Multi-Center Randomized Controlled Trial of Relay- NYC's Nonfatal Overdose Response Program
Phase: NA
Conditions: Opioid Overdose
Sponsor: NYU Langone Health

Official Title: 
Multi-Center Randomized Controlled Trial of Relay- NYC's Nonfatal 
Overdose Response Program  
NCT Number:
NCT04317053
Study Number:
19-01547 
Document Type:
Study Protocol and Statistical Analysis Plan
Date of the 
Document: 
 
January 17, 2023  

Study number: s19-01547
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Version date: 12/22/2022
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Multi-Center Randomized Controlled Trial of Relay- NYC's Nonfatal 
Overdose Response Program
Overall Study 
Principal Investigator: 
Kelly Doran, MD, MHS
NYU Langone Health
Ronald O. Perelman Department of Emergency Medicine
Department of Population Health
462 First Avenue
New York, NY 10016
kelly.doran@nyulangone.org
212-263-5850
Additional Investigators: 
Jennifer McNeely, MD, MS (MPI)
NYU Langone Health
Department of Population Health
180 Madison Ave., 17th floor 
New York, NY 10016
jennifer.mcneely@nyulangone.org
646-501-3551
Charles Cleland, PhD (Sub-I)
NYU Langone Health
Department of Population Health, Division of Biostatistics
180 Madison Avenue
New York, NY 10016
Charles.cleland@nyulangone.org
646-501-3692
Ethan Cowan, MD, MS (Site PI – Mount Sinai-Beth Israel; Co-I) 
Associate Professor, Department of Emergency Medicine
Icahn School of Medicine at Mount Sinai 
340 E 17th Street
New York, NY 10003
Ethan.cowan@mountsinai.org
212-240-2652
Robin Freeman (Consultant)
Qualitative Researcher 
John Jay College of Criminal Justice
205 Clinton Avenue, Apt 1C
Brooklyn, NY 11205
Rob.freem@gmail.com
646-501-5555

Study number: s19-01547
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Angela Regina, DO (Site PI – St. Barnabas) 
Assistant Director of Medical Toxicology 
SBH Health System 
4422 Third Avenue 
Bronx, NY 10457 
aregina@sbhny.org
718-960-9000 
 
Marya Gwadz, PhD (Sub-I) 
NYU Silver School of Social Work 
Department of Social Work 
1 Washington Square North, Room 301 
New York, NY 10003 
Marya.gwadz@nyu.edu
212-998-5965 
 
Ian Wittman, MD (Site PI – NYU-Brooklyn; Co-I) 
NYU Langone Health—Brooklyn  
Chief of Service, Department of Emergency Medicine 
150 55th Street  
Brooklyn, NY 11220 
Ian.wittman@nyulangone.org
718-630-6497 
 
Olumide Akindutire, MD (Sub-I) 
Assistant Chief of Service, Emergency Dept, TH 
550 1st Avenue 
New York, NY 10016 
Olumide.Akindutire@nyulangone.org
212-263-3293 
 
NYULH Study Number: 
s19-01547 
 
Funding Sponsor:  
 
Centers for Disease Control and Prevention  
2939 Brandywine Road 
Atlanta, GA 30341  
770-488-3081 
 
ClinicalTrials.gov 
Number                
NCT04317053 
Initial version: 
01/08/2020 
Amended versions: 10/01/2020; 10/09/2020; 01/11/2021; 05/25/2021; 06/21/2021; 07/19/2021; 12/22/2022 
 

Study number: s19-01547
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Behavioral Intervention Template Version: 11 January 2019
Statement of Compliance 
This study will be conducted in accordance with the Code of Federal Regulations on the Protection of 
Human Subjects (45 CFR Part 46), any other applicable US government research regulations, and 
institutional research policies and procedures. The Principal Investigator will assure that no deviation from, 
or changes to the protocol will take place without prior agreement from the sponsor and documented 
approval from the Institutional Review Board (IRB), except where necessary to eliminate an immediate 
hazard(s) to the trial participants. All personnel involved in the conduct of this study have completed Human 
Subjects Protection Training. 
 
 

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Table of Contents 
PROTOCOL SUMMARY .............................................................................................................................. 1
SCHEMATIC OF STUDY DESIGN ............................................................................................................... 3
1 
KEY ROLES ......................................................................................................................................... 4
2
INTRODUCTION, BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE.......................7
2.1 
BACKGROUND INFORMATION AND RELEVANT LITERATURE ................................................................ 7
2.2 
RATIONALE.................................................................................................................................... 9
2.3
POTENTIAL RISKS & BENEFITS......................................................................................................10
2.3.1 
Known Potential Risks ........................................................................................................... 10
2.3.2 
Known Potential Benefits ...................................................................................................... 10
3
OBJECTIVES AND PURPOSE .........................................................................................................11
3.1 
PRIMARY OBJECTIVE .................................................................................................................... 11
3.2 
SECONDARY OBJECTIVES............................................................................................................. 11
4 
STUDY DESIGN AND ENDPOINTS .................................................................................................. 11
4.1 
DESCRIPTION OF STUDY DESIGN .................................................................................................. 11
4.2 
STUDY ENDPOINTS....................................................................................................................... 11
4.2.1 
Primary Study Endpoints ....................................................................................................... 11
4.2.2 
Secondary Study Endpoints .................................................................................................. 11
4.2.3 
Exploratory Endpoints ........................................................................................................... 12
5 
STUDY ENROLLMENT AND WITHDRAWAL .................................................................................. 13
5.1 
INCLUSION CRITERIA .................................................................................................................... 13
5.1.1 
Patients .................................................................................................................................. 13
5.1.2 
ED Staff and Relay Peers (Qualitative Interviews)................................................................ 13
5.2 
EXCLUSION CRITERIA ................................................................................................................... 13
5.2.1 
Patients .................................................................................................................................. 13
5.2.2 
ED Staff and Relay Peers (Qualitative Interviews)................................................................ 13
5.3 
VULNERABLE SUBJECTS............................................................................................................... 13
5.3.1 
Inclusion of Patients who become Prisoners during the Study ............................................. 14
5.4 
STRATEGIES FOR RECRUITMENT AND RETENTION .......................................................................... 15
5.4.1 
Patients .................................................................................................................................. 15
5.4.2
ED Staff and Relay Peers (Qualitative Interviews)................................................................16
5.4.3 
Use of DataCore/Epic Information for Recruitment Purposes .............................................. 16
5.5
DURATION OF STUDY PARTICIPATION............................................................................................16
5.6 
TOTAL NUMBER OF PARTICIPANTS AND SITES ................................................................................ 17
5.7 
PARTICIPANT WITHDRAWAL OR TERMINATION................................................................................ 17
5.7.1 
Reasons for Withdrawal or Termination ................................................................................ 17
5.7.2 
Handling of Participant Withdrawals or Termination ............................................................. 17
5.7.3 
Premature Termination or Suspension of Study ................................................................... 17
6 
BEHAVIORAL/SOCIAL INTERVENTION ......................................................................................... 18
6.1 
STUDY BEHAVIORAL OR SOCIAL INTERVENTION(S) DESCRIPTION.................................................... 18
6.1.1 
Administration of Intervention ................................................................................................ 19
6.1.2 
Procedures for Training Interventionalists and Monitoring Intervention Fidelity ................... 19
6.1.3 
Assessment of Subject Compliance with Study Intervention ................................................ 20
7 
STUDY PROCEDURES AND SCHEDULE ....................................................................................... 20
7.1 
STUDY PROCEDURES/EVALUATIONS ............................................................................................. 20
7.1.1 
Study Specific Procedures Overall ........................................................................................ 20
7.1.2 
Standard of Care Study Procedures ..................................................................................... 21

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7.1.3 
ED Staff and Relay Peer Qualitative Interview Procedures .................................................. 21
7.2
LABORATORY PROCEDURES/EVALUATIONS ...................................................................................21
7.3 
STUDY SCHEDULE........................................................................................................................ 21
7.3.1 
Screening and Enrollment/Baseline ...................................................................................... 21
7.3.2
Intermediate Visits.................................................................................................................23
7.3.3 
Final Study Visit ..................................................................................................................... 23
7.3.4 
Withdrawal Visit ..................................................................................................................... 23
7.3.5
Unscheduled Visits................................................................................................................23
7.4 
CONCOMITANT MEDICATIONS, TREATMENTS, AND PROCEDURES .................................................... 24
7.5 
JUSTIFICATION FOR SENSITIVE PROCEDURES................................................................................ 24
7.5.1
Precautionary Medications, Treatments, and Procedures ....................................................24
7.6 
PROHIBITED MEDICATIONS, TREATMENTS, AND PROCEDURES ........................................................ 24
7.7 
PROPHYLACTIC MEDICATIONS, TREATMENTS, AND PROCEDURES................................................... 24
7.8
PARTICIPANT ACCESS TO STUDY INTERVENTION AT STUDY CLOSURE.............................................25
8 
ASSESSMENT OF SAFETY ............................................................................................................. 25
8.1 
SPECIFICATION OF SAFETY PARAMETERS...................................................................................... 25
8.1.1
Definition of Adverse Events (AE).........................................................................................25
8.1.2 
Definition of Serious Adverse Events (SAE) ......................................................................... 26
8.1.3 
Definition of Unanticipated Problems (UP) ............................................................................ 26
8.2 
CLASSIFICATION OF AN ADVERSE EVENT ....................................................................................... 26
8.2.1 
Severity of Event ................................................................................................................... 26
8.2.2 
Relationship to Study Intervention......................................................................................... 27
8.2.3 
Expectedness ........................................................................................................................ 27
8.3 
TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP.................................... 27
8.4 
REPORTING PROCEDURES – NOTIFYING THE IRB .......................................................................... 27
8.4.1 
Adverse Event Reporting ...................................................................................................... 28
8.4.2 
Serious Adverse Event Reporting ......................................................................................... 28
8.4.3 
Unanticipated Problem Reporting ......................................................................................... 28
8.4.4 
Reporting of Pregnancy ......................................................................................................... 28
8.5 
REPORTING PROCEDURES – NOTIFYING THE STUDY SPONSOR...................................................... 28
8.6 
REPORTING PROCEDURES – PARTICIPATING INVESTIGATORS......................................................... 29
8.7 
STUDY HALTING RULES................................................................................................................ 29
8.8 
SAFETY OVERSIGHT ..................................................................................................................... 29
9 
CLINICAL MONITORING .................................................................................................................. 31
10
STATISTICAL CONSIDERATIONS .................................................................................................. 31
10.1
STATISTICAL AND ANALYTICAL PLANS ...........................................................................................31
10.2
STATISTICAL HYPOTHESES ........................................................................................................... 31
10.3
ANALYSIS DATASETS .................................................................................................................... 31
10.4
DESCRIPTION OF STATISTICAL METHODS ......................................................................................32
10.4.1 
General Approach ............................................................................................................. 32
10.4.2 
Analysis of the Primary Efficacy Endpoint(s) .................................................................... 32
10.4.3 
Analysis of the Secondary Endpoint(s) ............................................................................. 32
10.4.4 
Safety Analyses ................................................................................................................ 33
10.4.5 
Adherence and Retention Analyses .................................................................................. 33
10.4.6 
Baseline Descriptive Statistics .......................................................................................... 33
10.4.7 
Planned Interim Analysis .................................................................................................. 33
10.4.8 
Additional Sub-Group Analyses ........................................................................................ 34
10.4.9 
Multiple Comparison/Multiplicity ........................................................................................ 34
10.4.10
Tabulation of Individual Response Data ........................................................................... 34
10.4.11
Exploratory Analyses ........................................................................................................ 35
10.5
SAMPLE SIZE............................................................................................................................... 35
10.6
MEASURES TO MINIMIZE BIAS ....................................................................................................... 35
10.6.1 
Enrollment/Randomization/Masking Procedures .............................................................. 35
10.6.2 
Evaluation of Success of Blinding ..................................................................................... 35

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10.6.3 
Breaking the Study Blind/Participant Code ....................................................................... 35
11
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS.................................35
12
QUALITY ASSURANCE AND QUALITY CONTROL ....................................................................... 36
13
ETHICS/PROTECTION OF HUMAN SUBJECTS ............................................................................. 37
13.1
ETHICAL STANDARD.....................................................................................................................37
13.2
INSTITUTIONAL REVIEW BOARD..................................................................................................... 37
13.3
INFORMED CONSENT PROCESS .................................................................................................... 37
13.3.1
Consent/Assent and Other Informational Documents Provided to Participants ...............37
13.3.2 
Consent Procedures and Documentation ......................................................................... 37
13.4
POSTING OF CLINICAL TRIAL CONSENT FORM ................................................................................ 38
13.5
PARTICIPANT AND DATA CONFIDENTIALITY ....................................................................................39
13.5.1 
Research Use of Stored Data ........................................................................................... 40
13.6
FUTURE USE OF STORED DATA .................................................................................................... 40
14
DATA HANDLING AND RECORD KEEPING...................................................................................41
14.1
DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES .............................................................. 41
14.2
STUDY RECORDS RETENTION ....................................................................................................... 42
14.3
PROTOCOL DEVIATIONS ............................................................................................................... 42
14.4
PUBLICATION AND DATA SHARING POLICY.....................................................................................42
15
STUDY FINANCES ............................................................................................................................ 43
15.1
FUNDING SOURCE ........................................................................................................................ 43
15.2
COSTS TO THE PARTICIPANT ......................................................................................................... 44
15.3
PARTICIPANT REIMBURSEMENTS OR PAYMENTS ............................................................................ 44
16
STUDY ADMINISTRATION ............................................................................................................... 44
16.1
STUDY LEADERSHIP ..................................................................................................................... 44
17
CONFLICT OF INTEREST POLICY .................................................................................................. 44
18
REFERENCES ................................................................................................................................... 46
19
ATTACHMENTS ................................................................................................................................ 49
 

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List of Abbreviations
AE
Adverse Event/Adverse Experience
BADUPCT
Bureau of Alcohol and Drug Use Prevention, Care and Treatment 
CDW 
NYC Health and Hospitals (H+H) Clinical Data Warehouse 
CFR 
Code of Federal Regulations
CRF 
Case Report Form
CSOC 
Clinical Study Oversight Committee
DCC
Data Coordinating Center 
DHHS
Department of Health and Human Services 
DOHMH 
New York City Department of Health and Mental Hygiene 
DSMB 
Data and Safety Monitoring Board
ED 
Emergency Department
EHR 
Electronic health record 
FFR 
Federal Financial Report
FWA 
Federalwide Assurance 
GCP
Good Clinical Practice 
HIPAA
Health Insurance Portability and Accountability Act
ICF
Informed Consent Form
IRB
Institutional Review Board 
ISM
Independent Safety Monitor
MOP 
Manual of Procedures 
MOUD 
Medication for opioid use disorder 
N 
Number (typically refers to participants)
NIH
National Institutes of Health
OEND 
Overdose education and naloxone distribution 
OD
Overdose
OHRP 
Office for Human Research Protections
OHSR 
Office of Human Subjects Research
OUD 
Opioid use disorder 
PI 
Principal Investigator
PM
Project Manager
QA
Quality Assurance 
QC
Quality Control 
RA 
Research Assistant (may also refer to Project Manager) 
RCT 
Randomized Controlled Trial
RHIO
Regional health information organization

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SAE
Serious Adverse Event/Serious Adverse Experience
SDC 
Site-directed Care
SOP 
Site-specific Operating Procedure 
US 
United States 

Study number: s19-01547
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writing by the study sponsor 
Protocol Summary 
Title 
Multi-Center Randomized Controlled Trial of Relay- NYC's Nonfatal 
Overdose Response Program
Short Title 
Relay RCT 
Brief Summary 
The New York City (NYC) Department of Health and Mental Hygiene 
(DOHMH) has implemented Relay, a novel program that engages and 
intervenes with individuals in the ED following an opioid OD and for the next 
90 days, with the goal of preventing subsequent OD events. The proposed 
randomized controlled trial will evaluate the impact of Relay on preventing 
subsequent opioid-related adverse events. A total of 350 eligible individuals 
with nonfatal opioid OD presenting to one of four participating EDs will be 
enrolled and randomized to one of two arms: 1) site-directed care (SDC) or 2) 
Relay—peer-delivered OD education and treatment linkage, including 90 
days of peer navigation. Outcomes will be measured for 12 months through 
interviews and administrative health data.
Phase 
Phase 3  
Objectives 
Aim 1: Evaluate the effectiveness of Relay to reduce the frequency of opioid-
related adverse events (any opioid-involved OD [fatal or nonfatal] or any other 
substance use-related ED visit), in the 12 months following the index visit, the 
primary outcome.  
 
Aim 2: Evaluate the impact of Relay on the following secondary outcomes: 
initiation of medication for opioid use disorder (MOUD); OD risk behaviors; self-
reported opioid-involved OD; time to next opioid-involved OD; and frequency 
of ED visits for any cause, opioid OD, and other substance use related 
reasons. 
 
Aim 3: Identify mediators (e.g., OD knowledge, support, experience of 
stigma, peer modeling) and moderators (e.g., substance use history, age, 
sex, housing status) of the effect of Relay. 
 
Aim 4:  Evaluate Relay’s implementation by assessing fidelity to the program 
model and exploring barriers and facilitators to its delivery and sustainability 
through qualitative interviews with patients, Relay peer navigators, and ED 
providers.
Methodology 
Randomized Controlled Trial of a behavioral intervention 
Endpoint 
Primary endpoints: opioid-related adverse events (OD deaths, nonfatal OD 
events, and other substance use related ED visits) 
Secondary endpoints: initiation of medication for opioid use disorder (MOUD); 
OD risk behaviors; self-reported opioid-involved OD; time to next opioid-
involved OD; and frequency of ED visits for any cause, opioid OD, and other 
substance use related reasons. 
Study Duration 
The estimated time from when the study opens to enrollment until completion 
of data analysis is approximately 33 months.
Participant Duration 
6 months active participation 

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Duration of behavioral 
intervention 
Total duration of intervention: 90 days
The behavioral intervention is comprised of two components, both delivered 
by the peer navigator. The first takes place in the ED, where the peer 
distributes naloxone and delivers tailored OD education, treatment referrals 
and support. The second component begins after discharge and consists of 
up to 90 days of peer navigation to provide ongoing support and linkage to 
services including MOUD, harm reduction programs, and social services.
Population 
Adults ( 18 years), English- or Spanish-speaking, presenting to a 
participating ED with nonfatal opioid OD
Study Sites 
Study sites are three health systems, representing four high-volume NYC 
hospital EDs. The sites are geographically dispersed and serve patient 
populations that are diverse with respect to age, sex, race, and ethnicity.
 
1. NYU Langone Health – Tisch Hospital & NYU Langone Hospital—
Brooklyn  
2. Mount Sinai Beth Israel 
3. St. Barnabas Hospital 
 
Number of participants 
350 participants expected to be enrolled in the RCT across 3 health system 
EDs (4 EDs total).  
 
Approximately 10-12 ED provider participants, approximately 10 Relay peer 
navigator participants, and approximately 12 patients will complete qualitative 
interviews.
Description of Study 
Intervention/Procedure 
Relay is a novel program that engages and intervenes with individuals in the 
ED following an opioid OD and for the next 90 days, with the goal of 
preventing subsequent OD events. Relay is delivered by trained peer 
navigators, who are DOHMH staff with lived substance use experience. 
Relay navigators provide counseling, linkage to services, and OD prevention 
education.
Reference Therapy 
Site-directed care (SDC): site-specific existing interventions delivered to 
patients with OUD as part of ED care. At a minimum SDC arm patients will 
receive OD education and naloxone distribution (OEND), a list of opioid 
treatment programs, and an informational flyer about Relay. 
 
Key Procedures 
Survey administration, education and counseling (for Relay arm), qualitative 
interviews
Statistical Analysis 
The primary analysis will use a Poisson generalized linear regression model to 
evaluate the intervention effect on the total number of opioid-involved OD and 
substance use-related ED visits. We anticipate the availability of 12 months of 
follow-up data on all participants, but in the event of death or withdrawal from 
the study, we will adjust the follow-up time appropriately using an offset term. 
We will include adjustment for study site, as well as other baseline factors that 
may be unbalanced across arms. The primary effect measure will be the 
incidence rate ratio comparing Relay to SDC. Some participants may be 
routinely high utilizers of the ED, and this may lead to overdispersion of the 
count outcome; we will use a negative binomial model instead of a Poisson 
model if warranted. Statistical analysis for other aims are described in the full 
protocol. 
 

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Schematic of Study Design
ED Staff calls Relay hotline
Follow-up assessments (RA)
1 month
3 months
6 months
RA enrolls patient, randomization
Exit interview (RA)
Administrative data
12 months
Patient with overdose
Baseline assessment (RA)
Site-Directed Care 
(SDC)
Relay 
(peer navigator)
Figure 3. Study design 
 
 

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1 Key Roles
Principal Investigator (for NYULH study site and overall study) 
Kelly Doran, MD, MHS 
NYU Langone Health 
Assistant Professor, Departments of Emergency Medicine and Population Health  
462 1st Avenue, Room A-345 
New York, NY 10016  
212-263-5850 
Kelly.doran@nyulangone.org 
Other NYULH Investigators 
Jennifer McNeely, MD, MS (MPI)
Department of Population Health 
180 Madison Ave., 17th floor  
New York, NY 10016 
646-501-3551 
Jennifer.mcneely@nyulangone.org 
Charles Cleland, PhD (Sub-I)  
NYU Langone Health 
Department of Population Health, Division of Biostatistics 
180 Madison Avenue 
New York, NY 10016 
Charles.cleland@nyulangone.org 
646-501-3692 
 
Robin Freeman (Consultant) 
Qualitative Researcher  
John Jay College of Criminal Justice 
205 Clinton Avenue, Apt 1C 
Brooklyn, NY 11205 
Rob.freem@gmail.com 
646-501-5555 
Marya Gwadz, PhD (Sub-I)  
NYU Silver School of Social Work  
Department of Social Work 
1 Washington Square North, Room 301 
New York, NY 10003 
Marya.gwadz@nyu.edu 
212-998-5965 
 
Ian Wittman, MD (Sub-I) 
NYU Langone Health—Brooklyn  
Chief of Service, Department of Emergency Medicine 
150 55th Street 
Brooklyn, NY 11220 
Ian.wittman@nyulangone.org 
718-630-6497 
 
Olumide Akindutire, MD (Sub-I) 
Assistant Chief of Service, Emergency Dept, TH 
550 1st Avenue 
New York, NY 10016 
Olumide.akindutire@nyulangone.org 

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212-263-3293 
 
Project Manager
Tingyee Chang, MSc 
Project Manager, Department of Emergency Medicine 
NYU Langone Health 
227 E 30th Street, Ground Floor 105 
332-323-2607 
Tingyee.chang@nyulangone.org 
 
Data Analyst
Katherine Siu
Assistant Research Scientist, Division of Biostatistics 
NYU Langone Health 
180 Madison Ave., 5th Fl.
New York, NY 10016 
Katherine.siu@nyulangone.org 
 
Volunteer 
Anna Silver 
Research Intern, NYU SARET Program  
NYU Langone Health  
227 East 30th Street, Ground Floor 105 
Anna.silver@nyulangone.org 
Other Participating Site Investigators  
Ethan Cowan, MD, MS (Site PI - Mount Sinai-Beth Israel; Co-I)  
Associate Professor, Department of Emergency Medicine 
Icahn School of Medicine at Mount Sinai  
340 E 17th Street 
New York, NY 10003 
212-240-2652 
Ethan.cowan@mountsinai.org 
 
Angela Regina, DO (Site PI – St. Barnabas) 
Assistant Director of Medical Toxicology 
SBH Health System 
4422 Third Avenue 
Bronx, NY 10457 
Aregina@sbhny.org 
718-960-9000 
 
 
Other Key Roles (Not Direct Study Personnel) 
NYC DOHMH BADUPCT Staff 
NYC DOHMH staff operate the Relay intervention across NYC, which is the intervention being studied. 
They operate Relay independently of the study. A Memorandum of Understanding with DOHMH will be 
signed to provide NYU study investigators with Relay program records. 
Hillary Kunins, MD, MPH, MS (Co-I)  
Assistant Commissioner, Bureau of Alcohol and Drug Use  
NYC Department of Health and Mental Hygiene 
42-09 28th Street, Room CN14 
Queens, NY 11101 
347-396-7189 

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Hkunins1@health.nyc.gov 
 
Denise Paone, EdD (Co-I)  
Senior Director, Bureau of Alcohol and Drug Use 
NYC Department of Health and Mental Hygiene 
42-09 28th Street, Room CN14 
Queens, NY 11101 
347-396-7189 
Dpaone@health.nyc.gov 
 
Angela Jeffers, MA (Relay Director) 
Director of Relay, Bureau of Alcohol and Drug Use Prevention, Care and Treatment 
NYC Department of Health and Mental Hygiene  
42-09 28th Street, 19th floor, CN 14 
Long Island City, NY 11101  
347-396-7019 
Ajeffers@health.nyc.gov 
 
Alice Welch, DrPH, MPH, RPh 
Director of Evaluation, Bureau of Alcohol and Drug Use, Prevention, Care, and Treatment  
NYC Department of Health and Mental Hygiene 
42-09 28th Street 
Long Island City, NY 11101 
Awelch1@health.nyc.gov 
 
Kelsey Kepler, MPH 
Evaluation Coordinator, Bureau of Alcohol and Drug Use, Prevention, Care, and Treatment  
NYC Department of Health and Mental Hygiene 
42-09 28th Street 
Long Island City, NY 11101 
Kkepler@health.nyc.gov 
 
Key CDC Contacts 
Sue Neurath, PhD 
Project Officer, Scientific Program Officer 
Extramural Research Program Office 
National Center for Injury Prevention and Control  
Centers for Disease Prevention and Control (CDC) 
1600 Clifton Road 
Atlanta, GA 30329 
770-488-3368  
SFN8@cdc.gov 
 
Linda Franklin 
Extramural Research Program Operations 
National Center for Injury Prevention and Control  
Centers for Disease Control and Prevention (CDC) 
1600 Clifton Road 
Atlanta, GA 30329 
770-488-4821 
llf0@cdc.gov 
 
 
 
 
 

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Advisors
Not involved in consent, data collection, or data analysis
Donna Shelley, MD, MPH (Advisor)  
Professor 
NYU College of Global Public Health  
665 Broadway 
New York, New York 10012 
Donna.Shelley@nyulangone.org 
John Rotrosen, MD (Advisor)  
Professor, Department of Psychiatry 
NYU School of Medicine 
One Park Avenue, 8th Floor 
New York, NY 10016 
646-754-4763 
John.Rotrosen@nyulangone.org 
 
 
 
 
 
 
 
2 Introduction, Background Information and Scientific Rationale 
2.1
Background Information and Relevant Literature 
The increasing rates of overdose (OD) deaths and prevalence of opioid use disorders (OUD) are urgent 
medical and public health issues in the US.1-3 The number of OD deaths has risen annually for the past 
decade.4,5 In 2016, the US saw over 63,000 drug OD deaths, an increase of 28% from the previous year.6
Two-thirds of these OD deaths involved opioids. Deaths are increasingly driven by heroin and synthetic 
opioids,2 and deaths involving fentanyl specifically have increased exponentially in recent years.7
As the opioid crisis worsens, the number of emergency department (ED) visits for opioid overdose is rising, 
to over 140,000 in 2017 (a 30% increase from the prior year).8 In the US, the northeast had the highest rate 
of opioid OD ED visits in 2017, with over 20 OD visits for every 10,000 ED visits for any cause.8 The largest 
increases in, and highest rates of, opioid-related ED visits occurred in large metropolitan areas.8 Mirroring 
national trends, from 2015-2016, New York City (NYC) saw its largest single-year increase in the number 
of drug OD deaths, with 483 more drug overdose deaths in 2016 than in 2015.9 In 2017, there were 1,487 
unintentional drug OD deaths in NYC, a rate of 21.2 per 100,000 New Yorkers.9 Opioids were involved in 
82% of these drug OD deaths.9 The increase in OD deaths is driven in large part by the penetration of 
fentanyl into the drug supply. In each year prior to 2015, fentanyl was present in fewer than 4% of OD 
deaths.10 In contrast, fentanyl was present in 16% of OD deaths in 2015, increasing to 44% in 2016. In 
2017, 57% of 1,487 total OD deaths involved fentanyl.11 
Public health authorities are looking for solutions. In March 2017, the NYC Mayor’s Office launched the 
HealingNYC initiative, which committed $38 million each year to programs intended to reduce opioid OD 
deaths.12 In March 2018, the NYC Mayor’s Office announced an additional $22 million investment into 
HealingNYC to expand existing initiatives and launch new strategies, bringing the total HealingNYC 
investment to $60 million.13 This initiative leverages the resources of the city’s Department of Health and 
Mental Hygiene (DOHMH) to prevent opioid OD and increase access to opioid treatment. HealingNYC has 

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spurred the rapid development and launch of innovative programs to address the opioid crisis, but does not 
provide resources for rigorous evaluation of their effectiveness.  
ED visits for nonfatal opioid overdose are a missed opportunity for intervention. Individuals with prior 
nonfatal OD are at greatly increased risk of having another OD14-16 and are 2-3 times more likely to 
subsequently die of OD,17-20 in comparison to individuals who use drugs and have not previously overdosed. 
A statewide study in Massachusetts found that 10% of those who had a nonfatal initial OD reversed by 
naloxone died within one year, many from opioid OD.21 Following a nonfatal overdose—whether or not 
naloxone is given—the most likely care setting for an individual is the ED.22,23 This high-risk population has 
few other contacts with health care  providers,24 and the ED visit for nonfatal opioid OD thus represents a 
rare opportunity to reach these patients and engage them in care.25 While national leaders in addiction and 
emergency medicine have called for a more coordinated and robust response in EDs following opioid OD, 
current practice in the majority of EDs nationwide and in NYC is to discharge patients after a brief 
observation period, without providing OEND or effectively linking patients to opioid treatment programs.25-
33 Some EDs do offer treatment referrals, but referrals alone are rarely effective; it takes considerable effort 
to engage individuals in care.34-38
The scale and urgency of the opioid crisis have led to the rapid development and implementation of novel 
strategies aimed at preventing overdose fatalities. Public health authorities are developing and deploying 
new, theory-based programs even in the absence of rigorous scientific evidence supporting their 
effectiveness. A cornerstone of DOHMH’s response to the opioid crisis is Relay, a novel program that uses 
peer navigators to reach New Yorkers following an OD.  
A large literature highlights the positive impact of peer navigation interventions for a range of public health 
problems and conditions, though they have only recently been deployed to address OD. Navigation 
approaches were originally developed to reduce racial/ethnic disparities in cancer outcomes, and peer 
navigation approaches have been found effective across a range of populations and cancer types.39,40
Similarly, a large body of evidence supports the peer navigation approach for improving HIV treatment 
outcomes. A peer navigation approach may be particularly well suited to patient populations that are highly 
stigmatized and mistrustful of health care professionals, such as those addressed in the proposed study.41
Peer navigators, by drawing on their lived experiences, can serve to reduce stigma.42 Further, peer 
navigators are positioned to serve as effective positive role models.42 These factors (social modeling, 
reduced stigma) are critical elements of social-cognitive behavior change models. Thus for stigmatized, 
wary, and distrustful populations, peer navigation interventions show high levels of acceptability, and this 
promotes feasibility, engagement, motivation to change behavior, and intervention effectiveness.  
Grounded in a theoretical model that integrates the theory of triadic influence43 and dynamic social impact 
theory,44 and incorporating a motivational interviewing counseling approach, Relay is a behavioral 
intervention that is carried out by trained DOHMH peer navigators who have lived experience with 
substance use. These peer navigators are deployed to collaborating EDs when the ED provider caring for 
an individual presenting after a nonfatal OD calls the Relay hotline (the hotline is a component of the 
DOHMH Relay program). The Relay intervention is designed to overcome the specific barriers to secondary 
prevention of subsequent OD experienced by these patients in the ED, in the immediate aftermath of the 
OD, and after discharge. The intervention is comprised of two well-integrated components, both delivered 
by the peer navigator. The first takes place in the ED, where the peer navigator engages individuals in 
patient-centered OD education, provides a naloxone kit if one was not given by ED staff (family/friends with 
the patient are also given kits), and facilitates initiation of treatment for OUD through motivational counseling 
and referrals. The second component begins after discharge and consists of up to 90 days of peer 
navigation to provide ongoing support and linkage to services including MOUD, harm reduction programs, 
and social services. Theoretically, in the ED and post-ED, peer navigators serve as positive role models 
while providing tangible and instrumental support and reducing stigma, which fosters motivation and 
capacity to change risk behaviors and initiate treatment, thereby reducing risk for future OD.  
Experts have called for EDs—open ‘24/7/365’ and uniquely accessible—to do more to address the opioid 
crisis.45 Some academic health systems have adopted peer ‘recovery coaches’ in the ED, whose primary 
role is to link patients to treatment. These programs are propagating in response to the opioid crisis in 
advance of strong evidence of their effectiveness.29,46,47 To date, there has been only one small 
retrospective study of the effectiveness of an ED-based peer opioid OD response program.48 This study 

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examined The Rhode Island Lifespan Opioid Overdose Prevention (LOOP) program—which is similar to 
Relay in using peers to engage and support patients after an OD event in the ED and for 90 days following 
the event—compared to OEND and usual care. Non-significant trends were observed that generally favored 
both the ‘recovery coach’ and OEND groups over usual care, though MOUD initiation rates appeared lower 
in the recovery coach group.48 The study authors suggested future randomized controlled trials to more 
rigorously examine the effectiveness of similar peer navigator programs.48
Overall, trials of other ED-based OD prevention interventions have been limited by small sample sizes and 
heterogeneous populations and interventions, which constrain the applicability of their results to real-world 
practice. A study by Bohnert et al.49 identified 204 ED patients at risk for prescription opioid OD in EDs and 
provided a single-contact motivational interviewing intervention. Participants reported significant reductions 
in OD risk behaviors, but the study did not examine repeat OD events. A study by Banta-Green et al.50
screened ED patients for risk of opioid OD, and tested a single-contact brief intervention in high-risk users 
of illicit and prescription opioids. This study found no significant difference in OD rates between groups 
(~20% experienced an OD within 12 months), but it was limited by low enrollment and loss to follow-up. 
There is also increasing interest in ED-initiated buprenorphine and referral to ongoing treatment. Past 
studies have shown promising, albeit mixed, results; for example, a study by D’Onofrio et al. showed that 
such an intervention resulted in increased connection to outpatient treatment and lower illicit opioid use at 
2 months but not at 6 or 12 months.38,51 Interventions focused on ED-based buprenorphine initiation tend 
not to address many of the potent barriers to treatment among vulnerable ED patients—including competing 
subsistence needs, lack of social support, and stigma—which peer navigator programs attempt to address.  
In summary, while ED-initiated peer navigator approaches appear to be well accepted and theoretically 
promising in reducing secondary opioid OD, rigorous study is urgently needed to determine their 
effectiveness. Because research has thus far not demonstrated a benefit of peer navigator approaches 
over other approaches to ED patients presenting after opioid OD (such as OEND alone), clinical equipoise 
exists to justify a randomized controlled trial. The proposed RCT promises to fill a critical research gap, 
providing important information about evidence-based responses to prevent OD among the population at 
highest risk.   
2.2
Rationale
The feasibility of Relay is already established, but its effectiveness has not yet been studied. DOHMH is 
interested in studying Relay’s effectiveness to inform critical decisions around whether the program should 
be modified, replaced, or further expanded. DOHMH is committed to optimizing NYC’s response to its 
continuing opioid OD crisis, including by evaluating existing programs to ensure that limited resources are 
being used effectively. Because programmatic funding for Relay does not support more than basic process 
evaluation, DOHMH has partnered with NYU researchers to develop this proposal to study Relay’s impact 
on preventing opioid-related adverse events (subsequent fatal or nonfatal OD, and substance use-related 
ED visits).  
This study seeks to add a rigorous evaluation component to the Relay program initiative, by introducing 
random assignment to Relay versus site-directed care (SDC) at five EDs. Our evaluation uses structured 
interviews, administrative data, and qualitative interviews with patients and other stakeholders to 
characterize Relay’s implementation, effectiveness, and potential for future dissemination and 
sustainability.  
By engaging individuals at high risk for OD at a reachable moment and providing a sustained peer-delivered 
intervention, the Relay approach has potential to reduce subsequent OD and opioid-related adverse events. 
In the midst of an opioid crisis, health authorities are developing programs aimed at reducing OD deaths, 
even in the absence of strong evidence. This is a critically important time to understand which of these new 
approaches are effective, and under what conditions, so that they can be brought to scale to improve 
population health. The Relay program is feasible, well accepted by EDs and patients, and holds promise 
as an OD prevention intervention that could be scaled up in NYC and nationally, but first its effectiveness 
must be established. The proposed randomized controlled trial will provide the quality of evidence that is 
required to determine whether peer interventions like Relay can impact the opioid crisis by reducing future 
opioid-related adverse events for patients who have presented to the ED for nonfatal opioid OD, above and 
beyond other interventions already being implemented in EDs in the wake of the opioid crisis.  

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2.3
Potential Risks & Benefits
2.3.1 Known Potential Risks 
This study poses no more than minimal risk to participants. The main risk of participation is loss of 
confidentiality. Personally identifiable information and personal health information collected for the study 
will be kept to the minimum required, though the study does involve collection of participant identifying 
information that is needed to allow examination of health care administrative data for the 12 month outcome. 
Participant contact information will also be collected for purposes of reaching participants for completion of 
study visits. Participant responses to questionnaires include sensitive questions such as questions about 
substance use. Risk of loss of participant confidentiality or participation information will be guarded against 
by the measures described in subsequent sections of this protocol. Additionally, this CDC-funded study will 
be covered by a Certificate of Confidentiality, as it meets the criteria specified by the 21st Century Cares 
Act. 
 
Patients. There is a possibility that patients may feel uncomfortable while completing some study 
assessments. We will minimize discomfort by having interviews conducted by a trained and qualified RA, 
who will take steps to maximize participant privacy even in a busy ED setting (e.g., asking visitors to leave, 
moving the patient to a more private area). Patients will be informed that all aspects of their participation 
are voluntary and that they may choose not to complete assessments or to discontinue their participation 
entirely, without repercussion or penalty. Participants in the Relay arm may feel uncomfortable while 
discussing sensitive topics with Relay peers. The Relay peers are highly experienced in discussing 
sensitive topics with participants, and participants may choose to end uncomfortable conversations at any 
time. In the informed consent process, participants will be told that if they become psychologically 
distressed during the study procedures they can request to speak to someone about their feelings (e.g., a 
physician). If a participant voices suicidal ideation during study procedures, RAs will follow procedures that 
include immediate reporting, as will be detailed in the study SOP/MOP and included in RA training 
materials. 
ED staff and Relay peers (qualitative interviews). ED staff are employees of the three study hospital system 
sites (NYULH, Mt. Sinai Beth Israel, St. Barnabas Hospital). Relay peers are employees of DOHMH. 
Adequate protections will be implemented to ensure that participation in the qualitative interviews does not 
jeopardize their employment or professional standing. Specifically, all audio recordings will be transcribed 
at the earliest opportunity and any personally identifying information will be removed from the transcripts. 
All analyses will utilize only the transcripts from which personally identifying information is removed. Audio 
recordings and transcripts will not be shared with supervisors of ED staff or Relay peers; only aggregate 
information will be shared with study team members who may hold supervisory roles over participants 
(DOHMH staff and ED site leads), such that individuals cannot be identified. No information about personal 
substance use will be solicited in the interviews. 
2.3.2 Known Potential Benefits 
Participants are not expected to benefit from the study directly, as they will not be receiving new 
interventions not otherwise available to them in the ED. We expect that overdose education and provision 
of naloxone (in both conditions) will reduce future opioid-related adverse events among patients presenting 
with nonfatal OD; of note, OEND is generally standard care at study sites already, but for the study we will 
ensure it occurs for all study participants. The Relay peer navigator intervention has the potential to provide 
additional benefit to patients, but its effectiveness has not been established. The community at large, 
including patients and providers, stands to benefit from the knowledge gained from this study about 
reducing OD fatalities, and barriers and facilitators to OD prevention programs. The results of this study are 
critical to advancing science around preventing OD fatalities, informing the allocation of resources in NYC, 
and informing other jurisdictions as they scale up opioid OD prevention efforts.  

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3 Objectives and Purpose
3.1 Primary Objective
Aim 1: To evaluate the effectiveness of Relay to reduce the frequency of opioid-related adverse events 
(any opioid-involved OD [fatal or nonfatal] or any other substance use-related ED visit), in the 12 months 
following the index visit, the primary outcome. 
3.2 Secondary Objectives 
Aim 2:  To evaluate the impact of Relay on the following secondary outcomes: initiation of medication for 
opioid use disorder (MOUD); OD risk behaviors; time to next opioid-involved OD; ED visits for opioid OD, 
other substance use reason, and any cause; and self-reported opioid-involved OD. 
Aim 3: To identify mediators (e.g., OD knowledge, support, experience of stigma, peer modeling) and 
moderators (e.g., substance use history, age, sex, housing status) of the effect of Relay.
Aim 4:  To evaluate Relay’s implementation by assessing fidelity to the program model and exploring 
barriers and facilitators to its delivery and sustainability through qualitative interviews with patients, Relay 
peer navigators, and ED providers. 
4 Study Design and Endpoints 
4.1
Description of Study Design
This 2-arm multi-center RCT compares site-directed care (SDC) to the Relay intervention among patients 
presenting to the ED with a nonfatal opioid-involved OD. When individuals present to the ED with opioid 
OD, ED staff call the Relay hotline. The hotline operator will notify the research team. A RA will meet the 
patient in the ED, assess study eligibility, complete informed consent, and randomize participants to the 
SDC vs. Relay arm. Participants in both arms will complete interviews with research staff at baseline and 
at 1, 3, and 6 months after enrollment, and will provide consent for viewing their information in administrative 
data sets. Administrative data provide measures for the primary 12-month outcome analysis. All appropriate 
and applicable permissions will be obtained from the holders of administrative data prior to their use for 
research. Qualitative interviews will provide additional information on implementation of Relay. 
4.2
Study Endpoints
4.2.1 Primary Study Endpoints 
The primary endpoint is the number of opioid-related adverse events in the 12 months following the index 
ED visit. Opioid-related adverse events include: any opioid-involved OD (fatal or nonfatal) or any other 
substance use-related ED visit. 
4.2.2 Secondary Study Endpoints 
Secondary endpoints include the impact of Relay on the following outcomes: 
 
Initiation of medication for opioid use disorder (MOUD) 
 
OD risk behaviors 
 
Time to next opioid-involved OD 
 
ED visits for any cause  
 
ED visits for opioid OD 
 
ED visits for other substance use reasons 
 
Self-reported opioid-involved OD 

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We expect that Relay will be effective in increasing MOUD initiation because it is built on a foundation of 
prior work demonstrating that ED interventions by non-medical staff can effectively link patients to 
treatment. Measures of MOUD initiation will be gathered at each study visit. MOUD is defined as use of 
methadone, buprenorphine, or naltrexone that is prescribed by an office-based provider or provided by a 
treatment program as treatment for OUD. Initiation is defined as receiving MOUD within the 90 days 
following the index visit, for individuals who received no MOUD for at least 2 weeks prior to the index 
visit.38 Though infrequent, if patients are initiated on MOUD during the index visit (in the ED or, if admitted 
from the ED, in the hospital), the first outpatient MOUD encounter post-discharge will be the measure of 
treatment initiation. We will include MOUD initiated in the ED in sensitivity analyses. Our primary analysis 
is limited to the individual’s first episode of outpatient MOUD in the 90 days (3 months) following 
enrollment because this is the duration of contact with the Relay peer navigator and thus, for individuals 
in the Relay arm, is most attributable to the intervention. However, we will measure the total number of 
MOUD initiation episodes and time receiving MOUD for a full 6 months, to capture any continued 
intervention effect. Assessments at baseline and follow-up will collect data on MOUD in the past 90 days.  
Relay offers motivational counseling as well as sustained peer navigation that provides support and access 
to services that could help individuals reduce their OD risk behaviors. As such, we expect to detect greater 
reductions in risk behaviors in the Relay compared to the SDC arm. We will measure OD risk behavior 
using questionnaires that were developed by a group of OD researchers based on knowledge of OD 
behavioral risk factors and used in 3 prior studies to capture OD risk behavior.49,50,52 These questions 
measure the frequency, in the past 3 months, at which individuals: 1) used >1 opioid; 2) used 
benzodiazepines, alcohol, or cocaine/stimulant within 2 hours of an opioid; 3) used alone or behind a locked 
door; 4) used in a place they had never used before; and 5) used more than usual amount. The total risk 
score is an aggregation of responses to the individual questions. 
Time to next OD is measured using self-report. Frequency of ED visits for any cause (including visits that 
are not substance use-related) will be measured to assess whether there are differences in overall acute 
care use representing potentially negative health events. Additionally, we will examine frequency of ED 
visits for opioid OD and frequency of ED visits for other (non-OD) substance use reasons. These three ED 
visit secondary endpoints will be count outcomes using administrative data at 12 months and based on 
documentation of visit diagnosis (including primary and secondary diagnosis ICD codes, text diagnosis, 
and/or chief complaint). Self-reported opioid-involved OD is based on participant self-report in the 1-, 3- 
and 6-month follow-up visits and includes nonfatal ODs that did or did not result in an ED visit.    
We will also examine multiple potential mediators and moderators of Relay program effectiveness as further 
described in later sections. 
4.2.3 Exploratory Endpoints 
Exploratory endpoints include the impact of Relay on the following outcomes: 
 
Health services contacts (medical, mental health, harm reduction program) 
 
Possession of naloxone; number of times naloxone used 
 
Naloxone carrying by members of social network 
 
Death from any cause  
 
Opioid-involved OD deaths 
 
Any OD deaths 
 
Relay peer navigators are trained to take a motivational and patient-centered approach to reducing OD 
risk, which includes working with clients to reduce opioid use-related harms even if they are not ready to 
enter treatment. Death outcomes will be tracked using Vital Statistics records and DOHMH OD death 
reports (accessed by DOHMH) since prior research shows high rates of death, including those unrelated 
to OD, among patients following ED visits for non-fatal opioid OD.48 Other exploratory outcomes will be 
ascertained by participant self-report at baseline and follow-up visits. 
 

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5
Study Enrollment and Withdrawal
5.1
Inclusion Criteria 
5.1.1
Patients
Participants in this study are patients presenting to a participating ED with non-fatal opioid OD. Because 
we seek to enroll a broad and representative sample of individuals experiencing nonfatal opioid OD, 
exclusion criteria are limited. To be eligible to participate in this study, an individual must meet all of the 
following criteria: 
1. Adults ( 18 years)  
2. English- or Spanish-speaking  
3. Patient at a participating ED presenting with nonfatal opioid OD. Nonfatal opioid OD is initially 
determined by the treating ED clinician(s) based on the patient’s clinical characteristics, history, 
and/or response to naloxone treatment and is operationalized as the treating ED clinician calling 
the Relay hotline. Patients and/or ED providers will confirm opioid-involved OD at the time of 
eligibility assessment. 
4. Currently residing in NYC 
5.1.2 ED Staff and Relay Peers (Qualitative Interviews)  
For ED staff interviews, purposeful sampling will be used to select individuals with a variety of roles who 
have experience with the Relay program (e.g., physician, social worker). For Relay peers, purposeful 
sampling will be used to select peers with a variety of experiences (e.g., different amounts of time with the 
program, both part-time and full-time employees). Specific eligibility criteria include: 
 
1. Adults ( 18 years) 
2. English speaking 
3. ED staff with current involvement with the Relay program or Relay peers  
4. Currently employed in the ED at a participating study site or by the Relay program as a peer 
navigator 
 
5.2
Exclusion Criteria
5.2.1 Patients 
An individual who meets any of the following criteria will be excluded from participation in this study:
1. Unable to provide informed consent 
2. Currently incarcerated, currently living in another controlled environment prohibiting research 
contacts, or currently in police custody  
3. Known to be currently pregnant, based on patient or provider report 
4. Already participating in the study (patients will only be enrolled into the study once)  
5. Already actively engaged in the Relay program (enrolled within the past 90 days) 
6. Speaks only Spanish, at a site and time period when no Spanish-speaking RA is available. 
 
Individuals admitted to the hospital from the ED are eligible to participate in the study. 
5.2.2 ED Staff and Relay Peers (Qualitative Interviews)  
1. Unable to provide informed consent 
5.3
Vulnerable Subjects

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This study will not enroll vulnerable subjects, which under federal regulation include children, pregnant 
women, fetuses, neonates, and prisoners. Children under the age of 18 will be excluded. Pregnant women 
are excluded from the study because they have specific needs and access to services that are not 
generalizable to other populations. Women will be asked if they are currently pregnant as part of the study 
screening process; no further testing or questioning about pregnancy during the study will be done.  
 
Prisoners, as defined by the federal Office for Human Research Protections (OHRP), will not be enrolled in 
the study. Under these definitions, “prisoner” means “any individual involuntarily confined or detained in a 
penal institution. The term is intended to encompass individuals sentenced to such an institution under a 
criminal or civil statute, individuals detained in other facilities by virtue of statutes or commitment procedures 
which provide alternatives to criminal prosecution or incarceration in a penal institution, and individuals 
detained pending arraignment, trial, or sentencing (45 CFR 46.303(c)).” Pertinent to the current study, 
“individuals who are detained in a residential facility for court-ordered substance abuse treatment as a form 
of sentencing or alternative to incarceration” as well as “parolees who are detained in a treatment center 
as a condition of parole” are defined as “prisoners.” However, in accordance with federal definitions, 
“individuals who are receiving non-residential court-ordered substance abuse treatment and are residing in 
the community” as well as “persons living in the community and sentenced to community-supervised 
monitoring, including parolees” are not considered prisoners. Patients who are not currently incarcerated, 
under arrest, or otherwise detained but who may be on probation or parole will not be excluded from 
the study as these patients are not considered prisoners for research.  
 
5.3.1 Inclusion of Patients who become Prisoners during the Study  
It is possible that during the course of the study, some individuals in our study population may become 
considered prisoners. Our study enrolls a population with high rates of criminal justice involvement as a 
consequence of their opioid use.  Incarceration is a major risk factor for opioid-related overdose, and data 
on overdose and other substance-related adverse among this population is important for evaluating the 
effectiveness of the Relay intervention in our population of interest.   
 
Though the study will not enroll people who are considered prisoners at the time of enrollment, participants 
could potentially become prisoners over the course of their participation in the study. We will seek OHRP 
approval to ascertain follow-up data using administrative data sources only from these participants during 
the periods in which they are considered prisoners. We will not attempt to complete follow-up surveys with 
prisoners who are currently detained in a residential facility, due to a lack of ability to contact them in a 
secure, HIPAA-compliant manner. We do plan to use hospital administrative data that may include dates 
during which these individuals are considered prisoners. This data will be gathered through data abstraction 
from a variety of administrative health databases, as described in section 14.1. As collection of this 
information does not involve directly contacting the participants, we do not expect that the use of this 
administrative data constitutes an increased risk to these individuals.  
 
We will not be notified when a study participant becomes considered a prisoner during the course of the 
study. We do include questions regarding whether a person has been incarcerated since the previous study 
visit in our follow-up surveys. For follow-up study visits that are conducted by phone, research staff will 
confirm that the participant has privacy and is not a prisoner prior to administering research assessments.  
 
If an individual is considered a prisoner past the end of the study, we will not conduct any additional follow-
up, but will use the hospital administrative data from the time that they were a study participant. If an 
individual is considered a prisoner at one point in the study, and later in the study is no longer considered 
a prisoner, we will attempt to conduct all follow-up assessments as scheduled.   
 
We do not expect any direct benefit to individuals who are considered prisoners over the course of the 
study. We do expect that the information gathered about these individuals will provide important information 
for the study and may benefit our population of interest in the longer term.   
 

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We do not expect that the collection of administrative data and select follow-up information from this 
population poses more than minimal risk. We will take steps to protect this data as outlined in section 13.5. 
 
5.4
Strategies for Recruitment and Retention 
5.4.1 Patients 
We plan to enroll 350 participants. Patients arriving to the emergency department (ED) with a nonfatal 
opioid overdose (OD) for which the ED providers have called the Relay hotline will be approached by 
trained RAs, after they are medically stable. RAs will be alerted to potentially eligible patients by the 
Relay Hotline, which is activated by the ED care providers or staff when a patient presents to the ED with 
a nonfatal opioid OD. RAs will request permission from the patient to inform them about the study, assess 
eligibility, explain the study procedures and incentive schedule, and offer enrollment to those who are 
eligible. We estimate that we will be able to meet recruitment goals over an approximately 15-month 
period.  
Inclusion of women and minorities. Patients will not be excluded on the basis of sex/gender, race or 
ethnicity. The sample is expected to be representative of the patient population presenting after opioid OD 
to the five diverse urban EDs chosen as study sites. Based on NYC Department of Health and Mental 
Hygiene Syndromic Surveillance data for opioid OD presentations at the study site EDs, women are 
anticipated to represent 33% of the study sample and the proportion of racial/ethnic minorities included in 
the sample will vary by site, and will range from 27% to 83%. To ensure the ability of diverse patients to 
participate in the study, study materials will be available in both English and Spanish.  
 
Retention Plan. Successful tracking and retention over time is a multifaceted effort requiring simultaneous 
strategies at the management, staff, participant, and compensation levels. To enhance retention in follow-
up procedures, we will use several methods that have yielded long-term retention rates above 80% in 
numerous prior studies with vulnerable populations.53-55 These methods include the following:  
 
1. Locator form and contact information. We will ask participants to provide detailed locator 
information at the time of enrollment. The locator information form will include participants’ phone numbers, 
addresses, email addresses, and at least three secondary contacts (e.g., friends, case workers) that we 
may use if we are unable to reach them directly. Collecting this information is necessary to improve ability 
to contact study participants for follow-up visits, given that participants’ own contact information may change 
during the course of the study. Further, locator form information will include information on places frequently 
visited by participants (e.g., methadone treatment programs, homeless shelters). We will collect information 
on participants’ social media “handles” for Facebook, Instagram, etc. so that we can also locate them via 
these methods if necessary. Of note, when using secondary contacts or social media accounts, research 
staff members will only say they are calling/reaching out from the “emergency department study,” “NYU 
health study,” or “health study” and will not divulge the nature of the research study. Participants will be 
informed they should only provide contact information they are comfortable with. Collecting such detailed 
locator information in addition to phone numbers is necessary given that some participants may not have a 
stable phone number of their own, and mobile phone numbers may change. Locator information will be 
confirmed and updated at each contact and at each follow-up assessment.  
 
2. Tracking. Retention efforts will begin shortly after enrollment. We will maintain regular contact 
via mail (e.g., a thank you card sent after the baseline interview, holiday cards). These are useful ways to 
maintain rapport and returned mail will help identify participants at risk of becoming lost to follow-up. All 
recruitment and retention materials will be approved by the IRB. Materials sent by mail do not mention 
substance use but instead reference a “emergency department study,” “NYU health study,” or “health 
study.” 
 
Tracking participants begins with a direct approach: contacting the participant by phone, email, 
social media, and/or mail. If direct tracking is not successful, we will begin more intensive outreach efforts. 
The first step will be to contact participants’ secondary contacts (e.g., friends, family, case workers) listed 

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on the locator form (for whom participants have given our consent to contact). If these tracking methods 
are unsuccessful, we will initiate systems-level tracking. At enrollment, participants will have been asked to 
list agencies with which they have contact, and we will send a letter or flyer to each of these agencies 
requesting that they forward the enclosed letter to the participant’s most current address. Additionally, we 
will use free systems-level tracking methods commonly used to locate participants in longitudinal studies. 
These include searching web-based phone and address directories, as well as criminal justice directories. 
In some cases we will attempt place-based tracking, canvassing locations where the participant reports 
often spending time. Further, we will monitor ED visits to study hospitals made by patients subsequent to 
the baseline visit, which may present an opportunity for performing follow-up visits. This monitoring will 
occur via Epic track boards and alerts provided to the study team via a secure and password protected 
online portal by the HealthIx RHIO (see Section 14.1).  
 
3. Compensation. We will reimburse participants for their time completing study activities, as 
described in more detail in the sections that follow. 
 
4. Reminders. Beginning approximately two weeks before each follow-up assessment is due, 
study staff will begin reaching out to participants. Staff will make multiple attempts at different times of day 
and days of the week, and via different contact modalities, to reach participants. Staff will conduct multiple 
contact attempts for participants who do not complete scheduled assessments; windows before and after 
the follow-up assessment due date will be allowed to complete the assessments (up to 1 month will be 
allowed for the final 6-month assessment), though attempts will be made to complete them as close as 
possible (+/- 3 days) to the due date. 
 
5.  Flexibility. Follow-up visits may be completed by telephone and may occur during evening or 
weekend hours. This will make it easier for participants to schedule and complete their assessments, 
without requiring them to travel to a research site.  
 
5.4.2 ED Staff and Relay Peers (Qualitative Interviews) 
We plan to enroll approximately 22 participants (10-12 ED staff and 10 Relay peer navigators) for qualitative 
interviews. ED staff who have current involvement with the Relay program and Relay peers will be 
contacted by study staff to inform them about the study, assess eligibility, explain the study procedures and 
incentives, and offer enrollment to those who are eligible. As described in Section 5.1.2, for ED staff 
interviews, purposeful sampling will be used to select potential participants who have a variety of roles who 
have experience with the Relay program (e.g., physician, social worker,), to maximize the amount we are 
able to learn about the program’s implementation. For Relay peers, purposeful sampling will be used to 
select peer participants with a variety of experiences (e.g., different amounts of time with the program, both 
part-time and full-time employees). As participation in the qualitative interviewing portion of the study is 
limited to one interview, retention of participants is not applicable.  
5.4.3 Use of DataCore/Epic Information for Study Procedures 
Study staff will use Epic to look up information about patients after receipt of a call about a potentially 
eligible patient from the Relay hotline (as described in the protocol), to gather information about potential 
study eligibility and likely duration of stay in the ED. Study staff will also monitor the Epic ED track boards 
for NYU Langone—Tisch and NYU Langone Hospital—Brooklyn to look for study participants presenting 
to the EDs subsequent to the baseline visit, which may present an opportunity to perform a follow-up visit. 
As described elsewhere in the protocol, Epic will also be used to complete the baseline visit exit survey 
and collect outcome data. 
5.5 Duration of Study Participation
The duration of active study participation is approximately 6 months. After screening and enrollment in the 
ED, participants in both arms will complete interviews with research staff at baseline and at 1, 3, and 6 
months and will provide consent for viewing their information in administrative data sets for 12 months. 

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5.6
Total Number of Participants and Sites 
Recruitment will end when approximately 350 evaluable participants are enrolled across all three study 
sites (representing 4 EDs). It is expected that approximately 355 total participants will be enrolled in order 
to produce 350 evaluable participants. If there are multiple participants who withdraw consent to use their 
data after they are enrolled or otherwise need to be terminated from the study, we may recruit additional 
participants as needed to evaluate the primary study endpoints. There are no specified target accrual 
numbers for NYU Langone vs. other study sites, as enrollment will occur based on ED providers having 
patients who present for opioid OD for whom they activate the Relay hotline; therefore, the researchers 
do not have control over at which site potentially eligible patients will present. 
 
We will also enroll approximately 10-12 ED provider participants and 10 Relay peer navigator participants 
in qualitative interviews to learn about barriers and facilitators to the intervention model; these are just 
estimates and the exact number of participants in the qualitative interviews will be guided by theoretical 
saturation as is standard best methodologic practice. Qualitative interviews are described in Section 
7.3.5.  
5.7
Participant Withdrawal or Termination
5.7.1 Reasons for Withdrawal or Termination 
Participants are free to withdraw from participation in the study at any time upon request.  
An investigator may choose to terminate a participant’s participation in the study if: 
 
Any clinical adverse event (AE), laboratory abnormality, or other medical condition or situation 
occurs such that continued participation in the study would not be in the best interest of the 
participant. 
 
A participant is discovered to have been enrolled in the study despite not having met study 
exclusion criteria at the time of enrollment (e.g., dementia / unable to understand study consent). 
Of note, while pregnancy and incarceration are exclusion criteria for enrollment in the study, if a 
participant becomes pregnant or a prisoner during the course of the study, they will not be terminated 
from the study. Administrative data will still be used for assessment of outcomes, and study interviews 
may be conducted with pregnant participants (See Section 5.3.1 for details on prisoner assessments).   
5.7.2 Handling of Participant Withdrawals or Termination 
If participants request to withdraw from the study, they will be asked whether the data already collected 
from them can still be used. Participants will be asked to provide their request for study withdrawal in 
writing, sent to the study PI. Participants may choose not to complete individual follow-up interviews 
without actually formally withdrawing from the study; in such cases investigators will affirm with 
participants that we can still access their health care data for measurement of the study outcomes. The 
primary outcome measures use administrative data, which will be available for all individuals who enroll in 
the study, even if they are lost to follow-up, unless they have withdrawn permission for us to use their 
data. Participants who withdraw or are terminated from the study may still receive continued services from 
the DOHMH Relay program if they desire them.   
 
If a participant is terminated from the study by the investigators, the participant will be informed in writing 
via a letter mailed to their primary address. Due to confidentiality concerns, details of the reason for 
termination will only be provided to the participant directly by phone. 
5.7.3 Premature Termination or Suspension of Study 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable 
cause for such suspension or termination. Written notification, documenting the reason for study 
suspension or termination, will be provided by the suspending or terminating party to Kelly Doran, 

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Jennifer McNeely, and the CDC. If the study is prematurely terminated or suspended, the PI will promptly 
inform the IRB and will provide the reason(s) for the termination or suspension. 
 
Circumstances that may warrant termination or suspension include, but are not limited to: 
 
Determination of unexpected, significant, or unacceptable risk to participants related to the study. 
 
Insufficient compliance to protocol requirements. 
 
Meeting the study stopping rule described in Section 8.7. 
 
The study may resume once concerns about safety and protocol compliance are addressed and satisfy 
the sponsor and/or IRB. 
 
6 Behavioral/Social Intervention 
6.1
Study Behavioral or Social Intervention(s) Description
Individuals assigned to the Relay arm will receive the Relay peer navigator-led intervention. The Relay 
program is designed and administrated by DOHMH; the NYULH study investigators do not have control 
over Relay program operations. DOHMH may modify the intervention components or administration. The 
Relay program model by design is tailored to patient needs and therefore exact intervention components 
delivered to individual Relay participants may differ; the study investigators will monitor but will not 
attempt to change intervention components delivered. The present study is adding 1) random assignment 
and 2) evaluation procedures to investigate the implementation and effectiveness of Relay.  
 
DOHMH’s Relay program comprises two components, both conducted by the peer navigator.  
The first component is conducted in the ED after the patient has been medically stabilized and consists of 
1) engagement and support, to build relationships and foster trust; 2) tailored overdose prevention 
information and risk reduction counseling; 3) training on naloxone and provision of a naloxone kit if one 
has not yet been provided by the ED (or additional kits if needed); and 4) offer to follow up with the 
individual for up to 90 days to provide ongoing support and linkage to services, including opioid treatment 
programs. Throughout this component, the peer navigator serves as a positive role model and seeks to 
reduce stigma by highlighting shared lived experiences. Patients may be uncomfortable, distressed, and 
anxious to be discharged; peer navigators address these concerns in a number of ways. Consistent with 
the motivational interviewing approach, peer navigators support patients’ autonomy and ‘roll with 
resistance.’ Engagement is fostered through tangible support (obtaining snacks, getting answers to 
questions) and instrumental (social) support. Tailored OD prevention education and training on naloxone 
is provided when patients are comfortable and engaged, and takes a motivational interviewing approach. 
The peer navigator obtains the patient’s contact information and makes plans to follow up with them.  
The second component comprises peer navigator follow-up in-person and by phone for up to 90 days. 
The goal of these contacts is to provide ongoing support and linkage to treatment, harm reduction, health 
care, and social services. Similar to the first intervention component, the peer navigator serves as a role 
model and shares his/her personal experiences as a means of reducing stigma and fostering 
engagement and motivation. Follow-up activities may vary depending on the needs of the participant but 
could include: ensuring that the participant has a naloxone kit and fostering discussion of how naloxone 
can be used to protect the participant and those in his/her social network from a fatal OD (e.g., provide 
kits to social network members, discuss naloxone with drug use partners); using a problem-solving 
approach to highlight and help resolve factors that might impede uptake of referrals, such as 
transportation challenges, lack of clarity on where to obtain services, and stigma; asking participants to 
clarify their personal goals regarding service use and risk reduction. In general, in these contacts, the 
peer navigator ‘checks in’ with the participant without applying pressure or judgment, monitors steps 
taken by the participant to achieve personal goals, and provides encouragement and support. Taken 
together, these activities in the ED and post-discharge are designed to foster motivation to engage in 
services, carry naloxone, initiate MOUD, and reduce risk for future OD; provide support for steps taken 
toward these outcomes; and foster access to services and resources.  

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Site-directed Care (SDC) arm. Patients randomized to the SDC arm will receive site-specific care 
delivered to patients with OUD/SUD. All of the site EDs included in this study have implemented a variety 
of their own initiatives—apart from Relay—for patients who present with OUD or after opioid OD. These 
initiatives include, but are not limited to: becoming credentialed as OOPP’s (opioid overdose prevention 
programs), employing health educators to distribute naloxone kits, implementing “hard stops” in the 
electronic medical record to prevent patient discharge prior to naloxone receipt, conducting universal 
screening for drug and alcohol use, providing SBIRT (screening, brief intervention, and referral to 
treatment) services, and ED-initiated buprenorphine (for X-waivered ED physician prescribers) with 
outpatient follow-up. The exact services / initiatives vary by site and are provided based on site-specific 
protocols. Study investigators will not attempt to influence SDC but will track the OD prevention-related 
ED care that participants receive with a patient exit survey administered during the baseline study 
assessments. The exit survey will document care delivered by ED staff including OEND, buprenorphine 
induction, substance use screening, counseling/brief intervention, and treatment referrals. Collecting this 
data will allow us to consider individual differences in ED services received in our analyses.   
In the SDC arm, RAs will ensure that—at a minimum—patients receive overdose education and naloxone 
distribution (OEND) as well as a list of opioid treatment programs. RAs will give patients DOHMH OD 
education materials (including general information on OD and specific instructions on how to use 
naloxone) and 1-2 DOHMH-supplied naloxone kits (if one has not already been given by the ED staff). 
RAs will also give SDC arm patients a printed list of information on addiction treatment programs. 
 
Patients in the SDC arm will also receive a flyer with information about Relay and a telephone number 
they can call to receive Relay services at any time after their ED visit. While we expect few patients will 
call for services, DOHMH and the study investigators agree that for fairness all study participants should 
be offered the ability to receive Relay services if they choose to do so. DOHMH and research staff will 
track any Relay services provided in this patient-initiated manner. After the 12 month study follow-up 
period (for the primary outcome analysis) has concluded, DOHMH will contact participants who had been 
assigned to the site-directed care arm to offer Relay services. 
 
All patients (in the study or otherwise) can receive the full range of services offered at the individual study 
ED per existing protocols at each site. 
6.1.1 Administration of Intervention 
The Relay intervention consists of two components, both administered by the peer navigator. The first 
component is delivered in-person in the ED after the patient has been medically stabilized. The peer 
navigator then obtains the patient’s contact information and makes plans to follow up over the next 90 
days. Follow-up visits are provided in person or by phone with a Relay peer navigator. The exact 
services, mode, timing, frequency, and duration may depend on individual participant needs and desire to 
participate. The intervention is administered by DOHMH. The NYU study investigators are not 
administering the intervention. 
6.1.2 Procedures for Training Interventionalists and Monitoring Intervention Fidelity 
Relay peer navigators receive thorough training and ongoing supervision from DOHMH. DOHMH may 
change training protocols without approval from the study investigators. The study investigators are not 
responsible for training Relay peer navigators. Currently, a standardized approximately 3-day new hire 
orientation and training covers all facets of the Relay program including OD education, naloxone 
distribution, MOUD, treatment referrals, tenets of peer navigation, building relationships, assessing and 
addressing patient needs, and documentation of patient contacts. Peer navigators additionally receive 
approximately 24 hours of formal training in motivational interviewing. Peer navigators meet with 
supervisors (Licensed Masters-Level Social Workers or Mental Health Counselors) regularly and participate 
in monthly group supervision meetings for ongoing training, program updates, and presentation of difficult 
cases. Supervisors also provide assistance and individual support for difficult cases. Additionally, peer 
navigators receive training in self-care and participate in voluntary group sessions with an external social 
worker to discuss any frustrations, stress, feelings, and emotions regarding their Relay work. 

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Study staff: Study RAs will complete privacy and security, HIPAA, and human subjects protections trainings. 
RAs will be employees of NYU School of Medicine as well as the study sites (for baseline visits at those 
site EDs). All RAs will receive standardized, thorough training in the study procedures prior to beginning 
work on the study. All RAs will receive ongoing supervision from the study Project Manager under direction 
from the PIs and Site PIs.  
Fidelity monitoring of intervention: We will assess fidelity as follows: 1) All participants will complete an RA-
administered exit survey interview at the conclusion of the baseline visit (in some cases the exit survey may 
be completed by phone the next day). The exit survey will assess what interventions the participant received 
in the ED that are relevant to opioid OD (e.g. substance use screening, OD education, naloxone kit(s) 
received, treatment referral/follow-up offered). The exit survey interview will also ensure that SDC arm 
participants receive, at a minimum, OEND, a list of treatment programs, and a handout with Relay program 
information. RAs will need to check off boxes in the exit survey indicating that the participant has received 
these items. Participants will also be asked at follow-up assessments what additional Relay program 
services they have received in the interval since the last assessment, 2) After each participant contact, 
Relay peer navigators complete content checklists to capture the duration of the interaction and activities 
performed during the session. To minimize burden to DOHMH and the peer navigators, the study will use 
the existing peer navigator contact content checklists used by DOHMH. Throughout the study, we will use 
this data to assess intervention dose, measured using the number, type (phone or in-person conversation, 
accompaniment to appointments), and duration of contacts; this information is routinely logged by the Relay 
peer navigator for DOHMH, as part of regular program activities. We will obtain a MOU/DUA to use these 
checklists to assess study fidelity.  
6.1.3 Assessment of Subject Compliance with Study Intervention 
Consistent with the motivational interviewing approach, participants who do not comply with the study 
intervention (e.g., decline referrals or decline to set substance use risk reduction goals) remain in the 
Relay intervention, and the peer navigator continues to offer support. Participant receipt of intervention 
components will be tracked both through self-report assessments and through Relay program data. 
7 Study Procedures and Schedule 
7.1
Study Procedures/Evaluations
Study procedures/evaluations in this protocol include: screening, consent, enrollment, randomization, 
research interviews (self-reported assessments and semi-structured qualitative interviews), overdose 
prevention education, as well as data extraction from administrative data sets and Relay programmatic 
data. All participants receive standard medical care in the ED. Those in the Relay intervention arm 
additionally receive the DOHMH Relay program, and those in the SDC arm additionally receive RA-
delivered OD prevention education. There are no laboratory results, biospecimens, or images collected as 
part of this research protocol.  
7.1.1 Study Specific Procedures Overall 
 
Eligibility assessment and study consent 
 
Randomization to study arm 
o 
Relay intervention: peer navigator administered OEND, motivational counseling, referrals 
and support and linkage to services while in the ED and for up to 90 days post-discharge.   
o 
Site-directed Care: RA will ensure that participant receives, at a minimum, overdose 
prevention education consisting of OEND, treatment program list, and Relay 
informational handout.  
 
Administration of questionnaires for patient-reported outcomes, at baseline, 1-month, 3-months, 
and 6-months. 
 
Baseline exit survey documenting opioid-related services received by the participant in the ED. 
 
Collection of participant information (to allow linkage with administrative data) 
 
Collection of participant locator form information 

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Data extraction from administrative datasets including vital statistics / mortality data, DOHMH OD 
deaths data, and health services use data (which may include Regional Health Information 
System [RHIO], Statewide Planning and Research Cooperative System [SPARCS], Medicaid, 
and electronic medical record [EMR] data, as available) 
 
Semi-structured qualitative interviews with Relay participants, peer navigators, and ED staff. 
 
Assessment of study intervention adherence (Relay contact content checklists and assessment of 
DOHMH Relay program data)  
 
7.1.2
Standard of Care Study Procedures
All patients in the study (Relay arm + SDC are) will receive standard medical care as they would regularly 
receive in the ED, including a range of relevant substance use services offered at the individual study ED 
per existing care protocols at each site. These services vary by site and are offered to patients either by 
clinician discretion or according to specific protocols at each study site. Relevant services vary by site and 
by patient and may include, but are not limited to: health education, distribution of naloxone kits, universal 
screening for drug and alcohol use, SBIRT (screening, brief intervention, and referral to treatment), and 
ED-initiated buprenorphine with outpatient follow-up. Patients also receive standard medical care as they 
would usually receive in the ED. The exact services vary depending on site- and patient-specific factors 
and will be captured using patient exit surveys. The study investigators will not attempt to change 
standard care provided at study sites. 
7.1.3 ED Staff and Relay Peer Qualitative Interview Procedures 
We will enroll approximately 10-12 ED provider participants and 10 Relay peer navigator participants in 
qualitative interviews to learn about barriers and facilitators to the intervention model; Interviews will be 
conducted one-on-one with an interviewer trained in qualitative research techniques. To allow flexibility 
given the ongoing COVID-19 pandemic, interviews will be conducted either in-person, by phone, or by 
secure web conferencing (e.g., WebEx). At the qualitative interview contact the interviewer will review the 
verbal consent script, attain verbal consent for the study and for audio recording, and complete a one-on-
one in-depth interview in which the interviewer uses an interview guide. Interviews will be semi-structured, 
guided by an interview guide (see Interview Guide Attachment), with flexibility to allow for additional 
questions as needed and to maximize interview flow. Interviews will be digitally recorded and professionally 
transcribed. As noted previously, any identifying information will be removed from transcripts prior to 
analysis. Basic characteristics of interview participants (e.g., age, race/ethnicity, gender, job role) will also 
be recorded, and the interviewer will record field notes at the conclusion of the interview with any additional 
pertinent observations. Qualitative interview participants will receive an incentive payment at the conclusion 
of the interview. 
7.2
Laboratory Procedures/Evaluations 
Not applicable. 
7.3
Study Schedule
7.3.1 Screening and Enrollment/Baseline 
Screening/Enrollment/Baseline Visit (Visit 1, Day 0) 
 
There is no separate screening visit for this study. Screening for study eligibility will occur during the same 
ED or hospital visit as the study enrollment / baseline visit. The only patients who are potentially eligible 
for the study and who will be screened by RAs are those for whom the ED staff has called the Relay 
program hotline. As part of existing protocols, ED staff at the study sites call the Relay program hotline for 
patients who have presented to the ED after a nonfatal opioid OD. ED staff are instructed to call the Relay 
hotline when a patient presents with nonfatal opioid OD, as determined by the treating clinician(s). The 
Relay hotline is operated by a HIPAA-compliant call center that provides 24-hour service, 365 days/year. 
It is used by all EDs participating in Relay, including the study sites. ED staff are instructed to call the 
Relay hotline as soon as they become aware of a patient presenting for nonfatal opioid OD, to help 

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ensure that there is adequate time for both study procedures and (if randomized to the Relay arm) 
delivery of the Relay intervention. 
 
Assignment of the RA. The Relay hotline operator contacts the appropriate research staff member 
based on date and time of day according to a call schedule that will be provided to the hotline. The 
PM/RC/ or RAs will receive information that the Relay hotline routinely collects to facilitate locating the 
patient in the ED (e.g., patient name, referring provider, location or bed number). The RA will determine 
whether the patient is already an active Relay participant and/or has already participated in the study and 
proceed according to study eligibility guidelines. The appropriate RA for the study site will go directly to 
the ED, arriving within 1 hour (typically within 15-45 minutes depending on study site). Upon arrival, the 
RA will confirm with ED staff that the patient is medically stabilized (as needed), and then approach the 
bedside and introduce themselves to the patient. After requesting permission from the patient to provide 
information about the study, the RA will explain the study procedures and assess eligibility. Clear 
protocols for RAs will be specified in the study SOP/MOP. 
 
Screening for Eligibility. RAs will follow a standardized series of questions on REDCap using a study 
iPad (see attachment) to screen patients for study eligibility. If there is any question about a patient’s 
capacity to provide informed consent, RAs will consult the ED treating team (e.g., attending physician) 
and/or complete the UBACC (see attachment), a brief consent capacity quiz that has been previously 
validated and used in other ED studies.57 If the patient is not eligible for the study, the RA will call the Relay 
peer navigator to inform him/her of a patient who is not eligible for the study but who could potentially 
receive Relay services (apart from the study). 
 
Enrollment and informed consent. RAs will enroll and obtain consent from eligible patients for 
participation in the research activities. The RA will explain the study procedures and incentive schedule, 
answer any questions, and offer enrollment. Patients will be informed that the decision to participate in 
the research is voluntary and will not affect the medical care they receive from the ED. If the patient is 
willing to participate and signs the informed consent form, only then will study staff commence collecting 
additional information. The informed consent process will be conducted in-person on a study iPad using 
REDCap (using electronic consent/signature). The participant will be given a paper or e-mailed copy 
(through REDCap) of the informed consent form and key information sheet. If the patient declines to 
participate in the study, the RA will call the Relay peer navigator to inform him/her of the patient who has 
declined to participate in the study but who could potentially receive Relay services (apart from the study, 
as part of standard DOHMH Relay practice).  
Randomization. Patients who meet eligibility criteria and agree to participate in the study will be 
randomized to the SDC vs. Relay arm. The RA will use an electronic system (REDCap) to create a 
random assignment to a treatment arm. Randomization uses a 1:1 ratio and is stratified by site; permuted 
blocks with variable blocks of size 4 and 6 will be used to maintain balance over time and prevent 
prediction of assignment by the RA. Upon randomization, the RA will immediately inform the participant of 
the treatment arm assigned. For Relay arm participants, the RA will then inform the Relay peer navigator 
by phone. If the participant is assigned to the Relay arm, the peer navigator will generally arrive at the ED 
within 30 minutes.   
 
Baseline data collection. RAs will administer a baseline self-reported assessment. RAs will also collect 
participant identifying information to allow future linkage with administrative data, and detailed locator 
form information to enable study staff to contact participants for follow-up assessments. The locator form 
collects multiple forms of contact information for the individual (e.g., phone numbers, e-mail, social media, 
addresses, ‘hang out’ locations) and phone numbers for at least 3 individuals who will know how to reach 
them in the future. The locator form is based on procedures used successfully by our team in prior 
studies, and is a crucial component of the retention strategy. RAs will follow procedures to maximize 
participant privacy. If at any point during baseline data collection an ED provider needs to provide clinical 
care to the patient, the RA will pause study procedures so as not to interfere with clinical care.  
Because participant identifiers and locator form information are not sensitive to the Relay intervention, 
RAs can collect this information at the time that is most appropriate to maximize patient flow and ensure 

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peer navigators can engage patients. As much as possible, RAs will complete the baseline assessment 
prior to participant receipt of the Relay intervention (for participants in the Relay arm). 
 
Administration of Relay intervention or SDC. Relay peer navigators will deliver the ED portion of the 
Relay intervention for participants in the Relay arm. For participants in the SDC arm, RAs will ensure that, 
at a minimum, participants receive (from the RA) OEND, a list of treatment programs, and an 
informational handout about Relay. RAs will document the number of naloxone kits (1-2) distributed as 
described in Section 14.1. Participants will receive other site-directed care as specific to the particular ED 
and/or care provider (not under the control of the study). See other sections of this protocol for a detailed 
description of the Relay intervention and SDC conditions. 
 
Exit survey. Near the end of the ED stay, the RA will complete an exit survey recording what intervention 
elements were received by participants. If needed (for example, in instances where the ED visit spans 
many hours), the RA may complete the exit survey by phone with the participant the day following the ED 
visit. 
 
Wrap up. RAs will schedule the first follow-up assessment and will give participants a study contact card 
with the appointment information and information on how to contact the study team. Participants will be 
given the study incentive payment and a FAQ document about the Greenphire ClinCards. Within the 
week following the baseline visit the participant will be mailed a thank you card. 
Hybrid Baseline visits due to COVID-19 
Due to COVID-19, baseline visits may be conducted in a hybrid manner in order to minimize staff time in 
the ED. In this instance, RAs would screen, enroll, consent, and randomize patients in person in the ED. 
They would then conduct the survey section of the baseline visit virtually from a private office location 
adjacent to the ED using iPads (one iPad will be handed to the participant) using video conferencing with 
a secure, HIPAA compliant platform (WebEx). 
7.3.2 Intermediate Visits 
Acceptable time windows are given for each study visit, but attempts will be made to conduct the visit as 
close as possible to the intended day (+/- 3 days when possible).  
 
Visit 2 (Day 30 +14/-7) (*All participants, conducted by RA or PM) 
 
RA administers structured interview over the phone or in person (30-40 minutes).  
 
Study incentive payment added to ClinCard. 
 
Visit 3 (Day 90 +30/-14) (*All participants, conducted by RA or PM) 
 
RA administers structured interview over the phone or in person (30-40 minutes). 
 
Study incentive payment added to ClinCard.   
7.3.3 Final Study Visit 
Final Study Visit (Visit 4, Day 180 +30/-14) (*All participants, conducted by RA or PM) 
 
RA administers structured interview over the phone or in person (30-40 minutes).   
 
Participant is provided with final study incentive payment via ClinCard.  
 
Any questions about the study are answered and participant is given contact information for the 
study if needed. 
7.3.4 Withdrawal Visit 
Participants may choose to withdraw from the study by informing the PI in writing. There will not be a 
separate withdrawal visit. See Section 5.7 for additional details. 
7.3.5  Unscheduled Visits 
Qualitative interviews with patients: A subset of study participants will be invited to participate in semi-

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structured qualitative interviews. Purposeful selection will be used to choose approximately 12 English-
speaking participants with a variety of experiences and perspectives to contribute to the interviews. The 
purpose of the qualitative interviews is to explore barriers and facilitators to delivery and sustainability of 
the Relay program. Interviews will be conducted one-on-one with an interviewer trained in qualitative 
research techniques. At the qualitative interview contact the interviewer will review the verbal consent script, 
attain verbal consent for participation and audio recording, and complete a one-on-one in-depth interview 
in which the interviewer uses an interview guide. Interviews will be digitally recorded and transcribed. Basic 
characteristics of interview participants (e.g., age, race/ethnicity, gender) will also be recorded, and the 
interviewer will record field notes at the conclusion of the interview with any additional pertinent 
observations. Qualitative interview participants will receive an incentive payment at the conclusion of the 
interview. 
 
Relay contacts: For participants in the Relay intervention arm only, the peer navigator stays in touch by 
phone for up to 90 days. In the Relay program, certain follow-up call attempts are mandated but otherwise 
may vary. The participant is encouraged to call or text the peer navigator any time if he/she has questions 
or unmet service needs. In these phone contacts, the peer navigator ‘checks in’ with the participant, 
monitors steps taken by the participant to achieve personal goals, and provides encouragement and 
support. Peer navigators log the number, type, and duration of contacts, which comprise the intervention 
‘dose.’ Participants in the SDC arm will receive a card or flyer with information about Relay and a telephone 
number they can call to receive Relay services at any time after their ED visit. DOHMH will track any Relay 
services provided in this patient-initiated manner so that we can account for this in our analysis. 
 
Additional unscheduled visits: Participants in both the SDC and Relay intervention arms will be given a 
study phone number and may reach out to the RA at any point during the study period. All such unscheduled 
encounters will be documented by the RA using a designated study form. RAs will also attempt to contact 
study participants between visits to confirm contact information and intermediate and final study 
appointment information. RAs will mail participants appointment reminder letters. If study staff is still unable 
to reach the participant after multiple attempts of contact, and the participant has given permission to do 
so, RAs may mail a letter to the participant’s contacts asking to help our study staff get in contact with the 
participant. Additionally, RAs will mail participants a thank you card and a holiday card when applicable. 
Finally, if participants present to the ED after a repeat opioid OD in which the Relay hotline is activated, 
RAs will attempt to visit the participant in the ED if possible (e.g., if an RA is available) to confirm contact 
information and visit appointments (or to conduct one of the scheduled intermediate or final study visits if 
within the appropriate time window).  
7.4
Concomitant Medications, Treatments, and Procedures 
All participants will receive care in the ED as they normally would during their baseline ED visit. 
Medications, treatments, procedures, and other care are at the discretion of the ED treatment team and 
will not be influenced by the study. 
7.5
Justification for Sensitive Procedures
7.5.1 Precautionary Medications, Treatments, and Procedures 
Not applicable. 
7.6
Prohibited Medications, Treatments, and Procedures
Not applicable. 
7.7
Prophylactic Medications, Treatments, and Procedures 
Not applicable. 

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7.8
Participant Access to Study Intervention at Study Closure
After the 12 month study follow-up period (for the primary outcome analysis) has concluded, the DOHMH 
will attempt to contact participants who had been assigned to the SDC arm to offer Relay services. 
Additionally, after study closure all participants will continue to be eligible for Relay services should they 
present again to an ED participating in the Relay program. Study participants will still be able to access all 
existing community/social services for which they are eligible and ED/health care at the end of the study 
as they would if they had not participated in the study. 
8 Assessment of Safety 
The Data and Safety Monitoring Plan submitted to the CDC is included as an attachment. Key elements 
are summarized below. 
8.1
Specification of Safety Parameters
The following safety parameters are study endpoints: 
 
Opioid-involved OD (fatal and nonfatal)  
 
Substance use-related ED visit 
 
These study endpoints will be captured using REDCap electronic data capture from interim and final 
study visit questionnaires, as well as at 12 months from administrative data analysis. Reports including 
these endpoints will be produced and discussed at regular DSMB meetings. Given the morbidity of the 
population being studied, we expect that these study endpoints will occur not infrequently. The stopping 
rule for the study will be based on the objective, serious endpoint of OD mortality and are specified in 
Section 8.7 and the DSMP which will be approved by the study sponsor. 
 
This is a minimal risk study; therefore, no causally related AEs or SAEs are anticipated. AEs and SAEs 
that are not study endpoints are described in the sections that follow. Event impact will be formally and 
informally monitored and formally documented, and the MPIs will implement steps to prevent future 
similar events from occurring.  
8.1.1 Definition of Adverse Events (AE) 
IRB required text: An adverse event (AE) is any symptom, sign, illness or experience that develops or 
worsens in severity during the course of the study. Intercurrent illnesses or injuries should be regarded as 
adverse events.  Abnormal results of diagnostic procedures are considered to be adverse events if the 
abnormality: 
 results in study withdrawal 
 is associated with a serious adverse event 
 is associated with clinical signs or symptoms 
 leads to additional treatment or to further diagnostic tests 
 is considered by the investigator to be of clinical significance 
 
Study specific text: For the purpose of this study, the following events will not be reported as AEs: 
 Mild unrelated event. 
 Moderate unrelated event. This would typically include physical events that were considered 
unrelated to study participation.  
 Substance use events expected for the population being studied, including:  
o 
Worsening of substance use  
o 
Need for higher level of care  
o 
Signs and symptoms of substance use disorder or withdrawal  
o 
Drug or alcohol craving  

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o 
Medical events, including but not limited to injuries, overdose, and medical conditions, 
that are directly or indirectly related to substance use 
8.1.2 Definition of Serious Adverse Events (SAE) 
Serious Adverse Event 
IRB required text: Adverse events are classified as serious or non-serious.  A serious adverse event is 
any AE that is:  
 
 fatal 
 life-threatening 
 requires or prolongs hospital stay 
 results in persistent or significant disability or incapacity 
 a congenital anomaly or birth defect 
 an important medical event 
 
Important medical events are those that may not be immediately life threatening, but are clearly of major 
clinical significance. They may jeopardize the subject, and may require intervention to prevent one of the 
other serious outcomes noted above. 
 
All adverse events that do not meet any of the criteria for serious should be regarded as non-serious 
adverse events.  
 
Study specific text: Given the population being enrolled in the study, it is expected that most participants 
will continue to have substance use, several may have overdose, and many may have hospitalizations or 
other treatments related to their substance use. We will be assessing these events at the 1-, 3-, and 6-
month participant interim visits and at the 12-month administrative data abstraction. We will also track any 
events that we learn of between these time periods, which may occur if participants reach out to the study 
team. Events will not be individually reported as AEs or SAEs unless they are also judged to be related to 
the study, as further described in the sections that follow. Frequency of events, however, will be tracked 
and reported at regular DSMB meetings. 
8.1.3 Definition of Unanticipated Problems (UP) 
Unanticipated Problems Involving Risk to Subjects or Others 
Any incident, experience, or outcome that meets all of the following criteria:  
 Unexpected in nature, severity, or frequency (i.e. not described in study-related documents such 
as the IRB-approved protocol or consent form, the investigators brochure, etc.) 
 Related or possibly related to participation in the research (i.e. possibly related means there is a 
reasonable possibility that the incident experience, or outcome may have been caused by the 
procedures involved in the research) 
 Suggests that the research places subjects or others at greater risk of harm (including physical, 
psychological, economic, or social harm). 
8.2
Classification of an Adverse Event 
8.2.1 Severity of Event 
The following guidelines will be used to describe AE severity. 
 
 
Mild – Events require minimal or no treatment and do not interfere with the participant’s daily 
activities. 
 
Moderate – Events result in a low level of inconvenience or concern with the therapeutic 
measures. Moderate events may cause some interference with functioning. 

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Severe – Events interrupt a participant’s usual daily activity and may require systemic drug 
therapy or other treatment. Severe events are usually potentially life-threatening or incapacitating. 
8.2.2
Relationship to Study Intervention
The clinician’s assessment of an AE's relationship to study intervention is part of the documentation 
process. If there is any doubt as to whether a clinical observation is an AE, the event should be reported. 
All AEs must have their relationship to study intervention assessed. In a clinical trial, the study 
intervention must always be suspect. To help assess, the following guidelines are used. 
 Related / Possibly Related – The AE is known to occur with the study intervention, there is a 
reasonable possibility that the study intervention caused the AE, or there is a temporal relationship 
between the study intervention and event. Reasonable possibility means that there is evidence to 
suggest a causal relationship between the study intervention and the AE. 
 Not Related – There is not a reasonable possibility that the administration of the study 
intervention caused the event, there is no temporal relationship between the study intervention 
and event onset, or an alternate etiology has been established. 
8.2.3 Expectedness 
Dr. Doran and Dr. McNeely will together be responsible for determining whether an AE is expected or 
unexpected (also called unanticipated), with input from the study DSMB. An AE will be considered 
unexpected if the nature, severity, or frequency of the event is not consistent with the risk information 
previously described for the study intervention. 
8.3
Time Period and Frequency for Event Assessment and Follow-Up 
The occurrence of an AE or SAE may come to the attention of study personnel at study visits (1-, 3-, and 
6- months after baseline) during study procedures as specified including participant surveys and 
interviews. Participants may also provide unsolicited information on AEs or SAEs during defined study 
visits or interim contacts. AEs or SAEs may also become apparent at the time of the final study 
administrative data review (12 months after baseline). Participants will be allowed to report problems, 
whether related or potentially related to study participation, to study personnel at and between scheduled 
intervention sessions and assessments. They will be instructed on how to contact study personnel should 
problems occur during intervals between visits. AEs or SAEs that are assessed through standard study 
surveys will be recorded in REDCap. Other events not captured in REDCap will be documented on an 
internal events log form. 
8.4 Reporting Procedures – Notifying the IRB 
The PI will report the following types of events to the IRB and DSMB: 
 
AE or SAE unanticipated AND related to the study. Study-specific descriptions of what will and will 
not be considered AEs or SAEs are provided in Sections 8.1.1 and 8.1.2. 
 
Other unanticipated problems involving risks to study participants or others. 
 
The following events will also be treated as Reportable Events, as required by the IRB: an unresolved 
participant complaint that indicates a potential increased or unexpected risk; new information that presents 
a change to the risks or potential benefits; a major deviation from the IRB approved protocol. 
 
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. Sites will be 
responsible for developing corrective action plans for both major and minor deviations as appropriate. Major 

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protocol deviations will be reported to the IRB. Major and minor protocol deviations and corrective actions 
implemented will be documented in study records as further described in the MOP/SOP. 
 
Events will be reported according to the NYU Langone Health IRB’s reporting guidelines. 
8.4.1
Adverse Event Reporting
AEs (see section 8.1.1) that are harmful, unanticipated, and related to the study will be reported to the 
IRB using the appropriate forms via Research Navigator within 24 business hours of becoming known to 
the PIs. Additionally, such AEs will be recorded on a summary report provided yearly to the IRB at the 
time of study continuation. The PI will have primary responsibility for reporting AEs, with assistance from 
the study staff.  
8.4.2 Serious Adverse Event Reporting 
SAEs (see section 8.1.2) that are unanticipated and related to the study, or any deaths of study participants 
related to study procedures will be reported to the IRB and DSMB as quickly as possible after becoming 
known to the PI, and within 24 business hours. Reporting will be completed using the appropriate forms via 
Research Navigator. When appropriate and possible the PI will also attempt to discuss by phone with IRB 
staff. Serious adverse events uncovered during the study that are not reportable because they are not 
related to the research but are harmful and unanticipated will be communicated to the IRB at the time of 
continuing review in summary or aggregate form, to the DSMB in aggregate form at each scheduled 
meeting, and to the Program Officer at CDC in aggregate/summary form in the annual Progress Report. 
Non-harmful/expectable events are not recorded or reported to the IRB. When an event is reported, it will 
be documented on an internal Events Log Form described in the study MOP/SOP. The Events Log Form 
will assess the details, seriousness, and outcome of the event. Event impact will be formally and informally 
monitored and formally documented, and the MPIs will implement steps to prevent future similar events 
from occurring. Additionally, SAEs will be recorded on a summary report provided yearly to the IRB at the 
time of study continuation. The PIs will have primary responsibility for reporting SAEs, with assistance from 
the study staff. When an event is reported, it will be documented on an internal Events Log Form described 
in the study MOP/SOP. The Events Log Form will assess the details, seriousness, and outcome of the 
event. Event impact will be formally and informally monitored and formally documented, and the MPIs will 
implement steps to prevent future similar events from occurring if possible. 
8.4.3 Unanticipated Problem Reporting 
In addition to AE and SAE reporting as specified above, other unanticipated problems (UPs) involving risks 
to study participants or others will be reported to the IRB and DSMB within 72 business hours of becoming 
known to the PI. UP reports will include the following information: 
 
 Protocol identifying information: protocol title and number, PI’s name, and the IRB project number; 
 A detailed description of the event, incident, experience, or outcome; 
 An explanation of the basis for determining that the event, incident, experience, or outcome 
represents an UP; 
 A description of any changes to the protocol or other corrective actions that have been taken or 
are proposed in response to the UP. 
8.4.4 Reporting of Pregnancy 
Not applicable. Pregnancy will not be followed or tested for within the context of this study. As noted, 
pregnant women are ineligible for study enrollment. Pregnancy at the time of enrollment is based on self-
report or provider report; women will not be tested for pregnancy prior to enrollment in the study, nor will 
their clinical data be reviewed. However, if a participant becomes pregnant during the course of the study 
they may remain in the study. 
8.5 Reporting Procedures – Notifying the Study Sponsor
Dr. Doran and Dr. McNeely will report the Reportable Event to the study’s Program Officer at the CDC by 
phone or email within 24 business hours of the event becoming known and follow up with a written report 

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(by email) within 72 hours, detailing any additional information and whether or not the event is related to 
participation in the study or may affect future participation in the study. They will make an initial report to 
the Chairperson of the DSMB within 24 hours of learning of the event, followed up with a written report 
within 72 hours. Next, the DSMB will review the Reportable Event (usually on the phone or via email) and 
make a report via email to the PI, who will forward the report to the IRB and Program Officer at the CDC. 
 
Adverse events uncovered during the study that are not reportable because they are not related to the 
research but are harmful and unanticipated will be communicated to the IRB at the time of continuing 
review in summary or aggregate form, to the DSMB in aggregate form at each scheduled meeting, and to 
the Program Officer at CDC in aggregate/summary form in the annual Progress Report. 
8.6 Reporting Procedures – Participating Investigators 
For any reportable events, the PIs will inform participating Site PIs in writing (email) upon determination of 
a course of action for the event or within 5 business days of the even, whichever comes first.  
8.7
Study Halting Rules
Decisions about halting or terminating the study will be made by the PIs in conjunction with the DSMB. 
The study will be halted if: 
 
 
There are significant deficiencies in study performance and/or quality control such that 
continuation of the study would be dangerous, unethical, or would not be expected to result in 
meaningful results despite modification. 
 
There are significant risks to participant safety as indicated by frequency of reportable serious 
adverse events or protocol violations that put participants at risk. 
 
The study stopping rule is met. The stopping rule will be based on the objective, serious, negative 
event of fatal opioid overdose. The study will be stopped if we observe a rate ratio of number of 
OD deaths in the SDC arm to number of OD deaths in the Relay arm of 3.0 and a one-sided p-
value of <0.01, or a one-side p-value of <.01 when the rate ratio is undefined due to zero deaths 
in the Relay arm. The DOHMH will provide the study investigators with data on any OD deaths for 
study participants biannually. The DSMB will review all overdose deaths of study participants at 
each biannual DSMB meeting. The DSMB will use the overdose death data to determine whether 
the stopping rule has been met at each biannual DSMB meeting after at least 80 total participants 
have been enrolled in the study, at which point differences between the study arms can be 
determined with reasonable statistical precision. 
 
In the event that the study is halted, researchers will attempt to contact participants to inform them and 
potentially offer additional services. 
8.8
Safety Oversight 
It is the responsibility of the Principal Investigators to oversee the safety of the study overall and the 
responsibility of the Site Principal Investigators to oversee safety of the study at their sites. This safety 
monitoring will include careful assessment and appropriate reporting of adverse events as noted above, 
as well as implementation of a data and safety monitoring plan. 
 
The DSMB is charged with monitoring the safety of study participants and quality of data. The DSMB will 
review the study protocol and recommend changes that may improve the protocol, as needed. 
Throughout the duration of the study, the DSMB will revisit the protocol to identify any emerging issues 
and recommend improvements and monitor the safety of study participants by assessing adverse event 
and other event reports. The DSMB will meet semi-annually to review interim analyses and efficacy 
reports to identify unanticipated or pre-specified harm or benefits that may be attributable to study 
activities. The Board will recommend any necessary modifications to the protocol or early termination of 
the study should overwhelmingly significant benefits or risks become apparent, or if they deem that the 
trial cannot be completed successfully. 
 

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The DSMB has five main objectives: 
 
1) Protocol review—to review and evaluate the research protocol and plans for data and safety 
monitoring before data collection begins, recommending any needed modifications to study 
protocols and finalizing the particulars of the DSMP; to review subsequent protocol changes 
proposed by the investigators and recommend any needed changes prior to implementation as 
well as an implementation timeframe. The Sponsor’s Program Officer will be informed of any 
changes recommended by the DSMB. 
 
2) Participant safety—to review therapeutic results, unanticipated consequences, event impact, 
adverse events, and Reportable Events, formulating recommendations to continue, amend, or 
terminate the study based on ad hoc interim analysis for safety and/or efficacy and according to 
established criteria (e.g., recommend termination because to continue the comparison treatment 
group in the face of overwhelming benefit accrued from the experimental intervention would be 
unethical).  
 
3) Study performance—to review study performance (e.g., eligibility of participants, accrual and 
follow-up rates, participation and retention rates, adherence to randomization protocol, program 
fidelity measures, data quality control/validity) and recommend that the study continue as is, be 
amended to achieve improvements, or be terminated (according to established criteria) because 
meaningful results would not result, regardless of modifications. 
 
4) Study efficacy—to review interim analyses of outcome data and cumulative statistical summaries 
to determine whether the trial should continue as originally designed, or be changed, or be 
terminated according to the established criteria for benefit-risk (favorable and unfavorable) and 
inability to answer the research questions. 
 
5) Quality control—to review quality control information for data collection and for program fidelity as 
obtained by the investigators and reported at each scheduled meeting to ensure and preserve 
study integrity and credibility; to assess this information and formulate recommendations that the 
study continue as is, be amended, or be terminated according to established criteria. 
 
The DSMB will meet its objectives by fulfilling the responsibilities listed below:  
 
1) Becoming familiar with the research protocols and plans for data and monitoring. 
 
2) Reviewing adverse event reports (in aggregate) for disproportionate distribution between the two 
treatment conditions or unexpected frequency of occurrence; reviewing adverse event reports (in 
aggregate) and evaluating for attribution to the intervention or to study activities; suggesting 
protocol modifications to improve participant safety. The Sponsor’s Program Officer will be 
informed of any changes recommended by the DSMB. 
 
3) Reviewing major proposed modifications to the study prior to their implementation (e.g., 
termination, increasing target sample size). 
 
4) Reviewing interim analyses of outcome data and cumulative data summaries to determine 
whether the trial should continue as originally designed, should be changed, or should be 
terminated according to the established criteria. 
 
5) Providing the MPIs with a verbal overview and a detailed written report following each DSMB 
meeting that describe deliberations and findings related to cumulative observations and that list 
the Board’s recommendations related to continuing, changing, or terminating the trial (the MPIs 
are responsible for distributing the written report to the appropriate parties). This report will be 
forwarded to the Sponsor’s Program Officer. Any report containing findings that the frequency or 
magnitude of harms or benefits may be different than initially presented to the IRB will be 
reported to the IRB. 

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9 Clinical Monitoring 
Clinical site monitoring is conducted to ensure that the rights and well-being of human subjects are 
protected, that the reported trial data are accurate, complete, and verifiable, and that the conduct of the 
trial is in compliance with the currently approved protocol/amendment(s), with GCP, and with applicable 
regulatory requirement(s). 
 
Ongoing monitoring will occur at all study sites. Monitoring will be conducted in collaboration between the 
study PIs, the site PIs / Clinical Leads, the Project Manager, and the Research Assistants. The primary 
purpose of monitoring will be to ensure that all study activities are being conducted in accordance with the 
study protocol. Site monitoring will also ensure that the study is not posing abnormal risk to study 
participants or other ED patients. Monitoring will occur via regular in-person direct supervision by the 
Project Manager and Site PIs / Clinical Leads. Frequency of monitoring will be highest in the initial study 
start-up period and will decrease over time. The PIs and Study Site PIs / Clinical Leads will have regular 
monthly meetings at which any non-urgent site-specific issues can be discussed.  
 
Monitoring will also occur by careful, regular review of all collected study participant information. Study 
participant consents and assessments are being collected at all study sites using REDCap that is 
centrally managed by NYU. As such, NYU study staff will have instant ability to review data collected at 
study sites. Data QA (of 100% of collected data) will be conducted by the PM under direction of the PIs 
weekly and will include independent evaluation by Study Site to ensure no irregularities.  
 
Any irregularities or other issues with study sites will be discussed between the PIs and Site PIs / Clinical 
Leads to determine reasons for such issues and an action plan.  
 
10 Statistical Considerations 
10.1 Statistical and Analytical Plans
A detailed statistical and analytical plan will be finalized in consultation with the study biostatistician and 
determined prior to study outcomes analysis. Preliminary approaches are described below but some 
details of specific statistical analysis plans may change upon biostatistics consultation and/or as the study 
progresses; no changes in the analysis plan would change the risk to study participants. For minor 
statistical plan changes, protocol modification approval will not be sought from the IRB.  
10.2 Statistical Hypotheses 
We hypothesize that ED patients receiving the Relay peer navigator intervention after a nonfatal OD will 
have significantly fewer opioid-related adverse events (opioid OD and substance use related ED visits) in 
the next 12 months compared to patients receiving site-directed care. 
10.3 Analysis Datasets
The primary dataset will contain all randomized study participants and will include data both from 
participant assessments (at baseline, 1-, 3-, and 6-months) and from a 12-month administrative data 
extraction/review. The primary analysis will be intent-to-treat (ITT). Depending on the amount of crossover 
between study arms other analyses may be conducted upon consultation with the study biostatistician. 
 
Secondary datasets will include the Relay program data as maintained by the DOHMH and a qualitative 
interview dataset (audio recordings which will be transcribed). Of note, Relay program data forms were 
developed and are administered by DOHMH. Relay program data forms may be changed by DOHMH 
without notice, as this is an element of the DOHMH-operated program not under the direct control of the 
researchers. Such modifications will not be submitted for IRB approval.  

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10.4 Description of Statistical Methods
10.4.1 General Approach 
Two-arm RCT comparing site-directed care (SDC) to the Relay intervention among patients presenting to 
the ED with a nonfatal opioid-involved OD. 
10.4.2 Analysis of the Primary Efficacy Endpoint(s)
The primary endpoint is the number of opioid-related adverse events in the 12 months following the index 
ED visit. Opioid-related adverse events include: any opioid-involved OD (fatal or nonfatal) or any other 
substance use-related ED visit. Overdose deaths are tracked using the DOHMH comprehensive 
database of NYC overdose deaths. Data on OD resulting in ED visits or other substance use related ED 
visits will be collected from administrative data at 12 months, as identified from visit chief complaint and/or 
diagnoses. We will collect additional self-reported data on OD using a questionnaire that has been used 
in prior studies. This questionnaire will be administered at each study visit. Participants will be asked 
whether the OD did or did not result in an ED visit. We will use this information to calculate an estimated 
12 month opioid-related OD event count. 
 
The primary outcome will be ascertained by administrative data abstraction with adjustment using self-
report data as described above. Administrative data extraction will be completed by members of the study 
team who are blinded to participant arm assignment. Results for the primary outcome will be compared for 
independent data abstraction completed by two members of the study team; disagreements will be resolved 
either by consensus or by a study PI.   
The primary analysis will use a Poisson generalized linear regression model to evaluate the intervention 
effect on the total number of opioid-related adverse events. We anticipate the availability of 12 months of 
follow-up data on all participants but, in the event of death or withdrawal from the study, we will adjust the 
follow-up time appropriately using an offset term. We will include adjustment for study site, as well as other 
baseline factors that may be unbalanced across arms. The primary effect measure will be the incidence 
rate ratio comparing Relay to SDC. Some participants may be routinely high utilizers of the ED, and this 
may lead to overdispersion of the count outcome; we will therefore use a negative binomial model instead 
of a Poisson model if warranted. 
In summary, the primary outcome is “opioid-related adverse events,” which will include fatal and non-fatal 
opioid-involved overdose as well as substance use-related emergency department (ED) visits. ED visits 
and fatal overdoses in the 12-month period after baseline will be captured in administrative data sources. 
Other non-fatal opioid-involved overdose events will be captured by self-report in follow-up interviews 
through six months after baseline, and estimated for the second half of the 12-month follow-up period.    
 
10.4.3 Analysis of the Secondary Endpoint(s) 
Secondary outcome analysis.  For secondary outcomes, we will use models similar to those for the 
primary outcome. Initiation of medication for opioid use disorder (MOUD) in the first 90 days will be 
evaluated using a logistic regression model with intervention arm as the primary predictor. In addition, we 
will explore multiple initiations of MOUD in the follow-up period using longitudinal generalized linear mixed 
models. These will use a logit link and incorporate random effects for participants to accommodate the 
correlation of repeated assessments. The OD risk behavior score will be evaluated using mixed effects 
models for continuous longitudinal data, incorporating random effects for participants as described. Item 
responses to the OD risk behavior questionnaire will be summed; higher scores indicate a higher number 
and/or frequency of risk behaviors. Time to first subsequent OD will be evaluated using Cox proportional 
hazards models. Frequency of ED visits for a) opioid OD, b) other substance use related reason, and c) 
any cause will be evaluated with Poisson regression models as described for the primary outcome. For all 
models, we will assess validity of assumptions regarding distributional characteristics of the outcomes and 
find suitable transformations if necessary. We will assess indicators of model fit and evaluate standard 
model diagnostics such as residual plots.  
Qualitative interview analysis. One-on-one interviews will be conducted with approximately 12 patients, 

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10-12 ED providers, and 10 peer navigators, though if we find that important new concepts are emerging 
in late interviews we will continue interviews until theoretical saturation is reached. Interviews will follow a 
semi-structured guide with a ‘start list’ of key questions drawn from the theoretical model and CFIR domains 
and will allow for exploration of unanticipated themes. Interviews will be digitally recorded and transcribed. 
Given the immediate pragmatic goals of the analysis (i.e., to identify factors impacting implementation and 
fidelity) and the desire to quickly translate research findings into practice, the initial analysis of the interviews 
will use rapid turn-around qualitative methods such as creating templated summaries of interviews and 
conducting matrix analysis focused on key domains. These techniques are action-focused, time-limited, 
and facilitate sharing of results, while still being rigorous. A subsequent analysis will include line-by-line 
coding of all content from the transcripts using an a priori coding scheme based on the theoretical model 
and CFIR domains; researchers will additionally identify any relevant emergent themes. Coding will be done 
by a core team of 2–3 trained researchers, and findings will be discussed among the investigators to reach 
consensus on the main themes. ATLAS.ti or Dedoose will be used to assist with coding and data 
organization.  
Relay programmatic data. Additional descriptive analyses will be conducted of Relay programmatic data 
(e.g., number and types of contacts with participants) to allow a fuller understanding of the Relay 
intervention. 
10.4.4 Safety Analyses 
AEs and SAEs will be recorded and reported as previously described. 
10.4.5 Adherence and Retention Analyses 
All participants will complete an RA-administered exit survey interview at the conclusion of the baseline 
visit (either while still in the ED or hospital, or by phone the following day as needed). The exit survey will 
assess what interventions the participant has received in the ED that are relevant to opioid OD (e.g. 
substance use screening, OD education, naloxone kit(s) received, treatment referral/follow-up offered). 
The exit survey interview will also ensure that SDC arm participants receive, at a minimum, OEND, a list 
of treatment programs, and a handout with Relay program information. RAs will need to check off boxes 
in the exit survey indicating that the participant has received these items. Participants will also be asked 
at follow-up assessments what additional Relay program services they have received in the interval since 
the last assessment. 
 
We will routinely monitor data on number of potentially eligible patients, reasons for ineligibility, refusals 
and reasons for refusal, and retention/loss to follow-up at all follow-up assessment time points. These 
data will be compiled and discussed at weekly meetings between the Project Manager and PI(s).  
10.4.6 Baseline Descriptive Statistics
Simple descriptive statistics will be examined for baseline characteristics of study participants, as collected 
on the baseline study survey. Baseline basic characteristics for Relay and SDC arm participants will be 
compared using bivariate analyses. We expect approximately equal distributions of baseline characteristics 
for the two study arms given random assignment. Significant differences in baseline characteristics between 
groups will be adjusted for in outcome analyses. 
10.4.7 Planned Interim Analysis 
10.4.7.1 Safety Review 
Safety review is described in Section 5.8 Premature Termination or Suspension of Study and Section 8.7 
Study Halting Rules. Safety endpoints will be monitored at least biannually, in conjunction with biannual 
DSMB meetings. 
10.4.7.2 Efficacy Review 
We do not plan formal interim analyses for efficacy. 

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10.4.8 Additional Sub-Group Analyses
Mediators and moderators. Relay may impact primary and secondary outcomes indirectly, by means of 
its impact on putative mediators grounded in our conceptual model, including OD knowledge, motivation, 
social support, peer role modeling, stigma, barriers to services, and access to naloxone. Also, the 
intervention may not be equally effective for all participants. The following individual factors may modify the 
relation between the Relay intervention and outcomes: age, gender, race/ethnicity, sexual orientation, 
marital status, ZIP code, housing status, mental and physical health, substance use history, and criminal 
justice involvement.[118] Understanding mediators and moderators of the Relay intervention will be 
critically informative for future efforts to scale up and/or modify the program, or replicate it in other settings. 
We will examine Relay intervention effect mediation and moderation in structural equations models (SEMs). 
We will estimate SEMs to measure the degree to which the Relay intervention improves knowledge (OD, 
naloxone), motivation (naloxone, MOUD, other treatment), social support, peer role models, and access to 
naloxone kits, as well as the degree to which the intervention reduces stigma and perceived barriers to 
services. Also estimated will be the impact of these putative mediators on the risk of opioid-related adverse 
events and other outcomes. Models will be fit that include paths from Relay to mediators and outcomes as 
well as paths from mediators to outcomes. The magnitude and significance of the direct and indirect effects 
of Relay will be provided. Bootstrapping methods will be used to derive estimates of mediated (i.e., indirect) 
effects. Bootstrapping approaches to indirect effect inferences rely on repeated random sampling from the 
data with replacement (e.g., 10,000 times) and use the resulting sampling variability of the estimate as the 
basis for an interval estimate. To capture potential effect moderation (regarding both the effects of Relay 
on mediators and the effects of mediators on outcomes), interaction terms will be included in these SEMs. 
This approach, described by Preacher, Rucker, and Hayes (2007), allows multiple types of effect 
moderation including moderation of: 1) effect of Relay on mediator; 2) effect of mediator on outcome; 3) 
indirect effect of Relay on outcome via mediator; and 4) direct effect of Relay on outcome. The software 
package Mplus accommodates model constraints to facilitate estimation and testing of complex moderated 
mediation hypotheses. When significant moderator effects are detected, we will estimate and present direct 
and indirect effects for specific subgroups defined by the moderating variable (e.g., the indirect effect of 
Relay on overdose via increases in social support among males). In addition to moderated mediation 
analysis based on the standard SEM approach and products of coefficients, we will employ analysis of 
causal mechanisms grounded in the potential outcomes framework, using marginal structural models. This 
approach highlights assumptions needed to identify direct and indirect effects of interest: no unmeasured 
cofounders of the exposure (Relay) and outcome relation; no unmeasured confounders of the mediator and 
outcome relation; no unmeasured confounders of the exposure and mediator relation; and no measured or 
unmeasured confounders of the mediator and outcome relation affected by exposure. Because the Relay 
intervention is randomly assigned, the key issue for the proposed study is addressing confounding of the 
relation between mediators and outcomes. Because unmeasured confounding of relations between 
mediators and outcomes may remain despite attempts to measure and include known confounders in the 
models, sensitivity analysis will be undertaken to determine how the size of the correlation between error 
for the mediator model and error for the outcome model impacts inferences for direct and indirect effects. 
Analyses will be undertaken with Mplus (Version 8) and the medflex package in R.  
Finally, we will assess the impact of intervention dose, measured using the number, type (phone or in-
person conversation, accompaniment to appointments), and duration of contacts; this information is 
routinely logged by the Relay peer navigator. We will examine the impact of dose using instrumental 
variables (IV) regression; this approach can substantially increase the strength of causal inference about a 
variable (such as dose) not fully under experimenter control. IV regression requires a variable related to a 
dose, but not correlated with any other determinants of dose. Random assignment to study condition meets 
these requirements; thus, IV regression illuminates the intervention’s effectiveness at different dose levels. 
10.4.9 Multiple Comparison/Multiplicity 
Not applicable. 
10.4.10 
Tabulation of Individual Response Data 
All planned analyses use aggregate data. Individual data will not be published. 

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10.4.11
Exploratory Analyses
Participants will be asked about any services received from an outpatient medical or mental health 
provider, or from a harm reduction program; for those reporting receipt of any services, we will measure 
the frequency of contact and the nature of services received. We will additionally assess use of naloxone 
by participants and naloxone carrying by friends/family. Death from OD, opioid-related OD, and any 
cause will be tracked using Vital Statistics and/or National Death Index records (accessed by DOHMH) 
since prior research shows high rates of death, including those unrelated to OD, among patients following 
ED visits for non-fatal opioid OD.48
10.5 Sample Size
The sample size for this study is 350. Our preliminary data indicate the average number of opioid-related 
adverse events per year in SDC arm will be in the range of 2-3 events/person; this rate is substantiated in 
the literature.19,50,52,58 We wish to be able to detect a decrease in this number of approximately 25% in the 
Relay arm, a modest effect size judged to be of public health significance. Using a Poisson regression 
model for the total number of events, 350 participants provide more than 80% power to detect this 
difference. Specifically, we have 83% power to detect a decrease in the mean event rate from 2.0 per year 
in SDC to 1.52 in Relay (an incidence rate ratio (IRR) of 1.32 and a 24% reduction). If average opioid-
related adverse events in the SDC arm are lower than anticipated, we still have 80% power to detect a 
decrease in the mean event rate from 1.75 per year in SDC to 1.32 in Relay (IRR = 1.33; a 25% reduction). 
All calculations assume a two-sided, 0.05-level test, and conservatively include adjustment for possible 
overdispersion in the primary outcome (overdispersion parameter = 1.6). While formal power and sample 
size calculations were based on our primary outcome, given that secondary outcomes are generally more 
common than our primary outcome (e.g., all-cause ED visits) or are time to events expected not to be rare 
(e.g., time to opioid-involved OD), we expect to have adequate power for secondary outcome analysis as 
well. 
10.6 Measures to Minimize Bias
10.6.1 Enrollment/Randomization/Masking Procedures 
At the enrollment visit, the RA will use an electronic system (REDCap) to trigger assignment to a 
treatment arm. Randomization will use a 1:1 ratio and is stratified by site; permuted blocks with variable 
blocks of size 4 and 6 will be used to maintain balance over time and prevent prediction of assignment by 
the RA. Upon randomization, the RA will immediately inform the participant of the treatment arm 
assigned. 
While the RA conducting the baseline assessment cannot be blinded to the intervention assignment 
(since it will occur during the same ED visit as the intervention), whenever possible a different RA will be 
assigned to conduct follow-up interviews in an attempt to maintain blinding. Blinding may be imperfect 
since participants may reveal their intervention assignment, including based on their answers to the 
follow-up assessments. Participants themselves cannot be blinded to the treatment condition due to the 
nature of the intervention. Study staff conducting the administrative data abstraction for the primary study 
outcomes will be blinded to the intervention assignment. Study analytic staff are blinded to treatment 
condition until the conclusion of the trial and finalization of the analytic database. 
10.6.2 Evaluation of Success of Blinding 
Not applicable. 
10.6.3 Breaking the Study Blind/Participant Code 
Not applicable. For any reportable events, the participant’s study arm will be noted. 
11 Source Documents and Access to Source Data/Documents 
Source data is all information, original records of clinical findings, observations, or other activities in a 
clinical trial necessary for the reconstruction and evaluation of the trial. Source data are contained in 

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source documents. Examples of these original documents, and data records include: hospital records, 
clinical and office charts, laboratory notes, memoranda, subjects’ diaries or evaluation checklists, 
pharmacy dispensing records, recorded data from automated instruments, copies or transcriptions 
certified after verification as being accurate and complete, microfiches, photographic negatives, microfilm 
or magnetic media, x-rays, subject files, and records kept at the pharmacy, at the laboratories, and at 
medico-technical departments involved in the clinical trial.  
 
For this study documents aside from the study-specific documents as described in this protocol are 
minimal. Study baseline and follow-up assessments and other participant information collected at 
baseline will be collected and maintained using REDCap. REDCap maintains a log of any changes to this 
information. Consent forms will also be collected on REDCap. Relay programmatic data is maintained by 
DOHMH on a separate system per their existing protocols.  
 
Access to study records will be limited to the study team, including DOHMH study team members as 
governed by an executed DUA. The investigator will permit study-related monitoring, audits, and 
inspections by the IRB/EC, the sponsor, government regulatory bodies, and University compliance and 
quality assurance groups of all study related documents (e.g. source documents, regulatory documents, 
data collection instruments, study data etc.). The investigator will ensure the capability for inspections of 
applicable study-related facilities (e.g. pharmacy, diagnostic laboratory, etc.). 
 
Participation as an investigator in this study implies acceptance of potential inspection by government 
regulatory authorities and applicable University compliance and quality assurance offices. 
 
12 Quality Assurance and Quality Control 
Multiple steps will be taken toward quality assurance (QA) and quality control (QC). 
 All study staff will be thoroughly trained both in overall GCP and human subjects protections and 
in study-specific procedures. 
o 
Formal training will occur prior to the study beginning recruitment. 
o 
RAs will be supervised until they are able to conduct study procedures independently. 
o 
Continuous training will occur in weekly staff team meetings. 
 RAs will be closely supervised by the PM, with PI oversight.  
 MOP and SOP documents will clearly outline all study procedures, including QA/QC procedures. 
 Multiple QA/QC protections are built into REDCap data collection software being used for this 
study, including forced question entry (i.e., specified questions cannot be left blank), automatic 
logging of all activities in REDCap including any entry changes, and study staff permission rules. 
 Weekly QA/QC reviews conducted by the PM and reviewed/discussed with the PI will include: 
o 
Review of numbers of patients approached, eligible/ineligible, refused, participated. 
o 
Review to ensure that all eligibility classifications were made correctly. 
o 
Review for missing or out of range data. 
o 
Review for completeness of forms and data.  
o 
Review of exit surveys for adherence to study protocols. 
o 
Review of any safety issues. 
o 
Review of any potential QA/QC issues identified by any study staff member (which did 
not warrant more immediate discussion). 
 
QC procedures will be implemented beginning with the data entry system and data QC checks that will be 
run on the database will be generated. Any missing data or data anomalies will be communicated to the 
site(s) and/or individual RA(s) for clarification/resolution. 

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13 Ethics/Protection of Human Subjects
13.1 Ethical Standard
The investigator will ensure that this study is conducted in full conformity with Regulations for the 
Protection of Human Subjects of Research codified in 45 CFR Part 46. 
13.2 Institutional Review Board
The protocol, informed consent form(s), recruitment materials, and all participant materials will be 
submitted to the IRB for review and approval. Approval of both the protocol and the consent form must be 
obtained before any participant is enrolled. Any amendment to the protocol will require review and 
approval by the IRB before the changes are implemented to the study. All changes to the consent form 
will be IRB approved; a determination will be made regarding whether previously consented participants 
need to be re-consented. 
13.3 Informed Consent Process
13.3.1 Consent/Assent and Other Informational Documents Provided to Participants 
Consent forms describing in detail the study intervention, study procedures, and risks, as well as key 
information sheets providing a concise summary of these factors, are given to the participant. 
Documentation of informed consent is required prior to starting study procedures. The following consent 
materials are submitted with this protocol:  
 
Relay Consent Form – Main Study 
 
Relay Key Information Sheet – Main Study  
 
Verbal Consent Form – Qualitative Interview Patients 
 
Verbal Consent Form – Qualitative Interview Providers 
13.3.2 Consent Procedures and Documentation 
Those eligible will be invited to complete the informed consent process. The RCT consent documents will 
be in English and Spanish, and consent will be obtained by trained, bilingual RAs. Consent will be obtained 
using e-consent on Open REDCap. A copy of the signed e-consent will be provided to the potential 
participant in one of three ways: 1) signed electronic consent copy will be e-mailed if the participant has an 
e-mail address and agrees to receive an e-mailed version of the consent copy, 2) signed electronic consent 
copy will be printed and provided to the participant, or 3) if the participant does not have or does not want 
e-consent e-mailed to them and printing isn’t available at the study site, he/she will be asked to sign a paper 
version of the consent form, which will be provided to them to keep. Multiple steps will be taken to ensure 
participant privacy during the consent process, including: asking any visitors to leave the area (though 
visitors will be allowed to stay for the consent process if preferred by participants); using a private room or 
treatment bay when available; research staff speaking in a quiet voice to avoid others overhearing the 
conversation. Potential participants will be given a written consent form that includes required language 
regarding HIPAA and the Certificate of Confidentiality, as well as name and contact information of the PIs 
and of the institutional review board, a description of the study, the payment schedule, a description of 
potential risks and benefits, a statement of confidentiality, and an indication of the right to refuse or withdraw 
participation at any time without any consequence. The consent form for patients will include consent for 
accessing their personal health information in administrative data sources (e.g., Bronx RHIO and HealthIx 
RHIO and DOHMH mortality data) for 12 months following enrollment. 
Informed consent will be obtained by the trained study researchers from all participants, per usual human 
subjects research procedures. RAs will review the IRB-approved consent form and key information sheet 
verbally and in detail, in simple and plain language, with potential participants. Participants will give signed 
informed consent prior to participation in all study activities. Study staff will emphasize that participation is 
voluntary, that participants are free to stop participation at any time and are free to refuse to answer specific 
questions in any assessment and can decline participation in any intervention activity or assessment 

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activity. Participants will be informed that their decision to participate or decline to enroll in the study or any 
aspect of the study will not affect any other services they receive in the ED or elsewhere.  
 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in the study 
and continues throughout the individual’s study participation. Discussion of risks and possible benefits of 
participation will be provided to the participants and their families. Participants will have the opportunity to 
carefully review the written consent form and ask questions prior to signing. Study staff will answer any 
questions that may arise. The participants will have the opportunity to discuss the study with their 
surrogates or think about it prior to agreeing to participate. The participant will sign the informed consent 
document prior to any procedures being done specifically for the study. The participants may withdraw 
consent at any time throughout the course of the trial. The rights and welfare of the participants will be 
protected by emphasizing to them that the quality of their medical care will not be adversely affected if 
they decline to participate in this study. 
 
The participant and the person obtaining informed consent will sign and date the informed consent 
document prior to any procedures being done specifically for the study. A copy of the signed electronic 
consent will be provided to the potential participant in one of three ways as described above. The 
electronic copy of the signed informed consent document will be stored electronically in the subject’s 
research record.  
 
The consent process, including the name of the individual obtaining consent, will be thoroughly 
documented in the subject’s research record. Any alteration to the standard consent process and the 
justification for such alteration will likewise be documented. Regular audits will be performed to ensure 
that consent forms are fully and properly completed for all study participants. 
 
Participant capacity and comprehension: Potential participants will be required to demonstrate adequate 
comprehension of the study and decision-making capacity to participate in the study. Only patients who 
have the capacity to give informed consent will be included in the study. Patients will not be included if 
they are too acutely intoxicated to give informed consent or otherwise medically unfit to participate, as 
determined by trained study staff. If there is any question about the patient’s capacity to provide informed 
consent, study staff will: a) ask ED clinical providers (e.g., physician, nurse) for advice about whether the 
participant has capacity to provide consent, and/or b) complete formal assessment of decisional capacity 
for participation in research using the University of California, San Diego Brief Assessment of Capacity to 
Consent (UBACC). The UBACC has been previously validated and generally takes less than 5 minutes to 
administer. 
 
Consent for Qualitative Interviews: 
Patient participants, ED providers, and Relay Wellness Advocates will verbally consent to take part in the 
qualitative interview. The Qualitative Researcher will review the IRB-approved verbal consent form in 
English with each participant. The Qualitative Researcher will review a description of the study, a 
description of potential risks and benefits, a statement of confidentiality, and an indication of the right to 
refuse or withdraw participation at any time without any consequence the study requirements. The verbal 
consent will include explicit consent for an audio recording.  
 
Consent processes, like the interviews, will take place by phone, video conferencing, or in person. 
Multiple steps will be taken to ensure participant privacy during the consent and interview process, 
including: requesting that the participant is in a private space; providing a private space for participants 
requesting to complete the interview in person; speaking in a quiet voice to avoid others overhearing the 
conversation.  
13.4 Posting of Clinical Trial Consent Form 
The informed consent form will be posted on the Federal website after the clinical trial is closed to 
recruitment, and no later than 60 days after the last study visit by any subject. 

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13.5 Participant and Data Confidentiality
All research data is stored in secure, password-protected storage drives maintained on a remote server by 
the NYU School of Medicine and accessible only to members of the research team. Access to research 
offices at NYU is restricted to research staff, and the buildings where these offices are located are secure 
and monitored by security staff. File drawers containing participant information are located only at the NYU 
research office. These files are kept locked when not in use, and only research staff members have keys 
to these file cabinets. When the researchers are collecting data at the clinical sites, they may hand-carry a 
minimum amount of participant information required for that day’s study visits on site (ex: name and location 
for potentially eligible patients). At the end of each recruitment day, this information will be carried back to 
the research office and stored in a locked cabinet or placed in a confidential shred bin per protocols to be 
specified in the MOP/SOP. Personal health information required to carry out the study (e.g., name, contact 
information, medical record number) will be stored in a separate REDCap form from study assessments. 
 
Administrative data: Existing administrative data sets will be secured according to standard protections at 
the institutions where the data are housed and maintained. 
Audio recordings: Interviews will be recorded using Webex or the Rev Voice Recorder app. Interviews 
conducted on WebEx, will be recorded using WebEx. Interviews conducted on the phone, will be recorded 
using Rev. As a back-up recording, a digital audio recorder may be used. Digital audio files will be 
transferred to NYULH protected secure drives, which are HIPAA-compliant and protected from 
unauthorized access. Audio files will then be deleted from the Rev recording app or WebEx system. 
Researchers will provide audio files to a professional transcription company that meets privacy and security 
requirements for research (e.g., Transcript Divas Transcription Services).  Audio files will be uploaded and 
transcripts downloaded from the transcription company’s secure website via the study’s password-
protected account. The transcription company limits access to audio recordings to only those who need 
access to provide the transcription service, and only for that purpose. Following completion of transcription, 
only written transcripts will be used for analysis. Transcripts will not contain names or other identifying 
information, and data will be analyzed and reported anonymously. Audio recording files will be deleted once 
required data retention periods have passed. 
Data security and disaster recovery: This study will use NYU Langone Health’s extensive information 
technology (IT) infrastructure and the comprehensive policies and standard operation procedures (SOPs) 
established for information security and the protection of data. All data processing follows NYU Langone 
Health’s strict security policies to ensure the privacy and confidentiality of patient data and guard against 
physical, accidental, or malicious loss of data or the hardware on which it resides. For example, all desktops 
and servers on the network run virus protection software that guard against the destruction of any data, and 
Network users cannot disable virus defense software. All NYU Langone Health servers are backed up using 
de-duplication technology. Data are stored on servers residing in the secured off-site data center, and NYU 
Langone Health has a comprehensive disaster recovery plan that allows for the expedient resumption of 
the processing of study data in the case of a disaster. 
REDCap. The secure and password protected REDCap database will be used for the majority of study 
activities. Consent forms will be signed and structured assessments will be conducted in REDCap; the 
study will use electronic consent. REDCap was designed specifically to protect patient and research 
participant privacy and confidentiality while assisting investigators in conducting clinical research. System-
level and application-level security features include SSL encryption of internet traffic (e.g., https pages), 
hosting in a secure data center with nightly backup, fine-grained control over user rights, detailed audit 
trails, record-locking, and de-identification functions for data export. Data can be downloaded from REDCap 
onto secure NYU School of Medicine maintained drives that have security protections suitable for research. 
Downloaded data will include minimum possible amount of participant identifying data. In cases when 
participant identifying information is downloaded it will be stored in separate files from participant study 
assessments. 

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Computers. All computerized data that are not in REDCap (transcripts, audio-recordings prior to deletion) 
are kept in secure network drives (in accordance with IT policy) that are password-protected and files are 
only labeled with study IDs when applicable. 
Individual participants and their research data will be identified by a unique study identification number. 
This number will be used for all materials, assessments, audio recordings, and transcripts. The study data 
entry and study management systems used by clinical sites and by NYU research staff will be secured and 
password protected. At the end of the study, all study databases will be de-identified and archived at NYU. 
 
As part of the informed consent process, participants will also be informed that all information they provide 
in study assessments/interviews is confidential, with the following exceptions: (1) If they are in imminent 
danger of committing suicide or homicide, the appropriate agency will be contacted (usually 911 will be 
called) or, if already in the emergency department, the participant’s attending physician will be notified, and 
(2) if they are physically or sexually abusing someone, the Administration for Children’s Services or other 
appropriate agency will be contacted. 
 
Information about study subjects will be kept confidential and managed according to the requirements of 
the Health Insurance Portability and Accountability Act of 1996 (HIPAA).  Those regulations require a 
signed subject authorization informing the subject of the following:  
 What protected health information (PHI) will be collected from subjects in this study 
 Who will have access to that information and why 
 Who will use or disclose that information  
 The rights of a research subject to revoke their authorization for use of their PHI.  
 
In the event that a subject revokes authorization to collect or use PHI, the investigator, by regulation, 
retains the ability to use all information collected prior to the revocation of subject authorization.  For 
subjects that have revoked authorization to collect or use PHI, attempts should be made to obtain 
permission to collect at least vital status (i.e. that the subject is alive) at the end of their scheduled study 
period. 
 
Participant confidentiality is strictly held in trust by the participating investigators, their staff, and the 
sponsor(s) and their agents. No information concerning the study or the data will be released to any 
unauthorized third party without prior written approval of the sponsor. The study monitor, other authorized 
representatives of the sponsor, or representatives of the IRB may inspect all documents and records 
required to be maintained by the investigator. The clinical study site will permit access to such records. 
 
The study participant’s contact information will be securely stored for internal use during the study. At the 
end of the study, all records will continue to be kept in a secure location for as long a period as dictated 
by local IRB and Institutional regulations. 
 
To further protect the privacy of study participants, a Certificate of Confidentiality is automatically granted 
for this research as it meets federal requirements for such a Certificate. This certificate protects 
identifiable research information from forced disclosure. It allows the investigator and others who have 
access to research records to refuse to disclose identifying information on research participation in any 
civil, criminal, administrative, legislative, or other proceeding, whether at the federal, state, or local level. 
By protecting researchers and institutions from being compelled to disclose information that would identify 
research participants, Certificates of Confidentiality help achieve the research objectives and promote 
participation in studies by helping assure confidentiality and privacy to participants. 
13.5.1 Research Use of Stored Data 
No human samples or specimens are being collected or stored for this study. Survey and other data 
being collected for this study will be handled as documented in Section 14 below. 
13.6 Future Use of Stored Data
Study data generated from the present study will not be stored for future research. 

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14 Data Handling and Record Keeping 
14.1 Data Collection and Management Responsibilities
Primary data collection from participants in the RCT will occur by approved, trained study RAs at the 
study EDs. Data collection will occur using REDCap on secure tablet computers (e.g., iPads), which will 
be password protected. Access to REDCap will only be granted to approved study personnel, each of 
whom will have a unique user ID and password to be used when collecting data. REDCap permissions 
and functionality will be restricted for RAs so that they do not have the ability to delete records or change 
forms. In addition to these protections, REDCap has other functionality that will ensure data collected are 
complete and reliable, including data entry field limitations and forced responses to indicated questions. 
REDCap also automatically maintains an audit log of all REDCap activity, including any changes made to 
records and who has made them. All information entered into REDCap is automatically saved in the 
NYULH REDCap project, accessible only to approved study personnel. All study sites will use the same 
approved NYULH REDCap project. For QA monitoring and data analysis, REDCap data will be 
downloaded in the form of Excel and/or statistical programming software files. These files will be 
password protected and saved in secure NYULH IT-managed network drive accessible only to the PI, 
PM, and any other approved personnel. Electronic consent forms will also be stored on REDCap. There 
are no paper questionnaires or other forms that will be saved from the RCT visits. 
 
The PI and PM will monitor data collection regularly via the QA/QC procedures outlined in Section 12. 
Further, all RAs will receive standard training in study procedures and will complete supervised shifts until 
they are fully competent in all study data collection. The PM and PI will be available in real-time to answer 
any RA’s questions about data collection. Further, weekly study team meetings will be used to continually 
reinforce standards of good data collection and management. 
 
The primary outcome will be ascertained in part by data abstraction from a variety of administrative health 
databases, including primarily the Regional Health Information System (RHIO) databases, also called 
Bronx RHIO and Healthix. We will also use individual health system electronic medical records (which 
may be accessed through data warehouses or directly for sites participating in the study). Other sources 
of administrative data that may be used if data is incomplete in the aforementioned sources include 
Medicaid and SPARCS. Study participants will provide informed consent for the study investigators to 
access information about them in these datasets. Approval and use of these datasets will follow defined 
procedures for research specific to each source dataset. Data abstraction will occur directly into a 
REDCap secure data collection form. Data will only be accessed for study participants. RHIOs may 
request and receive from the study investigators a list of participants (including personally identifying 
information) in the study, to allow them to conduct a data match with RHIO data and share results with 
the investigators. All appropriate and applicable permissions will be obtained from the holders of 
administrative data outside the study sites prior to their use for research (e.g., completion of RHIO 
application for research use), and DUAs will be executed prior to data sharing as necessary. 
 
Additionally, DOHMH collects Relay program data which it maintains in a programmatic database known 
as Maven. All data entered into Maven are stored in a secure, password protected, SQL Server Database 
on the DOHMH servers. Access is restricted to approved DOHMH staff and restricted access will be 
granted to approved NYU study team members. NYU study team members will enter limited participant 
information into Maven (see Attachment) for the following purposes: (1) participant identifying information 
(e.g., name, date of birth, race/ethnicity) so that DOHMH can match study participants to death records to 
allow ascertainment of the primary study outcome (Section 3.1) and also tracking for purposes of the 
study stopping rule (Section 8.7); (2) participant contact information so that the Relay program can 
contact SDC arm participants after the study is over to offer Relay services (see Section 6.1), and (3) 
information on NYU RA distribution of naloxone kits to SDC arm participants, as DOHMH is providing the 
naloxone kits to NYU and is legally required to monitor their distribution. Study participants will provide 
informed consent for the NYU study team to share this information about them with DOHMH. 
 

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DOHMH also keeps data on overdose and other deaths in NYC and has other administrative health data 
that we may use for this study. For any data to be shared by DOHMH with the NYU study team, we will 
execute a Data Use Agreement (DUA) and/or Memorandum of Understanding (MOU) with DOHMH to 
govern data use and sharing prior to access or use of any of these data.  
 
We will be providing a list of participant names and birthdates of people who have participated in the SDC 
arm to the Relay hotline call center. The call center will not be provided with any other participant 
information. Using a secure, password protected file transfer portal that only NYU and the Relay hotline 
call center will have access to, the PM or RC will transfer the list of participant names. This information 
will be provided securely to the Relay hotline call center because there is not a study RA on call 24/7 and 
therefore the call center needs an alternate way of knowing when a patient for whom Relay is activated is 
in the study SDC arm meaning a Wellness Advocate should not be dispatched to visit the patient 
(because this would cause crossover between study arms). This will only be relevant in the rare instances 
for which a study participant in the SDC arm has a repeat overdose visit to an emergency department 
participating in the study and the Relay hotline is called. In these cases a study RA will conduct an 
unscheduled visit or follow-up visit as appropriate (see Section 7.3) in the ED once available (if the 
participant remains in the ED) or will attempt to follow up by phone. The Relay hotline call center activities 
related to this study follow a comprehensive data privacy and security agreement with the NYC 
Department of Health and Mental Hygiene, which specify data security procedures, rules against data 
sharing, and other protections for privacy of the data. The Relay hotline call center will delete all 
participant lists after completion of the study follow-up period, one year after enrollment of the last study 
participant.  
 
The study PIs will have ultimate responsibility for overseeing data collection and management. The PIs 
are responsible for ensuring the accuracy, completeness, legibility, and timeliness of the data reported. 
14.2 Study Records Retention 
Study records retention will be compliant with the NYULH ‘Policy on Retention of and Access to Research 
Data’ which mandates retention periods of 6 years after any reporting, publication or presentation, or for 
the time period specified in the Sponsored Research Agreement. No records will be destroyed without the 
written consent of the sponsor, if applicable. It is the responsibility of the sponsor to inform the 
investigator when these documents no longer need to be retained. 
14.3 Protocol Deviations
A protocol deviation is any noncompliance with the clinical trial protocol, GCP, or MOP requirements. The 
noncompliance may be either on the part of the participant, the investigator, or the study site staff. As a 
result of deviations, corrective actions are to be developed by the site and implemented promptly. 
These practices are consistent with ICH E6: 
 4.5 Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3 
 5.1 Quality Assurance and Quality Control, section 5.1.1 
 5.20 Noncompliance, sections 5.20.1, and 5.20.2. 
 
Reporting of protocol deviations is described in Section 8.4. The site PI/study staff is responsible for 
knowing and adhering to their IRB requirements. Further details about the handling of protocol deviations 
will be included in the MOP. 
14.4 Publication and Data Sharing Policy 
The International Committee of Medical Journal Editors (ICMJE) member journals have adopted a clinical 
trials registration policy as a condition for publication. This study will be registered as a clinical trial on 
Clinicaltrials.gov.  
A publication plan will be made by the MPIs and other applicable co-investigators. A draft publication plan 
will be made and discussed with Site Co-Is and other Co-Is and agreed upon within the first year of the 

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study. The MPIs will have ultimate responsibility and decision-making authority regarding the publication 
plan. The International Committee of Medical Journal Editors (ICMJE) guidelines for authorship will be 
followed. 
 
Access to the data. After analysis, the final dataset will be incorporated into a secure computer database 
as soon as possible, and no later than within one year of the completion of the funded project period. 
Datasets will be archived within the secure NYULH data center but curated to be accessible for data 
sharing as required. Datasets will be made available in a non-proprietary format. The research database 
will contain no PHI (protected health information), and all appropriate procedures consistent with the 
Office of Civil Rights’ Privacy Rule (HIPAA) will be taken to preserve the anonymity of the records. As 
appropriate, the following steps will be taken to share and distribute the research data:  
1. Results will be presented at scientific meetings in the form of posters and oral presentations.  
2. Results will be published in a prompt fashion. We will fully comply with CDC policies on public 
access to publications. Further, de-identified data underlying publications will be made available 
at the time of the publication of the paper upon request, unless the dataset has already been 
made available as described. 
3. The rights of human subjects will be preserved at all times, including privacy and confidentiality of 
human subjects. The dissemination and disclosure of research results and findings will use only 
de-identified data. 
4. Data will be shared under confidentiality agreements with collaborators, partners, and sponsors in 
the project.  
5. Agreements may also be used to protect intellectual property rights while exchanging information 
with collaborators, partners and the larger scientific community, including mutual confidentiality 
(non-disclosure) agreements.   
Upon request, we will provide the research dataset to qualified investigators under a Data Use Agreement 
(DUA) that will require approval of the MPIs and each of the primary research team participating agencies 
(NYU, DOHMH). The DUA will be required to include: (1) a commitment to using the data only for 
research purposes and not to identify any individual participant; (2) a commitment to securing the data 
using appropriate computer technology; (3) a commitment to destroying or returning the data after 
analyses are completed; (4) reporting responsibilities; (5) restrictions on redistribution of the data to third 
parties or use for commercial purposes; (6) appropriate human subjects and institutional approvals on the 
part of the collaborator; and (7) proper acknowledgement of the data resources.    
 
Use of data standards. Where possible, we will use common data elements and data standards for the 
collection of data, as specified by the NIH Office of Extramural Research. A data dictionary will be made 
that documents and describes the data, including documenting potential limitations. The data dictionary 
will include details on the source, method of collection, description of the variable, and appropriate 
references for each data point.  
Plans for preservation of the data. Long term retention will be compliant with the NYULH ‘Policy on 
Retention of and Access to Research Data’ which mandates retention periods of 6 years after any 
reporting, publication or presentation, or for the time period specified in the Sponsored Research 
Agreement. 
15 Study Finances 
15.1 Funding Source 
This study is financed through a grant from the US Department of Health and Human Services, Centers 
for Disease Control and Prevention. Any referrals to treatment or counseling will be paid for by 
participants’ individual insurance plan, as applicable.  

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15.2 Costs to the Participant
There are no direct costs to participants related to participation in this study.  
15.3 Participant Reimbursements or Payments 
Participant compensation at all study sites will follow the same procedures, in accordance with the NYULH 
Policy on Human Subject Payment.  
Participants will receive compensation after completion of baseline visit study procedures as well as after 
completing follow-up assessments at 1, 3, and 6 months after enrollment. Participants will receive $75 after 
the baseline visit and will receive $30 after completion of 1 and 3 month follow-up assessments and $50 
after completion of the 6 month follow-up assessment. The total compensation for a patient who participates 
in all RCT assessments is thus $185. At the baseline visit participants will be given a Greenphire ClinCard 
which will be used loaded with the compensation amounts for follow-up visits upon completion of each visit. 
Payment for the baseline visit will occur using either cash or the Greenphire ClinCard.  
 
 
Participants, including patients, Relay peers, and ED staff, in the qualitative interviews will receive 
compensation of $50 at the completion of the approximately 45-minute interview. For Relay peers and ED 
staff, the interviews will be conducted outside of regular working hours, and thus participants will be 
compensated for their time. Relay peers and ED staff will receive a $50 gift card. Patients will be 
compensated the $50 via their Greenphire ClinCard. 
 
These participant reimbursement amounts are in line with reimbursement amounts that have been used in 
other studies with similar patient populations and for similar amounts of participant time. They are not 
expected to constitute undue inducement of patients to participate in the research or to continue beyond a 
point that they would have otherwise withdrawn. Participants have the right to withdraw from the study 
without financial penalty. In other words, any reimbursement already distributed to the participant will not 
be revoked. 
 
Participant reimbursement receipts will document the provision of the reimbursements. A disbursement log 
in accordance with the NYULH Policy on Human Subject Payments will be used to document distribution 
of payments with all study participants.  
 
16 Study Administration 
16.1 Study Leadership 
Overall study leadership is provided by the study MPIs, Dr. Kelly Doran and Dr. Jennifer McNeely. Clinical 
leads and advisors for the study who will not have a direct role in study conduct or data analysis will not 
be included on the IRB application. 
There is no Steering Committee for this low-risk study. The study DSMB is described in a separate 
section. 
 
17 Conflict of Interest Policy 
The independence of this study from any actual or perceived influence, such as by the pharmaceutical 
industry, is critical. Therefore, any actual conflict of interest of persons who have a role in the design, 
conduct, analysis, publication, or any aspect of this trial will be disclosed and managed. Furthermore, 
persons who have a perceived conflict of interest will be required to have such conflicts managed in a 
way that is appropriate to their participation in the trial. The study leadership in conjunction with the CDC 
has established policies and procedures for all study group members to disclose all conflicts of interest 
and will establish a mechanism for the management of all reported dualities of interest.  

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Any investigator who has a conflict of interest with this study (patent ownership, royalties, or financial gain 
greater than the minimum allowable by their institution, etc.) must have the conflict reviewed by the NYU 
Langone Conflict of Interest Committee with a Committee-sanctioned conflict management plan that has 
been reviewed and approved by the study sponsor prior to participation in this study.  All NYULH 
investigators will follow the applicable conflict of interest policies. Investigators from other study sites are 
expected to follow their own institution’s conflict of interest policies, as well as to report any relevant 
conflicts of interest to the study MPIs. 
 

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Study number: s19-01547
Page 49
Version date: 12/22/2022 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and NYU Langone Health.  Do not disclose or use except as authorized 
in writing by the study sponsor 
Behavioral Intervention Template Version: 11 January 2019
19 Attachments
These documents are relevant to the protocol, but they are not considered part of the protocol.  They are 
stored and modified separately. As such, modifications to these documents do not require protocol 
amendments, with the exception of key information sheets and consent forms, which require IRB 
approval for any changes. 
 
The following attachments are included: 
 
Attachment A. 
Schedule of Events 
Attachment B. 
Consent Form – Main Study 
Attachment C. 
Key Information Sheet – Main Study 
Attachment D. 
Verbal Consent Form – Qualitative Interview Patients 
Attachment E. 
Verbal Consent Form – Qualitative Interview Providers 
Attachment F. 
UBACC for RCT 
Attachment G. 
Baseline Screening and Survey (Questionnaire, Information Form, Exit Survey)  
Attachment H. 
Locator Form  
Attachment I. 
Baseline SDC Group Handouts  
Attachment J. 
Follow-up Questionnaires (1, 3, 6-month)  
Attachment K. 
Qualitative Interview Guide, ED Providers 
Attachment L. 
Qualitative Interview Guide, Patients 
Attachment M. 
Qualitative Interview Guide, Relay Peers 
Attachment N. 
Interim Contact Form  
Attachment O. 
Study Contact Card and Sticker  
Attachment P. 
Administrative Data Abstraction Tool  
Attachment Q. 
NYU Maven Data Entry Elements 
Attachment R. 
Prisoner Appendix 
Attachment S. 
Relay Scheduling Tool  
Attachment T. 
NYU Relay Evaluation DUA with DOHMH  
Attachment U. 
Appointment Reminder Mailing 
Attachment V. 
Contacts’ Card Letter Insert 
Attachment W. 
Contacts’ Card 
Attachment X. 
Happy Holidays Card 
Attachment Y. 
Thank you Card 
 
 

Study number: s19-01547 
 
Page 1 
Version date: 06/21/2021 
CONFIDENTIAL
This material is the property of the NYU School of Medicine and Langone Health.  Do not disclose or use except as authorized in writing by the study sponsor
Attachment A 
Schedule of Events 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Activity 
Baseline 
 
 
1 Month 
Visit 
 
 
3 Month 
Visit 
 
Interim 
Contacts 
6 Month 
Visit 
 
Qualitative 
Interviews 
12-Month 
Outcome 
Abstraction 
Screening 
  
  
  
 
  
ED provider calls Relay hotline
X
 
Assignment of RA
X
 
Screening for eligibility 
X
 
 
 
 
 
 
Informed consent process 
X
 
 
 
X 
 
Primary Study Procedures 
 
 
 
 
 
 
Randomization
X
 
Participant questionnaire
X
X
X
 
X
Participant information form
X
 
Locator form
X
 
Relay intervention or SDC* 
X
 
 
 
 
 
Exit survey 
X
 
 
 
 
 
Semi-structured interview
X
Administrative data extraction  
X
Additional Participant Contacts
Mail “Thank you” card (within week 
following baseline visit)
X 
Mail “Holiday” card (if applicable)
X
Mail “Appointment reminder” cards 
(if applicable)
X 
Confirm locator form information
X
X
X
X
Confirm next study appointment 
X
X
X
X
X
Additional Study Procedures
Give study contact card
X
Reimbursement and Greenphire 
ClinCard FAQ (if applicable)
X 
X 
X 
X 
X 

Study number: s19-01547
Page 1
Version date: 06/21/2021
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Health.  Do not disclose or use except as authorized in writing 
by the study sponsor