Development and Evaluation of Harm Reduction Talking Circles for Urban American Indians and Alaska Natives With Alcohol Use Disorders - Phase III Randomized Clinical Trial
Phase: NA
Conditions: Alcohol Use Disorder
Sponsor: Washington State University

PIs: Nelson, Collins 
HaRTC Phase 3 Protocol 
1 
 
 
 
 
 
 
 
Protocol for Phase 3: HaRTC Efficacy RCT 
Washington State University 
University of Washington 
Seattle Indian Health Board 
 
9/10/2020 
 
 
 
 
 
 
 
 
 
 

PIs: Nelson, Collins 
HaRTC Phase 3 Protocol 
2 
 
 
Phase 3 will comprise a partially nested randomized controlled trial comparing HaRTC and 
delayed HaRTC on alcohol outcomes, Quality of Life (QoL), and cost-effectiveness. Secondary 
analyses will test the hypothesized HaRTC effect on American Indian/Alaska Native/Indigenous 
cultural connectedness and investigate whether this effect mediates the effect of HaRTC on 
outcomes 
 
Participants 
We will enroll 300 AI/ANs with AUDs. Inclusion criteria are a) being urban AI/AN, b) being at 
least 21 years of age (for legal reasons), c) living in an urban area (RUCA defined) not on Tribal 
or Reservation land, d) meeting criteria for a current Alcohol Use Disorder (AUD) according to 
the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), e) 
technological literacy for video conferencing/text. Exclusion criteria are a) refusal or inability to 
consent to participation in research, and b) potential to place the safety or security of other 
patients or staff at risk. Based on prior experience, we expect study exclusions to be rare. Ability 
to consent will be assessed during the information session using the UCSD Brief Assessment of 
Capacity to Consent (UBACC).1 This 10-item, 3-point Likert-scale measure ensures participants 
understand the study protocol, potential risks/benefits and their rights as participants prior to 
study enrollment 
 
Measures and Materials (see Appendix C) 
Measures for tracking/sample description. The Tracking Information Sheet will assess 
participants' contact information to facilitate reminder contacts for future appointments. The 
Participant Information Questionnaire (PIQ) will assess age, sex assigned at birth, gender, 
race/ethnicity, education, employment, military experience, participation in other research and/or 
treatment, and experience of homelessness. 
Measures of Enculturation. The Cultural Connectedness Questionnaire comprises is a 29-
item Likert type measure consisting of 3 dimensions: identity, traditions, and spirituality. 
Criterion validity was demonstrated with cultural connectedness dimensions adequately 
correlating with other indicators of wellness. The resulting scale scores will represent the 
proposed mediator in this study. 
Measures of alcohol-use outcomes. The Structured Clinical Interview for the DSM-5 (SCID-5) 
is a validated, structured assessment of DSM-5 criteria for psychiatric disorders. The AUD 

PIs: Nelson, Collins 
HaRTC Phase 3 Protocol 
3 
 
portion of this measure will be used to document the presence of an AUD, a key criterion for 
study inclusion. The Alcohol and Substance Use Frequency Assessment items were adapted 
from the Addiction Severity Index-Fifth Edition (ASI-5th Ed) and will be used to assess 
frequency of alcohol and other drug use in the past 30 days. The Alcohol Quantity and Use 
Assessment was created by the research team for previous studies with a similar population 
and will be used to record the quantity of alcohol consumed on participants’ heaviest, typical, 
and lightest drinking days in the past month. The Short Inventory of Problems-2nd Revision 
(SIP-2R) is a psychometrically reliable and valid 15-item, Likert-scale questionnaire, measures 
social, occupational, and psychological problems related to alcohol use. Ethyl glucuronide (EtG) 
urine tests will be used to validate self-reported alcohol use at each assessment. EtG, a 
metabolite of ethyl alcohol formed in the body after ethanol exposure, reflects alcohol 
consumption over the previous 72 hours. The EtG cutoff (> 300ng/ml) will serve as a secondary 
outcome in analyses. 
Measures of Health-related Quality of Life (HRQoL). The EuroQoL-5 Dimensional-5 Level 
(EQ-5D-5L) is a standardized 5-item, 5-point Likert scale measure of health-related QoL 
(HRQoL). This reliable and valid measure comprises 5 dimensions: mobility, self-care, usual 
activities, pain/discomfort, and anxiety/depression.  
Measures of criminal justice and health-care system utilization. The Non-Study 
Resources Form documents resource utilization in cost-effectiveness research. It will assess 
participants’ use of non-study medical resources (e.g., medication and inpatient, outpatient, and 
emergency services) as well as non-medical resources (e.g., travel time to medical care). The 
HaRTC Cost Analysis Questionnaire comprises 9, yes/no and fill-in-the-blank questions 
assessing participant costs of attending the HaRTC sessions. The Criminal Justice Utilization 
Form comprises 8, yes/no and fill-in-the-blank questions assessing the extent of participants’ 
contact with the criminal justice system (jail, prison, arrests, probation). 
Participant satisfaction. The Participant Satisfaction Assessment is a semi-structured 
interview with open-ended questions and prompts to assess participants’ receipt of and 
satisfaction with HaRTC. The Participant Feedback Form features Likert-type items that 
document participants’ feedback on HaRTC. Both measures will be administered to HaRTC 
participants at the post-test session. 
 
Training of research staff 
Research ethics and integrity will be addressed in staff training and in weekly supervision. 
All research staff will complete human subjects and HIPAA training prior to data collection. 

PIs: Nelson, Collins 
HaRTC Phase 3 Protocol 
4 
 
Research staff, including bachelor-level research assistants and graduate students, will conduct 
assessment interviews under the weekly supervision of the Co-PIs, who are clinical 
psychologists, one with a current WA State license and nearly 25 years of experience 
conducting substance-use assessment and the other with 10 years of Native health research 
and assessment. An extensive training protocol developed during a prior evaluation will be 
utilized.7 Interviewers will receive 16 hours of training and supervision before they begin 
independently recruiting and assessing participants. Training will include training in cultural 
humility and Native health, written instructions (e.g., probe instructions, skip patterns, behavioral 
problem management) and mock interviews with feedback. Periodic interview observations by 
lead research staff will occur throughout Phase 3. Circle keepers will be identified and 
interviewed by HaRTC and SIHB Traditional Health Professionals and will be approved by the 
Community Advisory Board. They will identify as Indigenous, American Indian, and/or Alaska 
Native; have a background in Traditional Indian Medicine and/or chemical dependency 
counseling; have lived experience of substance use disorder; and have a working knowledge of 
and comfort with a harm-reduction orientation to substance-use treatment. Although they will be 
proficient and independent in their own practice, they will be introduced to the HaRTC protocol 
by SIHB Traditional Health Professionals, who will provide ongoing consultation as needed. 
 
Procedures 
Screening, information and recruitment. Flyers and brochure will be posted on Facebook 
and at SIHB and other service providers to Indigenous and Native people. Potential participants 
will contact study staff via phone or email. Research staff will screen participants to see if they 
fulfill study criteria (i.e., identify as Native and/or Indigenous, urban-dwelling and not on 
Tribal/Reservation land, >21 years old, ≥4 on AUDIT-C, technologically literate for use of video 
conferencing/text). If so, research staff will hold online informational sessions (lasting 
approximately 20 minutes) and baseline assessments with interested parties. During 
informational sessions, research staff will explain the study procedures, study participants’ rights 
and informed consent materials. The UBACC will be administered to assess capacity to provide 
informed consent. If they agree to participate, written informed consent will be obtained, and 
participants will be scheduled for a baseline visit and will be mailed a video-conferencing 
enabled smartphone (as needed) and at-home urine testing strips (i.e., 300 ng/ml one-step 
urine dipcards) to facilitate subsequent data collection and, as relevant, participation in the 
intervention. (Note: Participants will not be financially responsible for the smartphone in the case 
of its loss or damage, but only one replacement will be made available.) 

PIs: Nelson, Collins 
HaRTC Phase 3 Protocol 
5 
 
Baseline data collection sessions. At baseline sessions, which will last approximately 60 
minutes, participants will be administered the baseline measures, which will be recorded by 
research staff directly into REDCap. Then, they will dip the EtG dipcard in a urine sample cup 
they produced prior to the session into the provided specimen cup and show the results to staff, 
who will record the results in the same REDCap database (this will be the urine collection 
protocol throughout the study). Updated tracking/contact information will be collected and 
entered into a separate REDCap database. 
Randomization. Study group assignments will next be determined by permuted block 
randomization. After each participant completes the baseline assessment, the assessment 
interviewer will receive the participant assignment via REDCap and reveal the participant’s group 
assignment. Those randomized to HaRTC will be told the time and place of the first Circle in the 
next scheduled cycle and will be asked in the REDCap randomization section (not as data 
collection but for internal use): Would you like a medicine bundle sent to you? (y/n) Those 
randomized to the control group will be scheduled for the midpoint assessment, which is 
completed by all participants. 
Intervention conditions. HaRT-C participants will be scheduled for their first intervention 
session. (If this does not occur immediately following the assessment, participants must be 
scheduled within two weeks of the completion of their baseline assessment). Participants in the 
HaRTC group will be invited to attend 8, weekly, closed-group Circles. They will be provided 
with information and demonstrations in how to use Zoom. All participants will be assessed at 
baseline, midpoint (4 weeks), posttest (i.e., immediately after the course of 8 weekly HaRTC 
sessions or within same amount of time if in TAU group), and at 1-, 3-, and 6-month follow-ups. 
Prior to their first HaRTC, participants will be mailed a medicine bundle for personal use 
during the Circles as requested. HaRTC interventions will be led via videoconferencing (i.e., 
HIPAA-compliant Zoom connection) by Circle Keepers identified and trained by our partners at 
SIHB who are Traditional Health Professionals or who are recognized in their community as a 
Native health practitioner. They and will be hired as independent contractors at WSU or they will 
be SIHB employees. They will regularly attend CAB meetings and will undergo the same CITI and 
research ethics and confidentiality training and paperwork that WSU/UW research staff undergo 
prior to working with participants. 
We will deliver HaRTC in 8, weekly, closed-group sessions, according to the protocol 
collaboratively developed by SIHB Traditional Health Professionals and WSU/UW researchers 
(see Appendices). Although the circles have no official running length, they typically last 
approximately 2 hours each. Throughout the study period, both HaRTC and control participants 

PIs: Nelson, Collins 
HaRTC Phase 3 Protocol 
6 
 
will continue to have access to SIHB’s usual supportive services will continue to receive to 
services as usual at SIHB or wherever they receive services. No attempts will be made to limit 
participants’ access to community and clinical services during the study. Research staff will refer 
participants back to their clinical providers at SIHB, a fully licensed provider of medical, dental, 
mental health and substance-use treatment, or wherever they seek care in case the clinical need 
arises. Research staff will inform SIHB staff in case of a medical or mental health emergency. We 
can also refer participants to their local urban Indian health organization (UIHO; 
https://www.ncuih.org/UIHOs_locations), national crisis/suicide hotlines or emergency medical 
services, as appropriate.  
At each subsequent assessment, participants will connect with HaRTC staff using the Zoom 
app that is set up/they have set up on their smartphone devices. Prior to all appointments, 
reminder calls/texts/emails will be made to participants, and the assessment will be entered 
unto the participants’ REDCap calendar (which is also downloaded on the participants 
smartphone). Although HaRT-C participants will not be monetarily compensated for time in 
treatment sessions they attend, they will be offered a $40 incentive for attending all HaRT-C 
assessment sessions to facilitate complete in-session data collection.  
Control participants will follow the same schedule as HaRTC participants who were 
recruited during the same time period. Four weeks through each wave’s HaRTC administration 
(and corresponding timepoint for delayed HaRTC participants) participants will complete a mid-
point assessment.  At the posttest and the 1-, 3- and 6-month follow-ups, all participants will 
undergo the same procedures as at previous assessments. They will be paid $40 for attending 
each assessment. Control group participants will be informed that they will have the opportunity 
to participate in non-study, no-cost HaRTC after their 6-mo follow-up. 
 
Data Analysis Plan 
Preliminary Data Analysis. Project Leads and members of the Research Methods 
Core of NCARE will conduct analyses for Phase 3. We will use descriptive statistics and 
plots to examine all study variables for missing values, outliers, and compliance with 
distributional assumptions for planned analyses. Next, we will compare study completers and 
non-completers on drinking and sociodemographic variables to detect potential patterns in 
attrition and missing data. As necessary, we will conduct analyses to determine whether missing 
data can be considered “ignorable.” Research Methods Core staff will work with Project Leads 
to determine the most appropriate methods for addressing informative missing data. We will 

PIs: Nelson, Collins 
HaRTC Phase 3 Protocol 
7 
 
then use direct maximum likelihood estimation for our structural models. Finally, we will examine 
baseline data to detect possible group differences on the primary outcome variables. As 
necessary, we will control for baseline group differences by using covariates in the primary 
outcome analyses. 
 
Accounting for the Partially Nested Design. 
Participants who are in the HaRTC group but not 
the control group will be clustered or nested within 
Circles (cluster level). We expect correlations 
among the measured outcomes of HaRTC 
participants who attend the same Circles. Such 
correlations would violate the assumptions of 
independence required for appropriate estimation 
of standard error in some statistical tests. 
Appropriate data analytic strategies are thus 
needed to accommodate correlations among 
participants in the HaRTC group. Multilevel 
structural equation modeling is one strategy that 
can account for non-independence in one arm and model effects at different levels of data 
organization 
Analyses for RTC. A series of multilevel structural equation models will be fitted using 
Mplus 7.4127 to test the hypothesis that, compared to control participants, HaRTC participants 
will show significant improvements across outcomes over the short term (baseline to post-test) 
and longer term (baseline to 3- and 6-month follow-ups). Primary outcomes will include 
difference scores for alcohol (peak alcohol quantity, drinking frequency, alcohol-related harm, 
EtG, and QoL (general and HRQoL) outcomes.  
Analyses for Secondary Data. Economic analyses will follow well-established guidelines. 
led by Robert Rosenman, PhD, who is leading economic analyses for NCARE. The measures 
listed in the cost analysis section above will be used for these analyses. Next, a cost-benefit 
analysis will estimate the downstream savings and net benefit of HaRTC relative to control. This 
analysis will provide a measure of “true cost” to the payer of healthcare services for the 
observed time frame. Cost-effectiveness will be summarized by using the incremental cost-
effectiveness ratio (ICER), which is the incremental cost divided by the incremental effect of 
HaRTC relative to control. We will calculate ICERs with 2 types of effects. First, we will calculate 

PIs: Nelson, Collins 
HaRTC Phase 3 Protocol 
8 
 
the cost per QALY, which accounts for both the duration of a particular health state and the 
associated HRQoL. We will also calculate an ICER with the more field-specific and clinically 
meaningful effect of per-point reduction in alcohol problems as measured by the SIP. Analyses 
will be conducted from the perspectives of the Figure 3. The payer perspective is important 
because payers, such as health insurance companies, sustain treatment programs. The societal 
perspective is important because it also incorporates indirect costs (e.g., school and workplace 
productivity, criminal justice outcomes, patient travel time) that are relevant to patients and the 
general public. 
 Similar to the analyses for Specific Aim 2, we will use multilevel structural equation 
modeling to account for the partially nested design in predicting mean values for each resource 
category, per-point reductions in alcohol problems, and HRQoL preference weights at each time 
point. QALYs gained in the HaRTC group will be estimated by using the area under the curve 
methodology. The method of recycled predictions will be used to obtain the final predicted mean 
values for each study arm and resource, which will then be summed and tested from both the 
payer and societal perspectives. To account for sampling uncertainty in point estimates, the p 
values, standard errors, and confidence intervals for ICERs will be estimated by using 
nonparametric bootstrapping. Parameters obtained from bootstrapping will be used to estimate 
acceptability curves, which estimate the probability that HaRTC is a good value for different 
willingness-to-pay thresholds (e.g. cost per QALY). Sensitivity analyses will be conducted to 
assess precision in assumptions and parameter estimates.  
Secondary Mediation Analyses. If our primary analyses indicate a statistically significant 
HaRTC effect, we will conduct secondary analyses of AI/AN enculturation as a potential 
mechanism underlying improvements in alcohol and QoL outcomes. Such mediation analyses, 
however, require very large sample sizes to achieve the necessary power to detect statistically 
significant relationships. 
 Because it is impracticable to achieve an adequate sample size for mediation analyses in 
the proposed project, we will test mediation as an exploratory research question. In addition to 
their ability to accommodate data clustering at various levels, multilevel structural equation 
models allow for unbiased estimates of both individual- and cluster-level indirect effects. This 
makes multilevel structural equation modeling ideal for testing mediation. In our mediation 
model, intervention group (HaRTC versus control) will serve as a cluster-level predictor of 
outcome, and baseline-to-posttest change in AI/AN enculturation will serve as the mediator. To 
test mediation, we will follow procedures outlined by Lachowitz et al., which are essentially an 
adaptation of the product of coefficients method. First, we will constrain the cluster-level effect of 

PIs: Nelson, Collins 
HaRTC Phase 3 Protocol 
9 
 
the mediator on the outcome to be equal across HaRTC and control groups. Second, we will 
multiply the difference between the mediator means for the HaRTC and control groups by the 
effect of the mediator on the outcome. This parameter will provide an indirect, cluster-level 
effect for HaRTC on outcomes as mediated by change in AI/AN enculturation.