Co-I Jefee-
Bahloul, Addiction Psychiatrist, who will be available for on-call phone consultation. 
• 
Should a participant arrive at a virtual therapy session under the influence of drugs or alcohol, the study 
therapist will be trained to assess the participant’s level of safety, discontinue the session, and reschedule 
the visit for a later date. 
• 
Study therapists will be trained to follow written protocols and contact 911 in the event of a dangerous 
situation. The PI will also be available for on-call phone consultation for less urgent clinical crises. The PI 
will intervene if at any time a participant’s distress cannot be contained or in cases where anyone 
appeared truly unsafe (suicidal intent, threatening harm, or other unsafe behavior). Although it is 
anticipated that this reaction is highly unlikely, should it occur, the PI will provide debriefing and, if 
needed, will call for assistance. 
 
 
7.2 PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
It is unlikely that we will need to withdraw participants from the study. Participants will only be 
withdrawn if they pose harm to themselves or others (i.e., physical aggression, verbal threats). Although 
this reaction is highly unlikely, should it occur, the PI would debrief the participant and provide referral 
to crisis or therapy services outside of the research study as needed. In the event that a participant is 
found to pose imminent harm to themselves or others, as independently licensed mental health 
providers, the study therapists will implement any actions required by state law with regard to 
individuals who are determined to pose imminent harm to themselves or others. Available data 
collected prior to withdrawal will be included in statistical analyses, unless the participant revokes 
consent during the withdrawal process.  
  
  
 
 

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7.3 LOST TO FOLLOW-UP 
A participant will be considered lost to follow-up if they fail to return for 3 consecutive scheduled visits 
and study staff are unable to contact the participant after at least 3 attempts. 
The following actions must be taken if a participant fails to return to the clinic for a required study visit: 
• 
The research team will attempt to contact the participant, reschedule the missed visits, counsel the 
participant on the importance of maintaining the assigned visit schedule, and ascertain if the participant 
wishes to and/or should continue in the study. 
• 
Before a participant is deemed lost to follow-up, the research team will make every effort to regain 
contact with the participant (where possible, 3 calls and, if necessary, a certified letter to the participant’s 
last known mailing address or local equivalent methods). These contact attempts will be documented in 
the participant’s study file. 
• 
Should the participant continue to be unreachable, they will be considered to have withdrawn from the 
study on the date of the third missed visit with a primary reason of loss to follow-up. 
 
 

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8 STUDY ASSESSMENTS AND PROCEDURES 
8.1 ENDPOINT AND OTHER NON-SAFETY ASSESSMENTS 
ELIGIBILITY SCREENING 
Interested individuals will be sent a link to our eligibility screening survey via email or text. The screening 
survey will include self-report items for the inclusion and exclusion criteria outlined in Section 5, as well 
as the AUD Identification Test (AUDIT) and PTSD Checklist for DSM-5 (PCL-5). All screening items will be 
formally translated into ASL and uploaded into our Deaf-accessible REDCap survey (like our outcome 
measures described below). 
  
MEASURES 
Using measures validated in the general population and formally translated into ASL, we will assess 
clinical outcomes and mechanisms of change at five timepoints: baseline, mid-treatment/week 6, 
immediate post-treatment/week 12, three-month post-treatment follow-up/week 25, and six-month 
post-treatment follow-up/week 38. We will report the internal consistency of the newly translated study 
measures when administered within our national Deaf sample. 
At each timepoint, we will prompt participants to complete study measures via our Deaf-accessible 
REDCap survey. To increase the probability of retention in the assessment protocol, participants will 
receive stepwise increases in compensation: $50 for baseline, $75 for mid-treatment/week 6, $100 for 
end-of-treatment/week 12, $125 for three-month follow-up, and $150 for six-month follow-up. We will 
continue to prompt participants not retained in treatment for outcome information to enable the 
participant to contribute to intent-to-treat analyses and examine potential biases due to non-
adherence. 
Feasibility Findings: Exit interviews with Signs of Safety participants revealed high levels of perceived 
burden with study assessment. Participants felt that the number of questions was excessive and many 
items were repetitive. We have carefully redesigned our test battery to retain only those measures that 
are absolutely necessary. Our resulting battery of assessments includes 109 questions at each timepoint, 
with the exception of the end-of-treatment timepoint, which includes an additional 12 items on client 
satisfaction for those enrolled in treatment arms. Our shift to an online survey platform will further 
reduce participant burden by eliminating the need to schedule an assessment session and interact with 
a study assessor. 
Measures of clinical outcome (listed in table 3 below) are the Alcohol Timeline Followback,29 to assess 
daily drinking frequency and quantity for a selected time range (we will use “past 30 days” at baseline 
and “time since last assessment” for all other timepoints); the Timeline Followback – Drugs, Cigarettes, 
and Marijuana, which we will use to assess frequency and quantity of drug use for the same referent 
time period; the DSM-5 AUD Assessment Tool, to track AUD symptoms over time; the Short Inventory of 
Problems Revised, to assess alcohol-related consequences; two items querying alcohol and drug craving 
from the Brief Addiction Monitor – Revised; the PTSD Checklist for DSM-5,30 a measure of DSM-5 PTSD 
symptoms that is reliably used to monitor symptom change;75 and the Outcome Questionnaire (OQ-30.2) 
for Adults, to assess changes in psychosocial functioning over time. 

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We identified potential mechanisms of change from the Seeking Safety literature, alcohol treatment 
literature, and Deaf mental health literature. One key moderator is motivation for 
treatment.85,86,87 Potential mediators are participants’ reported ability to use coping skills,40,80,88,89 
practice self-compassion,80,90,91,92 and understand health information.24,35,36,37,58 These constructs will be 
measured by the Contemplation Ladder,93,94 a single-choice, visual analogue scale whose higher rungs 
represent greater levels of readiness to change; the Brief Resilient Coping Scale,95,96 a measure of 
perceived ability to effectively use coping strategies in flexible, committed ways to actively solve 
problems despite stressful circumstances; the Self-Compassion Scale – Short Form,97 a measure of self-
compassion in instances of perceived failure, inadequacy, or suffering; and, the Ask, Understand, 
Remember Assessment (AURA),98 a measure of one’s ability to obtain, understand, and remember health 
information communicated by a provider. 
A measure of client satisfaction will be administered to those participants assigned to active treatment 
arms. The Satisfaction with Therapy and Therapist Scale is a 12-item measure that assesses patients’ 
level of satisfaction with their therapeutic experiences. 
  

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8.2 SAFETY ASSESSMENTS 
Assessment and management of withdrawal risk. Study therapists will be trained to have a low 
threshold for alcohol withdrawal risk. For any participants reporting alcohol discontinuation, study 
therapists will ask participants if they are experiencing any significant symptoms of withdrawal - 
tremors, sweating, flushing, nausea, vomiting, hallucinations, or seizures. If a participant endorses any of 
these symptoms, the therapist will briefly pause the session to consult with Co-I Jefee-Bahloul, Addiction 
Psychiatrist, who will be available for on-call phone consultation. Given the potential lethality of alcohol 
withdrawal, Dr. Jefee-Bahloul will likely recommend voluntarily sending the participant to detox or the 
Emergency Department for evaluation (Note: Prior to study initiation, our team will work with National 
Deaf Therapy to identify detox programs in each state where study intervention will be provided). 
Following the therapy session, the therapist will report the event to PI Anderson. 
Identification of serious psychiatric problem. If at any time a participant is identified as having a serious 
psychiatric problem that requires a higher level of care than our study can provide, this concern will be 
immediately reported to PI Anderson, who will work with NDT referral specialists to identify appropriate 
local treatment options for stabilization. Once stabilized, the participant will have the option to return to 
our study. 
Clinical emergencies. For risk concerns, like suicidality, study therapists will follow established NDT 
protocols. This protocol includes (1) clear communication on the therapy request form that NDT is not a 
crisis center; (2) a structured Suicide Risk Assessment performed during the intake process; (3) a 
Telehealth Emergency Consent form that all clients/participants review and sign (see embedded form 
below); and (4) development of a safety plan for all clients/participants. Study therapists will contact 
911 in the event of a dangerous situation (or the PI for less urgent clinical crises) and will complete 
adverse events reports. 
Deterioration. The definition of clinical deterioration, i.e., worsening of AUD or PTSD symptoms, and 
detailed steps to be taken are outlined in the NIAAA Data and Safety Monitoring Plan. In the event of 
deterioration, the study therapists will consult with PI Anderson to determine the appropriate course of 
action.  
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8.3 ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
8.3.1 DEFINITION OF ADVERSE EVENTS 
This protocol uses the definition of adverse event from 21 CFR 312.32 (a): any untoward medical 
occurrence associated with the use of an intervention in humans, whether or not considered 
intervention-related.  
8.3.2 DEFINITION OF SERIOUS ADVERSE EVENTS 
Results in death, is life threatening, requires inpatient hospitalization or prolongs existing 
hospitalization, results in persistent or significant disability/incapacity, or any other event that may 
jeopardize the participant’s health and may require medical or surgical intervention to prevent one of 
the other outcomes listed in this definition. 
8.3.3 CLASSIFICATION OF AN ADVERSE EVENT 
The PI will distinguish a serious adverse event (SAE) from a non-serious adverse event (AE) and provide 
attributions (causality and severity) using the definitions below as a guide. If needed, the PI will consult 
with the DSMB and/or UMass Chan Institutional Review Board for assistance and clarification. 
8.3.3.1 SEVERITY OF EVENT 
The following guidelines will be used to describe the severity of adverse events (AEs) not included in the 
protocol-defined grading system: 
• 
Mild: Events require minimal or no treatment and do not interfere with the participant's daily activities. 
• 
Moderate: Events result in a low level of inconvenience or concern with the therapeutic measures. 
Moderate events may cause some interference with functioning. 
• 
Severe: Events interrupt a participant's usual daily activity and may require systemic drug therapy or 
other treatment. Severe events are usually potentially life-threatening or incapacitating. Of note, the term 
"severe" does not necessarily equate to "serious". 
8.3.3.2 RELATIONSHIP TO STUDY INTERVENTION/EXPERIMENTAL MANIPULATION 
• 
Unrelated: There is not a reasonable possibility that the adverse event may have been caused by 
participation in the study. 
• 
Possibly related: The adverse event may have been caused by participation in the study; however, there 
is insufficient information to determine the likelihood of this possibility. 

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• 
Related: There is a reasonable possibility that the adverse event may have been caused by participation in 
the study. 
8.3.3.3 EXPECTEDNESS 
• 
Expected/anticipated: Identified in nature, severity, or frequency in the current protocol, informed 
consent, investigator brochure, or with other current risk information. 
• 
Unexpected/unanticipated: Not identified in nature, severity, or frequency in the current protocol, 
informed consent, investigator brochure, or with other current risk information. 
8.3.4 TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
Any SAE, unanticipated problems, or breaches of confidentiality that occur during the study will be 
reported to the UMass Chan Institutional Review Board and the NIAAA project officer within 48 hours. 
The initial report will include a brief description of the situation and when it occurred. This report will be 
followed up with a written report no more than 72 hours later. 
The PI will develop follow-up plans for SAE and unresolved unanticipated problems in collaboration with 
the UMass Chan Institutional Review Board. 
Detailed guidance on reportable events can be found in UMass Chan Institutional Review Board HRP-
801: INVESTIGATOR GUIDANCE: Prompt Reporting Requirements: 
https://www.umassmed.edu/globalassets/ccts/ccts-media/irb/investigator-guidance-2015/hrp-801-
investigator-guidance---prompt-reporting-requirements.umass.pdf 
8.3.5 ADVERSE EVENT REPORTING 
An annual report will be submitted to the NIAAA project officer summarizing all adverse events. When 
completing the annual report, the PI will include a summary of all adverse events, confirmation of 
adherence to the DSMP, a summary of any data and safety monitoring issues since the prior reporting 
period, a description of the changes in the research protocol or DSMP, and all new and continuing IRB 
approvals. The annual DSMB report will also be forwarded to the NIAAA project officer, including listings 
and summary of all AEs and SAEs 
8.3.6 SERIOUS ADVERSE EVENT REPORTING 
Any SAE, unanticipated problems, or breaches of confidentiality that occur during the study will be 
reported to the UMass Chan Institutional Review Board and the NIAAA project officer within 48 hours. 
The initial report will include a brief description of the situation and when it occurred. This report will be 
followed up with a written report no more than 72 hours later. The follow-up report will include a) the 
date of the event, b) further description, c) actions taken by project staff, d) study condition, e) planned 
follow-up (if any), f) whether the event appears related to the study, and g) whether it will affect further 
participation. 
8.3.7 REPORTING EVENTS TO PARTICIPANTS 
N/A 

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8.3.8 EVENTS OF SPECIAL INTEREST 
N/A 
8.3.9 REPORTING OF PREGNANCY 
We will not knowingly include pregnant women as participants; however, we will not assess 
participants’ pregnancy status. 
 
 
8.4 UNANTICIPATED PROBLEMS 
8.4.1 DEFINITION OF UNANTICIPATED PROBLEMS 
This protocol uses the definition of Unanticipated Problems as defined by the Office for Human 
Research Protections (OHRP). OHRP considers unanticipated problems involving risks to participants or 
others to include, in general, any incident, experience, or outcome that meets all of the following 
criteria: 
• 
Unexpected in terms of nature, severity, or frequency given (a) the research procedures that are 
described in the protocol-related documents, such as the Institutional Review Board (IRB)-approved 
research protocol and informed consent document; and (b) the characteristics of the participant 
population being studied; 
• 
Related or possibly related to participation in the research ("possibly related" means there is a reasonable 
possibility that the incident, experience, or outcome may have been caused by the procedures involved in 
the research); and 
• 
Suggests that the research places participants or others at a greater risk of harm (including physical, 
psychological, economic, or social harm) than was previously known or recognized. 
8.4.2 UNANTICIPATED PROBLEMS REPORTING 
The PI will report unanticipated problems (UPs) to the reviewing Institutional Review Board (IRB) and to 
NIAAA. The UP report will include the following information: 
• 
Protocol identifying information: protocol title and number, PI's name, and the IRB project number 
• 
A detailed description of the event, incident, experience, or outcome 
• 
An explanation of the basis for determining that the event, incident, experience, or outcome represents 
an UP 
• 
A description of any changes to the protocol or other corrective actions that have been taken or are 
proposed in response to the UP 
To satisfy the requirement for prompt reporting, UPs will be reported using the following timeline: 

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• 
UPs that are serious adverse events (SAEs) will be reported to the IRB and to the NIAAA Project Office 
within 48 hours of the investigator becoming aware of the event 
• 
Any other UP will be reported to the IRB and to the NIAAA Project Office within 48 hours of the 
investigator becoming aware of the problem 
• 
All UPs should be reported to appropriate institutional officials (as required by an institution's written 
reporting procedures), the NIAAA Project Office, and the Office for Human Research Protections (OHRP) 
within 72 hours of the IRB's receipt of the report of the problem from the investigator 
8.4.3 REPORTING UNANTICIPATED PROBLEMS TO PARTICIPANTS 
N/A  
 
 

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9 STATISTICAL CONSIDERATIONS 
9.1 STATISTICAL HYPOTHESES 
Primary Efficacy Endpoint(s): 
We will compare study conditions using two primary clinical outcomes at immediate post-treatment and 
follow-up: (1) past 30-day alcohol use frequency/quantity (from the Alcohol Timeline Followback28) and 
(2) past 30-day PTSD severity (from the PTSD Checklist for DSM-529). 
  
Alcohol use outcomes are: % drinking days per week (i.e., days with 1+ drink); % binge drinking days per 
week (i.e., days with 5+ drinks for men, 4+ for women); and mean number of drinks per drinking day. 
We will calculate these variables from daily data collected with the Alcohol Timeline Followback for 30 
days prior to baseline assessment and, for all additional timepoints, the time to last assessment 
timepoint. 
  
The primary PTSD outcome is total symptom severity on the PCL-5. We will compare individual 
achievement of a 10-point decrease in the PCL-5 at each post-baseline timepoint (as a binary outcome) 
using a generalized estimating equations (GEE) longitudinal logistic model. 
  
Secondary Efficacy Endpoint(s): 
We will examine potential moderators and mediators of intervention effects (Table 3). We will classify 
baseline factors (e.g., stable patient characteristics, motivation for treatment) as moderators and 
intervention-related factors as mediators, such as coping skills, self-compassion, and understanding of 
health information. We will use forest plots in the subgroup analyses to display the treatment effects 
(and 95% confidence intervals) without statistical inference.  
  

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9.2 SAMPLE SIZE DETERMINATION 
Based on preliminary data from the Signs of Safety open pilot and pilot RCT, we predict that 108 of 144 
enrolled participants will complete the end-of-treatment assessment (conservative retention rate of 
75%), or 36 participants per study arm. The proposed follow-up periods for the present study exceed the 
Signs of Safety R34’s one-month follow-up period; therefore, we are unable to project the number of 
participants who will complete three-month and six-month follow-up assessments. 
A clinically significant effect was used for the current power calculation. Specifically, a clinically 
significant change score for the PCL-5 is 10 points for an individual.65 Our projected sample size of 36 
completers per study arm will have over 80% power to detect an increase in the percentage of 
participants in the intervention group who achieve a decrease of 10 points in the PCL-5 to 36% 
compared to an estimated 10% in the control group using an unadjusted likelihood ratio chi-square test 
with a two-sided alpha = 0.05. In the analysis described in section 9.4, we will use a longitudinal logistic 
model to adjust the treatment effect for other factors, such as gender and race. Because we do not have 
good estimates of the correlation among the measures of the PCL-5 among participants over time, we 
used the more conservative likelihood ratio chi-square for sample size estimates but expect the 
longitudinal models to have more power and, thus, be able to detect smaller differences due to the 
partitioning of the variance among the various components. 
 
 
9.3 POPULATIONS FOR ANALYSES 
• 
Per Protocol Population: Participants who receive all 12 sessions of their assigned treatment and 
complete the Week 12/Post-Treatment assessment.  
• 
Minimum Dose Population: Participants who receive at least 6 sessions of their assigned treatment and 
complete the Week 12/Post-Treatment assessment. 
• 
Intent-to-Treat Population: Participants who receive at least 1 session of assigned treatment and 
complete the Week 12/Post-Treatment assessment. Patients will be analyzed in the treatment group to 
which they were randomized. 
• 
Safety Analysis Dataset: All participants in the sample who receive at least one treatment session or 
participate in at least one assessment time point (after baseline assessment). Patients will be analyzed 
based on the treatment that they actually received. 
 
 
9.4 STATISTICAL ANALYSES 
  

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9.4.1 GENERAL APPROACH 
Data will be entered into REDCap, a secure web-based data capture application that provides real-time 
data entry validation (e.g., data types, range checks).89,90 Our team’s senior database developer will 
customize the database to track recruitment, intervention delivery, and outcome assessments. Data will 
be exported to SAS for analysis. 
  
Details of the statistical analyses will be contained in the Statistical Analysis Plan (SAP) to be developed 
prior to the first DSMB meeting. 
9.4.2 ANALYSIS OF THE PRIMARY ENDPOINT(S) 
We will compare study conditions using two primary clinical outcomes at immediate post-treatment and 
follow-up: (1) past 30-day alcohol use frequency/quantity (from the Alcohol Timeline Followback28); and 
(2) past 30-day PTSD severity (from the PTSD Checklist for DSM-529). 
  
Alcohol use outcomes are: % drinking days per week (i.e., days with 1+ drink); % binge drinking days per 
week (i.e., days with 5+ drinks for men, 4+ for women); and mean number of drinks per drinking day. 
We will calculate these variables from daily data collected with the Alcohol Timeline Followback for 30 
days prior to baseline assessment and, for all additional timepoints, the time to last assessment 
timepoint. 
  
For our initial unadjusted group comparisons at immediate post-treatment/week 12, at the end of the 
three-month post-treatment follow-up/week 25, and at the end of the six-month post-treatment follow-
up/week 38, will use a standard t-test (or Wilcoxon non-parametric test, depending on the outcome 
distribution). Below, we describe models for analyzing adjusted group differences and for analyzing the 
longitudinal data. 
  
We will use separate generalized estimating equations (GEE) models for each alcohol-use outcome as 
predicted by study condition, patient characteristics, clinician characteristics, and the time metric 
(baseline, week 6, week 12, week 25, and week 38). Part of our analysis will use two-level GEE models 
with participants nested within clinician/therapist. These models will also include the demographics and 
characteristics of the clinicians and participants to investigate the effects of those factors on the 
outcomes of that Aim. The GEE model will effectively handle the intra-clinician correlation among the 
participants who are assigned to each clinician. Because of the uncertainty of the magnitude of the 
intra-clinician correlation, we did not include an adjustment in the sample size estimation. As a 
sensitivity analysis, we will also use mixed effects models with repeated measures (MMRM), including 
random intercepts due to the expected baseline variability and participants as random effects to adjust 
for unmeasured covariates. From this model, we can generate custom comparisons for changes from 
baseline to each of the other timepoints and between the timepoints to estimate the change from post-
intervention as an indicator of retention of the intervention effect. In the mixed effects model, we will 
initially assume an unstructured correlation structure, but, if there are convergence problems, we will 
try other structures such as AR(1), heterogeneous AR(1), Toeplitz, and heterogeneous Toeplitz. We will 
also investigate if the study conditions exhibit different variance-covariance matrices, requiring different 

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R-side specifications. We will compare the GEE results with the MMRM results to identify any 
differences, requiring deeper analyses to determine the cause. 
  
The primary PTSD outcome is total symptom severity on the PCL-5. We will compare individual 
achievement of a 10-point decrease in the PCL-5 at each post-baseline timepoint (as a binary outcome) 
using a GEE longitudinal logistic model. Predictors are study condition, timepoint (baseline as the 
reference group), and interaction of study condition. As logistic models are sensitive to the number of 
predictors relative to the number of positive outcomes, we will add other predictors to the model while 
monitoring for overfitting. Possible predictors are participant and clinician characteristics and baseline 
PCL-5 score. Although the sample size is relatively small, limiting the use of interaction terms, we will 
use forest plots to illustrate treatment effects in subgroups of participants, as suggested by the FDA.91 
  
Handling missing data. Analyses will be conducted as intent-to-treat, with all participants assigned to a 
study condition included in the analysis regardless of treatment adherence or missing data in any 
timepoints. We will use the GEE procedure in SAS to analyze the longitudinal data by fitting the models 
described above – a procedure that allows for data that are missing at random by including all available 
data from each participant in the analysis. In the event that a participant has no available outcome data, 
we will examine their sociodemographic characteristics to compare with those participants who do have 
available outcome data. For outcomes with missing data, we will first determine if the data are missing 
at random (MAR) or missing not at random (MNAR), using a logistic model to identify predictors related 
to missingness. If none of the predictors are significantly related to missingness, we will assume that the 
data are MAR and will use multiple imputation to monotonically complete the data set. We will impute 
the missing data using a predictive model for the same treatment group as the participant with missing 
data. If the data are MNAR, we will initially use stratified models to obtain separate sets of results for 
each category of the variable that indicates MNAR. Other strategies to control the MNAR problem will 
depend on the exact nature of the MNAR. 
  
Multiplicity. To control the family-wise error rate (FWER) for this study, we will use a gatekeeping 
approach.92 The primary outcome, PCL-5 total symptom severity, will be tested at the two-sided alpha = 
0.05 level as indicated above. If the proportion of participants achieving a decrease of 10 points or 
greater in the intervention group is significantly greater than for the control group, we can recycle the 
alpha error to test the secondary outcome (alcohol-use frequency) at the same level. The other 
outcomes will be tested as supportive (but not binding) outcomes, reporting group comparisons (and p-
values) as descriptive information. 
9.4.3 ANALYSIS OF THE SECONDARY ENDPOINT(S) 
The secondary outcomes are the Timeline Followback – Drugs, Cigarettes, and Marijuana, which we will 
use to assess frequency and quantity of drug use for the same referent time period; the DSM-5 AUD 
Assessment Tool to track AUD symptoms over time; the Short Inventory of Problems Revised, to assess 
alcohol-related consequences; two items querying alcohol and drug craving from the Brief Addiction 
Monitor – Revised; and the Outcome Questionnaire (OQ-30.2) for Adults, to assess changes in 
psychosocial functioning over time. 

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We identified potential mechanisms of change from the Seeking Safety literature, alcohol treatment 
literature, and Deaf mental health literature. One key moderator is motivation for treatment .74,75,76 
Potential mediators are participants’ reported ability to use coping skills,39,72,77,78 practice self-
compassion,72,79,80,81 and understand health information.23,34,35,36,58 These constructs will be measured by 
the Contemplation Ladder,82,83 a single-choice, visual analogue scale whose higher rungs represent 
greater levels of readiness to change; the Brief Resilient Coping Scale,84,85 a measure of perceived ability 
to effectively use coping strategies in flexible, committed ways to actively solve problems despite 
stressful circumstances; the Self-Compassion Scale – Short Form,86 a measure of self-compassion in 
instances of perceived failure, inadequacy, or suffering; and, the Ask, Understand, Remember 
Assessment (AURA),87 a measure of one’s ability to obtain, understand, and remember health 
information communicated by a provider. 
  
The analysis of each of these outcomes will be described in detail in the SAP developed prior to the first 
DSMB meeting. 
  
9.4.4 SAFETY ANALYSES 
In addition to the oversight of the DSMB, the PI, a licensed clinical psychologist, will be responsible for 
monitoring the safety of this trial, executing the NIAAA-approved Data and Safety Monitoring Plan 
(DSMP), and complying with all reporting requirements. Diligent safety monitoring will be conducted 
throughout the study as follows: 
• 
Individual data will be monitored by the PI, Co-I Wilkins, and the study therapists over the course of the 
study to identify any participants who may need additional intervention. Data sources include: (1) 
frequency and quantity of weekly alcohol and drug use collected at the beginning of each therapy session 
during a structured check-in process; (2) suicidal thoughts, plans, or intent assessed during the structured 
check-in if the participant reports feelings of depression; (3) check-out process at the end of each therapy 
session that asks participants if any problems arose for them during the session; (4) PTSD symptoms and 
alcohol use data collected at five outcome assessment timepoints across the study. 
Safety endpoints: 
• 
Identification of serious psychiatric problem. If at any time a participant is identified as having a serious 
psychiatric problem that requires a higher level of care than our study can provide, this concern will be 
immediately reported to PI Anderson, who will work with NDT referral specialists to identify appropriate 
local treatment options for stabilization. Once stabilized, the participant will have the option to return to 
our study. 
• 
Clinical emergencies. For risk concerns, like suicidality, study therapists will follow established NDT 
protocols. This protocol includes: (1) clear communication on therapy request form that NDT is not a crisis 
center; (2) structured Suicide Risk Assessment performed during the intake process; (3) Telehealth 
Emergency Consent form that all clients/participants review and sign (see attached); and (4) development 
of a safety plan for all clients/participants. Study therapists will contact 911 in the event of a dangerous 
situation (or the PI for less urgent clinical crises) and will complete adverse events reports. 

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• 
After each assessment time point, the PI and/or Co-I Wilkins will review data to determine if any 
particular participants are reporting significant clinical deterioration (i.e., “clinically meaningful” increase 
of 10+ points on the PTSD Checklist for DSM-5, increase in AUD category of severity based on DSM-5 
criteria). Should a participant be identified as experiencing significantly worsening distress over the course 
of the study, the PI will determine appropriate course of action (e.g., withdrawal from study and referral 
to outside treatment). Once stabilized, the participant would have the option to return to our study. 
9.4.5 BASELINE DESCRIPTIVE STATISTICS 
Baseline data will include participant demographics and selected characteristics relevant to the study. 
For reporting to the DSMB (and for Table 1 in publications), we will generate a table (or potentially 
comparative bar charts) of these demographics and characteristics with summary statistics for each item 
by treatment group. For binary or categorical variables, such as biological sex (male/female) or age 
group (e.g., 18-35, 36-50,, etc.), we will present proportions of the participants in that group with that 
characteristic with the column adding up to 1.0 or 100% and the associated number n for that 
proportion. For continuous variables that are normally distributed (verified by the Wilk-Shapiro test of 
normality), we will present the number of participants with that measure (n), mean, and standard 
deviation. For continuous variables that are not normally distributed, we will present the median and 
inter-quartile range (IQR). If the standard deviations are markedly different, we will present comparative 
box plots to understand the distribution of the variable and, thus, the best way to present measures of 
central tendency (i.e., mean, median) and variance (i.e., standard deviation, inter-quartile range). This 
exploratory analysis (when needed) will also be presented to the DSMB to provide the justification for 
the chosen method of presentation (and, potentially, analysis). 
9.4.6 PLANNED INTERIM ANALYSES 
Given the proposed study’s classification as an NIH-defined Stage III clinical trial, this project will involve 
oversight from a Data Safety and Monitoring Board (DSMB). UMass Chan Medical School (UMass Chan) 
has a Population & Quantitative Health Sciences Department that provides DSMB services to University 
investigators and we will utilize these services for the proposed trial. Specifically, Co-I Barton, 
Biostatistician, will oversee the preparation of the DSM report, and he will present that report at DSMB 
meetings held every year until the end of data collection. The DSMB will be composed of three UMass 
Chan faculty unaffiliated with the project (e.g., a psychiatrist, an internal medicine physician, and a 
statistician/epidemiologist). The DSM report will include participants’ sociodemographic characteristics, 
expected versus actual recruitment rates, any quality assurance or regulatory issues that occurred 
during the past year, summary of adverse events, and any actions or changes with respect to the 
protocol. The DSM report will also include, when available, the results of any data analyses. The DSMB 
can request other data in the form of tables, listings, and figures as it determines the necessity to review 
other information. The DSMB will provide recommendations to NIAAA for the continuation or cessation 
of the study based on their review of the data. 
9.4.7 SUB-GROUP ANALYSES 
We will also display the treatment effect by subgroups (the equivalent of the interaction terms) in a 
forest plot, as recommended by the FDA/EMA for subgroup analyses.91 The subgroups can be defined 
for the demographics of clinicians and participants (and both together) as well as the characteristics of 

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each. In addition to these subgroup analyses, we will explicitly model sex as a biological variable in this 
research because we expect that the interactions identified in the mediator/moderator analysis 
described in the application may be substantially different between men and women – and this applies 
to both clinicians and participants. 
9.4.8 TABULATION OF INDIVIDUAL PARTICIPANT DATA 
We do not anticipate presenting individual participant data as part of our reporting and analysis, except 
for SAE data, which will include the specifics of the SAE and the resolution by patient and event. Only 
Study ID numbers will be used to identify the patient. This information will be contained only in the 
DSMB reports and any required reports for the NIAAA Project Office and the UMass Chan IRB. All other 
participant data will be presented as summarized within treatment groups only. 
9.4.9 EXPLORATORY ANALYSES 
We will examine potential moderators and mediators of intervention effects (Table 3). We will classify 
baseline factors (e.g., stable patient characteristics, motivation for treatment) as moderators and 
intervention-related factors as mediators, such as coping skills, self-compassion, and understanding of 
health information. We will use forest plots in the subgroup analyses to display the treatment effects 
(and 95% confidence intervals) without statistical inference. 
 
 

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10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
10.1 REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
10.1.1 INFORMED CONSENT PROCESS 
  
10.1.1.1 CONSENT/ASSENT AND OTHER INFORMATIONAL DOCUMENTS PROVIDED TO 
PARTICIPANTS 
Promptly following screening, eligible individuals will be offered a remote video appointment during 
which one of our Deaf Community Advisors will conduct informed consent procedures. The Deaf 
Community Advisors will follow HRP-090  SOP: Informed Consent Process for Research. 
  
Prior to the call, the individual will receive an electronic copy of the IRB-approved, written English 
informed consent form (e-Consent) via REDCap, a HIPAA-compliant, web-based electronic capture 
database used by UMass Chan. During the call, the Deaf Community Advisor will present each section of 
the e-Consent form in ASL (e.g., “What are the risks of being in this study?”, “What happens to 
information about me?”), pausing after each section for questions and discussion. Individuals who wish 
to enroll will sign the e-Consent form in REDCap, by typing in their name or using the “wet signature” 
feature. 
  
During the informed consent process, participants will be informed that they have the right to refrain 
from answering any questions. It will be emphasized that any information provided by the participant is 
completely voluntary and that they can leave the study at any time if they choose. 
10.1.1.2 CONSENT PROCEDURES AND DOCUMENTATION 
The Deaf Community Advisors will follow HRP-091 SOP: Written Documentation of Consent. Individuals 
who wish to enroll in our study will sign the e-Consent form in REDCap, by typing in their name or using 
the “wet signature” feature. All study procedures, potential risks, and potential benefits will be 
explained in detail by the Deaf Community Advisors in ASL prior to obtaining written consent. 
10.1.2 STUDY DISCONTINUATION AND CLOSURE 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable 
cause. If the study is prematurely terminated or suspended, the Principal Investigator (PI) will promptly 
inform study participants, the IRB, and the NIAAA project office and will provide the reason(s) for the 
termination or suspension. Study participants will be contacted, as applicable, and be informed of 
changes to study visit schedule. Circumstances that may warrant termination or suspension include, but 
are not limited to: 
• 
Determination of unexpected, significant, or unacceptable risk to participants 
• 
Demonstration of efficacy that would warrant stopping 

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• 
Insufficient compliance of study staff to the protocol (i.e., significant protocol violations) 
• 
Data that are not sufficiently complete and/or evaluable 
• 
Determination that the primary endpoint has been met 
• 
Determination of futility 
The study may resume once concerns about safety, protocol compliance, and data quality are 
addressed, and satisfy the NIAAA Project Office, the UMass Chan IRB, and the DSMB. 
10.1.3 CONFIDENTIALITY AND PRIVACY 
Every effort will be made to protect participants’ confidentiality. Only CITI-trained personnel with 
appropriate authorization and relevant project need will be allowed data access. An NIH Certificate of 
Confidentiality will protect participants from disclosure of sensitive data, especially information related 
to substance use. Study therapists will comply with confidentiality policies per the ethical requirements 
of their independent licensing board (e.g., Board of Registration of Psychologists). 
For each experimental participant, two out of 12 intervention sessions will be randomly selected for 
screen recording (for the purposes of fidelity monitoring). Study therapists will be instructed to 
immediately upload the recording to UMass Chan’s secure MoveIt file transfer system. Once received by 
the research team, the recording will be transferred to a password-protected file on the secure, 
password-protected, encrypted, internal, and HIPAA-Compliant server hosted by UMass Chan. 
All other study data will be recorded in a REDCap database (REDCap Consortium, Vanderbilt University) 
in the secure, regulated environment at UMass Chan. This environment and REDCap are only accessible 
by medical school staff with IRB approval who are assigned an account in this environment by UMass 
Chan IT. We will program the system for a single entry with validation rules at the time of entry and 
comprehensive edits conducted after the data have been submitted to the main data base. These edits 
will check for validity, consistency, and normal range values. Additional edit checks will be performed 
routinely to identify additional potential errors through multivariable edit approaches. Edit queries will 
be generated and resolved by research staff with corrections posted to the database through the 
REDCap system, which enforces an audit trail for all changes. REDCap will also have the audit trail 
capability enabled for tracing any data modifications. 
REDCap will be used within the secure environment to protect any PHI/PII data that are collected as part 
of the study. We will strive to minimize collection of such sensitive data and REDCap will be 
programmed to segregate that data from the main study data so that exports for analysis will be 
deidentified. Data will be exported from REDCap for import into the latest version of SAS for all analyses. 
All reports and analyses will be generated from these files. Data files that are used for reports, 
presentations, or publication will be archived as required past the end of the study. 
All paper records, video recording, and electronic data records will be destroyed three years after 
completion of the grant period, in accordance with NIH policy, including the master list linking 
participant code numbers with their identifying data.  

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10.1.4 FUTURE USE OF STORED SPECIMENS AND DATA 
We will submit and share data with the NIAAA Data Archive, a data repository housed within the NIMH 
Data Archive (NDA), per the requirements set forth in NOT-AA-23-002 
(https://grants.nih.gov/grants/guide/notice-files/NOT-AA-23-002.html). All data will be de-identified 
before submission to the data archive. Additional details can be found in the uploaded document 
“NIAAA Signs of Safety R01, NIAAA Data Archive Data Sharing Plan, 6.2.2023.docx”. 
10.1.5 KEY ROLES AND STUDY GOVERNANCE 
Principal Investigator  
Medical Monitor or Independent Safety 
Monitor 
Melissa L. Anderson 
Jefee-Bahlou 
UMass Chan Medical School 
  
222 Maple Ave., Chang Building 
Shrewsbury, MA 01545 
  
508-856-5820 
  
melissa.anderson@umassmed.edu 
  
  
10.1.6 SAFETY OVERSIGHT 
Given the proposed study’s classification as an NIH-defined Stage III clinical trial, this project will involve 
oversight from a Data Safety and Monitoring Board (DSMB). UMass Chan Medical School (UMass Chan) 
has a Population & Quantitative Health Sciences Department that provides DSMB services to University 
investigators and we will utilize these services for the proposed trial. Specifically, Co-I Barton, 
Biostatistician, will oversee the preparation of the DSMB report, and he will present that report at DSMB 
meetings held every six months until the end of data collection. The DSMB will be composed of three 
UMass Chan faculty unaffiliated with the project (e.g., a psychiatrist, an internal medicine physician, and 
a statistician/epidemiologist). The DSMB report will include participants’ sociodemographic 
characteristics, expected versus actual recruitment rates, any quality assurance or regulatory issues that 
occurred since the last meeting, summary of adverse events, and any actions or changes with respect to 
the protocol. The DSMB report will also include, when available, the results of descriptive (graphical) 
analyses of the study outcomes without any statistical testing. The DSMB can request other data in the 
form of tables, listings, and figures as it determines the necessity to review other information. The 
DSMB will provide recommendations to NIAAA for the continuation or cessation of the study based on 
their review of the data. 
10.1.7 CLINICAL MONITORING 
In addition to the oversight of the DSMB, the PI, a licensed clinical psychologist, will be responsible for 
monitoring the safety of this trial, executing the NIAAA-approved Data and Safety Monitoring Plan 
(DSMP), and complying with all reporting requirements. 
Study therapists will be trained to have a low threshold for alcohol withdrawal risk. For any participants 
reporting alcohol discontinuation, study therapists will ask participants if they are experiencing any 

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significant symptoms of withdrawal - tremors, sweating, flushing, nausea, vomiting, hallucinations, or 
seizures. If a participant endorses any of these symptoms, the therapist will briefly pause the session to 
consult with Co-I Jefee-Bahloul, Addiction Psychiatrist, who will be available for on-call phone 
consultation. Given the potential lethality of alcohol withdrawal, Dr. Jefee-Bahloul will likely recommend 
voluntarily sending the participant to detox or the Emergency Department for evaluation (Note: Prior to 
study initiation, our team will work with National Deaf Therapy to identify detox programs in each state 
where study intervention will be provided). Following the therapy session, the therapist will report the 
event to PI Anderson. 
10.1.8 QUALITY ASSURANCE AND QUALITY CONTROL 
Study data will be recorded in a REDCap database (REDCap Consortium, Vanderbilt University) in the 
secure, regulated environment at UMass Chan. This environment and REDCap are only accessible by 
medical school staff with IRB approval who are assigned an account in this environment by UMass Chan 
IT. We will program the system for a single entry with validation rules at the time of entry and 
comprehensive edits conducted after the data have been submitted to the main data base. These edits 
will check for validity, consistency, and normal range values. Additional edit checks will be performed 
weekly to identify additional potential errors through multivariable edit approaches. Edit queries will be 
generated and resolved by research staff with corrections posted to the database through the REDCap 
system, which enforces an audit trail for all changes. REDCap will also have the audit trail capability 
enabled for tracing any data modifications. 
REDCap will be used within the secure environment to protect any PHI/PII data that are collected as part 
of the study. We will strive to minimize collection of such sensitive data and REDCap will be 
programmed to segregate that data from the main study data so that exports for analysis will be 
deidentified. Data will be exported from REDCap for import into the latest version of SAS for all analysis. 
All reports and analyses will be generated from these files. Data files that are used for reports, 
presentations, or publication will be archived as required past the end of the study. All research records 
will be destroyed three years after completion of the grant period, in accordance with NIH policy. 
Individual data will not be available for release. 
Quality assurance of data entry and data management consists of a set of proactive tools that are 
implemented to increase the quality of the data processing components. Specifically, these include: (1) 
form design to avoid structural missingness, orphan questions, and as many “write-in” responses as 
possible; (2) training of the data entry operators on the study forms so that they are familiar with the 
required responses; (3) design of the data entry screens to look as much like the paper forms as 
possible; (4) specifications of the data fields to reflect the nature of the data to be entered; (5) 
specification of the edit parameters and checking algorithms so that every field is verified as completely 
as possible; and (6) validation of the database system to certify that data entered into the data entry 
screens are accurately recorded in the databases. 
For quality control measures, we will conduct regular analyses to investigate: (1) number of missing data 
items; (2) number and type of forms that are failing edit; and (3) distribution of data to look for outliers. 
A Quality Control report will be generated at the same time as the DSMB report for review by study 
leadership and by the DSMB. 

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In addition to the quality assurance/quality control plans for data entry described above, we will select a 
10% sample of patients to review select (high-risk) data for verification against the source documents, 
including patient characteristics and laboratory assay results. 
10.1.9 DATA HANDLING AND RECORD KEEPING 
10.1.9.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES 
The REDCap system will be programmed and maintained by study staff at the UMass Chan; data entry 
will be performed by the participants themselves by responding to REDCap online surveys. 
10.1.9.2 STUDY RECORDS RETENTION 
Data files that are used for reports, presentations, or publication will be archived as required past the 
end of the study. All research records will be destroyed three years after completion of the grant period, 
in accordance with NIH policy. Individual data will not be available for release. 
10.1.10 PROTOCOL DEVIATIONS 
This protocol defines a protocol deviation as any noncompliance with the clinical trial protocol, 
International Council on Harmonisation Good Clinical Practice (ICH GCP), or Manual of Procedures 
(MOP) requirements. The noncompliance may be either on the part of the participant, the investigator, 
or the study staff. As a result of deviations, corrective actions will be developed by the site and 
implemented promptly. These practices are consistent with ICH GCP: 
• 
Section 4.5 Compliance with Protocol, subsections 4.5.1, 4.5.2, and 4.5.3 
• 
Section 5.1 Quality Assurance and Quality Control, subsection 5.1.1 
• 
Section 5.20 Noncompliance, subsections 5.20.1, and 5.20.2. 
It will be the responsibility of the PI to use continuous vigilance to identify and report deviations within 3 
working days of identification of the protocol deviation, or within 3 working days of the scheduled 
protocol-required activity. All deviations must be addressed in study source documents, reported to our 
NIAAA Program Official and DSMB. Protocol deviations must be sent to the reviewing IRB per their 
policies. The PI is responsible for knowing and adhering to the reviewing IRB requirements. Further 
details about the handling of protocol deviations will be included in the MOP. 
10.1.11 PUBLICATION AND DATA SHARING POLICY 
This study will be conducted in accordance with the following publication and data sharing policies and 
regulations: 
National Institutes of Health (NIH) Public Access Policy, which ensures that the public has access to the 
published results of NIH funded research. It requires scientists to submit final peer-reviewed journal 
manuscripts that arise from NIH funds to the digital archive PubMed Central upon acceptance for 
publication. 
This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded 
Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. As 

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such, this trial will be registered at ClinicalTrials.gov, and results information from this trial will be 
submitted to ClinicalTrials.gov. 
We will submit and share data with the NIAAA Data Archive, a data repository housed within the NIMH 
Data Archive (NDA), per the requirements set forth in NOT-AA-23-002 
(https://grants.nih.gov/grants/guide/notice-files/NOT-AA-23-002.html). All data will be de-identified 
before submission to the data archive. Additional details can be found in the uploaded document 
“NIAAA Signs of Safety R01, NIAAA Data Archive Data Sharing Plan, 6.2.2023.docx”. 
10.1.12 CONFLICT OF INTEREST POLICY 
The independence of this study from any actual or perceived influence is critical. Therefore any actual 
conflict of interest of persons who have a role in the design, conduct, analysis, publication, or any aspect 
of this trial will be disclosed and managed. Furthermore, persons who have a perceived conflict of 
interest will be required to have such conflicts managed in a way that is appropriate to their 
participation in the design and conduct of this trial.  The study leadership in conjunction with UMass 
Chan Medical School has established policies and procedures for all study group members to disclose all 
conflicts of interest and will establish a mechanism for the management of all reported dualities of 
interest. 
  
 
 
10.2 ADDITIONAL CONSIDERATIONS 
 N/A 
 
 
10.3 ABBREVIATIONS AND SPECIAL TERMS 
AE 
Adverse Event 
ANCOVA Analysis of Covariance 
CFR 
Code of Federal Regulations 
CLIA 
Clinical Laboratory Improvement Amendments 
CMP 
Clinical Monitoring Plan 
COC 
Certificate of Confidentiality 
CONSORT Consolidated Standards of Reporting Trials 
CRF 
Case Report Form 
DCC 
Data Coordinating Center 
DHHS 
Department of Health and Human Services 
DSMB 
Data Safety Monitoring Board 

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DRE 
Disease-Related Event 
EC 
Ethics Committee 
eCRF 
Electronic Case Report Forms 
FDA 
Food and Drug Administration 
FDAAA 
Food and Drug Administration Amendments Act of 2007 
FFR 
Federal Financial Report 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practices 
GMP 
Good Manufacturing Practices 
GWAS 
Genome-Wide Association Studies 
HIPAA 
Health Insurance Portability and Accountability Act 
IB 
Investigator's Brochure 
ICH 
International Council on Harmonisation 
ICMJE 
International Committee of Medical Journal Editors 
IDE 
Investigational Device Exemption 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
ISM 
Independent Safety Monitor 
ITT 
Intention-To-Treat 
LSMEANS Least-squares Means 
MedDRA Medical Dictionary for Regulatory Activities 
MOP 
Manual of Procedures 
NCT 
National Clinical Trial 
NIH 
National Institutes of Health 
NIH IC 
NIH Institute or Center 
OHRP 
Office for Human Research Protections 
PI 
Principal Investigator 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SMC 
Safety Monitoring Committee 
SOA 
Schedule of Activities 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
UP 
Unanticipated Problem 
US 
United States 
 
 

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10.4 PROTOCOL AMENDMENT HISTORY 
Version 
Date 
Description of Change  
Brief Rationale 
1.0 
2/4/2024 
Initial Version 
Initial version for ClinicalTrials.Gov 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
 

Evaluating Signs of Safety: A Deaf-Accessible Therapy Toolkit for AUD and Trauma 
Version 1.016 
Protocol STUDY00001149 
16 February 2024 
NIH Protocol Template for Behavioral and Social Sciences Research Involving Humans – v4.0 2018-12-12 
60 
11 REFERENCES