Comparing Interventions for Opioid Dependent Patients Presenting in Medical Emergency Departments
Phase: NA
Conditions: Opioid Dependence
Sponsor: NYU Langone Health

Protocol s15-00862
COMPARING INTERVENTIONS FOR OPIOID DEPENDENT PATIENTS PRESENTING IN MEDICAL EDs
Version June 26, 2017
Version 5.0
Principal Investigator
Michael P. Bogenschutz, M.D.
Professor, Department of Psychiatry
NYU School of Medicine
646-501-4026
Michael.Bogenschutz@nyumc.org
Co-investigator 
Ryan McCormack, M.D.
Assistant Professor, Department of Emergency Medicine
NYU School of Medicine
Collaborator*
Richard Rapp, Ph.D.
Assistant Professor, Department of Community Health
Wright State University
*Dr. Rapp is the principal developer of Strengths-Based Case Management.  He will provide 
training and ongoing supervision to the interventionists providing brief Strengths-Based Case 
Management to participants in this study, but will not directly perform any study-related 
procedures. 

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SPECIFIC AIMS
We propose to investigate the effects of a promising brief treatment model on treatment initiation and 
engagement, substance use outcomes, and broader health outcomes for opioid dependent patients seen in 
a medical emergency department (ED) who are not currently engaged in treatment. The study will compare 
the effects of brief strengths-based case management (SBCM) to the effects of screening, assessment and 
referral alone (SAR). Participants will be screened and assessed in the ED using procedures based closely 
on those used in our recently-completed NIDA Clinical Trials Network trial of brief interventions for drug 
users presenting in EDs. Participants who report three or more opioid dependence criteria on the DSM-IV 
checklist will be randomly assigned (150 per group) to receive 1) up to 6 sessions of SBCM based on the 
model previously implemented by Rapp et al. (2008); or 2) SAR. Follow-up assessments will be completed 
at 3 and 6 months, by staff that is blinded to treatment condition.
Aims of the study are:
1. To identify the main effects of SBCM in mobilizing initiation of addiction treatment and engagement 
in pharmacotherapy for opioid dependence (in primary care or specialty care settings).

Hypothesis 1: SBCM will result in higher rates of initiation and engagement than SAR.
2. To identify the main effects of SBCM in reducing substance use.

Hypothesis 2: SBCM will result in greater reductions in opioid use than SAR.
3. To identify the main effects of SBCM on broader measures of health and life functioning.

Hypothesis 3: SBCM will result in greater improvement in quality of life related to psychological, 
social, environmental, and physical health domains than SAR.
4. To examine the interactions between treatment assignment and selected participant attributes in 
predicting treatment initiation, pharmacotherapy engagement, and substance use outcomes.

Hypothesis 4: SBCM will have a larger effect on initiation and engagement in participants with 
lower environmental stability at baseline.
5. To examine effects of treatment involvement on substance use outcomes.

Hypothesis 5: Treatment initiation and pharmacotherapy engagement will significantly mediate 
the effects of study interventions on substance use outcomes, accounting for the main effects of 
treatment assignment on opioid use.

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RESEARCH STRATEGY
a. Significance
a.1. SUDs are highly prevalent among ED patients
High rates of psychoactive substance use have been found in EDs, with prevalences far exceeding community 
rates [1-3]. For example, one large US study reported estimates of current use among male and female ED 
patients of 21% and 13% for marijuana, 14% and 12% for opioids, and 4% and 10% for stimulants, 
respectively [2]. Among a group of 1,933 patients admitted into a hospital emergency department, 198 (10%) 
had a substance use disorder which contributed to the emergency department admission [3]. The prevalence 
of illicit drug use is substantially greater in EDs than in primary care settings [4]. Illicit drug use significantly 
complicates the initial diagnosis and medical management of the substance abusing patient [5]. Despite this, a 
relatively large percentage of such substance abusing patients are not referred to appropriate psychosocial 
services [1, 3]. The resources required to attend to these conditions places increased burden on the medical 
system, including considerable costs that are often not recovered [6]. As an example, individuals seen in EDs 
in Tennessee who were judged to have a substance use disorder (SUD) and for whom some form of treatment 
would be appropriate were much more likely to require hospitalization and had higher rates of previous ED 
utilization than those not having a SUD, accounting for an estimated US $777.2 million in extra hospital 
charges in 2000 dollars [1]. 
a.2. ED interventions for SUDs
In response to the impact and cost, both to individuals and health care delivery systems, there has been an 
increased focus on developing, implementing, and evaluating methods to identify and provide appropriate 
services to individuals having problematic substance use who are seen in EDs [1, 2, 6-12]. With regard to 
alcohol use disorders, several efficacy and effectiveness trials in ED settings have demonstrated that 
screening, brief interventions, and/or referral to specialized substance abuse treatment for those with alcohol 
use disorders and alcohol related problems can contribute to both subsequent reductions in alcohol 
consumption [13-18] and alcohol-related consequences [17, 19, 20]. However, other well-designed studies did 
not find significant intervention effects [21-25]. A 2008 meta-analysis reported that brief interventions reduced 
subsequent alcohol-related injury (OR = .59), but did not find a significant effect on drinking [26]. Another 
recent review focusing on brief alcohol interventions for injury patients in the ED noted that more intensive 
interventions tended to yield more favorable results, and that the heterogeneity of populations and 
interventions among these studies limit the strength of the conclusions that can be drawn [27]. 
Considerably less is known about the best methods of identifying and intervening with individuals using 
illicit drugs or abusing prescription medications. As opposed to dealing with hazardous or harmful drinking in 
ED settings, the evidence of the effectiveness of such interventions has been considered only suggestive for 
drug use disorders [11] and there has been a call for further research on the efficacy of screening and brief 
interventions for drug use, as well as the need to test the effectiveness of such interventions in real world 
settings [12]. In general, brief motivational interventions appear to be somewhat less effective with drug 
abusers than with alcohol-involved individuals with respect to engaging them into treatment [28, 29] or 
modifying their drug use [30-32]; what positive effects are obtained tend to deteriorate over time [33]. 
Among the CSAT-funded SBIRT sites [10], Washington State chose to implement its SBIRT program in 
EDs [34]. From its inception in 2003 through July 3, 2008, a total of 89,901 patients had received services 
through the 9 emergency departments participating in the WASBIRT project. Of these, 23.4% (21,074) 
screened positive and received an intervention and/or additional services for substance use. Over 2,000 
patients, identified as either high or moderate drug use risk based on their screening scores, received either 
brief intervention or brief intervention followed by brief therapy or chemical dependency treatment, and were 
followed up at 6 months. Average days of drug use declined from 13.7 in the 30 days prior to the baseline 
assessment in the ED to 6.5 days in the 30 days prior to the 6-month follow-up. While a significant reduction in 
drug use was found in both high and moderate risk groups, the greatest reduction was seen in the high risk 
group, with more intensive treatment among the high-risk users associated with greater change. In addition to 
changes in substance use, Medicaid costs were reduced by $366 per member per month, and inpatient days 
were significantly reduced [35].
In spite of these encouraging results, randomized trials are necessary to draw inferences with 
confidence. Findings from a randomized trial of adolescent and young adult marijuana users in a pediatric ED 

4
indicated that a brief intervention plus booster session resulted in higher rates of marijuana abstinence and 
reduced consumption compared to the assessment control condition [36]. We recently completed a multi-site 
trial (N = 1285) of an SBIRT intervention for drug users presenting in EDs through the NIDA CTN (CTN 
Protocol 0047) which was the first large randomized trial of an SBIRT intervention focused on adult drug users 
in EDs. Methods and rationale for this study have been described [37]. Briefly, the study included three 
conditions. The first control group received minimal screening only. A second group received much more 
intensive assessment and, if they met criteria for probable substance dependence, a referral to treatment. This 
group served as both an attention control and a minimal intervention. The third group received an intervention 
consisting of a 30 minute motivational enhancement therapy session conducted in the ED, followed by two 
telephone “booster” sessions of approximately 20 minutes. This 3-session intervention, an abbreviated form of 
Motivational Enhancement Therapy, could be considered either a very robust brief intervention or a very brief 
treatment. In spite of robust implementation of the interventions and excellent follow-up rates, no meaningful 
significant differences in outcome were found among the three treatment groups [38]. Furthermore, no 
significant treatment effects were found for clinically meaningful sub-groups defined by primary drug of abuse 
(cannabis, opioids, or cocaine), gender, ethnicity, or severity. These findings, combined with negative findings 
from recent large-scale trials of brief interventions for drug users conducted in primary care settings [39, 40], 
indicate that more intensive interventions may be required to benefit individuals with serious drug use 
disorders.
a.3. The treatment needs of opioid dependent patients are not met by brief interventions
Opioid dependence is a major public health problem which has grown due to the persistent elevation in 
prescription opioid misuse in the past decade [41, 42]. It seems clear that patients with moderate to severe 
opioid use disorder, a disorder which is severe and often chronic, are likely to benefit from more intensive 
treatment. Opioid dependence is different from other drug use disorders in that highly effective 
pharmacotherapies exist. Decades of research support the efficacy of methadone and other full agonists [43, 
44]. Buprenorphine is well established as an effective partial agonist treatment [45, 46], and may be prescribed 
effectively in primary care settings [47, 48]. Both also reduce overdose deaths in comparison to drug-free 
treatment [49-51]. Although naltrexone in pill form has had only a small impact on treatment of opioid 
dependence, the depot formulation has been approved by the FDA for treatment of opioid dependence, and is 
another effective option that may be prescribed in medical settings [52, 53].
Brief interventions have limited effectiveness in getting drug dependent people to treatment. In an 
inner-city population of heroin and cocaine addicts receiving primary care, Bernstein et al. reported extremely 
low rates of addiction treatment involvement other than detoxification following brief intervention [54]. In an 
analysis of data from the SAMHSA-funded WASBIRT project in Washington State, Krupski et al. reported that 
patients receiving a brief intervention were somewhat more likely to engage in addiction treatment than 
propensity score-matched controls [55]. Overall, 33.8% of those receiving BI engaged in SUD treatment 
compared to 22.5% of controls. The effect of BI was less pronounced among those who had received prior 
SUD treatment. In a sample of substance users seeking treatment through a centralized intake unit, a single 
session intervention based on motivational interviewing did not significantly increase rates of linkage to 
treatment over standard of care (44.7% vs. 38.7%) [56]. One attractive alternative approach is to initiate 
buprenorphine treatment in the ED [57] (Currently being evaluated in R01DA025991, D’Onofrio PI ). However, 
this requires both acceptance of this responsibility by the ED, and immediate access to follow-up outside of the 
ED. These conditions appear to limit the applicability of this model outside of academic settings. 
a.4. Case Management is an effective method of linking dependent patients to definitive treatment
Case management has repeatedly been shown to be effective in improving treatment linkage and retention for 
substance abusers. Controlled trials of case management have included diverse substance abuse populations 
and settings, demonstrating improved linkage and retention among injection drug users and methadone 
maintenance programs [58-60], crack cocaine users and centralized intake units [56, 61], female welfare 
recipients [62], homeless substance abusers [63], dually diagnosed substance abusers [64], and crack cocaine 
users in aftercare treatment [65, 66]. In a large retrospective cohort study (N = 7,776) case managed clients 
were more likely to enter some form of on-going treatment following detoxification than non-case managed 
clients [67]. A recent meta-analysis co-authored by Collaborator Richard Rapp examined the case 
management literature relative to substance abusing populations and identified a mean effect size of d = .42 

5
for linkage outcomes [68]. The effectiveness of case management in improving linkage and retention predicted 
improvements in outcomes such as reduced drug use and legal severity [65, 66].
SBCM, the case management model we propose to use (described in detail in Section c.8.2), has a 
particularly strong evidence base in populations relevant to the proposed trial. Both long-term and brief 
adaptations of SBCM have improved linkage and retention rates in a general population of substance abusers 
[69], opioid dependent drug users entering agonist treatment programs [59], and crack cocaine users 
participating in aftercare treatment [65, 66] and linking with substance abuse treatment [56]. In a study 
involving 678 patients with substance use disorders (68% cocaine or heroin) presenting at a centralized intake 
unit, those randomly assigned to 5 sessions of SBCM were more likely to link to treatment than those receiving 
motivational interviewing (55.0% vs. 44.7%, p<.05) or standard-of-care referral (55.0% vs. 38.7%, p<.01) 
[56].The brief model of SBCM also demonstrated positive outcomes in a multi-site CDC clinical trial in which 
five session SBCM was used to improve linkage with care among newly diagnosed HIV positive individuals 
[70]. Those receiving SBCM were significantly more likely than those who received passive referral to have 
had at least one HIV primary care visit in each of 2 consecutive 6-month follow-up periods. The sites from this 
controlled trial also participated in a follow-up implementation study to determine whether the model would be 
as effective when implemented by community HIV/AIDS organizations as it was in a closely monitored clinical 
trial [71]. The linkage rate across the ten sites was 79%, matching that of the controlled trial.
b. Innovation
As addiction treatment becomes increasingly integrated into the medical care system [72, 73], two models 
have rightly received a great deal of attention. The first is the use of SBIRT models to identify cases, provide 
therapeutic contact, and refer the more severe cases to longer-term care [9, 11, 74]. The second is the 
treatment of addictions using medical models of care, including those that can be implemented in primary care 
settings. Prime examples of the latter are buprenorphine [47, 75-78] and pharmacotherapies for alcohol 
dependence [79-82]. However, much less attention has been paid to optimizing strategies for bridging the gap 
between SBIRT and more intensive/longer-term treatment for those with more severe substance use disorders. 
This factor is of critical importance for opioid dependent patients, whose needs are not met by brief 
interventions or brief treatment, and for whom pharmacotherapy is often indicated. 
Emergency room interventions for substance use disorders have been largely limited to brief 
interventions/SBIRT models, and these have focused primarily on alcohol. Although there is a substantial 
literature documenting the value of case management in linking drug users to treatment, this approach has not 
been applied to drug users in the ED setting. The proposed study will be the first to use a case management 
approach to link drug dependent patients presenting in EDs to longer-term addiction treatment. It will be one of 
the first trials focusing specifically on opioid dependent patients in medical EDs. A further innovative feature is 
that the case management approach will emphasize linkage to pharmacotherapy, facilitating linkage to office-
based buprenorphine, methadone, or naltrexone for patients who desire these treatments. 
c. Approach
c.1. Overview
We propose a 2-group design in which ED patients meeting criteria for opioid dependence are randomly 
assigned to receive up to 6 sessions of SBCM based on that used in prior trials [56, 70]; or Screening, 
Assessment, and Referral (SAR) without any on-site treatment.   The initial SBCM session will take place as 
soon as possible following the participant’s random assignment to the SBCM condition. If possible, this session 
will be completed before the participant leaves the ED, where patients have been successfully recruited for the 
now closed study: Screening, Motivational Assessment, Referral and Treatment in Emergency Departments 
(SMART-ED) (PI: Ryan McCormack, #i11-00298). Subsequent SBCM sessions will be conducted in the 
community or at Bellevue Hospital Center. Screening and assessment procedures will be similar to those used 
in the SMART-ED trial.
c.2. Participants 
Participants will be adult men and women presenting for medical treatment in the ED. 
c.2.1. Inclusion Criteria: 1) Registration as patient in the ED during study screening hours; 2)  Endorsement 
of three or more opioid dependence criteria by self-report on the DSM-IV checklist; 3) Age 18 years or older; 4) 
Adequate English proficiency; 5) Ability to provide informed consent; 6) Self-report use of opioids in last 30 
days.

6
c.2.2. Exclusion Criteria: 1) Inability to participate due to emergency treatment; 2) Significant impairment of 
cognition or judgment rendering the person incapable of informed consent. (e.g., traumatic brain injury, 
delirium, intoxication); 3) Status as a prisoner or in police custody at the time of screening; 4) Current 
engagement in substance use disorder treatment; 5) Inability to provide sufficient contact information (must 
provide at least 2 reliable locators); 6) Unavailable for follow-up (e.g., planning to relocate within 6 months); 7) 
Prior participation in the current study; 8) Current participation in a research study related to substance use.
c.2.3. Vulnerable Populations: Children will not be enrolled in the study. Pregnant women will be allowed to 
participate in the study. Because the interventions in this study are purely psychosocial (i.e., no medications 
are administered), the risks and benefits to pregnant women are not significantly different from those of other 
participants, so there is no justification for excluding them.  No inducements, monetary or otherwise, will be 
offered to terminate a pregnancy.  Individuals engaged in the research will have no part in any decisions as to 
the timing, method, or procedures used to terminate the pregnancy.  Individuals engaged in the research will 
have no part in determining the viability of a neonate.
Prisoners will not be enrolled in the study. If a subject becomes incarcerated during the study, the 
individual may remain in the study and treatment and follow-up procedures may be continued in accordance 
with IRB and OHRP approvals. It is expected that approximately 10% of randomized participants will become 
incarcerated during the six months of their study participation. It is ethically problematic to exclude the 
vulnerable population since they have an even greater need for effective linkage to treatment than those 
without criminal justice involvement. It deprives this significant group of opioid addicted patients of possible 
benefits from evidence that this intervention could help them. Additionally, excluding prisoners compromises 
the scientific integrity of the study by causing a significant decrease in the follow-up rate. Based on other 
studies in similar populations, the overall follow up rate would be about 85% including prisoners, so without 
prisoners, closer to 75%. It's particularly problematic because the cases won't be missing at random. 
Allowance to extend the study intervention and substance use assessments to this population allows for 
continued engagement with treatment-focused research and continuity of case management. Participants in 
the SAR treatment group who become incarcerated will continue to participate in study activities which are 
considered to be above treatment-as-usual, including substance use assessments and referral to treatment. 
Consequences of discontinuation for SAR participants includes loss of these activities and information to which 
they would be otherwise entitled, all of which are considered to be beneficial to study participants.  Participants 
in the SBCM treatment group who become incarcerated will participate in the same study activities as SAR 
participants and additionally engage in time-limited case management sessions. Consequences of 
discontinuation due to incarceration for participants in the SBCM group include loss of assessment, planning, 
linking, monitoring and advocacy provided by the case manager.  Local standard operating procedures for the 
collection of prisoner data will be approved by the IRB.  Data may be collected either in person, by phone, or in 
writing, provided that data collection follows the procedures approved by OHRP and the IRB. The research 
team will not share details of the nature of the research with staff at the jail/prison, or with parole or probation 
officers. Visits, whether in person or by phone, will only be conducted if the participant’s confidentiality can be 
maintained and no audio-taping occurs.  Incarcerated participants will be clearly informed in advance that 
participation in the research will have no effect on their probation or parole, nor will it confer any advantages or 
amenities beyond the potential benefits stated at the time of informed consent. Any possible advantages 
accruing to prisoners through participation in the research—when compared to the general living conditions, medical 
care, quality of food, amenities and opportunity for earnings in the jail/prison—are not of sufficient magnitude as to 
impair prisoners’ ability to weigh the risks of the research against the value of such advantages in the limited choice 
environment of the prison.
c.3. Recruitment and screening 
c.3.1. Recruitment. Participants will be recruited from the Bellevue Hospital Center ED, a large, urban, public-
sector ED. The recruitment target for the proposed study is 2 participants per week. 
c.3.2. Screening. Potential participants will be identified in two ways: 

Method 1) Patients with known opioid use will be referred to the study team by clinical ED staff. 
As part of an ongoing clinical (non-research) SBIRT program taking place in the Bellevue ED, ED 
staff screen and assess ED patients for unhealthy tobacco, alcohol, and drug use. ED staff will 
introduce patients who report illicit or non-medical use of opioids in the past year to study staff. 
Study RAs will then complete screening procedures (detailed below) with referred patients. This 
referral arrangement allows the ED staff to make the initial determination that the patient is 

7
appropriate for potential study inclusion with regard to patient’s medical stability and capacity to 
provide informed consent. 

Method 2) Study staff will introduce themselves to ED staff and inquire about patients who may 
be eligible to participate in the study. Study staff may approach ED patients directly only after ED 
staff has provided permission to do so.  
The study RA will then request the patient’s verbal consent, to complete the prescreen research assessment 
using an IRB-approved verbal consent script. After the patient has provided verbal (not signed) consent, the 
RA will collect anonymous information including English proficiency, age, gender, reason for ED visit, triage 
acuity level, non-prisoner status, days of opioid use in the past 30 days, and availability for treatment (See form 
entitled “Brief Information Tool”) in order to determine potential eligibility and to collect data on 
representativeness of the study sample. These data will be collected by interviewing the patient, except for the 
triage level and reason for ED visit, which will be obtained from the “white board” (a patient tracking system 
which is visible to all staff working in the ED). 
The RA will then administer the DSM-IV Checklist. Patients who meet DSM-IV criteria (endorsement of 
three or more opioid dependence criteria) will be further screened for eligibility using the Screening Instrument 
Secondary Screening Form. This form will provide a complete review of eligibility criteria. Those who are 
interested and eligible will then undergo the written informed consent process described in the Protection of 
Human Subjects section. Patients who screen out of the study will receive no further study intervention, but   
will receive the standard clinical intervention by ED staff as well as any patient education materials that are 
typically distributed after screening. Anonymous screening data will be kept to allow description of those who 
do not qualify. This is necessary to assess the representativeness of the included sample, and required by high 
quality medical journals.  
Screening data will be collected by research personnel using direct entry into tablet computers to 
facilitate rapid screening, electronic data capture, and mobility within the busy ED setting. Refusals and 
inability to participate (e.g., unavailable due to emergency medical treatment, left without being seen) will be 
recorded. Study staff will time their intervention to minimize interference with medical treatment. Patients who 
show signs of intoxication (e.g., somnolence, slurring of speech) will not be screened unless and until these 
signs resolve.
c.4. Baseline Assessment 
The baseline assessment for this trial will be kept considerably briefer than those traditionally used in addiction 
treatment trials. There are both methodological and practical reasons for this. It is important to keep the 
assessment battery brief in order to minimize assessment reactivity that can obscure treatment effects [83-87]. 
This is of particular concern for trials in which the dose of treatment is relatively small. The practical issue is 
that extensive assessments are likely to interfere with the rapid pace of clinical treatment in the ED setting. A 
cumbersome assessment process is also likely to impede the successful completion of the study through an 
adverse effect on recruitment and on the quality of the relationship between study staff and clinical ED staff. 
The baseline assessment will include an abbreviated Form-90 interview (described below) as the primary 
baseline measure of substance use. All consenting participants will also complete a demographic 
questionnaire, provide locator information, and provide a urine sample which will provide an objective measure 
of substance use, as well as the TCU-TMA, BTI, SIP-D, and WHOQoL Bref forms described in section c.10 
below.  None of the baseline assessments are clinical assessments.  All study personnel will be trained in the 
administration of the assessments via formal protocol training.  A Training Documentation Form, endorsed by 
the study’s Principal Investigator, will certify the research team member’s competence to complete the 
measures. The total time burden for the baseline assessment is approximately 100 minutes, comparable to 
that of the SMART-ED study (approximately 90 minutes). Participants who sign informed consent, complete 
the baseline assessment and meet all inclusion and exclusion criteria will proceed to randomization. 
c.5. Randomization
Eligible participants will be randomly assigned in 1:1 ratio to (1) screening plus assessment and referral (SAR), 
(2) up to 6 sessions of strengths-based case management (SBCM). Randomization will follow a randomly 
permuted block randomization schedule set up within REDCap prior to beginning the trial, and allocation for 
each participant will be revealed only at the point of randomization. The RA will use a Randomization Form to 
document eligibility, treatment assignment, if randomized and, if not, the reason an eligible participant was not 
randomized. Once eligibility has been established, randomization will be performed and documented by 

8
pushing the “Randomize” button on the Randomization form. There are a number of possible pre-treatment 
predictors of treatment engagement and opioid use outcomes, including age, gender, treatment history, 
addiction severity, psychosocial instability (e.g., housing), psychiatric comorbidity, and co-occurring other drug 
and alcohol use [88-91]. Studies are not consistent as to which factors are predictive, and existing studies may 
or may not be relevant to ED patients receiving SBCM.  Therefore, randomization will not be stratified.
c.6. Follow-Up
Follow-up assessments will be conducted at 3 and 6 months post randomization. Different RAs will be used to 
complete baseline and follow-up assessments, in order to maintain blinded follow-up assessment. If possible, 
follow-up will be conducted in person at Bellevue Hospital Center. If necessary, follow-ups may be completed 
in the community. If in-person follow-up is not possible, follow-up visits may be conducted by phone. 
Substance use measures (Barriers to Treatment, Short Inventory of Problems, TCU Treatment Motivation 
Scales, The World Health Organization Quality of Life [WHOQoL Bref], Form 90-D,  and Urine Drug Screen, 
and objective verification of pharmacotherapy through the New York Prescription Drug Monitoring Program and 
methadone programs where participants report receiving treatment) similar to those of the baseline 
assessment will be completed at follow-up, and comprehensive treatment utilization data will be collected using 
the Form 90-D. None of the follow up assessments are clinical assessments.  All study personnel will be 
trained in the administration of the assessments via formal protocol training.  A Training Documentation Form, 
endorsed by the study’s Principal Investigator, will certify the research team member’s competence to 
complete the measures.  If a participant comes in for his or her 6-month follow-up and he or she has missed 
the 3-month follow-up, the RA will reconstruct the Form 90-D for the first 3-month period and complete all 6-
month follow-up assessment items.  
c.7. Blinding
As in almost all psychosocial treatment protocols, study participants will not be blinded. However, RAs will be 
blinded to treatment condition at follow-up. At the beginning of the follow-up interview, the RAs will read a brief 
script that informs the participant that they should not reveal their treatment assignment. 
c.8. Interventions
c.8.1. Screening, Assessment and Referral. Following randomization, participants in the SAR condition will 
be provided with minimal scripted feedback to let them know that their assessment indicates substance 
dependence, and given a recommendation to seek treatment. The RA will provide these participants with an 
information sheet listing treatment (including both specialty treatment centers and primary care clinics that 
provide buprenorphine) and self-help resources in their community. The referral sheet includes names, 
addresses, and phone numbers of local addiction treatment agencies. Because the Bellevue Hospital Center 
ED does not currently screen or refer systematically, the SAR condition represents a level of care significantly 
higher than “treatment as usual.” Participants will also receive an informational pamphlet about drug use and 
its consequences, addiction, and treatment, as used in the SMART-ED study. 
c.8.2. Brief Strength-Based Case Management. The structure of SBCM follows the widely accepted 
functions of case management—assessment, planning, linking, monitoring and advocacy [92, 93]—and the 
theory-driven gestalt of the strengths perspective [94]. Strengths-based principles include an emphasis on 
client strengths, teaching clients a method for setting and completing goals, and development of a strong 
working alliance [94, 95]. The emphasis on client strengths is based on the work of Bandura who found that 
individuals are most likely to repeat successful behaviors if they can find precedent for those behaviors in their 
own experiences [96-98]. The importance of relationship development, or working alliance, has repeatedly 
been identified as one of the most crucial elements of client success, both in therapy and case management 
relationships [99-101]. The importance of client-driven goal setting was established in earlier clinical trials of 
SBCM [94, 95, 102]. SBCM addresses barriers in four broad areas—logistical, coordinative, individually and 
socially mediated—articulated by Messeri in a study of linkage to medical care [103]. Case managers are 
expected to be intimately familiar with community resources, including substance abuse treatment, housing 
services, medical clinics, job banks, etc., in order to help inform client’s selections of services. Additionally, 
case managers will provide resources to participants such as program brochures, printed applications for 
social services and informational pamphlets, etc., to help facilitate linkage with care. When logistical difficulties 
such as transportation, childcare and identification are present, case managers make transportation 
arrangements or provide transportation themselves. 

9
The six case management sessions for the proposed trial are based on those described in manuals 
developed by Dr. Rapp for two clinical trials, one supported by NIDA [56] and another by the CDC [70]. Each 
session is guided by specific objectives that promote linkage with and retention in substance abuse treatment, 
particularly pharmacotherapy for opioid dependence in a specialty or primary care setting. Objectives from the 
earlier trials will be adapted to fit the specific context of this trial, linking with and staying in treatment following 
an ED visit. Initiation of the relationship between client and case manager begins immediately following 
random assignment and termination takes place when either (1) six sessions have occurred; (2) ninety days 
have elapsed; or (3) clients discontinue involvement.
Session One. The first session will take place as soon as possible following patient’s random 
assignment to the SBCM condition. If possible, this session will be completed before the participant leaves the 
ED. The primary goal of session one is to begin development of a relationship between case manager and 
client. The following objectives guide the initial one-half hour session: discussion of services available with 
SBCM, discussion of the events preceding the emergency department visit, initial identification of strengths, 
assets and abilities, identifying the client’s opinion about going to substance abuse treatment and making plans 
for linkage to treatment (if the client has already decided to pursue substance abuse treatment) or a next 
meeting with the case manager (if the client has not yet decided to enter treatment). Whether the client is 
linking with treatment or working on other goals case managers will utilize the Linkage and Personal Goals 
Roadmap. The Roadmap will provide a structure for writing objectives in specific, measurable terms and 
identifying the strategies that will need to be implemented to accomplish objectives. 
Session Two. If the client has already linked with care the case manager will engage him/her in a 
discussion of early treatment experiences and actual or potential barriers to continuing retention. Together the 
client and case manager will develop a plan for addressing these barriers. Clients who have not yet linked with 
care will continue to work with the case manager on the objectives that were formulated during the first 
session. Case managers will integrate discussions about linking into the session, helping clients to identify the 
way in which substance use interferes with clients’ plans. Identification of client strengths enhances the case 
manager relationship with the client and increases clients’ sense of self-efficacy in accomplishing their goals.
Sessions Three - Five. These three sessions will follow objectives similar to the first two sessions. For 
clients already linked with care the continuing emphasis will be on identifying potential barriers to continued 
retention and making plans to mitigate those barriers before they actually occur. Efforts will often involve 
reducing tangible barriers to treatment such as transportation, scheduling, or intake procedures. Other barriers 
may become apparent during this time, such as lack of family or social support or a need to preserve 
confidentiality. If linkage to treatment has not yet occurred, the case manager will continue to help the client to 
consider their immediate needs and possible barriers to linkage. Throughout these sessions the case manager 
will remind the client of the limited number of sessions that they have remaining to work together. This is done 
as part of the disengagement process and to encourage the client to make best use of the time remaining, 
hopefully by linking with addiction treatment in a specialty or primary care setting.
Session Six (Final session). During this meeting the client and case manager will finalize the 
disengagement process. For linked clients, this includes a review of the barriers overcome, a reinforcement of 
the client’s strengths and self-identified rationale for linking to medical care, and a review of the plan for 
continuing in care. Clients who have not linked to care will also benefit from a review of their progress in 
transitioning to the community and a reiteration of the benefits of eventual linkage to treatment. At this time the 
case manager and client will develop a provisional outline for how to link to care if the client subsequently 
elects to seek treatment.
c.9. Assessment schedule. The selected assessment battery attempts to balance the value of 
comprehensive data against the costs of data collection in terms of staff time, feasibility of completion in the 
ED, financial cost, and assessment reactivity. Therefore, assessments have been limited to those that 
contribute directly to the objectives of the study. Estimated times for the baseline, 3-month, and 6-month 
assessments are 100 min., 80 min., and 80 min., respectively.
Table 1.  Assessment Schedule*
Procedure / Measure
Baseline
3-M follow up
6-M follow up
Form 90-D
X
X
X
Demographics
X

10
Locator form
X
X
X
Urine drug screen (UDS)
X
X
X
Texas Christian University – Treatment 
Motivation Assessment (TCU-TMA)
X
X
X
Barriers to Treatment (BTI)
X
X
X
WHO Quality of Life-BREF (WHOQoL Bref)
X
X
X
Short Inventory of Problems (SIP)
X
X
X
Assessment of AEs & SAEs
(if spontaneously reported)
X
X
X
*Working Alliance Inventory-Short Version (WAI-SR) is completed immediately after the first SBCM session for 
participants assigned to SBCM.
c.10. Measures
c.10.1. Screening instrument. The logistics of screening in the ED require that the screening process be 
relatively brief.  The screening instrument includes the Brief Information Tool (BIT), the DSM-IV Checklist and 
the Screening Instrument Secondary Screening Form. The BIT will collect anonymous information including 
English proficiency, age, gender, reason for ED visit, triage acuity level, non-prisoner status, and availability for 
treatment. The Screening Instrument Secondary Screening Form will provide a complete review of eligibility 
criteria prior to the informed consent.  
c.10.2. DSM-IV substance use disorder criteria. Substance use disorder criteria will be queried by self-report 
using the DSM-IV [112] checklist used in several past NIDA CTN trials involving patients with opioid 
dependence with or without co-occurring stimulant dependence [113-115]. A recent secondary analysis in a 
sample of 383 stimulant-using methadone maintenance patients demonstrated that all symptoms assessed in 
this manner had moderate to high discrimination of drug use severity, and that the internal consistency of item 
sets for both opioid dependence and cocaine dependence was high (Cronbach’s alphas > 0.8), supporting the 
use of this methodology in settings where efficiency and ease of administration is critical [116]. 
c.10.3. Form 90-D: Substance use and treatment participation. The Form 90, originally developed for 
Project MATCH, provides reliable measures of drug and alcohol use, treatment, and general functioning [117-
119]. For the proposed study we will use the Form 90-D, a version of the Form 90 which has been modified to 
assess for all substances rather than focusing on alcohol. The Form 90-D incorporates time-line follow-back 
procedures [120, 121] using a calendar-based interview which yields a continuous daily record of use of each 
category of illicit drug. For each substance, each day of use is categorized as light, medium, or heavy use, and 
mode of administration (e.g., IV use) is recorded. Test-retest reliability for current (past 90 days) substance use 
is very good [119, 122], and concurrence with urine drug screen data is good [119]. Three modifications will be 
made to the standard Form 90-D. First, as in the SMART-ED study the baseline assessment the period of 
assessment will be limited to 30 days. Second, the actual dates of counseling and pharmacotherapy will be 
recorded on the calendar, to allow temporal ordering of treatment activities and substance use, necessary for 
Aim 5. Third, separate items will be created for methadone, buprenorphine, oral naltrexone, depot naltrexone, 
and overdose reversal kits containing naloxone, and the form will capture setting of all addiction treatment 
services received (specialty vs. primary care). It is estimated that the Form 90-D assessment will take 
approximately 30 minutes to complete at baseline (30 day assessment period) and approximately 45 minutes 
at follow-up (approximately 90 day assessment period). 
c.10.4. Urine drug screens. As an objective measure of opioid use, a temperature-monitored urine sample 
will be obtained at baseline, the 3-month follow-up visit and the 6-month follow-up visit, and tested on site 
using an immunoassay for opiates, cocaine, oxycodone, methadone, propoxyphene, as well as 
methamphetamine, 
amphetamine, 
benzodiazepines, 
buprenorphine, 
MDMA, 
phencyclidine, 
tricyclic 
antidepressants, and cannabinoids. While we considered more frequent urine drug screening, we propose to 
defer all outcome assessments until the 3-month follow-up, as done in the SMART-ED study, in order to 
minimize the effects of contact, particularly in the SAR group, prior to the primary outcome assessment at 3 
months. These data will not be included in subjects’ medical records.
c.10.5. Objective verification of pharmacotherapy received. In order to verify self-reported use of 
medications for opioid dependence, two sources of information will be used. First, we will obtain dosing 
information from methadone and buprenorphine programs where participants report they have been treated. 

11
Second, the New York Prescription Drug Monitoring Program will be accessed to identify all opioid 
prescriptions that participants fill during the follow-up period. While this does not prove that the participant 
actually took the medication prescribed, it allows verification of self-report. 
c.10.6. Session Record Forms. Session Record Forms will be completed for each SBCM session and will 
capture basic information about each session. These forms will include session date, time, whether the session 
was interrupted, case management functions performed and whether a referral to treatment was made.
c.10.7. Non-Study Treatment Form (NTF). The NTF will be completed by RAs at approximately 1 month after 
the patient’s admission to the ED using chart review. This form will track ED discharge diagnoses, whether the 
patient was admitted to the hospital and length of stay, whether the patient received any additional substance-
related interventions during their ED visit, and whether the patient was discharged with any substance use 
medications (e.g., withdrawal medications).
c.10.8. Assessment of Motivation: The TCU-TMA. Several well-established scales exist for the assessment 
of motivation in substance abuse populations, including the SOCRATES [123], the URICA [124], the TREAT 
[125], the Readiness to Change Questionnaire [126], and the Texas Christian University-Treatment Motivation 
Assessment (TCU-TMA) [127], derived from the CMRS treatment motivation instrument [128]. The TCU-TMA 
was used in an earlier NIDA clinical trial of SBCM (Dr. Rapp, PI) [56] because of its widespread use in relevant 
populations including methadone maintenance patients [127, 129], probationers [130], patients in residential 
treatment [131], and cocaine abusers [132]; and its prediction of session attendance and treatment 
engagement in prior studies [129, 131, 133]. Analysis of TCU-TMA data from a pre-linkage population 
demonstrated that the factor structure was different than that of post-linkage populations [134, 135] . Twenty of 
the original 23 items from the TCU-TMA provided the best fit to the data, with factors: Problem Recognition 
(alpha = 0.90), Desire for Change (alpha = 0.57), Treatment Readiness (alpha = 0.82), and Treatment 
Reluctance (alpha = 0.69) [135]. The TCU-TMA will be administered at baseline, 3, and 6 months. 
c.10.9. Working Alliance Inventory – Short Version (WAI). The 12-item Working Alliance Inventory (WAI-
SR) [136] is a self-report measure based on Bordin’s [137] formulation of working alliance. The WAI-SR 
comprises 12 Likert-scaled items that assess the extent to which the individual experiences the therapist and 
therapy as helpful. Similar to the original 36-item WAI, the WAI-SR consists of three subscales: the Goal 
subscale addresses the extent to which therapy goals are important, mutual, and capable of being 
accomplished; the Task subscale focuses on the participant’s agreement about the steps taken to help 
improve the client’s situation; and the Bond subscale measures mutual liking and attachment. A psychometric 
evaluation of the WAI-SR [136] indicated that the instrument demonstrated adequate factor structure, 
differentiated between Goal, Task, and Bond alliance dimensions, and correlated well with other alliance 
measures. Tracey and Kokotovic [138] reported strong internal consistency (Cronbach’s alpha = .98) of the 
WAI-SR. The WAI-SR will be completed following initial SBCM session. 
c.10.10. Barriers to Treatment Inventory (BTI). Participants will complete the 25-item Barriers to Treatment 
Inventory [139] at baseline and at 3-month follow-up. This Likert-scaled questionnaire has seven internally 
consistent subscales relating to Absence of Problem, Negative Social Support, Fear of Treatment, Privacy 
Concerns, Time Conflict, Poor Treatment Availability, and Admission Difficulty. It may be used to identify 
perceived barriers regardless of whether the individual has sought or engaged in treatment. We will add three 
items to this scale related to child-care, child custody, and child protective services involvement. The BTI has 
demonstrated validity across gender, ethnicity, and age [140, 141]. 
c.10.11. Locator Questionnaire. An electronic locator form, including home address, will be completed at 
baseline and updated at the 3- and 6- month follow-up visits and in-between visits, if new locator information is 
obtained. Data collected on the Locator Questionnaire will be used to facilitate contact with the participants 
during the research and follow-up. Participants will be asked to provide locator information including their 
contact information and the contact information of friends or relatives who can reach the participant if the 
participant cannot be reached directly.
c.10.12. Consequences of substance use. The drug-specific form of the Short Inventory of Problems (SIP-D) 
[142] past 3 month version, will be used to measure consequences of drug use at each time point. The SIP-D 
is derived from the original alcohol-specific SIP, a short (15-item) form of Drinker’s Inventory of Consequences 
(DrInC) [143]. Psychometric evaluation of the SIP-D in a severely impaired population of patients entering 
substance abuse treatment yielded a single factor with Cronbach’s alpha = 0.97, and strong evidence 
convergent and discriminant validity [142]. Although versions of the SIP exist that combine alcohol and drug 

12
consequences [144, 145], the correlation between alcohol and drug consequences can be low [142], 
suggesting that it is important to assess drug consequences separately if they are of primary interest.
c.10.13. Physical, psychological, social, and environmental quality of life (WHOQoL Bref). Quality of Life 
will be assessed at baseline and at 3 and 6 months. At least 15 measures have been used to assess quality of 
life opioid dependent populations [146]. Quality of Life has consistently been found to improve following 
engagement in addiction treatment. Case Management addresses many different life domains that have an 
impact on quality of life, such as work, housing, and legal problems as well as medical, psychiatric, and dental 
needs; we hypothesize that people with more needs in these areas will benefit more from SBCM. For this 
reason we wish to use a broad measure of QoL rather than an instrument focusing narrowly on health-related 
QoL. Of available brief general QoL measures, The WHOQoL Bref [147] is an attractive option because it is 
well validated in a variety of populations including opioid dependent patients. Studies using the WHOQoL have 
demonstrated lower quality of life among opioid addicts than in controls [148, 149], and improvements in 
quality of life with opioid replacement therapy [150-152]. The WHOQoL Bref includes 26 items with 4 subscales 
covering the physical health, psychological, social, and environmental domains. The domain scores have good 
internal consistency, test-retest reliability, and discriminant validity [147]. 
c.11. Training, Supervision, and Fidelity Monitoring Procedures for Study Interventions 
c.11.1. Training and Credentialing in SBCM
Training for SBCM. A 2-day training in SBCM will be required of research study staff who will deliver the 
strengths based case management. The content of the training will be based on existing 2-day training 
formats, modified as needed for the specific content of the SBCM sessions described in the SBCM manuals. 
This training will consist of a basic introduction to the SBCM model, role-play exercises, complete review of the 
study treatment manual, and practice sessions of the study interventions. 
Pilot Delivery of Interventions. Upon completion of the basic training, interventionists conducting the 
brief interventions in the ED will be required to complete at least 2 practice cases (totaling no less than 5 
SBCM sessions) with consenting pilot/training patients, and receive satisfactory fidelity ratings in order to be 
certified.  If the pilot cases are judged by the supervisor to be satisfactory in quality, the data from the pilot 
participants will be included in the main trial. 
c.11.2. Treatment Fidelity for SBCM. 
Supervision of Interventionists. All SBCM sessions will be digitally audiotaped if possible. Participants 
may opt out of audiotaping. These files could theoretically be identifiable by voice quality or details of the 
conversation. The digital audio recordings will be transferred from the audio recorder to a password protected, 
HIPAA compliant secure storage drive.  Recordings will be identified by participant number, session number, 
date, and research study member.  The recordings will only be accessible to study team members including 
the SBCM supervisor. Supervision for SBCM will be provided by collaborator Richard Rapp, PhD., of Wright 
Stated University. Dr. Rapp is the person who developed the SBCM model of case management. His role on 
the project is limited to training and supervision/fidelity monitoring of staff who are conducting the SBCM 
intervention. Audiotapes of all interventionists will be reviewed and scored by Dr. Rapp (using the same 
Adherence Scale used by the fidelity monitor-see below) and reviewed in a biweekly telephone supervision 
session. Research study members will also have back-up available through the existing clinical hierarchy at the 
Bellevue Hospital Center ED.
Quality Control of SBCM. Following completion of the trial, a randomly selected sample of 20% of 
sessions completed during the trial will be coded using the SBCM Adherence Scale as a formal measure of 
treatment fidelity during the trial.  The digital audio recordings will be destroyed upon completion of the quality 
control of SBCM.
SBCM Adherence Scale. This scale includes 5 Likert-scaled items, 5 in each of 3 dimensions of the 
SBCM model.  The “Strengths” dimension rates the extent to which the case manager elicits and affirms client 
strengths, and incorporates these strengths into assessment and the planning of goals.  The “individual-driven” 
dimension supports participant autonomy and choice in the determination of goals and courses of action in 
working with the case manager.  The “relationship” dimension rates the extent to which the case manager 
establishes a strong alliance with the participant and demonstrates respect and empathy for their concerns. 
c.12. Statistical Methods
An extensive set of preliminary analyses are planned but are not fully described because of page 
restrictions. In addition to the assessment of the distributional properties of key measures at baseline and 

13
follow-up, we will evaluate the nature and pattern of missing data and assess treatment group equivalency 
at baseline on primary substance use measures and patient characteristics that are central to study aims. 
Three areas of preliminary analyses are highlighted below given their importance for the achievement of 
study aims. All primary analyses will be based upon an intent-to-treat (ITT) approach. 
c.12.1. Self-selection and Attrition. The DSM-IV will be administered as a measure of substance use prior 
to informed consent, a procedure that facilitates comparing (1) substance use patterns of eligible and 
ineligible participants, and (2) eligible prospects who do and do not elect to participate in the study. 
Contingent on the scale of measurement of the comparison variable, unprotected t-tests and Chi Squares 
will be done to compare these groups. Two strategies will be used to examine the impact of attrition on 
study internal validity, and both strategies will employ hierarchical linear modeling (HLM) with binary 
outcomes depicting attrition status (yes/no) jointly at three and six-months (Bernoulli function). First, we will 
examine attrition by group assignment. Here, the HLM will identify both the main effect of group assignment 
on later attrition as well as the potential for a group-by-time attrition effect. Second, group equivalency on 
factors potentially predictive of future treatment seeking will be evaluated with one-way ANOVA’s using 
scales from the BTI, TCU-TMA, and WHO-QoL scales as dependent measures. Third, using a lagged HLM 
we will examine how, if at all, substance use and general functioning at baseline and three-month follow-up 
predicts attrition at the three and six-month follow-up.  
c.12.2. Convergent validity of self-report of substance use and urine toxicology. The veracity of self-
reported illicit drug use will be examined by determining the concordance between positive urine toxicology 
screens and Form 90-D self-reported use at baseline, and at the 3 and 6 month follow-ups. Concordance 
will be determined both in categorical terms (agreement on the presence or absence of substance use) via 
Chi Square with kappa correction and, for continuous daily counts of substance use, Intraclass correlation. 
c.12.3. Convergent validity of pharmacotherapy initiation and engagement data. The initiation and 
engagement in treatment and pharmacotherapy for opioid dependence will be determined using three 
methods. The Form 90-D interview will collect retrospective report of frequency of counseling sessions, 
inpatient/residential treatment, ambulatory and hospital-based detoxification (items 9, 10, 11, 12, 13, 23, 
and 24) and pharmacotherapy for opioid dependence. Days use of one (or more) of four medications will be 
summed to indicate days of pharmacotherapy for opioid dependence: methadone, buprenorphine, P.O. 
naltrexone, and depot naltrexone (one injection of depot naltrexone will count as 30 days of 
pharmacotherapy). These events will be recorded on the day-by-day calendar to allow for the investigation 
of temporal associations between medication and substance use. As described in Section c.10.5, two 
objective methods will be used to verify self-reported use of medications for opioid dependence: methadone 
and buprenorphine clinic dosing records and New York State’s Prescription Monitoring Program. Days of 
pharmacotherapy will be estimated from these records based on days dispensed or administered, and 
concordance between the objective records and self-report will be computed. Discrepancies will be 
reconciled prior to conducting primary analyses (self-reported days of pharmacotherapy will be capped at 
the number of days of medication that was dispensed or administered).
c.12.4. Study Aim 1. The a priori pairwise contrast (SBCM vs. SAR) will investigate the main effect of study 
group assignment on initiation of addiction treatment and engagement in pharmacotherapy for opioid 
dependence. Following Rapp et al. [56], “Initiation” will be defined as a dichotomous outcome (yes/no), and 
will be considered to have occurred if patients report any substance abuse counseling sessions (excluding 
SBCM) from the time of the baseline assessment up to the day before the three-month interview. Using the 
same timeframe as “initiation,” “engagement” will be defined as the number days of medication use for 
opioid dependence, based on self-report verified by clinic dosing logs and Prescription Drug Monitoring 
Program records. Generalized linear modeling (GLM) will be used to test the planned contrasts, with group 
assignment as the between-subject factor (df = 1), and baseline measures of days substance use, number 
of lifetime treatment episodes for substance misuse, and readiness for change used as covariates. A logit 
link function will be used with the dichotomous outcome measure, initiation, while a linear distribution will be 
assumed with the continuous engagement outcome measure. Given the definitional overlap between the 
two primary dependent measures and our planned contrasts we will apply a Bonferroni correction of α = 
.05/2 = .025 (two-tailed) in rejecting the null hypothesis. 
c.12.5. Study Aim 2. Pairwise between-group contrasts analogous to those in Aim 1 are planned for Aim 2, 
with the difference that post-randomization opioid use is the outcome. The primary analysis will be based 
on a dichotomous measure of “successful outcome,” analogous to the outcomes used in a recent NIDA 

14
CTN trial of buprenorphine with and without opioid drug counseling [153], and in the NIAAA COMBINE trial 
[82]. For the present study “successful outcome” will be defined as 1) 3-month urine negative for opioids 
(opiates, oxycodone, methadone, buprenorphine, or propoxyphene) unless prescribed for opioid 
dependence, and 2) no more than two days of self-reported opioid use in the 4 weeks prior to the 3-month 
evaluation. Here, we will perform logistic regressions in which 3-month successful outcome (yes/no) is the 
dependent measure and baseline covariates are entered in step 1. Baseline days of opioid use will be used 
as a covariate as well as baseline readiness for change and number of lifetime treatment episodes for 
substance misuse. Treatment group will be dummy coded and entered in step 2 of the analysis. Secondary 
analysis will separately examine urine drug screen data and three-month self-reported opioid use, here 
defined as the total number of days of opioid use in the 30-day window before the 3-month interview (Form 
90). Additional parallel analyses will be conducted for other drugs of abuse, IV drug use, and six-month 
substance use defined using the same strategies described above. 
c.12.6. Study Aim 3. To test the effects of SBCM on other important life-functioning areas we will contrast 
SBCM with SAR (both groups combined) on each of the 4 subscales of the WHOQoL Bref. Baseline scores for 
each of these measures will be used as covariates when investigating its corresponding three-month value. 
GLM-based application of ANCOVA will be used to test the main effect of SBCM and alpha for each test will be 
set at .0125 (.05/4). Two sets of secondary analyses are planned. First we will investigate the extent, if any, 
that improvement in life-functioning areas (3-months) has a prognostic main effect on 6-month substance use 
reductions. Second, using longitudinal HLM we will investigate the trajectories of change in quality of life from 
baseline to the 6-month follow-up. 
c.12.7. Study Aim 4. We predict that (1) SBCM will have a larger effect (relative to SAR) on initiation and 
engagement in participants with higher levels of environmental instability at baseline. Definitions of initiation 
and engagement will parallel the definitions used in Aim 1. Environmental instability at baseline will be 
defined by summing five items in the Form 90-D interview, with higher scores reflecting more instability: 
number of days homeless, days living with others (not paying rent), days living in a halfway house, days 
incarcerated, and days not paid for work (all past 30 days). GLM will be used to test the predicted 
interactions. Covariates in these analyses will include baseline measures of days of opioid use and number 
of lifetime treatment episodes for substance misuse. Main effect terms representing treatment group and 
the selected participant attribute and the interaction term (group x attribute) will be entered simultaneously. 
For the environmental instability moderator we predict that the slope between instability and outcome will 
be significant and positive within the SBCM group while this parameter estimate within the SAR condition 
will be non-significant (ordinal interaction). 
c.12.8. Study Aim 5. This aim will identify the relative importance of study treatment effects and later initiation 
of/engagement in non-study treatment in predicting substance use reductions, i.e., does initiation or 
engagement mediate the relationship between study group assignment and outcome? Analyses will focus on 
3-month opioid use outcome although 6-month outcomes will be investigated to ascertain the stability of 
findings over time. Three-month substance use will be defined as the total number of days of opioid use in 
the 30-day window before the 3-month (Form 90-D). To provide for non-overlapping data initiation and 
engagement will be defined the same way as in all other aims (two measures), but this time only 
considering post-randomization months 1 and 2. Baseline days of opioid use as well as number of lifetime 
treatment episodes for substance misuse will be used as covariates. Aim 4 findings may result in one 
additional covariate, environmental instability. Using GLM, we plan to assess the mediating effect of 
initiation and engagement (separately for each measure) in two steps: in step 1, the main effect of 
treatment assignment (df = 2) and covariate effects will be tested against a protected alpha of .05/2 = .025. 
In step 2 the main effect of initiation or engagement will be entered into the model, with the prediction that 
this term will eliminate the main effect of treatment assignment. Parallel and confirmatory analyses will be 
done using “successful outcome” and 3-month opioid drug screen results as dependent measures. 
Following the same stepwise strategy used in the GLM, separate logistic regression models will be used to 
determine if initiation and engagement measures account for the dichotomous outcomes over and above 
the benefits from the SCBM intervention.  
Several additional secondary analyses are planned to 
investigate, in detail, the temporal relationship between daily substance use, use of medications for opioid 
dependence, and treatment group assignment. As an example, we will use a hierarchical generalized linear 
model (HGLM: Bernoulli sampling model and a logit link function) to prospectively determine if the initiation of 

15
medications for opioid dependence predicts, in a lagged design, reduction in opioid use, and whether the 
strength of this relationship varies by treatment condition, e.g., cross-level interactions [154]. 
c.13. Statistical power 
Power analyses were calculated for Aims 1 and 2 as these objectives involve between-group contrasts 
pertaining to the most important outcome measures: linkage to addiction treatment and opioid use. In our 
planned pairwise contrasts for both Aims 1 and 2 we anticipate an attrition rate of 15% leading to a reduced 
N of 127 per cell, and base our calculations on a desired power of .80. For Aim 1, effect size estimates are 
based on reported effects for case management relative to treatment as usual (TAU) or another less 
intensive treatment. In reviewing 10 studies investigating the effectiveness of case management versus 
TAU in facilitating later treatment engagement, the Cochrane group reported an effect size of d = .43 
favoring case management, with a larger effect (d = .70) for SBCM and for studies in which the treatment 
was manualized (d = .56) [68]. Assuming a two-tailed test, df = 1, our power projections suggest that the 
proposed cell sizes after attrition and Bonferroni correction (α = .025) are sufficiently powered to detect a 
differential effect as small as d = .32. Regarding drug use (Aim 2), studies contrasting the effectiveness of 
case management with that of treatment as usual or lower intensity treatments have yielded heterogeneous 
results. While the overall effect relative to TAU was small (d = .12), larger effects on drug use were found in 
three studies with above average linkage effects (d = .33) [68]. In the single most relevant trial, a large (n = 
711) study with an opioid dependent sample, case management yielded an intermediate (d = .23) reduction 
in drug use relative to psychoeducation and drug counseling [68]. We have calculated that with a two-tailed 
test, df = 1, α = .05, our proposed cell sizes will have sufficient power to detect effects as small as d = .20 
to reject the null hypothesis, an effect size that falls midway between small and moderate [155].

16
PROTECTION OF HUMAN SUBJECTS
1. RISKS TO HUMAN SUBJECTS
1.1. Human Subjects Involvement and Characteristics.  
The protocol will enroll approximately 400 women and men, age 18 or greater, with opioid dependence, 
recruited from the Bellevue Hospital Center Emergency Department.  Participants will be recruited between 
approximately January 2016 and December 2019. Participants will be screened and assessed in the ED 
using procedures based closely on those used in our recently completed CTN-0047 trial.  Participants 
identified as having opioid dependence will be randomly assigned (150 per group) to receive 1) up to 6 
sessions of Strength-Based Case Management (SBCM) based on the model previously implemented by 
Rapp et al. [56]; or 2) screening, assessment and referral alone (SAR).  Follow-up assessments will be 
completed at 3 and 6 months, by RAs who are blinded to treatment condition.
The treatment sessions will all be scheduled within a 90-day period for SBCM.  Including screening and 
follow-up visits, the total duration of participant involvement will be approximately 6 months.  Total time of 
contact during these 6 months is estimated at 5-10 hrs.  Participants will meet the aforementioned inclusion 
and exclusion criteria. As noted in section c.2.3, the study will not recruit prisoners. If a subject becomes 
incarcerated during the study, treatment and follow-up procedures may be continued in accordance with IRB 
and OHRP approvals.
1.1.1. Research sites
Screening, consent, baseline assessments, and the initial intervention session will be performed at Bellevue 
Hospital Center Hospital.  SBCM sessions 2-6 and follow-up assessments may be conducted at Bellevue 
Hospital Center, at NYULMC, or in the community. Should the initial intervention not occur on the date of 
consent and baseline, the session may take place as soon as possible and at locations noted for sessions 2-6 
and follow-up assessments. Supervision of the SBCM intervention will be performed remotely by Dr. Richard 
Rapp at Wright State University. 
1.2. Sources of Materials.  
Urine samples will be obtained from participants.  Data will be collected through use of interviews, 
questionnaires, and data collected from treatment providers and the New York Prescription Drug Monitoring 
Program.  These data will include measures of substance use and substance use disorder diagnoses, 
consequences of substance use, treatment participation, motivation, therapeutic alliance, barriers to treatment, 
demographics, contact information, and quality of life.  Case management sessions will be audiotaped for 
fidelity monitoring purposes.  Participants may opt out of audio-recording. 
These materials and data will be obtained specifically for research purposes, and the link to subject identifiers 
will be kept only on a separate enrollment log and in the REDCap database, accessible only to project staff.  
1.3.  Potential Risks
1.3.1. Risks of psychosocial treatments
There are no known specific risks to any of the psychosocial treatments employed in this study.  Non-specific 
risks of psychosocial treatments include discomfort with sharing personal information, and the risk of therapist 
misconduct.  These risks are judged to be very minor.
As a consequence of study participation, subjects may receive information concerning the severity of their 
substance use problems, and their participation implies that they may have an opioid use disorder.  This risk is 
judged to be minimal, since patients are already being screened for drug and alcohol use as part of standard of 
care treatment. It is very unlikely that qualifying participants are unaware that they have significant problems 
with opioid use.  In addition, the consent form explicitly states that the study is testing an intervention linking 
patients to treatment for substance use disorder.  Therefore, patients are unlikely to agree to participate if they 
do not already think that they have or may have an opioid use disorder. 

17
1.3.2. Risks of assessment procedures 
There are no known psychological risks associated with the questionnaires used in the study, all of which have 
been used extensively in clinical populations.  It is possible that discussing substance use and consequences 
may cause emotional discomfort in some participants.  To minimize such discomfort, the following steps will be 
taken.  The consent form will fully inform the participants about the nature of the information to be disclosed in 
the protocol, and the participants will be informed in the consent form that they can refuse to answer any 
questions or withdraw from the study at any time.  Participants will be informed that all information is 
confidential, and the steps taken to guard confidentiality, as well as the limits to confidentiality, will be 
described.  One of the investigators of the project will be available to meet with any participant who becomes 
distressed about any aspect of the protocol and wishes to discuss this.  
1.3.3. Risks to confidentiality and potential legal consequences.  
Records which identify subjects and the consent form signed by subjects may be inspected by the NYU 
Institutional Review Board.  The purpose for the review of this information would be to encourage and assess 
compliance with GCP requirements and to document the integrity of the trial progress. De-identified information 
may also be reviewed by NIH, the sponsor of this study. Because of the need to release information to these 
parties, absolute confidentiality cannot be guaranteed. No information will be shared with outside parties during 
objective verification of pharmacotherapy received. Because illicit substance use and addiction are 
stigmatized, there are possible social and legal consequences to breach of confidentiality concerning this 
information.  The results of this research project may be presented at meetings or in publications.  However, 
the identity of individual subjects will not be disclosed in those presentations.  
1.3.4. Risks and benefits of alternative treatments.  
There is no standard emergency department treatment for opioid dependence in the Bellevue Hospital Center 
ED. Patients who are noted to have opioid dependence are sometimes referred to social work to be referred 
for treatment.  It is possible for ED physicians with a CSAT waiver to initiate treatment with buprenorphine, but 
this happens rarely.  Because of the ethical problem of participants receiving a lower level of care due to 
participation in the study (particularly those in the SAR group), participation in the study will not preclude the 
participants’ receiving whatever clinical care would otherwise be provided by the ED.  Therefore such 
interventions are not actually “alternative” treatments but rather additional treatments that study participants 
may or may not receive independent of study participation. 
2. ADEQUACY OF PROTECTION AGAINST RISKS
2.1. Recruitment and Informed Consent
2.1.1. Recruitment  
Participants will be recruited from the Bellevue Hospital Center ED.  
2.1.2. Informed consent process and document.  
2.1.2.1
Bellevue ED staff will introduce the ED patient to study staff. 
2.1.2.2
Using a brief IRB-approved script, study staff will request the patient’s verbal consent, to complete the 
prescreen assessment.
2.1.2.3
The RA will collect anonymous information from potentially eligible patients including English 
proficiency, age, gender, reason for ED visit, triage level, non-prisoner status, days of opioid use in 
the past 30 days, and availability for treatment (See form entitled “Brief Information Tool”)  in order to 
determine potential eligibility and collect data on representativeness of the study sample.
2.1.2.4   A research study member will administer the DSM-IV Checklist.
2.1.2.5 ED patients who meet DSM-IV inclusion criteria (endorsement of three or more opioid dependence 
criteria on the DSM-IV Checklist.) will be further screened for eligibility by the RA using the Screening 
Instrument Secondary Screening Form. Those who are interested and eligible will then undergo the 
written informed consent process.

18
Trained research staff will conduct the informed consent process in private locations as noted below. 
Interested patients will be provided with an informed consent form including all pertinent details of the study 
including description of the following: the assessment interview and questionnaires; the follow-up interviews; 
description of experimental treatment; risks and benefits of study procedures; alternatives to participation in the 
study; confidentiality; emergency treatment and compensation for injury; payment for participation; a statement 
that patients will be informed of any new findings affecting the risks or benefits of the study; a statement that 
participation is voluntary and that the patient may withdraw at any time; and information about whom to contact 
with questions or in case of emergency.  The consent form will also include assurances of confidentiality and a 
statement that participation is entirely voluntary, that the decision to participate will in no way influence other 
aspects of the patient’s treatment or involvement in the main trial, and that the participant is free to withdraw 
participation at any time. Patients indicate their consent to participate in the study by signing and returning the 
informed consent form.  This form provides documentation that written informed consent has been obtained. A 
copy of the signed informed consent form will be given to the study participant.  
2.2. Protection Against Risk
2.2.1. Management of risk due to study treatments
The psychosocial treatments employed in this study are minimal risk.  Risks will be minimized by thorough 
training, supervision, and monitoring of those providing the interventions, as described in Section 3.c.11 of the 
Research Plan. 
2.2.2. Minimization of risk to confidentiality and privacy
Confidentiality of participant records will be secured by the use of study codes for identifying participants on 
CRFs, secure storage of any documents that have participant identifiers, and secure computing procedures for 
entering and transferring electronic data.  No identifying information will be disclosed in reports, publications or 
presentations. Confidentiality will be maintained in accordance with all applicable federal regulations and/or 
state law and regulations.
All project staff will be thoroughly trained in issues relating to confidentiality.  Data will be entered into 
“Research Electronic Data Capture” (REDCap) which is maintained by the NYU CTSI.  The link between 
participant identifiers and participant study ID will be maintained only in REDCap and on a password-protected 
electronic storage drive.  REDCap was designed specifically to protect patient privacy and confidentiality while 
assisting investigators in conducting clinical research.  System-level and application-level security features 
include:  SSL encryption of internet traffic (e.g. https pages); Hosting in the secure data centers with 
centralized nightly backup; Sanitization of database inputs against scripting or SQL injection attacks; Fine-
grained control over user rights; Detailed audit trails; Record-locking; De-identification functions for data export.  
At the conclusion of this study de-identified data will be downloaded and the project will be deleted off of 
REDCap. Confidentiality of hard copy (paper) research materials will be ensured by storing the research 
materials in locked cabinets.  Material will be available only to project staff, and only as needed.  Participants 
will be identified in CRFs by a unique identification code.  Documents containing participants’ identities 
(consent forms, source documents) will be stored in a separate locked cabinet.  Audio files of sessions will be 
stored on a password protected, HIPAA compliant secure server. Published reports will be based on group 
data; no individual data will be reported.  No information will be shared with outside parties during objective 
verification of pharmacotherapy received.
As a further protection to confidentiality, the principal investigator has obtained a federal Certificate of 
Confidentiality (CoC) from the Department of Health and Human Services (DHHS), protecting participants 
against disclosure of sensitive information (e.g., drug use). The NIH office that issues the CoC will be advised 
of changes in the CoC application information. With this Certificate, the investigators cannot be forced (for 
example by court order or subpoena) to disclose research information that may identify individual patients in 
any Federal, State, or local civil, criminal, administrative, legislative, or other proceedings.  Disclosure will be 
necessary, however, upon request of DHHS for audit or program evaluation purposes.  DHHS ensures 
confidentiality of requested data.  Data and study records (including consent forms, locator forms, source 
documents, session audio files, and CRFs) will be kept a minimum of 3 years after all final reports have been 

19
submitted to NIDA.  After that they will be destroyed. A de-identified database will be retained in electronic form 
as a permanent record of the study.  
Bellevue ED staff will introduce the potential participants to study staff at a time when they are deemed to be 
medically and psychiatrically stable, when their medical care will not be disrupted or delayed, and when the 
adequate privacy exists. 
The interviewer will ensure a private setting for the interview and will ask the patient’s comfort with the privacy 
prior to interview initiation. Screening, informed consent, assessment, and initial SBCM sessions may be 
completed in private rooms or other private treatment areas (e.g., ophthalmology room).  If the patient is 
moved, the staff member will notify patient’s doctor or nurse so that medical staff is aware of patient location. If 
the patient is unable to move easily, either due to lack of mobility or proximity to certain medical machines, the 
staff member will consult with a nurse as to whether it is possible to move participant. If it is not possible, the 
staff member will explore possibility with nurse as to whether patients surrounding the participant can be 
moved to afford the participant more privacy.
If the patient feels uncomfortable with or is emotionally disturbed by any portion of the interview, s/he may elect 
to not answer portions of the interview or may end the interview without loss of the compensation for their time.
3. POTENTIAL BENEFITS OF THE PROPOSED RESEARCH TO HUMAN SUBJECTS AND OTHERS 
3.1. Potential benefits to participants 
Participants in both groups will receive care above treatment-as-usual. All participants will receive substance 
use screening, assessment and information on local substance use treatment programs. Participants assigned 
to SBCM will additionally receive up to 6 SBCM sessions with a trained case manager who can provide 
additional resources and support to the participant. Referral to treatment and case management are evidence-
based treatments in other contexts. As stated in section c.2.3, incarcerated participants will be clearly informed 
in advance that participation in the research will have no effect on parole, nor will it confer any advantages or 
amenities beyond the potential benefits stated at the time of informed consent. 
3.2. Potential benefits to others.  
Knowledge gained through this study may aid the development of more effective treatments for individuals with 
opioid dependence and other addictive disorders.  
3.3. Risk-benefit assessment
Risks to individual participants appear to be outweighed by the likely benefits of study participation and the 
potential benefits to others.  
4. COMPENSATION TO PARTICIPANTS
Participants will receive reimbursement for research assessments as follows:  Screening and Baseline 
assessment: $50, 3-month follow-up: $75, 6-month follow-up: $75.  Participants completing all of the 
assessments would therefore receive a total of $200. Upon request, participants randomized to SBCM will be 
given a roundtrip Metro Card for each case management visit.  Upon request, both groups (SBCM and SAR) 
will be given a roundtrip Metro Card for the 3 and 6 month follow-up interviews.  If a participant is found to be 
incarcerated at time of follow-up, the participant will be compensated the agreed upon amount as approved by 
local IRB and/or collaborating correctional facilities.
5. COSTS TO PARTICIPANTS
None.
6. IMPORTANCE OF THE KNOWLEDGE TO BE GAINED

20
There is an urgent need to develop more effective methods to help people who suffer from opioid dependence.  
The knowledge gained through this study could help establish effective ways of facilitating engagement in 
addiction treatment by patients with opioid dependence who present for treatment in medical EDs.   
7.  DATA AND SAFETY MONITORING PLAN
7.1. General Considerations  
The risks of the interventions used in this study are minimal.  However, the population under study is at high 
risk for serious adverse events unrelated to study participation. The data and safety monitoring plan is 
therefore designed 1) to monitor study progress, including recruitment, retention, data quality, and adherence 
to the protocol; and 2) to ensure that the risks of study-related procedures are carefully monitored, and that all 
reportable adverse events are systematically evaluated.  
7.2. Institutional Review Board (IRB)  
All study procedures will be approved by the NYU IRB prior to beginning the study.  
7.3. Data and Safety Monitoring Committee
A Data and Safety Monitoring Committee will be established comprising the Principal Investigator and Co-
investigators, the Protocol Manager, and an external physician reviewer who is not otherwise affiliated with the 
study and does not report directly or indirectly to the PI.  This committee will meet at least twice per year to 
review data quality, recruitment and retention, and to review all serious or clinically significant adverse events.  
In addition, the committee will review safety data, including AEs/SAEs and reportable new information following 
any serious adverse event that appears to be study related.  Patterns of adverse events as well as individual 
events may indicate the need for operational changes or protocol modifications, or termination of the study.  
Because this study involves a very low-risk psychosocial intervention, there are no predefined stopping rules 
for the study. DSMC reports will be forwarded to the IRB with the annual continuing review.
7.4. Procedures for Monitoring and Reporting Adverse Events. 
AEs will be reported in accordance with federal law, NIH policies, and NYUSOM IRB policies to the NYU IRB.  
In addition, information on adverse events will be captured as follows.
7.4.1. Data Collection for Adverse Events and Serious Adverse Events 
7.4.1.1. Adverse Events.  For the purpose of this study, the following events will not be reported as AEs: 

Grade 1 (mild) unrelated event.

Grade 2 (moderate) unrelated event.  This would typically include physical events such as headache, 
cold, etc. that were considered unrelated to study participation. 

Substance Use Events, including:
o
Worsening of drug use 
o
Need for higher level of care 
o
Signs and symptoms of withdrawal 
o
Drug craving 
o
Medical events that are directly related to substance use 
Events that are severe, life threatening, or result in death will be recorded as AEs or SAEs as appropriate and 
documented in the study progress note and in the data system. 
7.4.1.2. Serious Adverse Events. For the purpose of this study, the following events will not be reported as 
SAEs: 
• Admission to a hospital or freestanding residential facility for drug detoxification or drug treatment. 
• Admission to a hospital/surgery center for preplanned/elective surgeries; 
• Admission to a hospital for scheduled labor and delivery; 

21
• Inpatient hospital admission for a medical event (i.e. gallbladder surgery, pneumonia, substance 
related). 
7.4.1.3
Reportable New Information.  For the purpose of this study, the following information will be 
reported to the NYU SoM IRB within 5 business days:

Information that indicates new or increased risk, or a safety issue.

Any harm experienced by a subject or another individual that, in the opinion of the investigator, is 
unexpected and at least probably related to the research procedures.  

Non-compliance with federal regulations governing the research or within the requirements or an 
allegation of such non-compliance.

Audit, inspection or inquiry by a federal agency.

Written reports of study monitors.

Failure to follow the protocol due to the action or inaction of the investigator or research staff.

Breach of confidentiality.

Unreviewed change to the protocol taken without prior IRB review to eliminate an apparent 
immediate hazard to a subject.

Complaint of a subject that cannot be resolved by the research team.

Premature suspension or termination of the research by the sponsor, investigator or institution.
8.  CLINICALTRIALS.GOV REQUIREMENTS
This application includes a trial which requires registration in ClinicalTrials.gov. The signature on the 
application of the Authorized Organizational Representative assures compliance for the registration of any 
such trial.

22
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