Clinical Decision Support for Opioid Use Disorders in Medical Settings: Pilot Usability Testing in an EMR
Phase: NA
Conditions: Opioid-use Disorder
Sponsor: HealthPartners Institute

 
 
 
 
 
 
 
 
 
 
 
 
NIDA CTN Protocol 0076-ot 
 
Clinical Decision Support for Opioid 
Use Disorders in Medical Settings: 
Pilot Usability Testing in an EMR 
(COMPUTE) 
 
 
 
 
Lead Investigators: Gavin Bart, MD, PhD; Rebecca Rossom, MD, MS 
 
 
 
 
May 8, 2018 
Version 1.2 
 
 

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
2 
 
 
COMPUTE Team Members 
 
 Gavin Bart, MD, PhD (Co-LI) 
 Rebecca Rossom, MD, MS (Co-LI) 
 Lauren Crain, PhD (Co-I) 
 Thomas Elliott, MD (Co-I) 
 Patrick O’Connor, MD, MS, MA (Co-I) 
 Anne Pylkas, MD (Co-I) 
 JoAnn Sperl-Hillen, MD (Co-I) 
 Laurel Nightingale (PM) 
 Debbie McCauley (Epic Programmer) 
 Rashmi Sharma (Epic Programmer) 
 Deepa Appana (Web Programmer) 
 Laurel Nightingale (Project Manager) 
 Kristen Huntley, PhD (NIDA CCTN Protocol Coordinator) 
 David Liu, MD (NIDA CCTN Protocol Coordinator) 
 Robert Lindblad, MD (NIDA CTN Clinical Coordinating Center, Emmes, Chief 
Medical Monitor) 
 Robert Gore-Langton, PhD (Emmes, Senior Investigator) 

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
3 
 
 
TABLE OF CONTENTS 
 
1.0 
LIST OF ABBREVIATIONS .............................................................................................................. 7 
2.0 
STUDY SYNOPSIS ........................................................................................................................... 7 
2.1 
Study Objectives ................................................................................................................. 7 
2.2 
Study Design and Outcomes .............................................................................................. 7 
2.3 
Sample Size and Study Population ..................................................................................... 8 
2.4 
Treatment/Assessment/Intervention and Duration ............................................................. 8 
2.5 
Safety Reporting ................................................................................................................. 8 
2.6 
Analyses .............................................................................................................................. 8 
3.0 
STUDY SCHEMA ............................................................................................................................. 9 
4.0 
INTRODUCTION ............................................................................................................................. 10 
4.1 
Background and Significance to the Field......................................................................... 10 
5.0 
OBJECTIVES.................................................................................................................................. 11 
5.1 
Primary Objectives ............................................................................................................ 11 
5.2 
Secondary Objective(s) ..................................................................................................... 12 
6.0 
STUDY DESIGN ............................................................................................................................. 12 
6.1 
Overview of Study Design ................................................................................................. 12 
6.2 
Duration of Study and Visit Schedule ............................................................................... 13 
7.0 
STUDY POPULATION ................................................................................................................... 13 
7.1 
Participant Inclusion Criteria ............................................................................................. 13 
7.2 
Participant Exclusion Criteria ............................................................................................ 13 
7.3 
Participant Recruitment ..................................................................................................... 13 
8.0 
SITE SELECTION ........................................................................................................................... 14 
8.1 
Number of Sites ................................................................................................................ 14 
8.2 
Site Characteristics ........................................................................................................... 15 
8.3 
Rationale for Site Selection ............................................................................................... 15 
9.0 
OUTCOME MEASURES ................................................................................................................ 15 
9.1 
Primary Outcome Measure ............................................................................................... 15 
9.2 
Other Outcome Measures ................................................................................................. 16 
10.0 
STUDY PROCEDURES .................................................................................................................. 16 
10.1 
Phase 1: Translating the White Paper to an Epic-compatible CDS and Building and 
Testing the CDS (15 months) ........................................................................................... 16 
10.1.1 
Project Initiation ................................................................................................................. 16 

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
4 
 
 
10.1.2 
Design and Planning ......................................................................................................... 17 
10.1.3 
Development ..................................................................................................................... 18 
10.1.4 
Testing .............................................................................................................................. 19 
10.2 
Phase 2: Deploying and Testing the CDS in Primary Care (6 months) ............................ 20 
10.3 
Phase 3: Analysis and Reporting (3 months) ................................................................... 20 
10.4 
Informed Consent Procedures for Participants ................................................................. 20 
10.5 
HIPAA Authorization and Medical Record Release Forms............................................... 20 
10.6 
Baseline Visit ..................................................................................................................... 21 
10.7 
Randomization .................................................................................................................. 21 
10.8 
Treatment/Intervention ...................................................................................................... 21 
10.9 
Collection of Biospecimens ............................................................................................... 21 
10.10 Premature Withdrawal of Participants............................................................................... 21 
10.11 Study Halting Rules........................................................................................................... 21 
10.12 Follow-Up .......................................................................................................................... 21 
10.13 Blinding ............................................................................................................................. 21 
10.14 Participant Reimbursement ............................................................................................... 21 
10.15 Retention Plan ................................................................................................................... 21 
11.0 
STUDY ASSESSMENTS ................................................................................................................ 22 
11.1 
Study Assessments........................................................................................................... 22 
11.1.1 
PCP Surveys ..................................................................................................................... 22 
11.2 
PCP Use Reports .............................................................................................................. 30 
11.3 
General Measures............................................................................................................. 30 
11.3.1 
Inclusion/Exclusion............................................................................................................ 30 
11.4 
Locator Form ..................................................................................................................... 31 
11.5 
Demographics Form.......................................................................................................... 31 
11.6 
PhenX Tier 1 ..................................................................................................................... 31 
11.7 
End of Medication/End of Treatment Form ....................................................................... 31 
11.8 
Study Completion Form .................................................................................................... 31 
11.9 
Measures of Primary and Secondary Outcomes .............................................................. 31 
11.10 Clinical and Safety Assessments ...................................................................................... 32 
11.10.1 
Adverse Events (AEs) and Serious Adverse Events (SAEs) ............................................ 32 
11.11 Compliance Measures ...................................................................................................... 32 
11.12 Drug Use Measures .......................................................................................................... 32 
11.12.1 
Urine Drug Screen ............................................................................................................ 32 
11.12.2 
DSM-5 Checklist ............................................................................................................... 33 

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
5 
 
 
12.0 
TRAINING REQUIREMENTS ......................................................................................................... 33 
12.1 
Overall ............................................................................................................................... 33 
13.0 
STATISTICAL DESIGN AND ANALYSES .................................................................................... 34 
13.1 
General Design ................................................................................................................. 34 
13.1.1 
Study Hypothesis .............................................................................................................. 34 
13.2 
Primary and Secondary Outcomes (Endpoints) ............................................................... 34 
14.0 
RECRUITMENT .............................................................................................................................. 34 
15.0 
RANDOMIZATION AND FACTORS FOR STRATIFICATION ...................................................... 35 
16.0 
PREDICTION MODELS .................................................................................................................. 35 
16.1 
Rationale for Sample Size and Statistical Power .............................................................. 35 
16.1.1 
Projected Number of Sites ................................................................................................ 35 
16.1.2 
Projected Number of Participants per Site ........................................................................ 35 
16.2 
Statistical Methods for Primary and Secondary Outcomes .............................................. 35 
16.3 
Significance Testing .......................................................................................................... 35 
16.4 
Types of Analyses ............................................................................................................. 35 
16.5 
Interim Analysis ................................................................................................................. 36 
16.6 
Exploratory Analysis.......................................................................................................... 36 
16.7 
Missing Data and Dropouts ............................................................................................... 36 
16.8 
Demographic and Baseline Characteristics ...................................................................... 36 
16.9 
Safety Analysis .................................................................................................................. 36 
17.0 
REGULATORY COMPLIANCE AND SAFETY .............................................................................. 36 
17.1 
Regulatory Compliance ..................................................................................................... 36 
17.2 
Statement of Compliance .................................................................................................. 37 
17.3 
Institutional Review Board Approval ................................................................................. 37 
17.4 
Informed Consent .............................................................................................................. 37 
17.5 
Quality Assurance and Safety Monitoring ......................................................................... 37 
17.6 
Confidentiality .................................................................................................................... 38 
17.7 
Health Information Portability Accountability Act (HIPAA) ................................................ 38 
17.8 
Investigator Assurances .................................................................................................... 38 
17.9 
Financial Disclosure .......................................................................................................... 39 
17.10 DEA Registration (Component for medication studies using controlled substances studies 
– use if applicable) ............................................................................................................ 39 
17.11 IND Requirements (Component for IND studies – use if applicable) ............................... 39 
17.12 Clinical Monitoring ............................................................................................................. 39 
17.13 Inclusion of Women and Minorities ................................................................................... 39 

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
6 
 
 
17.14 Regulatory Files ................................................................................................................ 40 
17.15 Records Retention and Requirements .............................................................................. 40 
17.16 Reporting to Sponsor ........................................................................................................ 40 
17.17 Audits ................................................................................................................................ 40 
17.18 Study Documentation ........................................................................................................ 40 
17.19 Protocol Deviations ........................................................................................................... 41 
17.20 Safety Monitoring .............................................................................................................. 41 
17.20.1 
Data and Safety Monitoring Board (DSMB) ...................................................................... 41 
17.20.2 
Adverse Events (AEs) ....................................................................................................... 41 
18.0 
DATA MANAGEMENT ................................................................................................................... 42 
18.1 
Study Timeline .................................................................................................................. 42 
19.0 
PUBLICATIONS AND OTHER RIGHTS ........................................................................................ 43 
20.0 
SIGNATURES ................................................................................................................................. 44 
21.0 
REFERENCES ................................................................................................................................ 45 
22.0 
APPENDIX A: ADVERSE EVENT REPORTING AND PROCEDURES ........................................ 49 
23.0 
APPENDIX B: DATA AND SAFETY MONITORING PLAN .......................................................... 50 
23.1 
Brief Study Overview......................................................................................................... 50 
23.2 
Oversight of Clinical Responsibilities ................................................................................ 50 
23.3 
Management of Risks to Participants ............................................................................... 51 
23.4 
Data Management Procedures ......................................................................................... 52 
23.4.1 
Data and Statistics Center Responsibilities ...................................................................... 52 
23.5 
Data Collection and Entry ................................................................................................. 52 
23.6 
Data Monitoring, Cleaning and Editing ............................................................................. 52 
23.7 
Data Lock and Transfer .................................................................................................... 52 
 
 
 
 

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
7 
 
 
1.0 LIST OF ABBREVIATIONS  
Abbreviation Definition 
CDS 
Clinical decision support 
CTN 
Clinical trials network 
DEA 
Drug Enforcement Agency 
DSMB 
Data Safety Monitoring Board 
EMR 
Electronic medical record 
HPMG 
HealthPartners Medical Group 
MAT 
Medication-assisted therapy 
MD 
Medical doctor 
NIDA 
National Institute on Drug Abuse 
NIH 
National Institutes of Health 
NP 
Nurse practitioner 
OUD 
Opioid use disorder 
PA 
Physician assistant 
PCP 
Primary care provider 
PNMG 
Park Nicollet Medical Group 
2.0 STUDY SYNOPSIS  
2.1 
Study Objectives 
The primary objective of this pilot study is to program an opioid use disorder (OUD) clinical 
decision support (CDS) tool for use in an electronic medical record (EMR) and obtain high primary 
care physician (PCP) usability and acceptability. The OUD-CDS is based on the NIDA-Blending 
Initiative white paper, “Clinical Decision Support for Opioid Use Disorders: Working Group 
Report,” which itself is based on national evidence-based guidelines (American Society of 
Addiction Medicine (ASAM 2015), VA (VA 2015). As such, this pilot study aims to help PCPs 
achieve accepted standards of care in OUD treatment. The secondary objectives of this pilot study 
are to evaluate the usefulness of the tool by comparing OUD case-finding, medication-assisted 
therapy (MAT) and referral patterns pre- and post-CDS deployment for PCPs with and without 
CDS access. 
2.2 
Study Design and Outcomes  
This pilot study will test the usability and acceptability of a CDS tool for OUD in primary care 
clinics. Details of each phase are found in Section 10.0. Phase 1 of the study involves translating 
the Blending Initiative White Paper into algorithms that are compatible with Epic and HPMG and 
PNMG workflows and then building and extensively testing the CDS. Phase 1 lasts 15 months. 
Phase 2 of the study involves deploying and testing the usability of the CDS in primary care. We 
will recruit 16 non-waivered PCPs from multiple clinics to receive access to the OUD-CDS (8 MDs 
and 8 nurse practitioners (NPs) or physician assistants (PAs)), as well as 16 non-waivered PCPs 
from multiple clinics who will not receive access to the OUD-CDS (8 MDs and 8 NPs/PAs). 

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
8 
 
 
Additionally, all 11 waivered PCPs (10 MDs, 1 NP) will be invited to participate and will receive 
access to the OUD-CDS.  All PCPs will complete baseline and 6-month surveys; PCPs with 
access to the OUD-CDS will also be asked and incentivized to submit feedback about the CDS 
via the feedback tab in the CDS. A recruitment diagram can be found in Section 7.3. Phase 2 
lasts 6 months. Phase 3 involves analysis and reporting of data and lasts 3 months.  
The study outcomes are delineated in the specific aims in Sections 5.0 and 9.0.  
2.3 
Sample Size and Study Population  
This pilot study will include 16 non-waivered volunteer PCPs from multiple HPMG and PNMG 
primary care clinics in the HealthPartners integrated healthcare organization who will receive 
access to the OUD-CDS. This pilot study will also include 16 non-waivered volunteer PCPs who 
will not receive access to the OUD-CDS but, similar to intervention PCPs, will complete baseline 
and 6-month surveys. Additionally, all 11 PCPs waivered to prescribe buprenorphine will be 
invited to participate in this pilot.   
2.4 
Treatment/Assessment/Intervention and Duration  
The intervention involves access to the OUD-CDS for approximately half of recruited PCPs. 
Survey-based assessment of confidence in OUD screening, assessment, treatment and referral 
will be compared before and after the 6-month pilot for PCPs with and without CDS access. 
 
Metrics of OUD-CDS use will be monitored for each PCP with CDS access throughout the 6-
month intervention period. Specifically, we will monitor rates of OUD-CDS use for eligible 
encounters (i.e., PCP with CDS access who has an encounter with a patient with OUD or with a 
patient identified by the OUD-CDS to be at high risk of OUD).  
2.5 
Safety Reporting  
In this pilot study, we are not trying to change the standard of care for OUD treatment in primary 
care, but rather we are helping PCPs achieve this standard of care in OUD treatment. PCPs are 
trained that, as with other clinical decision tools, the OUD-CDS is meant to supplement but not 
supersede clinical judgment. PCPs can choose to follow or not follow the guidance of the CDS at 
any given time for any given patient, and PCPs are trained to let the research team know via the 
Feedback tab in the CDS when their clinical judgment is inconsistent with the CDS. This feedback 
will be monitored by the treatment team and the CDS algorithms adjusted if indicated.   
 
An independent CTN DSMB will monitor this study.  The DSMB will communicate regarding what 
type of reports will be needed, as well as frequency.  The CTN DSMB is responsible for conducting 
periodic reviews of accumulating safety and efficacy data. It will determine whether there is 
support for continuation of the trial, or evidence that study procedures should be changed, or if 
the trial should be halted, for reasons relating to the safety of the study participants, the efficacy 
of the treatment under study, or inadequate trial performance (e.g., poor recruitment). 
2.6 
Analyses  

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
9 
 
 
This pilot study for OUD-CDS feasibility and usability will not have a statistical endpoint. Provider 
characteristics and OUD-CDS use data will be tracked and descriptively analyzed. Pre- and post-
surveys of provider confidence in OUD screening, assessment, treatment and referral, as well as 
satisfaction with the OUD-CDS, will be described.  
3.0 STUDY SCHEMA  
Phase 1:
18 Months
Phase 2: 
6 Months
Phase 3:
6 Months
Translating the White Paper to an Epic compatible 
CDS and Building and Testing the CDS
Recruit PCPs at HP and PN
16 MDs, 16 NPs/PAs
All 11 waivered PCPs
11 PCPs with buprenorphine 
waiver: all will be assigned to 
arm with CDS access
32 PCPs without 
buprenorphine waiver: 
randomly assigned to arms 
with or without CDS acces
16 non-waivered PCPs 
(8 MDs, 8 PAs/NPs)
Up to 11 waivered PCPs (10 
MDs, 1 NP)
16 non-waivered PCPs 
(8 MDs, 8 PAs/NPs)
All PCPs complete baseline survey
6-month pilot period
PCPs with CDS access submit feedback via tab in CDS or via 
email
All PCPs complete baseline survey
Analysis and Reporting
 
 
 

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
10 
 
 
4.0 INTRODUCTION  
4.1 
Background and Significance to the Field  
We are in the midst of an epidemic of opioid misuse (Centers for Disease Control and Prevention 
2012). Between 2007 and 2012, past-month heroin use increased 75% while past-month non-
medical prescription opioid use remained relatively stable (Substance Abuse and Mental Health 
Services Administration 2008; Substance Abuse and Mental Health Services Administration 
2014). In 2015 there were approximately 2.5 million Americans with moderate-to-severe OUD 
(Grant et al. 2016; Substance Abuse and Mental Health Services Administration 2014). 
Approximately 20% of these individuals entered into addiction treatment programs but, of these, 
only about 25% received MAT (Substance Abuse and Mental Health Services Administration 
2012). Overall, less than 10% of these 2.5 million Americans received treatment in a doctor’s 
office (Substance Abuse and Mental Health Services Administration 2014).  
Because primary care is the most common point of healthcare contact in the United States, 
identification and treatment of OUD in primary care may help reduce this significant treatment 
gap. While methadone is highly regulated, of limited geographic availability, and allowed only in 
licensed treatment programs, buprenorphine is a cost effective treatment for OUD that can be 
deployed in specialty and primary care settings (Alford et al. 2011; Liebschutz et al. 2014; Moore 
et al. 2007; Schackman et al. 2012; Soeffing et al. 2009; Weiss et al. 2011) and monthly injections 
of extended-release naltrexone (XR-NTX) are showing promise for OUD in some general medical 
settings (Coviello et al. 2012). Further, treating OUD in primary care may facilitate the diagnosis 
and treatment of unrecognized chronic medical conditions (Rowe et al. 2012). 
Since its introduction in 2003, more than 35,000 physicians have been licensed to prescribe 
buprenorphine for the treatment of OUD. Under current law, 23,982 of these can prescribe for up 
to 30 patients, 9,285 for up to 100 patients, and 2,525 for up to 275 patients 
(http://www.samhsa.gov/programs-campaigns/medication-assisted-treatment/physician-
program-data, accessed November 28, 2016). Fewer than 30% of trained physicians go on to 
prescribe buprenorphine and less than 60% of the overall buprenorphine treatment capacity is 
filled (Arfken et al. 2010; Hutchinson et al. 2014; Kunins et al. 2012). It is too soon to know if the 
recent addition of advance practice clinicians to those eligible to prescribe will impact access or 
capacity. Whatever the case, at least for physicians, there is an additional barrier beyond 
certification and training that is preventing the uptake of buprenorphine prescription. Compared 
to those who do prescribe buprenorphine, those who do not are more likely to endorse lack of 
institutional support as being a barrier. Other barriers identified by both prescribers and non-
prescribers include lack of staff training, lack of confidence, poor access to clinical guidelines, and 
time constraints (Barry et al. 2009; Hutchinson et al. 2014; Netherland et al. 2009; Walley et al. 
2008). Similar barriers have been identified as limiting use of XR-NTX (Alanis-Hirsch et al. 2016). 
The various iterations of the Physician Clinical Support System (PCSS) have attempted to provide 
free education and mentoring support to assist providers in using MAT for OUD (Egan et al. 2010). 
This assistance is available as web-based documents, webinars, telementoring, and even as site 
visits arranged between mentors and providers. Unfortunately, these valuable services are rarely 
deployed or utilized during actual patient encounters.  

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
11 
 
 
In the last decade, EMR-linked web-based point-of-care CDS systems designed to improve 
quality of chronic disease care have become increasingly sophisticated and successful 
(Ammenwerth et al. 2012; Druss & Dimitropoulos 2013; Roshanov et al. 2012). Our team has 
developed CDS systems that have been shown to improve glucose and blood pressure control in 
adults with diabetes, increase recognition of adolescents with previously unrecognized 
hypertension, have 60-80% use rates at targeted primary care clinical encounters, and have 95% 
primary care provider satisfaction ratings (Desai et al. 2013; Gilmer et al. 2012; Kharbanda et al. 
2015; O'Connor et al. 2009; O'Connor et al. 2011; Sperl-Hillen et al. 2010). These CDS systems, 
which focus on cardiovascular risk factor identification and management, have been used daily 
for the past 3-4 years in the care of 1.5 million patients in 3 large healthcare delivery systems and 
will soon be deployed to an additional large healthcare system. NIH funding has been secured to 
expand this CDS system to include identification and management of additional chronic 
conditions. It is now technically feasible to extend this technology to support the systematic, 
timely, and safe management of those with OUD in primary care and other settings.  
Currently, providers lack real-time CDS tools that can efficiently facilitate personalized 
identification, assessment, and treatment of patients with OUD prior to or during a clinical 
encounter. The NIDA CTN Blending Initiative has developed an expert panel framework for an 
OUD-CDS. The framework has been previewed by PCPs at the 2015 International Network on 
Brief Interventions for Alcohol and Other Drugs (INEBRIA) conference. It is felt that any further 
refinements needed are best identified through piloting so that provider acceptance and feasibility 
of use, including workflow issues, can be addressed. 
5.0 OBJECTIVES  
5.1 
Primary Objectives  
1) To program an OUD-CDS tool based on a NIDA-Blending Initiative white paper “Clinical 
Decision Support for Opioid Use Disorders: Working Group Report” and national guidelines 
(VA (VA 2015), ASAM (ASAM 2015)) for use in an EMR.  
Measure 1.  Demonstrate that the OUD-CDS is functional and accurate through:  
a) 
Testing in the EMR test environment, 
b) 
Chart audit validation of CDS output, and 
c) 
Approval of the tool by specialty addiction physician and PCP pilot testers prior to the 
full rollout. 
2) To descriptively analyze PCP acceptability, satisfaction and use rates high enough to 
demonstrate proof of concept  
Measure 2A.  By the end of the 6-month pilot intervention, the monthly PCP use rate of the 
CDS for targeted high-risk patient encounters for PCPs with CDS access will be >60%.  
Measure 2B.  By the end of the 6-month pilot intervention, >60% of PCPs with CDS access 
will report feeling confident in assessing and treating OUD 

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
12 
 
 
Measure 2C. At the end of the 6-month pilot intervention, >80% of PCPs with CDS access 
will rate the OUD-CDS >4 on a 5-point Likert scale of likeliness to recommend use of 
the tool to their colleagues. 
5.2 
Secondary Objective(s)  
We will examine the usefulness of the OUD-CDS tool by comparing pre- and post-intervention 
rates of screening for OUD in high-risk patients, Tobacco, Alcohol, Prescription Medication, and 
Other Substance Use (TAPS) use, OUD diagnosis, use of medication-assisted therapy, as well 
as treatment referral patterns, for 3 groups of PCPs: (1) those with CDS access and 
buprenorphine certification, (2) PCPs with CDS access but without buprenorphine certification, 
and (3) PCPs without CDS access.  
 
Where possible, we will structure these secondary outcome measures to be similar to nationally-
used clinical quality measures, such as: 
a) 
Initiation of pharmacotherapy upon new episode of OUD (Number of patients who 
receive at least 1 prescription for MAT within 30 days following index visit with a 
diagnosis of OUD, divided by the number of patients with index visit associated with 
an OUD diagnosis after 60-day clean period without OUD documentation)(Washington 
Circle Group; DHHS 2015)  
b) 
Maintenance pharmacotherapy for OUD (patients who receive at least 30 days’ 
treatment with buprenorphine or naltrexone for OUD, divided by patients who receive 
a diagnosis of OUD during the 6-month pilot phase)(American Psychiatric Association; 
DHHS 2015) 
6.0 STUDY DESIGN  
6.1 
Overview of Study Design  
This 24-month pilot study will primarily entail programming the OUD-CDS into an EMR 
environment. This will be an iterative process with input from addiction specialists and PCPs to 
make sure bugs that may arise during clinical implementation are identified and corrected. We 
anticipate that programming the CDS into the EMR will take 12 months to complete. 
Upon completion of the programming phase, the OUD-CDS will be tested in multiple ways: 1) We 
will test the algorithms using real patient data in the EMR testing environment, 2) We will run the 
algorithms in the background of the production EMR environment without PCP displays, testing 
primarily data capture and operability, 3) We will pilot the OUD-CDS with one or more providers 
with extensive experience in OUD care.  
Once live EMR assessment has been completed and any programming adjustments made, the 
OUD-CDS will be deployed for all PCPs with CDS access at PNMG and HPMG. Confidence in 
assessing and treating OUD prior to and 6-months following the go-live date will be assessed via 
survey for all PCPs with and without CDS access. PCPs with CDS access will also be surveyed 
about the usefulness and ease of use of the CDS at 6-months.   

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
13 
 
 
6.2 
Duration of Study and Visit Schedule 
PCPs with CDS access will use the OUD-CDS for 6 months. During the 6-month intervention 
phase, data on use patterns of the OUD-CDS will automatically be collected for both PCPs with 
CDS access and PCPs without access by the OUD-CDS. For PCPs without access, the OUD-
CDS will run behind the scenes, without displaying, to collect these data. In this way, patterns of 
OUD-related care can be compared on similar patients presenting to PCPs with and without CDS 
access to quantify the impact of the OUD-CDS on OUD identification and care. Automatic 
identification of eligible patients is done by the OUD-CDS algorithms, independent of any PCP 
actions.  
7.0 STUDY POPULATION  
We will recruit 16 non-waivered PCPs from multiple clinics to receive access to the OUD-CDS (8 
MDs and 8 nurse practitioners (NPs) or physician assistants (PAs)), as well as 16 PCPs from 
multiple clinics who will not receive access to the OUD-CDS (8 MDs and 8 NPs/PAs). Additionally, 
all 11 waivered PCPs (10 MDs, 1 NP) will be invited to participate and will receive access to the 
OUD-CDS.  All PCPs will complete baseline and 6-month surveys; PCPs with access to the OUD-
CDS will also be asked and incentivized to submit feedback about the CDS via the feedback tab 
in the CDS. Including multiple PCPs across multiple clinics, including both MDs as well as PAs 
and NPs, will provide a better understanding of the feasibility and usefulness of the OUD-CDS 
across different providers, locations and patient populations.  
7.1 
Participant Inclusion Criteria  
Eligible clinicians will: 
a) Be an MD, Doctor of Osteopathy, Nurse Practitioner or Physician’s Assistant engaged in 
independent primary care of adults  
b) Have at least schedule 3 DEA prescribing privileges 
c) Voluntarily provide written informed consent to participate in this study 
7.2 
Participant Exclusion Criteria  
Less than half-time clinical primary care responsibilities  
7.3 
Participant Recruitment  
PCPs will be voluntarily recruited from HPMG and PNMG in person and via emailed invitations 
and other IRB-sanctioned methods. We will preferentially recruit those PCPs who have or will 
soon have buprenorphine waivers, as they will be able to use the entirety of the OUD-CDS tool. 
In our invitation to participate in the study, we will inform PCPs that they will receive $150 (PCPs 
without CDS access) to $300 (PCPs with CDS access) each to compensate them for their time 
to complete electronically administered surveys at the beginning and end of the 6-month pilot 
intervention phase (PCPs with or without CDS access) and submission of feedback via the 
feedback tab in the CDS itself (PCPs who have access to the CDS). Approximately half of 
recruited PCPs will receive access to the OUD-CDS; all PCPs with buprenorphine certification 
will be allotted to this group. Approximately half of recruited PCPs will not receive OUD-CDS 

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
14 
 
 
access. PCPs without buprenorphine certification will be randomized to receive or not receive 
access to the CDS.  
Recruitment diagram:  
Phase 1:
18 Months
Phase 2: 
6 Months
Phase 3:
6 Months
Translating the White Paper to an Epic compatible 
CDS and Building and Testing the CDS
Recruit PCPs at HP and PN
16 MDs, 16 NPs/PAs
All 11 waivered PCPs
11 PCPs with buprenorphine 
waiver: all will be assigned to 
arm with CDS access
32 PCPs without 
buprenorphine waiver: 
randomly assigned to arms 
with or without CDS acces
16 non-waivered PCPs 
(8 MDs, 8 PAs/NPs)
Up to 11 waivered PCPs (10 
MDs, 1 NP)
16 non-waivered PCPs 
(8 MDs, 8 PAs/NPs)
All PCPs complete baseline survey
6-month pilot period
PCPs with CDS access submit feedback via tab in CDS or via 
email
All PCPs complete baseline survey
Analysis and Reporting
 
8.0 SITE SELECTION 
8.1 
Number of Sites  
We anticipate approximately twenty HPMG and PNMG primary care clinics will be represented 
by the PCPs enrolled in this trial..  

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
15 
 
 
8.2 
Site Characteristics  
HealthPartners is the largest consumer-governed nonprofit health care organization in the 
country, providing care, coverage, research, and education to improve health and well-being in 
partnership with its members, patients and community. HealthPartners serves more than 1.5 
million medical and dental health plan members and more than1 million patients in its HPMG and 
PNMG clinics and hospitals. In 2013, HealthPartners and Park Nicollet combined under the name 
HealthPartners and a single consumer-governed board of directors. The new organization 
includes a multispecialty group practice of more than 1,700 physicians, seven hospitals, 47 
primary care clinics, 22 urgent care locations, 22 dental clinics, and numerous specialty practices 
in Minnesota and western Wisconsin. The majority of HPMG and PNMG patients (>80%) have 
commercial health insurance, while approximately 6% are insured via Medicare and 4% via 
Medicaid. HPMG and PNMG offer outpatient primary and specialty addiction care, day programs, 
partial hospitalization programs and inpatient treatment for OUD and other substance use 
disorders.  The medical groups refer out for methadone maintenance. 
PCPs who practice at least half-time and who have at least schedule 3 DEA prescribing privileges 
at HPMG or PNMG will be invited to participate in this study. PCPs with buprenorphine prescribing 
waivers will be particularly encouraged to participate in the study.  
8.3 
Rationale for Site Selection  
Rather than restricting the intervention to a single primary care clinic, particularly given the low 
prevalence of buprenorphine-certified PCPs in any one clinic, we propose inviting PCPs across 
HPMG and PNMG to participate. This approach will allow for maximum exposure of the OUD-
CDS across different providers, locations and patient populations. Making this intervention 
voluntary ensures maximum support of primary care leadership at both Park Nicollet and 
HealthPartners, and the timing of our study is ideal, with 12 PCPs intending to become newly 
buprenorphine-certified in the first half of 2017 across HPMG and PNMG.  
9.0 OUTCOME MEASURES  
9.1 
Primary Outcome Measure  
Primary Aims: 
1) To program an OUD-CDS tool based on a NIDA-Blending Initiative white paper “Clinical 
Decision Support for Opioid Use Disorders: Working Group Report” and national guidelines 
(VA (VA 2015), ASAM (ASAM 2015)) for use in an EMR.  
Measure 1.  Demonstrate that the OUD-CDS is functional and accurate through:  
a) 
Testing in the EMR test environment, 
b) 
Chart audit validation of CDS output, and 
c) 
Approval of the tool by specialty addiction physician and PCP pilot testers prior to the 
full rollout. 
2) 
To descriptively analyze PCP acceptability, satisfaction and use rates high enough to 
demonstrate proof of concept  

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
16 
 
 
Measure 2A.  By the end of the 6-month pilot intervention, the monthly PCP use rate of 
the CDS for targeted high-risk patient encounters for PCPs with CDS access will be 
>60%.  
Measure 2B.  By the end of the 6-month pilot intervention, >60% of PCPs with CDS 
access will report feeling confident in assessing and treating OUD 
Measure 2C. At the end of the 6-month pilot intervention, >80% of PCPs with CDS access 
will rate the OUD-CDS >4 on a 5-point Likert scale of likeliness to recommend use of 
the tool to their colleagues. 
Secondary Aims.  We will examine the usefulness of the OUD-CDS tool by comparing pre- and 
post-intervention rates of screening for OUD in high-risk patients, TAPS use, OUD diagnosis, use 
of medication-assisted therapy, as well as treatment referral patterns, for 3 groups of PCPs: (1) 
those with CDS access and buprenorphine certification, (2) PCPs with CDS access but without 
buprenorphine certification, and (3) PCPs without CDS access.   
Where possible, we will structure these secondary outcome measures to be similar to nationally-
used clinical quality measures, such as: 
a) Initiation of pharmacotherapy upon new episode of OUD (Number of patients who receive 
at least 1 prescription for MAT within 30 days following index visit with a diagnosis of OUD, 
divided by the number of patients with index visit associated with an OUD diagnosis after 
60-day clean period without OUD documentation)(Washington Circle Group; DHHS 2015)  
b) Maintenance pharmacotherapy for OUD (patients who receive at least 30 days’ treatment 
with buprenorphine or naltrexone for OUD, divided by patients who receive a diagnosis of 
OUD during the 6-month pilot phase)(American Psychiatric Association; DHHS 2015) 
9.2 
Other Outcome Measures 
MAT has been shown to reduce adverse outcomes, such as overdoses, emergency room visits, 
hospitalizations and deaths, for patients with OUD (Mohlman 2016; WHO 2013; Cornish 2010; 
Lo-Ciganic 2016). As a quality measure to inform future implementation studies of this OUD-CDS, 
we will collect and report available EHR data on overdoses, ER visits, hospitalizations and deaths 
for patients identified by the CDS as being at high-risk for OUD or as having been diagnosed with 
and/or treated for OUD. This data will be collected for patients of both PCPs with and without CDS 
access; for PCPs without CDS access, the CDS will still be collecting data behind the scenes 
without any displays to the PCP.  
10.0 STUDY PROCEDURES  
10.1 Phase 1: Translating the White Paper to an Epic-compatible CDS and 
Building and Testing the CDS (15 months) 
10.1.1 
Project Initiation 

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
17 
 
 
1. The original Blending Initiative team that developed the OUD CDS white paper will serve as 
an advisory panel to this project. 
2. The project team includes a co-chair of the Blending Initiative OUD CDS white paper team, 
Dr. Gavin Bart, a co-lead of this project, and a working group of clinicians and researchers 
with multidisciplinary expertise in OUD and EMR-based CDS, programmers experienced in 
web development, and programmers who are experienced in programming changes to the 
EMR.  
3. The project team will meet frequently (on average weekly) throughout the duration of this 
project. 
10.1.2 
Design and Planning 
4. The entire team needs to gain a deep understanding of the whitepaper. Since the CDS has 
to work in a real-world setting, we will collaborate with personnel who work in these settings 
and have knowledge-sharing meetings with them. Investigators and project managers will also 
visit clinics to perform work-site analyses and obtain advice and input from PCPs and clinic 
managers on how to integrate OUD-CDS within clinic workflows and strategies to optimize 
use rates. Once these data are collected, a plan is laid out that inserts CDS interactions at 
key points of the clinic workflow.  
5. We will refine the OUD algorithm and trouble-shoot potential operational issues using Visio 
and other software. Each step in the algorithm requires decisions about multiple aspects of 
care, including definitions of conditions and medical comorbidities, exclusion criteria, 
identification of pertinent labs and medications, and appropriate look-back periods. The CDS 
algorithms will be simplified and will include decision trees that will direct PCPs towards a 
referral for specialty addiction treatment for complicated cases, such as if a patient has both 
OUD and at least one other substance use disorder or uncontrolled behavioral health 
conditions. 
6. The CDS programs will then be designed to fit into the primary care clinic workflows. As 
envisioned currently: (a) When the rooming staff enter a blood pressure and close the vitals 
section in Epic, this triggers communication between Epic and the web server and the OUD 
CDS will run the algorithms. (b) For patients identified at high risk for OUD, a best practice 
advisory will display for the rooming staff to open and print the CDS.  The rooming staff will 
give the CDS to the PCP prior to the office visit so that the PCP is aware that the patient is 
potentially at risk for OUD and requires screening, diagnosis and/or treatment. The PCP will 
then re-enter the CDS during the encounter. (c) We train both the PCP and rooming staff in 
these procedures and the importance of this workflow. (d) Use rates are monitored by the 
research team with active outreach to clinics and providers who have lower than expected 
CDS use rates. (e)  We will survey PCPs about the support staff and services they currently 
have in place and what kinds of support or staff they would like to see in place to further inform 
our study and implementation. 
7. We will program OUD clinical algorithms in a web-based platform and ensure secure and 
timely communication between the web-based platform and HealthPartners’ EpiCare EMR 

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
18 
 
 
(Epic; Verona, WI). Steps 5 and 6 are time-consuming and require multiple iterative tests to 
optimize the process and assure data validity.  
8. While the CDS will always be available to be manually triggered by PCPs for any patient 
encounter, we will also set thresholds for the CDS to present a prompt or reminder for PCPs 
to suggest use of the CDS for screening patients identified at high risk for OUD. We will identify 
the criteria for automatic deployment in an iterative process, informed by preliminary data of 
the prevalence of comorbid diagnoses from our EMR and a recent big data study on the risk 
of OUD in patients receiving an initial opioid prescription (Cochran 2014). We anticipate a 
waterfall approach that may, for example, identify patients with (1) one inpatient or two 
outpatient diagnoses of OUD in the past 2 years, (2) 4 or more prescriptions for opioids in the 
past 2 years, and (3) diagnoses of non-opioid drug or alcohol use disorders, including 
sedative/hypnotics, cocaine, or cannabis. The process to trigger the CDS will be modified 
based on feedback we receive from PCPs in the pilot so as not to be overly burdensome to 
their workflow. PCPs will be encouraged to open the CDS for patients identified by the CDS 
to be at elevated risk for OUD and screen such patients using the sections of the Tobacco, 
Alcohol, Prescription Medication, and Other Substance Use (TAPS) tool specific to OUD 
(McNeely 2016) that will be programmed as a smartform within Epic. 
9. The programs have many layers of abstraction achieved by each layer performing a specific 
task. The layer above it can work in generalizations without specific knowledge of the tasks 
performed in the previous layer. The top layer of this stack will run the high-level decisions 
involved in the CDS. Design decisions are also based on what type of information is needed 
and where and when it is available for extraction from the EMR. In certain cases, the data 
required are not in the EMR and we will have to make alternate plans to collect such data from 
the patient and/or provider.  
10. We will design provider and patient print-outs for the OUD-CDS that PCPs can use as shared-
decision-making tools with their patients. Traditionally, the provider print-out has had more 
details and specific treatment suggestions, while the patient version has included the same 
basic information without relying on high literacy or numeracy. However, we have found that 
some PCPs prefer to review the provider print-out with patients, and keep this in mind as we 
design these forms.  
10.1.3 
Development 
11. Once the design of the system is in place, we will begin programming. We will use a Java 
Platform, with the components of the stack being Oracle databases hosted on AIX LAPR, a 
Tomcat web server that is hosted on Linux VM. The server infrastructure is designed for 
maximum uptime and is hosted in a secure offsite data center. The network is designed to 
handle data requested in a round robin fashion, thereby providing load balancing and failover 
capabilities. The CDS is implemented as a SOAP web service, which enables flexible 
maintenance and upgrade that is independent of the EMR. 
12. Data storage and structures will be defined and used to store data for later analysis. The data 
model will be created in a modeling platform that will be shared with the database 

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
19 
 
 
administrators for approval. The necessary security measures will be put into place to ensure 
minimum necessary access to data. Provider interfaces will be designed and implemented 
based on best practices. Data exchange formats will be decided upon for exchange of data 
between the web service and EMR. 
13. Our expert EMR programmers will create builds in the EMR to insert CDS into the workflow. 
They will also code the routines that extract patient data and package and format it for 
exchange. Additionally, they will configure and code hooks that will create and customize 
smartsets into the EMR that will help PCPs order the components suggested by the CDS. For 
patient reported data not already minable within the EMR, we will develop a section within a 
dynamic smartset tool to use for additional data collection. 
14. Development and programming will be iterative processes with multiple cycles of development 
and testing until a product is finalized.  Multiple rounds of chart audits will be conducted to 
identify problems in the algorithm or in data capture for use in the algorithms. Drs. Rossom 
and Sperl-Hillen will audit a minimum of 25 charts, increasing the sample by 10 charts each 
time we deem further review necessary, stopping when they agree they are no longer 
identifying additional issues to troubleshoot in the sample.  Depending on what issues are 
identified in this iterative, ongoing process, the team may need to complete several series of 
chart audits to further test any changes in programming indicated by previous testing.   
10.1.4 
Testing 
15. Once internal testing is performed and approvals are in place, the CDS will be turned on in 
the background for PCPs without any displays or visual indicators to the PCPs that the CDS 
is running. This allows us to test the CDS for data flow back and forth between the EMR and 
web platform and assess adequate capture of data in the web service.  
16. Once this testing is complete, the CDS will then be tested for clinical use by one or more 
providers with extensive experience with OUD care in an Epic testing environment.  
17. After this testing is completed by a provider with content expertise, we will conduct usability 
testing with at least three clinicians, observing them using the CDS in person in the production 
or testing environment. We will use a “talk or think aloud” protocol to identify any screen design 
or other usability issues. 
18. During these testing phases, we will test output of the care algorithms in batch process. We 
continuously validate collected data and closely monitor usage, traffic and accuracy. 
19. Infrastructure and data security will be maintained by having regular system-wide scans and 
by following documented standards and procedures to delegate access to data. Systems will 
be constantly monitored for errors.  
20. We will modify the smartsets and active guidelines as needed to provide actionable order sets 
for medications, labs, and referrals, automatic population of patient instructions, and 
facilitation of diagnostic coding based on algorithmic suggestions.  
21. We will develop reports to monitor usage at the provider level, provide feedback to PCPs and 
trouble-shoot low use rates. 

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
20 
 
 
22. We will recruit PCPs in-person and via emailed invitations approved by the IRB.  
23. We will assign PCPs to receive or not receive OUD access.  
24. We will assess confidence in assessing and treating OUD at baseline via an electronic survey 
for PCPs with and without CDS access  
10.2 Phase 2: Deploying and Testing the CDS in Primary Care (6 months) 
25. We will deploy OUD-CDS to approximately half of consented PCPs  
26. We will obtain feedback on OUD-CDS from PCPs in real-time in association with patient 
encounters via the feedback tab in the CDS and update the algorithms when indicated by this 
feedback 
27. We will measure and report use rates of the OUD-CDS at targeted visits by each PCP and 
trouble-shoot low use rates. For PCPs with use rates <60% of targeted visits, we will meet 
with the PCP to better understand why use rates are low, trouble-shoot any identified barriers, 
and encourage increased use.  
28. We will update and troubleshoot the CDS algorithms as needed, based on internal monitoring, 
provider feedback, FDA changes in treatment indications, or changes in the clinical evidence 
base or guideline recommendations.  
10.3 Phase 3: Analysis and Reporting (3 months) 
29. After the 6-month pilot phase, we will reassess provider confidence in assessing and treating 
OUD for PCPs with and without CDS access, and obtain feedback on OUD-CDS usability and 
satisfaction from PCPs with CDS access, via electronic survey 
30. Data will be consolidated, cleaned and analyzed 
31. We will disseminate findings locally and nationally, and submit manuscripts for publication 
10.4 Informed Consent Procedures for Participants  
We are asking PCPs to give informed consent to use the OUD-CDS on a voluntary and optional 
basis (if in the group of PCPs who are assigned to receive CDS access) and complete the pre- 
and post-intervention surveys. As the OUD-CDS is essentially operationalizing national and 
regional clinical guidelines, we will not be consenting PCPs to specifically change any clinical 
behavior related to managing patients with OUD. There is a small but important risk that the OUD-
CDS could provide the wrong treatment advice at the wrong time. As with other clinical decision 
tools, the CDS makes suggestions for patient care and is meant to supplement but not supersede 
the PCP’s clinical judgment. This point is made clear in the training, in the consent, and on the 
provider display for the CDS. We will seek an IRB waiver of written informed consent for primary 
care clinic patients, as the CDS does not recommend any new care procedures and is being 
applied within the EMR as an aid to the PCP to facilitate recommended standards of care. 
HealthPartners IRB has granted waivers for other studies of CDS in the past. 
10.5 HIPAA Authorization and Medical Record Release Forms 
Not applicable.  

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
21 
 
 
10.6 Baseline Visit  
Not applicable. 
10.7 Randomization  
PCPs who are recruited and are buprenorphine-certified will be placed into the group of PCPs 
who have OUD-CDS access. PCPs who are recruited and do not have buprenorphine certification 
will be randomized to receive or not receive access to the OUD-CDS. 
10.8 Treatment/Intervention  
The intervention is the availability of the OUD-CDS to approximately half of enrolled PCPs.  
10.9 Collection of Biospecimens 
Not applicable. 
10.10 Premature Withdrawal of Participants  
All consented PCPs will be followed for the duration of the study unless they withdraw consent, 
die, leave HPMG or PNMG or the investigator or sponsor decides to discontinue their enrollment 
for any reason. Reasons for the investigator or sponsor terminating a participant from the study 
may include, but are not limited to lack of funding or early termination of the study for safety or 
effectiveness reasons. 
10.11 Study Halting Rules 
While not anticipated, if it becomes clear that it is technically too difficult or otherwise unfeasible 
to program the CDS into a web-based platform that displays within the EMR, the study may be 
stopped early. 
10.12 Follow-Up  
We will collect follow-up survey information from PCPs 6 months after the OUD-CDS go-live date. 
During the 6-month intervention phase, we will be monitoring PCP use of the CDS, providing use 
rate reports for PCPs, and contacting PCPs whose use rates fall below 60% to trouble-shoot low 
use and understand any barriers to use. 
10.13 Blinding  
This study is not blinded. All consented PCPs will be aware of their access or lack of access to 
the OUD-CDS. 
10.14 Participant Reimbursement  
PCPs will be reimbursed $150 (PCPs without CDS access) to $300 (PCPs with CDS access) for 
their time to complete pre- and post-implementation surveys, and, for PCPs who have access to 
the CDS, to submit feedback via the feedback tab in the CDS. 
10.15 Retention Plan 
PCP engagement with the OUD-CDS will be measured by OUD-CDS use reports that determine 
for what percent of eligible encounters PCPs are using the CDS tool. These reports are provided 

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
22 
 
 
to both the PCP and the study team on a weekly and then, after 6-8 weeks, on a monthly basis. 
For PCPs with low use rates, the study team will contact the PCP directly to determine any barriers 
to use and to encourage increased use. 
11.0 STUDY ASSESSMENTS  
11.1 Study Assessments 
11.1.1 
PCP Surveys 
Prior to going live with the OUD-CDS, PCPs with and without CDS access will complete a baseline 
survey via a unique emailed link. The survey will be administered via the Survey Research Center 
at HealthPartners Institute via RedCap, and will be maintained in a secure HealthPartners server. 
This initial survey will be focused on PCP confidence in their ability to screen for, assess, 
diagnose, treat and refer patients with OUD appropriately, assessed via 5-point Likert scales. 
After the 6-month intervention, all PCPs will again be surveyed about their confidence in OUD 
care. Additionally, the PCPs with CDS access will complete survey questions specific to the OUD-
CDS, including questions regarding usability, accuracy, and provider likelihood to recommend the 
tool. A draft of specific items in the surveys follows. 
SURVEY DRAFT 
1. What is your primary clinic? 
 
2. What is your age? 
 
3. What is your gender 
 
4. With which race/ethnicity do you identify? 
o Asian 
o Hispanic 
o Native American/Alaskan Native 
o Non-Hispanic black 
o Pacific Islander/Native Hawaiian 
o White 
o Mixed race or other 
o Prefer not to answer 
 
 
 

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
23 
 
 
5. How many years have you been in practice following residency or fellowship? 
o 0-5 
o 6-10 
o 11-15 
o 16-20 
o 21+ 
 
6. What is your medical specialty? 
o Family Practice 
o Internal Medicine 
o Med Peds 
o Other (please specify) 
 
7. On average, how many days a week do you see patients in clinic?  
o 0 
o 1 
o 2  
o 3 
o 4 
o 5 or more 
 
Answer the questions below about your knowledge and approach to management of patients 
with Opioid Use Disorder (OUD). Choose only one answer. 
8. How often do you formally assess patients for opioid use disorder (OUD)? 
 
Very often 
Often 
Sometimes 
Occasionally 
Never 
 
9. How confident do you feel about screening your patients for OUD? 
Very confident 
Moderately 
confident 
Somewhat 
confident 
Not at all 
confident 
 
10. How often do you provide treatment or refer your patients for treatment of OUD? 
Very often 
Often 
Sometimes 
Occasionally 
Never 
 
11. How confident are you at diagnosing patients with OUD?  
Very confident 
Moderately 
confident 
Somewhat 
confident 
Not at all 
confident 
 

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
24 
 
 
12. How confident are you at treating your patients with medications such as buprenorphine or 
naltrexone for OUD?  
Very confident 
Moderately 
confident 
Somewhat 
confident 
Not at all 
confident 
 
13. How confident are you at knowing when to refer your patients with OUD for treatment by 
addiction specialists? 
 
Very confident 
Moderately 
confident 
Somewhat 
confident 
Not at all 
confident 
 
14.  (Skip if certified in buprenorphine prescribing) To what extent do you agree or disagree with 
the following statement: The availability of EHR-integrated clinical decision support for how 
to use buprenorphine and/or naloxone and manage OUD would make it more likely that I 
would become a certified buprenorphine prescriber.  
Strongly agree 
 Somewhat 
Agree 
Somewhat 
Disagree 
Strongly 
disagree 
 
 
 

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
25 
 
 
15. Please rate your ability to effectively manage patients with the following treatment 
strategies:  
 
High ability 
(on par with 
subspecialist
s) 
Moderately 
high ability 
Adequate 
ability 
Some ability; 
could use 
improvement 
Low 
ability 
Brief 
motivational 
counseling 
1 
2 
3 
4 
5 
Overdose 
prevention 
1 
2 
3 
4 
5 
Extended-
release 
naltrexone 
(Vivitrol) 
1 
2 
3 
4 
5 
Buprenorphine 
(as 
monotherapy 
or in 
combination 
with naloxone 
(Suboxone)) 
1 
2 
3 
4 
5 
Referral for 
methadone or 
other 
treatment 
1 
2 
3 
4 
5 
 
. Post-Implementation Survey 
Answer the questions below about your knowledge and approach to management of patients 
with Opioid Use Disorder (OUD). Choose only one answer. 
1. How often do you formally assess patients for opioid use disorder (OUD)? 
Very often 
Often 
Sometimes 
Occasionally 
Never 
 

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
26 
 
 
2. How confident do you feel about screening your patients for OUD? 
Very confident 
Moderately 
confident 
Somewhat 
confident 
Not at all 
confident 
3. How often do you provide treatment or refer your patients for treatment of OUD? 
Very often 
Often 
Sometimes 
Occasionally 
Never 
 
4. How confident are you at diagnosing patients with OUD?  
Very confident 
Moderately 
confident 
Somewhat 
confident 
Not at all 
confident 
 
5. How confident are you at treating your patients with medications such as buprenorphine or 
naltrexone for OUD?  
Very confident 
Moderately 
confident 
Somewhat 
confident 
Not at all 
confident  
 
6. How confident are you at knowing when to refer your patients with OUD for treatment by 
addiction specialists?  
Very confident 
Moderately 
confident 
Somewhat 
confident 
Not at all 
confident 
 
7. (Skip if certified in buprenorphine prescribing) To what extent do you agree or disagree with 
the following statement: The availability of EHR-integrated clinical decision support for how 
to use buprenorphine and/or naloxone and manage OUD would make it more likely that I 
would become a certified buprenorphine prescriber.  
Strongly agree 
Agree 
Disagree 
Strongly 
disagree 
 
 

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
27 
 
 
8. Please rate your ability to effectively manage patients with the following treatment 
strategies:  
 
High ability 
(on par with 
subspecialist
s) 
Moderately 
high ability 
Adequate 
ability 
Some ability; 
could use 
improvement 
Low 
ability 
Brief 
motivational 
counseling 
1 
2 
3 
4 
5 
Overdose 
prevention 
1 
2 
3 
4 
5 
Extended-
release 
naltrexone 
(Vivitrol) 
1 
2 
3 
4 
5 
Buprenorphine 
(as 
monotherapy 
or in 
combination 
with naloxone 
(Suboxone)) 
1 
2 
3 
4 
5 
Referral for 
methadone or 
other 
treatment 
1 
2 
3 
4 
5 
 
 
NOTE: **These questions will only be present in the post (6-month) surveys for 
PCPs with CDS access** 
Please answer the questions below concerning work flow and ease of use of the Opioid Wizard 
Clinical Decision Support.  
9. How likely are you to recommend Opioid Wizard to a colleague?  

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
28 
 
 
Very 
likely 
Moderately 
likely 
Somewhat 
likely 
Not very 
likely 
Not at all likely 
10. Opioid Wizard is a tool that helps me screen for OUD. 
Strongly agree 
Somewhat 
Agree 
Somewhat 
Disagree 
Strongly 
disagree 
11. Opioid Wizard makes me feel more comfortable prescribing medications for OUD in my 
practice.  
Strongly agree 
Somewhat 
Agree 
Somewhat 
Disagree 
Strongly 
disagree 
12. Using the Opioid Wizard makes it easier for me to discuss treatment options of OUD with 
patients and determine their preference. 
Strongly agree 
Somewhat 
Agree 
Somewhat 
Disagree 
Strongly 
disagree 
13. Opioid Wizard helps me know when to refer patients for methadone or other specialty 
treatment. 
Strongly agree 
Somewhat 
Agree 
Somewhat 
Disagree 
Strongly 
disagree 
14. When I want or need to address OUD with patients, the Opioid Wizard saves me time.  
Strongly agree 
Somewhat 
Agree 
Somewhat 
Disagree 
Strongly 
disagree 
 
15. Opioid Wizard improves my office efficiency.    
Strongly agree 
Somewhat 
Agree 
Somewhat 
Disagree 
Strongly 
disagree 
 
16. Time using the Opioid Wizard with patients is time well spent. 

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
29 
 
 
Strongly agree 
Somewhat 
Agree 
Somewhat 
Disagree 
Strongly 
disagree 
17.  Opioid Wizard influences my treatment recommendations. 
Strongly agree 
Somewhat 
Agree 
Somewhat 
Disagree 
Strongly 
disagree 
 
18. How useful are the following Opioid Wizard features? 
Feature 
Very 
useful 
Moderately 
useful 
Somewhat 
useful 
Slightly 
useful 
Not at all useful 
Screening tools (TAPS) 
 
 
 
 
 
Diagnosis tools 
 
 
 
 
 
Prescribing overdose 
kits 
 
 
 
 
 
Guidance for screening 
for comorbidities such 
as alcohol use disorder, 
hepatitis, pregnancy 
 
 
 
 
 
Deciding which 
treatment approach is 
best for the patient 
(medication-assisted 
therapy by primary 
care, referral to an 
addiction specialists for 
medication-assisted 
therapy, safer use, 
further discussion, etc.) 
 
 
 
 
 
Deciding between 
different strategies of 
medication-assisted 
 
 
 
 
 

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
30 
 
 
therapy (naltrexone vs. 
buprenorphine vs. 
methadone) 
Safety alerts for 
drug/drug interactions 
 
 
 
 
 
Urine drug screen 
testing reminders  
 
 
 
 
 
19. How could we make Opioid Wizard more useful? 
________________________________________________________________________ 
________________________________________________________________________ 
20. Do you have any other feedback you’d like to share, or ways in which you think Opioid 
Wizard could be improved? 
________________________________________________________________________ 
 
Thank you for your participation. Your input is greatly appreciated! 
 
11.2 PCP Use Reports  
Each PCP will receive weekly use reports indicating the percentage of eligible encounters for 
which the OUD-CDS was opened and engaged. Eligible encounters are considered encounters 
in which the OUD-CDS displayed a best practice alert to the PCP, letting them know that the 
patient has a diagnosis of OUD, is on MAT for OUD, or may be at increased risk of OUD and the 
PCP should considering OUD screening. Reports will show the PCP use rates in relation to other 
PCPs with CDS access in order to encourage high levels of use for all PCPs. Research study 
team members will contact PCPs who fall below a use rate of 60% to determine if there are any 
issues or concerns with the OUD-CDS and to problem-solve any barriers to use. 
11.3 General Measures  
11.3.1 
Inclusion/Exclusion 
Inclusion criteria for PCPs: 
a) An MD, DO, NP, or PA engaging in independent primary care of adults  
b) At least schedule 3 DEA prescribing privileges 
c) Voluntarily consent to participation 
 
Exclusion criteria for PCPs: 
a) Less than half-time clinical primary care responsibilities 

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
31 
 
 
11.4 Locator Form 
We will keep a list of consented PCPs (both those who have CDS access and those who do not) 
on a secure server at HealthPartners. This list will include the PCP name, primary care clinic 
name, phone number of the clinic and provider email address.  
11.5 Demographics Form 
We will collect age, gender, race/ethnicity, years of practice and medical specialty (primary care 
vs. internal medicine) for PCP participants. Patient-level data required to assess study objectives 
will be stored in a secure analytic database.  
11.6 PhenX Tier 1 
We will not be utilizing the PhenX Toollkit. We will be collecting data via the OUD-CDS tool itself, 
with data stored in a secure server located behind multiple HealthPartner firewalls. These data 
are captured from Clarity, largely using standard Health Care Systems Research Network Virtual 
Data Warehouse data elements (Ross TR 2014).  
11.7 End of Medication/End of Treatment Form 
Not applicable.  
11.8 Study Completion Form 
Not applicable.   
11.9 Measures of Primary and Secondary Outcomes  
Primary Aims: 
1) To program an OUD-CDS tool based on a NIDA-Blending Initiative white paper “Clinical 
Decision Support for Opioid Use Disorders: Working Group Report” and national guidelines 
(VA (VA 2015), ASAM (ASAM 2015)) for use in an EMR.  
Measure 1.  Demonstrate that the OUD-CDS is functional and accurate through:  
a) Testing in the EMR test environment, 
b) Chart audit validation of CDS output, and 
c) Approval of the tool by specialty addiction physician and PCP pilot testers prior to the full 
rollout. 
2) To descriptively analyze PCP acceptability, satisfaction and use rates high enough to 
demonstrate proof of concept  
Measure 2A.  By the end of the 6-month pilot intervention, the monthly PCP use rate of the 
CDS for targeted high-risk patient encounters for PCPs with CDS access will be >60%.  
Measure 2B.  By the end of the 6-month pilot intervention, >60% of PCPs with CDS access 
will report feeling confident in assessing and treating OUD 

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
32 
 
 
Measure 2C. At the end of the 6-month pilot intervention, >80% of PCPs with CDS access 
will rate the OUD-CDS >4 on a 5-point Likert scale of likeliness to recommend use of the 
tool to their colleagues. 
Secondary Aims.  We will examine the usefulness of the OUD-CDS tool by comparing pre- and 
post-intervention rates of screening for OUD in high-risk patients, TAPS use, OUD diagnosis, use 
of medication-assisted therapy, as well as treatment referral patterns, for 3 groups of PCPs: (1) 
those with CDS access and buprenorphine certification, (2) PCPs with CDS access but without 
buprenorphine certification, and (3) PCPs without CDS access. 
 
11.10 Clinical and Safety Assessments  
11.10.1 
Adverse Events (AEs) and Serious Adverse Events (SAEs) 
This study is being conducted at the provider level using CDS prompts for evidence-based best 
practice standards related to OUD. Prior to implementation, we will train all intervention PCPs and 
their rooming staff on the importance of helping us identify any safety events or near-misses that 
may be related to the EHR or CDS.  We will systematically educate them in identification of 
potential safety events and near-misses and appropriate use of the Feedback button in the CDS 
or email to promptly notify us about such events. We will also ask PCPs to notify us of any clinical 
situations where their clinical judgment differs from the CDS.   
 
Use of the Feedback button automatically generates an email that is sent to Drs. Rossom and 
Sperl-Hillen and the web programming team. The research team then discusses this feedback 
and any necessary actions, and connects with the PCP to answer the question, discuss steps 
taken to address the issue, or gather additional information if needed to further trouble-shoot. 
PCPs will be asked to submit feedback any time their clinical judgment is inconsistent with the 
CDS tool. Additionally, the emails of Drs. Rossom and Sperl-Hillen are listed on the CDS interface 
for providers, and PCPs are encouraged to contact us directly with any questions or concerns if 
they’d rather not use the feedback tab in the OUD-CDS. This feedback will be provided to the 
DSMB twice during the study period or at a frequency the DSMB requests.   
 
11.11 Compliance Measures 
Each PCP will receive weekly use reports indicating the percentage of eligible encounters for 
which the OUD-CDS was opened and engaged. Study team members will contact PCPs who 
fall below a use rate of 60% to determine if there are any issues or concerns with the OUD-CDS 
and problem-solve any barriers to use. We will consider the OUD-CDS to be effectively 
implemented if it is used by PCPs in at least 60% of targeted patient encounters.   
11.12 Drug Use Measures 
11.12.1 
Urine Drug Screen 
Not applicable.   

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
33 
 
 
11.12.2 
DSM-5 Checklist 
Not applicable.   
12.0 TRAINING REQUIREMENTS  
12.1 Overall 
Enrolled PCPs who will use the OUD-CDS will be trained on how to use the tool and the 
importance of using the feedback tab to let the study team know of any issues or questions to 
help us continue to improve the CDS. Traditionally, we have completed such trainings at in-person 
lunch meetings with clinic personnel, but will also consider web-based trainings depending on 
clinic leadership preference.   
 
 

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
34 
 
 
13.0 STATISTICAL DESIGN AND ANALYSES  
13.1 General Design  
13.1.1 
Study Hypothesis  
A web-based EMR-integrated point-of-care CDS tool for OUD is both feasible and usable in the 
primary care setting. 
13.2 Primary and Secondary Outcomes (Endpoints)   
Primary Aims: 
1) 
To program an OUD-CDS tool based on a NIDA-Blending Initiative white paper “Clinical 
Decision Support for Opioid Use Disorders: Working Group Report” and national guidelines 
(VA (VA 2015), ASAM (ASAM 2015)) for use in an EMR.   
Measure 1.  Demonstrate that the OUD-CDS is functional and accurate through:  
a) 
Testing in the EMR test environment, 
b) 
Chart audit validation of CDS output, and 
c) 
Approval of the tool by specialty addiction physician and PCP pilot testers prior to the 
full rollout. 
2) 
To descriptively analyze PCP acceptability, satisfaction and use rates high enough to 
demonstrate proof of concept  
Measure 2A.  By the end of the 6-month pilot intervention, the monthly PCP use rate of the 
CDS for targeted high-risk patient encounters for PCPs with CDS access will be >60%.   
Measure 2B.  By the end of the 6-month pilot intervention, >60% of PCPs with CDS access 
will report feeling confident in assessing and treating OUD 
Measure 2C. At the end of the 6-month pilot intervention, >80% of PCPs with CDS access 
will rate the OUD-CDS >4 on a 5-point Likert scale of likeliness to recommend use of 
the tool to their colleagues. 
Secondary Aims.  We will examine the usefulness of the OUD-CDS tool by comparing pre- and 
post-intervention rates of screening for OUD in high-risk patients, TAPS use, OUD diagnosis, use 
of medication-assisted therapy, as well as treatment referral patterns, for 3 groups of PCPs: (1) 
those with CDS access and buprenorphine certification, (2) PCPs with CDS access but without 
buprenorphine certification, and (3) PCPs without CDS access.     
14.0 RECRUITMENT  
PCPs will be voluntarily recruited from HPMG and PNMG in person and via emailed invitations. 
We will recruit all PCPs who have or will soon have buprenorphine waivers, as they will be able 
to use the entirety of the OUD-CDS tool. In our invitation to participate in the study, we will inform 
PCPs that they will receive $150 (PCPs without CDS access) or $300 (PCPs with CDS access) 
each to compensate them for their time in completing emailed surveys at the beginning and end 

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
35 
 
 
of the 6-month pilot intervention phase (all PCPs), and for their time in submitting feedback via 
the feedback tab in the CDS (PCPs with access to the CDS). 
15.0 RANDOMIZATION AND FACTORS FOR STRATIFICATION  
PCPs who are recruited and are buprenorphine-certified will be placed into the group of PCPs 
who have OUD-CDS access. PCPs who are recruited and do not have buprenorphine certification 
will be randomized to receive or not receive access to the OUD-CDS. We will be aware of practice 
location, patient panel size and number of patients for whom the CDS-OUD was triggered and 
can analyze results based on individual practice location or panel, but given the small nature of 
this pilot project we do not anticipate statistically meaningful information from these factors. 
16.0 PREDICTION MODELS 
Not applicable.   
16.1 Rationale for Sample Size and Statistical Power  
16.1.1 
Projected Number of Sites  
This study will occur at PNMG and HPMG, both of which are divisions of HealthPartners. This 
pilot intervention will occur at primary care clinics at which one or more eligible PCPs have 
consented to participate. We anticipate a total of 37-43 PCPs from twenty primary care clinics will 
participate. 
16.1.2 
Projected Number of Participants per Site 
We anticipate 37-43 PCPs from approximately twenty primary care clinics will participate.   
16.2 Statistical Methods for Primary and Secondary Outcomes  
This pilot study for OUD-CDS feasibility and usability will not have a statistical endpoint. Provider 
characteristics, patient characteristics, and OUD-CDS use rates will be tracked and described. 
Pre- and post-intervention surveys of provider confidence in OUD assessment and treatment as 
well as satisfaction and usability of the OUD-CDS will be described. 
16.3 Significance Testing  
This pilot study for OUD-CDS feasibility and usability does not entail statistical testing or power 
calculations. Provider characteristics, patient characteristics, and OUD-CDS use rates will be 
tracked and described. 
16.4 Types of Analyses  
Provider characteristics, patient characteristics, and OUD-CDS use rates will be tracked and 
descriptively analyzed. 
 
 

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
36 
 
 
16.5 Interim Analysis  
Not applicable for a pilot study that will be in the field for 6 months.   
16.6 Exploratory Analysis  
MAT has been shown to reduce adverse outcomes, such as overdoses, hospitalizations and 
deaths, for patients with OUD (Mohlman 2016; WHO 2013). As a quality measure to inform future 
implementation studies of this OUD-CDS, we will collect available EHR data to examine 
overdoses, ER visits, hospitalizations and deaths for patients with OUD treated by PCPs with and 
without CDS access. While this information will likely not be useful for statistical considerations, 
trends observed could be hypotheses-generating and inform future study needs. 
16.7 Missing Data and Dropouts  
All eligible providers may not respond to surveys or to particular survey questions. In order to 
minimize survey non-response we will administer the survey electronically in a format that will 
prompt PCPs to answer missed questions. We will also send multiple reminders of the survey 
and provide PCPs who do not have CDS access an incentive of $150 to complete baseline and 
6-month surveys, and PCPs who do have CDS access an incentive of $300 to complete baseline 
and 6-month surveys and submit feedback via the CDS feedback tab.  
16.8 Demographic and Baseline Characteristics  
Baseline demographic and practice variables (e.g., years in practice, size of patient panel, etc.) 
will be summarized for PCPs enrolled in this study.  
16.9 Safety Analysis  
In this pilot study, we are not trying to change the standard of care for OUD treatment in primary 
care, but rather helping PCPs achieve this standard of care in OUD treatment. PCPs are trained 
that, as with other CDS tools, the OUD-CDS is meant to supplement but not supersede clinical 
judgment. PCPs can choose to follow or not follow the guidance of the CDS at any given time for 
any given patient encounter, and PCPs are trained to let the research team know via the 
Feedback tab in the CDS when their clinical judgment is inconsistent with the CDS 
recommendations. This feedback will be monitored by the treatment team and the CDS algorithms 
adjusted if indicated. 
An independent CTN DSMB will monitor this study.  The DSMB will communicate regarding what 
type of reports will be needed, as well as frequency.    
17.0 REGULATORY COMPLIANCE AND SAFETY 
17.1 Regulatory Compliance  
This study will be conducted in accordance with the current version of the protocol, in accordance 
with the ethical principles outlined in the Declaration of Helsinki, International Conference on 
Harmonization Good Clinical Practice (GCP) Guidelines, and all other applicable regulatory 
requirements.   

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
37 
 
 
17.2 Statement of Compliance  
This trial will be conducted in compliance with the appropriate protocol, current Good Clinical 
Practice (GCP), the principles of the Declaration of Helsinki, and all other applicable regulatory 
requirements. The participating clinic sites are all within the HealthPartners system and therefore, 
protocol review, consent forms, and other pertinent regulatory materials will be reviewed by 
approved by the HealthPartners IRB prior to participant recruitment and enrollment. While the 
intervention is only 6 months, appropriate annual progress reports will be submitted to the 
HealthPartners IRB as needed. 
17.3 Institutional Review Board Approval  
Prior to initiating the study, site investigators will obtain written HealthPartners’ IRB approval to 
conduct the study. Should substantive changes to the study protocol become necessary, protocol 
amendments will be submitted in writing by the investigators for IRB approval prior to 
implementation. In addition, the IRB will approve all consent forms and recruitment and survey 
materials. Progress reports will be submitted to the IRB annually or at a frequency requested by 
the IRB so that continuous study approval is maintained without lapse. The lead investigator is 
responsible for maintaining in her research files copies of current IRB/IEC approval notice and 
IRB-approved consent document(s), including approval for all protocol modifications. These 
materials must be available at any time for audit.  
17.4 Informed Consent  
The informed consent process is a means of providing study information to each prospective PCP 
participant and allows for an informed decision about participation in the study. The informed 
consent form will include all of the required elements of informed consent. Every study participant 
is required to electronically sign a valid, IRB-approved current version of the study informed 
consent form prior to the initiation of any study-related procedures. The site will maintain the 
electronically signed informed consent for every participant on a secure server that is in 
compliance with the HealthPartners IRB and institutional policies. Every study participant will have 
the opportunity to print or save a hard copy of the electronic consent form. 
Prior to informed consent, research staff will provide a detailed description of the study to the 
potential participant PCP and provide a copy of the consent to read. If the participant is interested 
in participating in the study, he or she will have the opportunity to ask any questions related to 
participation. The participant will consent by electronically signing the consent document. 
The informed consent form will be updated or revised whenever important new safety information 
is available, or whenever the protocol is amended in a way that may affect participants’ 
participation in the trial. The participant will be informed that their participation is voluntary and 
they may withdraw from the study at any time, for any reason without penalty. Individuals who 
refuse to participate or who withdraw from the study will be treated without prejudice. Study sites 
will be responsible for maintaining signed consent forms as source documents for quality 
assurance review and regulatory compliance. 
17.5 Quality Assurance and Safety Monitoring  

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
38 
 
 
Quality assurance monitoring will be accomplished via pre-implementation testing to confirm that 
the CDS is collecting and storing the data as expected. After implementation and throughout the 
6-month pilot phase, data will be repeatedly tested to ensure all data elements necessary for 
analysis are collected on secure servers, and Dr. Crain will conduct periodic test analyses to 
ensure that all of the data she requires for analysis are complete. Additionally, Drs. Rossom and 
Sperl-Hillen will conduct periodic chart audits to ensure that data collected by the CDS is accurate 
and complete. Drs. Rossom and Sperl-Hillen will also monitor all PCP feedback during the 
intervention, work together with the programming team to determine whether the CDS needs to 
be altered to address the issues raised in the feedback, and make adjustments to the CDS as 
clinically indicated. 
17.6 Confidentiality  
Confidentiality will be maintained in accordance with all applicable federal and state regulations. 
By signing the protocol signature page the investigator affirms that information furnished to the 
investigator by NIDA will be maintained in confidence and such information will be divulged to the 
IRB, Ethical Review Committee, or similar expert committee; affiliated institution; and employees 
only under an appropriate understanding of confidentiality with such board or committee, affiliated 
institution and employees. Participant records will be held confidential by the use of study codes 
for identifying participants on CRFs, secure storage of any documents that have participant 
identifiers, and secure computing procedures for entering and transferring electronic data.  
17.7 Health Information Portability Accountability Act (HIPAA)   
Participants in this study are answering surveys regarding usability of an OUD-CDS. No personal 
health information is collected from participants as a part of this study. The OUD-CDS will be used 
by PCPs in the course of routine medical care. The CDS has automated algorithms to identify 
patients for whom it may be appropriate to use the OUD-CDS. These patients are not participants 
in the research but their data is utilized by the OUD-CDS. HIPAA itself makes specific provision 
for waiver of authorization to use PHI for research recruitment purposes under some specific 
conditions, all of which this study meets: “For research uses and disclosures of PHI, an IRB or 
privacy board may approve a waiver or an alteration of the authorization requirement in whole or 
in part. A complete waiver occurs when the IRB or privacy board determines that no authorization 
is required for a covered entity to use and disclose PHI for a particular research project. A partial 
waiver of authorization occurs when an IRB or privacy board determines that a covered entity 
does not need authorization for all PHI uses and disclosures for research purposes, such as 
disclosing PHI for research recruitment purposes. An IRB or privacy board may also approve a 
request that removes some PHI, but not all, or alters the requirements for an authorization (an 
alteration).” See: 
 http://privacyruleandresearch.nih.gov/pr_08.asp#8c. 
17.8 Investigator Assurances  
Health Partners maintains a current Federal Wide Assurance (FWA) with the DHHS Office for 
Human Research Protection setting forth the commitment of the organization to establish 

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
39 
 
 
appropriate policies and procedures for the protection of human research subjects. This 
documentation will be sent to NIDA or its designee. Research covered by these regulations 
cannot proceed in any manner prior to NIDA receipt of certification that the research has been 
reviewed and approved by the IRB provided for in the assurance (45 CFR 46.103(b) and (f)). Prior 
to initiating the study, the principal investigator will sign a protocol signature page, providing 
assurances that the study will be performed according to the standards stipulated therein. 
17.9 Financial Disclosure  
All investigators will comply with the requirements of 42 CFR Part 50, Subpart F to ensure that 
the design, conduct, and reporting of the research will not be biased by any conflicting financial 
interest. Everyone with decision-making responsibilities regarding the protocol will confirm to the 
sponsor annually that they have met their institutional financial disclosure requirements. 
17.10 DEA Registration (Component for medication studies using controlled 
substances studies – use if applicable) 
All enrolled PCPs will have appropriate DEA registration. As this is required for them to be able 
to prescribe medications as part of their medical practice at Park Nicollet and HealthPartners 
clinics, research staff will not verify or monitor DEA registration status of participants. We will not 
be receiving any shipments of study drug. 
17.11 IND Requirements (Component for IND studies – use if applicable) 
Not applicable.   
17.12 Clinical Monitoring 
Drs. Rossom and Sperl-Hillen will monitor all PCP feedback during the intervention, work together 
with the programming team to determine whether the CDS needs to be altered to address the 
issues raised in the feedback, and make adjustments to the CDS as clinically indicated. Drs. 
Rossom and Sperl-Hillen will also conduct periodic chart audits during Phase 2 to determine that 
data collected by the CDS is accurate and complete, and that all relevant clinical information is 
correctly identified and used by the CDS. 
17.13 Inclusion of Women and Minorities  
Enrollment is at the provider level. We anticipate enrolling about 21 PCPs who will have access 
to the CDS and 16 PCPs who will not, and that these PCPs will be generally representative of the 
HPMG and PNMG provider pools in terms of gender and racial/ethnic distribution. 
 
 

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
40 
 
 
17.14 Regulatory Files  
The regulatory files will contain all required regulatory documents, study-specific documents, and 
all important communications. Regulatory files will be checked for regulatory document 
compliance prior to study initiation, throughout the study, as well as at study closure. 
17.15 Records Retention and Requirements  
The regulatory files should contain all required regulatory documents, study-specific documents, 
and all important communications. Regulatory files will be checked for regulatory document 
compliance prior to study initiation, throughout the study, as well as at study closure. Regulatory 
and other research records should be maintained by the investigator in a secure location for a 
minimum of 3 years after the study is completed and closed. These records are also to be 
maintained in compliance with IRB, state and federal requirements, whichever is longest. The 
sponsor and Lead Investigator must be notified in writing and acknowledgment must be received 
by the site prior to the destruction or relocation of research records. 
17.16 Reporting to Sponsor 
The site principal investigator agrees to submit accurate, complete, legible and timely reports to 
the Sponsor, as required. These include, but are not limited to, reports of any changes that 
significantly affect the conduct or outcome of the trial or increase risk to study participants. At the 
completion of the trial, the Lead Investigator will provide a final report to the Sponsor. 
17.17 Audits  
The Sponsor has an obligation to ensure that this trial is conducted according to good research 
practice guidelines and may perform quality assurance audits for protocol compliance. The Lead 
Investigator and authorized staff from the NorthStar Node; the National Institute on Drug Abuse 
Clinical Trials Network (NIDA CTN, the study sponsor); NIDA’s contracted agents, monitors or 
auditors; and other agencies such as the Department of Health and Human Services (HHS), the 
Office for Human Research Protection (OHRP) and the sites’ Institutional Review Board may 
inspect research records for verification of data, compliance with federal guidelines on human 
participant research, and to assess participant safety. 
17.18 Study Documentation  
Study documentation includes all source documents, monitoring logs and appointment schedules, 
sponsor-investigator correspondence, and signed protocol and amendments, Ethics Review 
Committee or Institutional Review Committee correspondence and approved consent form and 
signed participant consent forms. Source documents include all recordings of observations or 
notations of clinical activities and all reports and records necessary for the evaluation and 
reconstruction of the clinical research study. Whenever possible, the original recording of an 
observation should be retained as the source document; however, a photocopy is acceptable 
provided that it is a clear, legible, and exact duplication of the original document. 
 
 

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
41 
 
 
17.19 Protocol Deviations  
Any departure from procedures and requirements outlined in the protocol will be classified as 
either a major or minor protocol deviation. The difference between a major and minor protocol 
deviation has to do with the seriousness of the event and the corrective action required. A minor 
protocol deviation is considered an action (or inaction) that by itself is not likely to affect the 
scientific soundness of the investigation or seriously affect the safety, rights, or welfare of a study 
participant. Major protocol deviations are departures that may compromise the participant safety, 
participant rights, inclusion/exclusion criteria or the integrity of study data and could be cause for 
corrective actions if not rectified or prevented from re-occurrence.   
 
Since the intervention of this study is access to the OUD-CDS and pre- post-intervention surveys, 
we do not anticipate safety issues related to the participants or for the opportunity for protocol 
deviations. Because the OUD-CDS programming may have unanticipated bugs that may lead the 
CDS to recommend (or fail to recommend) a clinical action that is inappropriate for a given patient, 
we will use a live “Feedback” tab that displays in the OUD-CDS to let the study team know of any 
questions or concerns with the CDS. This automatically generates an email that is sent to Drs. 
Rossom and Sperl-Hillen and the web programming team. The research team will then discuss 
this feedback and any necessary actions, and will connect with the PCP to answer the question, 
discuss steps taken to address the issue, or gather additional information and further trouble-
shoot. Identification of protocol deviations through this mechanism will be adjudicated by this team 
who will also develop a corrective action plan for both major and minor deviations as appropriate. 
Those corrective action plans may be reviewed/approved by the Lead Node with overall approval 
by the site’s IRB. All protocol deviations will be monitored at each site for (1) significance, (2) 
frequency, and (3) impact on the study objectives, to ensure that site performance does not 
compromise the integrity of the trial.   
17.20 Safety Monitoring  
17.20.1 
Data and Safety Monitoring Board (DSMB)  
An independent CTN DSMB will monitor this study.  The DSMB will communicate regarding what 
type of reports will be needed, as well as frequency.  The CTN DSMB is responsible for conducting 
periodic reviews of accumulating safety and efficacy data. It will determine whether there is 
support for continuation of the trial, or evidence that study procedures should be changed, or if 
the trial should be halted, for reasons relating to the safety of the study participants, the efficacy 
of the treatment under study, or inadequate trial performance (e.g., poor recruitment). 
17.20.2 
Adverse Events (AEs)  
This study is being conducted at the provider level using CDS prompts for evidence-based best 
practice standards related to OUD. As such, we are not trying to change the standard of care for 
OUD in primary care, but rather to help PCPs achieve this standard of care in their care of patients 
with OUD. To monitor usability, PCPs will be instructed to use the “Feedback” tab that displays in 
the OUD-CDS to let the study team know of any questions or concerns with the CDS. In particular, 
PCPs are trained to let the research team know via the Feedback tab in the CDS when their 

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
42 
 
 
clinical judgment led them to a different action than that suggested by the CDS. This automatically 
generates an email that is sent to Drs. Rossom and Sperl-Hillen and the programming team. The 
research team then discusses this feedback and any necessary actions, and connects with the 
PCP to answer the question, discuss steps taken to address the issue, or gather additional 
information and further trouble-shoot.  In addition, the emails of Drs. Rossom and Sperl-Hillen are 
listed on the CDS interface for providers, and PCPs are encouraged to contact us directly with 
any questions or concerns if they’d rather not use the feedback tab in the OUD-CDS. This PCP 
feedback will be provided to the DSMB at a frequency the DSMB requests. 
18.0 DATA MANAGEMENT  
Apart from data collected from the PCPs via surveys and feedback mechanisms, data for analysis 
will be largely collected by the OUD-CDS itself. This web-based tool houses the algorithms, 
communicates with and displays within the EMR, and stores data required to assess study 
objectives will be retained in a secure analytic database at HealthPartners Institute. These data, 
supplemented by Epic Clarity data, will be used to assess CDS use rates, MAT rates and referral 
patterns (described in secondary aims). We will not be using Advantage eClinical to collect or 
house data, and as this is a pilot study at one medical group, we will not use a centralized Data 
and Statistics Center.   
18.1 Study Timeline 
CTN Protocol Milestone 
Expected Date 
Completed 
Comments 
Protocol 
Development 
Concept finalized 
  
  
  
  
  
Submit protocol including DSMP and informed consent in 
preparation for DSMB meeting (also- site selection plan, leadership 
plan, proposed budget, single IRB plan, recruitment and retention 
plan) 
2/28/2017 
Final protocol and other 
materials due to CCTN at 
least one month prior to 
DSMB meeting.  
DSMB Meeting/Review 
3/27/2017 
*tentative target date, 
exploring what type of 
review required 
Full protocol reviewed and approved by NIDA 
4/18/2017 
* if significant changes 
are required following 
the DSMB meeting, 
dates will need to be 
adjusted 
Budget finalized 
5/31/2017 
  
Pilot Study Stages 
and Milestones 
Protocol approved by NIDA for implementation 
4/18/2017 
Assuming quick DSMB 
and CCTN feedback  
Lead Node initial Protocol IRB submission 
3/1/2017 
  
Initial review of all Case Report Forms by Lead Team 
N/A 
  
IRB Protocol approval date 
4/30/2017 
  

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
43 
 
 
CTN Protocol Milestone 
Expected Date 
Completed 
Comments 
Registration in clinicaltrials.gov website 
5/15/2018 
  
  
  
  
Stage 1 (CDS Build) 
6/6/2018 
  
Includes:   
Adapt OUD CDS whitepaper to CDS algorithms 
Program algorithms 
Create provider CDS interfaces 
Test algorithms in testing environment 
Recruit PCPs, administer baseline survey 
Pilot test/modify intervention with one provider with experience 
in OUD assessment and treatment, and several les experienced 
providers 
 
  
  
  
  
Phase 2 (CDS Deployment) 
 11/7/2018 
  
Includes: 
Go Live: Active intervention phase 
Monitor CDS use with feedback 
Update and/or troubleshoot algorithms 
 
  
  
  
  
Phase 3 (Analysis and Reporting) 
4/30/2019  
  
Includes: 
Conduct follow-up provider surveys 
Consolidate/analyze data to test hypotheses 
Dissemination activities, manuscript submission 
 
  
  
 
 
 
Final Study Report submitted to NIDA 
4/30/2019 
  
Provide study results via clinicaltrials.gov website 
(at the end of a trial) 
4/30/2019 
  
Primary outcome paper submitted to journal 
4/30/2019 
  
Primary outcome paper accepted 
8/31/2019 
  
Data posted on CTN's Public Data Share 
10/31/2020 
  
 
19.0 PUBLICATIONS AND OTHER RIGHTS  
The authors agree to follow NIH’s policy requiring all investigators to submit or have submitted for 
them to the National Library of Medicine’s PubMed Central an electronic version of their final peer-
reviewed manuscripts upon acceptance for publication, to be made publically available no later 
than 12 months after the official date of publication.   
 
 

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
44 
 
 
20.0 SIGNATURES  
 
SPONSOR’S REPRESENTATIVE (CCTN DESIGNEE) 
 
 
 
 
 
      
 
 
 
 
Printed Name 
 
Signature 
 
Date 
ACKNOWLEDGEMENT BY INVESTIGATOR: 
• 
I am in receipt of version X of the protocol and agree to conduct this clinical study in 
accordance with the design and provisions specified therein. 
• 
I agree to follow the protocol as written except in cases where necessary to protect the 
safety, rights, or welfare of a participant, an alteration is required, and the sponsor and IRB 
have been notified prior to the action. 
• 
I will ensure that the requirements relating to obtaining informed consent and institutional 
review board (IRB) review and approval in 45 CFR 46 are met. 
• 
I agree to personally conduct or supervise this investigation at this site and to ensure that 
all site staff assisting in the conduct of this study are adequately and appropriately trained 
to implement this version of the protocol and that they are qualified to meet the 
responsibilities to which they have been assigned. 
• 
I agree to comply with all the applicable federal, state, and local regulations regarding the 
obligations of clinical investigators as required by the Department of Health and Human 
Services (DHHS), the state, and the IRB. 
SITE’S PRINCIPAL INVESTIGATOR 
      
 
 
 
 
Printed Name 
 
Signature 
 
Date 
 
Clinical Site Name  
 
      
Node Affiliation  
 
      
 
 
 

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
45 
 
 
21.0 REFERENCES  
Alanis-Hirsch,K., Croff,R., Ford,J.H., Johnson,K., Chalk,M., Schmidt,L., McCarty,D., 2016. 
Extended-Release Naltrexone: A Qualitative Analysis of Barriers to Routine Use. J Subst. 
Abuse Treat., 62, 68-73. 
Alford,D.P., LaBelle,C.T., Kretsch,N., 2011. Collaborative care of opioid-addicted patients in 
primary care using buprenorphine: Five-year experience. Arch Intern Med, 171, 425-431. 
Ammenwerth E, Schnell-Inderst P & Hoerbst A. (2012). The impact of electronic patient portals 
on patient care: a systematic review of controlled trials. J Med Internet Res, 14(6), e162. doi: 
10.2196/jmir.2238 
Arfken,C.L., Johanson,C.E., di,M.S., Schuster,C.R., 2010. Expanding treatment capacity for 
opioid dependence with office-based treatment with buprenorphine: National surveys of 
physicians. J Subst. Abuse Treat., 39, 96-104. 
ASAM. 'The ASAM National Practice Guideline for the Use of Medications in the Treatment of 
Addiction Involving Opioid Use.'  2015.  http://www.asam.org/docs/default-source/practice-
support/guidelines-and-consensus-docs/asam-national-practice-guideline-
supplement.pdf?sfvrsn=24. Accessed February 3, 2017. 
Barry,D., Irwin,K., Jones,E., Becker,W., Tetrault,J., Sullivan,L., Hansen,H., O'Connor,P., 
Schottenfeld,R., Fiellin,D., 2009. Integrating Buprenorphine Treatment into Office-based 
Practice: a Qualitative Study. J Gen Intern Med, 24, 218-225. 
Birnbaum,H.G., White,A.G., Schiller,M., Waldman,T., Cleveland,J.M., Roland,C.L., 2011. 
Societal costs of prescription opioid abuse, dependence, and misuse in the United States. Pain 
Med, 12, 657-667. 
Centers for Disease Control and Prevention, 2012. CDC grand rounds: Prescription drug 
overdoses -- a U.S. epidemic. MMRW, 61, 10-13. 
Cochran, B. N., A. Flentje, N. C. Heck, J. Van Den Bos, D. Perlman, J. Torres, R. Valuck, and J. 
Carter. 2014. 'Factors predicting development of opioid use disorders among individuals who 
receive an initial opioid prescription: mathematical modeling using a database of commercially-
insured individuals', Drug Alcohol Depend, 138: 202-8. 
Cornish R, Macleod J, Strang J, Vickerman P, Hickman M. Risk of death during and after opiate 
substitution treatment in primary care: prospective observational study in UK General Practice 
Research Database. BMJ. 2010 Oct 26;341:c5475.  
 
Coviello,D.M., Cornish,J.W., Lynch,K.G., Boney,T.Y., Clark,C.A., Lee,J.D., Friedmann,P.D., 
Nunes,E.V., Kinlock,T.W., Gordon,M.S., Schwartz,R.P., Nuwayser,E.S., O'Brien,C.P., 2012. A 
multisite pilot study of extended-release injectable naltrexone treatment for previously opioid-
dependent parolees and probationers. Subst. Abus., 33, 48-59. 

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
46 
 
 
Desai JR, Sperl-Hillen JM, & O‘Connor PJ. (2013). Patient preferences in diabetes care: 
overcoming barriers using new strategies. Journal of Comparative Effectiveness Research, 2(4), 
351-354. doi: 10.2217/cer.13.36 
DHHS (Department of Health and Human Services, Assistant Secretary for Planning and 
Evaluation, Office of Disability, Aging and Long-Term Care Policy)(2013).  Review of 
medication-assisted treatment guidelines and measures for opioid and alcohol use. Accessed 
Feb 6, 2017.  https://aspe.hhs.gov/sites/default/files/pdf/205171/MATguidelines.pdf 
Dimitropoulos L. (2014). Health IT Research Priorities To Support the Health Care Delivery 
System of the Future. (Prepared for the Agency for Healthcare Research and Quality under 
Contract No. 290-2009-00023-I.). AHRQ Publication No. 14-0072-EF. Rockville, MD,. 
Egan,J., Casadonte,P., Gartenmann,T., Martin,J., McCance-Katz,E., Netherland,J., Renner,J., 
Weiss,L., Saxon,A., Fiellin,D., 2010. The Physician Clinical Support System-Buprenorphine 
(PCSS-B): a Novel Project to Expand/Improve Buprenorphine Treatment. J Gen Intern Med, 25, 
936-941. 
Gilmer TP, P. J. O'Connor, J. M. Sperl-Hillen, W. A. Rush, P. E. Johnson, G. H. Amundson, . . . 
H. L. Ekstrom. (2012). Cost-Effectiveness of an Electronic Medical Record Based Clinical 
Decision Support System. Health Serv Res. doi: 10.1111/j.1475-6773.2012.01427. 
Grant,B.F., Saha,T.D., Ruan,W.J., Goldstein,R.B., Chou,S.P., Jung,J., Zhang,H., Smith,S.M., 
Pickering,R.P., Huang,B., Hasin,D.S., 2016. Epidemiology of DSM-5 Drug Use Disorder: 
Results From the National Epidemiologic Survey on Alcohol and Related Conditions-III. JAMA 
Psychiatry, 73, 39-47. 
Hutchinson,E., Catlin,M., Andrilla,C.H., Baldwin,L.M., Rosenblatt,R.A., 2014. Barriers to primary 
care physicians prescribing buprenorphine. Ann. Fam. Med, 12, 128-133. 
Kharbanda EO, J. D. Nordin, A. R. Sinaiko, H. L. Ekstrom, J. M. Stultz, N. E. Sherwood, . . . P. 
J. O'Connor. (2015). TeenBP: Development and Piloting of an EHR-Linked Clinical Decision 
Support System to Improve Recognition of Hypertension in Adolescents. EGEMS (Wash DC), 
3(2), 1142. doi: 10.13063/2327-9214.1142 
Kunins,H.V., Sohler,N.L., Giovanniello,A., Thompson,D., Cunningham,C.O., 2012. A 
Buprenorphine Education and Training Program for Primary Care Residents: Implementation 
and Evaluation. Substance Abuse, 34, 242-247. 
Liebschutz,J.M., Crooks,D., Herman,D., 2014. Buprenorphine treatment for hospitalized, opioid-
dependent patients: A randomized clinical trial. JAMA Internal Medicine, 174, 1369-1376. 
Lo-Ciganic WH, Gellad WF, Gordon AJ, Cochran G, Zemaitis MA, Cathers T, Kelley D, 
Donohue JM. Association between trajectories of buprenorphine treatment and emergency 
department and in-patient utilization. Addiction. 2016 May;111(5):892-902.  
 
McNeely J, Wu LT, Subramaniam G, Sharma G, Cathers LA, Svikis D, Sleiter L, 

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
47 
 
 
Russell L, Nordeck C, Sharma A, O'Grady KE, Bouk LB, Cushing C, King J, Wahle A, Schwartz 
RP. Performance of the Tobacco, Alcohol, Prescription Medication, and Other Substance Use 
(TAPS) Tool for Substance Use Screening in Primary Care Patients. Ann Intern Med. 2016 Nov 
15;165(10):690-699. doi: 10.7326/M16-0317. PubMed PMID: 27595276; PubMed Central 
PMCID: PMC5291717. 
 
Mohlman MK, Tanzman B, Finison K, Pinette M, Jones C. Impact of Medication-Assisted 
Treatment for Opioid Addiction on Medicaid Expenditures and Health Services Utilization Rates 
in Vermont. J Subst Abuse Treat. 2016 Aug;67:9-14. doi: 10.1016/j.jsat.2016.05.002. PubMed 
PMID: 27296656. 
Moore,B.A., Fiellin,D.A., Barry,D.T., Sullivan,L.E., Chawarski,M.C., O'connor,P.G., 
Schottenfeld,R.S., 2007. Primary care office-based buprenorphine treatment: comparison of 
heroin and prescription opioid dependent patients. J Gen Intern Med, 22, 527-530. 
Netherland,J., Botsko,M., Egan,J.E., Saxon,A.J., Cunningham,C.O., Finkelstein,R., 
Gourevitch,M.N., Renner,J.A., Sohler,N., Sullivan,L.E., Weiss,L., Fiellin,D.A., 2009. Factors 
affecting willingness to provide buprenorphine treatment. J Subst. Abuse Treat., 36, 244-251. 
O'Connor P. (2011). Opportunities to Increase the Effectiveness of EHR-Based Diabetes 
Clinical Decision Support. Appl Clin Inform, 2(3), 350-354. doi: 10.4338/ACI-2011-05-IE-0032 
O'Connor P, J. R. Desai, J. C. Butler, E. O. Kharbanda, & J. M. Sperl-Hillen. (2013). Current 
status and future prospects for electronic point-of-care clinical decision support in diabetes care. 
[Research Support, Non-U.S. Gov't]. Curr Diab Rep, 13(2), 172-176. doi: 10.1007/s11892-012-
0350-z 
O'Connor PJ, Sperl-Hillen JM, Rush WA, Johnson PE, Amundson GH, Asche SE, Gilmer TP. 
(2011). Impact of Electronic Health Record Clinical Decision Support on Diabetes Care: A 
Randomized Trial. Ann Fam Med, 9(1), 12-21. doi: 10.1370/afm.1196 
Roshanov PS, N. Fernandes, J. M. Wilczynski, B. J. Hemens, J. J. You, S. M. Handler, R. B. 
Haynes. (2013). Features of effective computerised clinical decision support systems: meta-
regression of 162 randomised trials. Research Support, Non-U.S. Gov't]. BMJ, 346, f657. doi: 
10.1136/bmj.f657 
Ross TR, Ng D, Brown JS, Pardee R, Hornbrook MC, Hart G, Steiner JF.  The HMO Research 
Network Virtual Data Warehouose: A Public Data Model to Support Collaboration.  eGEMs 
2014.   
Rowe,T.A., Jacapraro,J.S., Rastegar,D.A., 2012. Entry into primary care-based buprenorphine 
treatment is associated with identification and treatment of other chronic medical problems. 
Addict. Sci. Clin. Pract., 7, 22. 
 

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
48 
 
 
Schackman,B., Leff,J., Polsky,D., Moore,B., Fiellin,D., 2012. Cost-Effectiveness of Long-Term 
Outpatient Buprenorphine-Naloxone Treatment for Opioid Dependence in Primary Care. J Gen 
Intern Med, 27, 669-676. 
Soeffing,J.M., Martin,L.D., Fingerhood,M.I., Jasinski,D.R., Rastegar,D.A., 2009. Buprenorphine 
maintenance treatment in a primary care setting: Outcomes at 1 year. Journal of Substance 
Abuse Treatment, 37, 426-430. 
Sperl-Hillen JM, Averbeck B, Palattao K, Amundson J, Rush B, & O'Connor PJ. (2010). 
Outpatient EHR-Based Diabetes Clinical Decision Support That Works: Lessons Learned From 
Implementing Diabetes Wizard. Diabetes Spectrum, 23(3), 150-154. 
Substance Abuse and Mental Health Services Administration. Results from the 2007 National 
Survey on Drug Use and Health: National Results. DHHS Publication No. SMA 08-4343. 2008. 
Rockville, MD, Office of Applied Studies. NSDUH Series H-34.  
Substance Abuse and Mental Health Services Administration. Treatment episode data set - 
admissions (TEDS-A). http://wwwdasis.samhsa.gov/webt/quicklink/US09.htm. 2012.  
Substance Abuse and Mental Health Services Administration. Results from the 2013 National 
Survey on Drug Use and Health: Summary of National Findings. HHS Publication No. (SMA) 
14-4863. 2014. Rockville, MD, Office of Applied Studies. NSDUH Series H-48.  
VA.  Va/Dod Clinical Practice Guideline for the Management of Substance Use Disorders.  
2015.  http://www.healthquality.va.gov/guidelines/MH/sud/VADoDSUDCPGRevised22216.pdf 
Accessed February 3, 2017.   
Walley,A., Alperen,J., Cheng,D., Botticelli,M., Castro-Donlan,C., Samet,J., Alford,D., 2008. 
Office-Based Management of Opioid Dependence with Buprenorphine: Clinical Practices and 
Barriers. J Gen Intern Med, 23, 1393-1398. 
Weiss,L., Netherland,J., Egan,J.E., Flanigan,T.P., Fiellin,D.A., Finkelstein,R., Altice,F.L., 2011. 
Integration of buprenorphine/naloxone treatment into HIV clinical care: lessons from the 
BHIVES collaborative. J Acquir. Immune. Defic. Syndr., 56 Suppl 1, S68-S75. 
WHO (World Health Organization). Opioid overdose: Preventing and reducing opioid overdose 
mortality. UNODC/WHO discussion paper. www.unodc.org/docs/treatment/overdose.pdf. 2013.   
 
 
 
 
 

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
49 
 
 
22.0 APPENDIX A: ADVERSE EVENT REPORTING AND PROCEDURES  
This study is being conducted at the provider level using CDS prompts for evidence-based best 
practice standards related to OUD. As such, we are not trying to change the standard of care for 
OUD in primary care, but rather to help PCPs achieve this standard of care in their care of patients 
with OUD. To monitor usability, PCPs will be instructed to use the “Feedback” tab that displays in 
the OUD-CDS to let the study team know of any questions or concerns with the CDS. In particular, 
PCPs are trained to let the research team know via the Feedback tab in the CDS when their 
clinical judgment led them to a different action than that suggested by the CDS. This automatically 
generates an email that is sent to Drs. Rossom and Sperl-Hillen and the programming team. The 
research team then discusses this feedback and any necessary actions, and connects with the 
PCP to answer the question, discuss steps taken to address the issue, or gather additional 
information and further trouble-shoot. In addition, the emails of Drs. Rossom and Sperl-Hillen are 
listed on the CDS interface for providers, and PCPs are encouraged to contact us directly with 
any questions or concerns if they’d rather not use the feedback tab in the OUD-CDS.   
 
 

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
50 
 
 
23.0 APPENDIX B: DATA AND SAFETY MONITORING PLAN  
23.1 Brief Study Overview 
This study aims to program and pilot test an opioid use disorder (OUD) clinical decision support 
(CDS) tool in primary care clinics at HealthPartners and Park Nicollet medical groups. The CDS 
is based on the NIDA-Blending Initiative white paper, “Clinical Decision Support for Opioid Use 
Disorders: Working Group Report,” and will be programmed for use in an electronic medical 
record (EMR) and tested by consented primary care providers (PCPs) across the healthcare 
system. Success of these aims will be measured by high PCP use and satisfaction rates. The 
secondary objectives of this pilot study are to evaluate the usefulness of the tool by comparing 
pre- and post-intervention OUD case-finding, medication-assisted therapy (MAT) and referral 
patterns for PCPs with and without CDS access.  
23.2 Oversight of Clinical Responsibilities 
Site Principal Investigator 
The Lead Investigators are responsible for study oversight, including ensuring human research 
subject protection by designating appropriately qualified, trained research staff and medical 
clinicians to assess, report, and monitor adverse events.  
CCC Medical Monitor 
It is not anticipated that a CCC Medical Monitor will be assigned to this pilot study, although this 
will be determined by the DSMB. Additionally, Drs. Rossom and Sperl-Hillen and the programming 
team will monitor all PCP feedback and make adjustments to the CDS as clinically indicated. 
Data and Safety Monitoring Board (DSMB) 
An independent CTN DSMB will monitor this study.  The DSMB will communicate regarding what 
type of reports will be needed, as well as frequency.  The CTN DSMB is responsible for conducting 
periodic reviews of accumulating safety and efficacy data. It will determine whether there is 
support for continuation of the trial, or evidence that study procedures should be changed, or if 
the trial should be halted, for reasons relating to the safety of the study participants, the efficacy 
of the treatment under study, or inadequate trial performance (e.g., poor recruitment). 
 
Quality Assurance (QA) Monitoring 
It is not anticipated that this study will be assigned a NIDA CCTN CCC monitor. Quality assurance 
monitoring will be accomplished via pre-implementation testing to confirm that the CDS is 
collecting and storing the data as expected. After implementation and throughout the 6-month 
pilot phase, data will be repeatedly tested to ensure all data elements necessary for analysis are 
collected on secure servers, and Dr. Crain will conduct periodic test analyses to ensure that all of 
the data she requires for analysis are complete. Additionally, Drs. Rossom and Sperl-Hillen will 
conduct periodic chart audits to ensure that data collected by the CDS is accurate and complete.  
 
 

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
51 
 
 
23.3 Management of Risks to Participants 
Confidentiality 
Confidentiality of participating PCPs will be secured by the use of study codes for identifying 
participants on CRFs, and secure storage of any documents that have participant identifiers on 
site, as well as secure computing procedures for entering and transferring electronic data. The 
documents or logs linking the study codes with the study participant on site will be kept locked 
separately from the study files and the medical records. PCPs will receive reports of their use of 
the OUD-CDS, and these will not be confidential. Additionally, PCPs will be asked to provide 
feedback on the OUD-CDS, either by using the feedback tab in the CDS or via email, and this 
feedback will not be confidential. No identifying information will be disclosed in publications or 
presentations. 
Information Meeting Reporting Requirements 
The consent form will specifically state the types of information that are required for reporting 
and that the information will be reported as required.  
Participant Protection 
This is a pilot study that will provide OUD-CDS to approximately half of consented PCPs. Practice 
decisions made during the course of any patient encounters will not be reported to the practice 
group, thus preventing adverse employment or incentive-based decisions being made solely as 
a result of study participation.   
 
Pregnancy 
Not applicable.  
Study Specific Risks 
There is a small but important risk that the OUD-CDS could provide the wrong treatment advice 
at the wrong time. As with other clinical decision tools, the Opioid Wizard makes suggestions for 
patient care that are meant to supplement but not supersede clinical judgment. PCPs can choose 
to follow or not follow the guidance of the CDS at any given time in any given patient encounter. 
PCPs will be trained to let the research team know via the Feedback tab in the CDS when their 
clinical judgment leads them to a different action than that suggested by the CDS. These events 
will be monitored by the treatment team and the CDS algorithms adjusted if there are found to be 
errors. Every clinical encounter requires medical judgment and poses some element of risk to 
patients. In the situation of a PCP who is unfamiliar or uncomfortable with OUD, use of the CDS 
will likely make care safer by providing suggestions to screen and assess for OUD using validated 
tools, and to encourage referrals when patients are classified as high risk. We will not be 
encouraging buprenorphine use in non-certified providers, and this will be reinforced thoroughly 
in provider training on the CDS. For buprenorphine-certified providers, the use of the CDS may 
improve the likelihood of using MAT in high risk situations; however, the risks of MAT are generally 
considered lower than untreated OUD in high-risk situations.   

NIDA CTN Protocol -0076-ot 
Protocol Version 1.2 
COMPUTE 
May 8, 2018 
 
 
52 
 
 
23.4 Data Management Procedures 
As this is a single-site pilot study, we will not be using a centralized Data and Statistics Center or 
Advantage eClinical to collect or house data. All data will be stored on secure servers behind 
multiple firewalls at HealthPartners Institute in a secure project folder only accessible by 
authorized study personnel.   
23.4.1 
Data and Statistics Center Responsibilities 
Not applicable.   
23.5 Data Collection and Entry 
Data from surveys completed by PCPs at baseline and 6-months and PCP CDS use will be 
collected and stored on a secure server protected by multiple firewalls at HealthPartners Institute, 
only accessible by authorized personnel only after entering highly secure system passwords.   
23.6 Data Monitoring, Cleaning and Editing 
Data will be monitored, cleaned and edited at HealthPartners Institute on secure servers and 
accessible only by study personnel.  
23.7 Data Lock and Transfer 
Not applicable for this single site pilot study.