Health and Justice: A Continuum of Care for HIV and SU for Justice-Involved Young Adults (PHASE 2)
Phase: NA
Conditions: HIV/AIDS, HIV Infections, Substance Use, Substance Abuse, Substance Use Disorders, Sexually Transmitted Diseases
Sponsor: New York State Psychiatric Institute

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Health and Justice: A Continuum of Care for HIV and SU for 
Justice-Involved Young Adults (PHASE 2) 
 
 
NCT03369249 
 
 
 
Study Protocol and Statistical Analysis Plan 
 
 
 
(10/20/17) 
 
 
 
 
 
 
 
 
 

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Health and Justice: A Continuum of Care for HIV and SU for Justice-involved Youth 
(R01 DA 043122) 
 
Principal Investigator: 
Katherine S. Elkington, Ph.D., Columbia University and New York State Psychiatric Institute 
 
 
Project Overview 
Statement of Responsibility for developing and executing DSMP 
The Principal Investigator accepts full responsibility for the development and execution of this Data and Safety 
Monitoring Plan. 
 
Brief protocol description and study design 
This protocol concerns the adaptation, efficacy-testing and implementation evaluation of a multi-component 
service delivery model (Link2CARE) that aims to increase HIV/STI testing and substance use (SU) screening; 
reduce HIV and SU risk; and increase linkage to HIV, STI and SU services in justice involved youth (JIY) who 
are enrolled in an alternative sentencing program (Brooklyn Justice Initiatives; BJI). We propose to adapt and 
integrate the following evidence-based strategies to create Link2CARE: (i) Screening: Offer an onsite rapid 
oral HIV test and STI urine test at intake into BJI and screen HIV risk behavior and SU; (ii) Brief intervention: 
use brief interventions (1-2 sessions) to reduce HIV risk and SU behavior and promote treatment/service 
readiness (MOVE1 and NYSBIRT2,3); (iii) Linkage to HIV and SU care: use a strengths-based patient 
navigator approach to mobilize JIY strengths and reduce barriers to treatment, while establishing formal 
relationships and referral protocols with service providers.  We have initiated a partnership with BJI, which 
serves 9000 JIY annually, and Project STAY, a youth-focused, hospital- and community-based, health and HIV 
treatment program; Project STAY HIV testing outreach workers will be embedded into BJI to deliver 
Link2CARE.  We will test the efficacy of Link2CARE in a randomized controlled trial among N=450 BJI-enrolled 
JIY (18-24 y.o.), randomized to either Link2CARE or standard of care (SOC) and conduct implementation 
evaluation to explore individual-, staff, and system-level influences on implementation of this new model to 
inform scale-up and dissemination.  Youth will be assessed at baseline and 3-, 6-, and 12-months post-
intervention.  BJI and Project STAY staff will be assessed before launch of Link2CARE and 12 and 24 months 
later.   
 
 
Study aims and primary and secondary outcomes 
The study has three aims. 
1. Among 450 (18-24 y.o) JIY in BJI randomized to either Link2CARE or standard of care (SOC), to 
determine the efficacy of Link2CARE delivered by STAY staff embedded within BJI on (a) HIV outcomes: 
HIV testing/repeat testing; HIV risk behaviors; (b) STI outcomes: STI testing/repeat testing; linkage to care 
of JIY with STIs; (c) SU outcomes: SU screening; SU; linkage to care of JIY with SU/D; and (d) 
(exploratory) linkage to care of HIV+ youth and linkage to PrEP for (behaviorally) eligible HIV– youth.   
 
2. To determine the influence of theoretically-based mechanisms of change of Link2CARE (e.g., 
predisposing characteristics, enabling resources, perceived need, organizational climate; staff attitudes) on 
the proposed HIV, STI and SU outcomes. 
 
3. To describe Link2CARE implementation and elucidate the system/organizational-, staff-, and youth-
level factors that influence implementation (i.e. acceptability, sustainability, feasibility) of 
Link2CARE in an ASP to develop a plan for dissemination and scale-up of Link2CARE in New York City 
 
 
The study has the following primary, secondary, and exploratory outcomes (related to aim 1)   
 
Domain 1 (primary outcomes: HIV outcomes): (a) total number of unprotected anal and vaginal sex occasions 
in past three months at 12 month FU; (b) acceptance of HIV testing at initial offering (y/n), (c) any HIV 

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testing between 6-month and 12-month FU (y/n).   
 
Domain 2 (secondary outcomes: SU outcomes): (a) frequency of youth substance use in past 30 days at 3-, 6- 
and 12-month FUs; (b) number of youth referred to SU treatment at 3-, 6- and 12-month FUs; at (c) number 
of youth attending intake plus one treatment session at 3-, 6- and 12-month FUs. 
 
Domain 3 (secondary outcomes: STI testing outcomes): a) acceptance of STI testing at initial offering (y/n), (b) 
any STI testing between 6-month and 12-month follow up; (c) number of STI+ youth referred to STI 
treatment at 3, 6, and 12 months FUs; (d) number of STI+ youth attending ≥1 treatment appointment at 3, 
6, 12 months FUs. 
 
Domain 4 (exploratory outcomes: HIV/PrEP linkage outcomes): (a) number of HIV+ youth referred to HIV 
treatment at 3, 6, and 12 months FUs, (b) number of HIV+ youth attending at least one treatment 
appointment at 3, 6, and 12 months FUs; (c) number of youth behaviorally PrEP eligible referred to 
PrEP/medical care at 3, 6, and 12 months FUs, (b) number of youth behaviorally PrEP eligible attending 
at least one HIV care appointment care at 3, 6, and 12 months FUs. 
 
 
TRIAL MANAGEMENT 
Study/data collection sites  
Data will be collected at Brooklyn Justice Initiative (BJI), run by Center for Court Innovation.  BJI is an 
alternative sentencing program (ASP) for JIY processed through Brooklyn Criminal Court.  BJI aims to reduce 
re-offending and increase public safety; promote use of meaningful social services; provide rigorous 
compliance monitoring; and reduce criminal convictions and use of jail.  Located in the Brooklyn Criminal 
Courthouse, BJI serves 9,000 youth/year; almost all (94%) are mandated to BJI for ≤15 days.  
 
Study sample description 
To address the study aims we will collect data from a sample of youth aged 18-24 who have been placed in 
BJI (sample 1), from a sample of HIV testing outreach staff (sample 2) and from staff at BJI (Sample 3). 
 
Sample size and power 
The total sample size of sample 1 will comprise N=472 youth currently enrolled at BJI: n=14 youth will serve 
on an advisory panel to provide feedback as MOVE and NYSBIRT are adapted; n=8 youth will pilot test the 
adapted Link2CARE protocols prior to the efficacy test of Link2CARE; and n=450 youth will be randomly 
assigned (1:1) to either Link2CARE or standard of care.  Sample 2 will comprise N=2 Project STAY 
outreach workers who will be embedded at BJI and will deliver all elements of Link2CARE to youth.  
Sample 3 sample size is expected to be all 15 staff who work at BJI. 
 
Based on our previous work, the retention rate for studies of JYI was about 75% to 80%. Even though we 
anticipate being able to maintain 20% attrition, we conservatively use 25% attrition at 12-month FU in this power 
calculation.  Under such assumptions and with a baseline sample of 450 participants, we estimate a final 
sample of at least n=338 with complete data for the primary analysis at 12-month FU.  With 169 participants 
per group and the use of Bonferroni correction, we will be able to provide 80% power to detect a standardized 
effect size of .35 or more on any of the three primary outcomes (i.e., total number of unprotected anal and 
vaginal sex occasions in past three months, acceptance of HIV testing at initial offering; and frequency of 
substance use in past 30 days). The standardized effect size of .35 is considered as a relatively small to 
moderate effect size according to Cohen4 and our previous study suggests that it is an achievable effect.  A 
substantial increase in sample size will not strongly impact effect size – e.g. to reduce the standardized effect 
size from .35 to .32, 100 more participants (22% increase in current sample size) would be required.  Even if  
actual attrition is greater than expected e.g. say 30%, the detectable standardized effect size will only increase 
slightly to .36.  Furthermore, as we will impute missing data using informative covariates for the primary 
analyses and using a less conservative Holm procedure for multiple comparison adjustment, power to detect 
such effects will actually be greater than 80%. 
 

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Table 1. Inclusion/exclusion criteria 
Study Phase 
Study Sample 
Inclusion Criteria 
Exclusion Criteria 
Phase 1: 
Adaptation for 
Link2CARE 
Peer advisory 
panel 
n=14 
1) Between 18-24 years of 
age  
2) Currently enrolled in BJI  
3) Conversant in English (in 
the past two years, only 
two JIY at BJI have 
required language 
assistance).  
  
1) Medical or psychiatric 
illness requiring 
hospitalization 
2) Serious suicidal or 
homicidal ideation 
 
 
 
BJI staff  
n=6 
1) Currently employed at BJI  None 
Pilot Youth  
n=8 
1) Between 18-24 years of 
age  
2) Currently enrolled in BJI  
3) Conversant in English (in 
the past two years, only 
two JIY at BJI have 
required language 
assistance).  
  
1) Medical or psychiatric 
illness requiring 
hospitalization 
2) Serious suicidal or 
homicidal ideation 
 
 
 
Phase 2: 
Link2CARE 
Efficacy Trial 
and 
Implementation 
Evaluation 
Youth  
n=450 
1) Between 18-24 years of 
age  
2) Currently enrolled in BJI  
3) Engaged in any 
unprotected sexual activity 
(lifetime),  
4) Conversant in English (in 
the past two years, only 
two JIY at BJI have 
required language 
assistance).  
 
1) Medical or psychiatric 
illness requiring 
hospitalization 
2) Serious suicidal or 
homicidal ideation 
3) HIV+ status by self-
report and linked to 
care 
Project STAY 
staff  
n=2 
1) Currently employed 
Project STAY and 
involved in delivering 
Link2CARE.  
 
None 
BJI staff  
n=15 
1) Currently employed at BJI  None 
 
Target population distribution  
Inclusion of Women. There is no inclusion or exclusion of participants based on gender. Based on 
demographic data from the Brooklyn Justice Initiative, we anticipate females will comprise 28% of the youth 
sample, representing the demographics of the justice system nationwide. 

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Inclusion of Minorities. We will not exclude participants based on ethnicity.  The majority of youth 
enrolled in the Brooklyn Justice Initiative are minority (56% African American, 18% Hispanic), representing the 
demographics of the justice system nationwide. 
Children: The proposed study does not include children aged 18 or younger.  The application proposes 
to develop a screening, brief intervention and linkage-to-care service delivery model that targets those at 
significant risk for HIV and SU.  In the US, youth age 18-24 carry the burden of HIV and substance use 
problems compared to youth younger than 18.  Moreover, the development of a linkage-to-care program f or 
youth younger than 18 would have to involve caregivers who can provide consent for youth to receive both SU 
and HIV treatment.  Involvement of caregivers would necessitate a different linkage-to-care intervention, which 
is beyond the scope of the proposed study.  
 
Project Timeline 
TABLE 2: Projected Timetable 
 
Year 1 
Year 2 
Year 3 
Year 4 
Year 5 
Months 
1 – 6 
7 – 12 
13 – 18 
19 – 24 
25 – 30 
31 – 36 
37 – 42 
43 – 48 49 – 54 54 – 60 
Adaptation and pilot testing of 
MOVE and NSYBIRT 
 
 
 
 
 
 
 
 
 
 
Train staff 
 
 
 
 
 
 
 
 
 
 
 
Recruit JIY 
 
 
 
 
 
 
 
 
 
 
 
Implement Link2CARE 
 
 
 
 
 
 
 
 
 
 
 
 
JIY assessment (3-month) 
 
 
 
 
 
 
 
 
 
 
JIY assessment (6-month) 
 
 
 
 
 
 
 
 
 
 
 
 
JIY assessment (12-month; 
main outcomes) 
 
 
 
 
 
 
 
 
 
 
 
 
Staff assessments 
(implementation outcomes) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Acknowledgment permission requirement 
The PIs acknowledge the requirement to request and receive permission from the PO for protocol or DSMP 
changes in advance of their implementation. 
 
 
DATA MANAGEMENT AND ANALYSIS 
Data acquisition, entry and transmission 
Study data will be collected in Phases 1 and 2. All Phase 1 and all baseline assessments (Phase 2) will be 
collected at BJI.  Subsequent Phase 2 assessments will occur at BJI, in the participant’s home or at another 
agreed upon location.  Note: BJI is not involved in survey administration, data entry and management, or data 
storage.   
Phase 1: Advisory Panel data: Peer (n=14) and Staff (n=6) Advisory Panels will meet in a series of Panel 
workgroups during Phase 1 to provide feedback on the adaption of the SU and HIV interventions. Data from 
these Panel workgroups will be gathered in note form by work group facilitators and will not contain any 
participant identifying information.  These data will be transcribed by research assistants and will be used 
between workgroups to inform adaptation of interventions.    
Pilot data: n=8 youth who participate in a pilot of the SU and HIV protocols will complete paper-and-
pencil process measures following the completion of the pilot which will be administered by human subject-
trained research assistants (RAs). These research assistants will bring completed questionnaires to the 
research offices at NYSPI on the day of data collection. These data will be entered in an electronic database 
by human subject-trained research assistants. This database will be stored on password-protected computers 
in encrypted files. Researchers will retain the pilot process assessments until the completion of all project 
activities in Year Five when they will be destroyed following HIPAA standard document destruction services.  
 

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Phase 2: Substance use and HIV behavioral risk screen. Following randomization and baseline 
assessments, n=225 JIY randomized to Link2CARE will complete substance use and HIV behavioral risk 
screeners. Screening will take place at BJI in private rooms or other agreed upon location (for follow-up 
survey assessments). Data will be captured on encrypted, password protected computers, entered directly 
by human subjects-trained RA’s into CiW using Sawtooth Software. Sawtooth Software allows for all 
standard question types, skip patterns, and data piping. Web-based data collection will not be used.  
Following interview completion, RAs will then transport interview data to NYSPI in the encrypted password 
protected computer, and immediately upload it upon return into the master database at NYSPI held on a 
secure server.   
HIV and STI testing: Following randomization and baseline assessment, all youth will be offered an HIV 
and an STI test for Chlamydia and gonorrhea; initial testing will take place onsite at BJI. All youth will also be 
offered HIV and STI testing at each follow-up interview (3m, 6m and 12m).  HIV testing will be done using 
Oraquick advance rapid HIV test.  Following brief pre-test counseling, an oral swab will be used to collect 
saliva to conduct HIV rapid test.  Once conducted, the embedded Project STAY staff member (LINK2CARE 
condition) or human subjects-trained RA (standard of care) will provide results to the participant and HIV+ JIY 
will be immediately linked to care following Link2CARE linkage protocols. The Project STAY staff or RA will 
then place the swab in a closed Developer Solution vial, then back into the package. The entire package will 
be placed in a baggie.  The baggie with the used test will be brought back to NYSPI by human-subjects trained 
RAs and turned in to the Project Director who will enter the results into a the project database at NYSPI that is 
held on a secure server.  The baggie containing the used OraQuick test and materials will then be disposed of  
in the appropriate waste container.  Staff (interviewers and office staff) will wear gloves when manipulating test 
materials.  STI testing will occur by the collection and processing of the urine specimens using a Gen-probe 
APTIMA Urine Specimen Collection Kit for Male and Female Urine Specimens.  The testing kits are provided 
and the urinalysis will be performed by the New York City Department of Health (NYCDOH) at no cost as part 
of an ongoing agreement with Project STAY. The client is instructed about how to provide the urine sample, 
and is sent to the bathroom by either the embedded Project STAY staff member (LINK2CARE condition) or 
human subjects-trained RA (standard of care). Upon return, the Project STAY staff member or RA packages 
the sample and arranges for pickup by the Department of Health's (DOH) Bureau of STD control. NYCDOH 
uses the third generation nucleic acid amplification test (NAAT), yielding qualitative testing results. Specimens 
will be collected and transferred into their respective specimen transport tubes. The transport solutions in these 
tubes release the rRNA targets and protect them from degradation during storage. When the APTIMA Combo 
2 Assay is performed in the laboratory, the target rRNA molecules are isolated from specimens by the use of  
capture oligomers in a method called target capture. After the target capture steps are completed, the 
specimens are ready for amplification. The GEN-PROBE APTIMA Combo 2 Assay replicates a specific region 
of the 23S rRNA from CT and a specific region of the 16S rRNA from GC via DNA intermediates. A unique set 
of primers is used for each target molecule. Differences in the kinetic profiles of the CT and GC labeled probes 
allow for the differentiation of signal; kinetic profiles are derived from measurements of photon output during 
the detection read time. The chemiluminescent detection reaction for CT signal has very rapid kinetics and has 
the “flasher” kinetic type, while the detection reaction for GC signal is relatively slower and has the “glower” 
kinetic type. Assay results are determined by a cut-off based on the total RLU and the kinetic curve type.  
Written documentation of the test results will be obtained by the research office from the NYCDOH  
Microbiology laboratory within 7 days after the urine sample was delivered. The Project Director who will enter 
the results into a the project database at NYSPI that is held on a secure server Respondents randomized to 
Link2CARE who test positive will be informed by embedded Project STAY staff of their results and will 
immediately be linked to care by STAY staff following Link2CARE linkage protocols. Respondents randomized 
to SOC who test positive will be contacted by study staff using a succession of methods (telephone, registered 
letter, and, if refused or undelivered, regular mail). Participants will be informed that antibiotics are used to treat 
Chlamydia and Gonorrhea. We will counsel that all sex partners within the last 60 days should be evaluated 
and treated and to avoid sex until they and their partners have been treated for at least 7 days or 7 days after a 
single dose treatment.  Specific referral procedures will be followed to maximize chances that participants will 
seek treatment.  
Face-to-face survey interviews - youth. Phase 2 youth survey interviews will be completed at 
baseline, 3m, 6m, and 12 months post baseline with n=450 youth.  Interviews will take place at BJI in private 
rooms or other agreed upon location (for follow-up survey assessments). Data will be captured on encrypted, 

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password protected computers, entered directly by human subjects-trained RA’s into CiW using Sawtooth 
Software. Sawtooth Software allows for all standard question types, skip patterns, and data piping. Web-
based data collection will not be used.  Following interview completion, RAs will then transport interview data 
to NYSPI in the encrypted password protected computer, and immediately upload it upon return into the 
master database at NYSPI held on a secure server.   
Face-to-face survey interviews - staff. Phase 2 staff survey interviews will be completed pre-
implementation of Link2CARE, at 12m (during implementation of Link2CARE and at 24m (post-
implementation of Link2CARE) with n=15 BJI staff and n=2 embedded Project STAY staff.  Interviews will 
take place at BJI in private rooms. Data will be captured on encrypted, password protected computers, 
entered directly by human subjects-trained RA’s into CiW using Sawtooth Software. Sawtooth Software 
allows for all standard question types, skip patterns, and data piping. Web-based data collection will not be 
used.  Following interview completion, RAs will then transport interview data to NYSPI in the encrypted 
password protected computer, and immediately upload it upon return into the master database at NYSPI 
held on a secure server. 
Post-implementation focus group. Project STAY and BJI staff will participate in a one-time focus 
group following the implementation of Link2CARE, which will take place in a private room at BJI. The focus 
group will be digitally recorded, transported by RAs in a locked pouch back to NYSPI and uploaded onto a 
secure server at NYSPI. The recordings will then be transcribed for analysis.  These recordings will be 
retained until the completion of all project activities in Year Five when they will be destroyed following 
HIPAA standard document destruction services. 
 
Data analysis plan 
Intent-to-treat principles will be invoked in the primary analysis. The primary aim is to determine whether 
participants randomized to Link2CARE show greater improvement in HIV outcomes from baseline to 12-
month follow up than participants in SOC.  Measurement of primary HIV outcomes includes three variables: 
number of unprotected sex occasions, whether participants accept HIV testing at initial offering (y/n), and 
any (repeat) HIV testing between 6-month and 12-month follow up (y/n).  Other behavioral and linkage 
variables to be examined as secondary and exploratory outcomes are described in Section 3.3.9.3.  
Implementation outcomes to be examined include feasibility, acceptability, and sustainability.  In addition, we 
will examine potential CFIR correlates of implementation, such as organization culture and climate and staff 
attitudes.  Finally, mediators associated with service use as specified by the Andersen model will be 
examined, including motivation for treatment, perceived barriers to treatment, prior service utilization.  
 
Analysis plan for Specific Aim 1.  Prior to conducting our multivariable analyses, we will examine study 
variables using descriptive statistics, testing for differences across demographic characteristics (e.g., 
race/ethnicity, age) using t-tests, ANOVAs, and Chi-squares, as appropriate.  Systematic baseline differences 
are not expected; however, any parameters that differ across conditions at baseline will be included as covariates 
in subsequent models.   We will calculate descriptive summary statistics corresponding to study variables at each 
follow-up (FU) to understand any temporal patterns, as well as compare the two groups in terms of average 
change from baseline to 12-months post-baseline.  We will use the general framework of generalized linear 
models (GLM) to model the longitudinal outcome trajectories and GEE method to account for within-subject 
correlation across the four time points (baseline, 3-, 6-, and 12-months).  Stratified randomization of 
participants to the groups based on their gender requires that the analysis also include gender as covariate.  
The general form of the analysis model will be g(μ)=α0+α1X+βI+∑γiTi+∑δiTiI, where g denotes the link f unction 
(identity for continuous outcome, logit for binary outcome and natural log for count outcomes) X represents the 
indicator of female (vs. male), I is the group indicator for Link2CARE (vs. SOC), and Ti is the indicator f or time 
at 3-month, 6-month, and 12-month evaluation (vs. baseline) for i=1, 2, and 3.  The interaction coefficients δi 
are of interest, measuring the difference in the rate of change in outcome across the two treatment groups at 
each follow-up assessment.  We will employ the above analytic approach to examine differences between youth 
in Link2CARE and in the SOC condition with respect to key study parameters within these four domains detailed 
below. Proposed hypotheses are that the experimental arm (Link2CARE) would have better outcomes (e.g. 
greater reduction on total number of unprotected anal and vaginal sex occasions in past three months from 
baseline to 12 month FU; greater increase in proportion of acceptance of HIV testing at initial offering; greater 
reduction on frequency of substance use in past 30 days at 3-, 6- and 12-month FUs; and of those referred to SU 
treatment, a greater  number of youth attending intake plus one treatment session at 3-, 6- and 12-month FUs) 

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compared to the standard of care; all hypothesis tests will be conducted under the control of familywise error 
rate no greater than 0.05 level. The Holm step down procedure will be employed to adjust for multiple 
comparisons.  
1. Domain 1 (primary outcomes: HIV outcomes): (a) total number of unprotected anal and vaginal sex 
occasions in past three months at 12 month FU; (b) acceptance of HIV testing at initial offering (y/n), (c) 
any HIV testing between 6-month and 12-month FU (y/n).   
2. Domain 2 (SU outcomes): (a) frequency of youth substance use in past 30 days at 3-, 6- and 12-month 
FUs; (b) number of youth referred to SU treatment at 3-, 6- and 12-month FUs; at (c) number of youth 
attending intake plus one treatment session at 3-, 6- and 12-month FUs. 
3. Domain 3 (exploratory outcomes: HIV/PrEP linkage outcomes): (a) number of HIV+ youth referred to 
HIV treatment at 3, 6, and 12 months FUs, (b) number of HIV+ youth attending at least one treatment 
appointment at 3, 6, and 12 months FUs; (c) number of youth behaviorally PrEP eligible referred to 
PrEP/medical care at 3, 6, and 12 months FUs, (b) number of youth behaviorally PrEP eligible 
attending at least one HIV care appointment care at 3, 6, and 12 months FUs. 
4. Domain 4 (STI testing outcomes): a) acceptance of STI testing at initial offering (y/n), (b) any STI testing 
between 6-month and 12-month follow up; (c) number of STI+ youth referred to STI treatment at 3, 6, 
and 12 months FUs; (d) number of STI+ youth attending ≥1 treatment appointment at 3, 6, 12 months 
FUs. 
 
 
Analysis plan for Specific Aims 2 and 3.  Descriptive statistics will be computed to quantify implementation 
at every step, by participant and by provider.  Thus, we will be able to compute uptake of LINK2CARE, 
dose/intensity of intervention received, number of providers delivering each intervention, and other 
implementation parameters.  Of note for Aim 2, which seeks to examine the proposed mechanisms of  change 
of the intervention on HIV, STI and substance use outcomes, a given outcome (e.g. HIV/STI testing uptake, or 
PrEP uptake or reduced substance use) of this analysis will only be examined among those for whom it is 
relevant.  For example, if a youth does not meet criteria for PreP and as such is not offered PrEP, we would 
not include this youth in analyses of mechanisms of change of Link2CARE as they influence substance use or 
PrEP uptake as an outcome.  We will examine the changes in specific outcomes (e.g. sexual behavior post-
intervention) as a function of proposed theory-based intervention mediators (e.g. predisposing characteristics, 
enabling resources, perceived need for treatment/services).  We will use structural equation models f or these 
analyses.  Structural equation modeling is preferred to multiple regression techniques because of the potential 
measurement error in our mediating variables and because of the possible feedback between dependent and 
mediating variables.  We will test the model described in Figure 1 in the application, entering intervention 
condition as exogenous variables and the mediating factors included in Figure 1 as endogenous variables.  
Prior to conducting the structural analyses, however, we will examine the effects of the intervention on the 
putative mediating variables; a condition for inclusion in the equation will be a significant intervention effect on 
the potential mediators. Using standardized path coefficients, we will examine the relative associations of 
mediators to behavior change.  We will also examine the path coefficient for the direct effect of the intervention 
after removing the effects of mediating constructs. For example, Link2CARE may have a more positive effect on 
acceptance of HIV (and STI) testing among JIY with greater perceived HIV risk, greater motivation to receive 
services, or positive HIV-testing history.  Similarly, Link2CARE may have more positive effect on linkage 
outcomes when operating in an ASP that is more supportive of concepts perceived as innovative by both BIJ and 
STAY staff.  Here, organizational culture would appear to modify Link2CARE’s impact on youth service referral 
and engagement outcomes.  We will examine the Lagrange Multiplier and Wald Tests to consider the deletion or 
inclusion of paths5; ultimately, however, deletion or inclusion of paths will be informed by theoretical 
underpinnings.  Once the model is identified, we will test for group differences between intervention conditions in 
latent constructs and in the proposed paths between these constructs.  This method will allow us to estimate the 
intervention effects on the constructs directly as well as their relationships to one another.6  We will use three 
goodness-of-fit indices: Bentler-Bonnet’s Normed Fit Index, Bentler-Bonnet’s Non-Normed Fit Index, and the 
Comparative Fit Index.  We will also verify the root mean-square error of approximation (RMSEA) as an index of 
misfit. Well-fitting models will have fit indices of.90 or higher and <.06 for RMSEA.  
Analysis of participant attrition and missing data.  We will make every effort to retain participants in the 
study to avoid bias due to attrition.  For those individuals who refuse continued participation, we will document 
reasons for study discontinuation and Rubin’s multiple imputation method with 11 repeated imputations will be 

10 
 
employed to impute the missing endpoint for conducting the intent-to-treat analysis.  
 
QUALITY ASSURANCE 
Procedures in place to ensure the validity and integrity of the data 
All data collection protocols include a form on which research staff members record any problems with the data 
collection or unusual occurrences during the collection. They also are encouraged to bring problems to the 
attention of the Project Director, or PI. These members of the research staff also meet on a regular basis to 
identify and address any issues that arise. These procedures allow our research staff an opportunity to quickly 
review and respond to any possible concerns. We expect missing data to be minimal, nevertheless regular 
(quarterly) quality assurance checks will be made by the Project Director to identify any systematic missing 
information and remedies will be enacted. 
 
Procedures to guarantee the accuracy and completeness of the data, during data collection, entry, 
transmission, and analysis.  
To check for errors in data entry, we will adhere to the following protocol.  All face-to-face surveys will be 
recorded.  One out of every seven recordings for each interviewer will be compared to the entered interview.  If 
we identify a proportion of errors that is more than 1% error, we will temporarily suspend the interviewer from 
active interviewing.  We will listen to all interviews for comparison purposes, identifying any errors and will re-
train the interviewer to ensure accuracy and completeness of all face-to-face survey interviews. A subset 
(10%) of all data from hard-copy/paper-pencil instruments that is entered into the project database will be 
similarly checked.  If we identify a proportion of errors that is more than 1% error, we will reenter all 
questionnaires and subsequently compare both data sets. We will go back to the original surveys to resolve all 
inconsistencies. To prevent data entry problems we will prepare a data entry system that will alert us when 
data are entered that are out of range. 
 
Procedures for preventing and addressing breaches of confidentiality 
Above we described how data are protected during collection and transportation. Once at NYSPI, all data will 
be saved on secure, password-protected servers. The information gathered will be used only for scientific, 
educational, or instructional purposes.  All interviewers and all other study staff are trained on the importance 
of subject confidentiality.  
 
 
 
REGULATORY ISSUES 
Procedures for research team management of AEs, SAEs and other study risks such as mandatory 
reporting requirements (e.g., child abuse, infectious disease, etc.)  
The Principal Investigator, Dr. Elkington has the ultimate responsibility for reviewing conduct of the study and 
data produced from it, including the reporting of any adverse events to the respective IRBs. 
 
AEs and SAE that come to the attention of any staff person involved in the study, have to be reported 
directly to the PI using an Adverse Event Report Form. If no action has yet been taken, the PI ensures that 
these events are addressed by the timely intervention of either herself, Dr. Cohall or one of the Project STAY 
staff at BJI. The PI furthermore ensures that the respective IRBs are informed, in line with the seriousness of 
the event. And follows NYSPI IRB protocol to report (S)AEs and receives feedback about appropriate course of 
action to follow.  Below is a table of potential AEs and SAEs and the proposed procedures to detect them.    
 
Procedures to prevent the violation of confidentiality in accordance with reporting requirements are 
limited by the mandatory nature of these requirements. Therefore, all subjects are informed in the consent 
document that the only times other people will find out what they said during the study are: (1) If they describe 
the physically or sexually abusing a child. This will be reported to the New York State Central Registry (NSCR) 
which takes calls for child abuse and neglect allegations. If accepted, the NSCR will forward to Bronx field 
office for the City’s Administration for Children’s Services (ACS). (2) If they say they want to harm themselves 
or another person, the researchers can break confidentiality to refer them for further evaluation. (3) In cases of 
a positive HIV or STI diagnosis, we will follow standard procedures, in line with legal requirements. The 
mandate for HIV is for the provider doing posttest counseling is to assess for partner notification within 30 days 
of diagnosis. This will be handled by Project STAY staff or staff from the specific clinic the youth has been 

11 
 
linked to if not project STAY. Patients will be asked if they can contact sexual partners themselves. If not, 
sexual partners can be brought in by the patient and clinic staff notifies partners. The third option is to inform 
the New York City Department of Health and Mental Hygiene (DOHMH), which does anonymous notification 
and advices sexual partners to go to their physician and get tested. The assessment for partner notification 
includes a check for domestic abuse risk. For other STIs, partner notification is voluntary not mandatory but 
Project STAY staff will assess for partner notification and ask the patient to notify partners themselves, the 
patient can bring partner in, DOHMH can assign a field worker for anonymous notification; Project STAY staff 
will never call the partner down. All STI, including Chlamydia, Gonorrhea and HIV require an individual, 
identified report to the city as they occur; this is a direct online report into the DOHMH website. 
 
Table 3 Potential AEs and SAEs and the proposed procedures to detect them. 
Types/Categories of Events Anticipated 
(whether or not occurred) 
Procedure to detect 
Extreme psychological distress in participants  
• General follow-up and check-in with all 
participants during and following each 
scheduled baseline, 3, 6- and 12-month 
interviews (Phase 2). 
• Check-in and debriefing with participants 
following each HIV/STI testing occasion; 
pre- and post-interview question “scale 1-
10, how do you feel…” 
• Check-in with provider at 3, 6- and 12-
month interviews (Phase 2). 
 
 
Negative feedback from participant upon 
debriefing (e.g., thought participation might be 
harmful or upsetting to others) 
Suicidality (thoughts or intentions) 
Homicidality 
Suspicion of safety concerns in the home 
Increase in sexual risk behaviors or substance 
use 
Increase in conflict/distress between 
participants and partners 
Youth detention/incarceration 
Non-voluntary Disclosure of HIV or STI 
diagnosis 
Non-adherence to treatment and care for HIV+ 
or STI+ youth 
Loss of Confidentiality 
 
Staff training (including NIH-required human subjects training and other related training) 
All staff involved in the study (researchers, clinic staff, the Implementation Coach, the Youth Outreach Worker) 
has successfully completed a mandatory, training/testing program on human subject protection; staff is 
required to keep their ethics certification up to date. In addition, clinic staff are trained in issues related to 
ethnic and cultural diversity and to concerns and needs of the adolescents they will interview and in 
procedures for addressing any problems that may arise. Furthermore, research and program staff are trained 
to identify events that would fall under mandatory reporting guidelines, to respond to distress and in emergency 
procedures that are activated if an adolescent admits to thoughts of harming himself or others. The Program 
furthermore contains specific training activities to ensure skillful implementation of activities in line with ethical 
guidelines, e.g., Peer Navigators will be thoroughly trained on the imperative of confidentiality and other ethical 
aspects of being a peer navigator. 
 
Certificate of confidentiality 
A Certificate of Confidentiality will be obtained from NIH to protect the privacy of our research subjects by 
protecting the research team and our institutions from being compelled to release information that could be 
used to identify subjects with a research project. 
 
Procedures and timeline for reporting AEs and SAEs to NIDA 
Adverse Events (AEs) will be reported to the NIDA PO at least once per year as part of the annual progress 
report.  This report will describe the event, when it occurred, the study arm of the participant, and the 
outcome/resolution.  If there were no AEs, we will include a statement in the progress report that no AEs 
occurred.  In case of SAEs, the contact PI will ensure that they will be reported to the NIDA PO within 24 hours 
by email and that a written report is submitted to the PO no more than two days later. 

12 
 
 
Reporting of IRB actions to NIDA 
Any IRB actions that negatively impact the implementation of the study will be will be reported to the NIDA PO 
within 24 hours by email. 
 
Acknowledgment permission requirement 
The PIs acknowledge the requirement to request and receive permission from the PO for protocol or DSMP 
changes in advance of their implementation. 
 
Trial Stopping Rules 
Only two of the three co-primary endpoints will be monitored for early stopping: (1) total number of unprotected 
anal and vaginal sex occasions in past three months at 12 month FU; (2) any HIV testing between 6-month 
and 12-month FU (y/n).  We will follow a modified Haybittle-Peto rule7  to propose early stopping as follows: the 
z-score for testing the null hypothesis for each of the two primary outcomes will be calculated once during 
interim analyses (see below) when one-quarter of the expected total 12-month outcome data has been 
observed (after approximately 6-months of 12-month data collection).  This will allow the PSMB to recommend 
continuing to recruit subjects or stop the trial for strong positive or negative efficacy prior to the end of subject 
recruitment.   
 
The z-score for early stopping will be Z = 3.6623 for either monitored outcome, corresponding to a normal two-
tailed critical value cutting off nominal probability 0.00025 in each tail.  It follows that either endpoint may 
suggest early stopping with total two-tailed probability 0.0005 under the null hypothesis and therefore the 
probability of early stopping under the null hypothesis for either endpoint in either direction will be no greater 
than 0.001.  This stopping rule is less conservative than an O’Brien-Fleming-like alpha spending function 
monitoring plan, yet is still sufficiently conservative to leave the terminal significance criteria nearly unaffected.  
In particular, assuming no early stopping, if either of the two monitored co-primary endpoints specified above 
possesses the smallest P-value among all three co-primary endpoints, the group comparison will be declared 
significant at the 0.05 level (adjusted for multiple comparisons) if the terminal z-score criterion is Z = 2.3978 or 
greater.  This Z-score is very close to the nominal 0.05/3 ≈ 0.01667 two-tailed normal critical value of 2.3940, 
which is the initial required criterion under the Holm step-down procedure without sequential monitoring.  If the 
unmonitored co-primary endpoint (acceptance of HIV testing at initial offering, y/n) should have its P-value as 
smallest and less than or equal to 0.05/3 ≈ 0.01667, then it will be declared significant (at the two-tailed 0.05 
level, adjusted for multiple comparisons).   
 
Assuming no early stopping and with neither of the two preceding possibilities occurring at terminal analysis, 
testing stops under the Holm step-down procedure and none of the three null hypotheses will be rejected.  
Assuming no early stopping but with one of the two preceding possibilities occurring at terminal analysis, the 
next step in the Holm step-down procedure will use either the nominal P-value for the unmonitored co-primary 
endpoint (if it has the second smallest P-value) or, if not, the P-value for the monitored endpoint with the 
second smallest P-value adjusted for the interim analysis.  This P-value will again be very close to the nominal 
P-value due to use of the conservative modified Haybittle-Peto stopping boundary.  The appropriate two-tailed 
P-value must equal 0.05/2 = 0.025 or less to declare significance; if not, testing stops and only the first 
endpoint result will be reported as significant.  If so, then testing proceeds under the Holm step-down 
procedure to the remaining endpoint with criterion P-value 0.05, unadjusted if for the unmonitored endpoint or 
adjusted for interim monitoring if for one of the monitored endpoints.  If the 0.05 P-value criterion is not 
achieved, only the preceding two endpoints will be declared significant.  If the 0.05 P-value criterion is 
achieved, all three endpoints will be declared significant at the 0.05 level (adjusted for multiple comparisons). 
 
The analyses on the two primary endpoints will be presented to the PSMB (see Efficacy Data below) in a 
blinded fashion (i.e. A vs B) with a brief description as to whether or not we meet the stopping rule.  Of course, 
the PSMB may request additional information and/or unblinding on a need-to-know basis.  Other reasons for 
stopping the trial, e.g., unexpectedly low recruitment or poor retention, will be considered by the PSMB during 
their regular pooled-data reviews at six-month intervals.  The PSMB has substantial experience with oversight 
of trial integrity issues and will come to a recommendation around stopping related to poor enrollment or 

13 
 
retention issues as necessary.  Prior to the start of the trial we will propose recruitment and retention 
benchmarks for their review and approval. 
   
 
TRIAL SAFETY 
Potential risks and benefits for participants  
The benefits of this study include gaining knowledge that may be fundamental to improving the continuum of  
HIV and SU care for JIY and developing innovative models of service delivery to a highly vulnerable 
population.  There are very few programs designed to screen, reduce risk and link to HIV and SU care for JIY, 
most are developed for adults and do not take into consideration developmental needs of the youth.  A 
screening, risk reduction and linkage model that addresses organizational and staff level- barriers to linkage 
and engagement, as well as directly targeting youth-level barriers to reducing risk behavior and service uptake 
is critical to providing JIY with skills necessary to navigate multiple systems (substance use treatment, HIV 
care and justice system), remove barriers to service use, enroll in and remain in services.  The fact that rates 
of HIV are elevated in correctional populations compared to the general population, targeting youth who are 
attending community programs in lieu of jail or detention represents a critical point for intervention.  Moreover, 
substance use/disorder in JIY are much higher than youth in the general population, and that these youth have 
much worse outcomes associated with substance use but receive services at much lower rates warrants 
immediate attention.  This study will provide an opportunity to improve identification, risk reduction and 
enrollment in care for youth who are at the highest risk of HIV and substance use, yet least likely to receive 
services.  For these reasons, this study has the potential to impact the health and functioning of high-risk 
youth.  Additionally, JIY will be asked specifically for their experience with the operation of Link2CARE in their 
agency and input into how to improve linkage to HIV substance use services for JIY.  Study participants of ten 
derive a sense of altruism, accomplishment, and contribution to furthering understanding of the problem 
through their participation, and past participants in similar studies by the PI, co-Is and consultants have 
indicated the process was enjoyable and beneficial. 
 
The importance of Knowledge to be gained 
Prevalence of HIV and substance use disorders among JIY is significantly higher compared to youth in the 
general population. Ultimately, a study of this kind has the potential to (a) improve the outcomes f or youth by 
detecting HIV risk, infection and problematic substance use, reducing risky behaviors and linking high risk 
youth to necessary care and treatment, while overcoming system and youth level-barriers to this process; and 
(b) identify multilevel factors that are associated with adopting and sustaining innovative practices.  Risks to 
participation in the study (discussed above in the section 5.2) are reasonable given the importance of 
knowledge expected from the study.   
 
 
TRIAL EFFICACY 
Responsibility for data and safety monitoring  
The project will use the Performance and Safety Monitoring Board (PSMB) of the HIV Center for Clinical and 
Behavioral Studies (P30-MH43520) at the New York State Psychiatric Institute. The HIV Center’s PSMB is an 
external advisory group comprising community and clinical psychologists, a biostatistician, an ethicist, and a 
clinician not affiliated with HIV Center research projects or our home institutions. This PSMB has specifically 
been established to deal with studies focused on HIV infection and has the necessary expertise to address 
urgent issues that might arise in relation to the current protocol and to support us when protocol changes might 
be necessary. This PSMB, coordinated by the Statistics, Epidemiology, and Data Management (SED) Core of 
the HIV Center, monitors intervention projects associated with the Center on a yearly basis. The project will be 
reviewed at least once each year and more often if necessary or to follow up on PSMB recommendations. In 
addition, we will call on the PSMB as needed to address urgent matters that arise, including SAES/AEs, 
questions and concerns from the IRB, and discussions about possible protocol changes.  
 
Composition of the PSMB  
Bette Crigger, Ph.D. (Chair), Director of Ethics, American Medical Association, Chicago, IL.   
Patricia Hawkins, Ph.D., Clinic Director, DC Community AIDS Network in Washington, DC 

14 
 
Joseph Hogan, Sc.D., Professor and Graduate Program Director, Department of Biostatistics and Co-Director, 
CFAR Outcomes and Biostatistics Core, Brown University, Providence, RI  
Steven Morin, Ph.D., Emeritus Professor of Medicine, University of California, San Francisco, CA 
Nina Regevik, M.D., Director, HIV Early Intervention Program, Raritan Bay Medical Center, Perth Amboy, NJ 
 
Charge of the HIV Center PSMB  
The PSMB is appointed by the HIV Center to ensure and maintain the scientific integrity of human subject 
research projects and to protect the safety of human subjects. The PSMB has the responsibility to assure the 
HIV Center that participants in research projects are not being exposed to unnecessary or unreasonable risks 
as a result of the pursuit of scientific objectives. The PSMB also assures the HIV Center that research projects 
involving human subjects maintain high standards of quality throughout the duration of these projects. The 
PSMB will review the study protocol and any protocol changes in relation to both the safety of participants and 
the overall scientific integrity of the project. Comments and recommendations will be directed to the Director of 
the HIV Center and to the Principal Investigators of the project. 
 
Through the HIV Center Director or the SED Core Director, the PSMB has the authority to request 
summary reports, data listings, research documents, and any information determined to be necessary to fulfill 
its duties and responsibilities. The PSMB can request that the HIV Center Director obtains independent 
verification of some or all data relevant to the safety of human research participants and the scientific 
objectives of the trial. Independent verification may include examination of relevant medical and research 
records. Under extraordinary circumstances – for instance, continued failure on the part of an investigator to 
take appropriate measures for the protection of research participants from significant risk – the chair of the 
PSMB, with the agreement of the PSMB, can communicate directly with the Director of the funding agency. 
 
Statement of no conflicts of interest 
None of the members of the PSMB has an appointment at our institutions or research collaborations with the 
Principal Investigators or team.   
 
Frequency of meetings  
The PSMB typically meets on-site at the HIV Center at least once each year to monitor projects and through 
conference calls both among the board members and with the HIV Center leadership and investigators during 
the year to assure that PSMB recommendations are enacted. Regarding this specific protocol, the PSMB will 
meet as needed to address any of the above or other urgent or timely sensitive matters that might arise. 
 
Plans for Interim Analysis of efficacy data 
The aims of early interim analyses (in six-month intervals) are to (a) ensure that assumptions about mission-
critical parameters (means, standard deviations, and prevalence of main outcomes) made for purposes of 
power are approximately correct; and (b) to monitor safety of the trial participants, reviewing all adverse events 
(AEs) and serious adverse events (SAEs).  Interim analyses for safety and data monitoring of mission critical 
parameters, including recruitment and retention rates, will be conducted every 6 months by the trial statistician 
who will prepare the report for the PSMB (see Monitoring activities below).  A third aim of interim analysis is (c) 
to check at a strategic point in the trial whether sufficiently strong evidence of positive or negative efficacy has 
accumulated to warrant consideration of stopping the trial (see Trial Stopping above). For all analyses the PI 
will remain blinded as to treatment assignments.  As far as is feasible, the PSMB will also remain blinded, 
reviewing interim analyses prepared by the unblinded statistician in A/B format.  They may, of course, request 
additional information for any safety concerns or risk-benefit analyses on an as-needed basis.  Agreement on 
these procedures will be obtained with the PSMB prior to trial start.  As described above, interim analyses for 
trial stopping will be conducted once after one-quarter of the 12-month data has been collected.   
 
Monitoring activities  
Although the Principal Investigator will have ultimate responsibility for reviewing conduct for the study and data 
emanating from it, including the reporting of any adverse events to the Institutional Review Boards of Columbia 
University/the New York State Psychiatric Institute (NYSPI) and NIDA, the PSMB will also review this project 
twice each year (every 6 months).  The Principal Investigator will identify a list of adverse outcomes (e.g., 
significant psychological distress, loss of privacy) that might occur as a result of participation in the study.  In 

15 
 
addition, in preparation for the presentation of the project to the PSMB, a blinded report will be sent to the 
PSMB members in the weeks before the meeting and include a 1) a brief description of the trial, 2) summary of  
progress to date, including participant baseline sociodemographic characteristics, 3) blinded data such as 
participant accrual and retention, prevalence of main outcomes, 4) a description of any AEs or SAEs, and 5) an 
interim efficacy comparison when one-quarter of the 12-month primary endpoints have been observed.  
Typically, this information is reviewed during the open session of the PSMB meeting.  In closed session, the 
PSMB will review the data in blinded A versus B format (and, if needed, in unblinded fashion) after which, the 
PSMB members will present feedback to the project research team with respect to whether the study should 
be continued.    
 
Communication Plan Acknowledgment of Reporting Requirement 
The PIs acknowledge the requirement to report PSMB activity (meeting notes on the Board meeting, 
discussions, decisions, etc. pertaining to this project) as part of Annual Progress Report to NIDA. 
 
 
 
 
 
 
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