Improving Retention Across the OUD Service Cascade Upon Reentry From Jail Using Recovery Management Checkups Experiment
Phase: PHASE3
Conditions: Opioid-use Disorder
Sponsor: Chestnut Health Systems

 
 
 
 
Study Title:  Chestnut Health Systems Justice Community Opioid Innovative Network 
Research Hub:  Improving Retention Across the OUD Service Cascade Upon Re-entry 
From Jail Using Recovery Management Check-Ups (RMC-A) Experiment 
PI: Christy K Scott, Ph.D. 
Clinical Trial Protocol and Statistical Analysis Plan 
Version 1.0 
December 19, 2019 
 
 
 

Section 1:  Basic Information 
1.1. 
Study Title:  Improving Retention Across the OUD Service Cascade Upon Re-entry 
From Jail Using Recovery Management Check-Ups (RMC-A) Experiment 
 
1.2. 
Study is exempt from Federal regulations:  No 
 
1.3. 
Exemption number:  n/a 
 
1.4. 
Clinical Trial Questionnaire:  
1.4.a.  
Study involves human participants:  Yes  
1.4.b.  
Participants are prospectively assigned to an intervention:  Yes  
1.4.c.  
Study is designed to evaluate the effect of the intervention on the 
participants: Yes 
1.4.d.  
The effect that will be evaluated a health-related biomedical or behavioral 
outcome: Yes  
1.5.  
ClinicalTrials.gov Identifier:  TBD 
 
 

Section 2 - Study Population Characteristics  
2.1. Conditions or Focus of Study: Opioid use disorders (OUD) 
2.2. Eligibility Criteria 
Inclusion criteria are: 
(a) meets DSM-5 opioid use disorder criteria in the past year 
(b) heroin or other opioid use in the 90 days prior to entering jail and 
(c) is released from 1 of the participating jails. 
Exclusion criteria include: 
(d) is under age 18 or 
(e) cognitive impairment that precludes ability to give informed consent, and 
(f) resides outside the service area. 
2.3. Age Limits  
 
Min Age: 18 Years  
 
Max Age: N/A (No limit) 
2.4. Inclusion of Women, Minorities, and Children  
Study participants will be recruited from individuals with opioid use disorders who are 
discharging from one of five jails within Illinois and are eligible for treatment with medications for 
OUD (MOUD). The numbers below are each based on information obtained from the 
participating OTPs about their admissions in the past year. 
 
Women. We anticipate that overall 57% of study participants will be female. This distribution 
reflects the patient population in these participating OTPs as well as the broader population of 
patients seeking treatment within the targeted areas in Chicago. All efforts will be made to 
ensure that male and female participants are recruited into the study and Urn Randomization 
will be used to maximize the extent to which they are assigned to condition without bias or 
preference. This distribution is consistent with and justified by study scientific objectives and the 
proposed study design. Sex (female/male) will be included as a key moderator variable in the 
statistical analyses in order to estimate and compare intervention effects by sex, based on prior 
research findings that suggest sex differences in the outcomes of treatment in OTPs. Evaluation 
of study outcomes, as specified in the specific aims/hypotheses, and all statistical analyses will 
be conducted without bias regarding sex. 
 
Minorities. We anticipate that the study sample will be 26% Hispanic; 49% African Americans, 
25% whites, and 26% of mixed/other race. This distribution reflects the patient population in 
these participating OTPs as well as the broader population of patients seeking treatment within 
the targeted areas in Chicago. All efforts will be made to ensure that participants of all 
racial/ethnic groups are recruited into the study and randomly assigned to condition without bias 

or preference. This distribution is consistent with and justified by study scientific objectives and 
proposed study design. The sample distribution includes at least 25% of each racial/ethnic 
subgroup, which will enable us to evaluate the extent to which the observed intervention effects 
are invariant (i.e., similar) by ethnicity and by race. Prior research suggests that there are 
differences in outcomes of treatment for OUD by race/ethnicity. Evaluation of study outcomes, 
as specified in the specific aims/hypotheses, and all statistical analyses will be conducted 
without bias regarding race/ethnicity. 
 
Children Under Age 21. Participants will be adults, aged 18 and older, who are incarcerated in 
jail in Illinois.  Of the six participating OTPs, none reported having any patients less than age 18, 
and only one reported having patients between ages 18–20 (2%). Although we will not exclude 
18–20 year olds, adults are the focus of the treatment programs in this study, consistent with the 
study design and specific aims. It is unlikely that sufficient numbers of 18–20 year olds will be 
recruited to test for whether the effects are invariant between these young adults and older 
adults. Thus, the study sample reflects the population in the participating OTPs and is 
scientifically justified by the study’s focus on incarcerated adults with OUD. Evaluation of study 
outcomes, as specified in the specific aims/hypotheses, and all statistical analyses will be 
conducted without bias regarding age group.  
 
2.5 Recruitment and Retention Plan 
 
Recruitment Plan 
 
Phase I: In Jail Screen for Study Eligibility. The study team will use two methods that have 
been successfully used in prior studies to recruit eligible individuals from jail settings and to 
engage them in the study. In the first method, staff at the jail (these may be corrections staff, 
medical staff, or staff from contracted OTPs) will identify individuals who have already been 
assessed with OUD (as part of the jail's usual screening protocol), provide them with an 
overview of the study, and, for those interested in learning more about the study, will secure 
their permission for a study research assistant (RA) to contact the candidate, confirm their 
eligibility (based on age and residency), and discuss transportation to the research office upon 
their release. In the second method, the RA will meet with the candidate immediately following 
their release, briefly overview the study, and discuss transportation to the research office post-
release. Both procedures will allow the study team to contact individuals who have initiated 
treatment with MOUD pre-release as well as those who are quickly released, and may not have 
initiated treatment with MOUD.  The study procedures may vary across the different jail sites 
dependent upon the established procedures for screening individuals for OUD upon their 
admission and for engaging them into MOUD prior to their release. 
 
Phase II: Re-entry Meeting, Baseline Data Collection and Randomization. To maximize 
timely participation in the initial re-entry meeting, participants will be transported to the research 
office and given a $45 gift card upon completion of the baseline interview. Using similar 
procedures in the RMC re-entry trial, from the date of release, 35% were enrolled within 2 days, 
69% within 4 days, and 90% within 7 days (mean=4.2 days, S.D.=3.8 days). RAs will then 
provide a detailed description of the study, and for those who agree to participate, RAs will 
administer the informed consent, complete the baseline research interview, update the locator, 
notify the Research Manager to randomize participants, and schedule the next research 
interview. The Research Manager will use gRand Urn Randomization (Version 1.1049) to 
randomly assign participants to one of 3 conditions: control, RMC, RMC-A. Urn randomization 
adjusts the probability of assignment to each condition in ways that simultaneously minimizes 
differences in multiple stratification variables. The base rate will be set at 33% to each condition, 

and software set to simultaneously balance assignment by the county, days of opioid use in the 
90 days prior to incarceration, and probation status at the time of release. It will also take into 
account participant characteristics that have been previously associated with differences in 
retention and outcomes for treatment with MOUD, including sex,45,51 age,52-53 cocaine use,54 and 
mental health problem severity.55-57 Controlling for these factors further improves the study’s 
statistical power. The Research Manager will enter the information into the program, generate 
the assignment, and inform the participant’s RA of the assignment. Next, persons assigned to 
the RMC or RMC-A conditions will meet with a linkage manager. 
 
Retention Plan 
 
RAs will complete 90-minute enrollment and quarterly follow-up research interviews with 
participants in all conditions. Study participants will receive a $45 gift card - $35/interview and 
$10/urine test. To retain people in the study, the team will implement Dr. Scott’s58 structured 
follow-up model which has reliably produced over 90% follow-up rates across studies involving 
over 70,000 patients regardless of population, primary drug type including heroin, and over 
follow-up periods ranging from 3 months to 18 years. Steps include: (a) contacting participants 
within 24-48 hours of study enrollment to collect additional locator information and mailing a 
schedule card for the next interview, (b) tracking status of interviews and locator 
information in a secure data base, (c) assigning each case to a follow-up case tracker, (d) 
verifying locator data, (e) conducting outreach for unverified cases and discussing them at 
weekly meetings, (f) mailing thank-you cards to participants and collaterals, (g) scheduling 
follow-up appointments in advance, (h) mailing 3 and 6 week post-enrollment flyers, (i) 
implementing returned-mail procedures, (j) calling participants 6 weeks before appointment to 
confirm date and location (phone vs. research office), (k) conducting outreach for unconfirmed 
cases and reviewing them at weekly meetings, (l) completing follow-up interviews and 
scheduling next appointments, (m) implementing a no-show protocol, and (n) incentives for both 
completing the interview and urine drug test. Progress will be monitored with daily management 
reports. 
 
2.6. Recruitment Status:  Not yet recruiting 
2.7 Study Timeline 
 
Following this section are two exhibits that support the discussion of the study timeline:  
 
Exhibit 1.   Project Timeline shows activities by project year and month, with 
associated number of subjects/activities per month where applicable. 
 
Exhibit 2.   Data Collection Summary gives counts by year 
Both exhibits show peaks in data collection and intervention work in years 2-4 that are common 
in experiments with multiple waves of intervention and data collection per person.  Below is a 
section by section explanation of activities shown on the timeline in months from the award date 
(7/15/19).   
 
Study Start-Up. During months 1 to 7.5, the team will convene the Chestnut Hub 
collaborative researchers and representatives from the participating jails and OTPs to review 
the proposal and finalize the design instrumentation, study methods, and schedule for reports. 
We will finalize the site-specific issues for recruiting study participants (i.e., referral to study 
team for eligibility assessment) and establish Business Agreements with the participating OTPs 
in order to collect data from treatment records. The study team will be trained on all instruments 
and study procedures, and study-specific software and databases will be developed.  We will 
participate in required JCOIN workgroup activities and develop plans for common measures, 

protocols or analytic approaches and methods for data transmission to meet JCOIN 
requirements. 
Enrollment Interview and Randomization. The next row shows the expected rate 
(varying from 20-40 per month) of recruitment in months 8 to 33 to obtain the target sample size 
(N = 750). Note that the rate of recruitment is reduced beginning in month 15 to compensate for 
concurrent baseline and follow-up interviews that peak in interviews in years 3 to 4.   
Follow-up Research Interviews. The next 8 rows show the quarterly follow-up 
assessments (3, 6, 9, 12, 15, 18, 21, and 24) – each starting and ending 3 months after the prior 
row.  This is followed by the total number of interviews.   
Check-ups.   RMC and RMC-Adaptive will be provided in months 8 to 57 to 1/3RD of 
those randomized to each. For RMC the checkups will happen at months 1, 2, and the same 
time as each of the quarterly interviews (every 3rd month). For RMC-Adaptive, the schedule will 
be individualized but we anticipate an average of every other month.   
Transportation;   Round-trip transportation (typically via Lyft or Uber drivers) will be 
provided to all interviews and checkups between months 8 to 57.  It is based on 90% of the 
number of interviews plus an additional 1/17th for RMC-Adaptive sessions occurring between 
quarterly interviews for the 1/3rd in this group. 
Data Cleaning and Analysis.  Data cleaning and analysis will be done continuously 
from months 8 to 60.  This includes automated range checks and skip outs during on-line 
surveys, matching to field management records of what is expected to have been done, variable 
and preliminary/final analysis file creation for the DSMB reports and papers.  
Data Safety Plan Reports and Review.  A preliminary Data Safety Plan (DSP) will be 
submitted to the Data Safety Monitoring Board (DSMB) prior to field work in approximately 
month 6. Annual DSMB reports with preliminary data, psychometric, analyses of the direct 
effects, and any negative event forms will then be submitted to the DSMB for review 
approximately 2 months prior to the annual NIDA progress reports (months 23, 35, 47) and prior 
to publishing the main findings (month 57).  Although not shown above, the DSMB, IRB and 
NIDA will also be informed about any unexpected serious adverse events within 48 hours. 
 
Work on Preliminary Presentations and papers.  Work on the study design 
presentation and paper will begin in month 10.  Other papers based on baseline participant 
needs, psychometrics, and lessons learned about working better with patients still in need after 
3 months will also be done through month 60.    
 
Work on Main Findings.  Work on the main findings will begin around month 53 when 
sufficient data have been accumulated from the follow-up assessments to begin preliminary 
analyses, with the goal of submitting it for publication between months 58 to 60. 
 
Other JCOIN Cooperative Agreement Activities. Although not shown on the project 
timeline, the PI and Co-I’s and other study partners will attend the planned 2 JCOIN steering 
committee meetings each year.   We will work with the Coordinating Translation Center (CTC) 
on topics that might be appropriate for dissemination and the Methodological and Advance 
Analytic Resource Center (MAARC) to identify opportunities to collaborate on more detailed 
analyses than what we have proposed here. 

Exhibit 1.  Project Timeline 
 
 
 
 
    
 
 
Year
Month
J
A
S
O
N
D
J
F
M
A
M
J
J
A
S
O
N
D
J
F
M
A
M
J
J
A
S
O
N
D
J
F
M
A
M
J
J
A
S
O
N
D
J
F
M
A
M
J
J
A
S
O
N
D
J
F
M
A
Activity
1
2
3
4
5
6
7
8
9
10
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Study Start-Up
Enrollment Interview and 
    Randomization
20 40 40 40 40 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30
1 Month Research Interview
20 40 40 40 40 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30
2 Month Research Interview
20 40 40 40 40 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30
3 Month Research Interview
20 40 40 40 40 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30
6 Month Research Interview
20 40 40 40 40 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30
9 Month Research Interview
20 40 40 40 40 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30
12 Month Research Interview
20 40 40 40 40 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30
15 Month Research Interview
20 40 40 40 40 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30
18 Month Research Interview
20 40 40 40 40 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30
21 Month Research Interview
20 40 40 40 40 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30
24 Month Research Interview
20 40 40 40 40 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30
   Total interviews/urine
20 60 100 140 160 150 160 170 160 180 200 190 210 230 220 240 260 250 270 290 280 300 320 310 300 290 250 220 220 210 180 180 180 150 150 150 120 120 120 90 90 90 60 60 60 30 30 30
RMC and RMC-A (2/3rds of 
interviews)
13 40 67 93 107 100 107 113 107 120 133 127 140 153 147 160 173 167 180 193 187 200 213 207 200 193 167 147 147 140 120 120 120 100 100 100 80 80 80 60 60 60 40 40 40 20 20 20
Person Trips of Transportation 
(90% of Total interviews x 1.17) 
21 63 105 147 168 158 168 179 168 190 211 200 221 242 232 253 274 263 284 305 295 316 337 326 316 305 263 232 232 221 190 190 190 158 158 158 126 126 126 95 95 95 63 63 63 32 32 32
Data Cleaning 
    and Analysis
Data Plan/Report 
    and Review
Work on Preliminary 
    Presentations & Papers
Work on Main Findings
Year 4
(5/1/22-4/30/23)
Year 5
(5/1/23-4/30/24)
Year 1 
(7/15/19-4/30/20)
Year 2
(5/1/20-4/30/21)
Year 3
(5/1/21-4/30/22)

8 
 
 
Exhibit 2.  Data Collection and Intervention Summary 
 
 
 
2.8. Enrollment of First Subject:  March 15, 2020 
Inclusion Enrollment Report: see following page 
 
 
Field Staff Tasks
Hours
Year 1\c
Year 2
Year 3
Year 4
Year 5
Total
Enrollment Interview and 
    Randomization
 
100
380
270
0
0
750
1 Month Research Interview
 
60
390
300
0
0
750
2 Month Research Interview
 
20
400
330
0
0
750
3 Month Research Interview
 
0
390
360
0
0
750
6 Month Research Interview
 
0
300
360
90
0
750
9 Month Research Interview
 
0
210
360
180
0
750
12 Month Research Interview
 
0
100
380
270
0
750
15 Month Research Interview
 
0
0
390
360
0
750
18 Month Research Interview
 
0
0
300
360
90
660
21 Month Research Interview
 
0
0
210
360
180
570
24 Month Research Interview
 
0
0
100
380
270
480
   Total interviews/urine
 
180
2170
3360
2000
540
7710
     Hours per interview/urine\a
7
1260
15190
23520
14000
3780
53970
     Minimum FTE field work (Hour/2080)
0.61
7.30
11.31
6.73
1.82
25.95
RMC Q+ RMC Q (2/3rds of interviews)
 
120
1446.67
2240 1333.333
360
5140
     Hours per RMC\b
3
360
4340
6720
4000
1080
15420
     Minimum FTE for RMC(Hour/2080)
0.17
2.09
3.23
1.92
0.52
7.41
Person Trips of Transportation (90% of Tot  
190
2285
3538
2106
569
8119
\c 7.5 months (7/15/19 - 4/30/20)
\a  Average times to do recruitment, enrollment, collect & verifying locator data, randomization, tracking between 
interviews, actual   interviews, saliva/ urine testing, field edits, data entry and provide transportation to research 
interviews.
\b  Average times per RMC to conduct BTNA, checkup, provide transportation/assistance to treatment, and follow-
up to ensure treatment engagement/retention. 

9 
 

10 
 
Section 3: Protection and Monitoring Plans 
3.1. Protection of Human Subjects 
3.1.1. Risks to Human Subjects 
a. Human Subjects Involvement, Characteristics, and Design.  
Study Design. The goal of the proposed experiment is to compare linkage and retention 
rates as well as public health and public safety outcomes of 750 male and female detainees 
who will be randomly assigned to 1 of 3 groups upon their release from jail: a) re-entry as usual 
(control), b) the original Recovery Management Checkup (RMC) on a fixed schedule, and c) an 
RMC-Adaptive version in which the frequency and content of checkups will be based upon the 
participant’s ongoing progress. The study will be conducted in collaboration with 6 county jails in 
Illinois (Cook, Dupage, Grundy, McLean, Tazewell, and Will) and the adjacent OTPs in each 
county. Pre-release participants will be screened for history of OUD. All participants will receive 
research follow-up assessments quarterly for 2 years which will also include urine testing and 
records checks (OUD treatment, mortality, recidivism). The specific aims are to evaluate: 
Aim 1. The direct effects of RMC on the OUD service cascade of care (initiation, engagement, 
retention, and re-linkage, and months of MOUD treatment).  
Aim 2. The indirect effects of RMC (via months of MOUD treatment) on public health outcomes 
(days of opioid use, OUD symptoms, quality of life and the cost-of-healthcare-utilization). 
Aim 3.  The indirect effects of RMC (via months of MOUD treatment and public health 
outcomes) on public safety outcomes (illegal activity, re-arrest, re-incarceration, and 
cost-of-crime) 
Aim 4.  The incremental costs and cost-effectiveness of the control vs. RMC vs. RMC-Adaptive 
in terms of both public health outcomes (days of opioid use, quality adjusted life years 
(QALYs), cost-of-health-care utilization) and public safety outcomes (re-incarceration 
and cost-of-crime). 
Subject Populations 
Inclusion criteria are: (a) meets criteria for DSM-5 opioid use disorder in the past year, 
(b) heroin or other opioid use in the 90 days prior to entering jail, and (c) is being released from 
1 of the participating jails. Exclusion criteria include: (d) is under age 18 or (e) exhibits cognitive 
impairment that precludes ability to give informed consent, and (f) resides outside the service 
area.  
To estimate the number of eligible individuals, we used a 2-step process. First, we 
obtained the number of people booked and charged in each participating county during 2016 
(includes duplicated people) (109,422 bookings). Second, the 2017 National Survey on Drug 
Use and Health (NSDUH) data was subset to adults who had been charged and booked into a 
jail to estimate the rate of our target population that has a past-year OUD (11%). Based on this 
we expect 12,023 (11%) of the above bookings will involve people with OUD.  
We further subset the NSDUH to those who had been charged and booked in jail AND 
had a past-year OUD as a proxy for eligibility for OUD treatment (to reflect the target population) 
and to estimate expected demographic characteristics. We anticipate that overall 34% will be 
female; 11% will be Hispanic; 75% white, 16% black; and 7% mixed/other race. We expect 5% 
to be ages 18-20, 26% ages 21-25, 48% ages 26-49, and 19% to be 50 to 64, and less than 1% 

11 
 
to be age 65 or older. OTPs estimate that about half of patients drop out of treatment within 3 to 
12 months. About 10%-20% of the patients that drop-out are readmitted within one year.  
Collaborating Sites  
Research Sites 
 
The primary site for managing study recruitment, enrollment and delivery of interventions is 
Chestnut Health Systems, Lighthouse Institute, 221 W. Walton St., Chicago, IL 60610 under 
the supervision of Dr. Scott. 
 
The GAIN Q3 will be hosted at an internet co-location site at 303 E. Washington St., 
Bloomington, IL 61701 under the supervision of Dr. Dennis. 
 
All data will be downloaded, linked, cleaned, and de-identified at Chestnut Health Systems, 
448 Wylie Dr., Normal, IL 61701 under the supervision of Dr. Dennis. 
 
Analyses using de-identified files will be conducted at the Chestnut offices by Drs. Scott and 
Dennis and their staff at the above addresses.  
 
A secondary site for managing the intervention is the sub awardee, American Institutes for 
Research (AIR), 10 S Riverside, Suite 600, Chicago, IL  60606, under the supervision of Dr. 
Salisbury-Afshar. 
 
Analyses of economic data will be done primarily at the University of Miami, Coral Gables, 
FL 33124, under the supervision of Dr. McCollister.  
As part of the study design and specific aims, study participants will be recruited from six 
county jails in the Chicago Metropolitan Area / Cook County and central Illinois:  
 
Cook County Department of Corrections, 2700 S. California Ave., Chicago, IL 60608  
 
DuPage County Jail, 501 N. County Farm Rd., Wheaton, IL 60187 
 
 
Grundy County Jail, 111 E. Illinois Ave., Morris, IL 60450 
 
McLean County Detention Facility, 104 W. Front St., Bloomington, IL 61701 
 
Tazewell County Jail, 101 S. Capitol St., Pekin, IL 61554 
 
 
Will County Adult Detention Facility, 95 S. Chicago St., Joliet, IL 60436 
The experiment will attempt to improve the rates of linkage to and retention of individuals 
who are released from each of these jails and are referred to their affiliated OTPs:  
 
Cook County Health and Hospital Systems (CCHHS), 2800 S. California Ave., Chicago, IL 
60608 
 
 
Amita Health, 740 Pasquinelli Dr.,Westmont, IL 60559 
 
Family Guidance Centers, 2400 Glenwood Ave., Joliet, IL 60435 
 
 
Chestnut Health Systems, 702 W. Chestnut St., Bloomington, IL 61701 
 
 
Gateway Foundation, 11 S. Capitol St., Pekin, IL 61554 
 
Family Guidance Centers, 2400 Glenwood Ave., Joliet, IL 60435 (serves both Grundy and 
Will County from the same facility) 
All OTPs are licensed by the State of Illinois Department of Health Services, Substance Use 
Prevention and Recovery Division (IHS/SUPR) to provide medication-assisted treatment for 
individuals with opioid use disorders in accordance with state and federal guidelines. These 
programs will: a) coordinate with the research team regarding information on case flow and 
treatment admissions and alert the study team regarding potential study participants who 
consent to meeting with project staff; b) utilize appropriate releases obtained via (1) Business 
Agreements between our agencies and (2) during a research consent process with participants; 
c) share the following information from study participants’ treatment files with the study team: 
dates of admission, dosing days and amount, missed doses, date of discharge (if relevant) and 

12 
 
reason for discharge; and d) maintain regular communication with the Linkage Managers about 
appointments, no shows, and utilization.  
b. Study Procedures, Materials, and Potential Risks 
Materials. The primary sources of material include: 
All participants: 
 
Interview Data.  Face-to-face Interviews conducted at study enrollment at release to the 
community and quarterly follow-ups for 2 years post study enrollment. These interviews will 
consist of the Global Appraisal of Individual Needs (GAIN), quality of life measures from the 
Patient Reported Outcomes Measurement Information System (PROMIS)-R, and several 
study specific questions.  
 
Urine Tests. To increase the validity of self-reported opioid and other substance use, at the 
time of each in-person research assessment, on-site urine screens will be conducted with 
DrugCheck cups and fentanyl test strip using an immunoassay for rapid (2–5 minutes) 
qualitative results based on SAMHSA-standard cutoffs for any kind of heroin/morphine/ 
opioids in general (at 2000 ng/ml), 5 other specific opioids (Buprenorphine, Fentanyl, 
Heroin/Opioid 2000, Methadone, Oxycodone, Tramadol) and 10 other drugs (Alcohol, 
Amphetamine,  Barbiturates, Benzodiazepines, Cocaine, Ecstasy, Marijuana, 
Methamphetamine, Phencyclidine, Synthetic Marijuana ). Each of these tests has 98%+ 
accuracy, as well as temperature and validity strips to check for 6 types of adulterants 
(oxidants, specific gravity, acidity, nitrite, glutaraldehyde, creatinine). On-site urine test 
results will be shared with participants before asking questions about their recent substance 
use.  
 
Treatment Records Data. Each collaborating OTP will be asked to sign a Business 
Associate Agreement to collaborate with researchers on the extraction of information from 
patient records on their admission dates, treatment received, discharge dates, and 
discharge status. Each participant will also be asked to sign a release for parallel treatment 
data from any other OTPs or other MOUD treatment providers, including physician office-
based practice with buprenorphine or naltrexone, or other outpatient or residential SUD 
treatment programs from which they receive treatment.  Consistent with prior trials and 
current studies, OTPs will provide weekly treatment updates.  
 
Death Records Data. With the help of the State of Illinois and respective County 
Departments of Public Health, the research team will obtain information from the County 
Medical Examiner’s office when applicable on participants who are suspected to be 
deceased and/or who could not be located for the final follow-up.  
 
Justice Records Data. With the State of Illinois’ Law Enforcement Agencies Data System 
and help of each participating jail, we will abstract information on the charges, admission 
and release dates from jail at the time of recruitment through 24 months post-release. 
Across state and local official records and self-reports, in our prior studies these measures 
were largely consistent (kappa = .64), with each source identifying some unique cases of re-
arrest or incarceration. 
Participants in the RMC and RMC-Adaptive Conditions: 
 
Brief Treatment Needs Assessment (BTNA). At the beginning of each check up in the two 
RMC conditions, participants will be asked to complete a Brief Treatment Needs 
Assessment (BTNA) to facilitate the intervention. The BTNA includes sections on a) need for 
treatment (i.e., weekly or more frequent substance use since the last assessment, any past 
month SUD symptoms, or a current self-perceived need for treatment; alpha=.85; Test-
retest Kappa=.78), b) potential barriers to treatment access,  c) motivational readiness for 

13 
 
treatment,  d) non project related re-entry services, and e) current treatment and 
incarceration status  
 
Digital recordings of all RMC and RMC-A linkage meetings and RMC-Adaptive case 
conferences will be made and 10% will be reviewed and rated for fidelity to their respective 
strategies. The number of linkage meetings and case conferences, and the participants at 
each, will be documented. 
 
Potential Risks. The main risks associated with this study include: a) the possibility of 
unauthorized disclosure of sensitive information collected by research staff during interviews 
conducted at study enrollment and follow-ups; b) the possibility that interview questions may 
raise some psychological discomfort for the individual regarding their past or current substance 
use; and c) the potential discomfort about being asked about their past criminal behavior 
involvement.    
During the research protocol and interviewer trainings, the PI will be very clear that if 
participants are uncomfortable with any question then the participant does not need to respond. 
The interviewing protocol also requires interviewers to contact their supervisor or PI immediately 
if such instances arise, so they can check in with the participant to determine whether the 
participant needs assistance. Participating OTPs also provide clinical backup when needed. In 
addition, participants are informed that if they report a recent situation involving child or elder 
abuse or neglect, these will be reported to the appropriate authorities. The appropriate 
authorities are also contacted in situations involving threat of harm to self or others.  
2. Adequacy of Protection Against Risks 
a. Recruitment and Informed Consent. Extensive training will be provided by the study 
team to ensure that the study protocols are implemented in a uniform manner and that all 
human subject requirements are observed. As part of the informed consent process, research 
staff will provide participants a copy of the informed consent document, read through it, provide 
them time to ask any questions, address the questions, and solicit their voluntary consent. The 
consent process includes specific releases regarding: (1) audio-recording of RMC sessions if 
they are randomized to the RMC or RMC-Adaptive conditions, (2) the strategies that will be 
used to locate them for follow-up interviews, and (3) permission to obtain information from the 
jail about subsequent recidivism and their OTP or other SUD treatment provider about 
admission, discharge and services received (if applicable).  Participants will also be informed 
that the data collected as part of this study will be shared, without any identifying information, 
with NIH and the JCOIN project for analyses. If they agree, they will be asked to provide oral 
and written consent while being digitally recorded. Participants will also be asked for their 
consent to contact them for the follow-up interviews and urine tests scheduled for 3, 6, 9, 12, 15, 
18, 21 and 24 months post-study enrollment.  Whenever possible, follow-up interviews will be 
conducted at the Lighthouse Institute or OTP offices. If participants no longer reside in the 
county in which they were incarcerated and/or receive treatment, or have become re-
incarcerated, follow-up interviews will be conducted by telephone. A detailed locator form will be 
completed at the time of study intake and it will be updated at each contact. There will be no 
penalties for anyone choosing not to participate. Participants will be compensated $45 for 
assessment ($35 for each 45–60 minute interview and $10 for each urine screen), for a 
potential total of $495 for completion of all 11 interviews.  
b. Protections Against Risk. The investigators and senior staff have all completed the 
required Human Subjects and HIPAA training in protecting people and their privacy during a 
research study and are under the supervision of Chestnut’s IRB. The project will also have an 
independent Data Safety Monitoring Plan. Because there is the risk that some participants might 

14 
 
be in jail or prison at some time during the follow-up period, the IRB has a prisoner 
representative, and we will secure approval from the NIH Office for Human Research 
Protections (OHRP) as well as secure a certificate of confidentiality from NIDA. All key research 
staff at CHS are or will be trained on the principals and process of informed consent through 
NIH’s OHRP online training program (https://phrp.nihtraining.com/users/login.php) and then 
tested by their supervisors. They will also be required to complete NIDA’s training on good 
clinical practice (GCP) for clinical trials (https://gcp.nidatraining.org/). All informed consents will 
be audiotaped for random review. If problems arise from the review, the PI and supervisors will 
meet with staff to correct the problem and meet with the participant when needed to clarify any 
potential confusion.  
All staff involved in data collection will be trained on human subject protections and 
procedures and will provide written agreement to maintain the confidentiality and privacy of the 
information. Data will be managed by research staff via a secured web application that uploads 
each webpage view from the PCs (interviews and urine results). This application was developed 
by and is managed by Chestnut’s GAIN Coordinating Center using a co-location site (i.e., an 
actual node on the internet vs. a connection to the internet). The software can be used for online 
interview while on the phone, when conducted in person, and/or for data entry. It uses secured 
sockets (like a bank), individual password and role authorization, auditing of all access/changes, 
and requires a two-way secure exchange to download data. The current generation of web-
based software was implemented in 2008 and is updated quarterly; as of 12/30/18, it had been 
used to collect 893,846 GAIN interviews by 16,590 staff from 1,349 agencies.   
When starting an interview, research interviewers can see a list of who is participating (in 
order to link records) but not their responses to earlier interviews. Once an interview is 
completed, only the Project Coordinator, Supervisors, Data Managers and IT support staff can 
see the responses to earlier interviews. All access to the system and to individual data is 
automatically logged and the audit trail is reviewed regularly for any inappropriate access. 
Confidential fields (e.g., names and other personal identifiers) are marked and not 
downloadable or visible to data managers. Data managers download, clean, and merge data 
using research ID and dates. They then replace the research ID with a second (randomly 
assigned) linkage ID, convert all dates into “days from randomization,” and check all verbatim 
fields and remove any unexpected names or identifiers. These de-identified files are then used 
by scientists for analysis.  
With regards to the participating OTPs, each will obtain permission to release 
information from patient records to Chestnut Health Systems, in accordance with the Health 
Insurance Portability and Accountability Act of 1996, Public Law 104-191, as amended, and the 
Privacy, Security, Breach Notification, and Enforcement Rules promulgated thereunder at 45 
C.F.R. Parts 160 and 164 (collectively, “HIPAA”). Under HIPAA, “covered entities”, generally 
defined as providers of health care services, may share personal health information of 
individuals they serve with other entities for certain purposes. This permissible arrangement 
under HIPAA will be documented by a “Business Associate Agreement”. The Business 
Associate Agreement will set forth the purposes for which each Department may share 
individuals’ personal health information with Chestnut Health Systems/Lighthouse Institute, 
specify HIPAA-compliant safeguards that Chestnut Health Systems/Lighthouse Institute will take 
to ensure the privacy of personal health information, and prohibit further disclosure of such 
personal health information. Further, each Business Associate Agreement will contain “qualified 
service organization” language, consistent with the Federal Regulations on the Confidentiality of 
Substance Abuse Patient Records found at 42 C.F.R. Part 2. This language is similar in nature 
to the business associate language discussed above but focused on the unique privacy 
safeguards for substance abuse patient records.  

15 
 
All PCs and web/server applications include password protection. Both use technical 
safeguards mandated by Health Information Technology for Economic and Clinical Health Act 
(HITECH) of 2009 for the transmission and maintenance of protected health information (PHI) 
and personal health records (PHR). As noted above, this includes using two-way encryption, 
check sum, double-keying, message authentication, digital signature, Secure Sockets Layer 
(SSL), and password-protected accounts that define levels of access. The possibility of risk 
regarding confidentiality will be minimized by stripping all participant identifying information such 
as name, driver’s license number, and social security number from all interview notes and 
electronic data files. Electronic study information will be kept on a file server that is secure, 
encrypted, and protected by password. Only authorized staff will be allowed to see this 
information. Any study information that is kept on paper will be kept in a locked cabinet in a 
secure place. At the end of all study activities, the Chestnut Health Systems’ research team will 
destroy all information that can identify participants.  
 
The data security officers have also been identified for both CHS’s GAIN ABS interview 
applications (Barbara Estrada) and all of Chestnut’s corporate systems (Jeff Koski). 
Responsibilities of the security officers include developing information technology (IT) security 
policies, increasing security awareness for all project staff, providing virus protection for IT 
resources, maintaining security patches on computing equipment, developing and implementing 
back up procedures, performing periodic vulnerability scanning on IT equipment, reviewing and 
updating firewall strategies and policies, and enhancing the physical security of IT resources. 
c. Vulnerable Subjects.  Individuals who have a history of OUD, as well as involvement 
with the criminal justice system are considered to be vulnerable subjects. Thus we have 
explicitly proposed including an additional data safety plan.  Chestnut’s IRB also includes 
substance use treatment clinicians and prisoner representatives to provide additional 
perspectives related to how we explain the study activities, eligibility for study participation, the 
participant’s rights, the consent process, protections taken to protect participants from any 
identified risks, and the balance of risks and benefits.  
All three groups (including control) will have access to treatment for OUD as usual by the 
jail’s primary provider or other providers.  RMC has previously been shown to be effective with 
people who have SUD and for SUD treatment in general; however, the RMC model has not 
specifically been tested with a focus on individuals who have OUD and are involved with the 
criminal justice system with regard to its effectiveness in treatment linkage and engagement and 
on the specific study outcomes. Thus we have included a replication of RMC with this 
population as the middle condition.  While we have presented preliminary evidence suggesting 
that there is considerable heterogeneity in how fast people respond to RMC, and have proposed 
to test a varying schedule of RMC check-ups in the RMC-A condition, we have included several 
safeguards against reducing the treatment dose to a level that has unintended consequences 
for the participant’s sustained recovery. Specifically we will only increase the interval between 
RMC-A checkups at one-month increments and up to a maximum interval of 5 months. The 
latter would only occur after 5 checkups in a row without assessed need at the prior check-up.  
According to the proposed schedule of RMC-A check-ups, if an individual is not assessed as 
having a need for treatment at any of the scheduled check-ups, he/she will still receive a 
minimum of 5 checkups over 2 years.  
3. Potential Benefits of the Proposed Research to Human Subjects and Others 
Participants may benefit directly by receiving an intervention (RMC or RMC-Adaptive) 
that helps them to initiate and stay in treatment, to reduce their risk of relapse to opioid use and 
overdose, to reduce their use of other substances, and to sustain recovery. At each study 

16 
 
assessment participants will be compensated at a rate of $45 per assessment ($35 for 
completing the interview and $10 for proving a urine sample) for a possible total of $495 for a 
total of 11 interviews over 2 years.  
Participation may also benefit other people in the future by helping the field learn more 
about factors that reduce their risk of relapse to opioids and overdose, and/or other substance 
use, and drop-out of treatment and that promote their sustained treatment retention and 
improvements in quality of life and overall psychosocial functioning, ultimately leading to 
reductions in opioid-related morbidity and mortality and improvements in physical and mental 
health status. For this sample these may also combine to reduce recidivism and improve other 
public safety outcomes. 
4. Importance of the Knowledge to Be Gained  
Opioid use disorders are chronic conditions that have high risk of relapse and are 
associated with poor clinical outcomes, including relapse to opioid use and opioid-related 
overdose, use of other substances, treatment drop-out, and associated high rates of illegal 
activity and recidivism. Successful engagement and retention in treatment with MOUD are 
essential for improving patients’ public health and public safety outcomes. If the experimental 
trial demonstrates the effectiveness and/or cost-effectiveness of RMC or RMC-Adaptive relative 
to re-entry as usual or relative to each other, this information will have important implications for 
reducing risk of relapse to opioid use following re-entry from jail, reducing the risk of opioid-
related overdose, and improving jail and MOUD treatment outcomes, which can be widely 
generalized beyond the immediate study community to other jails/OTPs and potentially 
broadened to address other patient populations with OUD.   
3.2. Multi-site study that will use the same protocols to conduct non-exempt human 
subjects research at more than one domestic site:  Yes 
3.3  Data and Safety Monitoring Plan 
The process for determining whether an adverse event occurs, and for classifying it as 
unexpected, and/or possibly related to participation in the research study, and/or as series, will 
entail continuous review of information collected from study assessments, the participating 
OTPs, and administrative records that are relevant to the status of study participants. 
Definitions of critical events to be monitored are:  
•  The expected Adverse Events (AE) measured directly as part of quarterly observations are 
the days of problems from SUD use, health problems interfering with responsibilities, mental 
health problems interfering with responsibilities, being disturbed by memories, behavioral 
problems, being homeless, family problems, illegal activity, arrests, in trouble with 
parole/probation. 
•  The expected Serious Adverse Events (SAE) measured directly as part of the quarterly 
observation are any medical ER/hospitalization, any mental health ER/hospitalization, and any 
re-incarceration. Deaths are documented both in follow-up logs and (if we have firsthand or 
reliable information) in the negative event report discussed below.  
•  Unexpected AE/SAE (including deaths where we have details) will be documented the same 
day we are informed with the negative event report. This includes documentation to code who 
was there, when/how it happened, where it happened, what actions were taken (e.g., referral to 
clinical supervisor, police report, hotline call).  

17 
 
In terms of timing, the DSM Plan will be reviewed by the IRB and funder prior to starting 
fieldwork. Annual reports of data collected to date (including case flow, checks on 
randomization, implementation, method checks on measures, preliminary outcome analyses, 
expected and unexpected AE/SAE, and all negative event forms) will be reviewed by the PI and 
used to generate our annual progress report to DSMB, IRB and NIDA. If any review reveals a 
significant difference in AE, SAE, or dependent variables that go AGAINST the experimental 
condition or appears to be related to a study specific procedure, we will consult with the IRB 
regarding the need to modify the protocol, study procedure, or stop the study. The stopping rule 
would be based on a statistically significant (p<.05) and clinically significant (d<-0.2) in the 
wrong direction. 
Note that all unexpected AE/SAE and actions taken will be documented on the negative event 
form and reviewed within 48 hours by the PI (who will classify the incident as a SAE, AE, or 
other), the degree to which it is related to intervention or research procedures, and document 
any actions taken (with client, reporting to IRB). Any SAE or other events that are attributed to 
the intervention or research procedure and any sentinel event will be reported with 48 hours to 
the IRB and NIDA project officer for further review. For sentinel events, we follow the Joint 
Commission definition of a sentinel event as “any unanticipated event in a healthcare setting 
resulting in death or serious physical or psychological injury to a patient or patients, not related 
to the natural course of the patient's illness.” (See 
https://www.jointcommission.org/assets/1/18/Sentinel%20Event%20Policy.pdf )  
3.4  Data and Safety Monitoring Board   
We will use the JCOIN DSMB convened by NIDA.  
Section 4: Protocol Synopsis 
4.1 Brief Summary  
This project aims to complement HEAL’s Justice Community Opioid Innovation Network 
(JCOIN) initiative by focusing on post-release recovery in 6 Illinois county jails with the goal of 
increasing linkage to and retention in community based Medication Assisted Treatment (MAT), 
and reducing both opioid use disorder (OUD) relapse and criminal recidivism over 2 years. We 
will conduct a randomly controlled trial comparing: a) re-entry as usual, b) Recovery 
Management Checkups (RMC), and c) an adapted version of RMC, RMC-A, that varies the 
intensity of recovery monitoring based on the person’s need for treatment.  
The Nation’s Justice System provides a unique opportunity to help address this crisis as the 
justice population has a significantly higher rate of OUD than the household population, with 
roughly 1 in 4 people with OUD passing through the justice system each year. Re-entry into the 
community is a critical intercept point for linkage to opioid treatment programs (OTP), as there is 
ample evidence that the risk of relapse peaks in the initial period following release. Yet research 
has shown that only 25 to 50% of those receiving justice referrals to community-based OTPs or 
other providers of MOUD initiate treatment within 90 days. Justice referrals are also significantly 
less likely than non-justice referrals to remain in treatment for OUD for 90 days or longer. The 
combination of high rates of OUD and low treatment linkage and retention rates following 
release underscore the importance of improving the transition between incarceration and 
community-based treatment.  
 
To date, 3 randomized controlled trials have demonstrated RMC’s effectiveness by increasing 
treatment engagement and retention in substance use treatment (not focused on treatment with 
MOUD), re-linking recovering participants to treatment when indicated, and improving their 
treatment outcomes. Relative to controls, participants in the RMC condition reported more 

18 
 
treatment initiation, more days of treatment, fewer days of substance use, and fewer health 
symptoms overall. Within the RMC condition of the 3rd trial, there was considerable variation in 
how quickly people responded to checkups, as well as their pattern of treatment need over time. 
This trial provided a large enough  subset of detainees (n=101) with OUD re-entering the 
community from jail and enrolled in RMC to examine multiple predictors of treatment need 
during two time periods, monthly and quarterly. In both cases, the best predictor of future need 
for treatment was the participant’s need for treatment at the prior two checkups. Relative to 
RMC participants not in need of treatment, RMC participants who needed treatment in the prior 
2 monthly checkups were almost 5 times more likely to “need treatment at 6 months post-
release”. Likewise, between 12 to 24 months, RMC participants who needed treatment at either 
of their two prior quarterly checkups were almost 18 times more likely to need treatment at the 
next checkup. These findings suggest that tailoring the checkup frequency to the individual’s 
need for treatment may help target resources to those in need and reduce the burden on those 
with lower need, thus resulting in an improved overall effectiveness and cost-effectiveness of 
RMC checkups. 
 
The goal of the proposed experiment is to compare linkage and retention rates, as well as public 
health and public safety outcomes of 750 male and female detainees who will be randomly 
assigned to 1 of 3 groups upon their release from jail: a) re-entry as usual (control), b) the 
original RMC on a fixed schedule, and c) an RMC-Adaptive version in which the frequency and 
content of checkups will be based upon the participant’s ongoing progress. The study will be 
conducted in collaboration with 6 county jails in Illinois and the organizations approved to 
provide pre- and post-release MAT. Pre-release participants will be screened for history of 
OUD. All participants will participate in baseline and quarterly research interviews for 2 years, 
which will also include urine testing and records checks (OUD treatment, mortality, recidivism). 
The specific aims are to evaluate: 1) The direct effects of RMC on the OUD service cascade of 
care (initiation, engagement, retention, and re-linkage, and months of MOUD treatment); 2) The 
indirect effects of RMC (via months of MOUD treatment) on public health outcomes (days of 
opioid use, OUD symptoms, quality of life and the cost-of-healthcare-utilization); 3) The indirect 
effects of RMC (via months of MOUD treatment and public health outcomes) on public safety 
outcomes (illegal activity, re-arrest, re-incarceration, and cost-of-crime); and 4) The incremental 
costs and cost-effectiveness of the control vs. RMC vs. RMC-Adaptive in terms of both public 
health outcomes (days of opioid use, quality adjusted life years (QALYs), cost-of-health-care 
utilization) and public safety outcomes (re-incarceration and cost-of-crime). 
 
4.2 Study Design 
 
The RMC experiment will be conducted in collaboration with 6 jails representing discrete 
geographic counties in Illinois and the OTPs that serve them. It will compare a re-entry as usual 
control group with two experimental groups in terms of their impact on the OUD service 
cascade, as well as public health and public safety outcomes. Five participating jails provide 
MOUD for inmates with OUD prior to their release and the sixth will begin offering it later this 
summer. At the time of their release to the community, 750 men and women will be randomly 
assigned to 1 of 3 groups: a) a re-entry as usual control, b) RMC with monthly checkups for 3 
months post-release followed by quarterly checkups up to 2 years, or c) an adaptive version of 
RMC (RMC-A) that includes a modified checkup schedule based on each individual’s pattern of 
treatment need. All participants will complete research interviews at release and quarterly 
thereafter up to 2 years post-enrollment.  
 
Study Aims and Hypotheses 
 

19 
 
Aim 1. The direct effects of RMC on the OUD service cascade (initiation, engagement, 
retention, and re-linkage, and months of MOUD treatment).  
H1a. Relative to the control group over 24 months, the participants in the two RMC groups 
will be more likely to initiate MOUD and participate in MOUD treatment more months.  
H1b. Relative to the RMC group over 24 months, the participants in the RMC-Adaptive 
group will be more likely to initiate MOUD and to participate in MOUD treatment more 
months. 
Aim 2. The indirect effects of RMC (via months of MOUD treatment) on public health outcomes 
(days of opioid use, OUD symptoms, quality of life and the cost-of-health-care utilization). 
H2a. Relative to the control group, the participants in the two RMC groups will have better 
public health outcomes (fewer days of opioid use, fewer OUD symptoms, better quality of 
life, and lower cost-of-health-care-utilization) in the next quarter.  
H2b. Relative to the RMC group, the participants in the RMC-Adaptive group will have 
better public health outcomes in the next quarter.  
H2c. More months of MOUD treatment (regardless of group assignment) in a given quarter 
will be associated with fewer days of opioid use in the next quarter. 
H2d The months of MOUD treatment will mediate the relationship between group 
assignment and public health outcomes.  
Aim 3. The indirect effects of RMC (via treatment and public health outcomes) on public safety 
outcomes (illegal activity, re-arrest, re-incarceration, and cost-of-crime) 
H3a. Relative to the control group, the participants in the two RMC groups will have better 
public safety outcomes (illegal activity, re-arrest, re-incarceration, and cost-of-crime) in the 
next quarter.  
H3b. Relative to the RMC group, the participants in the RMC-Adaptive group will have 
better public safety outcomes in the next quarter.  
H3c. More months of MOUD treatment and better public health outcomes (regardless of 
group assignment) in a given quarter will be associated with better public safety outcomes 
in the next quarter. 
H3d The months of MOUD treatment and public health outcomes will mediate the 
relationship between group assignment and public health outcomes.  
Aim 4. The incremental costs and cost-effectiveness of the control vs. RMC vs.  RMC-Adaptive 
in terms of both public health outcomes (days of opioid use, quality adjusted life years (QALYs), 
cost-of-health-care utilization) and public safety outcomes (re-incarceration and cost-of-crime). 
H4a. Relative to the control group over 24 months, the participants in the two RMC groups 
will have lower cost-per-outcome (e.g., days of opioid reduced; QALYs gained).  
H4b. Relative to the RMC group over 24 months, the participants in the RMC-Adaptive 
group will have a higher cost, but also greater effectiveness in reducing opioid use and in 
QALYs gained. 

20 
 
H4c. Relative to the control group over 24 months, the participants in the two RMC groups 
will have significantly lower healthcare utilization, criminal activity, and criminal justice 
system costs.  
H4d. Relative to the RMC group over 24 months, the participants in the RMC-Adaptive 
group will have significantly lower healthcare utilization, criminal activity, and criminal justice 
system costs.  
 Experimental Conditions 
 
(1) Re-Entry as Usual  
 
The type and level of services provided to individuals at re-entry will vary across jails and will be 
carefully documented. For the most part, individuals released to the community will receive a 
referral to an OTP, and a subset may potentially be mandated to participate in community based 
treatment and/or recovery programs such as recovery coaching, and/or sentenced to varying 
levels of probation. Referrals and services provided to all participants will be documented at 
each research interview.  
 
(2) Recovery Management Checkups (RMC) 
 
In the RMC condition, participants will have access to services provided as a part of re-entry as 
usual. In addition, checkups will be provided on a fixed schedule that includes face-to-face 
monthly checkups for 3 months, and quarterly for the rest of the two years. Participants will have 
access to referrals and services provided by the jail and MOUD treatment provider as part of 
their usual re-entry procedures. Individuals will meet with a Linkage Manager (LM) upon study 
enrollment and during each quarterly checkup, during which they will complete a Brief 
Treatment Needs Assessment, receive motivational interviewing, linkage assistance, or a 
check-in on continuing care and recovery support. The priority is to engage the individual into 
treatment with MOUD as soon as possible at the time of release, however, if individuals express 
a preference for another form of SUD treatment, the LM will work with that individual to link, 
engage, and retain them in that form of treatment.  
 
(3) RMC-Adaptive 
 
The RMC and RMC-A conditions differ in three significant ways. First, in the RMC-Adaptive 
condition, checkups will be provided based on the participant’s current need for treatment. In 
contrast, those in the RMC condition receive checkups on a fixed quarterly schedule regardless 
of need. The interval between RMC-A check-ups will vary (in one-month increments) depending 
upon the individual’s assessed need for treatment at the prior check-up. Second, in cases 
where participants have 3 consecutive checkups in which they need treatment, the intervention 
strategy will be adapted to include a meeting of the LM and treatment staff to determine how to 
better meet the participant’s needs, e.g., a different treatment provider, different type of MOUD 
or other types of treatment, and/or additional services. Third, if RMC-Adaptive participants are 
re-incarcerated at the time of their checkup, the LM will meet with the individual while 
incarcerated to discuss a recovery plan, which may include initiation of MOUD while 
incarcerated and/or re-linkage to treatment with MOUD upon release.  
 
Instruments, Data Sources, and Measures 
 

21 
 
Interview data. Baseline participant characteristics, days of MOUD treatment and other SUD 
treatment received, days of opioid use, symptom counts and health-care-utilization-costs (for 
Aims 2-3) will come from the 25-minute Global Appraisal of Individual Needs - Quick (GAIN-Q3) 
administered at study enrollment and quarterly for 24 months post-study enrollment. The GAIN-
Q3 includes 8 primary domains: 1) background, 2) school problems, 3) work problems, 4) 
physical health, 5) sources of stress, 6) HIV risk behaviors, 7) substance use, and 8) crime and 
violence. In each area, there are 5–10 item symptom counts that are correlated ~.9 with the 
respective 16 to 43 item versions in the full 2-hour GAIN and have 90% sensitivity and 90% 
specificity for diagnosis from the full GAIN. The response set captures the recency of these 
symptoms (lifetime, past year, past 90 days, past month) and treatment involvement, then the 
frequency (days) of behaviors/treatment utilization in the past 90 days. The GAIN-Q3 also 
includes the behavioral health screener and healthcare-utilization measures recommended by 
NIH’s PhenX common data platform. The GAIN-Q3 includes measures of days of MOUD 
treatment and other SUD treatment received, and heroin and other opioid use (for Aims 1-2), as 
well as symptom counts for SUD, other internalizing and externalizing mental health disorders, 
physical health disorders. It also includes questions on health-care-utilization and costs (for Aim 
4).   
 
The interview will be supplemented with the GAIN-I’s Opioid Use Disorder Scale to give a more 
specific DSM-5 based symptom count at baseline and each quarter, as well as the General 
Crime Scale to obtain a more detailed measure of illegal activity and the cost-of-crime (for Aims 
2-4). The interview will include questions on quality of life from the Patient Reported Outcomes 
Measurement Information System (PROMIS-R), with U.S. norms to generate quality adjusted 
life years (QALYs) for Aim 4. QALYs comprise a single metric ranging from 0 to 1, where 0 is 
equivalent to death and 1 is equivalent to optimal health.  
 
The Brief Treatment Needs Assessment (BTNA) will be administered at the beginning of each 
RMC/RMC-A checkup to facilitate the intervention. It includes sections on a) eligibility for 
linkage, b) need for treatment (weekly or more frequent substance use since the last 
assessment, any past month SUD symptoms, or a current self-perceived need for treatment), c) 
potential barriers to treatment access, and d) motivational readiness for treatment. 
 
Interviews will also document services and activities provided via re-entry as usual, such as: 
receipt of MOUD received outside of the project-related OTPs and other SUD treatment; 
assistance with Medicaid; and transportation assistance, referrals, recovery coaching, or case 
management. Data will be collected via a cloud-based computer program that controls ranges 
and skip outs and identifies major inconsistencies. All interviews will be taped, and two tapes a 
month will be randomly selected and reviewed for quality assurance. 
 
Urine Drug Testing  
 
On-site urine screens will be conducted with DrugCheck cups and fentanyl test strip using an 
immunoassay for rapid (2–5 minutes) qualitative results based on SAMHSA-standard cutoffs for 
any kind of heroin/morphine/ opioids in general (at 2000 ng/ml), 5 other specific opioids 
(Buprenorphine, Fentanyl, Heroin/Opioid 2000, Methadone, Oxycodone, Tramadol) and 10 
other drugs. Each of these tests has 98%+ accuracy, as well as temperature and validity strips 
to check for 6 types of adulterants. On-site urine test results will be shared with participants 
before asking questions about their recent substance use in order to minimize false negatives to 
3% or less, as has been done in our prior RMC studies. Dr. Dennis will train the research staff 
on the protocol and conduct cross-validation of the self-report and urine test data. 
 

22 
 
Treatment Records Data  
 
Each collaborating OTP will be asked to sign a business associate agreement allowing 
researchers to extract information from patients’ case files on admission dates, treatment 
received, discharge dates, and discharge status. Each participant will also be asked to sign a 
release for parallel treatment data from any other MOUD provider or SUD treatment provider 
from which they receive treatment. Consistent with prior trials and current studies, agencies will 
provide weekly treatment updates. 
  
Death Records Data 
 
The research team will obtain information from the County Medical Examiner’s office when 
applicable on participants that staff interview logs suggest have died and/or who could not be 
located for the final follow-up.  
 
Justice Records Data  
 
The study team will abstract information on the charges, admission, and release dates from jail 
at the time of recruitment through 24 months post-release. In prior studies, measures were 
largely consistent (kappa = .64) across state and local official records and self-reports, with 
each source identifying some unique cases of re-arrest or incarceration. 
 
Drug Abuse Treatment Cost Analysis Program (DATCAP)  
 
The cost of standard RMC and RMC-Adaptive will be estimated using the Drug Abuse 
Treatment Cost Analysis Program (DATCAP), a standardized and widely used costing survey 
that estimates the direct and opportunity costs of interventions in terms of staff/personnel 
salaries (plus fringe benefits), other direct costs, value of donated or subsidized resources, and 
overhead. The DATCAP is designed to facilitate data collection from agency/provider 
accounting systems and research records. Data are organized in an Excel workbook with built-
in algorithms to generate summary statistics using data on intervention engagement and patient 
case flow: total annual program cost, average annual cost per patient; average cost per 
treatment episode (per patient).  
 
Measures 
 
The primary outcome measure for the study is Months of MOUD treatment across 24 months 
post-release for Aims 1 and 4, as well as quarterly for Aims 2 & 3.This is a continuous measure 
from OTP records (Interclass Correlation Coefficient [ICC]=.37 when measured quarterly). The 
count will be based on days of medication received (including any take-home dosages), with 
injectable naltrexone being counted as treatment for 30 days. See section 4.3 for more details 
on secondary outcomes.   
 
Participants  
 
Inclusion criteria are: meeting the Diagnostic and Statistical Manual version 5 (DSM-5) opioid 
use disorder (OUD) criteria in the past year, heroin or other opioid use in the 90 days prior to 
entering jail, and being released from one of the participating jails to the community.  Exclusion 
criteria are: less than age 18, cognitive impairment that precludes ability to give informed 
consent, and resides outside the service area.  
 

23 
 
We anticipate that overall, 34% of participants will be female; 11% will be Hispanic; 75% white, 
16% black; and 9% mixed/other race. We expect 5% to be ages 18-20, 26% ages 21-25, 48% 
ages 26-49, and 19% to be 50 to 64, and less than 1% to be age 65 or older. OTPs estimate 
that about half of patients drop out of treatment within 3 to 12 months.  
 
Opioid Treatment Programs 
 
All OTPs use a clinical assessment to make a diagnosis based on the Diagnostic and Statistical 
Manual version 5 (DSM-5) placement based on the Patient Placement Criteria version 3, and 
are licensed by the Illinois Department of Human Services/ Division of Substance Use 
Prevention and Recovery (SUPR) for the provision of outpatient medication assisted treatment 
and other SUD treatment services.   
 
Recruitment 
 
Phase I: In Jail Screen for Study Eligibility. The study team will use two methods that have been 
successfully used in prior studies to recruit eligible individuals from jail settings and to engage 
them in the study. In the first method, staff at the jail (these may be corrections staff, medical 
staff, or staff from contracted MOUD providers) will identify individuals who have already been 
assessed with OUD (as part of the usual screening protocol), provide them with an overview of 
the study, and, for those interested in learning more about the study, will secure their permission 
for a study research assistant (RA) to contact the candidate, confirm their eligibility (based on 
age and residency), and discuss transportation to the research office upon their release. In the 
second method, the RA will meet with the candidate immediately following their release, briefly 
overview the study, and discuss transportation to the research office post-release. Both 
procedures will allow the study team to contact individuals who have initiated treatment with 
MOUD pre-release as well as those who are quickly released, and may not have initiated 
treatment with MOUD.  The study procedures may vary across the different jail sites dependent 
upon the established procedures for screening individuals for OUD upon their admission and for 
engaging them into MOUD prior to their release. 
 
Phase II: Re-entry Meeting, Baseline Data Collection and Randomization. To maximize timely 
participation in the re-entry meeting, participants will be transported to the research office and 
given a $45 gift card upon completion of the baseline interview. Using similar procedures in the 
RMC re-entry trial, from the date of release, 90% were enrolled within 7 days). RAs will then 
provide a detailed description of the study, and for those who agree to participate, RAs will 
administer the informed consent, complete the baseline research interview, update the locator, 
notify the Research Manager to randomize participants, and schedule the next research 
interview. The Research Manager will randomly assign participants to one of 3 conditions: 
control, RMC, RMC-A. Urn randomization adjusts the probability of assignment to each 
condition in ways that simultaneously minimizes differences in multiple stratification variables. 
The base rate will be set at 33% to each condition, and software set to simultaneously balance 
assignment by the county, days of opioid use in the 90 days prior to incarceration, and probation 
status at the time of release. It will also take into account participant characteristics that have 
been previously associated with differences in MOUD treatment retention and outcomes, 
including sex, age, cocaine use, and mental health problem severity. The Research Manager 
will enter the information into the program, generate the assignment, and inform the participant’s 
RA of the assignment. Next, persons assigned to the RMC or RMC-A conditions will meet with a 
linkage manager. 
 
Quarterly Research Interviews 

24 
 
 
RAs will complete 90-minute enrollment and quarterly follow-up research interviews with 
participants in all conditions. Study participants will receive a $45 gift card - $35/interview and 
$10/urine. The team will implement Dr. Scott’s structured follow-up model which has reliably 
produced over 90% follow-up rates across studies involving over 70,000 patients regardless of 
population, primary drug type including heroin, and over follow-up periods ranging from 3 
months to 18 years. Steps include: (a) contacting participants within 24-48 hours of study 
enrollment to collect additional locator information and mailing a schedule card for the next 
interview, (b) tracking status of interviews and locator information in a secure database, (c) 
assigning each case to a follow-up case tracker, (d) verifying locator data, (e) conducting 
outreach for unverified cases and discussing them at weekly meetings, (f) mailing thank-you 
cards to participants and collaterals, (g) scheduling follow-up appointments in advance, (h) 
mailing 3 and 6 week post-enrollment flyers, (i) implementing returned-mail procedures, (j) 
calling participants 6 weeks before appointment to confirm date and location (phone vs. 
research office), (k) conducting outreach for unconfirmed cases and reviewing them at weekly 
meetings, (l) completing follow-up interviews and scheduling next appointments, (m) 
implementing a no-show protocol, and (n) incentives for both completing the interview and urine 
drug test. Progress will be monitored with daily management reports.  
 
Analytic Plans and Statistical Power 
 
Missing data  
 
Participants will complete their enrollment interviews prior to randomization. Based on prior 
studies conducted by the applicants, it is expected that approximately 90% or more of the 10 
post-enrollment interviews will be completed. Among these completed interviews, prior studies 
indicate that there will be less than 1% additional missing data on any of the core items required 
to test the hypotheses. “Item-level” missing data will be replaced within subject where possible, 
or with multiple imputations or restricted maximum likelihood to provide the least biased 
estimate for each analysis. To further reduce potential bias, analyses will be rechecked by 
running them without missing data. If there are any clinically significant differences (d>|.2|), a 
general latent variable framework will be used to analyze non-ignorable or systematic missing 
data that tests whether missing data is qualitatively different by condition. “Observation level” 
missing data from when an interview was not conducted will be evaluated in an intent-to-treat 
analysis using the average of the available observations or the last observation. 
 
Analysis of Comparative Effects (Aim 1) 
 
The analysis for Aim 1 is designed to evaluate, (H1a) relative to the re-entry as usual control 
group, the extent to which providing RMC and RMC-Adaptive significantly increases the rates of 
initiating treatment with MOUD and months of MOUD treatment over 24 months, and (H2a) 
these same outcomes for RMC-Adaptive relative to RMC. The marginal effects will be initially 
evaluated with a Chi-square (for MOUD treatment initiation) and Mann Whitney U rank test of 
the distributions (for months of MOUD treatment) comparing the main effect. Duration of MOUD 
treatment ranges from 0 to 24 months but is expected to be zero saturated, right skewed and 
multimodal with concentrations at none (no initiation), 1-3 months (first half to drop out) and then 
another distribution between 3 and 24 months (longer term patients). Mann-Whitney U tests 
address these issues by ranking observations (regardless of condition) and then comparing 
conditions on the distributions of the ranks.  For non-normal distributions it is more powerful 
than a t-test. The proposed samples are sufficiently large that U will approximate a normal 
distribution and can be transformed into a z-score and/or Cohen’s effect size d.  

25 
 
 
Because the size of the RMC effects increase with repeated intervention exposure, we will 
evaluate the changes in the observed effects on months of MOUD treatment over time using 
multilevel structural equation modeling (MSEM) with mixed effects in MPlus (version 6.1) 
controlling for the number of months (i.e., % of months of participation). The analysis will model 
observations (Level 1) nested within participants (Level 2), and participants nested within 
counties (Level 3). Random assignment to 1 of 3 groups, being released on probation and being 
mandated to treatment will each be modeled as a Level 2 predictor. We will test differences in 
the a-intercept and slope over time. Participants will be modeled as a random factor to control 
for repeated observations on the same person. Because probation status and type of 
medication received may change over 24 months, these are represented as time-varying 
covariates by observation (Level 1). The impact of dosage is evaluated with growth curve 
analysis to see if the difference between RMC-A and the control group increases with checkup 
dosage (i.e., by observation at level 1). As a function of ICC, these kinds of repeated measures 
analyses in general increase the effective number of n for the analysis to somewhere between 
the number of unique individuals (n=750; when ICC=1) and the number of observations 
(o=6750; when ICC=0). MSEM also incorporates measurement error corrections. 
 
Analysis of Indirect Effects on public health outcomes (days of opioid use, OUD symptoms, 
quality of life, and the cost-of-health-care utilization) (Aim 2) 
 
The first part of the analysis for Aim 2 is designed to evaluate H2a relative to community re-
entry as usual control group. It will examine the extent to which providing RMC and RMC-
Adaptive in one quarter significantly improve public health outcomes in the next quarter, and 
H2b, relative to RMC, to determine if RMC-Adaptive further improves public health outcomes in 
the next quarter. It will parallel the analysis for Aim 1. The second part of the analysis for Aim 2 
is to examine the extent to which the months of MOUD treatment in the prior quarter mediates 
these two relationships H2c and H2d respectively, as shown in Figure 3. Evaluation across two 
quarters also serves to establish temporal order, and strengthen our ability to make causal 
inferences. Modeling the effects of MOUD treatment is important as even the re-entry as usual 
control group will have some level of it, and to the extent they do, it is included in this effect. We 
will test these correlations and then use them to separate the direct and indirect effects of the 
experimental intervention on each outcome using MSEM. To do so, we will arrange records in a 
hyper-vertical file with each record having data from a given quarter and the next available 
quarter as we have done before in prior studies.  We will control for repeated observations by 
including person as a random effect, and include the duration between observations to partial 
out any methods effects. This suggests the likelihood of an indirect effect via MOUD treatment. 
Note that at the time, other types of MOUD had not yet become widely used. Indirect effects of 
the experimental intervention on each outcome will be evaluated using MacKinnon’s joint-
significance testing of the path z-scores with a Sobel test using a standard error based on 
bootstrapping and criteria of p<.05 on the degree of difference between conditions. We will also 
examine the effects of pre-release treatment with MOUD, type of MOUD, county, checkup 
dosage, and sex by testing whether the observed SEM paths are ‘invariant’ across each. 
 
Analysis of Indirect Effects of RMC (via treatment and public health outcomes) on public safety 
outcomes (illegal activity, re-arrest, re-incarceration, and cost-of crime) (Aim 3) 
 
The analysis for Aim 3 is designed to evaluate: (H3a) relative to community re-entry as usual, 
the extent to which providing RMC and RMC-Adaptive in a given quarter significantly improves 
public safety outcomes in the next quarter; and (H3b) relative to RMC, whether RMC-A in a 
given quarter improves public safety outcomes in the next quarter. It will parallel the analysis for 

26 
 
Aims 1 & 2. The second part of the analysis for Aim 3 is to examine the extent to which the 
months of MOUD treatment and public health outcomes in the prior quarter mediates these two 
relationships (H3c and H3d), respectively, as shown in Figure 3. We will test these relationships 
in a manner similar to the analysis for Aim 2, but here we will allow all three of the opioid 
predictors to enter the model and examine their ability to predict the other outcomes together in 
a MSEM. Data from these analyses will be combined into a path model, and the indirect effects 
of the experimental intervention on longer-term outcomes will be evaluated using MacKinnon’s 
joint-significance testing of the path z-scores with a Sobel test using a standard error based on 
bootstrapping and criteria of p<.05 on the degree of difference between conditions. 
 
Cost-Effectiveness Analysis (Aim 4)  
 
The Cost-Effectiveness Analysis (CEA) will be framed from the healthcare sector (e.g., OTP 
provider, third party payers) and societal (i.e., factoring in costs of criminal activity and criminal 
justice events) perspectives. For each site, differences in costs and effects between study 
conditions will be estimated using multilevel general linear models (e.g., generalized linear 
mixed models or GLMM). These models can control for factors that are unbalanced between 
study arms and allow for the inclusion of random effects that can account for clustering at the 
site-level as well as the individual (client) level. With GLMM, the most appropriate mean and 
variance functions can be selected based on the fit of the data. Predicted mean effectiveness 
and mean costs of the RMC interventions and control are compared and used to calculate 
incremental cost-effectiveness ratios (ICERs), the main result for Aim 4. The ICER reports the 
marginal cost to achieve a unit of desired outcome (e.g., a QALY or one fewer overdose) in an 
RMC strategy relative to control (or in RMC-Adaptive relative to RMC). ICERs must be 
interpreted according to the value society places on this “per unit” improvement or reduction. 
Such a value is known as willingness-to-pay (WTP) and is used to designate the cost-
effectiveness threshold. Although it is not intelligible exactly what society is willing to pay for one 
less overdose or other outcome, the analyst can project a value or range of values for WTP per 
unit of outcome to interpret the ICER in terms of net benefit (NB) and incremental net benefit 
(INB). For instance, if society values one fewer opioid overdose at $1,000, the NB of each study 
condition is the number of avoided overdoses over follow-up multiplied by 1,000, minus 
condition costs. The INB is simply the difference in NB between study conditions. The proposed 
analyses will use a nonparametric bootstrapping method within the multivariable framework to 
compute confidence intervals for assessing uncertainty in the ICERS for RMC-Adaptive versus 
control, RMC versus control, and RMC-Adaptive versus RMC. These confidence intervals form 
cost-effectiveness acceptability curves (CEACs) based on what society may be willing to pay to 
achieve an additional unit of effect (e.g., one day of abstinence or one QALY). Given that 
commonly accepted value thresholds do not exist for most outcomes, the CEACs provide 
context for interpreting the CEA results by illustrating the probability that a strategy is a good 
value for different value thresholds. For instance, in the context of RMC-Adaptive versus control, 
the ICER reports the marginal cost of achieving one percentage point reduction in overdose for 
individuals receiving RMC-Adaptive relative to controls. The calculation of the ICER can be 
modified such that the numerator, incremental costs, includes any savings generated by 
reductions in healthcare or criminal justice costs.  
 
Interventions  
 
(1) Re-entry as usual  
The types and levels of community services provided individuals at re-entry will vary across 
jails. For the most part, upon their release to the community, individuals who have been 
diagnosed with opioid use disorders will receive a referral from the jail or their OTP to a local 

27 
 
OTP that includes the location, date, and time of their next treatment appointment. Referrals 
and services provided to all participants related to their treatment for opioid use disorders will be 
documented at each research interview. 
 
(2) Recovery Management Check-up (RMC) 
In the RMC condition, participants will have access to referrals and services provided by the jail 
as part of their usual re-entry procedures. In addition, RMC checkups will be provided on a fixed 
schedule that includes face-to-face monthly checkups for 3 months and quarterly checkups for 
the remainder of the two-year intervention period. The priority will be to engage the individual 
into treatment with MOUD as soon as possible at the time of their release to the community. 
However, if individuals decline to participate in treatment with MOUD, but express an interest in 
another form of substance use disorder (SUD) treatment, they will receive the standard linkage 
and referral components of the RMC to their preferred form of treatment. Individuals will meet 
with a Linkage Manager (LM) at each quarterly checkup, during which they will complete a Brief 
Treatment Needs Assessment, receive motivational interviewing and recovery support, and 
linkage or re-linkage to treatment, if needed. 
  
(3) RMC-Adaptive (RMC-A) 
In the RMC-A condition, participants will have access to referrals and services provided by the 
jail as part of their usual re-entry procedures. The RMC-A condition differs in 3 ways from the 
standard RMC. First, participants will receive monthly checkups during the first 2 months post-
release with additional checkups dependent upon the participant’s progress. The interval 
between RMC-A check-ups will be adjusted (in monthly increments) based on the individual’s 
status at the prior check-up. Second, after 3 consecutive checkups in which the individual has 
an assessed need for treatment, the LM will meet with treatment staff to determine if changes to 
the treatment plan or additional support are needed. Third, if an RMC-A participant is re-
incarcerated at the time of their checkup, the LM will meet with the individual in the jail to 
discuss a recovery plan, re-linkage to treatment, and transportation to the research office upon 
release.    
 
4.3 Outcome measures 
 
Name  
Type  
Time Frame  
Brief Description  
Months of 
MOUD 
treatment 
Primary 
Across 24 
months post 
release for Aim 
1 and 4; 
quarterly for 
Aims 2 & 3 
A continuous measure from OTP records 
(Interclass Correlation Coefficient [ICC] =.37 
when measured quarterly). The count will be 
based on days of medication received 
(including any take-home dosages); 
injectable naltrexone will be counted as 
treatment for 30 days. Missing records data 
will be estimated from self-report.  
Opioid Use 
Disorder (OUD)  
service 
cascade   
Secondary Across 24 
months post- 
release for Aim 
1 
Calculated from justice and treatment 
records, these will include both dichotomous 
measures of whether each of the following 
events happen and continuous measures of 
the days from jail release to: a) initiation of 
treatment with MOUD, b) engagement in 
MOUD treatment for at least 6 weeks, c) 
retention in MOUD treatment for at least 90 
days (median in national data), and d) 
retention for at least 6 months, as well as 

28 
 
times from post-drop out and relapse to re-
linkage to treatment with MOUD. Largely 
used descriptively.  
Days of Opioid 
Use 
Secondary Quarterly for 
Aims 2 and 3; 
across 24 
months for Aim 
4 
A self-reported count 0 to 90 days of using 
any kind of opioids each quarter (test-retest 
rho=.95; ICC=.34 across quarters). There 
will also be additional measures of the days 
of using heroin, fentanyl, and prescription 
opioid misuse for descriptive use.  All come 
from a standardized assessment tool called 
the Global Appraisal of Individual Needs 
(GAIN). 
Opioid Use 
Disorder (OUD) 
Symptoms 
Secondary Quarterly for 
Aims 2 and 3; 
across 24 
months for Aim 
4 
A self-reported count of the 0 to 11 the 
Diagnostic and Statistical Manual version 5 
(DSM-5) symptoms of Opioid Use Disorders 
(OUD) each quarter from the GAIN 
(alpha=.95; ICC=.28 across quarters). There 
will also be alternative measures for OUD 
symptoms in the past month, year, and 
lifetime, as well as a measure of DSM-5 
symptoms across other SUD each quarter.  
Quality of Life 
(QoL) 
Secondary Quarterly for 
Aims 2 and 3; 
across 24 
months for Aim 
4 
This measure is based on the Patient 
Reported Outcomes Measurement 
Information System (PROMIS) – R. It is the 
self-reported frequency of problems in with 
reference to the past 7 days in 8 domains: 
physical function, anxiety, depression, 
fatigue, sleep disturbance, ability to 
participate in social roles and activities, pain 
interference, and cognitive function ability, 
and an overall measure of pain intensity.  
Costs-of-
Healthcare-
Utilization 
Secondary Quarterly for 
Aims 2 and 3; 
across 24 
months for Aim 
4 
This cost measure is based on the self-
reported frequency of healthcare services 
related to substance use, mental health, and 
physical health, measured in units such as 
“days,” “visits,” or “episodes”, which are 
multiplied by corresponding monetary 
conversion factors (price weights for a unit 
of service) to estimate a continuous “total 
healthcare costs” variable and trimmed at 
the 99% percentile due to sharp right skews 
(ICC=.27 across quarters). We will 
collaborate with the JCOIN economic 
studies across hubs on the measures to be 
used for this variable. Dr. McCollister and 
her colleagues updated these cost estimates 
to 2017 and will adjust them forward using 
the consumer price index. 
Illegal Activity 
Secondary Quarterly for 
Aims 3; across 
This is a self-reported count of 19 items 
across different types of illegal activities 

29 
 
24 months for 
Aim 4 
related to property crimes (e.g., vandalism, 
bad checks, theft, breaking and entering), 
personal crime  (e.g., assault, rape, murder), 
and substance use (driving under the 
influence, distribution, prostitution, gang 
membership, gambling) in the past quarter 
(alpha=.9; ICC=.20 across quarters). An 
alternative version collects the frequency of 
each crime above. Another alternative is a 
shorter 5-item score of the average of 
proportional items (divided by their range) 
for the recency and days (during the past 
90) of illegal activity and of supporting 
oneself financially with illegal activity. These 
self-report questions come from the GAIN. 
Re-arrest and 
Re-
incarceration  
Secondary Quarterly for 
Aim 3; across 
24 months for 
Aim 4 
A dichotomous measure of whether the 
person has been re-arrested and/or re-
incarcerated, as well as the associated 
charges for descriptive purposes (ICC=.35).  
Also alternative measures of the days to 
each event and the number of events. All 
measure are both within and across 
quarters. 
Costs-of-Crime 
Secondary Quarterly for 
Aim 3; across 
24 months for 
Aim 4 
This cost measure is based on the self-
reported frequency of 12 criminal offenses 
times their respective societal cost per 
offense based on the most recent economic 
estimate, which will be used to estimate a 
continuous “total cost-of-crime” variable in 
whole dollars and trimmed at the 99% 
percentile due to sharp right skews 
(ICC=.03). We will collaborate with the 
JCOIN economic studies across hubs on the 
measures to be used for this variable. Dr. 
McCollister and her colleagues updated 
these cost estimates to 2017 and will adjust 
them forward using the consumer price 
index. 
Quality 
Adjusted Life 
Years (QALYs) 
Secondary Across 24 
months post 
release for Aim 
4 
This measure is based on the Patient 
Reported Outcomes Measurement 
Information System (PROMIS) – R. It is the 
self-reported frequency of problems in with 
reference to the past 7 days in 8 domains: 
physical function, anxiety, depression, 
fatigue, sleep disturbance, ability to 
participate in social roles and activities, pain 
interference, and cognitive function ability, 
and an overall measure of pain intensity. 
QALY (0-100%) times 0.25 years for each 
quarter and summed across 8 quarters/24 
months post-release. While missing data will 

30 
 
be imputed, from a point of death on will be 
treated as 0. In addition to being compared 
between groups, data can be scaled to U.S. 
norms using the AHSR data. 
 
4.4 Statistical Design and Power 
 
Primary Outcome.  Based on the proposed design and data presented earlier, this power 
analysis for the primary variable, “Months of MOUD treatment,” is based on the assumptions 
that:  
1) 750 adults with OUD who are released from the 6 county jails can be recruited  
2) Participants will be randomized to 3 conditions (250 per group)  
3) Data will be collected at enrollment and 8 follow-up observations (at 3, 6, 9, 12, 15, 18, 21, 
and 24 months post enrollment) and combined with continuous records data to create an 
observation for every person  
4) H1a will have unequal sample sizes (250 control vs. 500 for RMC+RMC-adaptive) 
5) H1b will have equal sample sizes (250 RMC vs. 250 RMC-Adaptive)  
6) The range of effect sizes in prior experimental studies of RMC (without focusing on MOUD 
treatment) was 0.21 to 0.50.  
 
Under these assumptions, there is over 99% power with two-tailed alpha of .05 to detect a 
Cohen’s effect size d of 0.35 or more for H1a and 0.40 or more for H1b. There is over 80% 
power to detect effect sizes of d=0.22 and 0.25 respectively. Use of multi-level modeling, 
multiple sources of data, and baseline covariates should further improve power and/or allow the 
detection of smaller effects. The effects of RMC and RMC-Adaptive on the months of MOUD 
treatment will be initially evaluated with a Mann Whitney U test of the distributions comparing 
the main effect of Re-entry as Usual vs. RMC. This Mann-Whitney U test is proposed as a 
conservative test in case the variables have a non-normal and potentially bimodal distributions 
(e.g., zero saturation or a small group with perfect retention or 24 months). The proposed 
samples are sufficiently large that U will approximate a normal distribution and can be 
transformed into a z-score and/or Cohen’s effect size d. 
 
For the power analysis of later hypotheses, we also assumed that: 
1) Data will be available for at least 90% of each of the follow-up observations (225 per group 
at follow-up and 2050 observations per group based on enrollment plus 90% of 8 quarterly 
follow-up waves) 
2) The inter-item correlation (ICC) across repeated observations will range from 0.03 (cost-of-
crime) to .37 (quality of life) with the later reducing the effective observations to 1694 to 571 
respectively) 
3) There will again be unequal number of observations when comparing control (1694 to 571) 
vs. RMC+RMC-Adaptive (3388 to 1142), and when comparing RMC (1694 to 571) and 
RMC-Adaptive (1694 to 571).  
 
We have over 99% power to detect an effect size of 0.22 or more and 0.25 respectively for the 
smallest sample size. It has over 80% power to detect an effect size of 0.16 or more for both. 
The variable (or a transformed version of it) will then be analyzed in a multilevel structural 
equation model (MSEM). For Aim 4, the power follows what is presented above for Aim 1. 
 
The table below summarizes the number of participants/observations, expected effect size, 
estimated power, and proposed statistical method for each of the primary and secondary 

31 
 
outcome measures. Sample sizes below are per group. Power given below is for the RMC vs. 
RMC-A comparison – the control vs RMC+RMC-A will always have more n and power. 
 
 
 
Primary*and 
Secondary Outcome 
Measure  
Number of Participants 
& Observations Per 
Group (from Survey 
Observations and 
records if ** ) 
Expected 
Effect size 
Estimated 
Power 
Statistical Method 
Months of Treatment 
Participation with 
MOUD for H1a & H1b 
(*Primary) 
250 Participants per 
group (Combined over 
observations) **  
 
Cohen’s 
d=.4 or 
more 
99% power 
or more 
Mann Whitney U (MWU) test of 
the distributions comparing the 
main effect of groups 
Opioid Use Disorder 
(OUD) Service 
Cascade  for H1a & 
H1b* 
250 Participants per 
group (Combined over 
observations) **  
 
Odds 
Ratio=1.5 
90% or 
more 
Odds Ratio of random 
assignment controlling for site 
and other urn randomization 
variables  
Days of Opioid Use for 
H2a-d, H4a & H4b 
(ICC=.34) 
250 Participants with 
607 effective  
observations per group 
Cohen’s d or 
path 
coefficient of 
0.2 or more 
90% or 
more 
MWU test as above and 
Multilevel structural equation 
modeling (MSEM) with mixed 
effects in MPlus (version 8). 
The analysis will model 
observations (Level 1) nested 
within participants (Level 2), 
with participants modeled as a 
random factor. Random 
assignment to the 2 groups will 
be modeled as a Level 2 
predictor. We will test 
differences in the a-intercept 
and slope over time.  \  
Opioid Use Disorder 
(OUD) Symptoms for 
H2a-d (ICC=.28) 
250 Participants with 
693 effective  
observations per group 
Cohen’s d or 
path 
coefficient of 
0.2 or more 
90% or 
more 
MWU and MSEM – same as 
above  
Quality of Life (QoL) 
for H2a-d, H4a & H4b 
(ICC=.37) 
250 Participants with 
394 effective  
observations per group 
Cohen’s d or 
path 
coefficient of 
0.2 or more 
80% or 
more 
MWU and MSEM – same as 
above  
Costs-of-Healthcare-
Utilization for H2a-d, 
H4a & H4b (ICC=.27) 
250 Participants with 
709 effective  
observations per group 
Cohen’s d or 
path 
coefficient of 
0.2 or more 
95% or 
more 
MWU and MSEM – same as 
above  
Illegal Activity for H3a-
d (ICC=.20) 
250 Participants with 
854 effective  
observations per group 
Cohen’s d or 
path 
coefficient of 
0.2 or more 
99% or 
more 
MWU and MSEM – same as 
above  
Re-arrest and Re-
incarceration H3a-d, 
H4c & H4d (ICC=.35) 
250 Participants with 
594 effective  
observations per group 
Cohen’s d or 
path 
coefficient of 
0.2 or more 
90% or 
more 
MWU and MSEM – same as 
above  

32 
 
Costs-of-Crime H3a-d, 
H4c & H4d (ICC=.03) 
250 Participants with 
1694 effective  
observations per group 
Cohen’s d or 
path 
coefficient of 
0.2 or more 
99% or 
more 
MWU and MSEM – same as 
above  
Quality Adjusted Life 
Years (QALYs) for 
H4a & H4b 
250 Participants per 
group (combined over 
observations) 
Cohen’s d or 
path 
coefficient of 
0.2 or more 
90% or 
more 
MWU and MSEM – same as 
above  
4.5.   Subject participation duration:  24 months 
 
4.6.   FDA-regulated intervention  
 
This study meets the criteria for Investigational New Drug exemption status for the following 
reasons:  
 
a. 
Burprenorphonine with or without naloxone (including Suboxone®, Subutex®, Zubsolv®, 
Bunavail®, Butrans®, Buprenex®, Probuphine®, and Belbuca®), methadone (including 
Methadose®, Dolophine®, Diskets®, and Methadone Intensol®), and naltrexone 
(including Vivitrol®,  ReVia®, Adepend®, Depade®, Nalorex®, and Trexan®) are each 
FDA-approved medications for treating OUD that are lawfully marketed in the United 
States; 
b. 
The study is not intended to be reported to FDA in support of new indications or to 
support any other significant changes in the labeling of the drugs, nor to support 
significant changes in advertising for the drugs; and  
c. 
The study does not involve a route of administration, dose, patient population, or other 
factor that significantly increases the risk (or decreases the acceptability of the risk) 
associated with the use of the drugs. 
d. 
MOUD will only be provided in the context of regular care by organizations and staff 
already licensed to do so by the state.  
 
4.7   Dissemination Plan 
 
The Principal Investigator (Scott) and all Co-Investigators ensure the following:  
 
 
We will provide requested data to the CTC and MAARC in a timely fashion in accordance 
with the policies and procedures established in study protocols and by the SC.  In addition, 
we will provide NIDA with access to all data generated under this award, subject to rules 
specified in our Certificates of Confidentiality. We will also share our data upon request with 
the SC and subcommittees reporting to the SC when appropriate 
 
JCOIN is intended to be a national resource, and as such, and as one of the Clinical 
Research Center we will share our data under provisions that safeguard the privacy and 
confidentiality of respondents.  
 
We will cooperate to ensure the timely and broad dissemination of lessons learned, to 
inform researchers and health care systems engaged in research and beyond.  
 
We will work closely with NIDA, the Coordination and Translation Center, the Methodology 
and Advanced Analytics Resource Center, and Steering Committee members to 
disseminate findings and products from our work.  
 
Qualified members of our team will actively participate in a wide variety of network activities 
designed to facilitate dissemination, including, but not limited to: providing mentorship to 
participants in the Coordination and Translation Center Research Education Core, 

33 
 
participating in reviews of network publications, actively engaging in harmonization activities, 
making data from their study available to others, serving as a reviewer for Coordination and 
Translation Center Rapid Response and Pilot Research Project proposals. 
 
The study will be registered and the results stemming from this study will be submitted to 
ClinicalTrials.gov as outlined in the policy and according to the specific timelines stated in 
the policy;  
 
All informed consent documents for the study will include a specific statement relating to 
posting of clinical trial information at ClinicalTrials.gov; and 
 
Chestnut Health Systems, the recipient institution, has an internal policy in place to ensure 
that clinical trials registration and results reporting occur in compliance with policy 
requirements. 
 
In addition to the above, as the investigators have consistently done in their prior clinical trials 
studies, findings from this study will be widely disseminated in several ways. These include:  
 
 
Presentations at scholarly and research-oriented conferences, such as the College on 
Problems of Drug Dependence (CPDD), Addiction Health Services Research (AHSR), 
American Public Health Association (APHA), and American Psychological Association 
(APA);  
 
Publications in peer-reviewed journals in the areas of opioid treatment, opioid treatment 
programs, and overdose prevention, such as Addiction, Drug and Alcohol Dependence, 
Journal of Substance Abuse Treatment, JAMA – Psychiatry and JAMA Internal Medicine; 
public health and health policy, such as the American Journal of Public Health, American 
Journal of Preventive Medicine, Health Affairs, Chronic Disease Prevention; and health 
services research, such as Health Services Research and Journal of Behavioral Health 
Services Research;  
 
Presentations for policy makers, treatment and prevention providers, such as meetings of 
the National Association of State Alcohol and Drug Abuse Directors (NASADAD), the 
American Association for the Treatment of Opioid Dependence (AATOD), and relevant 
meetings sponsored by the Centers for Disease Control and Prevention (CDC) and the 
Substance Abuse and Mental Health Services Administration (SAMHSA).