An Adaptive Treatment Intervention for Depression and Engagement in HIV Care Among Latinos Living With HIV
Phase: NA
Conditions: Depression
Sponsor: University of California, San Francisco

Feasibility and acceptability of an adaptive treatment 
intervention for depression and engagement in HIV 
Care among Latinos living with HIV 
National Clinical Trial (NCT) Identified Number: NCT03668379
Principal Investigator: John A. Sauceda 
Sponsor: National Institutes of Health
Grant Title: An adaptive treatment intervention for depression and engagement 
in HIV care among Latinos living with HIV 
Grant Number: K01MH113475
Funded by: National Institute on Mental Health (NIMH) 
Version Number:  v.1.4 
Revised 09.08.22
Last IRB Approval - 09.08.22

NIH Protocol Template for Behavioral and Social Sciences Research Involving Humans 
CONFIDENTIALITY STATEMENT 
This document is confidential communication. Acceptance of this document constitutes agreement by the 
recipient that no unpublished information contained herein will be published or disclosed without prior 
approval of the Principal Investigator or other participating study leadership and as consistent with the 
NIH terms of award.  
 

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Table of Contents 
STATEMENT OF COMPLIANCE ............................................................................................................................. 1 
INVESTIGATOR’S SIGNATURE .............................................................................................................................. 2 
1 
PROTOCOL SUMMARY ............................................................................................................................... 3 
1.1 
Synopsis ................................................................................................................................................ 3 
1.2 
Schema .................................................................................................................................................. 3 
1.3 
Schedule of Activities .......................................................................................................................... 4 
2 
INTRODUCTION ............................................................................................................................................ 5 
2.1 
Study Rationale .................................................................................................................................... 5 
2.2 
Background ........................................................................................................................................... 5 
2.3 
Risk/Benefit Assessment .................................................................................................................... 6 
2.3.1 
Known Potential Risks ..................................................................................................... 6 
2.3.2 
Known Potential Benefits ................................................................................................ 6 
2.3.3 
Assessment of Potential Risks and Benefits ............................................................... 6 
3 
OBJECTIVES AND ENDPOINTS ................................................................................................................ 7 
4 
STUDY DESIGN ............................................................................................................................................. 7 
4.1 
Overall Design ...................................................................................................................................... 7 
4.2 
Scientific Rationale for Study Design ................................................................................................ 7 
4.3 
Justification for Intervention ................................................................................................................ 7 
4.4 
End-of-Study Definition ....................................................................................................................... 7 
5 
STUDY POPULATION ................................................................................................................................... 8 
5.1 
Inclusion Criteria................................................................................................................................... 8 
5.2 
Exclusion Criteria ................................................................................................................................. 8 
5.3 
Lifestyle Considerations ...................................................................................................................... 8 
5.4 
Screen Failures .................................................................................................................................... 8 
5.5 
Strategies for Recruitment and Retention ........................................................................................ 9 
6 
STUDY INTERVENTION(S) OR EXPERIMENTAL MANIPULATION(S) ............................................ 10 
6.1 
Study Intervention(s) or Experimental Manipulation(s) Administration ..................................... 10 
6.1.1 
Study Intervention or Experimental Manipulation Description ................................ 11 
6.1.2 
Administration and/or Dosing ....................................................................................... 15 
6.2 
Fidelity .................................................................................................................................................. 17 
6.2.1 
Interventionist Training and Tracking .......................................................................... 17 
6.3 
Measures to Minimize Bias: Randomization and Blinding........................................................... 17 
6.4 
Study Intervention/Experimental Manipulation Adherence ......................................................... 17 
6.5 
Concomitant Therapy ........................................................................................................................ 17 
6.5.1 
Rescue Therapy ............................................................................................................. 18 
7 
STUDY INTERVENTION/EXPERIMENTAL MANIPULATION DISCONTINUATION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL ......................................................................................... 18 
7.1 
Discontinuation of Study Intervention/Experimental Manipulation ............................................. 18 
7.2 
Participant Discontinuation/Withdrawal from the Study ............................................................... 18 
7.3 
Lost to Follow-Up ............................................................................................................................... 19 
8 
STUDY ASSESSMENTS AND PROCEDURES...................................................................................... 19 
8.1 
Endpoint and Other Non-Safety Assessments .............................................................................. 19 
8.2 
Safety Assessments .......................................................................................................................... 20 
8.3 
Adverse Events and Serious Adverse Events ............................................................................... 20 
8.3.1 
Definition of Adverse Events ........................................................................................ 20 
8.3.2 
Definition of Serious Adverse Events .......................................................................... 20 

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8.3.3 
Classification of an Adverse Event .............................................................................. 20 
8.3.4 
Time Period and Frequency for Event Assessment and Follow-Up ...................... 21 
8.3.5 
Adverse Event Reporting .............................................................................................. 22 
8.3.6 
Serious Adverse Event Reporting ............................................................................... 22 
8.3.7 
Reporting Events to Participants ................................................................................. 22 
8.3.8 
Events of Special Interest ............................................................................................. 22 
8.3.9 
Reporting of Pregnancy................................................................................................. 22 
8.4 
Unanticipated Problems .................................................................................................................... 22 
8.4.1 
Definition of Unanticipated Problems .......................................................................... 22 
8.4.2 
Unanticipated Problems Reporting .............................................................................. 23 
8.4.3 
Reporting Unanticipated Problems to Participants ................................................... 23 
9 
STATISTICAL CONSIDERATIONS ........................................................................................................... 23 
9.1 
Statistical Hypotheses ....................................................................................................................... 23 
9.2 
Sample Size Determination .............................................................................................................. 23 
9.3 
Populations for Analyses .................................................................................................................. 24 
9.4 
Statistical Analyses ............................................................................................................................ 24 
9.4.1 
Analysis of the Primary Endpoint(s) ............................................................................ 24 
9.4.2 
Analysis of the Secondary Endpoint(s) ....................................................................... 24 
9.4.3 
Safety Analyses .............................................................................................................. 24 
9.4.4 
Baseline Descriptive Statistics ..................................................................................... 25 
9.4.5 
Planned Interim Analyses ............................................................................................. 25 
9.4.6 
Sub-Group Analyses ...................................................................................................... 25 
9.4.7 
Tabulation of Individual Participant Data .................................................................... 25 
9.4.8 
Exploratory Analyses ..................................................................................................... 25 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS .............................. 25 
10.1 
Regulatory, Ethical, and Study Oversight Considerations........................................................... 25 
10.1.1 
Informed Consent Process ........................................................................................... 25 
10.1.2 
Study Discontinuation and Closure ............................................................................. 26 
10.1.3 
Confidentiality and Privacy ........................................................................................... 26 
10.1.4 
Future Use of Stored Specimens and Data ............................................................... 27 
10.1.5 
Key Roles and Study Governance .............................................................................. 27 
10.1.6 
Safety Oversight ............................................................................................................. 27 
10.1.7 
Clinical Monitoring .......................................................................................................... 28 
10.1.8 
Quality Assurance and Quality Control ....................................................................... 28 
10.1.9 
Data Handling and Record Keeping ............................................................................ 28 
10.1.10 
Protocol Deviations ........................................................................................................ 29 
10.1.11 
Publication and Data Sharing Policy ........................................................................... 29 
10.1.12 
Conflict of Interest Policy............................................................................................... 29 
10.2 
Additional Considerations ................................................................................................................. 29 
10.3 
Abbreviations and Special Terms .................................................................................................... 30 
10.4 
Protocol Amendment History ........................................................................................................... 32 
11 
REFERENCES .............................................................................................................................................. 33 
 

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STATEMENT OF COMPLIANCE 
 
The trial will be conducted in accordance with applicable United States (US) Code of Federal 
Regulations (CFR), and the NIMH 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 
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. 
 
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. 
 
 

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INVESTIGATOR’S SIGNATURE 
The signature below constitutes the approval of this protocol and provides the necessary assurances 
that this study will be conducted according to all stipulations of the protocol, including all statements 
regarding confidentiality, and according to local legal and regulatory requirements and applicable US 
federal regulations and ICH guidelines, as described in the Statement of Compliance above. 
 
Principal Investigator or Clinical Site Investigator: 
Signed: 
 
Date: 
 
 
Name: John A. Sauceda, PhD 
 
Title: Assistant Professor, Department of Medicine, U.C. San Francisco 
 
 
Investigator Contact Information 
Affiliation: Center for AIDS Prevention Studies, Division of Prevention Science, Department of Medicine, 
U.C. San Francisco 
Address: 550 16th Street, 3rd Floor, San Francisco, CA 94618 
 
Telephone: 512-787-4353  
Email: john.sauceda@ucsf.edu 
 
 
 
 
 
 

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1 
PROTOCOL SUMMARY 
1.1 
SYNOPSIS  
 
Title: 
Feasibility and acceptability of an adaptive treatment intervention for 
depression and engagement in HIV Care among Latinos living with HIV 
Grant Number: 
K01MH113475 
Study Description: 
This is the evaluation of the feasibility and acceptability of an adaptive 
intervention for depression and engagement in HIV care among Latinos 
living with HIV. The adaptive intervention is the sequencing of two 
low-risk behavioral interventions with text-messaging support. The 
focus of the study is on the sequencing of the interventions.  
Objectives*: 
 
Primary Objective: Feasibility of the intervention (i.e., execution of 
enrollment and intervention session completion rates).  
Secondary Objectives: Acceptability of the intervention (i.e., evaluation 
of engagement with intervention). Full details listed in the protocol. 
Endpoints*: 
Primary Endpoint: Half-way through active engagement with 
intervention (4 of 8 sessions completed) - this is the follow-up period 
dictating the sequencing decision.  
Secondary Endpoints: 12 weeks after enrollment - this is the final 
follow-up period.  
Study Population: 
A total of 45 Latino(a)/ Hispanic adult patients (18 or older) that are 
English or Spanish speaking, are living with HIV, report a mild level of 
depressive symptoms, and receive care at San Francisco General 
Hospital Ward 86. 
Phase or Stage: 
Not applicable  
Description of 
Sites/Facilities Enrolling 
Participants: 
Participants are recruited from Ward 86, at Zuckerberg San Francisco 
General Hospital in San Francisco, CA. This is a clinic setting with 
exam rooms, waiting room, and office space. Mission Hall is a research 
building at the Mission Bay Campus at U.C. San Francisco and includes 
private office and research study space. 
Description of Study 
Intervention/Experimental 
Manipulation: 
The interventions are behavioral activation therapy (BAT), cognitive-
behavioral therapy (CBT) and text-messaging support. BAT is a 8-
session one-on-one, in-person or video conferencing, intervention. CBT 
is an 11-session, one-on-one, in-person or video conferencing, 
intervention. Text-messaging support are one- and two-way SMS 
messages.  
Study Duration*: 
We expect a total of 12-months are needed to enroll 45 participants.  
Participant Duration: 
Participants are expected to be followed for 3 months.  
1.2 
SCHEMA  
 
Flow Diagram - See Attached Figure of Sequential Multiple Assignment Randomized Trial Design.  
 
 
 
 

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1.3 
SCHEDULE OF ACTIVITIES  
 
*Participants will all start with the first stage treatment - This is BAT with or without text-messaging support. After 3 of 5 sessions - 
approximately half-way through the intervention - their depression ratings are assessed that specifically inform the next course - This is called 
the second-stage treatment. Participants may either continue to complete the 5 sessions their first-stage treatment (i.e., BAT), get one extra 
booster session (denoted by *1), or switch to CBT, which includes up to 11 sessions (denoted by *). 
 
 
 
Pre-screening 
(Pre-consent) 
 
Visit 1 
Day 1 
Visit 2 
Day 7 
Visit  3 
 Day 14 ±7 
Visit  4 
Day 21 ±7 
Visit  5 
Day 28 ±7 
Visit  6 
Day  35 ±7 
 
Visit  7 
Day  42 ±7 
Visit  8 
Day  49 ±7 
Visit  9 
Day  56  ±7 
Visit  10 
Day  63 ±7 
Visit  11 
Day  70 ±7 
Final Visit 
Day  84 ±7 
Screen for Eligibility 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Informed Consent 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Depression and Text-
Message Criteria 
 
X 
 
 
 
 
X 
 
 
 
 
 
 
Outcome Evaluation 
 
 
 
 
 
 
 
 
 
 
 
 
 
Depression Ratings 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Randomization 
 
X 
 
X 
 
 
 
 
 
 
 
 
 
1st Stage Intervention 
 
X 
X 
X 
X* 
X* 
X*1 
 
 
 
 
 
 
Primary Tailoring 
Variable - Decision 
Point on Sequencing 
 
 
 
X 
 
 
 
 
 
 
 
 
 
2nd Stage Intervention  
 
 
 
 
X 
X 
X* 
X* 
X* 
X* 
X* 
X* 
 
Adverse Events 
Reporting 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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2 
 
INTRODUCTION 
 
2.1 
STUDY RATIONALE  
Effective and efficacious treatments yield benefits to individuals, but the magnitude of those benefits is 
not equal in size. This study is attempting to understand how to optimize the benefits of efficacious 
treatments by building an adaptive treatment intervention using a Sequential Multiple Assignment 
Randomized Trial (SMART) design. The process of an adaptive intervention (i.e., specifically an Adaptive 
Treatment Strategy; ATS) is similar to the process of a medical diagnosis and treatment plan. A patient is 
diagnosed, a treatment is prescribed, and the patient is monitored. If a patient gets better, their 
treatment is maintained, if they get worse, a provider makes a decision to switch to a stronger 
treatment, hold off on a change, or add an additional treatment. Similarly, an ATS is a set of decision 
rules that dictate how to sequence treatments for depression; which are “adaptive” because they are 
not delivered uniformly to all patients. Instead, treatments are sequenced based on a patient’s progress 
(e.g., get better, worse, non-adherent to treatment) before deciding the next course of action (i.e., 
maintain, augment or switch). Because the impact (i.e., efficacy) of an intervention is not the same for 
each patient, SMARTs individualize treatment interventions to optimize the efficacy that has already 
been demonstrated. We are evaluating the feasibility and acceptability of an ATS.  
 
2.2 
BACKGROUND  
The official Significance section in the NIMH K01 Award is available upon request. Below is an 
abbreviated summary.  
We have not adequately addressed HIV-related health disparities among Latinos in the U.S. In 2012, only 
39% of Latinos diagnosed with HIV were estimated to have achieved viral suppression.  In 2013, Latinos 
accounted for nearly 23% of new HIV diagnoses in the U.S., yet only made up 16% of the U.S. population 
(60% of Latinos newly diagnosed with HIV were foreign-born).  Moreover, national HIV surveillance data 
showed that Latinos were less likely to be retained (at least 1 visit in the past year) or engaged in care 
(>2 visits 3 months apart in the past year) compared to Whites and African Americans.  However, once 
retained in HIV care, Latino HIV outcomes improve and are equal to their White counterparts. Thus, the 
challenge is to develop a strategic response that overcomes the specific barriers to care affecting 
Latinos. 
Mental health problems among Latinos living with HIV are pervasive. The most rigorous and nationally 
representative study to date found that up to 48% of people living with HIV (PLWH) met criteria for a 
depressive or anxiety disorder, which was primarily major depression (33%). Recently, similar 
estimates of depression were found in a diverse cohort of PLWH in the U.S. And while estimates of 
depression among HIV+ Latinos are as high as national estimates, they are crude because Latinos 
have only made a small percent of the study samples (< 15%) and must have been able to speak 
English. For context, nearly 1 in 3 Latinos in the U.S. are not proficient in English. Excluding Latinos 
from mental health studies based on language alone suggests we are missing key segments of the 
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To achieve sustained viral suppression and engagement in HIV care, we must identify and treat mental 
health problems. Depression is consistently associated with poorer ART adherence, poorer HIV care 
retention, worse HIV treatment outcomes, and faster mortality.  Thus, the impact of the “Treatment 
as Prevention” strategy will be limited if depression impedes on the behaviors that lead to achieving 
and sustaining viral suppression. And among Latinos, there is little use of mental health services for the 
treatment of depression. For example, Latinos use general medical services at rates comparable to non-
Latino Whites, but show less use of mental health services. And even when formally diagnosed with 
depression, Latinos (not specific to HIV) were less likely to access treatment compared to non-Latinos 
Whites; a result exacerbated for those living in poverty. In one systematic review, Latinos diagnosed 
with depression and prescribed antidepressant medication showed pervasive adherence problems. 
Therefore, poor depression treatment outcomes abound. 
Cultural and language barriers are complex but need to be addressed in HIV and mental health research. 
Lower use of mental health services suggest that Latinos may have difficulty recognizing and/or 
reporting depressive symptoms because of language difficulties (i.e., poor communication with 
providers, inability to relay psychological distress) or cultural reasons (i.e., attitudes towards mental 
health, psychotherapy and psychotropic treatment beliefs, familiarity with psychotherapy). Other 
cultural barriers to HIV and mental health care include concepts of mental illness, treatment readiness, 
and integration with the health care system. And since Spanish-speaking Latinos have also been 
underrepresented in trials to test interventions’ efficacy, use of “culturally blind” interventions for 
depression may have low acceptance and efficacy. Ongoing disparities in HIV, and in access and use of 
mental health services, make clear that the current health systems and approaches are inadequately 
suited to make strides in improving the health of HIV+ Latinos with depression.  
2.3 
RISK/BENEFIT ASSESSMENT  
 
2.3.1 KNOWN POTENTIAL RISKS  
 
1. Breaches of confidentiality.  
2. Inconvenience to the participant.   
3. Intervention does not relieve depression symptoms in participant.  
4. Mood changes - Participant experiences greater depressive symptoms during the course of the study.  
 
2.3.2 KNOWN POTENTIAL BENEFITS  
 
1. No direct benefits are guaranteed.  
2. Data can help researchers learn how to treat and manage depression.  
3. Given the evidence-base and designation of interventions as effective, we expect depression to 
improve, but this cannot be guaranteed nor the primary outcome of the study.  
2.3.3 ASSESSMENT OF POTENTIAL RISKS AND BENEFITS  
 
The risks involved in participation in the pilot study include learning that participants may have a mild 
severity level of depression, and if enrolled, the possibility that the interventions may not work, which 
may lead participants to feel discouraged, upset or hopeless (i.e., worse depression ratings). There is a 

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risk that they may feel some discomfort in talking about their feelings of sadness and maladaptive 
behaviors they have developed. As always, there is a risk for a loss of privacy if others learn they are 
participating in a study for depression. As described above, we have carefully developed all treatment 
protocols to ensure all risk are minimized and find no reason to believe any physical risks are present. 
Even if the potential risks were to occur we do not judge them to be grave or likely to affect the long-term 
mental health of the participant. The potential benefits include immediate reductions in the number and 
severity of depressive symptoms. Given the difficulties of being fully engaged in HIV care, the risks to 
participate described are reasonable given a need to address depression in a minority group 
disproportionately impacted by HIV and that ranks at the bottom among groups that have access to or 
benefit from mental health treatment programs. 
3 
OBJECTIVES AND ENDPOINTS  
 
The primary objective is feasibility, which is defined as the measures “to determine whether an 
intervention [pilot SMART] is appropriate for further testing [and] to enable researchers to assess 
whether or not the ideas and findings can be shaped to be relevant and sustainable.” The secondary 
objective is acceptability, defined as the tolerability or appropriateness of the SMART being studied 
from participant and clinician perspectives. 
 
4 
STUDY DESIGN 
 
4.1 
OVERALL DESIGN 
The study design is a pilot sequential multiple assignment randomized trial (SMART).  
4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
No one treatment intervention equally benefits all persons. Thus, personalized/adaptive interventions 
may be one way to optimize the benefits people receive from treatment interventions. The goal of a 
pilot SMART is to yield feasibility and acceptability outcomes. These outcomes justify the decision rules 
that guided whether, when and how the intervention components (i.e., BAT, CBT and the text-
messaging support) are adapted to a patient and informs the future full-scale SMART. It should also be 
noted that pilot SMARTs do not test the clinical impact of the interventions, which is already 
established. Pilot SMARTs optimize an intervention’s efficacy by identifying how to best to sequence 
them.  
4.3 
JUSTIFICATION FOR INTERVENTION 
The PI was a co-author of the first CBT intervention for Latinos living with HIV. In this study, there were 
improvements in self-reported depression and medication adherence, but a large portion of participants 
failed to complete all sessions, and weekly homework completion rates were also low. These limitations 
led to the current study, which focuses on starting individuals with a brief intervention first, and then 
supporting homework completion with text-message support.  
4.4 
END-OF-STUDY DEFINITION 
The end of the study is defined by the feasibility and acceptability outcome timelines. We expect the full 
study to be completed in 3 months.  

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5 
STUDY POPULATION 
 
5.1 
INCLUSION CRITERIA 
Inclusion criteria include: 
• 
HIV positive 
• 
18 years of age and older 
• 
Self identifies as Latino/Hispanic 
• 
Speak English or Spanish 
• 
Receives HIV care at Ward 86 
• 
Screened in with at least mild depression severity score to start (Patient Health Questionnaire-9 
score >3; PHQ) 
• 
Agrees to discuss depression, treatment preferences, and mobile health 
• 
Owns a mobile phone that can send/receive short-message service (SMS) text messages 
• 
Agrees to participate in the intervention that lasts three months 
• 
Agrees to have medical and clinical data abstracted 
• 
Able and willing to consent to participate 
5.2 
EXCLUSION CRITERIA 
Exclusion criteria include: 
• 
Not HIV positive 
• 
Under 18 years of age 
• 
Screened as having normal (PHQ-9 score of <2) or severe depression rating score (PHQ-9 score 
of 20 or higher). 
• 
Does not self-identify as Latino/Hispanic 
• 
Does not speak English or Spanish 
• 
Does not receive HIV care at Ward 86 
• 
Does not agree to discuss depression, treatment preferences, and mobile health 
• 
Does not owns a mobile phone that can send/receive short-message service (SMS) text 
messages 
• 
Does not agree to participate in the intervention that lasts three months 
• 
Does not agree to have medical and clinical data abstracted one year after baseline 
• 
Not able and willing to consent to participate 
5.3 
LIFESTYLE CONSIDERATIONS 
There are no lifestyle considerations that are expected to affect the ability of a person to enroll who also 
meets all inclusion criteria.  
 
5.4 
SCREEN FAILURES 
 

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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. Our study team is not going to 
reach out to 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. Screen failures are 
documented in the patient demographic data file at screening.  
5.5 
STRATEGIES FOR RECRUITMENT AND RETENTION 
 
All participants will be recruited from the Salud Clinic and Women’s Clinic (housed within the Ward 86 
HIV clinic at SFGH). Protection of the Latino clientele is a priority and informs the recruitment and 
screening process. Because the Salud Clinic specifically serves monolingual and bilingual Latino clients, 
Spanish-language services are easily accessible and nearly all providers and staff members are bilingual, 
including the PI of this K01 (Dr. Sauceda) and the Salud Clinic Director (Dr. Carina Marquez).  All 
recruitment processes will be in full collaboration with Dr. Marquez and the Ward 86 Medical Director 
(Dr. Monica Gandhi) and take place during Salud Clinic and Women’s Clinic hours.  
 
Dr. Sauceda is in regular contact with Dr. Marquez and always ensure the privacy and protection of 
patients and that all services go uninterrupted. Therefore, all communication with patients will occur 
before or after their appointment. 
 
Our proposed recruit plan is based on the experience of conducting two previous studies with the 
same population at the study site, and after many discussions with clinic staff and the clinic direct. 
 
Our process first begins with presentations about our study at the Salud Clinic monthly staff meetings. 
We will present on our scheduling plan and re-introduce the inclusion and exclusion criteria. This is to 
inform the study staff and providers that we are actively recruiting patients. The Salud Clinic staff and 
providers assign their patients to a panel, and thus, are familiar and discuss the circumstances of each 
patient and their care. The clinic director, Dr. Marquez, prefers that all staff are aware of the studies 
that are currently enrolling participants so that if that they can make informal assessments if their 
patients generally fits the inclusion criteria. At monthly clinic meetings, we announce that we are 
recruiting from the waiting room on a set schedule and they can are free to walk over or refer patients 
to our clinical coordinator who can introduce the study. Importantly, no participants are ever enrolled 
the same day they are greeted or referred to us in the waiting room. 
 
For direct referrals, we attend the Salud and Women’s Clinic services, which start each Wednesday at 
1:30PM. At 1PM, our clinical coordinator sets up in the waiting room and greets each staff member and 
provider, reminding them they are going to be in the waiting room. After each appointment, a provider 
or staff may choose to walk over any patients that are interested to our clinical coordinator in the 
waiting room who can assess their pre-eligibility (i.e., assess if interested in learning more about the 
study and exchanging contact information). Again, participants are never consented the day they are 
greeted. Further, there are also no incentives for providers or staff to recruit patients into our study, 
thus, patients should not feel coerced into seeking to participate. The Salud clinic staff prefer this 
method of outreach because it minimizes disruptions in clinic service provision as all contact happens 
after or in-between appointment activities. 
 
For self-referrals, we will post flyers in the waiting room and the exam rooms. Typically, when a patient 
shows interest in the study, they will call or text our study phone line. At this point, the eligible 

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participant will be directly contacted within the week (i.e., delayed recruitment) to re-introduce the 
study, review and confirm the eligibility criteria, and schedule a day to begin the informed consent 
process (described below). Because participants will be recruited at their HIV care site, we have 
purposefully selected this delayed recruitment strategy to reduce any coercion to participate at the time 
they are introduced to the study. All communication and materials will be available in Spanish and 
English. 
 
At the onset of the COVID-19 outbreak in March 2020, the research staff faced a significant challenge 
accessing the clinic premises. To address this challenge, research staff relied on doctor referrals and self-
referrals to recruit participants. We will also add review of medical records of patients at the study site 
who may be eligible to participate and reach out to them at study visits.  
Retention - The pilot SMART will require participants be followed over a three-month period. One of the 
benefits of the formative work that was completed for this project is that test ran the communication 
plans to increase the likelihood that the participant views the intervention and the study staff favorably, 
which will increase the likelihood of being retained over the follow-up period.   
At the baseline interview, all participants will be asked to complete a locator form, which includes the 
listing of a current home address, phone number, and text or email information (if available), and 
preferences for how they would like to be contacted. The locator form also requests the names of three 
persons who they agree can be contact in the event they cannot be reached. The locator form also 
includes information we are allowed to relay over the phone or email (e.g., a participant may not mind 
that we state this is a call from the “Salud or Women’s Clinic” whereas another participant might prefer 
we state “UCSF”).  
For subsequent appointments, each participant is sent a text-message and asked to confirm their next 
appointment. If they do not respond to the text-message within 24 hours, a second text-message is sent. 
Lastly, if the first two text-messages are not responded to, then a phone call is placed the following day. 
After three attempts, we make no additional outreach as to not burden the participant. Instead, we 
discuss communication efforts during the next face-to-face session.  For participants randomized to the 
text-message tool, we have preliminary scheduled one-way text-message reminders to also be sent 
prior to their appointment. All participants have the option to reschedule if needed. If a participant 
misses a study appointment, they will be contacted to reschedule within 48 hours. A total of three 
attempts will be made to reschedule a missed appointment and we will make note of the reason for the 
missed appointment if provided. At each appointment a participant does attend, we will review their 
residence and contact information to ensure it is up to date and resolve any issues regarding future 
work or travel schedules should they arise. Additionally, all patients will have a monthly check-in call to 
verify their current home address and information and answer any questions about their participation. 
Given this comprehensive approach, we anticipate at least an 90% retention rate and have oversampled 
to ensure we have enough participants. All participants will be reimbursed with $30 per session to cover 
all costs related to travel, and effort. We feel this reimbursement amount is not coercive and is 
necessary when adjusting for the high cost of living in the San Francisco Bay Area of California. 
 
6 
STUDY INTERVENTION(S) OR EXPERIMENTAL MANIPULATION(S) 
6.1 
STUDY INTERVENTION(S) OR EXPERIMENTAL MANIPULATION(S) ADMINISTRATION 

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6.1.1 STUDY INTERVENTION OR EXPERIMENTAL MANIPULATION DESCRIPTION 
 
The intervention activities are peer-reviewed and published manualized non-invasive programs that 
are based on psychoeducation principles, cognitive theory, and behavioral theory for 
depression. They are featured in Simoni, Wiebe, Sauceda (PI), et al., 2013, and from the manual 
titled CBT for Depression and Adherence in Individuals with Chronic Illness: Client and Therapist 
Workbook, Oxford University Press, 2007.  
The intervention is comprised of three psychological theories to improving depression: 
1. Psychoeducation is a standard educational approach to inform patients about the foundations of 
depression (i.e, what it is, what it looks like, how it affects people), and provides them with general 
knowledge around how to cope with and self-manage it. It is the foundation of behavioral therapy 
and cognitive-behavioral therapy.  
2. Behavioral therapy attempts to improve a person's depressed mood by helping them to plan to 
engage in social activities or activities associated with mastery. When one engages in social or 
physical activities, they are inherently learning to associate the activity with feelings of elevated 
mood, thus, reinforcing them to continue to engage in the activity. The goal of the brief intervention 
is to help patients systematically plan to be more active and social, and to track how these activities 
are associated with changes in mood. Cognitive-behavioral therapy takes it one step further, but all 
patients first start with the behavioral therapy component first. For this reason, we are starting with 
assignment to what is known as behavioral activation therapy (BAT) - a brief behavioral therapy.   
3. Cognitive therapy attempts to improve a person's depressed mood by teaching them that how a 
person feels and behaves is a function of how they think about themselves and the world around 
them. The key feature of depression in cognitive theory is negative thinking. To remedy negative 
thinking requires specific skills to learn how to monitor one's thoughts, and then to use strategies to 
think more adaptively to counteract the negative thinking. In cognitive therapy, by changing 
thoughts you change behavior and emotions. Cognitive theory requires more time and is a higher-
order approach, which is why all participants are not starting with it. The cognitive component in 
"cognitive-behavioral" therapy typically comes later on in the program after the behavioral 
component has been learned. For this reason, we are only randomizing participants to receive this 
more time-intense program if the behavioral therapy is not sufficient to change depression ratings.  
Participants in this study will be HIV+ Latino/as receiving care at the Ward 86 Salud or Women’s 
Clinic, a Latino-serving HIV clinic at ZSFG. The SMART trial has three components: 1) brief, Behavioral 
Activation Therapy (BAT) 2) cognitive-behavioral therapy (CBT), and a text-messaging tool (mHealth).  
• 
Delivery Method-Texts and interventions sessions will be completed either in person or 
via secure video chat platforms hosted by UCSF (i.e., HIPAA-compliant Zoom Video Conference 
platform). All text-messages are sent on secured encrypted UCSF Apple iPhones and with text-
message platforms, such as Signal or Mosio.  
• 
Session Length- Each session will ideally last 50-60 minutes.  

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• 
Intro Session-  The study counselor will meet with the participant individually to complete a 
brief assessment and to identify topics to address during the counseling sessions. The counselor 
and the participant will discuss pressing issues, ongoing concerns, and areas identified as 
priorities by the participant. 
1. BAT is a brief, 8-session manualized intervention that teaches participants about depression, how 
depression affects one's behavior (activities) and vice versa - this is the psychoeducation feature. 
Then, the focus of the remainder of sessions are on an action plan to identify new activities, schedule 
new activities, evaluate their development, and how to overcome barriers to engaging in new 
activities. For example, BAT would help a patient who states they feel isolated learn to understand 
how depression reduces energy, which is why they may not feel motivated to start their day. It 
would then help the patient create a plan to systematically schedule social activities (e.g., calling a 
friend to chat), how to make a plan for overcoming not feeling motivated, and then have them self-
monitor their activities and evaluate their own progress.  
Materials: Paper and pencil, calendars and monitoring forms, and mood rating scales. All 
documentation is stored in secured filing cabinets in badge-access only UCSF offices.  
• 
Session 1 (Building Trust and Introduction to BAT) Introduce psycho-education about 
depression, the BAT rationale, daily monitoring forms and importance of engagement in HIV 
care.  
• 
Session 2 & 3 (Review and Introduce "High" value activities; Barriers to BAT): Review Session 1 
and introduce “high value” activity domains (i.e., activities key to relationships, mind- body 
health, spirituality, and daily life), discuss barriers to activities and monitoring (e.g., rumination 
as a “covert” maladaptive behaviors), and social “contracts” to engage network members (e.g., 
family) with scheduled activities, and discuss engagement in HIV care.  
• 
Session 4 & 5 (Review Progress, Challenges, & Maintenance Strategies): Review Sessions 2-3, 
BAT rational and gains, maintenance strategies and adherence to BAT post-intervention (e.g., 
rank activities by difficulty or according to daily schedule), discuss communication with 
providers and the importance of engagement in HIV care. 
Materials: Paper and pencil, calendars and monitoring forms, and mood rating scales. All 
documentation is stored in secured filing cabinets in badge-access only UCSF offices.  
 
2. CBT combines BAT with cognitive therapy. CBT goes a step further in stating that negative thinking 
also affects behavior and emotions, and vice versa. It teaches patients how to "think about negative 
thinking," creates a plan to monitor their negative thoughts, and how to use specific strategies to 
think more adaptively. For example, a key feature of depression is use of cognitive distortions. In this 
example, patients may have the habit of using the distortion of "all-or-none" thinking, where if they 
feel they are not perfect then they have negative evaluations of themselves, rather than thinking 
more realistically that perfection is likely unattainable and that not reaching perfection does not 
equate to failure. In CBT, there are specific action plans to monitor how changes in thinking change 
are leading to changes in feelings and behaviors. CBT requires more time and more contact with an 
interventionist. Thus, we are starting with BAT and only sequencing CBT when patients are deemed 
to need it.  

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Session 1 (Building upon BAT & Introduce CBT Rationale): Review principles of BAT and 
psychoeducation about the cognitive component in CBT.  
• 
Session 2-4 (Cognitive Restructuring): Introduce how to monitor negative thoughts, record 
thought patterns, learn to identify new strategies for managing negative thoughts.  
• 
Session 4-6 (Problem-Solving): Review previous sessions and discuss barriers to activities and 
thought monitoring, and barriers to completing the activities discussed in the intervention.  
• 
Session 7-8 (Relaxation Training & Maintenance): Discuss the rationale of progressive muscle 
relaxation and how negative thoughts and feelings can start from physical arousal. Introduce 
monitoring forms and strategies to practice relaxation plans.   
Participants will be identified as eligible by clinic staff or our research team (ZSFG staff prefer a 
flexible approach), complete the informed consent process, and then randomized to either: 
(A1) BAT alone or (A2) BAT & mHealth text-messaging.  
Participants randomized to (A1) BAT alone will complete a total of five, 1-hour sessions of behavioral 
activation therapy with a trained bi-lingual interventionist every two weeks. This intervention is 
publically available and manualized already. (Our prior work has shown that the intervention can be 
delivered by a wide-range of clinic and research personnel, not just mental health professionals; 
Simoni et al., 2013).  
Conversely, participants randomized to the (A2) BAT & text-message support will receive an identical 
BAT program with the addition of one and two-way personalized text messages that will be delivered 
twice a week to facilitate engagement with the intervention activities.  
Text-Messages - One-way messages will be sent as appointment and BAT adherence reminders (e.g., 
"Please remember to fill out your social activity planner?", while two-way text messages will be sent 
as "check-ins" with participants in the form of a mobile interventionist (e.g., "How is your activity 
planning going? If you need assistance, I can remind you of what activities you said you could do"). 
Participants will be asked to respond to these two way-text messages at their earliest convenience.  
After three sessions of the five planned sessions have been completed, an assessment of the 
participants depression will be made using a cutoff score on the Patient Health Questionnaire-9 
(PHQ-9), a self-reported rating scale for depression (this is called a “primary tailoring variable”). This 
primary tailoring variable will dictate the second sequence. Based on their PHQ-9 score, participants 
are coded as a “responder” or “non-responder;” a code that dictates whether their initial 
randomization assignment is 1) maintained, 2) augmented, or 3) switched to a second component 
(this is the second randomization and "adaptive" component). 
Participants who were randomized to BAT alone and were coded as "non-responders" will be 
randomized to: 1. additionally receive text-message support, or 2. switched to receive CBT & text-
message support. If switched to CBT & text-message support, participants will complete a total of 
eight intervention sessions that can be re-arranged to fit patient needs. CBT sessions will be 
scheduled once a week for 60 minutes (as described above, CBT integrates cognitive theory 
principles with behavioral theory principles, and thus, is more intensive). If participants randomized 
to BAT alone during their first stage of treatment and responded, they continue with maintenance of 
their BAT sessions.  

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Participants who were randomized to BAT & text-message support and were coded as "non-
responders" will be randomized to: 3. augment BAT & text-message support treatment in the form 
of an extra booster session, or 4. similarly switched to receive CBT and text-message support. If 
participants who were randomized to BAT & text-message were coded as "responders", they will 
continue with maintenance of their BAT & text-message support sessions. 
Participants will be asked to attend intervention sessions, respond to text messages, and participate 
in post-intervention exit interviews. Research team staff will be responsible for recruiting eligible 
participants to the study, coordinating intervention sessions (including reimbursements), and 
coordinating the text-message support component. Bilingual and English-speaking licensed clinical 
psychologists will supervise the conduct of the interventions and discuss updates during weekly and bi-
weekly meetings. 
Text-Messaging Protocol - One-way messages will be sent as appointment and BAT adherence 
reminders.  Two-way messages will be sent during the protected time for “check-ins” with participants 
in the form of a “mobile therapist.” 
 
Security - All phones are reviewed and encrypted by the UCSF IT service desk and Mission Hall on the 
Mission Bay Campus and meet the UCSF Minimum Security Standards for Electronic Information 
Resources. The protocol for text-messages will be explained and demonstrations will be conducted in 
the first session to ensure participants comprehend the rationale. All study phone hardware, 
authentication of hardware (log-in credentials), and transmission networks (cellular-data networks, Wi-
Fi) of patient health information will be protected through encryption software. We will show 
participants how to modify their phone settings and install free applications (e.g., Signal, TigerText) to 
encrypt the text-messages or have them delivered in discreet form (e.g., content not to appear on home 
screen). 
 
Data Collection - All study phones will store text-message communication and will be downloaded from 
the smart phone into a Microsoft Word document. From this document, all responses are then pasted 
into a secure and password protected Microsoft Excel file. The excel file lists all participant unique ID 
numbers, message history, and schedule preferences. The file is stored on the UCSF Box cloud storage.  
 
One-way Messages - One-way messages require no confirmation of receipt and are for the purposes of 
reminders. For example, for appointment reminders (in English), we will send the following reminder 
tailored to the participant - “Hi Lorena, this is Dr. Sauceda reminding you of your appointment on 
Monday, June 1st at 11:30AM at the Salud or Women’s Clinic. To cancel or reschedule, please call or text 
the study phone line @415-476-6045.” For a reminder to adhere to the intervention activities, we will 
send the following - “Hi Lorena, this is Dr. Sauceda reminding you to list your activities and rate 
how you feel afterwards” 
Timing - 1) Reminders will be sent 3 and 1 day prior to the appointment date. 2) BAT activity reminders 
will be sent once a week during a set block of working hours, which will be determined after initial 
screening visit.  
Two-Way Messages - All two-way messages will be initiated once a week during blocked hours of 
protected time (determined after screening). This will allow for messages to be sent and responded to.  
If two-way messages are NOT responded to during the blocked hour(s), a follow-up message will be sent 
to end the conversation: Example: "Hi Miguel, please respond at your earliest convenience. I will be 

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available to respond again on Thursday from 9AM and 11AM". We will minimize the risk for breaches of 
confidentially by never using potentially stigmatizing words in any text-messages, such as “HIV” or 
“depression” and acting immediately on any emergencies. All conversations will end with “If you have 
an emergency, please call 911.” 
During the start of all intervention sessions that are face-to-face (in person or video conference), we 
always discuss the acceptability of the text-message protocol. This is to discuss challenges in responding 
and successes, and is part of the overall evaluation of acceptability.  
Content of Two-Way Messages - During designated time, the interventionist will initiate text-message 
conversation with participants. This is because personalizing BAT and CBT support and advice requires 
real-time problem-solving opportunities so participants can complete the program. For this reason, 
standardized messaging is not recommended as the purposes of the messaging is to continue the 
discussion around intervention activities that were discussed in session. Message content is derived 
from activities discussed in session and on file in the Microsoft Excel sheet.  
 
Standard mood ratings sent once per week: - 1) “Hi Miguel, this is Dr. Sauceda. How is your mood today? 
Reply with a number from 1 (poor) to 5 (Excellent) when convenient.” “Thank you for the response. 
Remember, doing a social activity like talking to a friend can help you feel better.”  
 
Problem-Solving Messages: “Hi Miguel, do you need any help remembering the activities you planned? 
Reply Y for Yes, N for No.” “You replied Y. You mentioned wanting to call to chat with your brother.” “Can 
you do that today?” “How is your homework going? Can I help you in any way with the homework?” 
“Remember, rate how you are feeling. Let me know if you need help with the ratings.” “If you have an 
emergency, please call 911.” 
 
Data Collection - All study phones will store text-message communication and will be downloaded from 
the smart phone into a Microsoft Word document. From this document, all responses are then pasted 
into a secure and password protected Microsoft Excel file. The excel file lists all participant unique ID 
numbers, message history, and schedule preferences. The file is stored on the UCSF Box cloud storage.  
 
6.1.2 ADMINISTRATION AND/OR DOSING 
We are taking a brief behavioral intervention for depression, a text-message support intervention, and a 
cognitive-behavioral intervention, and sequencing how each is rolled out based on how participants 
respond. In a traditional approach, we would be comparing each component individually as standalone 
interventions compared to a control condition, and evaluating their effects. In a SMART, you start with 
the lowest burden/low dose intervention, and only increase as needed. This study is solely focused on 
feasibility and acceptability.  
There are situations where multiple treatments are known to be effective, but what is unknown is 
whether every person benefits the same from all of them. In the depression field, we do not know how 
best to package what are considered efficacious interventions - 1) behavioral activation therapy, 2) 
cognitive-behavioral therapy, and 3) text-message support to treat depression and promote adherence 
to medication and clinic appointments. We will use a SMART design to evaluate if it is feasible and 
acceptable to sequence these behavioral interventions for depression. 

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STARTING POINT: Patients are recruited and then randomized to one of two active arms. The first 
randomization is to one of two interventions (A1 and A2). Both A1 and A2 are an already-established 
efficacious brief behavioral intervention, the only difference is that one will include a text-message 
support intervention (A1 versus A2 + Text-message support), which is the experimental factor we are 
testing, i.e., whether text-message support is the key factor between A1 and A2. At baseline, where 
participants are randomized, we will measure their depression using a standard rating scale. 
FIRST OPTION: All participants will complete 4 of 8 sessions of A1 or A2, at which point we will make 
another depression assessment. This assessment will indicate if participants responded well to this first 
"assignment" (i.e., improved depression ratings) or did not respond well (i.e, no change in depression 
ratings or worse depression ratings). If the respond well, nothing changes and they proceed as normal 
through the 5-session program. If they do not respond, i.e., show no improvement or show worse 
ratings, we "adapt" the intervention because we have evidence that the intervention is not currently 
relieving depressive symptoms. 
SECOND OPTION: If participants do not respond to their first assignment (e.g., no change in depression 
ratings or worse ratings), they are eligible to be randomized again to a second assignment (B1, B2, B3, or 
B4). This is why the term "sequential multiple assignment" is used because the goal is to identify how to 
start with A1 and "sequence" other intervention components through an "assignment" to "multiple" 
components (B1-B4). 
Participants who did not respond to A1 or A2 (only difference is A2 has text-message support) have 
four options: 
1. If participants in the A1 arm DO NOT improve, they can be re-randomized to either B1 to receive the 
text-message support component; or 
2. B2 to switch to more intensive intervention, which is known as cognitive-behavioral therapy and text-
message support. 
3. If participants in the A2 arm DO NOT improve, they can be re-randomized to either B3 to receive one 
booster session of same program; or 
4. B4 and switch to more intensive intervention of cognitive-behavioral therapy & text-message support. 
The components are: 1) a brief Behavioral Activation Therapy (BAT), 2) cognitive-behavioral therapy 
(CBT), and a text-messaging tool (mHealth). 
Patients (N=45) will first be randomly assigned to the first intervention component of either: A1) BAT by 
itself or A2) BAT & text-message support. 
DICTATING CHANGE: At the first follow-up point, which is half-way through the first assignment, we will 
make an assessment of how they responded to the first intervention. Our goal is to measure changes in 
their depression ratings using a cut-off score on a clinical depression assessment tool. If their depression 
ratings have improved, they will maintain their initial treatment (Stay with A1 or A2), which is either: 
1) BAT by itself or 2) BAT & text-message support. 

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If their depression ratings have not improved or get worse, we will re-randomize them to one of 
four additional components they have not received: B1-B4. 
To summarize: BAT and CBT and mHealth are efficacious approaches to helping patients self-manage 
their depression. However, rather than given all patients a complex package (CBT with mHealth), we are 
seeking to evaluate the feasibility and acceptability of starting with a brief intervention, and then 
sequentially to add more intensive components only when needed. 
6.2 
FIDELITY 
6.2.1 INTERVENTIONIST TRAINING AND TRACKING 
 
We have two licensed psychologists and a trained cognitive-behavioral therapist on the research team 
who are supervising all activities. We are also using a published fidelity monitoring coding sheet to score 
adherence to the intervention. Interventionist will write Data-Assessment-Plan notes (DAP) for each 
session, which is discussed in weekly team meetings and additional trainings are discussed if fidelity to 
the intervention is sub-optimal.  
6.3 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
 
All randomization is done blinded. Prior to the start of the intervention, we will use the National Cancer 
Institutes Clinical Trial Randomization Tool stratified by English and Spanish. These randomizations will be 
relayed to the study coordinator who will inform the participant of their intervention starting point.  
6.4 
STUDY INTERVENTION/EXPERIMENTAL MANIPULATION ADHERENCE 
 
The acceptability outcomes are what is being evaluated to determine adherence to the intervention. 
Acceptability: 1) > 90% adherence to the BAT and CBT session schedule; 2) responsiveness to text 
messages as: a) >80% of all two-way messages replied to during the set of blocked hours; b) >90% of 
participants reporting direct benefit from one-way text-messages; 3) positive responses coded from 
post-intervention exit interview transcripts; 4) limited number of barriers to participation reported in 
exit interviews; and 5) responses to a brief survey (to be developed) assessing clinic staff acceptability of 
the intervention. Given the focus on feasibility and acceptability, the focus remains on studying whether 
these adherence markers can be achieved.  
 
6.5 
CONCOMITANT THERAPY 
All participants will be able to receive pharmacotherapy, other psychotherapy, case management and 
social work services during the study, as this does not affect their eligibility and reflects the real-world 
circumstances of patients who may benefit from our study in the future.  The implementation of the 
pilot SMART at ZSFG will integrate an adaptive intervention into an HIV care site, and use Spanish and 
English text-messages to promote adherence to the intervention. Importantly, this study will not 
interfere in any way with the standard of HIV primary care regularly received by patients at the ZSFG 
Ward 86 Clinic. Participants in a SMART are randomized to an evidence-based treatment intervention 
for depression, with the only differentiating factor being the use of text-messaging to support 

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adherence to the intervention's protocol. It is only when a patient does not respond to their assigned 
treatment do we investigate the next course of action in the form of a second-stage treatment, which is 
adapted to their particular case. Furthermore, no other services for depression, including 
pharmacotherapy, will be denied. For each patient, we are writing a formal letter to their HIV care 
provider to let them know that their patient is in this study because they reported mild to moderate 
depression severity and to continue to prescribe any treatment they deem appropriate. All together, we 
believe that our study design, and feature of not withholding any treatment, does not place any 
participant at greater risk than what they would encounter with any other services available for their 
depression.  
6.5.1 RESCUE THERAPY 
Not applicable 
 
7 
STUDY INTERVENTION/EXPERIMENTAL MANIPULATION DISCONTINUATION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
 
7.1 
DISCONTINUATION OF STUDY INTERVENTION/EXPERIMENTAL MANIPULATION 
All participants who wish to discontinue the study will be asked for the reasons for discontinuing. This is 
part of the evaluation. If a clinically significant finding is identified (including, but not limited to changes 
from baseline) after enrollment, the investigator or qualified designee will determine if any change in 
participant management is needed. This is part of the Data and Safety Plan that was submitted to the NIH 
and approved (This file is available upon request). Any new clinically relevant finding will be reported as 
an adverse event (AE). 
 
The data to be collected at the time of study intervention discontinuation will include the following: 
• 
The reason(s) for discontinuing the participant from the intervention, and methods for 
determining the need to discontinue. 
• 
If the participant is due to complete the first assessments within 2 weeks of being discontinued 
from the study intervention (asking to stop with the intervention activities but willing to come in for the 
assessment), those assessments will be administered at the time of discontinuation; if the next scheduled 
assessments are more than 2 weeks from the discontinuation date, the discontinued participant will wait 
for the next scheduled assessment (unless they wish to completely discontinue with all study activities). 
Thereafter, the participant will be included in all future scheduled assessments, even though not 
participating in the intervention. 
 
7.2 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
Participants are free to withdraw from participation in the study at any time upon request. 
An investigator may discontinue a participant from the study for the following reasons: 
 
• 
Significant study intervention non-compliance, unless varying compliance is an aspect of the study 
objectives  

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• 
Lost-to-follow up; unable to contact subject. 
• 
Any event or medical condition or situation occurs such that continued collection of follow-up 
study data would not be in the best interest of the participant or might require an additional 
treatment that would confound the interpretation of the study. 
• 
The participant meets an exclusion criterion (either newly developed or not previously 
recognized) that precludes further study participation. 
 
The reason for participant discontinuation or withdrawal from the study will be recorded. Subjects who 
sign the informed consent form and are randomized but do not receive the study intervention may be 
replaced. Subjects who sign the informed consent form, and are randomized and receive the study 
intervention, and subsequently withdraw, or are discontinued from the study.  
7.3 
LOST TO FOLLOW-UP 
 
A participant will be considered lost to follow-up if he or she fails to return for 3 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 site will attempt to contact the participant, reschedule the missed visit within 1 week, 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 investigator or designee will make every 
effort to regain contact with the participant (where possible, 3 text-messages and 2 telephone 
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 medical 
record or study file.  
• 
Should the participant continue to be unreachable, he or she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up. 
8 
STUDY ASSESSMENTS AND PROCEDURES 
8.1 
ENDPOINT AND OTHER NON-SAFETY ASSESSMENTS 
 
The focus of this study is on the feasibility of carrying out the assessment of a primary tailoring variable 
(PTV). A PTV is the cutoff score to decide whether a participant showed a clinically meaningful response 
to BAT or BAT & mHealth at a 1-month follow-up point. The preliminary cutoff score for the pilot SMART 
is defined as a decrease in a PHQ-9 score from the “moderate” to “mild” (or below) depression 
symptom severity category after 4 weeks (or after 4 of 8 sessions of BAT). The rationale for the follow-
up period is to identify early who is a “responder” or “non-responder” to a 1st-stage treatment. The 
“responder/non-responder” decision is used to decide whether, when, and how to adapt a 1st-stage 
treatment. The follow-up point is the mid-way point of the brief intervention, that is, after 3 of 5 BAT 
sessions are complete. This cutoff score is supported by a randomized placebo-controlled trial that 
showed BAT to be associated with reduced depression more per week than a cognitive therapy on a 
self-rating scale. The same depression rating is done at the final follow-up period at the end of the final 
intervention session.  

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8.2 
SAFETY ASSESSMENTS 
Not applicable as this intervention does not involve any medical or pharmacological components that 
would warrant a physical safety assessment.  
 
8.3 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
 
8.3.1 DEFINITION OF ADVERSE EVENTS 
The definition of adverse events followed is from the U.S. Department of Health and Human Services 
Office for Human Research Protections. An adverse event is defined as any undesirable experience 
associated with the engagement with any aspect of the study activities. While the risks of any adverse 
events are deemed to be extremely rare, we will follow the guidance in the following sections.   
 
8.3.2 DEFINITION OF SERIOUS ADVERSE EVENTS 
 
An adverse event is serious when the patient outcome is death, life-threatening, hospitalization, 
disability, or other serious and important medical events.  
 
8.3.3 CLASSIFICATION OF AN ADVERSE EVENT 
8.3.3.1 SEVERITY OF EVENT 
We will follow the Federal Guidance on this issue.  
For adverse events (AEs) not included in the protocol defined grading system, the following guidelines 
will be used to describe severity.  
 
• 
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. Moderate events may 
cause some interference with functioning. 
• 
Severe – Events interrupt a participant’s usual daily activity and may require systemic 
intervention. Severe events are usually potentially life-threatening or incapacitating.  
8.3.3.2 RELATIONSHIP TO STUDY INTERVENTION/EXPERIMENTAL MANIPULATION 
 
All adverse events (AEs) will have their relationship to study procedures, including the intervention, 
assessed by an appropriately-trained interventionist and discussion in team meetings. The degree of 
certainty about causality will be graded using the categories below.  
 

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• 
Related – The AE is known to occur with the study procedures, there is a reasonable possibility 
that the study procedures caused the AE, or there is a temporal relationship between the study 
procedures and the event. Reasonable possibility means that there is evidence to suggest a causal 
relationship between the study procedures and the AE. 
• 
Not Related – There is not a reasonable possibility that the study procedures caused the event, 
there is no temporal relationship between the study procedures and event onset, or an alternate 
etiology has been established. 
 
Our diverse team of psychologist and infectious disease and internal medicine physicians is sufficient to 
determine the relationship of the AE to the intervention activities.  
 
8.3.3.3 EXPECTEDNESS  
 
The PI along with his senior mentor have the appropriate expertise in depression and HIV care research 
to be responsible for determining whether an AE is expected or unexpected. An AE will be considered 
unexpected if the nature, severity, or frequency of the event is not consistent with the risk information 
previously described for the study procedures. In this behavioral intervention, we expect no serious AEs.  
 
8.3.4 TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
 
The occurrence of an AE or serious AE (SAE) may come to the attention of study personnel during study 
visits and interviews of a study participant presenting for medical care, or upon review during team 
meetings. 
 
All AEs, not otherwise precluded per the protocol, will be captured following the Reporting Requirements 
Summary Sheet from the UCSF IRB (Attached in the IRB application). Information to be collected includes 
event description, time of onset, clinician’s assessment of severity, relationship to study procedures 
(assessed only by those with the training and authority to make a diagnosis), and time of 
resolution/stabilization of the event. All AEs occurring while on study will be documented appropriately 
regardless of relationship. All AEs will be followed to adequate resolution. 
 
Any medical or psychiatric condition that is present at the time that the participant is screened will be 
considered as baseline and not reported as an AE. However, if the study participant’s condition 
deteriorates at any time during the study, it will be recorded as an AE.  
 
Changes in the severity of an AE will be documented to allow an assessment of the duration of the event 
at each level of severity to be performed. Documentation of onset and duration of each episode will be 
maintained for AEs characterized as intermittent. 
 
The interventionist will record events with start dates occurring any time after informed consent is 
obtained.  At each study visit, the interventionist will inquire about the occurrence of AE/SAEs since the 
last visit.  Events will be followed for outcome information until resolution or stabilization. This is 
determined during weekly team meetings for AEs, and immediate scheduling of meetings for SAEs.  

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ALL SAFETY PLANS HAVE BEEN APPROVED BY THE NIMH. 
8.3.5 ADVERSE EVENT REPORTING  
The Reporting Requirements outlined by the UCSF Office of Ethics and Compliance will guide all 
reporting. The principal and co-investigators on this project will report any adverse events to the UCSF 
IRB within 5 working days should they be deemed related to the study AND are considered serious 
(defined above) or unexpected (i.e., an adverse event that exceeds the nature, severity or frequency 
described in the current IRB Application including the protocol and consent form) 
8.3.6 SERIOUS ADVERSE EVENT REPORTING  
The principal and co-investigators on this project will report to the UCSF IRB of any adverse events 
within 5 working days should they be deemed related to the study AND are considered serious (defined 
above) or unexpected (i.e., an adverse event that exceeds the nature, severity or frequency described in 
the current IRB Application including the protocol and consent form) 
8.3.7 REPORTING EVENTS TO PARTICIPANTS  
Any adverse event reported to the UCSF IRB will only be reported to the participant if it is deemed 
related to the study AND severe, as this is outside the scope of the risks that were discussed in the 
consent form, but also that the likelihood of a serious adverse event is extremely rare. Our Data and 
Safety Monitoring Plan approved by the NIMH also includes the ability to schedule an immediate 
meeting of the PI, the senior faculty mentor, and internal medical monitor.  
8.3.8 EVENTS OF SPECIAL INTEREST  
N/A 
8.3.9 REPORTING OF PREGNANCY  
N/A 
 
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 UCSF IRB approved research protocol 

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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  
Dr. Sauceda will report unanticipated problems (UPs) to the UCSF IRB. 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:   
 
• 
UPs that are serious adverse events (SAEs) will be reported to the IRB immediately and no later 
than 48 hours after the discovery was made that a UP occurred.   
• 
Any other UP will be reported to the IRB and to the DCC/study sponsor/funding agency within 5 
working days of the Dr. Sauceda becoming aware of the problem . 
• 
All UPs should be reported to appropriate institutional officials (UCSF IRB), the NIMH Program 
Officer, within five days of Dr. Sauceda becoming aware of the problem.  
8.4.3 REPORTING UNANTICIPATED PROBLEMS TO PARTICIPANTS  
Unless the risk/benefit ratio changes or there are risks to breaches of confidentiality for the participant, 
no UP will be reported to them. If an UP is deemed to directly affect a participant, they will be notified 
that a meeting is needed to discuss how the issue will be resolved after discussion with the PI, primary 
mentor, and the UCSF IRB.  
9 
STATISTICAL CONSIDERATIONS  
 
9.1 
STATISTICAL HYPOTHESES 
There are no statistical hypotheses as this is an evaluation of feasibility and acceptability.  
9.2 
SAMPLE SIZE DETERMINATION 
 

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Daniel Almirall is a leading expert in SMART designs and developed a sample size estimation tool 
specifically for pilot SMARTs. First, we propose six treatment sequences and a minimum of four 
participants to receive them (called “outcome groups” in Figure 1). Second, one must estimate from the 
literature the percentage of participants who will not show a clinically meaningful response (i.e., “non-
response rate”) to a treatment they will be initially randomized to. We used data from a non-inferiority 
trial of cognitive therapy versus a behavioral activation therapy in general population sample. This trial 
used clinician-administered diagnostic tools, self-report ratings, fidelity monitoring, and had all 
interventions delivered by psychologists and social workers. Under these rigorous conditions, 50-60% of 
participants with mild depression at baseline (range based on self-report and clinician ratings) did not 
achieve a 50% reduction in depressive symptoms at a 4-month follow-up. Similar results were found for 
participants with a higher severity of depression at baseline. This estimation tool yielded a total sample 
size of 45 participants if we observe a non-response rate of 50-60%, a fixed probability of 80% 
(suggested by Almirall), a minimum of four participants per “outcome group,” and a 10% attrition rate. 
 
9.3 
POPULATIONS FOR ANALYSES 
The same will consist of Latinos living with HIV, no sub-analyses are planned regarding the evaluation of 
feasibility and acceptability.  
9.4 
STATISTICAL ANALYSES 
 
9.4.1 ANALYSIS OF THE PRIMARY ENDPOINT(S) 
Basic demographic tables will be generated for all depression ratings from baseline through follow-up 
periods, as well as general measures of central tendency for each variable (e.g., Mean, SD), measured 
categorical and continuously, and highlighted by measures of variability. For Feasibility, the following 
outcomes will be evaluated using descriptive statistics to identify: 1) the number of participants 
screened, eligible and enrolled; 2) at least 80% of all BAT and CBT sessions completed; and 3) 80% 
retention in all “outcome groups” (see attached figure in the IRB application).  
 
9.4.2 ANALYSIS OF THE SECONDARY ENDPOINT(S) 
 
The Microsoft Excel file will have all participant appointment attendance records and responses to 
schedule text-messages, which were downloaded to determine acceptability as: 1) > 90% adherence to 
the BAT and CBT session schedule; 2) responsiveness to text-messages as: a) >80% of all two-way 
messages replied to during the set of blocked hours; b) >90% of participants reporting direct benefit 
from one-way text messages; 3) positive responses coded from post-intervention exit interview 
transcripts (to be determined at future date); 4) limited number of barriers to participation reported (to 
be determined at a future date).  
 
9.4.3 SAFETY ANALYSES 
This section is not applicable for behavioral clinical trials.  

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9.4.4 BASELINE DESCRIPTIVE STATISTICS 
Basic demographic tables will be generated for all characteristics at baseline, and then from baseline 
through follow-up periods. We will have general measures of central tendency for each variable (e.g., 
Mean, SD) measured categorical and continuously, and highlighted by measures of variability.  
 
9.4.5 PLANNED INTERIM ANALYSES  
 
There are no statistical interim analyses planned that would determine the need to stop the study given 
the size of this pilot study.  
 
9.4.6 SUB-GROUP ANALYSES 
There are not sub-group analyses planned as the focus of this pilot study is on Latinos living with HIV as a 
whole and only 10% of the clinic population is registered as female sex.  
9.4.7 TABULATION OF INDIVIDUAL PARTICIPANT DATA 
 
For descriptive purposes, depression ratings will be tabulated over the course of the intervention for each 
participant and in aggregate.  
9.4.8 EXPLORATORY ANALYSES 
There are currently not exploratory analyses that can be listed here given the pilot study was not 
powered to identify statistical significant relationship among the variables. Any exploratory analyses will 
be determined by the PI and research team.  
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
 
10.1 REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
 
10.1.1 INFORMED CONSENT PROCESS 
A copy of the informed consent processes submitted to the IRB will be available upon request.  
10.1.1.1 CONSENT/ASSENT 
AND 
OTHER 
INFORMATIONAL 
DOCUMENTS 
PROVIDED 
TO 
PARTICIPANTS 
Participants will always be given copies of the Human Subject Bill of Rights, the HIPAA authorization form, 
and the consent form, unless they verbally decline to accept them.  
10.1.1.2 CONSENT PROCEDURES AND DOCUMENTATION 

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All consenting procedures and discussions happen in-person and in a private room or office at the study 
site.  
The informed consent process is informed by the UCSF IRB Consent Process and Documentation 
guidelines and Title 45-Code of Federal Regulations regarding human subject involvement in research. 
The obtainment of consent will be guided by a written document and an interactive, ongoing 
conversation between the PI, a research assistant, or Salud and Women’s Clinic staff member and a 
participant. All documentation and conversations are readily available in English or Spanish. 
The required eight elements of consent will be sectioned paragraph-by-paragraph in the informed 
consent document, which will be discussed in detail with a participant. At the start of the consent 
process, we will let the participant know that we prefer to have the consent form read out loud while 
they follow along. They will have the option to read the document by themselves, but we will strongly 
discourage this so as to ensure all elements of consent are fully acknowledged and comprehended. 
As the consent process starts, each participant must acknowledge that they understand and agree to 
each section before continuing on to the next section (i.e., element of consent). At each section, we will 
ask a participant if they understand that they have the right to refuse to participate and that there are 
no consequences of doing so. We will inquire about their understanding of the study 
procedures (including the process of notifying their provider of their participation in the study), which 
include the possibility of multiple treatment reassignments, participation over a three-month follow-up 
period, and all risks that may result from participating. 
 
10.1.2 STUDY DISCONTINUATION AND CLOSURE 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable 
cause. Written notification, documenting the reason for study suspension or termination, will be provided 
by the suspending or terminating party to study participants, the study site, and the NIMH. If the study is 
prematurely terminated or suspended, Dr. Sauceda will promptly inform study participants, IRB, and the 
NIMH, 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;    
• 
Insufficient compliance of study staff to the protocol  (ie, 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 NIMH and UCSF IRB. 
 
10.1.3 CONFIDENTIALITY AND PRIVACY  
 

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Given the sensitivity of the study subject matter and possible disclosure of a psychiatric or HIV diagnosis, 
there is the potential to face consequences. This is primarily in having their participation disclosed - a 
study on depression for people living with HIV. There are no direct consequences associated with not 
participating, participating and dropping out of the study, or completing the study. There is the possible 
consequence of having others (e.g., family, friends, co-workers) find out about their participation. To 
guard against any potential consequences, we will collect our Certificate of Confidentially (CoC) from the 
NIH. The CoC is available to all NIH-funded research, but can only be collected after IRB approval has 
been received. 
The CoC information will also be specified on the consent form and described to each participant during 
the informed consent process. Only Dr. Sauceda, the faculty mentor, and research staff will have access 
to a participant’s contact information and raw data. All data that will be shared with the mentoring team 
will be de-identified. For participants in the trial, we will create a case file that is denoted by patient ID 
number that is generated at the time of the enrollment. All intervention paper files will be stored in an 
office space and locked inside a file drawer. All consent forms and tracking forms that have identifying 
information will be separated from all case files. All case files will be uploaded into a password 
protected file and stored on a UCSF secure server. All patient text-message conversations will be stored 
on encrypted study mobile phones before being downloaded into a password-protected and encrypted 
text or EML file and stored on UCSF’s secure severs. 
10.1.4 FUTURE USE OF STORED SPECIMENS AND DATA  
All data will be used for presentation and scientific conferences and peer-review publications. Aggregated 
data will be shared at monthly Salud Clinic meetings. No personal or identifying or singular data are ever 
presented.  
 
10.1.5 KEY ROLES AND STUDY GOVERNANCE 
Dr. Sauceda serves as the PI and Dr. Fernandez serves as the medical monitor (internal medicine 
physician). Each week, Dr. Sauceda also meets with Dr. Mallory Johnson, a licensed clinical psychologist 
and his senior mentor.  
Principal Investigator 
Medical Monitor or 
Independent Safety Monitor 
John A. Sauceda, PhD 
Alicia Fernandez, MD 
U.C. San Francisco  
U.C. San Francisco 
550 16th Street, Mission Hall, San 
Francisco, CA 94618 
1001 Potrero Ave., Room 1307, 
San Francisco, CA 94110 
512-787-4353 
415 206-5394 
 
John.sauceda@ucsf.edu 
Alicia.fernandez@ucsf.edu 
 
10.1.6 SAFETY OVERSIGHT 
 
All safety risks will be regularly monitored during the study. Dr. Sauceda and his senior faculty mentor (Dr. 
Mallory Johnson) will be in-person weekly during the study. Dr. Sauceda will also meet with Dr. Fernandez 

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(Internal Medical Monitor) bi-weekly during the same time period. Patient safety and data monitoring will 
be included as a meeting agenda item during individual meetings. The entire monitoring group will 
convene quarterly DSM meeting at the start of the study and up until the pilot study is completed. 
 
10.1.7 CLINICAL MONITORING 
Clinical monitoring refers to independent monitoring plans. An agreement will be made with the PI and 
Drs. Marquez and Gandhi (Clinic Director and Medical Director) to immediately report any detection 
of significant distress and breaches of confidentiality given that the study will take place at the Salud 
Clinic at ZSFGH. Should any breach of confidentially or adverse events occur, the PI will convene an ad 
hoc meeting with Drs. Johnson (faculty mentor) and Fernandez (internal medical monitor) to review 
options to stop the study, recommend removing the participant from the study, or change any 
intervention procedures to eliminate any potential risks that are occur at unacceptable levels.   
 
10.1.8 QUALITY ASSURANCE AND QUALITY CONTROL 
The nature and sources of data/materials collected for this study are fully described in the Protection of 
Human Subjects Section that is available upon request and that was approved by the NIMH. Quality 
assurance measures following the E6 Good Clinical Practice Guidance 1.46 will guide all research 
activities for this study. This will include weekly meetings with Dr. Sauceda senior faculty mentor to 
review each individual case and formally documented written reports of participant activity. Further, 
together, they will oversee the annual all-mentoring team meeting to outline progress and benchmarks 
of the research activities and to discuss and address any barriers and challenges to the progress of the 
research activities. The frequency of meetings between the PI and faculty mentor, along with co-
mentors and scientific advisors, will ensure that the study progresses in accordance with the timeline 
outlined. Any significant delays for any study activities will be reported to the NIMH program officer.  
10.1.9 DATA HANDLING AND RECORD KEEPING  
 
10.1.9.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
 
Data collection will be the responsibility of the research staff and Dr. Sauceda who directly supervises 
them. The investigator will be responsible for ensuring the accuracy, completeness, legibility, and 
timeliness of the data reported. 
 
All source documents will be completed in a neat, legible manner to ensure accurate interpretation of 
data.   
 
Hardcopies of the study visit worksheets will be provided for use as source document worksheets for 
recording data for each participant consented/enrolled in the study.  
 

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The data systems used in this study our directly sourced from the UCSF IT Systems and includes password 
protection and internal quality checks, such as automatic range checks, to identify data that appear 
inconsistent, incomplete, or inaccurate. Clinical data will be entered directly from the source documents. 
 
10.1.9.2 STUDY RECORDS RETENTION  
 
Study documents will be retained for a minimum of three years after the official closeout of the study per 
NIH guidance.   
 
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). The noncompliance may be 
either on the part of the participant, the investigator, or the study site 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 Dr. Sauceda to use continuous vigilance to identify and report deviations 
within 3 working days of identification of the protocol deviation, or within 5 working days of the scheduled 
protocol-required activity. All deviations will be addressed in study source documents, reported to the 
NIMH and Program Officer Teri Senn, PhD if required. Protocol deviations will be sent to the UCSF IRB per 
their policies. Dr. Sauceda will be responsible for knowing and adhering to the reviewing IRB 
requirements.  
10.1.11 
PUBLICATION AND DATA SHARING POLICY  
 
All study results and data will be compliant with the NIH Data Sharing Policy.  
10.1.12 
CONFLICT OF INTEREST POLICY 
 
No persons involved with this study have any conflicts of interest.  
10.2 ADDITIONAL CONSIDERATIONS 
 
Not applicable 

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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 
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 
01/20/19 
Original protocol 
 
1.1 
10/24/19 
Response to initial IRB review 
 
1.2 
10/25/19 
Additional changes in response to 
IRB review.  
 
1.3 
3/09/20 
Limited time spent on-site for 
recruitment due to Covid-19 
COVID-19 disruptions 
1.4 
06/01/2021 
Change in recruitment strategies and 
videoconference 
COVID-19 disruptions 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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11 REFERENCES  
 
Almirall D, Compton SN, Gunlicks, Stoessel M, Duan N, Murphy SA. Designing a pilot sequential multiple 
assignment randomized trial for developing an adaptive treatment strategy. Stat Med. 2012; 31: 1887-
1902. 
 
Simoni JM, Wiebe JS, Sauceda JA, et al. A preliminary RCT of CBT-AD for adherence and depression 
among HIV-positive Latinos on the U.S.-Mexico Border: The Nuevo Día Study. AIDS Behav. 2013;17: 
2816-2829. 
 
 

STATISTICAL ANALYSIS PLAN 
 
AIM: To test a pilot sequential multiple assignment randomized trial of a depression and mHealth treatment strategy 
among HIV+ Latinos for feasibility and acceptability. 
 
Analysis of the Primary Endpoint(s) 
Basic demographic tables will be generated for all depression ratings from baseline through follow-up periods, as well as 
general measures of central tendency for each variable (e.g., Mean, SD), measured categorical and continuously, and 
highlighted by measures of variability. For Feasibility, the following outcomes will be evaluated using descriptive 
statistics to identify: 1) the number of participants screened, eligible and enrolled; 2) at least 80% of all BAT and CBT 
sessions completed; and 3) 80% retention in all “outcome groups” (see attached figure in protocol).  
 
Analysis of the Secondary Endpoint(s) 
The Microsoft Excel file will have all participant appointment attendance records and responses to schedule text-
messages, which were downloaded to determine acceptability as: 1) > 90% adherence to the BAT and CBT session 
schedule; 2) responsiveness to text-messages as: a) >80% of all two-way messages replied to during the set of blocked 
hours; b) >90% of participants reporting direct benefit from one-way text messages; 3) positive responses coded from 
post-intervention exit interview transcripts (to be determined at future date); 4) limited number of barriers to 
participation reported (to be determined at a future date).