Pilot Test of a Substance Use Treatment and Recovery Team (START) for Medical Inpatients With Opioid and Alcohol Use Disorders
Phase: NA
Conditions: Opioid-use Disorder, Opioid-Related Disorders, Alcohol Use Disorder, Alcohol-Related Disorders
Sponsor: RAND

 
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Pilot Test of a Substance Use Treatment and Recovery Team (START)  
for Medical Inpatients with Opioid and Alcohol Use Disorders 
 
 
Version 3.1  
08APRIL2021 
 
 
Principal Investigators: 
Allison Ober (RAND) 
 Itai Danovitch, MD (Cedars-Sinai) 
 
 
 
Cedars-Sinai Medical Center 
NCT04314648 
 
 
 

 
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TABLE OF CONTENTS  
 
PROTOCOL SUMMARY ............................................................................................................................. 3 
GENERAL INFORMATION ......................................................................................................................... 3 
1.0 BACKGROUND, RATIONALE ................................................................................................................ 3 
2.0 STUDY OBJECTIVES ............................................................................................................................. 4 
3.0 STUDY POPULATION .......................................................................................................................... 4 
 
3.1 SELECTION OF THE STUDY POPULATION ................................................................................ 4 
 
3.2 INCLUSION CRITERIA ............................................................................................................... 5 
 
3.3 EXCLUSION CRITERIA ............................................................................................................... 5 
 
3.4 SUBJECT SCREENING AND ENROLLMENT ............................................................................... 5 
 
3.5 SUBJECT RECRUITMENT .......................................................................................................... 5 
4.0 STUDY DESIGN AND METHODS .......................................................................................................... 7 
5.0 DATA COLLECTION AND MANAGEMENT ......................................................................................... 12 
 
5.1 DATA PROCUREMENT ........................................................................................................... 12 
 
5.2 TIME PERIOD OF DATA UNDER REVIEW ............................................................................... 12 
 
5.3 VARIABLES COLLECTED ......................................................................................................... 12 
 
5.4 SOURCE DOCUMENTS ........................................................................................................... 15 
 
5.5 DATA COLLECTION AND STORAGE ........................................................................................ 15 
 
5.6 CONFIDENTIALITY AND SECURITY OF DATA .......................................................................... 15 
6.0 DATA AND SAFETY MONITORING .................................................................................................... 16 
 
6.1 DATA AND SAFETY MONITORING PLAN ................................................................................ 16 
 
6.2 QUALITY CONTROL AND QUALITY ASSURANCE .................................................................... 19 
7.0 STATISTICAL CONSIDERATIONS ........................................................................................................ 19 
 
7.1 STUDY OUTCOME MEASURES ............................................................................................... 19 
 
7.2 SAMPLE SIZE CONSIDERATIONS ............................................................................................ 19 
8.0 APPENDICES ..................................................................................................................................... 20 
9.0 REFERENCES ..................................................................................................................................... 22 
 
 
 

 
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PROTOCOL SUMMARY  
Purpose and Knowledge to be 
Gained 
 
• The purpose the research is to conduct a pilot test of a 
substance use treatment and recovery team (START) for 
medical inpatients with opioid and alcohol use disorders 
• If the aims of the research are achieved, we hope to improve 
Medication-Assisted-Treatment (MAT) initiation and linkage to 
follow-up care and clinical outcomes, and, ultimately, reduce 
90-day readmission rates for inpatients with OAUDs 
Research Procedures 
 
The primary research procedures are  
• Baseline interview with patient 
• 1-month follow-up interview with patient 
• Provider interviews 
Subject Population 
• Inpatients at CSMC 18 or older who screen positive for 
moderate to severe OAUDs 
Duration 
• The study includes 2 visits (Baseline interview, 1-month follow-
up interview).  
• The total study duration is 1 month 
  
GENERAL INFORMATION  
CSMC Co-Investigators  
Waguih Ishak, MD  
Teryl Nuckols, MD 
Bradley Rosen, MD 
Rebecca Hedrick, MD 
Responsibilities include consenting of subjects and delivery of 
intervention. 
Sponsor/Funder 
NIDA (National Institute on Drug Abuse) 
Collaborating Institutions 
Involved in the Research 
Allison Ober, MSW, PhD, Behavioral Scientist (PI at this site) 
RAND Corporation, 1776 Main Street, Santa Monica, CA  90407; 
310-393-0411 ext. 6639, No research activities will be conducted 
at this site. All research activities will be conducted at CSMC. 
 
1.0 BACKGROUND, RATIONALE  
• 
There is a large unmet need for substance-use disorder (SUD) treatment in the U.S. In 2015, 20.4 
million adults in the U.S. (8.4 % of all adults) needed treatment for an illicit drug or alcohol use 
problem; of these, 18.1 million did not receive it. 1  The consequences of untreated SUDs are 
enormous: premature death, billions of dollars in avoidable health care and criminal justice 
costs, decreased economic productivity, individual suffering, and long-term harmful effects on 
families and communities. 2-6  Opioid and alcohol use disorders (OAUDs) are of particular 
concern because of high rates of morbidity, mortality, hospitalizations and readmissions, 7-10   
and because of the increasing incidence of opioid-use disorders (OUD) and associated 
consequences from the non-medical use of prescription opioids.11   Medication-Assisted-
Treatment (MAT) is available for OAUDs, but less than a quarter of publicly funded treatment 
programs12 and fewer than half of private sector treatment programs offer MAT. 
• 
Despite high prevalence, few inpatients with OAUDs receive evidence-based treatments while in 
the hospital.13-15  Most physicians and other providers in acute hospital settings are not trained 
to assess or manage patients with OAUDs, 16  contributing to low rates of OAUD identification 

 
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and treatment initiation.17-21   Pharmacotherapies to address AUDs (acamprosate, oral and 
injectable naltrexone, and disulfiram) and OUDs (buprenorphine/naloxone, methadone, and 
oral and injectable naltrexone) are effective for use across medical settings22-28  but are seldom 
administered in hospitals or recommended as part of follow-up care. 29,30  New research 
demonstrates that initiating buprenorphine/naloxone in the emergency department with 
follow-up in primary care for patients with OUDs can increase SUD treatment entry and 
abstinence,31  and that inpatients with complications from OUDs are amenable to initiating 
medication in the hospital and being linked with follow-up care.32  The current standard of care 
for hospitalized patients with OAUDs is screening, brief intervention outcomes for people with 
moderate to severe AUDs or for people with OUDs.33,34,16,35  Two possible reasons are that SBIRT 
does not incorporate MAT initiation or address the needs of those needing more than a brief 
intervention prior to referral. Barriers to initiating MAT for hospitalized patients may include 
lack of OAUD treatment expertise on the medical team and absence of a patient-centered, 
measurement- and population-based system for assessing and treating patients with OAUDs. 
Embedding a collaborative care team (START) for inpatients with OAUDs within an existing 
hospital consultation-liaison psychiatry service could improve MAT initiation and linkage to 
follow-up care and clinical outcomes, and, ultimately, reduce 90-day readmission rates.  
• 
Collaborative care is a systematic approach to organizing and coordinating care for patients with 
complex conditions.36 Based on the Chronic Care Model developed by Wagner et al.,37  
collaborative care addresses barriers to assessing and providing comprehensive, patient-
centered care and leads to improved care and patient outcomes.38,39  Collaborative care has 
four core attributes: (1) Team-driven: a behavioral health team is integrated into the medical 
team to provide coordinated care and develop patient-centered care plans; (2) Population-
focused: the team provides care to a defined group of patients; (3) Measurement-based: The 
team 1 of 12 uses systematic, patient-reported measures to drive clinical decision-making; and 
(4) Evidence-based: the team facilitates use of evidence-based practices in the clinical setting.40-
43  Collaborative care approaches have enhanced integration of specialized care for depression 
and other chronic diseases into busy medical practices where providers do not have time or 
expertise to fully assess or manage care for patients with complex chronic conditions,36  but 
they have not been tested for OAUDs in the inpatient setting. Moreover, recent research on the 
experience of medical inpatients identified with SUDs suggests the importance of access to MAT 
while in the hospital and coordinated care post-discharge.44   
2.0 STUDY OBJECTIVES  
Primary Objectives: 
Test if embedding a collaborative care team called START the substance use treatment and 
recovery team (START) for inpatients with OAUDs within an existing hospital consultation-liaison 
psychiatry service could improve MAT initiation and linkage to follow-up care and clinical 
outcomes, and, ultimately, reduce 90-day readmission rates.  
 
Secondary Objective: 
In a larger study, subsequent to the pilot, we will test 90-day readmission rates and whether 
lower readmission rates are mediated by MAT initiation and linkage to follow-up care. 
 
3.0 STUDY POPULATION  
 
3.1 SELECTION OF THE STUDY POPULATION 
CSMC inpatient population. Approximately 80 patients will be enrolled over the course of 5 
months. Additionally, we will conduct semi-structured in-person or remote (telephone or 

 
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video) interviews with up to 10 physicians, 10 nurses, and 10 social workers from within the 
hospital who treat START patients during the pilot period, as well as up to 10 telephone 
interviews with follow-up providers who received patients referred from the hospital during 
the pilot period. 
 
3.2 INCLUSION CRITERIA 
1. Inpatient at CSMC 
2. Age 18 and older 
3. Screens positive for moderate to severe OAUDs based on the alcohol and opioid 
questions on the World Health Organization (WHO) Alcohol, Smoking, and Substance 
Involvement Screening test (ASSIST).45  Patients with scores >10 for alcohol or >3 for 
opioid use will be eligible for the study 
4. Speaks English as primary language 
5. Willing to participate in, and able to provide contact information for, telephone 
follow-up calls and follow-up interview 
6. Able to provide informed consent 
 
3.3 EXCLUSION CRITERIA  
1. Currently receiving FDA-approved medication treatment for an opioid or alcohol use 
disorder 
2. Life expectancy of <6 months 
 
3.4 SUBJECT SCREENING AND ENROLLMENT 
• 
Data for screening will be procured using a daily data extract of potentially eligible 
subjects (variables include demographics, alcohol and/or opioid history and screenings). 
• 
The Principal Investigator, Co-Investigators, and approved study staff will have access to 
these records. 
3.5 SUBJECT RECRUITMENT 
The study will recruit adults with moderate to severe OAUDs who are admitted to the 
inpatient medical center. Patients will be identified through physician referral, or through 
review of an existing daily EPIC workbench report of opioid and alcohol misuse (Daily 
Report). The approved CSMC study staff will identify patients with probable moderate-to-
severe OAUD through a daily printout from EPIC or by direct provider referrals from 
physicians and social workers (see Figure 1 below).  
• 
The CSMC approved study staff will identify patients with probable moderate-to-
severe OAUD through a Daily Report or by direct provider Medical Staff referrals.  
• 
Once a potential patient is identified, someone from the study team will contact the 
attending physician, briefly explain the study, and ask the physician for permission to 
contact the patient.  
• 
If the attending physician agrees, the physician or someone from the medical team 
will explain the study to the patient and ask for their permission to be visited by study 
staff. 
• 
Advertising and recruitment materials: 
For providers: 
o Study Physician Flyer 
o Physician Screening Card 
o Physician Recruitment Letter 

 
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For patients: 
o Physician to Patient Letter (Dear Patient Letter) to be provided by the treating 
physicians to patients deemed eligible for the study.

 
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Figure 1: Recruitment, Enrollment, and Randomization Diagram 
 

 
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4.0 STUDY DESIGN AND METHODS 
• 
Eligibility screening - Assessments, demographics (conducted in person or remotely) 
• 
Informed Consent, if eligible (to be obtained in person either on paper or electronically using an 
approved platform or remotely using an approved platform)  
• 
Enrollment - the CSMC study staff will enroll consented, eligible patients.  
• 
Baseline interview - after enrollment, the CSMC approved study staff will conduct an in-person 
or remote 30-40-minute baseline interview. Interview data will be recorded on a tablet or 
computer into a web-based survey system (REDCap). Patients will be compensated with a $50 
Forte payment card (given in person or mailed).  
• 
Randomization - following consent and the baseline interview, the CSMC approved study staff 
will randomize the patient to the START or UC arm using REDCap. 
• 
All patients will be given patient education materials on alcohol and/or opioid use disorder, as 
well as harm reduction materials (OUD only). If the visit is remote, the research team will give 
these materials to a member of the medical team to deliver to the patient or place them in the 
patient’s room. 
• 
1-month post discharge follow-up interview - the CSMC approved study staff will conduct a 
follow-up interview by telephone 1-month after the patient is discharged from the hospital. 
Patients will receive $50 loaded onto their existing Forte payment card for participation. 
 
The components of the START workflow process are as follows (also shown in Figure 2):  
1. Triage (Care Manager CM and Addiction Medicine Specialist AMS):  
The CM assesses the patient for acute biomedical needs related to the OAUD. The AMS 
addresses acute biomedical needs (e.g. facilitates withdrawal management).   
2. Engage, assess, plan (CM and AMS) (conducted in person or remotely based on 
circumstances): 
3. If there is not an urgent need for medical intervention or after the urgent medical need is 
addressed, the CM and/or AMS:   
o 
engages with the patient (CM and AMS)  
o 
conducts a diagnostic and biopsychosocial assessment (CM)   
o 
conducts a complete biomedical assessment and addresses comorbidities (AMS)  
o 
delivers the brief negotiated interview (BNI), an evidence-based intervention, to 
assess to increase readiness and develops a plan for initiating evidence-based 
treatment for OAUD (MAT) and/or psychosocial treatment) during and after the 
hospital stay (CM)  
o 
ensures the patient understands the follow-up plan and addresses barriers (CM). 
4. Treat (AMS) The AMS:  
o 
facilitates MAT initiation 
o 
facilitates psychosocial treatment for the substance use disorder, if indicated 
and available.  
5. Communicate and Coordinate (CM, AMS)  
o 
The CM and AMS communicate with each other to continue care through one-
month (or more) after the patient is discharged.   
o 
The CM and AMS communicate with the patient and medical team, and, when 
appropriate, the patient’s family and outpatient providers.  
6. Follow-up (CM):  

 
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o 
The CM calls the patient once a week for 1 month after the patient is discharged 
from the hospital to assess whether the patient is following through with the 
discharge plan.  
o 
The CM may also call outpatient providers to determine if the patient linked to 
care and has encountered barriers.  
7. 
Monitor (AMS):  
o 
The AMS continues to monitor the patient after discharge through the CM’s 
follow-up work.  

 
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Figure 2: START Workflow Diagram 
 

 
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INNOVATION 
 
• This proposed study identifies the inpatient hospital stay as a new opportunity to initiate MAT and 
link patients with follow-up care for their OAUD. Hospitalization is an opportune time to initiate 
MAT and provide linkage to follow-up care for patients with either an OUD or AUD.16  To our 
knowledge, no experimental studies have focused on initiating MAT and providing focused 
discharge planning and follow-up monitoring for hospitalized patients with either an AUD or OUD. 
• The study offers a new model—a consultation-liaison service-based START—for improving care 
processes for hospitalized patients with OAUDs. Hospitals have extensive experience using care 
managers to improve in-hospital and follow-up care for several patient populations at high risk of 
readmission,46,47  including acute medical patients,48 and many have a consultation-liaison service 
to support the medical team with patients in need of behavioral health care. However, to our 
knowledge, there are no experimental studies of care management strategies in general or 
collaborative care models to improve outcomes for inpatients with OAUDs. Further, leveraging the 
existing consultation-liaison service is an innovative and generalizable approach to managing the 
large number of hospital inpatients with untreated OAUDs without burdening inpatient physicians 
and unit case managers who may not have the expertise or time to prescribe medications or 
resolve barriers to OAUD-focused discharge and follow-up. The consultation-liaison service-based 
START is a novel, comprehensive program for facilitating MAT initiation in the hospital and linking 
patients to follow-up care for two of the most common SUDs among inpatients. 
• This study will provide several types of new knowledge: 
(1) Whether a START compared with usual care improves care for hospitalized patients with an 
OAUD. That is, whether START leads to improved initiation of medication and linkage to follow-
up care for patients who are admitted to the hospital, either for a problem related to their OAUD 
or for another medical issue.   
(2) Whether a START compared with usual care reduces substance use.
 
(3) Whether a START is feasible and acceptable with in the inpatient medical setting. These 
knowledge gains will provide invaluable, preliminary information on how to improve the quality 
of care for hospitalized patients with OAUD and on how to address an unmet need that has 
severe individual and societal consequences. The knowledge obtained in the study (and even 
more so in the larger, subsequent RCT) not only will benefit individual patients who participate in 
the study but also hospitals looking for a pragmatic and feasible way to improve OAUD care. On a 
societal level, providing a new way to identify and initiate treatment for patients with OAUD 
could fill a previous unmet need and bring down healthcare costs related to untreated OAUD. We 
believe that the long-term gains of the study, in terms of knowledge and substantive gains to the 
community, far exceed any risks for participants. 
 
 

 
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Table 2: Flowchart of Procedures 
 
LEGEND 
R = Research item/procedure done only for research purposes and covered by the study 
S = Standard of care item/procedure that is part of regular care and billed to the 
patient/insurance 
 
Footnotes: 
a. Only for patients randomized to the START intervention arm of the study. 
b. For both groups: Usual Care and Start intervention. Includes Brief Negotiated Interview and 
addiction focused discharge planning and follow-up. 
c. The START intervention utilizes established standard-of-care services and procedures (care 
manager, addiction medicine specialist, medication treatment, therapy, etc.) and helps 
integrate them into the patient’s care in a systematic way. It is this planned coordination 
and integration that are the intervention, not the services themselves. 
 
 
 
 
Research Procedures  
Baseline 
visit 
During course of 
hospital stay 
1-month post-
discharge 
Eligibility 
R 
 
 
Informed Consent 
R 
 
 
Randomization 
R 
 
 
Sociodemographic Data  
R 
 
 
Mental health symptoms (PHQ-9, GAD 7); pain 
(PEG); substance use (WHO ASSIST, NSDUH) 
consequences of use (SIP-AD), service 
utilization (NSDUH, GAIN), stigma (SASS) 
R 
 
R 
Satisfaction with START interventiona 
 
 
R 
Medication for alcohol or opioid use disorder b 
 
S 
 
Therapy for alcohol or opioid use disorder b 
 
S 
 
START Addiction Medicine Specialist (AMS) 
coordinates team-based carec 
 
R 
R 
START Care Manager (CM)c 
coordinates team-based care 
 
R 
R 

 
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• 
A list of written materials that will be part of the research is included in Appendices - section 
8.0 below. 
 
Behavioral Intervention  
The START Manual with a full description of the behavioral intervention is provided in a separate 
document. 
 
Surveys 
• Survey methodology – Patient baseline surveys will be conducted in person or remotely by 
the approved study staff and responses entered directly into the REDCap database using a 
mobile device or computer. Patient follow-up surveys will be conducted by the approved 
study staff via telephone.  
• Survey selection – validated surveys that are most relevant to the primary and secondary 
study outcomes and covariates. 
• Surveys are available only in English – only subjects fluent in English will be enrolled. 
• Surveys used are validated as listed in Table 2: Flowchart of Procedures. 
 
5.0 DATA COLLECTION AND MANAGEMENT 
 
5.1 DATA PROCUREMENT 
• 
Recruitment information will be procured through physician referral, or through 
review of an existing daily EPIC workbench report* of opioid and alcohol misuse. 
• 
Administrative outcomes will be procured through a monthly EPIC report.** 
• 
Patient Baseline Survey Measures will be procured through patient interviews and 
will be recorded on a tablet or computer into a web-based survey system (REDCap).  
• 
Some demographic and all diagnosis variables will be procured from eligibility 
screener conducted in REDCap. (Eligibility screener variables from all patients that 
screen will be used to assess study feasibility. Data from patients not enrolled in the 
study will be anonymous, i.e., they will not be linked to an MRN or any identifying 
information.) 
• 
Patient Follow-up Survey Measures will be procured through a telephone interview 
by 1-month after the patient is discharged from the hospital. During collection of 
contact information at the baseline visit, patients may opt-in to receive text message 
reminders about this interview. These reminders will be sent via Twilio SMS through 
REDCap and will not contain any identifying information regarding the patient or the 
specific study. 
• 
Provider Survey Measures will be procured through provider interviews and will be 
recorded and transcribed. 
 5.2 TIME PERIOD OF DATA UNDER REVIEW 
• 
Data will be collected prospectively at the following timepoints: Baseline interview 
(patient); 1-month follow-up interview (patient); Follow-up interview (providers) to 
be collected post-intervention, in the 3-4 months after the last patient has completed 
the study. 

 
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• 
Consent forms will be retained at CSMC for seven years after completion of the 
study. Linking files and identifiable information will be destroyed within a year after 
study completion.   A limited data set will be retained for five years after study 
completion to allow ample time for analysis and publication. 
 
 
5.3 VARIABLES COLLECTED  
• 
The following data points/variables will be collected:  
 
Baseline Measures: 
 
Variable 
Source Document 
Demographics 
• 
Age 
• 
Sex (Biological at Birth) 
• 
Gender (Identity) 
• 
Race/ethnicity 
• 
Housing status 
• 
Marital status 
• 
Income 
• 
Education 
Demographics Form 
Mental Health Symptoms  
• 
Depression 
• 
Anxiety 
 
PHQ-9 survey51,52   
GAD 7 survey53-55 
Pain intensity and frequency  
PEG56 
Alcohol/Opioid Diagnosis 
WHO ASSIST57 
30-day Alcohol/Opioid Use: National Survey on 
Drug Use and Health 30-day use questions  
Patient Survey (Adapted from NSDUH58) 
SUD Treatment Utilization 
Patient Survey (Adapted from NSDUH58) 
Healthcare Utilization Related to SUD 
Patient survey (Adapted from GAIN59) 
Employment 
Patient Survey 
Negative Consequences 
Short Inventory of Problems Alcohol and 
Drugs (SIP-AD)60 
Patient Experience of Stigma 
Adapted from Grosso et al. 2019.61 
Questions to assess stigma experience.  
Self- Stigma 
Substance Abuse Stigma Scale (SASS)62 
Receipt of START Intervention Components (Patient) 
 
START Intervention Received (Assessment, 
Engagement, Treatment/Discharge Planning);  
Length of Intervention (hours) 
START Patient Registry 
START Intervention Follow Up Received (Number 
of follow up calls made) 
START Patient Registry 

 
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Follow-up Survey Measures (Patient) 
 
Mental Health Symptoms  
• 
Anxiety 
• 
Depression  
PHQ-9 Survey51,52   
GAD 7 Survey53-55 
30-day Alcohol/Opioid Use: National Survey on 
Drug Use and Health 30-day use questions  
Patient Survey (Adapted from NSDUH58) 
SUD Treatment Utilization 
Patient Survey (Adapted from NSDUH58) 
Healthcare Utilization Related to SUD 
Patient survey (Adapted from GAIN59) 
Negative Consequences  
Short Inventory of Problems Alcohol and 
Drugs (SIP-AD)60 
Employment 
Patient Survey 
Patient Experience of Chronic Illness Care 
PACIC63 
Satisfaction with START intervention 
Patient Survey 
Provider Interviews (Provider) 
 
Acceptability/feasibility of START Intervention 
(Provider Interview Guide) 
Provider Interview Guide 
 
Outcome Measures: 
Outcome 
Measure, Assessment (Type of Variable) 
Data Source 
Primary Outcomes 
In-hospital MAT initiation 
Received an OAUD MAT between admission and 
discharge (Binary) 
CSMC admin data 
Linkage to follow-up care 
Received at least one visit post-discharge for 
MAT and/or psychosocial care for OAUD (Binary) 
Appointment dates 
1-month interview 
Past 30-day frequency of heavy 
drinking days and/or all days of any 
opioid use 
Days of use in the past 30 – Adapted National 
Survey of Drug Use and Health (NSDUH)58  
(Continuous) 
Baseline interview 
1-month interview 
Secondary Exploratory Outcome 
 
 
90-day readmission to CSMC 
Readmitted to CSMC up to 90-days after discharge 
during study period 
CSMC admin data 
Covariates 
Sociodemographics 
Gender, sex, age, race/ethnicity, income, 
education, occupational status, marital status, 
zip code, 
homelessness in past six months. 
Eligibility screener; 
Baseline interview 
OAUD diagnosis 
Moderate or Severe, ASSIST45   
Eligibility screener 
Pain Level 
Pain level between 1-10; Pain interference level 
between 1-10, PEG56  (Continuous) 
Baseline interview 
1-month interview 
Primary and secondary 
diagnosis (inpatient stay) 
Medical or mental health conditions as 
determined by the inpatient physician 
(Categorical) 
CSMC admin data 
Length of hospital stay 
Number of days of hospital stay (Continuous) 
CSMC admin data 
Intervention “dose”; exposure 
Amount time spent with patient (Continuous) 
START Registry 
Insurance 
Payer name 
CSMC admin data 

 
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*Daily EPIC Report Elements: 
 
• 
Demographics: Patient name; MRN; CSN; Sex; DOB 
• 
Hospital encounter data: Hospital admission date and time; Inpatient admission date and 
location; Reason for admission; Admission diagnosis; Admitting physician; Attending provider 
• 
Interpreter needed – exclusion criterion 
• 
Patient PCP 
• 
Homeless status 
• 
DRGs (Diagnosis Related Group): ICD10 F10 (Alcohol Use Disorders); F11 (Opioid Use Disorders); 
F19 (Other psychoactive substance use); Overdose 
• 
CIWA (Clinical Institute Withdrawal Assessment)  
• 
Flowsheet Data: RN Alcohol and Drug Screening Questions 
o CIWA Assessment 
o CIWA Score 
o Current alcohol usage information 
o Current drug usage information 
o Withdrawal risks 
• 
Blood alcohol test 
• 
Urine toxicology screen 
• 
Past Medication orders: Buprenorphine; Naloxone; Naltrexone; Disulfiram; Acamprosate; 
Topiramate 
• 
Social History: Alcohol usage; Drug usage 
 
**Monthly EPIC Report Elements 
 
• 
Demographics: MRN; Age; Age at encounter; Date of Birth; Sex; Race; Ethnicity; City; Zip Code 
• 
Hospital encounter data: Type; Dates; Disposition; Attending provider; PCP; Psychiatry consult; 
• 
Diagnoses during encounter: ICD 10s: F10-F19; Problem list items  
• 
CIWA Protocol and measure information 
• 
Inpatient and discharge medication information: Suboxone; Buprenorphine; Subutex; Methadone; 
Naltrexone; Naloxone; Disulfiram; Acamprosate; Topiramate; Gabapentin; Narcan; Naloxone. 
• 
Lab results: AST; ALT; GGT; Urine Toxicology Screen; Blood Alcohol Level 
• 
Flowsheet Data: RN Alcohol Screening Questions  
• 
Social History: Tobacco usage; Alcohol usage; Drug usage 
• 
Family history of substance use disorder 
• 
Notes: Physician, Nursing and Allied health Professional documentation 
• 
Hospital Utilization Metrics: Length of Stay; Inpatient admissions in prior 12 months; ED admissions 
in prior 12 months; Number of 30-day readmissions 
 
5.4 SOURCE DOCUMENTS 
• Paper source documents include the patient informed consent form, if collected on 
paper. All other patient information and data will be entered directly into the REDCap 
database via computer or mobile device. 
• Provider information will be collected via in-person or telephone interview which will 
be recorded and transcribed. There will be a NDA in place with the transcriber. The 

 
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transcriber will not be a part of the study team. With guidance from the Office of 
Research Administration, all appropriate agreements will be in place prior to the 
transcriber having any access to research materials. The interviews will take place only 
after the last patient has completed the study. 
5.5 DATA COLLECTION AND STORAGE  
• Patient data will be collected in hard copy and electronically, as previously described. 
All provider interviews will be recorded using a digitally-encrypted recorder and 
transcribed. There will be a Non-Disclosure Agreement in place with the transcriber. 
• Paper consent forms will be stored inside a locked cabinet or locked office. Electronic 
data will be stored in a secure REDCap database. Recorded interviews will be stored 
on a digitally-encrypted recorder. Transcribed interviews will be uploaded to a secure 
file transfer protocol (SFTP) program such as Kiteworks. 
• Only members of the study team will have access to study data. A limited date set will 
be transferred to RAND (collaborating institution) using SFTP programs and may 
include hospital and study visit dates, patient age, and patient zip codes. 
• Linking files and identifiable information will be destroyed within a year after study 
completion.   A limited data set will be retained for five years after study completion 
to allow ample time for analysis and publication. 
 
5.6 CONFIDENTIALITY AND SECURITY OF DATA 
As with any study that involves substance use, an additional risk of the proposed study is 
breach of confidentiality. Although this would be very serious if it were to occur, breach of 
confidentiality is unlikely. The hospital already has ample protections in place to protect 
patient privacy and we will protect interview and administrative data by using password-
protected computers and encrypted files.  
Verbal permission to discuss a subject’s study participation in front of family members will 
be obtained. Written permission to discuss a subject’s condition with family will be 
obtained as part of the consent form prior to any dissemination of a subject’s 
information.One or more investigators with access to identifiable data are not at Cedars-
Sinai, and the study team will work with the Office of Research Administration to execute 
an appropriate Data Use Agreement before sharing the limited data set. 
6.0 
DATA AND SAFETY MONITORING  
6.1 DATA AND SAFETY MONITORING PLAN 
I. Responsibility for Data Safeguarding   
PI’s Ober and Danovitch have joint responsibility for overseeing data safeguarding.  They 
will train the designated CSMC approved study staff and project manager in data 
safeguarding techniques and will be responsible for the secure transmission of data from 
CSMC to secure research computers at RAND.   
Additional oversight will be provided by our Data and Safety Monitoring Committee, 
consisting of Dr. Scott Irwin and Dr. Karl Wittnebel of CSMC.  Drs. Ober and Danovitch will 
consult the committee as needed (e.g., to assess randomization issues, patterns of SAEs, 
etc.)  during the course of the 6- 7- month data collection period. This committee is in lieu 
of a full DSMB due to the short data collection period and small patient size (N=80) of this 

 
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pilot study. 
II. Risks associated with study participation 
The collaborative care START intervention, called substance use treatment and recovery 
team (START) itself is inherently low-risk and therefore adverse events (AEs) experienced 
by study subjects are likely to be due to participants’ underlying opioid and alcohol use 
disorders (OAUD) and other illnesses.  Based on our prior research with this population, we 
expect depression and anxiety, medical illness and injury associated with OAUD, and, in 
some cases, unstable living conditions. Thus, adverse events may be related more to these 
underlying issues than to the START itself. 
III. Handling of adverse events and serious adverse events and safety reporting 
AEs and SAEs will be handled the same way in which hospital emergencies are handled.  
The hospital has several standard procedures in place for emotional or physical distress.  If 
a client presents as suicidal, a social worker meets with him/her and then consults with a 
licensed mental health clinician (e.g., the CSMC PI Danovitch). The hospital will intervene as 
necessary, assess the client’s state, and develop an appropriate plan. Clients with medical 
emergencies will be treated with usual hospital services.  AEs occurring while the patient is 
hospitalized will be reported to PI Danovitch.  AEs/SAEs occurring after discharge will be 
assess by the START psychiatrist or care manager and reported to PI Danovitch. Incident 
reports will be written within one business day. All adverse and serious adverse events will 
be reported to the IRB and NIH according to CSMC IRB and NIH policies and procedures 
guidelines. 
IV. Availability of trained personnel and referral resources 
Prior to data collection Dr. Ober (or designee) will conduct training for the designated 
CSMC approved study staff and CSMC project manager. The training will address good 
clinical research practices, including data safeguarding and confidentiality.  The approved 
study staff will be trained to promote standardized and objective collection and recording 
of participant information. All research staff will complete a human subjects protection 
course.  
V. Procedures for data quality assurance and protecting confidentiality of participant data 
A. Types of data needing safeguarding 
a. Patient contact information – name, telephone number, address, alternate contact 
information, entered on a tablet into an electronic record management system. 
b. Consent forms.  Patients will provide written consent to participate in the study. 
c. Patient interview data – baseline and follow-up data from computer-assisted interview, 
entered on a tablet. (Appendix A). 
d. CSMC patient administrative data. Patient data obtained from the hospital electronic 
medical record (EPIC). (Appendix A). 
 
B. Data sensitivity.  This study will collect participant names, phone numbers, addresses, 
and alternate contact information. These personal identifiers are necessary to obtain 
informed consent, to notify and contact participants about the follow-up interview and 
to conduct follow-up monitoring for patients in the START experimental arm of the 
study. A study ID connecting identifiable information with confidential data will be 
assigned to each participant. Signed consent forms and contact information will not be 

 
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stored in the same database forms as interview or administrative data. 
 
C. Data safeguarding procedures  
1. Patient contact information. CSMC will create a secure, encrypted and password-
protected record management system using a secure, web-based system called 
Research Electronic Data Capture (REDCap) (see Appendix B).  REDCap will allow the 
CSMC approved study staff to assign participant IDs to interviews, to maintain a link file 
between study ID and medical record number through a tablet that is securely linked to 
the web.  REDCap is a secure, web-based tool used by CSMC researchers to build and 
manage surveys and databases.  REDCap was developed at Vanderbilt University in 
Nashville, Tenn., and is available at no charge. It has become the primary standard for 
most Clinical and Translational Science Institutes (CTSIs), a national consortium of 
medical research institutions. The UCLA CTSI, to which Cedars-Sinai belongs, has helped 
support access to REDCap. There are two production websites — one that handles data 
that can be linked to an individual (known as protected health information, or PHI, 
under the federal HIPAA Privacy Rule) and another for non-patient-identified data. 
Research may build their own database after completing REDCap training or have the 
REDCap database developed at no charge.  The link file will have read and write access 
restricted to approved study staff and the CSMC project manager. 
2. Patient consent forms.  If collected on paper, signed consent forms will be stored in a 
locked file cabinet at CSMC, separate from all study data. 
3. Patient interview data. 
a. Baseline. CSMC will also use REDCap to house the electronic computer-assisted 
patient interview. REDCap will allow the CSMC approved study staff to collect 
baseline data through a tablet that is securely linked to the web.  The CSMC project 
manager will transmit baseline data (identifiable only by study ID) to RAND via secure 
file transfer protocol (SFTP) site. A program, such as PGP, that provides RSA-level 
security will be used to encrypt files.  These data will not be shared with individuals 
who are not part of the project team, and no data shared with any members of the 
project study team will contain participant names. 
b. 1-month follow-up. 1- month follow-up interview data will be collected by 
telephone, encrypted on a password-protected tablet that is connected to the survey 
through REDCap, only identified by study ID.  Data will be collected by the CSMC 
approved study staff and entered directly into the secure tablet. The CSMC project 
manager will transmit baseline data (identifiable only by study ID) to RAND via secure 
file transfer protocol (SFTP) site. A program, such as PGP, that provides RSA-level 
security will be used to encrypt files.  These data will not be shared with individuals 
who are not part of the project team, and no data shared with any members of the 
project study team will contain participant names. 
4. CSMC administrative data. CSMC administrative data will be pulled from the 
electronic medical record system, EPIC, via a request submitted to the Research 
Informatics and Scientific Computing Core (RISCC). The CSMC project manager will 
replace all medical record numbers with study IDs. The CSMC project manager will 
then transmit the administrative data to RAND via the SSH File Transfer Protocol 
(SFTP) which is a network protocol that provides file access, file transfer, and file 
management functionalities over secure connection. It was designed by the Internet 
Engineering Task Force (IETF) as an extension of the Secure Shell protocol (SSH) 

 
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version 2.0 to provide secure file transfer capability.  
D. Disclosure Risks  
If private information about substance use is disclosed, possible psychological and social 
harm could result. However, the risk of such disclosure is rated as minimal given the 
safeguarding plan, and the magnitude of the harm were a breach of confidentiality to occur 
is likely to be little harm. We plan to minimize the possibility of a breach of confidentiality 
by instituting data safeguarding procedures as described above and maintaining 
identifiable data for only a limited period.  We have several mechanisms in place to ensure 
data integrity and confidentiality. All data will be stored in a password-protected database.  
Paper files (i.e., consent forms) will be stored in locked file cabinets at CSMC, and 
electronic files will be stored in encrypted and password-protected files. Furthermore, 
electronic files transmitted to the RAND research team will be identified only by participant 
ID numbers. Identifying information linking patients to their study ID number will be 
retained in an encrypted and password protected record management system at CSMC.  
Confidentiality policies and procedures will be reviewed with all new staff.   
E. Destruction of Data 
Consent forms will be retained at CSMC for three years after completion of the study. 
Linking files and identifiable information will be destroyed within a year after study 
completion. A limited date set will be retained for five years after study completion to 
allow ample time for analysis and publication. 
 
VI. Stopping rules for clinical trial 
We will employ the following stopping rule for the clinical trial: if there is clear evidence of 
harm. Although we do not expect any physical harms or serious psychological harms 
beyond minimal distress, we have several procedures for monitoring harm from the 
intervention, including asking participants to contact us if they experience any adverse 
events, offering additional resources to those with very high levels of mental health 
symptoms and problem drinking or drug use, and providing resources after baseline and at 
follow-up. We do not expect there to be overwhelming evidence of the benefit of START 
during this pilot study due to the small sample size, but we will monitor this and stop the 
trial if this is indicated. We also do not expect that there will be no likelihood of 
demonstrated treatment benefit (futility) for the intervention as compared to control. 
6.2 QUALITY CONTROL AND QUALITY ASSURANCE 
• PI Ober and the quantitative analysis team will be responsible for evaluating data for 
adherence with the protocol and for accuracy in relation to source documents.     
• PI Ober and the quantitative analysis team at RAND will be responsible for evaluating 
data quality. Reports generated from the database will provide a basis for ongoing 
monitoring of subject accrual and retention, as well as completeness of data. These 
will be used to identify and resolve problems that may arise.  EPIC data will be 
exported and checked monthly during the study and survey data will be transmitted 
and checked monthly.  Under the direction of a statistician, a quantitative analyst will 
check the data for completeness. 

 
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• Fidelity to intervention methods may be monitored and assessed by anonymous 
audio recording of up to 5% of intervention sessions of subjects randomized to the 
intervention arm. Patient confidentiality will be maintained by 1) uploading 
recordings to a secure Box folder; 2) allowing access to the Box folder by only one 
RAND study co-investigator (Karen Osilla, PhD); 3) ensuring recordings will be 
listened to in Box and not downloaded or saved; 4) ensuring recordings are deleted 
after listening. Verbal permission to record the session will be obtained from subjects 
prior to the start of recording. 
7.0 STATISTICAL CONSIDERATIONS  
 
7.1 STUDY OUTCOME MEASURES 
Although we do not anticipate that this pilot study will be sufficiently powered to detect 
treatment effects, we will estimate models with the primary goals of learning the variance 
of the treatment effect estimator, which will be used in power calculations for future study 
design, and detecting areas of potential concern. This model would look for differences in 
outcomes between intervention (START) and control (UC) conditions, controlling for 
baseline measure of the outcome, where appropriate, using a generalized linear modeling-
based framework. For dichotomous outcomes, we will employ a logistic regression model 
of the form Pr (𝑦𝑦𝑖𝑖 = 1) =1/(1 + exp (−(𝛽𝛽0 + 𝛽𝛽1𝑥𝑥𝑖𝑖 + 𝛽𝛽2𝑧𝑧𝑖𝑖))). Here i indexes 
individuals, 𝛽𝛽0 represents the overall intercept, 𝑥𝑥𝑖𝑖 represents the treatment status of 
individual i, 0 for control, and 1 for intervention, and 𝛽𝛽1 is the effect of the intervention. 
The variable 𝑧𝑧𝑖𝑖 represents the baseline measure and 𝛽𝛽2 associated coefficient. 
Continuous outcomes will be modeled using linear regression. We will also perform 
exploratory analyses to investigate whether there are subgroups that may be responding 
better or worse to the intervention by interacting the covariates in Table 2 with the 
treatment indicator. Because there will be nearly as many potential covariates as 
observations, we will employ the “horseshoe prior” in Bayesian analyses of the outcome. 64  
Qualitatively, this model starts from the assumption that most (if not all) of the covariates 
are unimportant for predicting the outcome, and attempts to learn which covariates are 
important. The intention is not so much to detect significant differences, but rather to 
highlight areas of potential concern. For example, if individuals with high pain levels 
respond less well to START recipients, this exploratory approach could draw attention to 
potential issues that could be optimized ahead of a future trial. 
 7.2 SAMPLE SIZE CONSIDERATIONS  
• Due to the short 1-month duration of participation, subject withdrawal from the study 
is not anticipated to be significant. 
• The proposed sample size (40/condition) is consistent with those recommended for 
small intervention tests in staged intervention development. 65  Based on 
administrative data for 54,466 hospitalizations in 2014, 1,037 hospitalizations involved 
implementation of CIWA protocols (indicating moderate to severe alcohol use) and 719 
involved a diagnosis of an opioid use disorder. We expect that the majority (at least 
1400) of these are unique patients, suggesting that about 117 patients per month will 
be identified through EPIC, with more referred directly by physicians and social 
workers. Although, we believe our enrollment rate of 16 per month over 5 months is 
realistic, if not conservative, this pilot provides the opportunity to confirm feasibility of 
this enrollment rate. 

 
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• It is not feasible to blind the staff to study condition because the study condition 
requires specific care by the START. While it is likely (and expected) that medical teams 
will treat patients in both the experimental and usual care (UC) conditions, patients in 
the START will have an enhanced experience because they (unlike patients in the UC 
condition) will be receiving START components designed to increase their readiness to 
take the medication and link to follow-up care. Moreover, the support provided by the 
START to medical teams for each START patient is the component that we hypothesize 
will take the burden off of the medical team and increase the likelihood of the patient 
receiving medication. Even as medical teams become more aware of medication for 
OAUD and perhaps increase prescribing, we hypothesize that patients whose medical 
teams receive support for their START patients will still be more likely to receive 
medication, even if medical teams are aware they can prescribe these medications. 
Thus, over time, while we might see increased medication initiation for patients in both 
study conditions, we still hypothesize statistically and clinically significant differences 
for patients in the CCT group. Nevertheless, we still plan to safeguard against any 
biases and effects of UC patients receiving the START. The research team will review 
electronic health record data to determine whether the START AMS or CM accidentally 
treated UC patients. Further, as part of this developmental study and pilot test, we are 
carefully assessing whether (and why) contamination occurs and, if it does, we will take 
additional steps to further safeguard the experimental condition in the future RCT. 
 
 
 
8.0 APPENDICES (MAY BE FOUND AS SEPARATE DOCUMENTS AS LISTED BELOW) 
8.1 RECRUITMENT AND ENROLLMENT 
• ELIGIBILITY SCREENER 
• ELIGIBILITY CHECKLIST  
• STUDY PHYSICIAN FLYER 
• PHYSICIAN SCREENING CARD 
• PHYSICIAN RECRUITMENT LETTER 
• PHYSICIAN TO PATIENT LETTER 
• PATIENT & FAMILY EDUCATION MATERIALS 
 
8.2 EVALUATION  
• BASELINE SURVEY 
• FOLLOW-UP SURVEY 
• PROVIDER INTERVIEW INFORMATION SHEET 
• PROVIDER INTERVIEW GUIDE 
 

 
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8.3 INTERVENTION 
• START MANUAL & APPENDICES 
o APPENDIX A: START ROLES AND RESPONSIBILITIES TABLE 
 
o APPENDIX B: START ASSESSMENT FORM 
o APPENDIX C: REGISTRY INSTRUCTIONS  
o APPENDIX D: CARE MANAGER HANDOUTS 
 
o APPENDIX E: START REFERRAL RESOURCE GUIDE 
 
o APPENDIX F: MEDICATION ASSISTED TREATMENT START CARDS – ALCOHOL 
USE DISORDER  
o APPENDIX G: MEDICATION ASSISTED TREATMENT START CARDS – OPIOID USE 
DISORDER 
 
 
 
 

 
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