Nurse-Led Community Health Worker Adherence Model in 3HP Delivery Among Homeless Adults at Risk for TB Infection and HIV
Phase: NA
Conditions: Latent Tuberculosis Infection
Sponsor: University of California, Irvine

Study Protocol and Statistical Analysis Plan 
Title of the study: Nurse-Led Community Health Worker Adherence Model in 3HP 
Delivery Among Homeless Adults at Risk for TB Infection and HIV (3HP-LTBI) 
NCT Number: NCT03702049 
Document Date: January 2, 2024 

Procedures 
Recruitment, Informed Consent, and Compensation 
A well-trained RN and CHWs visited shelters and informed residents frequenting the 
sites about the study. Approved flyers were posted, and informational session 
presentations were given by the staff in the lobbies of the shelters where residents and 
visiting homeless awaited services. After informed consent was administered, a brief 2-
minute structured questionnaire, which assessed TB history, followed. All potentially 
eligible participants were escorted to our community-based partner clinic in Skid Row 
and were tested with a blood assay using QuantiFERON-TB Gold Plus, a tuberculin 
skin test alone, or a combination of screening with the tuberculin skin test followed by 
the QuantiFERON-TB Gold Plus, as well as other routine testing (i.e., liver function and 
HIV tests). LTBI-positive homeless adults were escorted back to the clinic and 
completed a CXR to rule out active TB. 
Following a subsequent clinic visit, all eligible participants were cleared for 3HP 
treatment for LTBI and were administered a second informed consent, followed by a 60-
minute questionnaire that assessed general health and psychosocial and behavioral 
variables. All participants were paid $3 for the screening questionnaire and, if eligible, 
$5 for further laboratory tests at the clinic and $20 for the completion of baseline 
measures. 
RN/CHW LTBI Program Training and Competency Evaluation 
Upon development of the intervention protocol, the RN/CHW team was trained to 
deliver the 3HP LTBI intervention. The team was composed of a research RN and four 
part-time CHWs. CHWs were selected because they were formerly homeless adults 
who had transitioned out of homelessness, had excellent social skills, were positive role 
models, and had knowledge of the community and culture of homelessness. During the 
research team training, each member completed human subjects and Health Insurance 
Portability and accountability Act of 1996 (HIPAA) training, quizzes evaluating 
knowledge, baseline and follow-up questionnaire administration and mock training, and 
case studies of PEH with corresponding discussions. After the research leadership 
team introduced all content and knowledge that were assessed verbally using 
discussions, role play, and teach-back methods, the RN/CHW team was evaluated by 
the primary investigator and research investigators using a comprehensive competency 
checklist. 
Development of RN/CHW 3HP LTBI Weekly Operations, Fidelity Monitoring, 
and Oversight 
During the study implementation, a weekly operations and fidelity report on Research 
Electronic Data Capture was used to track outreach (e.g., flyer distribution, recruitment, 
information sessions, and screening), participant clinic appointments (e.g., laboratory 
tests, CXRs, and purified protein derivative test/CXR test result), physician clearance, 

daily monitoring, weekly activities, and sessions. On a daily basis, the RN/CHW team 
reported to the research investigators and project coordinator. Every week, the research 
team went over the weekly operations, discussed, and evaluated research study 
progress. Based on these reports, concerns that arose during intervention 
implementation were addressed using constant evaluation and brainstorming, and 
creative approach to mitigating further challenges was discussed. 
Intervention: RN/CHW Intervention Delivery 
Each CHW was assigned seven to eight participants. At a mutually convenient time, the 
RN/CHW team met weekly with participants, under the direction of the RN, and 
assessed any side effects before the next dose. If none, the CHW provided directly 
observed treatment in a screened and private area. After the first dose of 3HP 
treatment, CHW conducted weekly one-on-one, 20-minute case management sessions 
over 12 weeks, where detailed information was provided about the program, along with 
coaching support to identify personal values and goals participants set for themselves. 
Education about TB and LTBI, its dangers, and the need for support to counteract the 
barriers of drug and alcohol use and mental health issues to 3HP medication completion 
was provided. Participants were encouraged to apply the problem-solving model to 
different hypothetical situations that served as triggers to engage in substance use and 
so forth. Progress was reviewed in overcoming barriers to medication adherence and 
appointment keeping. 
The team also provided health and social service referrals (e.g., physical, mental health, 
substance treatment, and housing) and regularly tracked (detailed searching) 
participants who missed a 3HP dose. This tracking process was explained during the 
consenting process. If the participant failed to meet the team for the next dose, the team 
would begin making calls to reconnect based upon the locator information provided by 
the participant. This process occurred when a dose was missed on a specific date or a 
follow-up appointment was missed. Based on guidelines, participants who received 11 
of 12 doses over 16 weeks were considered completers. Those who had a gap of >4 
weeks between doses were noncompleters and were encouraged to restart the 
treatment. 
Historical Control Group 
In our comparison group, the historical control was provided the 3HP LTBI treatment to 
PEH attending a clinic. As a result of an outbreak in the Skid Row area of Los Angeles 
in 2014, the county investigated and screened 727 homeless adults. Over two thirds of 
the sample participants were between the ages of 35 and 54 years, whereas the 
remainder were 55 years and older. Three quarters of the sample participants were 
equally distributed as Black or Hispanic, whereas 13% were White and 2% were Asian. 
Among the 727 screened, 159 (21.8%) were LTBI positive, and 107 (67.3%) were 
recommended for 3HP treatment. Among the 56 who initiated treatment, 37 (66%) 
completed treatment. 

Instruments 
In this study, the primary dependent variable was completion of a 12-dose 3HP LTBI 
treatment compared to a historical, clinic-based control group that obtained 66% 
completion among homeless adults. Secondary outcome variables included an 
assessment of decline over time of the mental health symptoms of depression and 
anxiety and the drug use score and problematic alcohol use. 
Independent Variables 
Sociodemographic factors included age, gender, race/ethnicity, country of birth, and 
housing history (e.g., own/living with family or friends; shelter, street, living with family, 
friends). 
General health was measured using five items from the general health perceptions 
subscale of the RAND 36-Item Short-Form Health Survey (SF-36; Ware & Sherbourne, 1992). 
Participants responded to five statements, such as “my health is excellent” or “I expect 
my health to get worse,” with response options ranging from “true” to “definitely false” 
and end points 100, 75, 50, 25, and 0, with several items reverse scored. A total score 
was determined by calculating the average, where higher scores of 80+ were termed as 
“more favorable,” scores of 60–80 were termed as “favorable,” and scores of <60 were 
termed as “less favorable” perception of health. For this measure, Cronbach’s α = .78. 
Social support was measured using the Medical Outcome Study Social Support Survey 
(Sherbourne & Stewart, 1991), a 19-item instrument that assesses availability of social support and 
includes four subscales: emotional/informational support (eight items, α = .95), tangible 
support (four items, α = .94), positive support (three items, α = .98), and affectionate 
support (three items, α = .96). Participants respond on a 5-point Likert scale, ranging 
from 1 (none of the time) to 5 (all of the time), with higher scores indicating more social 
support. We have thus labeled the scores as high (75+), moderate (25–74), 
and low (<25) social support. An overall support index was also calculated (α = .98). 
Primary Dependent Variables 
3HP Treatment Completion 
As further clarified in the data analysis section, treatment completion was calculated by 
totaling the number of doses completed by each individual, with completion defined as 
11 of 12 doses. The percentage of treatment completion was calculated using 95% 
confidence intervals. 
Secondary Outcome Variables 
Drug use score and problematic alcohol use, as well as the mental health symptoms of 
depression and anxiety, were assessed to observe the effect on the primary outcome of 
treatment completion, as well as the decline over time, and constitute secondary 

outcomes of this study. These variables were of critical importance as they are 
historically considered significant barriers to treatment completion. 
Drug use score and problematic alcohol use were measured using the Texas Christian 
University (TCU) Drug Screen 5 (Institute of Behavioral Research, 2020), a 17-item measure that screens 
for mild to severe substance use disorder per the Diagnostic and Statistical Manual for 
Mental Disorders (5th Edition). Participants indicated either “yes” or “no” responses to 
substance dependency questions and frequency of drug use based on a 5-point scale 
from 1 (never) to 5 (daily). The TCU Drug Screen 5 is scored on a point system, ranging 
from 0 to 11. Participant scores correspond to the number of symptoms endorsed by the 
participant and the severity of substance use disorder, including mild disorder (2–3 
points), moderate disorder (4–5 points), or severe disorder (6 or more points). 
Problematic use of alcohol and specific drugs was defined as self-identified as being a 
problem (TCU Item 12) or daily consumption. For this measure, Cronbach’s α = .89. 
Depression was assessed using the Center for Epidemiological Studies Depression 
Scale–Revised, a 10-item measure used to screen for depression (Eaton et al., 2004). This scale 
assesses depressive symptoms using a 4-point Likert scale that reflects the frequency 
of a symptom in the past week, ranging from 0 (rarely or none of the time) to 3 (most of 
the time). Example items include “I was bothered by things that do not usually bother 
me,” “I felt depressed,” and “I felt fearful.” Responses are summed (range: 0–30); a total 
score above 10 indicated depression. Reliability was good (Cronbach’s α = .79). 
Anxiety was measured using the Generalized Anxiety Disorder-7, a seven-item self-
report instrument used to screen and assess for anxiety, using a 4-point Likert scale 
ranging from 0 (not at all) to 3 (nearly every day; Spitzer et al., 2006). Example items include 
“worrying too much about different things,” “trouble relaxing,” and “not being able to 
control worrying.” Scores were summed and ranged from 0 to 21. The severity of 
anxiety was determined with cutoff scores of 5 (mild anxiety), 10 (moderate anxiety), 
and 15 (severe anxiety). In this study, reliability was very good (Cronbach’s α = .87). 
Statistical Analysis 
Descriptive statistics, including frequency and percentages, were computed for all 
variables. We assessed reliability of psychosocial scales used in our study by 
estimating Cronbach’s alpha. Our primary outcome was 3HP treatment completion, 
defined as completing 11 of 12 3HP doses. We estimated this outcome by dividing the 
number of participants with treatment completion by the total eligible participants and 
calculated the 95% confidence intervals using the scoring method. The lower bound of 
the 95% confidence limit was compared to 66% historical completion to assess 
successful improvement. We used mixed-effects models to account for within-
participant correlation across time for the secondary outcomes of changes in drug use 
severity, anxiety, and depression scores. 
For each model, the secondary outcome was specified as the dependent variable, time 
point as an ordinal independent variable, and subject identification as the random 

variable. We also investigated the changes in problematic use of alcohol (binary 
outcome, yes vs. no) over time by fitting a generalized estimating equation to account 
for repeated measures over time for each subject. R v4.0.2 packages Hmisc, gee, and 
lme4 were used for analysis (R Core Team, 2020).