Collaborating to Heal Addiction and Mental Health in Primary Care
Phase: NA
Conditions: Opioid-use Disorder, Mental Health Disorder
Sponsor: University of Washington

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Collaborating to Heal Addiction and Mental Health in Primary care (CHAMP) 
  
Protocol Number: MH121942 
National Clinical Trial (NCT) Identified Number:  NCT04600414 
Principal Investigators: John Fortney, Anna Ratzliff, Andrew Saxon 
Sponsor: National Institute of Mental Health (NIMH) 
Grant Title: Collaborating to Heal Addiction and Mental Health in Primary care (CHAMP) 
Grant Number: MH121942 
Funded by: NIMH 
Version Number:  11.0 
2024.02.16 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Summary of Notifications/Clarifications made from Previous Version: 
We have attached a revised DSMB Protocol for the board’s review.  
 
Affected Section(s) 
Summary of Revisions for the  
March 202 DSMB meeting 
Rationale 
3.0 Objectives and 
Endpoints 
Tertiary/Exploratory Objective and 
Hypothesis  – Revised from comparing 
clinics randomized to low and high 
intensity sustainability strategies to 
conducting a pre-post evaluation.  
Because we extended the recruitment period for 
the effectiveness trial, there was insufficient time to 
conduct the implementation trial.  
4.1 Overall Design 
Overall Design – Sustainability 
Implementation trial changed to Pre-
Post Sustainability Evaluation 
 
Specific Aims and Hypotheses – 
Revised Specific Aim #3 from 
comparing clinics randomized to low 
and high intensity sustainability 
strategies to conducting a pre-post 
sustainability evaluation.  
 
Randomization – Dropped 
randomization for Specific Aim #3. 
Because we extended the recruitment period for 
the effectiveness trial, there was insufficient time to 
conduct the implementation trial.  
 
Because we are now planning to conduct a pre-post 
analysis, there is no need for randomization.  
9.1 Statistical Hypotheses 
Exploratory Hypothesis for 
Exploratory Aim – Revised exploratory 
hypothesis from comparing clinics 
randomized to low and high intensity 
sustainability strategies to conducting 
a pre-post sustainability evaluation. 
Because we extended the recruitment period for 
the effectiveness trial, there was insufficient time to 
conduct the implementation trial.  
9.2 Sample Size 
Determination 
Dropped sample size determination 
for Specific Aim #3 
Because we are not conducting the implementation 
trial, there is no need for a sample size 
determination.  
9.4.6 Exploratory Analyses 
Exploratory Outcomes – Changed 
number of participating clinics and 
the timeframe for the pre-post 
sustainability evaluation. 
 
Quantitative Analysis - Changed 
number of participating clinics and 
the timeframe for the pre-post 
sustainability evaluation. 
 
Qualitative Analysis – Added a 
qualitative data collection and 
analysis component to the 
exploratory analyses. 
Because not all clinics wanted to participate in the 
sustainability evaluation, there were fewer clinics 
than anticipated.  
 
Because we extended the recruitment period for 
the effectiveness trial, there was less time for the 
pre-post sustainability evaluation.  
 
 
 
Because of the small sample of clinics, we added a 
qualitative component to the exploratory analyses 
to yield richer findings.   
 

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CONFIDENTIALITY STATEMENT 
This document is confidential communication. Acceptance of this document constitutes agreement by 
the recipient that no unpublished information contained herein will be published or disclosed without 
prior approval of the Principal Investigator or other participating study leadership and as consistent with 
the NIH terms of award.  
 

Collaborating to Heal Addiction and Mental Health in Primary care (CHAMP) 
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Table of Contents 
STATEMENT OF COMPLIANCE ............................................................................................................................. 1 
INVESTIGATOR’S SIGNATURE .............................................................................................................................. 1 
1 
PROTOCOL SUMMARY ............................................................................................................................... 2 
1.1 
Synopsis .............................................................................................................................. 2 
1.2 
Schema ............................................................................................................................... 3 
1.3 
Schedule of Activities ........................................................................................................ 4 
2 
INTRODUCTION ............................................................................................................................................ 5 
2.1 
Study Rationale .................................................................................................................. 5 
2.2 
Background ......................................................................................................................... 5 
2.3 
Risk/Benefit Assessment .................................................................................................. 7 
2.3.1 
Known Potential Risks ..................................................................................................... 7 
2.3.2 
Known Potential Benefits ................................................................................................ 7 
2.3.3 
Assessment of Potential Risks and Benefits ................................................................ 7 
3 
OBJECTIVES AND ENDPOINTS ................................................................................................................ 8 
4 
STUDY DESIGN ............................................................................................................................................. 9 
4.1 
Overall Design .................................................................................................................... 9 
4.2 
Scientific Rationale for Study Design ............................................................................ 10 
4.3 
Justification for Intervention ............................................................................................ 10 
4.4 
End-of-Study Definition ................................................................................................... 11 
5 
STUDY POPULATION ................................................................................................................................ 11 
5.1 
Inclusion Criteria .............................................................................................................. 13 
5.2 
Exclusion Criteria ............................................................................................................. 13 
5.3 
Screen Failures ................................................................................................................ 14 
5.4 
Strategies for Recruitment and Retention .................................................................... 14 
6 
STUDY INTERVENTION(S) OR EXPERIMENTAL MANIPULATION(S) ............................................ 14 
6.1 
Study Intervention(s) or Experimental Manipulation(s) Administration .................... 14 
6.1.1 
Study Intervention or Experimental Manipulation Description ................................. 14 
6.1.2 
Administration and/or Dosing ....................................................................................... 18 
6.2 
Fidelity ............................................................................................................................... 18 
6.2.1 
Interventionist Training and Tracking .......................................................................... 18 
6.3 
Measures to Minimize Bias: Randomization and Blinding ......................................... 19 
6.4 
Study Intervention/Experimental Manipulation Adherence ........................................ 19 
7 
STUDY INTERVENTION/EXPERIMENTAL MANIPULATION DISCONTINUATION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL ......................................................................................... 19 
7.1 
Discontinuation of Study Intervention/Experimental Manipulation ........................... 19 
7.2 
Participant Discontinuation/Withdrawal from the Study ............................................. 20 
7.3 
Lost to Follow-Up ............................................................................................................. 20 
8 
STUDY ASSESSMENTS AND PROCEDURES ..................................................................................... 21 
8.1 
Endpoint and Other Non-Safety Assessments ............................................................ 21 
8.2 
Adverse Events and Serious Adverse Events ............................................................. 22 
8.2.1 
Definition of Adverse Events ........................................................................................ 22 
8.2.2 
Definition of Serious Adverse Events .......................................................................... 22 
8.2.3 
Classification of an Adverse Event .............................................................................. 23 
8.2.4 
Adverse Event Reporting .............................................................................................. 24 
8.2.5 
Serious Adverse Event Reporting ............................................................................... 24 

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8.2.6 
Reporting Events to Participants ................................................................................. 25 
8.3 
Unanticipated Problems, Protocol DEVIATIONs, and non-Compliance .................. 25 
8.3.1 
Definition of Unanticipated Problems .......................................................................... 25 
8.3.2 
Problem Reporting ......................................................................................................... 26 
8.3.3 
Reporting Problems to Participants ............................................................................. 27 
9 
STATISTICAL CONSIDERATIONS .......................................................................................................... 27 
9.1 
Statistical Hypotheses ..................................................................................................... 27 
9.2 
Sample Size Determination ............................................................................................ 27 
9.3 
Populations for Analyses ................................................................................................ 28 
9.4 
Statistical Analyses .......................................................................................................... 29 
9.4.1 
General Approach .......................................................................................................... 29 
9.4.2 
Analysis of the Primary Endpoint(s) ............................................................................ 29 
9.4.3 
Analysis of the Secondary Endpoint(s) ....................................................................... 30 
9.4.4 
Baseline Descriptive Statistics ..................................................................................... 31 
9.4.5 
Sub-Group Analyses ..................................................................................................... 31 
9.4.6 
Exploratory Analyses ..................................................................................................... 31 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS .............................. 32 
10.1 
Regulatory, Ethical, and Study Oversight Considerations ......................................... 32 
10.1.1 
Informed Consent Process ........................................................................................... 32 
10.1.2 
Study Discontinuation and Closure ............................................................................. 33 
10.1.3 
Confidentiality and Privacy ........................................................................................... 34 
10.1.4 
Key Roles and Study Governance .............................................................................. 35 
10.1.5 
Safety Oversight ............................................................................................................. 36 
10.1.6 
STUDY Monitoring ......................................................................................................... 37 
10.1.7 
Quality Assurance and Quality Control ....................................................................... 37 
10.1.8 
Data Handling and Record Keeping ............................................................................ 38 
10.1.9 
Publication and Data Sharing Policy ........................................................................... 39 
10.1.10 
Conflict of Interest Policy .............................................................................................. 40 
10.2 
Additional Considerations ............................................................................................... 40 
10.3 
Abbreviations and Special Terms .................................................................................. 41 
11 
REFERENCES ............................................................................................................................................. 48 
 

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STATEMENT OF COMPLIANCE 
 
The trial will be conducted in accordance with International Council on Harmonization Good Clinical 
Practice (ICH GCP), applicable United States (US) Code of Federal Regulations (CFR), and the NIMH 
Terms and Conditions of Award. The Principal Investigator will assure that no deviation from, or changes 
to the protocol will take place without prior agreement from the funding agency and documented 
approval from the Institutional Review Board (IRB), except where necessary to eliminate an immediate 
hazard(s) to the trial participants. All personnel involved in the conduct of this study have completed 
Human Subjects Protection and ICH GCP Training. 
 
The protocol, informed consent form(s), recruitment materials, and all participant materials willbe 
submitted to the IRB for review and approval. Approval of both the protocol and the consent form(s) 
must be obtained from both the IRB and NIMH DSMB before any participant is consented. Any 
amendment to the protocol will require review and approval by the IRB and the DSMB before the 
changes are implemented to the study. All changes to the consent form(s) will be IRB approved; a 
determination will be made regarding whether a new consent needs to be obtained from participants 
who provided consent, using a previously approved consent form. 
INVESTIGATOR’S SIGNATURE 
The signature below constitutes the approval of this protocol and provides the necessary assurances 
that this study will be conducted according to all stipulations of the protocol, including all statements 
regarding confidentiality, and according to local legal and regulatory requirements and applicable US 
federal regulations and ICH guidelines. 
 
Principal Investigator or Clinical Site Investigator: 
Signed: 
 
Date: 
02/16/2024 
 
Name: John Fortney 
 
Title: 
Professor 
 
Investigator Contact Information 
Affiliation:  University of Washington 
Address: 1959 NE Pacific Street, Box 356560, Seattle, WA  98195-6560 
Telephone: 206.685.6955 
Email: fortneyj@uw.edu 
 
 
 
 

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PROTOCOL SUMMARY 
1.1 
SYNOPSIS  
 
Title 
Collaborating to Heal Addiction and Mental Health in Primary care (CHAMP) 
 
Grant Number 
MH121942 
 
Study Description 
The gold-standard intervention for Opioid Use Disorder (OUD) is Medication 
for Opioid Use Disorder (MOUD).  Because more patients with OUD need 
access to MOUD in primary care, we are testing whether the Collaborative 
Care model (CoCM) is effective at treating both mental health symptoms 
(MHS) and OUD concurrently in primary care settings. The intervention is 
CoCM for MHSand OUD.  The active control is CoCM for MHS, but not 
treating OUD.  The primary objective is to compare patient-reported 
outcomes in the intervention and control groups, and will be tested with in 
an Effectiveness trial.  The secondary objective is to compare the detection of 
OUD pre- versus post-OUD screening implementation, and will be tested 
using a Pre-Post trial design.  The exploratory objective is to compare 
intervention clinics randomized to a low-intensity sustainability 
implementation strategy or a high-intensity sustainability strategy, and will 
be tested in an Implementation trial. 
Objectives 
 
The CHAMP study addresses three important objectives including:  
Primary Objective - Does implementing Collaborative Care for OUD and MHS 
improve MHS and OUD outcomes? 
Secondary Objective - Can OUD screening be effectively incorporated into 
primary care mental health screening protocols?  
Exploratory Objective - What implementation strategies are effective at 
sustaining Collaborative Care programs that concurrently manage mental 
health disorders and OUD?   
Endpoints 
The multiple primary outcomes for the Effectiveness trial are self-reported 
use of opioids and mental health functioning.   
 
Study Population 
We will recruit 1,200 adult primary care patients screening positive for OUD 
and MHS from  42 clinics in 11 states and the District of Columbia.  Age, 
gender and race/ethnicity will be representative of the demographics and 
epidemiology of the clinics. 
Description of 
Sites/Facilities Enrolling 
Participants 
Sites include a range of primary care settings in the United States. Fourty-
two clinics from 15 healthcare systems.  
Description of Study 
Intervention/Experimental 
Manipulation 
Collaborative Care - The treatment of OUD will be integrated with the 
treatment of MHDs, other substance use disorders (SUDs), and physical 
health disorders in the primary care setting. Primary care providers will 
prescribe MOUD in consultation with a psychiatrist and support from a care 
manager who will also provide brief psychotherapy. 
 
Study Duration 
The Effectiveness trial will be 39 months in duration.  
 
Participant Duration 
Those enrolled in the Effectiveness trial will participate for 6 months. 
 
 
 
 

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1.2 
SCHEMA  
 
 
 
 
 

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1.3 
SCHEDULE OF ACTIVITIES  
 
 
 
 
 
 
Pre-consent 
 
Baseline 
Day 1-14 
Multiple Visits 
Day 1-90 
3 Month 
Follow-Up 
Multiple Visits 
Day 91-181 
6 Month 
Follow-Up 
Clinic Randomization 
X 
 
 
 
 
Screen for OUD 
-NIDA–Assist (OUD Items) 
-Short Opioid Screen (SOS) 
X 
 
 
 
 
Eligibility Assessment 
- PHQ-9 
- GAD-7 
- PC-PTSD-5 
- OUD DSM5 Checklist OR 
OUD diagnosis documented 
in the electronic health 
record. 
X 
 
 
 
 
Informed Consent 
X 
 
 
 
 
Encounter with Primary Care 
Provider 
 
X 
 
X 
 
Encounter with Care Manager 
- PHQ-9 
- GAD-7 
- PCL-5 
- Opioid use, withdrawal,  
  craving, side-effects 
 
X 
 
X 
 
Psychiatric Case Review 
 
X 
 
X 
 
Outcome Evaluation 
 
 
 
 
 
Demographics 
 
X 
 
 
 
 
Drug Use  
- BAM-R 
 
X 
 
X 
 
X 
Mental Health Symptoms 
- SCL20 
- Neuro-QOL Anxiety – Short  
  Form 
- PCL-5 
-Audit/Audit-C 
-Veterans Short Form-12 
 
X 
 
X 
 
X 
Attitudes and Beliefs 
- Readiness to Change-ICR 
- Assessment of Perceived 
  Access to Care 
 
X 
X 
 
 
 
X 
 
 
 
X 
Recent Service Use 
 
 
X 
 
X 
Adverse Events Reporting 
 
X 
X 
X 
X 
X 

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INTRODUCTION 
 
2.1 
STUDY RATIONALE  
An estimated 11.4 million Americans misuse opioids, and 2.1 million have an Opioid Use Disorder (OUD).  
Medication for OUD (MOUD) is the gold-standard treatment for OUD, but is not offered in most primary 
care settings.  As a result, only 20% of Americans with OUD receive any addiction treatment.  While 
MOUD could prevent many of the estimated 47,600 fatal opioid overdoses a year (130 per day), we 
currently lack the means to deliver this treatment to the majority of people who need it.  Making MOUD 
for OUD more widely available in primary care settings could help address this national crisis. The 
Collaborative Care Model (CoCM) is a primary care- based intervention developed at the University of 
Washington that improves access to effective treatments for a wide range of Mental Health Disorders 
(MHD).  CoCM has the potential to substantially improve access to MOUD for patients with co-occurring 
OUD and MHS.  
 
2.2 
BACKGROUND  
Excessive opioid use is a national emergency. There were >350,000 emergency department visits in 2015 
due to opioid poisoning.1 There were 47,600 opioid overdose deaths in 2017,2 and the death rate is 
growing fastest in rural areas (325% since 1999).3  There are an estimated 2.1 million Americans meeting 
diagnostic criteria for an OUD, including 1.7 million with a prescription pain reliever use disorder and 0.7 
million with a heroin use disorder.4  Medication Assisted Treatment ( MAT) with either buprenorphine, 
methadone, or naltrexone represents the gold-standard intervention for OUD5 and significantly reduces 
risk for overdose or death.6 However, only 20% of Americans with OUD received any formal or informal 
addiction treatment in the past year.7  Moreover, even in addiction treatment settings in the US, only 
32% of patients with OUD were prescribed MOUD in 2016.8 Lack of access and engagement in MOUD is 
clearly a driver of poor OUD outcomes, especially in rural areas lacking addiction services. 
To close this engagement gap, more 
patients with OUD need access to 
MOUD in primary care settings.9,10 
We conceptualize access to care as 
the potential ease of having 
encounters with a broad array of 
healthcare providers (Figure 1).11  
Integrating OUD treatment into 
primary care improves geographical 
(i.e., travel), temporal (e.g., wait 
time), and cultural (e.g., stigma) 
access.  Our conceptualization of 
engagement is participating 
sufficiently in a treatment plan to 
potentially experience a therapeutic 
effect.  Treatment engagement 
depends on patient perceptions 
about access to care, and the perceived need for and expectations from treatment.11  With adequate 
access and engagement, individuals have the opportunity to receive high quality care and improved 
Figure 1 – Theory of Access and Engagement 

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outcomes.  However, MOUD delivered in primary care can only improve outcomes if the quality of care 
is high. 
Unfortunately, there are barriers to providing high quality MOUD in primary care, especially in rural 
areas.  Federal regulations prevent prescribing methadone for MOUD in primary care.12  Naltrexone 
requires complete withdrawal from opioids for 7-10 days, which is difficult to achieve in an outpatient 
setting.  For buprenorphine, training (8 hours for primary care physicians and 24 hours for mid-level 
providers) must be completed in order to receive a DATA 2000 waiver to prescribe, and 56% of rural 
counties do not have any providers with a waiver.13  In addition, primary care providers report 
inadequate expertise in addiction treatment, lack of institutional support, insufficient remuneration, and 
limited ancillary support.14,15 However, the biggest barrier to MAT, according to both primary care 
providers who do and do not prescribe buprenorphine, is the lack of support for treating MHDs.15  Over 
the last 25 years, models of integrated care have emerged that provide the support needed by primary 
care providers to effectively manage MHDs, such as depression and anxiety disorders, and we believe 
that a similar cultural shift is possible for MOUD for OUD. 
CoCM is an evidence-based model of integrated care 
developed by the Department of Psychiatry at the 
University of Washington.16,17  CoCM operationalizes the 
principles of the chronic care model to improve access to 
evidence-based MHD treatments for primary care patients. 
CoCM is based on six key principles: 1) evidence-based, 2) 
measurement-based, 3) team-based (Figure 2), 4) 
population-based, 5) patient-centered, and 6) 
accountable.18  CoCM supports the delivery of evidence-
based pharmacological and psychosocial treatments.  
CoCM is measurement-based with screening and 
monitoring of patient-reported outcomes over time to 
assess treatment response and facilitate treatment 
adjustments.19  CoCM is team-based led by a primary care 
provider with support from a care manager in consultation 
with a psychiatrist who provides treatment 
recommendations for patients who are not achieving 
clinical goals.  CoCM is population-based whereby a registry20,21 is used to monitor treatment 
engagement and facilitate the identification of patients falling through the cracks.  CoCM is patient-
centered with proactive outreach to engage and activate patients, shared decision making, and support 
for treatment adherence and self-management.  Collaborative care is accountable with continuous 
quality improvement to meet clinic performance benchmarks. 
Evidence for CoCM - Meta-analysis demonstrates that CoCM is cost-effective across diverse practice 
settings, patient populations, and disorders.22  Co-I Unützer conducted Project IMPACT, the definitive 
study demonstrating the cost-effectiveness of CoCM for depression (n=1,801).23,24  Other CoCM trials 
conducted at the University of Washington demonstrate its effectiveness for anxiety 
disorders,25,26_ENREF_24 postpartum depression27 and PTSD.28  MPI Fortney conducted three trials 
(∑n=1,024) demonstrating the cost-effectiveness of telepsychiatry CoCM for rural patients.29-34       
Integrated OUD Treatment - Patients in OUD treatment have high rates of co-occurring MHS.35-37 Thus, 
concurrent treatment of OUD and MHS has great potential.38-40  CoCM represents an ideal approach to 
co-managing OUD and MHS.41,42  Yet, little rigorous research has examined the co-management of OUD 
and MHS, and the evidence to date is mixed.  One trial with patients in methadone treatment found that 
those with MHSs randomized to evidence based psychotherapy had fewer psychiatric symptoms AND 
Figure 2. Collaborative Care Model 
 

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less illicit opioid use.43  Of the three antidepressant trials with patients in methadone treatment, two 
demonstrated positive benefits of tricyclics (for depression symptoms but not OUD outcomes)44,45 and 
one found no benefit of an SSRI.46  Importantly, the one previous CoCM trial focused on patients with 
OUDs and alcohol use disorders  (SUMMIT trial) found that the proportion of patients remaining 
abstinent from opioids in the past 30 days was no higher in the CoCM group than the usual care group 
(p=.33).47  However, only 13.4% of the patients in the CoCM group received MOUD compared to 12.6% 
in usual care (p=.053)47 suggesting that difficulties with implementation were driving results rather than 
the ineffectiveness of MOUD in the context of CoCM.   This highlights the critical importance of using 
effective implementation strategies to support the delivery of MOUD for OUD in the context of CoCM 
for MHS.   
 
2.3 
RISK/BENEFIT ASSESSMENT  
 
2.3.1 KNOWN POTENTIAL RISKS  
 
Psychological distress - Some of the survey questions may make participants feel uncomfortable.  An 
example of such a question is “Overall, in the past two weeks how much were you distressed by thoughts 
of ending your life?” 
 
Loss of Confidentiality - A risk of participating in this study is possible loss of privacy.   
 
2.3.2 KNOWN POTENTIAL BENEFITS  
 
Meta-analysis of collaborative trials has demonstrated significant clinical benefits to participants.  While 
collaborative care will be available to patients at participating clinics who do not enroll in the trial, all 
patients enrolling in the Effectiveness trial will receive treatment from the collaborative care team.  We 
do not know if patients at clinics randomized to the intervention will benefit more than patients at 
clinics randomized to the active control.  However, those at clinics randomized to the intervention will 
be offered treatments for OUD that are known to be clinical effective. 
 
2.3.3 ASSESSMENT OF POTENTIAL RISKS AND BENEFITS  
 
Although the population enrolled in this Effectiveness trial is at high risk for adverse outcomes, the 
increased risk of participating in this study is minimal. The importance of the knowledge gained 
potential clinical benefit to study participants justifies the additional risk faced by study participants.   
 
The psychological distress associated with survey questions will be mitigated by being able to skip any 
questions that participants are not comfortable with.  
 
The possible loss of privacy is mitigated by keeping the answers to the survey questions strictly 
confidential.  Survey data will be stored on a secure computer at the University of Washington and will 
only be available to the study team.  The data will be stored and eventually destroyed in compliance 
with the University of Washington’s data policies.  

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OBJECTIVES AND ENDPOINTS  
  
OBJECTIVES 
ENDPOINTS 
Primary 
 
Objective: Compare patient-reported 
outcomes in the intervention and control 
groups. 
Hypothesis a: Compared to patients with MHS 
and OUD at clinics randomized to the control, 
patients at clinics randomized to the intervention 
group will have better patient-reported 
outcomes.  
Hypothesis b: Persistent use of MOUD will 
completely mediate any improvements in patient-
reported outcomes observed in intervention 
clinics compared to control clinics.   
 
 
 
Primary endpoint-  
Self-reported opioid use, and self-reported mental 
health functioning 
 
Secondary endpoints- Persistent use of MOUD from 
PMID and self-report, disorder specific mental health 
symptoms (depression, anxiety and PTSD), self-reported  
access to OUD treatment, risk factors for premature 
mortality  
 
Secondary 
 
Objective: Compare the Detection of OUD pre- 
versus post-OUD screening implementation.  
Hypothesis: The proportion of patients 
enrolled in the clinic with a MHD diagnosis 
and a new OUD diagnosis documented in the 
electronic medical record will be higher in 
the post-period than the pre-period. 
 
Secondary endpoint - the proportion of patients in the 
pre-screening sample with a new OUD diagnosis divided 
by the proportion of patients in the post-screening 
sample with a new OUD diagnosis  
 
Tertiary/Exploratory  
 
Objective:  To conduct a pre-post evaluation 
(quantitative and qualitative) of a high-intensity 
sustainability implementation strategy delivered to 
the CHAMP intervention clinics to sustain the 
implementation of Collaborative Care for OUD co-
occurring with MHD. 
Exploratory Hypothesis: CHAMP intervention 
clinics receiving the high-intensity sustainability 
implementation strategy will maintain their 
implementation outcomes (adoption, reach, 
intervention fidelity and effectiveness) after the 
effectiveness trial has been completed (post) 
compared to during the effectiveness trial (pre).  
 
Exploratory Endpoints –  
 
Reach (number of patients engaged in the intervention) 
 
Adoption (number of providers delivering the 
intervention) 
 
Effectiveness (symptom change) 
 
Implementation fidelity (adherence to intervention 
protocols) 
 
 
 

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4 
STUDY DESIGN 
 
4.1 
OVERALL DESIGN 
 
Overall Design  
 
This multi-site study involves a sequence of trials (Pre-Post -> Effectiveness -> Implementation 3) to 
examine our primary, secondary and exploratory objectives. 
 
1. Pre-Post trial (secondary objective) - Screening for OUD will be integrated into MHD screening and 
electronic health record (EHR) data will be used to determine if screening improves the detection of new 
cases of OUD during the first six months of the trial compared to the six months prior. 
 
2. Cluster randomized Effectiveness trial (primary objective) - The primary objective of the trial is to 
test the effectiveness of delivering MOUD in the context of CoCM for MHS, hereafter termed the 
“intervention” compared to CoCM for MHS only hereafter termed the “control”.  After monitoring 
CoCM for MHS fidelity during a three month “run in” phase, we will categorize clinics into one of two 
cohorts and then randomize them.   
• 
Cohort 1 (n=600) - Randomize clinics with high CoCM for MHS fidelity to sequentially adding 
MOUD for OUD (intervention group) or maintenance CoCM for MHS only (control group).   
• 
Cohort 2 (n=600) - Randomize clinics with low CoCM for MHS fidelity to simultaneous 
implementation of CoCM for MHS and OUD (intervention group ) or CoCM for MHS only (control 
group).   
 
3.  Pre-Post Sustainability Evaluation (exploratory objective) - At the end of the Effectiveness trial, 
participating intervention clinics will receive a high-intensity implementation strategy to promote 
sustainability  
 
Specific Aims and Hypotheses 
Specific Aim 1 (Secondary Objective): Diagnostic data from electronic health records will be used 
to compare the detection of OUD pre-versus post-OUD screening implementation.  
Hypothesis 1: The proportion of patients enrolled in the clinic with a MH diagnosis and a new 
OUD diagnosis documented in the electronic medical record will be higher in the post-period than 
the pre-period. 
Specific Aim 2 (Primary Objective): Patient reported outcomes will be analyzed to compare the 
effectiveness of the intervention versus the control. 
Hypothesis 2a: Compared to patients with MHS and OUD at clinics randomized to the control group, 
patients at clinics randomized to the intervention group (both Cohorts 1 and 2) will report better 
access to and engagement in OUD treatment, less opioid use (primary outcome), better mental health 

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functioning (primary outcome), fewer disorder specific mental health symptoms, better quality of life, 
and fewer risk factors for premature mortality.   
Hypothesis 2b: Engagement in MOUD (e.g., buprenorphine initiation and adherence) will completely 
mediate any improvements in patient reported outcomes observed in intervention clinics compared to 
control clinics.   
Specific Aim 3 (Exploratory Objective):  To conduct a pre-post evaluation (quantitative and qualitative) 
of a high-intensity sustainability implementation strategy delivered to the CHAMP intervention clinics 
to sustain the implementation of Collaborative Care for OUD co-occurring with MHD. 
Exploratory Hypothesis 3: CHAMP intervention clinics receiving the high-intensity sustainability 
implementation strategy will maintain their implementation outcomes (adoption, reach, intervention 
fidelity and effectiveness) after the effectiveness trial has been completed (post) compared to during the 
effectiveness trial (pre).  
Randomization  
Effectiveness Trial Randomization into Arms – Twenty-four clinics will be stratified according to fidelity 
cohort and healthcare organization and then randomized in a 1:1 ratio by our statistician into one of two 
arms (intervention or control).  The intervention group is CoCM for OUD and MHS.  The control group is 
CoCM for MHS only.  Stratification serves two purposes.  First, stratifying on healthcare organization 
(each has 2 or 4 clinics in the study) should balance the intervention and control groups according to key 
system level factors that influence quality and outcomes (e.g., EHR).48  Second, stratifying on cohort 
ensures balance with regard to fidelity to the CoCM model which is likely to be correlated with our 
primary outcomes.  
 
Rationale for Control Groups 
Effectiveness Trial Control Group – The CoCM for MHS only was chosen as the control group because it 
represents high quality usual care.  It is an active control.  In addition, an active control is specified as 
the comparator because it would be unethical for patients with a life-threatening illness to be 
randomized to a treatment that is known to be ineffective.   
 
4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
 
The active control condition is CoCM for MHSs, but not OUD.  CoCM for MHSs is now a reimbursable 
service and is being widely adopted in primary care clinics. Therefore, this control group represents high 
quality usual care.  The evidence base clearly indicates that CoCM is effective for treating mild to 
moderate MHSs like depression and anxiety.   Patient with more severe MHSs or addiction disorders are 
typically referred to specialty care.  However, there is growing evidence that CoCM can also be used to 
treat more complex psychiatric disorders like PTSD.  It is unknown whether CoCM can be used to 
effectively managed OUD, hence the scientific justification for the CHAMP study.   
 
4.3 
JUSTIFICATION FOR INTERVENTION 

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As noted above, it is unknown whether CoCM can be used to effectively managed OUD.  Given the co-
occurrence of MHS and OUD, testing an intervention which addresses both is critical.  Furthermore, 
providing this treatment in primary care settings using a CoCM model will investigate the question of 
how to make high quality OUD treatment more available to patients.   
  
4.4 
END-OF-STUDY DEFINITION 
 
The end of study is defined as the last participant completing the 6-month follow-up survey. 
5 
STUDY POPULATION 
  
The following graphic depicts patients enrollment in the Effectiveness trial along with the inclusion 
criteria.  Stakeholders will be also recruited for qualitative interviews to support and evaluate 
implementation efforts.  Stakeholders will also be recruited for qualitative interviews to evaluate 
sustainability efforts for the Implementation trial.  
 
 

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5.1 
INCLUSION CRITERIA 
 
In order for patients to be eligible to participate in the Effectiveness trial, they must meet all of the 
following criteria: 
 
1. Screen positive on the NIDA-Modified ASSIST OUD items OR the Short Opioid Screen (SOS) OR 
referred to the trial by one of the clinic’s providers AND  
2. Meet clinical criteria for ≥2 symptoms of OUD on the DSM-5 checklist (administered by a 
clinician) AND/OR OUD diagnosis recorded in the electronic medical record AND a patient 
encounter in the last 6 months OR OUD diagnosis on problem list PCP reviewed in the last 6 
months. 
3. Screen positive for depression on the PHQ-9 (≥ 5) OR generalized anxiety on the GAD-7 (≥ 5) OR 
PTSD on the PC-PTSD-5 (≥ 1) within past 6 months.  
 
5.2 
EXCLUSION CRITERIA 
 
An individual who meets any of the following criteria will be excluded from participation in this study: 
 
1. Patient prefers, or is currently being prescribed psychotropic medication (including MOUD) by a 
Mental Health Care Specialist or board certified Addiction Medicine Specialist. (NOTE:  it is 
acceptable if the addiction specialist is a primary care provider in your clinic or health system) 
2.  PaƟent is currently in, or is planning on entering a federally licensed opioid treatment program 
(i.e. methadone treatment program) (NOTE: if patient actually does not enter an opioid 
treatment program or is later discharged from an opioid treatment program, patient could then 
become eligible). 
3.    Patient is currently in, or is planning on entering a specialty substance use disorders treatment 
program (NOTE: If patient actually does not enter a residential treatment program or is later 
discharged from a residential treatment program, patient could then become eligible). 
4.    Patient enrolled in CoCM for MHS and OUD for more than 14 days (NOTE: relevant to 
intervention clinics only) 
5.    Patient does not speak English or Spanish 
6.  Patient is younger than 18 years of age 
7.  Patient has a diagnosis of dementia 
8.  Patient lacks the capacity to provide informed consent 
9.  Patient does not plan on getting care at the clinic for the next 6 months. 
 
For stakeholders to participate in the qualitative interviews to support and evaluate implementation of 
the intervention (CoCM for OUD and MHS), they must have been involved in the intervention either as a 
patient, provider or administrator in the past three months.  
  
 
 
 
 
 

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5.3 
SCREEN FAILURES 
 
Patients who are consented, but do not meet inclusion and exclusion criteria, will be withdrawn from 
the trial by the PI. 
5.4 
STRATEGIES FOR RECRUITMENT AND RETENTION 
 
Recruitment will occur at 42 clinics and enrollment of women and minorities will reflect the underlying 
epidemiology of OUD in the clinical populations.  We will enroll 1,200 patients during the course of the 
trial over a 33-month period (<2 patients per month).   
 
As a quality improvement initiative, all clinics will implement universal screening for OUD.  Screening 
procedures will follow those already in place of depression (PHQ-9) and other substance use and mental 
health disorders.  Universal screening will identify undetected cases of OUD and support enrollment.  
Universal screening for OUD is a quality improvement activity that the clinics agreed to implement in 
order to be able to participate in the trial.  The U.S. Preventive Services Task Force recommends 
screening for drug use in adults when services for accurate diagnosis, effective treatment, and 
appropriate care can be offered or referred.49  
 
All participating clinics will identify staff to be trained in human subject’s protection and designated to 
obtain informed consent.  Having local staff recruit and consent will support enrollment.   
 
If recruitment is lagging in the first six months, we will actively seek referrals from hospitals, emergency 
rooms or other community agencies serving people with OUDs/MHSs.  We could also add more clinics 
(in randomized pairs) from the participating healthcare systems (see letters of support). 
 
Patients will receive incentives to complete surveys and this remuneration increases with each 
subsequent survey, staring at $50 for the baseline and increasing to $50 for the 3-month follow-up and 
$50 for the 6-month follow-up as an incentive to complete all three surveys. 
 
6 
STUDY INTERVENTION(S) OR EXPERIMENTAL MANIPULATION(S) 
 
6.1 
STUDY INTERVENTION(S) OR EXPERIMENTAL MANIPULATION(S) ADMINISTRATION 
 
6.1.1 STUDY INTERVENTION OR EXPERIMENTAL MANIPULATION DESCRIPTION 
 
As described in Section 2.2 Background, CoCM is a stepped care model, and the intensity of treatment is 
determined by the needs of the patient and is therefore variable (i.e., there is no fixed number or 
duration for interventions contacts).  Study participants in both arms of the study will be offered 
enrollment in the CoCM, but engagement is not required for the participant to contribute data to the 
evaluation.  
 

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Table 1 – Description of CoCM Fundamental Principles and MOUD Core Components 
 
CoCM Principles 
Intervention 
Control Group 
Additions for Intervention Group 
Team Based:   A 
team of providers 
working together 
using a shared 
care plan 
• Prepared, proactive primary care 
practice 
• Minimum three-person CoCM team  
o PCP diagnoses MH disorders 
o PCP prescribes psychotropic 
medications 
o CM provides care coordination 
o Psychiatrist provides TX 
recommendations  
• Case reviews with CM and 
psychiatrist to discuss MHS 
• Clear communication strategies  
• Shared medical record 
• Integration 
o Intervention team 
 PCP diagnoses OUD 
 Case reviews with CM and 
psychiatrist to discuss OUD 
 OUD TX included in shared 
medical record 
• Pharmacological TX 
o PCP is waivered to prescribe 
MOUD 
o PCP prescribes MOUD 
o Psychiatrist is waived to prescribe 
MOUD 
Patient-Centered:  
Shared decision 
making.    
• Patient education 
o Patients presented with both 
pharmacotherapy and 
psychotherapy TX options for 
MHS 
• Treatment preferences assessed 
• Shared decision making 
• TX and self-management goals set 
• Patient activation 
• Pharmacological TX 
o Patients presented with 
pharmacotherapy TX options for 
OUD with emphasis that 
medication is essential for good 
outcomes 
 Transmucosal 
buprenorphine/Naloxone  
 Extended-release injectable 
buprenorphine 
 Extended-release injectable 
naltrexone 
• Psychosocial 
o Patients presented with 
psychotherapy TX options for 
OUD 
Population-Based:  
Tracking all 
patients 
proactively with a 
registry  
• Track patients in registry 
• Use registry to proactively identify 
patients not engaged in care  
• Conduct outreach to patients falling 
through the cracks 
• Pharmacological TX 
o CM tracks urine drug screen labs 
o CM checks the state prescription 
drug monitoring program for 
prescription fills 
o CM uses call back protocol to 
assess for medication diversion 
Measurement-
Based: Systematic 
use of clinical 
outcome 
measures to 
support treatment 
to target 
• Screen for MHS using PHQ-9 and 
GAD-7, and PC-PTSD-5 
• Monitor symptoms over time with 
PHQ-9, GAD-7 and PCL-5 
• Identify patients not responding to 
TX 
• Intensify TX 
o Switch/Augment psychotropic 
o Augment with psychotherapy 
o Refer  for specialty mental health 
consultation 
o Refer for specialty mental health 
TX 
o Stepped care  
  
• Integration 
o Screen for OUD using NIDA-
ASSIST 
o Screen for SUDs using AUDIT-C 
and BAM 
• Pharmacological TX 
o Monitor OUD patients 
 Opioid withdrawal symptoms 
 Illicit opioid craving 
 Illicit opioid use 
 Medication side effects  
 Urine drug screens 
o Identify patients not responding 
to treatment 
o Intensify TX  
 Switch/Augment OUD 
medications 
 Augment with psychotherapy 
 Refer for specialty addiction 
consultation 
 Refer for specialty addiction 
TX 
 Stepped care 
Evidence-Based: 
Delivery of 
evidence-based 
psychosocial and 
pharmacological 
treatments 
• Deliver high fidelity evidence-based 
psychotherapy for MHS  
o Behavioral Activation 
• Prescribe evidence-based 
psychotropic medications for MHS   
o Side effect management 
o Address adherence barriers 
• Psychosocial  
o Deliver high fidelity evidence-
based psychotherapy for OUDs  
 Behavioral Activation for SUD 
o Encourage attendance at mutual 
help groups  
• Pharmacological TX 
o Prescribe MOUD for OUD  

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• Conduct suicide risk assessment and 
safety planning 
• OUD Treatment Options 
o Refer to specialty addiction 
treatment for OUD 
o SAMHSA Providers Clinical 
Support System (MPI Saxon – 
Mentor) 
 
Accountable: The 
team and the 
health care 
organization 
monitor process 
and outcome 
measures and 
conduct QI 
activities 
• Specify process of care and outcome 
metrics for MHS 
• Set metric benchmarks for MHS 
• Monitor MHS metrics for providers 
and clinics 
• Conduct QI for any lower than 
expected performance on MHS 
metrics 
• Integration 
o Specify process of care and 
outcome metrics for OUD 
o Set metric benchmarks for OUD 
o Monitor OUD metrics for 
providers and clinics 
o Conduct QI for any lower than 
expected performance on OUD 
metrics 
o Monitoring to meet regulatory 
requirements for 
buprenorphine/naloxone 
prescribing 
Abbreviations: PCP – Primary Care Providers, CM – Care Manager, TX – Treatment, QI – Quality 
improvement, SAMHSA - Substance Abuse and Mental Health Services Administration, MHS – Mental 
Health Symptoms, OUD – Opioid Use Disorder, SUD – Substance Use Disorder. 
Intervention 
Based on a recent evidence synthesis,50 MOUD has three core components: 1) integration of OUD 
treatment with other MHS and physical health disorders, 2) pharmacological treatment, and 3) 
psychosocial support.50  Table 1 describes the core components of the intervention and the active 
control.  Primary care providers will provide all psychotropic and MOUD medications with consultation 
from a psychiatrist and support from a care manager.  Care managers monitor symptom response using 
structured instruments and provide behavioral activation.  In contrast to the control group, care 
managers in the intervention group specifically monitor OUD outcomes and the behavioral activation 
will focus on opioid addiction.  Primary care providers in the intervention group will be waivered and 
expected to prescribe MOUD.  Primary care providers in the control group will also be allowed to be 
waivered and prescribe MOUD.   
Mechanism of Action – The hypothesized mechanism of action is MOUD persistence defined as the ratio 
of the number of days they reported taking the MOUD medication (numerator) to the number of days 
during the 6-month follow-up period for which it was prescribed (denominator).51  
Integrated Treatment – The treatment of OUD will be integrated with the treatment of MHS, other 
substance use disorders (SUDs), and physical health disorders.  Team-Based: The integrated care team 
will include a care manager, primary care providers and consulting psychiatrist. Consulting psychiatrists 
will have a buprenorphine waiver and be trained by MPI Saxon.  Patient-Centered: The care manager 
will educate, activate, promote self-management, assess treatment preferences, and engage in shared 
decision making. Population-Based: The care manager will enter patients in the CMTS registry and 
conduct outreach activities with those who miss appointments.  Measurement-Based: OUD, other SUD, 
and MHS will be assessed over time and stored in CMTS.  Care managers will use the PHQ-9 for 
depression, the GAD-7 for anxiety and the PCL-5 for posttraumatic stress disorder (PTSD).  For patients 
not experiencing a 50% decrease in symptom severity, options for “treating to target” include: 1) 
increasing dose, 2) switching medications, 3) augmenting medications, and/or 4) intensifying 
psychosocial interventions.  Treatment adherence and side effects will also be monitored and managed. 
Monitoring OUD symptoms and adherence is described below.  Evidence-based: The primary care 
provider will prescribe FDA approved psychotropic medications for depression, anxiety and PTSD 
concurrently with pharmacologic treatment of OUD (as described below).  Care managers will also be 

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trained to deliver Behavioral Activation (described below). For alcohol, the primary care provider will 
prescribe one of two FDA approved medications (disulfiram or acamprosate) that can be used with 
buprenorphine.  The care manager will use the AUDIT-C52 for measurement based care.  For 
benzodiazepines, the care manager will screen for anxiety and sleep disorders, and if present the 
consulting psychiatrist will recommend a trial of an SSRI or trazodone.  For other SUDs, we will deliver 
Behavioral Activation and encourage abstinence.  Primary care providers will offer appropriate 
management of physical health disorders common among patients with OUD and MHS such as chronic 
obstructive pulmonary disease, viral hepatitis, human immunodeficiency virus, and chronic pain.     
Pharmacological Treatment/MOUD - Pharmacologic treatment of OUD will rely mainly on transmucosal 
buprenorphine/naloxone prescribed by primary care providers with DATA 2000 waivers. Frequency of 
medication self-administration will be tailored for each patient (from 7 day to 30 day supply) based on 
regularity of appointment attendance, evidence of illicit substance use, and evidence of treatment 
adherence.  Extended-release injectable buprenorphine will also be available for patients with 
inadequate medication adherence.  Some selected patients who agree to complete opioid withdrawal 
and prefer antagonist treatment can receive extended-release injectable naltrexone.  Methadone will 
not be used because it cannot be prescribed in the primary care setting.  Referral to federally licensed 
opioid treatment programs that dispense methadone will be an option if needed. Measurement-Based: 
Though no studies to our knowledge have used measurement-based care to support OUD treatment, 
measurement-based care and “treat to target” are fundamental principles of CoCM and will be 
incorporated into the intervention. Care managers will ask four yes/no questions about: 1) opioid 
withdrawal symptoms, 2) illicit opioid craving, 3) illicit opioid use, 4) medication side effects.  Whenever 
possible, we will corroborate negative self-reports of illicit opioid use with urine drug screens.  In 
addition, care managers will ask patients about medication adherence to make sure patients are taking 
the medication as prescribed and not waiting for withdrawal symptoms, swallowing the transmucosal 
medication, or smoking/eating before taking the medication.  Self-reported adherence will be 
corroborated by regular checking of the state prescription drug monitoring program to assure that 
patients are picking the medication up from the pharmacy. To monitor for medication diversion, we will 
use a call-back protocol developed by MPI Saxon and colleagues.53  All patients will be told about the 
call-back protocol (as a prevention intervention), but the protocol will only be used when clinically 
indicated.  If called back, patients will be asked to return to the clinic within 24 hours with their MOUD 
medication supply. If the pill count is short, medication diversion will be presumed, and the patient will 
be switched to injectable buprenorphine if possible or limited to a 7 day supply.  Treatment to Target: If 
the patient is experiencing opioid withdrawal symptoms, illicit opioid craving, or illicit opioid use, the 
care manager will alert the consulting psychiatrist during the case review.  The consulting psychiatrist 
will then recommend a change to the treatment plan to the primary care provider.  In the case of 
buprenorphine/naloxone, options for changing the treatment plan include: 1) increasing  the dosage 
(max dose 32mg), 2) augmenting with clonidine,54 3) switching to injectable buprenorphine, and/or 4) 
intensifying psychosocial interventions. If the patient is experiencing medication side effects, but not 
opioid withdrawal symptoms or illicit opioid craving, consideration will be given to lowering the 
medication dosage.  In the case of extended-release naltrexone, only a single dosage is available, so 
options include: 1) switching to buprenorphine/ naloxone, 2) augmenting with clonidine, and/or 3) 
intensifying psychosocial interventions.  
Psychosocial Support - Psychosocial support will be provided by the care manager under the guidance 
of the consulting psychiatrist. Care managers will be trained by Co-I Simpson to deliver behavioral 
activation (BA), an established psychosocial intervention for depression and anxiety, and an emerging 
intervention for PTSD,55-57 OUD,58,59, and other SUDs.60  BA is a brief and relatively simple therapy that 
can be delivered by mid-level providers.  BA benefits patients with OUD and comorbid MHS because it 

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helps to counter behavioral avoidance by assisting patients in identifying valued activities and 
developing strategies for pursuing them in healthy, non-drug use ways.  Additionally, because 
individuals with OUD and comorbid MHS often neglect important aspects of their lives (e.g., wellness 
and financial obligations), BA is well-suited to helping them systematically address these problems that 
if left unaddressed are risk factors for relapse.  Importantly, use of non-opioid psychoactive substances, 
including alcohol, will be monitored and addressed in the context of BA treatment as needed.60  We will 
also use BA to assist patients in identifying and engaging family and friends who are supportive of their 
recovery efforts.61 This component will also include gentle encouragement to attend mutual help groups 
such as Narcotics Anonymous. Receipt of specific BA elements will be tracked at the encounter level in 
the CMTS registry. 
Control 
The active control will provide integrated treatment for MHS described above, but not treat OUD.  
Treatment for OUD will involve referral to specialty settings. 
 
6.1.2 ADMINISTRATION AND/OR DOSING 
Providers – Providers include the patients regular primary care provider, their assigned care manager 
and the psychiatric consultant.  All providers are routine care staff at the participating clinics.   
Care Management Tracking System (CMTS) – For the evaluation, CMTS will be used to measure the 
number of care manager encounters, the number of care manager encounters with recorded elements 
of BA, number of psychiatric case reviews, urine test results, medications prescribed for OUD and MHS, 
as well as results of state prescription drug monitoring checks to obtain an objective measure of MOUD 
initiation and adherence.   For injectable buprenorphine or naltrexone, clinic staff will likewise record 
the administration of these injections in the CMTS.   
 
6.2 
FIDELITY 
 
6.2.1 INTERVENTIONIST TRAINING AND TRACKING 
 
Intervention fidelity will play a critical role in this study.  If fidelity is artificially controlled, the trial would 
lack external validity.62  If fidelity is poor, we would run the risk of incorrectly concluding that the 
potential clinical effectiveness of the intervention is not better than the control.  Therefore, we will take 
a balanced approach whereby the implementation team will monitor fidelity and use real-world 
implementation strategies to ensure that each clinic achieves and maintains a sufficient level of fidelity 
required for the intervention to potentially be clinically effective. External facilitation63,64 will be used to 
deliver a combination of implementation strategies that the AIMS Center has practice-tested and 
refined over the years.  These implementation strategies are known to be effective for CoCM for MHS65, 
and thus will not be evaluated.  For the 12 clinics randomized to implement the intervention only, we 
will conduct an ongoing mixed methods formative evaluation to assess implementation success, identify 
emergent barriers and tailor implementation strategies to improve fidelity. Implementation fidelity will 
be measured using the intervention fidelity rubric and process measures available in the CMTS registry 
(e.g., % of patients with regular care manager contacts and psychiatric case reviews).  

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The AIMS Center has an established implementation approach that includes training and external 
facilitation to support practice change required to implement CoCM.  Each practice will identify a clinic 
implementation team, comprised of clinic managers, primary care provider champions, and 
practice/program managers.  Additional team members can include clinic leaders, psychiatric 
consultant, care manager, and finance/compliance officers.  In the Exploration phase, the clinic 
implementation team develops a shared vision, business plan and rationale for undertaking the CoCM 
practice change including consideration of the Outer Setting, Inner Setting, and Intervention Fit with 
current clinical capacities and workflow.  In the Preparation phase, the clinic implementation team 
focuses on developing clear workflows to deliver the six CoCM fundamental principles.  The 
CoCM/CHAMP team members all complete basic training on CoCM/CHAMP role responsibilities and role 
specific didactics such as BA training for the care manager or MOUD training/waiver for the primary care 
provider.  During the Implementation phase, external facilitation supports the CoCM/CHAMP team to 
meet process and outcome benchmarks. Role specific learning communities are established to promote 
adaptations of skills to deliver patient care as a team. 
6.3 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
 
The Effectiveness and Implementation trials use cluster (site-level) randomization. Sites will be stratified 
by fidelity and healthcare organization prior to randomization.   Those administering the surveys to 
patients will be masked to randomization status (and site).   If survey administrators are inadvertently 
unmasked, that will be recorded and the rate of unmasking will be monitored.  The analysis will examine 
the potential for bias as a result of making. 
 
Study Multiple PIs will not have access to survey data until the last patient has completed the 6-month 
follow-up survey.  The study statisticians and data analysts will have access to survey data, adverse 
events and randomization status to generate reports for DSMB meetings.    
 
6.4 
STUDY INTERVENTION/EXPERIMENTAL MANIPULATION ADHERENCE 
 
Patient adherence is not required for participation in the Effectiveness trial.  Patient engagement in 
MOUD is hypothesized as the clinical Mechanism of Action. Patient self-report will be used to determine 
whether the patient engaged in MOUD, defined as the ratio of the number of days they reported taking 
the MOUD medication (numerator)  to the number of days during the 6-month follow-up period for 
which it was prescribed (denominator).   
 
7 
STUDY INTERVENTION/EXPERIMENTAL MANIPULATION DISCONTINUATION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
 
7.1 
DISCONTINUATION OF STUDY INTERVENTION/EXPERIMENTAL MANIPULATION 
 
Stopping the Effectiveness Trial –  All medications for OUD and MHS are FDA approved, and the BA 
psychotherapy has been demonstrated to be effective in numerous RCTs.  Therefore, we are not 
specifying any criteria for suspending or stopping the Effectiveness trial (intervention or evaluation). The 

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DSMB will review reports about enrollment, adverse events, protocol implementation, and data quality 
at their meetings and could decide to discontinue the Effectiveness trial.   
Discontinuing Treatment – The clinic providers can choose to initiate or discontinue any OUD or MHS 
treatment at any time during the Effectiveness trial.  In this case, the patient would remain enrolled in 
the study for evaluation purposes.  Study participants may also refuse or discontinue treatment at any 
time during the Effectiveness trial and will remain enrolled in the study for evaluation purposes.   
Refusing to Participate in the Evaluation – Study participants may refuse to complete the surveys.  
Survey refusers will remain in the Effectiveness trial and may continue to receive CoCM for OUD and/or 
MHS (contributing CMTS data).    
 
7.2 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
 
Patient Requests Study Withdrawal – If a study participant writes to the PI stating that they would like 
to withdraw from the Effectiveness trial, we will stop collecting survey data and we will not use CMTS 
data for evaluation purposes after that date.  Patients withdrawing from the Effectiveness trial may 
continue to receive CoCM for OUD and/or MHS or decline further treatment.   
PI Withdraws Patient from Study – A PI may terminate a enrollee’s participation in the Effectiveness 
trial for the following reasons:   
• 
The PI learned that the study participant did not meet inclusion criteria or did meet exclusion 
criteria at the time of enrollment.   
• 
Other unanticipated reasons 
Patients withdrawn from the study by the PI may continue to receive CoCM for OUD and/or MHS. 
7.3 
LOST TO FOLLOW-UP 
 
Definition of Lost to Follow-Up – A study participant will be considered to have been lost to follow-up 
by the survey team if it has been more than 14 days after the baseline survey was scheduled to be 
completed or more than 30 days after the 3-month or 6-month follow-up survey was scheduled to be 
completed. 
Retention – Study participants will be able to complete the survey on the phone or on the web.  
Consenting patients will be asked to provide at least four alternative contacts, in addition to their own 
telephone number and email address, and to agree for us to contact these alternates if we lose touch 
with the patient.  In addition, to mailing reminders about completing the follow-up surveys, we will also 
request permission from patients to text and/or email them reminders with a link to the web-based 
survey.  We will identify ourselves as representing the primary care clinic but will not disclose any other 
details about the purpose for trying to reach the participant. Clinics will be alerted if the data collection 
team loses touch with the patient and asked to flag the registry so the patient can provide updated 
contact information at their next visit to the clinic. Patients will receive incentives to complete surveys 
and this remuneration increases with each subsequent survey. 
 
 
 

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8 
STUDY ASSESSMENTS AND PROCEDURES 
 
8.1 
ENDPOINT AND OTHER NON-SAFETY ASSESSMENTS 
 
Screening and Eligibility Assessment – To be enrolled/consented in the Effectiveness trial, a patient 
must have screened positive for OUD and a MHS in the past six months AND currently meet clinical 
criteria for ≥2 symptoms of OUD on the DSM-5 checklist AND/OR OUD diagnosis recorded in the 
electronic medical record AND a patient encounter in the last 6 months OR OUD diagnosis on problem 
list PCP reviewed in the last 6 months. 
 
Survey Administration – Surveys will be administered at baseline, and at 3- and 6-month follow-ups.   
 
Construct/Instrument 
Baseline 
3-Month 
Follow-Up 
6-Month 
Follow-Up 
Demographics   
X 
 
 
Social Determinants  
X 
 
 
Homelessness Screening Clinical Reminder  
X 
 
 
Legal involvement question (Addiction Severity 
Index – modified) 
X 
 
 
Insurance  
X 
 
 
Pain (PEG) 
X 
X 
X 
Alcohol Use (AUDIT) 
X 
X 
X 
Opiate Use (BAM-R) 
X 
X 
X 
Opiate Craving Question (Addiction Severity Index – 
modified) 
X 
X 
X 
Readiness to Change (ICR) 
X 
 
 
Other Drug Use (BAM- R) 
X 
X 
X 
Recent Experience of Overdose 
X 
X 
X 
Health Related Quality of Life (Veterans Short Form-
12) 
X 
X 
X 
Depression (SCL20) 
X 
X 
X 
Anxiety (Neuro-QOL Measure - Anxiety, Short Form) 
X 
X 
X 
Trauma (PC-PTSD-5 Criteria A screener) 
X 
X 
X 
PTSD (PCL-5)  
X 
X 
X 
Access to Care (SPIRIT Perceived Access Inventory)  
X 
X 
X 
Service Utilization  
X 
X 
X 
Medication Use 
X 
X 
X 
Side Effects 
X 
X 
X 
 
 
Care Management Tracking System (CMTS) – After the last study participant has completed the 6-
month follow-up, we will extract information from CMTS.  CMTS is a web-based registry hosted by the 
AIMS Center and used by the care managers to track process and outcomes.20  The CMTS contains clinic-
level process of care and patient-level clinical outcome data that shows how patients receive care. For 
the evaluation, CMTS will be used to measure the number of care manager encounters, the number of 

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care manager encounters with recorded elements of BA, number of psychiatric case reviews, urine test 
results, medications prescribed for OUD and MHS, as well as results of state prescription drug 
monitoring checks to obtain an objective measure of MOUD initiation and adherence.   For injectable 
buprenorphine or naltrexone, clinic staff will likewise record the administration of these injections in the 
CMTS.   
 
8.2 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
 
8.2.1 DEFINITION OF ADVERSE EVENTS 
 
Definition of an Adverse Events: Any untoward or unfavorable medical occurrence in a human subject, 
including any abnormal sign (for example, abnormal physical exam or lab finding), symptom, or disease 
temporally associated with the subject’s participation in the research, whether or not considered 
related to the subject’s participation in the research.  
We will report the following Adverse Events: 
01. Non-suicidal self-injury that did not result in Hospitalization or ED Visit 
02. Other____________________ 
Adverse Events will be classified as serious or non-serious; expected or unexpected; and as definitely 
study-related, probably study-related, possibly study-related, or definitely not study-related. 
 
8.2.2 DEFINITION OF SERIOUS ADVERSE EVENTS 
 
Definition  of a Serious Adverse Events: Any adverse event temporally associated with the subject’s 
participation in research that is potentially life threatening, results in death, requires hospitalization, 
results in persistent or significant disability/incapacity, or any other adverse event that, based upon 
appropriate medical judgment, may jeopardize the medical or surgical intervention to prevent one of 
the other outcomes listed here. 
  We will report the following Serious Adverse Events: 
01. Suicide attempt  
02. Suicide resulting in death 
03. Death (not suicide or unsure if suicide) 
04. Non-suicidal self-injury that resulted in Hospitalization 
05. Non-suicidal self-injury that resulted in ED Visit 
06. Non-lethal overdose (that resulted in hospitalization or ED visit) 
07. Non-lethal overdose (that did not result in hospitalization or ED visit)06. Hospitalization (not 
due to suicide attempt or non-suicidal self injury) 
07 ED Visit (not due to suicide attempt or non-suicidal self injury) 
08. Non-lethal Overdose (with no hospitalization or ED visit) 
09. Serious Medication Reaction (that resulted in a clinical encounter) 
10. Other: _____________ 
 

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Serious Adverse Events will be classified as expected or unexpected; and as definitely study-related, 
probably study-related, possibly study-related, or definitely not study-related. 
 
 
8.2.3 CLASSIFICATION OF AN ADVERSE EVENT 
8.2.3.1 SEVERITY OF EVENT 
 
Adverse Events will be considered either serious or non-serious based on the definition of Serious 
Adverse Event Above. 
 
8.2.3.2 RELATIONSHIP TO STUDY INTERVENTION/EXPERIMENTAL MANIPULATION 
 
All Adverse Events and Serious Adverse Events will be classified as: 
 
01 - Definitely study related (100%) 
There is clear evidence to suggest a causal relationship, and other possible contributing 
factors can be ruled out. The clinical event occurs in a plausible time relationship to 
study procedures administration and cannot be explained by concurrent disease or 
other drugs or chemicals. The event must be pharmacologically or phenomenologically 
definitive. 
02 - Probably study related (50-99%) 
There is evidence to suggest a causal relationship, and the influence of other factors is 
unlikely. The clinical event occurs within a reasonable time after administration of the 
study procedures, is unlikely to be attributed to concurrent disease or other drugs or 
chemicals.  
03 - Possibly study related (1-49%) 
There is some evidence to suggest a causal relationship (e.g., the event occurred within 
a reasonable time after administration of study procedures). However, other factors 
may have contributed to the event (e.g., the participant’s clinical condition, other 
concomitant events). Although an adverse event may rate only as “possibly related” 
soon after discovery, it can be flagged as requiring more information and later be 
upgraded to “probably related” or “definitely related”, as appropriate. 
04 - Definitely not study related (0%) 
The event is completely independent of study procedures administration, and/or 
evidence exists that the event is definitely related to another etiology. There must be an 
alternative, definitive etiology documented by the clinician. 
8.2.3.3 EXPECTEDNESS  
 
There are numerous risks that are anticipated for this population of patient with OUD and comorbid 
MHS.  These risks are both study-related and non-study-related.   
Anticipated study-related risks associated with evaluation activities include:  

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01 psychological distress due to survey questions 
02 potential loss of confidentiality 
Study participants in both the intervention and control groups will be more likely to be started on FDA 
approved medications or have their dosages increased than non-study participants.  Therefore, 
anticipated study-related risks associated with clinical activities include:  
01 anticipated side-effects  
02 opioid craving for those initiating MOUD.   
Because of the severity and comorbidity of addiction and mental illness in our study population, it also 
anticipated that study participants will experience the following non-study related Adverse Events and 
Serious Adverse Events with a high degree of frequency: 
01 Non-lethal self-harm (Adverse Event) 
02 Suicide attempt (Serious Adverse Event) 
03 Death by suicide (Serious Adverse Event) 
04 Accidental overdose (Serious Adverse Event) 
05 Emergency department visits and/or hospital admissions (Serious Adverse Event) 
 
8.2.4 ADVERSE EVENT REPORTING  
 
 
Event Type 
Report To DSMB 
Reporting Timeframe 
Adverse Event 
Summary Report 
Annually 
Unanticipated Problem  
IRB Unanticipated Problem 
Report 
Report within 10 business 
days 
NIMH Unanticipated Problem 
Report 
Report within 10 business 
days 
IRB Determination is Serious or 
Continuing Noncompliance 
NIMH Noncompliance Report 
Report within 10 business 
days of IRB determination 
IRB Determination is Study 
Suspension or Termination 
NIMH Study Suspension Report 
Report within 3 business 
days of IRB determination 
Protocol Deviation 
Summary Report 
Annually 
 
 
8.2.5 SERIOUS ADVERSE EVENT REPORTING  
 
Event Type 
Nature of Event 
Study Related 
Report To 
Reporting 
Timeframe 
Serious Adverse 
Event 
Unexpected 
The event is 
related 
IRB Serious Adverse 
Event Report 
Report within 10 
business days  

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(possibly, 
probably, 
definitely 
related) to the 
research 
NIMH Serious 
Adverse Event 
Report 
Report within 10 
business days 
Serious Adverse 
Event 
Expected 
Related or 
Unrelated 
DSMB 
Report 3 times a 
year 
Serious Adverse 
Event 
The Nature of 
Event is: 
“Suicide 
resulting in 
death” 
OR 
“Death (not 
suicide or 
unsure if 
suicide)” 
The death is 
related 
(possibly, 
probably, or 
definitely 
related) to the 
research 
NIMH Death Report 
Report no later 
than within 5 
business days 
Serious Adverse 
Event 
The Nature of 
Event is: 
“Suicide 
resulting in 
death” 
OR 
“Death (not 
suicide or 
unsure if 
suicide)” 
The death is  
definitely not 
related to the 
research 
DSMB 
Report 3 times 
per year 
 
8.2.6 REPORTING EVENTS TO PARTICIPANTS  
 
If our Single IRB determines that an Adverse Event or Serious Adverse Event needs to be reported to an 
individual study participant, one of the multiple PIs will telephone that person and notify them of the 
event and explain the risk.  If our Single IRB determines than an Adverse Event or Serious Adverse Event 
needs to be reported to all study participants, notifications will be emailed and mailed to study 
participants. 
 
8.3 
UNANTICIPATED PROBLEMS, PROTOCOL DEVIATIONS, AND NON-COMPLIANCE 
 
8.3.1 DEFINITION OF UNANTICIPATED PROBLEMS 
 
Definitions 
1. Unanticipated Problems:  
a. Unexpected in terms of nature, severity, or frequency, given the research procedures 
that are described in the protocol-related documents, such as the IRB-approved 

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research protocol and informed consent document and (b) the characteristics of the 
subject population being studies 
b. Related or possibly related to a subject’s participation in the research  
c. Suggests that the research places subjects or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) related to the research than was 
previously known or recognized.  
 
2. Protocol Deviation: An accidental or unintentional change to the IRB-approved protocol that 
may cause harm to subjects or others, indicates that the subjects or others are at an increased 
risk of harm, or has adversely impacted data integrity. Protocol deviations will be reported to the 
Single IRB as either an unanticipated problem or noncompliance.    
 
3. Noncompliance: any action or activity associated with the conduct or oversight of research 
involving human subjects that fails to comply with applicable regulations, the IRB’s Handbook, 
and/or the determinations and requirements of the IRB. Noncompliance may range from minor 
to serious; be unintentional or willful; and may occur once, sporadically, or continuously.  
a. Serious Noncompliance: any action or omission in the conduct or oversight of research 
involving human subjects that affects the rights and welfare of subjects, increases risk to 
subjects, or compromises the scientific integrity or validity of the research. 
 
b. Continuing Noncompliance: a pattern of repeatedly failing to comply with applicable 
regulations, the IRB’s Handbook, and/or the determinations and requirements of the 
IRB that may affect subjects’ rights and welfare, increase risk to subjects, or may 
compromise the scientific integrity or validity of the research. Continuing 
noncompliance also includes frequent instances of minor noncompliance or failure to 
respond to a request to resolve an episode of noncompliance. 
 
8.3.2  PROBLEM REPORTING  
 
Unanticipated problems, protocol deviations, or instances of non-compliance will be reported to our 
Single IRB within 10 business days, along with any corrective actions that have been or will be taken.  
Our Single IRB will determine whether an unanticipated problem, protocol deviation, or instance of non-
compliance needs to be reported to an individual or to all study participants. All Unanticipated 
Problems, protocol deviations, or instances of non-compliance will be compiled and reported to the 
NIMH DSMB as per the adverse event reporting table above.   
 
It will be the responsibility of the site investigator to use continuous vigilance to identify and report 
deviations to the Single IRB.  As specified in Section 8.3.5, Adverse Event Reporting, the PIs will report 
protocol deviations to the Single IRB that are considered to be unanticipated problems or 
noncompliance within 10 business days.  The PI will be responsible for knowing and adhering to any 
actions required by the Single IRB, including modifying the protocol and/or report to the NIMH and the 
NIMH DSMB, as noted in the event reporting table above. 
 

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8.3.3 REPORTING PROBLEMS TO PARTICIPANTS  
 
If our Single IRB determines that an unanticipated problem, protocol deviation, or instance of non-
compliance needs to be reported to an individual study participant, will telephone that person and 
notify them of the event and explain the risk.  If our Single IRB determines than an unanticipated 
problem, protocol deviation, or instance of non-compliance needs to be reported to all study 
participants, notifications will be emailed and mailed to study participants.    
9 
STATISTICAL CONSIDERATIONS  
 
9.1 
STATISTICAL HYPOTHESES 
 
Hypotheses for Primary Objective (Effectiveness Trial) 
Hypothesis a: Compared to patients with MHS and OUD at clinics randomized to the control, patients 
at clinics randomized to the intervention group (both Cohorts 1 and 2) will report better access to and 
engagement in OUD treatment, less opioid use (primary outcome), better mental health functioning 
(primary outcome), fewer disorder specific mental health symptoms, better quality of life, and fewer 
risk factors for premature mortality.     
Hypothesis b: Engagement in MOUD will completely mediate any improvements in patient reported 
outcomes observed in intervention clinics compared to control clinics.   
 
Hypothesis for Secondary Objective (Pre-Post Trial) 
Hypothesis: The proportion of patients enrolled in the clinic with a MH diagnosis and a new OUD 
diagnosis documented in the electronic medical record will be higher in the post-period than the 
pre-period. 
 
Exploratory Hypothesis for Exploratory Objective (Pre-post evaluation) 
Exploratory Hypothesis : CHAMP intervention clinics receiving the high-intensity sustainability 
implementation strategy will maintain their implementation outcomes (adoption, reach, intervention 
fidelity and effectiveness) after the effectiveness trial has been completed (post) compared to during 
the effectiveness trial (pre).   
9.2 
SAMPLE SIZE DETERMINATION 
 
Power Analysis For Pre-Post Trial –   Under the assumption of 24 clinics, at least 500 eligible MHS 
patients in each clinic in each six-month period, a rate of documented OUD of 1% pre-screening, a 
conservative estimate of 0 correlation between pre- and post-percentages, and an alpha significance 
level of 0.05, we will have 80% power to detect an increase from a pre-screening percentage of 1% to a 
post-period percentage of 1.7%.  
Power Analysis For Effectiveness Trial - Assuming a coefficient of variation of 0.33 for the continuous 
outcome of days of illicit opioid use676 and SF12V MCS scores6687, a highly conservative intraclass 
correlation within clinics of 0.03, 12 clinics per group and 40 patients per clinic (n=960, accounting for 

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20% attrition), we will have 80% power to detect an effect size of 0.31. We chose to use a highly 
conservative intraclass correlation to ensure sufficient power for secondary outcomes and mediation 
analyses (Hypothesis 2b).  Thus, conservatively we will have 80%  power to detect a 10 % difference in 
number of days using illegal opioids in the past month (e.g., 15.00 days compared to 13.5 days) and 10% 
difference in MCS scores (e.g., 40 compared to 36) between CHAMP and CoCM for MHS only clinics.  
Because these are multiple primary outcomes (and not co-primary outcomes), this power analysis 
assumes a Bonferroni correction for the two multiple primary outcomes.  Specifically, the intervention 
will be interpreted to have been successful if there is a significance group different between either 
primary outcome, not both primary outcomes.  Because of recruitment challenges, power analyses are 
also now provided for the lower bounds of expected enrollment. The lower-bounds power analysis 
assumes that we will recruit 360 study participants instead of 1200. For this lower-bounds power 
analysis, we assume a more realistic intraclass correlation of 0.01 instead of 0.03. Collaborative care 
trials conducted by Dr. Fortney (MPI) and Dr. Schoenbaum (NIMH collaborator) found intraclass 
correlation coefficients in the range of 0.008-0.001).30,66 Assuming a coefficient of variation of 0.33 for 
the continuous outcome of days of illicit opioid use67 and SF12V MCS scores68, an intraclass correlation 
within clinics of 0.01, 12 clinics per group, 15 patients enrolled per clinic (n=288 accounting for 20% 
attrition), we will have 80% power to detect an effect size of 0.41.  The sample size of 360 does not 
represent a revised enrollment target, and we will continue to enroll as many study participants as 
possible (up to 1,200) using enhanced recruitment methods and by extending the recruitment period if 
possible. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
• 
 
 
9.3 
POPULATIONS FOR ANALYSES 
 
Intention-to-Treat 
 

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9.4 
STATISTICAL ANALYSES 
 
9.4.1 GENERAL APPROACH 
 
Statistical Analysis Plan - There will be a formal Statistical Analysis Plan that will be completed prior to 
unblinding of the Effectiveness trial data.  The statistical plan will be posted publicly or registered before 
the study begins. 
 
Reporting of Descriptive Statistics – Categorical data collected at baseline will be presented as 
percentages.  Continuous data will be presented as means with standard deviations.  
 
Statistical Tests – An alpha level of 0.05 and two-tailed tests will be used to determine statistical 
significance. 
 
Covariates – Covariates will be included if they are theoretically related to both the dependent variable 
and the probability of having missing data, and will be specified later in the SAP. 
 
Test of Distributional Assumptions – We will examine residuals for normality. If residuals are not 
approximately normally distributed, we will use a sandwich estimator (e.g., robust maximum likelihood 
estimator) to correct standard errors. Note that the treatment effect is a binary indicator and 
consequently, the point estimate for treatment condition will be unbiased, conditional on other model 
effects being specified correctly. For continuous covariates, we will examine scatterplots and partial 
regression plots to ensure the linearity assumption is reasonable. If linearity appears to be meaningfully 
violated, we will transform either the predictor variables or the outcome, depending on the patterning 
of nonlinearity. 
 
9.4.2 ANALYSIS OF THE PRIMARY ENDPOINT(S) 
 
Primary Outcomes of Effectiveness Trial - The multiple primary outcomes evaluated will be patient-
reported measures of illicit opioid use, and mental health functioning. Opioid use will be measured using 
item 7E from the Brief Addiction Monitor (BAM)68:  “ In the past 30 days, how many days did you use 
opiates such as Heroin, Morphine, Dilaudid, Demerol, Oxycontin, oxy, codeine (e.g., Tylenol 2,3,4), 
Percocet, Vicodin, Fentanyl, etc.? Do not count times you used buprenorphine, suboxone, or methadone 
as directed by a healthcare provider.”    Mental health functioning will be measured using the Mental 
Component Summary score of the SF-12.  
 
Intent to Treat Analysis of Primary Outcomes of Effectiveness Trial – Given the cluster-randomization 
we will use appropriate mixed models (also known as multi-level models) to account for clinic effects 
that are shared by subjects from the same clinic.  Measurement occasions (level 1) will be nested within 
individuals (level 2) which are then nested within clinics (level 3).   All outcomes will be analyzed with a 
multilevel model accounting for clustering of observations (level 1) within patients (level 2) and clinics 
(level 3).  The model will include a random intercept and random linear slope to account for person-level 
clustering and repeated measures on individual subjects over time that may be associated with variable 
time trends across participants. To allow for curvilinear change over time, time will be entered as a 
nominal variable by including dummy codes for the 3- and 6-month time points. The explanatory 

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variable of interest will be group randomization status (e.g., intervention versus control). Main effects 
and interaction terms with time-indicator variables capture the difference between intervention and 
control group at each wave.  Covariates will be included if they are theoretically related to both the 
dependent variable and the probability of having missing data. An alpha level of 0.05 and two-tailed 
tests will be used to determine statistical significance. Results will be presented as adjusted differences 
between groups with confidence intervals. Missing Data - We will examine patterns of missing data to 
determine the degree to which the missing at random assumption (the degree to which missingness is 
related to variables included in the model) is plausible.  With high missing rates, we may use missing 
data methods to account for missing not at random mechanisms.  If warranted, multiple imputation or 
similar methods will be used to account for missing data on completed or partially completed baseline 
and follow-up surveys (e.g., skipped items).   
 
9.4.3 ANALYSIS OF THE SECONDARY ENDPOINT(S) 
 
Secondary Outcomes of Effectiveness Trial - The secondary outcomes are perceived access, quality of 
life and risk factors for premature mortality.   Access: Perceived access to OUD services will be measured 
using a modified version of the 9-item SPIRIT Perceived Access Scale developed for our PCORI trial.  The 
scale is based on theory,11 has excellent internal consistency (κ - 0.89), and concurrent validity with 
number of mental health encounters (p=0.016).  PTSD symptoms will be assessed using the PCL-5.69 
Depression symptoms will be assessed using the SCL-20.70  Anxiety will be measured using the Neuro-
QOL Measure - Emotional Distress, Anxiety, Short Form 7a.71,72 Health Related Quality of Life will be 
measured using the Veterans Short Form-12.73  Risk factors for premature mortality: Risks, including 
suicidal ideation (two items from SCL-20), discontinuing MOUD6, overdose, suicide attempts, emergency 
department admission, hospitalization74 and death, will be collected from participating clinics as part of 
the adverse event reporting process.  Depending on their observed frequency, these risk factors will be 
analyzed separately or grouped. 
Clinical Mechanism of Action (MOUD Persistence) - Patient self-report will be used to determine 
whether the patient engaged in MOUD, defined as the ratio of the number of days they reported taking 
the MOUD medication (numerator)  to the number of days during the 6-month follow-up period for 
which it was prescribed (denominator).51  
Intent to Treat Analysis of Secondary Outcomes and Clinical Mechanism of Action of Effectiveness 
Trial   - Measurement occasions (level 1) will be nested within individuals (level 2) and nested within 
clinics (level 3).  All outcomes will be analyzed with a multilevel model accounting for clustering of 
observations (level 1) within patients (level 2) and clinics (level 3).  Regression models will be specified 
with the appropriate distribution and link functions to match the dependent variable (linear for the 
continuous scores, logistic for MOUD engagement and presence of risk factors). The model includes a 
random intercept and random linear slope to account for person-level clustering and estimate variable 
time trends across participants. To allow for curvilinear change over time, time will be entered as a 
nominal variable by including dummy codes for the 3- and 6-month time points. The explanatory 
variable of interest will be group randomization status (e.g., intervention versus control). Main effects 
and interaction terms capture the difference between intervention and control group at each wave.  
Covariates will be included if they are theoretically related to both the dependent variable and the 
probability of having missing data.  An alpha level of 0.05 and two-tailed tests will be used to determine 
statistical significance. Results for continuous variables will be presented as adjusted differences 
between groups with confidence intervals. Results for dichotomous variables will be presented as 

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adjusted odds ratios with confidence intervals.  Missing Data - We will examine patterns of missing data 
to determine the degree to which the missing at random assumption (the degree to which missingness 
is related to variables included in the model) is plausible.  With high missing rates, we may use missing 
data methods to account for missing not at random mechanisms.  If warranted, multiple imputation or 
similar methods will be used to account for missing data on completed or partially completed baseline 
and follow-up surveys (e.g., skipped items).   
Pre-Post Screening Analysis of Pre-Post Trial – Because the clinics will not have the capacity to analyze 
data at the level of the individual patient, each clinic will calculate the proportion of patients in the pre-
screening sample with a new OUD diagnosis and the proportion of patients in the post-screening sample 
with a new OUD diagnosis.  Each clinic will report these two proportions to the investigative team, and 
we will compile a dataset with 24 observations (2 observations from each of the 12 clinics in each trial) 
and two variables: 1) proportion with a new OUD diagnosis and 2) a dummy variable indicating pre- or 
post-screening time period).  For each clinic we will compute the change in proportion from pre- to post-
screening.  Because the pre-screening proportions are expected to be low (~1%)75, the change measures 
will likely be skewed due to a floor effect.  Also, the homogeneity of variance assumption could be 
compromised if the numbers of patients in the denominators vary considerably.  For these reasons, we 
plan to use the non-parametric sign test to evaluate the statistical evidence indicating whether the 
proportions have changed.  The numbers and proportion of the 12 clinics in each trial that see an 
increase in proportion of documented OUDs will be tabulated. The overall increase in proportion will be 
estimated with the mean of the clinic changes, weighted by the inverse variances, assuming binomial 
distributions for the pre- and post-screening numbers of documented OUDs. A bootstrap empirical 95% 
confidence interval will be computed for the estimate of overall proportion increase.   
 
9.4.4 BASELINE DESCRIPTIVE STATISTICS 
 
Categorical data collected at baseline will be presented as percentages.  Continuous data will be 
presented as means with standard deviations. Because we are using cluster randomization with a 
relatively small number of randomization units, t-tests and chi-squares will be used to test for group 
differences at baseline.   
 
9.4.5 SUB-GROUP ANALYSES 
 
Because there is evidence that CoCM is more effective for women and minorities, we will conduct a 
moderation analysis (interaction term between sub-group and intervention group) for our primary 
outcomes.  
 
9.4.6 EXPLORATORY ANALYSES 
 
Exploratory Implementation Outcomes for Pre-Post Sustainability Evaluation–  Participating 
intervention clinics continuing into the sustainability phase will continue to use the CMTS registry, and 
we will rely on data from CMTS and provider and clinic level surveys to monitor the implementation 
success metrics (adoption, reach, effectiveness and intervention fidelity). Reach will be measured by the 
number of patients receiving MOUD and evidence-based treatments for MHS.  Adoption will be 
measured by the number of primary care providers prescribing MOUD and psychotropics for MHS. 

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Effectiveness will be measured using measurement-based care data.  Implementation fidelity will be 
measured using the CoCM principles fidelity rubric modified for CHAMP.   These six implementation 
outcomes will be measured at the end of the effectiveness trial and again after six months.   
 
Quantitative Analysis for Pre-Post Sustainability Evaluation - These implementation outcomes 
measured at end of effectiveness trial will be compared to the implementation outcomes measured at 
the end of the sustainment period ( after six months).  The small sample size (n=6 clinics from 4 
healthcare systems) will not give us sufficient power to detect anything but large effects.  However, we 
will be able to see trends over time and to compare these distal implementation outcomes to those 
measures obtained during the effectiveness trial.   
 
Qualitative Data Collection and Analysis for Pre-Post Sustainability Evaluation - We will supplement 
the quantitative data with qualitative data collected from clinic staff. Purposive sampling will be used to 
identify stakeholders from each of the 6 clinics.  All interviews will be conducted via interactive video 
(Zoom).  Recruitment/Consent - Eligible stakeholders will be identified by the study lead at each clinic. 
After a stakeholder has been identified, research staff will recruit them by email and or phone. 
Stakeholders will be considered study participants. We will mail or email stakeholders the “CHAMP 
Summative Evaluation Information Sheet”.  We will obtain an audio-recorded verbal agreement to 
participate in the qualitative interviews rather than written informed consent because the signed 
consent form would be the only identifying information collected (thereby increasing the risk of loss of 
confidentiality).  In addition, participation in the qualitative interviews is considered to be no more than 
minimal risk.   Interview Guide: The interview guide is organized by type of implementation outcome 
(sustainment mechanisms of action, proximal, distal), and three types of determinants that can be a 
barrier or facilitator of implementation success: 1) outer setting, 2) inner setting, and 3) fit between the 
clinical intervention and the outer and inner settings.  A blend of grand-tour and specific probe 
questions will be used.  Analysis - Using a typology of mixed method approaches, we will use the 
qualitative data to provide convergence with the quantitative data. This will include: 1) triangulation 
across data streams to corroborate findings (focusing on distal outcomes), 2) complementarity to gain 
additional depth of understanding and focus on process and context (across all outcomes), and 3) 
development of a conceptual model used to generate hypotheses. Two qualitative data analytic 
approaches will be used.  A directed content analytic approach will be used to assess the distal 
implementation outcomes.  This approach blends deductive and inductive analysis and will be used to 
provide depth and context to site level performance data on reach, adoption, and fidelity.  A more 
grounded thematic analysis approach will be used to examine the potential impacts of the sustainment 
strategies on the proposed mechanisms of action and proximal outcomes.  This approach will be largely 
inductive and focused on developing an initial model of mechanisms of action. 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
 
10.1 REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
10.1.1 INFORMED CONSENT PROCESS 
 
10.1.1.1 CONSENT/ASSENT AND OTHER INFORMATIONAL DOCUMENTS PROVIDED TO 
PARTICIPANTS 

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Consent forms describing in detail the study intervention, study procedures, and risks will be given to 
the participant and written documentation of informed consent will be completed prior to starting the 
study intervention.  The consent form is included with this protocol. 
10.1.1.2 CONSENT PROCEDURES AND DOCUMENTATION 
 
After a patient has been determined to be eligible (see eligibility workflow in section 5), clinic staff will 
recruit and consent the patient. Clinics will maintain electronic or hardcopies of the original consent 
form.  Patients will be given an electronic or hardcopy of the signed consent form. Staff will not sign the 
consent form as a witness to the signature.  Clinics may consent patients in one of two ways: in-person 
consenting or virtual e-consenting.  
1. In-person consenting: clinic staff will provide information about the study to the patient in 
person using a REDCap e-consent form or a hardcopy of the informed consent form. Clinic staff 
will facilitate patient comprehension by providing opportunity for patient to consider the 
information and ask questions. Clinic staff will document consent using a REDCap e-consent 
form on a tablet or a hardcopy of the informed consent form. The signed REDCap e-consent 
form will automatically save a PDF of the electronic consent form that is immediately accessible 
to the UW study team to verify that the patient has enrolled in the study. A scanned PDF of the 
signed hardcopy consent form will be sent to UW to verify that the patient has enrolled in the 
study and to ensure that signatures are valid and dates are present.   
2. Virtual e-consenting: clinic staff will provide information about the study to the patient virtually 
by tele-video or audio-only telephone. Clinic staff will facilitate patient comprehension by 
providing opportunity for patients to consider the information and ask questions. Clinic staff will 
document consent using a REDCap e-consent form or a hardcopy of the informed consent form. 
The REDCap e-consent form will be emailed to the patient to sign on their phone or computer. 
The hardcopy informed consent form can be mailed to the patient and returned if email is not 
available to the patient. The signed REDCap e-consent form will automatically save a PDF of the 
electronic consent form that is immediately accessible to the UW study team to verify that the 
patient has enrolled in the study. A scanned PDF of the signed hardcopy consent form will be 
sent to UW to verify that the patient has enrolled in the study and to ensure that signatures are 
valid and dates are present.   
 The modified76 informed consent process will disclose the general purpose of the study, the evaluation 
data collection research activities, the risks of participating in the data collection activities, the 
protection against those risks, and the alternatives to participating, but patients will not be told which 
study arm their clinic has been randomized to.77  We chose to not disclose this information to support 
the internal and external validity of the Effectiveness trial.    
Consent forms will be available both in English and in Spanish. 
 
10.1.2 STUDY DISCONTINUATION AND CLOSURE 
 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable 
cause. Written notification, documenting the reason for study suspension or termination, will be 
provided by the suspending or terminating party to the study participants, funding agency, and 

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regulatory authorities. If the study is prematurely terminated or suspended, the Principal Investigator 
(PI) will promptly inform study participants, the Institutional Review Board (IRB), and sponsor/funding 
agency and will provide the reason(s) for the termination or suspension. Study participants will be 
contacted, as applicable, and be informed of changes to study visit schedule. 
 
Circumstances that may warrant termination or suspension include, but are not limited to: 
• 
Determination of unexpected, significant, or unacceptable risk to participants 
• 
Demonstration of efficacy that would warrant stopping    
• 
Insufficient compliance to protocol requirements 
• 
Data that are not sufficiently complete and/or evaluable 
• 
Determination of futility 
 
10.1.3 CONFIDENTIALITY AND PRIVACY  
 
Participant confidentiality and privacy is strictly held in trust by the participating investigators, their 
staff, the safety and oversight monitor(s), and funding agency. This confidentiality is extended to the 
data being collected as part of this study. Data that could be used to identify a specific study participant 
will be held in strict confidence within the research team. No personally-identifiable information from 
the study will be released to any unauthorized third party.  
The data files with eligibility criteria, survey response and information extracted from CMTS will not 
contain any identifying information about study participants, but will contain a unique study ID.  We will 
maintain a separate file that contains the study ID and participant’s identifying information.  This 
separate file containing participant’s identifying information will only be available to the study team, 
and organizations that make sure studies like this are done safely. Specifically, the Institutional Review 
Board, the National Institutes of Health, and the federal Office for Human Research Protections  will be 
able to inspect and copy confidential study-related records which identify study participants’ by name. 
This is to make sure the research team is conducting the Effectiveness trial safely and legally.   
Certificate of Confidentiality – This research is covered by a Certificate of Confidentiality from the 
National Institutes of Health. The researchers with this Certificate may not disclose or use information, 
or documents that may identify study participants in any federal, state, or local civil, criminal, 
administrative, legislative, or other action, suit, or proceeding, or be used as evidence, for example, if 
there is a court subpoena, unless a study participant has consented for this use. Information, or 
documents protected by this Certificate cannot be disclosed to anyone else who is not connected with 
the research except, if there is a federal, state, or local law that requires disclosure or if a study  
participant has consented to the disclosure, or if it is used for other scientific research, as allowed by 
federal regulations protecting research subjects.  The Certificate cannot be used to refuse a request for 
information from personnel of the United States federal or state government agency sponsoring the 
project that is needed for auditing or program evaluation by the agency which is funding this project or 
for information that must be disclosed in order to meet the requirements of the federal Food and Drug 
Administration (FDA).  The Certificate of Confidentiality will not be used to prevent disclosure as 
required by federal, state, or local law of, for instance, child abuse or neglect, harm to self or others, and 
communicable diseases.  If we learn that study participants intend to harm others, we will report that to 
the authorities.  Also, if a study participant reports that they intend to harm themselves, we will connect 
them with professionals trained in suicide prevention and notify their primary care team.    

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10.1.4 KEY ROLES AND STUDY GOVERNANCE 
 
Principal Investigator 
John Fortney, PhD, Professor 
University of Washington 
1959 NE Pacific Street, Box 
356560, Seattle, WA  98195-6560 
206.685.6955 
fortneyj@uw.edu 
 
 
 
The organizational chart shows the structure that will be used to manage the trial and insure timely 
accomplishment of study aims. Each key area of the trial (Intervention, Implementation, Evaluation) will 
be led by one of the MPIs. Content areas within each of these will be led by one or more co-
investigators who have relevant expertise. The weekly meetings associated with each of these key areas 
will produce agendas and minutes posted on a shared password-protected project management 
website for all investigators and members of the Steering Committee to review and in case of absence. 
Coordination of communication among the committees and teams will be the responsibility of the 
project manager who will establish a password-protected project management website where study 
materials, schedules and meeting minutes and other study documents can be shared. The program 
manager will support the easy flow of information among the multiple layers of trial staff, faculty and 
clinical organizations, including the external IRB, and Institute for Translational Health Sciences (ITHS), 
which will conduct data collection, provide bioethics consultation, and data safety monitoring. 
Executive Committee – This committee consist of the three MPIs and the project manager.  It will meet 
weekly to review ongoing progress of the study and to resolve operational issues as they arise. This 
group will regularly review data collection reports produced by the Institute for Translational Health 
Sciences (ITHS), data management reports produced by the Data Manager and Statistician, training and 

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implementation updates and intervention updates. These reports will assist the Executive Committee 
with insuring the study is accomplishing milestones on time. This committee will regularly review 
budget and expenditures to ensure that the study spends funds at the appropriate and proposed rate 
and has the resources to complete the tasks as outlined in the grant.  This committee will have 
responsibility for publications arising from the trial, including CHAMP scientific conference 
presentations, prioritization of manuscripts that arise from CHAMP. According to the publications policy 
approved by the Steering Committee, this team will be proactive about inviting investigators to author 
and co-author papers and presentations. This group will produce a semi-annual report of activities and 
progress toward study goals for the Steering Committee.  
Steering Committee – This is the governing body of the trial. The Steering Committee will be comprised 
of the MPIs, key personnel, NIH Project Scientist(s), clinicians and/or health system leadership for each 
of the participating clinics,  an ITHS bioethics expert, and five (5) additional members that reflect the 
diversity of mental health and addiction stakeholders, such as patients and health policy makers will 
meet semi-annually to plan research activities, review study progress, and establish priorities, policies, 
and procedures related to the CHAMP trial. Each member of the committee will have one vote in 
decisions made by the Steering Committee with respect to study policies and procedures. Adoption of 
policies and procedures will require a majority vote. These policies and procedures will include 
publication policies. The chair of this committee will rotate among the MPIs on a yearly basis such that 
the chair of the Executive Committee and Steering Committee are not the same person in a given year. 
NIH Program Officials may attend Steering Committee meetings as non-voting members. 
CHAMP Intervention Team – This group, led by MPI Saxon, will meet weekly during the 
implementation phase of the trial. The purpose of this team is to monitor the CHAMP clinical 
intervention at participating clinics, insuring the intervention protocol is aligned with current 
evidence-based treatment guidelines for co-occurring OUD and mental health conditions. This group 
will meet with the ITHS bioethics consultant in Year 1 to refine the Intervention Treatment manual 
and will meet with the bioethicist, as needed, on an ad hoc basis. This team includes MOUD experts 
(led by Saxon and Duncan), Collaborative Care experts (Unützer and Ratzliff), and clinical content 
experts representing primary care (Merrill, Duncan), child psychiatry and substance use (Hsiao), 
psychosocial supports (Simpson), and perinatal psychiatry (Bhat). This group will produce a semi-
annual report of activities and progress toward study goals for the Steering Committee. 
Implementation Team – This group, led by MPI Ratzliff, will meet weekly during the implementation 
and sustainability phases of the trial. The purpose of this team is to monitor training, CoCM and 
CHAMP external facilitation during the Effectiveness trial, internal and external facilitation during the 
sustainability phase, and formative evaluation activities during both the Effectiveness trial and 
sustainability phase. This team includes the two Clinical Implementation Support Leads from the 
AIMS Center conducting practice facilitation with participating clinics (Shields, Barker) and the 
formative evaluation experts (Williams, Lewis). This group will produce a semi-annual report of 
activities and progress toward study goals for the Steering Committee. 
Evaluation Team - This group, led by MPI Fortney, will meet every other week during the data 
collection and analysis phases of the trial. It will have responsibility for designing, monitoring, and 
supporting all evaluation activities for CHAMP, including reviewing data collected, data quality, and 
similar throughout the trial. Membership include the quantitative leads (Heagerty, Bowen) and the 
summative evaluation leads (Curran, , and Drummond) as well as the data manager and other 
evaluation staff as needed.  
10.1.5 SAFETY OVERSIGHT 

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Data and Safety Monitoring Plan 
General Procedures – The Multiple PIs will be primarily responsible for day to day data safety and 
monitoring. The PIs will ensure that informed consent is obtained prior to performing any research 
procedures, that all subjects meet eligibility criteria, and that the study is conducted according to the 
IRB-approved research plan. Random audits for data safety may be performed by the IRB. 
DSMB -- Monitoring for the study will be provided by a NIMH appointed DSMB, including data and 
safety monitoring and review three times a year. The DSMB will meet to review enrollment data, 
adverse events, data quality and integrity of protocol implementation. The DSMB will provide a written 
report to the study team with recommendations for study modification, and has decisional authority 
with respect to study initiation, and study continuation/discontinuation. The UW study team will be 
responsible for forwarding DSMB decisions to the IRB. 
 
10.1.6 STUDY MONITORING 
 
Research staff at the University of Washington will meet with sites biweekly to review recruitment 
procedures including eligibly assessment and consenting, as well as facilitate to adverse event reporting.  
Adverse Events reported from the sites will be promptly reviewed by a multiple PI to determine study 
relatedness.  Adverse Events will be logged by sites into RedCap, which will automatically alert the 
multiple PIs via email until they are resolved.  The multiple PIs and research coordinators will review 
eligibility and adverse event reports during weekly meetings.  
 
10.1.7 QUALITY ASSURANCE AND QUALITY CONTROL 
 
Federal Wide Assurances (FWA) – Federal Wide Assurance documents issued from OHRP (including 
expiration dates) will be kept on file. 
 
IRB Records – All single IRB and local IRB records and correspondence will be maintained in electronic 
format. 
 
Training in Human Subjects Training – The Project Coordinator will ensure that all study personnel have 
documentation of completing all required human subjects protection training.  In addition, the Project 
Coordinator will ensure documentation that those obtaining informed consent have completed the 
consent training specific to this study.   
 
Eligibility Tracking – All patients screening positive for OUD (potentially eligible) will be entered into the 
Eligibility RedCap project where exclusion criteria and refusals will be documented.  The Eligibility 
RedCap project will also be the repository of all scanned signed consent forms.   
 
Informed consent – A UW research coordinator will review the documentation of the consenting 
process, as well as a percentage of eligible patients completing the consent process.  This review will 
evaluate compliance with GCP, accuracy, and completeness.  Feedback will be provided to the on-site 
study team to ensure proper consenting procedures are followed, and that all consented patients were 
eligible.  

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Source documents and the electronic data – All data will be captured electronically (see Section 10.1.9, 
Data Handling and Record Keeping).   
Intervention Fidelity – Consistent delivery of the study interventions will be monitored throughout the 
intervention phase of the study. Procedures for ensuring fidelity of intervention delivery are described in 
Section 6.2.1, Interventionist Training and Tracking.  
Data Integrity –  The data analyst will review electronically collected study data for any problems (e.g., 
missing, out of range data).  
Adverse Event Report – All adverse events will be entered in the AE/SAE log of the RedCap Study 
project. All site-specific SAE reports will be on file, including documentation of reporting to the NIMH 
and the DSMB. 
Protocol Deviations – The study team will review protocol deviations on an ongoing basis and will 
implement corrective actions.  Should independent monitoring become necessary, the PI will provide 
direct access to all trial related sites, source data/documents, and reports for the purpose of monitoring 
and auditing by the sponsor/funding agency, and inspection by local and regulatory authorities.  See 
Section 8.4.1, Definition of Unanticipated Problems and Section 8.4.2, Unanticipated Problems 
Reporting.  
 
10.1.8 DATA HANDLING AND RECORD KEEPING  
10.1.8.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
 
Sources of Materials 
Sources of research materials include the following: 
EHR Data (Non-Indefinable) – Pre- and Post-Screening data (numerator [OUD diagnosis] and 
denominator [unique patients] will be calculated by each healthcare organization using EHR queries and 
recorded in an excel spreadsheet.  The excel spreadsheet (which contains no patient health or 
identifying information), will be emailed to the study team at the University of Washington.  Data will be 
reviewed by University of Washington statisticians and data managers and discussed with the on-site 
study team.  This data will be used for the Secondary Objective (Pre-Post Trial). 
Eligibility Data and Consent Forms – The eligibility information for all patients screening positive for 
OUD will be entered directly into RedCap by the on-site study team.  Signed consents forms, will be 
scanned and attached to the RedCap study portal.  Eligibility data will be reviewed by a University of 
Washington PI and the study coordinators, and discussed with the on-site study teams.  This data will be 
used for the Primary Objective (Effectiveness trial).  
Personal Identifying Information – Identifying information (e.g., name, address, telephone number, 
email, and contacts) about patients consenting to be in the Effectiveness trial will be stored in a single 
file along with a unique study identifier.  This data will be used for the Primary Objective (Effectiveness 
trial).  
Surveys - The patient web/telephone survey will be administered at baseline, 3- and 6-month follow-
ups. All survey responses are stored directly into a RedCap database.  This data will be used for the 
Primary Objective (Effectiveness trial).  

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Adverse Events – Information about all Adverse Events, Serious Adverse Events, Unanticipated 
Problems, and Potential Loss of Confidentiality will be entered directly into RedCap by the on-site study 
team and reviewed/edited by the research team. This data will be used for the Primary Objective 
(Effectiveness trial), as well as for regulatory purposes.    
CMTS (Care Management Tracking System) registry – The CMTS, a registry that facilitates delivery of 
CoCM, contains clinic-level process of care and patient-level clinical outcome data that shows how 
patients receive care. The CMTS registry already contains the mental health and substance use 
diagnoses, as well as results from the OUD, depression, anxiety and PTSD measure-based care scales 
that will be used to monitor treatment response for this trial. CMTS also records care manager 
encounters, delivery of behavioral activation, and psychiatric case reviews. 
Data Security – Standard safeguards to protect research data will be followed. All study participants will 
be assigned a unique identification number. All data will be collected with only this unique identifier 
attached and no identifying information. All de-identified and identifiable information about participants 
will be maintained in separate password-protected folders on encrypted secure servers hosted behind 
the University of Washington’s network firewall.  The file with Personal Identifying Information will be 
stored separately from deidentified information.  These eligibility, survey, adverse events, and CMTS 
data streams will eventually be merged using the unique participant identifier to create an analytical 
dataset.  A data dictionary will created for this analytical dataset. Only certain research staff will have 
access to these databases. All study staff will undergo human subjects training. Study data will only be 
kept as long as required by law before it is destroyed in a manner that will protect confidentiality. We 
expect that these measures will be effective in protecting against loss of confidentiality. 
10.1.8.2 STUDY RECORDS RETENTION  
 
Study documents will be retained for a minimum of 3 years after the study end date.  
 
10.1.9 PUBLICATION AND DATA SHARING POLICY  
 
Publications – The Executive Committee will have responsibility for publications arising from the trial, 
including CHAMP scientific conference presentations, prioritization of manuscripts that arise from 
CHAMP. According to the publications policy approved by the Steering Committee, this team will be 
proactive about inviting investigators to author and co-author papers and presentations. This study will 
be conducted in accordance with the National Institutes of Health (NIH) Public Access Policy, which 
ensures that the public has access to the published results of NIH funded research. It requires scientists 
to submit final peer-reviewed journal manuscripts that arise from NIH funds to the digital archive 
PubMed Central upon acceptance for publication. 
Data Sharing – This study will be conducted in accordance with the NIH Data Sharing Policy and Policy 
on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and 
Results Information Submission rule. As such, this trial will be registered at ClinicalTrials.gov, and results 
information from this trial will be submitted to ClinicalTrials.gov. In addition, every attempt will be made 
to publish results in peer-reviewed journals.  Data from this study may be requested from other 
researchers 1 year after the completion of the primary endpoint by contacting the AIMS Center at the 
University of Washington.  Considerations for ensuring confidentiality of these shared data are 
described in Section 10.1.3. 
 

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10.1.10 
CONFLICT OF INTEREST POLICY 
 
The independence of this study from any actual or perceived influence is critical. Therefore, any actual 
conflict of interest of persons who have a role in the design, conduct, analysis, publication, or any aspect 
of this trial will be disclosed and managed. Furthermore, persons who have a perceived conflict of 
interest will be required to have such conflicts managed in a way that is appropriate to their 
participation in the design and conduct of this trial. The Executive Council will establish policies and 
procedures for all study group members to disclose all conflicts of interest and will establish a 
mechanism for the management of all reported dualities of interest.  Importantly, this study is not 
testing a drug, device or treatment manual, and thus the potential for a financial conflict of interest is 
minimal.  The University of Washington requires all investigators to sign annual conflict of interest 
forms, and all investigators signed a conflict of interest form for the CHAMP study specifically.    
 
10.2 ADDITIONAL CONSIDERATIONS 
 
Oversight for the CHAMP study is being provided by the Advarra Single IRB.  Due to the COVID 
pandemic, we may need to make protocol modifications to the approved protocol, including requesting 
to obtain e-consents in the event that COVID-19 prevents in-person healthcare encounters.  We will be 
considering these as we get closer to fielding the trial and have a better sense of the impact of the 
COVID pandemic on the functioning of our sites. 
 
 

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10.3 ABBREVIATIONS AND SPECIAL TERMS 
AE 
Adverse Event 
CFR 
Code of Federal Regulations 
COC 
Certificate of Confidentiality 
DSMB 
Data Safety Monitoring Board 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
ICH 
International Council on Harmonisation  
IRB 
Institutional Review Board 
ISM 
Independent Safety Monitor 
NCT 
National Clinical Trial 
NIH  
National Institutes of Health 
NIDA 
National Institute on Drug Abuse 
NIMH 
National Institute of Mental Health 
OHRP 
Office for Human Research Protections 
PI 
Principal Investigator 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
UP 
Unanticipated Problem 

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Study Specific Acronyms Definitions 
AIMS – University of Washington’s Advancing Integrated Mental Health Solutions 
ASSIST – Alcohol, Smoking and Substance Involvement Screening Test screener 
AUDIT-C – Alcohol use/consequence rating scale 
BA – Behavioral Activation psychotherapy 
BAM-R– Drug use/consequence rating scale - revised 
CDC – Centers for Disease Control and Prevention 
CESATE – Center of Excellence in Substance Abuse Treatment and Education 
CHAMP – CoCM for MHS and OUD 
CMTS – Care Management Tracking System 
CoCM – Collaborative Care Management 
DAP – Dynamic Adaption Process framework 
DATA 2000 – Drug Addiction Treatment Act of 2000  
DSM-5 – Diagnostic and Statistical Manual 5 
EHR – Electronic Health Record 
FDA – Food and Drug Administration 
GAD-7 – Generalized Anxiety Disorder scale 
ICR – Importance-Confidence-Readiness 
MCS – Mental Health Composite Summary 
MOUD – Medication for Opioid Use Disorder 
MHD – Mental Health Disorder  
MHS – Mental Health Symptoms 
MPI – Multiple Principal Investigator 
OUD – Opioid Use Disorder 
PC-PTSD-5 – Primary Care PTSD Screener for DSM5 
PEG -- Pain, Enjoyment of Life and General Activity scale 
PCL-5 – PTSD Checklist for DSM-5 
PCORI – Patient Centered Outcomes Research Institute 
PHQ-9 – Depression scale 
PMID –  Prescription Drug Monitoring Program 
PROMIS -- Patient-Reported Outcomes Measurement Information System 
PTSD – Post-traumatic stress disorder 
RCT – Randomized Controlled Trial 
SAMHSA – Substance Abuse and Mental Health Services Administration 
SCL-20 – Symptom Checklist 20 
SOS – Short Opioid Screen 
SSRI – Selective serotonin reuptake inhibitor 
SUD – Substance Use Disorder 

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Protocol Amendment History 
The table below is intended to capture changes of IRB-approved versions of the protocol, including a 
description of the change and rationale. A Summary of Changes table for the current amendment is 
located in the Protocol Title Page.  
 
Version Date 
Description of Change  
Brief Rationale 
2 
3.27.2020 
1. Changed the name of the intervention 
group from “CHAMP” to “intervention 
group” and the control group from “CoCM 
for MHD” to ”control group”. 
2. Change the trial design from two parallel 
trials to one trial with two cohorts. 
3. Excluded children under the age of 18. 
4. Dropped the requirement to recruit clinics 
from areas with high levels of opioid 
overdoses.  
5. Revised the specifications of the 
numerator and denominator groups for 
Aim 1. 
6. Added inclusion criteria that patients 
could be referred into the study. 
7. Added inclusion criteria that study 
participants must have at least two 
symptoms of opioid use disorder as assess 
by a clinician use the DSM-5 checklist.  
8. Added that we will be collecting 
information from the state Prescription 
Drug Monitoring Program. 
9. Added information about the anticipated 
risks.  
10. Revised the consent form to reflect these 
modifications. 
11. Revised the HIPPA authorization form. 
1.This was done to increase clarity and to 
not conflate the study name with the name 
of the intervention group.  
2. This was done to improve the balance of 
the intervention and control groups. 
3. The clinics prefer that we know enroll 
children in the trial. 
4. We needed to relax this requirement in 
order to recruit enough clinics.  
5.These changes were made to 
accommodate limitations of EHR queries 
and to increase clarity. 
6.This change was made at the request of 
the participating clinics.  
7. This was added to ensure that referred 
patients meet criteria for opioid use 
disorder. 
8.This information about dispensing was 
added to triangulate information about 
prescriptions and patient self-reported use 
of prescribed opioids. 
9.This was added so that we could classify 
adverse events as anticipated or 
unanticipated. 
10. These revisions were made to that the 
consent form was consistent with changes 
to the protocol. 
11.The HIPPA authorization form was 
revised to be compliant with Washington 
state law.   
 
 
 
 

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Version Date 
Description of Change  
Brief Rationale 
3 
8.24.2020 
1. Dropping the word “pragmatic” from the 
description of the trial. 
2. Revised Eligibility Criteria  
a. No longer excluding new clinic 
patients from the trial in the first 
six months 
b. Spanish Speaking Patients are now 
eligible.  
c. 
We will exclude patients who are 
receiving or seeking treatment in 
specialty mental healthcare 
setting. 
d. Replacing the PCL-5 with the PC-
PTSD-5 screener to determine 
PTSD inclusion criterion. 
3. Adding that the PCL-5 will be used for the 
Measurement Based Care component of 
the interventions 
4. Adding more details about the Formative 
Evaluation and requesting a Waiver of 
Written Informed Consent for Formative 
Evaluation research activities.   
5. Adding e-consenting and dropping the 
requirement that staff sign as witnesses to 
consenting. 
6. Redefining how one of the outcomes (MAT 
Persistence) will be measured.  
7. Adding that chart review will be used to 
identify opioid prescriptions. 
8. Revisions to the safety planning protocol for 
patient reporting suicide intent on the 
survey. 
9. Replacing the PDS-5 with the PCL-5 as the 
way to measure PTSD severity in the survey. 
10. Changing in the ICF that we will collect data 
about their care from “three months before 
today until seven months from today” 
instead of “today until thirteen months 
from today.” 
 
1. We determined that this term was in 
inaccurate description of the trial since 
we would be controlling fidelity of the 
intervention delivery. We also made 
some non-significant wording changes 
throughout and corrected typos.  
2a. We determine that clinics could drop 
new patients from the EHR queries and 
thus recruitment of new patients into the 
trial would no long bias the results of Aim 
1. 
2b. Participating clinics wanted us to 
include Spanish speaking patients. 
2c. We added this exclusion criteria to 
include those receiving non-
pharmacologic treatments in specialty 
settings.  This is consistent with our 
similar exclusion criteria of receiving 
prescriptions for psychotropic 
medications from a mental health 
specialist. 
2d. Replacing the PCL-5 with the PC-
PTSD-5 screener to determine PTSD 
inclusion criterion. 
3.We inadvertently neglected to include 
the PCL-5 previously.  
4.The Formative Evaluation activities 
were only vaguely described in the 
previous protocol.  All Formative 
Evaluation activities are considered 
minimal risk and we a request a waiver of 
documentation of written informed 
consent.  
5.Because of Covide-19 we need to be 
able to obtain consent remotely using e-
consenting procedures.  Staff obtaining 
informed consent cannot witness e-
signatures, so we are removing that 
element of the ICF. 
6. Because we have determined that we 
may not be able to obtain data from the 
state Prescription Drug Monitoring 
Programs, we changed how we would 
measure MAT persistence.  We are now 
relying on self-report.  

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7.Because we have determined that we 
may not be able to obtain data from the 
state Prescription Drug Monitoring 
Programs, we are now using chart review 
to identify prescriptions for opioids 
written in the primary care clinic.   
8.We broke up the safety plan question 
into separate questions in an attempt to 
encourage survey respondents to agree 
to the best safety plan (the questions are 
now ordered by our ranking of safety). 
9.Tthe PDS-5 had inferior face-validity 
than the PCL-5 
10.The 13 months from today was a typo.  
Also, we wanted to be able to collect pre-
baseline opioid prescription information 
from the chart review and the 
Prescription Drug Monitoring Program. 
 
4 
3.17.21 
1. Clarifying the language for patient eligibility 
exclusion criteria to clarify that we will:  
a. allow patients receiving a current 
prescription if the prescriber is an  
addiction specialist and is a primary 
care provider in the clinic or health 
system).  
b. who are or have been enrolled in 
CoCM for co-occurring disorders for 
more than 14 days because their 
baseline survey responses will not be 
documented prior to receiving the 
intervention.   
 
2. Adding information to Virtual e-consenting 
process to clarify that the and the patient can 
receive the e-consent form via text and will 
receive an signed PDF of the e-consent form via 
email or text. 
1. to clarify the exclusion ctieria for the 
clinics and to make study criteria more 
inclusive.  
 
2. Required by the IRB to clarify the e-
consent process in the ICF and the 
protocol.  
5 
6.25.21 
Submitted the IRB protocol changes in review 
 
1. Screen positive on the NIDA-ASSIST OUD or 
the Short Opioid Screen (SOS) for OUD 
items OR referred to the trial by one of the 
clinic’s providers.  
2. Added to inclusion criteria “meet clinical 
criteria for ≥2 symptoms of OUD on the 
DSM-5 checklist (administered by a 
clinician)” to include “and/or  OUD 
diagnosis recorded in the electronic medical 
record and a patient encounter in the past 6 
1. Many of the clinics reported that  
patients did not understand the NIDA-
Modified Assist for OUD questions and 
staff found it difficult to score. Therefore 
we created a shorter, simpler, two-item 
screener for OUD an are giving the clinics 
the option to use the two-item screener for 
OUD instead of the NIDA-Modified 
Assist for OUD.  We have named this 
screen the Short Opioid Screen (SOS)  
2. We were finding that many patients 
screening positive for OUD were being 
diagnosed with OUD but the number of 

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months or OUD diagnosis on problem list 
PCP reviewed in the past 6 months.“ 
3. Added language to clarify the patient 
baseline survey interviews will be 
completed within 14 days of the consent 
signed date and follow-up interviews will be 
completed within 42 days of the target 
date.   
 
DSM-5 checklist symptoms were not 
being recorded in the Electronic Health 
Record. As a result, we have been unable 
to enroll many patients who met inclusion 
criteria due to the lack of documentation 
of the number of DSM-5 checklist 
symptoms. 
3. This was not previously specified, but 
we wanted to update the protocol with 
these details. ` 
6 
3.15.22 
1. Description of Sites/Facilities Enrolling 
Participants: Twenty-four clinics from 8 
healthcare systems are participating.    
Updated 1.1  SYNOPSIS, Page 2   
Modified text to address changes since the 
last review. 
2.We will encourage chain recruitment from 
existing CHAMP patients.  We will offer 
referring patients $50 for each patient that meets 
inclusion criteria for CHAMP.  We will send 
eligible patients to the clinic that is closest in 
proximity to their home.   
Updated 5.4 STRATEGIES FOR RECRUITMENT 
AND RETENTION, Page 14. 
Due to continued slow recruitment, we 
have introduced payment to existing 
patients to refer other patients to the 
CHAMP study.   
3.UW staff will be trained to obtain written 
informed consent to the patient virtually by tele-
video or audio-only telephone 
Updated 10.1.1.2 CONSENT PROCEDURES AND 
DOCUMENTATION, Page 32. 
To address clinic expressed anxiety and 
lack of time to consent, we have added the 
option for a UW staff person to virtually 
consent an eligible patient for CHAMP. 
4.We have updated the power analysis to include 
a lower bound scenario. 
Updated 9.2 9.2 SAMPLE SIZE 
DETERMINATION, Page 28 
To address reduced enrollment. 
7 
7.15.22 
1. Updated Study Duration (to 39 months total) 
to reflect the extension of enrollment to 33 
months total  Updated 1.1 SYNOPSIS, Page 2   
Modified text to address changes since the 
last review due to the extension of 
recruitment timeline. Total treatment 
period will be 39 months. 
2.Updated Study Design to reflect the extension 
of enrollment. 
Updated 1.2 SCHEMA, Page 3   
Modified text to address changes since the 
last review due to the extension of 
recruitment timeline. 
3.Updated the enrollment timeline from 24 
months to a 33-month period. 
Updated 5.4 Page 15, STRATEGIES FOR 
RECRUITMENT AND RETENTION 
Modified text to address changes since the 
last review due to the extended timeline. 
4.  Updated to include non-lethal overdose 
categories per DSMB requestion 
06. Non-lethal overdose (that resulted in 
hospitalization or ED visit) 
07. Non-lethal overdose (that did not result in 
hospitalization or ED visit) 
Updated 8.2.2, Page 23 SERIOUS ADVERSE 
EVENTS 
To address the request of the DSMB to 
include these categories. 
Version Date 
Description of Change  
Brief Rationale 

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8 
3.15.2023 
1.1 Synopsis  
Study Population  – increased the # of 
Clinics and states participating in 
CHAMP. 
1.3 Schedule of Activities 
8.1 Endpoint and Other Non-Safety Assessments 
9.4.3 Analysis of the Secondary Endpoint(s) 
The label for the anxiety measure in the 
survey was Neuro_QOL, but was 
mislabeled as PROMIS. 
 
 
9 
6.26.23 
Study Population  – increased the # of Clinics 
and states participating in CHAMP. 
We updated the number of clinics and 
states from 24 to 38 clinics and from 8 to 
10 states.  Age, gender and race/ethnicity 
will be representative of the demographics 
and epidemiology of the clinics. 
Description of Sites/Facilities Enrolling 
Participants – increased the # of Clinics and 
states participating in CHAMP. 
Sites include a range of primary care 
settings in the United States.  38 clinics 
from 10 healthcare systems are 
participating.     
10 
10.16.23 
Study Population  – increased the # of Clinics 
and states participating in CHAMP. 
We updated the number of clinics and 
states from 38 to 42 clinics and from 10 to 
12 states.  Age, gender and race/ethnicity 
will be representative of the demographics 
and epidemiology of the clinics. 
Description of Sites/Facilities Enrolling 
Participants – increased the # of Clinics and 
states participating in CHAMP. 
Sites include a range of primary care 
settings in the United States.  42 clinics 
from 15 healthcare systems are 
participating.     
11 
9.16.24 
Aim 3 – Change the sustainability 
implementation trial to a pre-post evaluation. 
Because we extended the recruitment 
period for the effectiveness trial, there 
was insufficient time to conduct the 
implementation trial.  
 
 

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