Conditions: Drug Overdose Opioid-Related Disorders Drug Addiction Drug Abuse Substance Abuse
Keywords: Opioid Substitution Treatment Telephone intervention secondary prevention naloxone
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 80
Healthy volunteers: no

Brief summary:
This project will further develop and test the Tailored Telephone Intervention delivered by Peers to Prevent Recurring Opioid Overdoses (TTIP-PRO), a promising, low-cost, intervention to facilitate entry into medication assisted treatment (MAT) for individuals experiencing a non-fatal opioid overdoses (OOD). A prior small-scale pilot/feasibility study of TTIP-PRO (NCT02282306) found that the participating patients and the Peer Interventionists were satisfied with their participation, the intervention was acceptable, and the system for generating patient-tailored intervention information performed well. The overall goal of the present study is to conduct a pilot randomized controlled trial of TTIP-PRO versus a control group. It is hypothesized that patients in the TTIP-PRO group will have more favorable drug-abuse-related outcomes than patients in the control group.

Detailed description:
This pilot study is a randomized controlled intent-to-treat (ITT) clinical trial. Approximately eighty eligible participants will be randomized in a 1:1 ratio to the control condition (Information and NARCAN® (naloxone) Nasal Spray kit) or to the experimental condition (TTIP-PRO in addition to the elements provided in the control condition). All participants will complete a follow-up phone call approximately 3-weeks post-randomization, during which process measures will be completed, and in-person visits at approximately 3, 6-, and 12-months following enrollment.

This is a single site study; all data will be collected at the University of Cincinnati. Approximately 80 participants will be randomized into this pilot efficacy trial. The hypotheses to be tested include that participants assigned to the TTIP-PRO intervention will: have a higher rate of enrollment in MAT, have a lower rate of recurring opioid overdose, and have greater reduction in illicit opioid use.

Arms:
arm 1: PTOEND: Personally-tailored opioid overdose prevention education and naloxone distribution.

Participants in this arm will be given a NARCAN (naloxone) nasal spray kit and personally-tailored information packet about opioid overdose and treatment. arm 2: PTOEND+PI: Personally-tailored opioid overdose prevention education and naloxone distribution, plus Peer Intervention.

In addition to a NARCAN (naloxone) nasal spray kit and personally-tailored information packet about opioid overdose and treatment, participants randomized to this arm will also receive the experimental Peer Intervention.

Interventions: intervention 1: Peer Intervention intervention 2: naloxone nasal spray kit intervention 3: Personally-tailored opioid overdose prevention education (information packet)
Intervention descriptions: intervention 1: The Peer Intervention is a 20-minute telephone call delivered by a Peer Interventionist, who is trained to answer questions about the content of the personally-tailored information packets. The primary goal of the call is for the participant and the Peer Interventionist to have an open exchange of information about medication-assisted treatment (MAT) for opioid use disorder. intervention 2: Naloxone nasal spray (NARCAN) is a potentially life-saving medication that can stop or reverse the effects of an opioid overdose. This nasal spray is approved by the FDA for reversing OODs and has a favorable side-effects profile. A take-home kit will be provided to the patient participants, which may be useful in the event of a future opioid overdose. intervention 3: Personally-tailored information packet with three participant-specific reports ("Personal Overdose Risk Factors Report"; "Medication Assisted Treatment (MAT) Report"; and the "Opioid Overdose Information Report"), and general written information about opioid overdose and treatment for opioid use disorder.

Protocol document:
Prot_SAP_001.pdf: 
TTIP-PRO Protocol Version 4.1 – 11/8/17  
 
 
 
Page 1 of 39 
 
A Tailored, Peer-delivered Intervention to Reduce Recurring Opioid Overdoses 
 
NCT02922959 
 
Protocol version date: 11/8/2017 
 


TTIP-PRO Protocol Version 4.1 – 11/8/17  
 
 
 
Page 2 of 39 
 
 
 
 
 
 
A Tailored, Peer-delivered Intervention to Reduce Recurring Opioid Overdoses  
 
 
 Principal Investigator: Theresa Winhusen, Ph.D.  
Co-Investigators: Michael Lyons, M.D., M.P.H., Christine Wilder, M.D. 
 
November 8, 2017 
 
Version: 4.1 
 
 
 
 
 


TTIP-PRO Protocol Version 4.1 – 11/8/17  
 
 
 
Page 3 of 39 
 
 
Table of Contents 
 
A. SPECIFIC AIMS ........................................................................................................................................... 4 
B. BACKGROUND AND SIGNIFICANCE .................................................................................................... 4 
C. PRELIMINARY STUDIES .......................................................................................................................... 6 
D. INVESTIGATOR EXPERIENCE ................................................................................................................ 6 
E. METHODS .................................................................................................................................................... 7 
1.0 Study Design ............................................................................................................................................ 7 
1.1 Overview of study design .................................................................................................................... 7 
1.2 Number of sites and participants .......................................................................................................... 7 
1.3 Study eligibility .................................................................................................................................... 7 
1.4 Study assessments ................................................................................................................................ 8 
1.5 Randomization Plan ........................................................................................................................... 10 
2.0 Study Treatments ................................................................................................................................... 10 
2.1 Control condition ............................................................................................................................... 10 
2.2 TTIP-PRO .......................................................................................................................................... 11 
3.0 TTIP-PRO Training, Certification, and Monitoring .............................................................................. 12 
3.1 Finalizing Training Materials ............................................................................................................. 12 
3.2 Approach for developing training materials ...................................................................................... 12 
3.3 Training and Certification of Peer Interventionists ............................................................................ 13 
3.4 Fidelity and Adherence Monitoring ................................................................................................... 13 
4.0 Study Procedures .................................................................................................................................... 14 
4.1 Schedule of Assessments and Procedures .......................................................................................... 14 
4.2 Study Schema ..................................................................................................................................... 15 
5.0 Data Storage and Analysis ..................................................................................................................... 16 
5.1 Data Storage and Confidentiality ....................................................................................................... 16 
5.2 Data Analysis ..................................................................................................................................... 16 
6.0 Study completion time ........................................................................................................................... 17 
F. HUMAN SUBJECTS .................................................................................................................................. 17 
G. RISK/BENEFIT ASSESSMENT ................................................................................................................ 17 
H. PAYMENT ................................................................................................................................................. 19 
I. SUBJECT COSTS ........................................................................................................................................ 19 
J. CONSENT FORMS ..................................................................................................................................... 19 
K. LITERATURE CITED ............................................................................................................................... 20 
Appendix A: Examples of TTIP-PRO-generated reports for fictional patient ................................................ 23 
Appendix B: Data Safety and Monitoring Plan (DSMP) ................................................................................. 31 
 
 
 
 


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A. SPECIFIC AIMS 
 
Recurring opioid overdose (OOD) is a significant problem in the U.S. The only completely effective method 
of preventing subsequent OOD is successful treatment of the underlying opioid use disorder (OUD). Despite 
this, there are no interventions to facilitate treatment entry for patients experiencing a non-fatal OOD.  This 
project will further develop and test the Tailored Telephone Intervention delivered by Peers to Prevent 
Recurring Opioid Overdoses (TTIP-PRO), a promising, low-cost, intervention to facilitate entry into 
medication assisted treatment (MAT) for individuals experiencing a non-fatal OOD.  
 
The specific aims of this project are to:  
 
1) Finalize the Peer Interventionist training materials by creating training files and evaluating the inter-rater 
reliability of TTIP-PRO’s competence assessment; and  
 
2) Conduct pilot testing in preparation for a full-scale clinical trial 
 
Exploratory aims are to:  
 
E1) Test the validity of two assessments developed for TTIP-PRO;  
 
E2) Test our conceptual model of TTIP-PRO’s mechanisms of change. 
 
 
B. BACKGROUND AND SIGNIFICANCE  
 
In recent years, the U.S. has experienced a growing opioid-use epidemic accompanied by a dramatic rise in 
OOD deaths.1-3 In 2012, prescription opioids were involved in 16,000 overdose deaths, while heroin was 
involved in 5,925 overdose deaths; this equates to an average of 60 deaths per day.4 Non-fatal OODs have 
also drastically increased in recent years. In 2011, there were 420,000 emergency department (ED) visits 
related to abuse of prescription opioids, representing an increase of over 150% since 2004. In the same year, 
there were 258,482 ED visits for heroin use,5 resulting in a combined average of over 1,800 opioid-abuse-
related ED visits per day. In addition to the human cost of OODs, there are significant financial costs as well: 
the median cost of treatment was $4,521 for non-hospitalized, and $22,460 for hospitalized, OOD patients.6  
 
Individuals experiencing a non-fatal OOD are at heightened risk for future OODs.7-10 A recent study revealed 
that 7% of all patients who were treated for an OOD in an ED were treated for more than one OOD within a 
single year.6  The proportion of patients with more than one OOD was higher in particular subsamples, with 
31% of Medicare and 25% of Medicaid OOD patients having more than one OOD ED visit in one year.6 
Patients with repeated OODs accounted for 15% of all OOD ED visits and were more likely to be 
hospitalized.6 Attempts to mitigate OOD deaths have largely focused on naloxone, an opioid antagonist that 
is effective in OOD reversal. Specifically, there have been concerted efforts to increase the accessibility of 
naloxone 3 and to train opioid-abusing individuals and their families on the signs of OOD and naloxone 
administration.11-14 Although naloxone can reverse an acute overdose there is no guarantee that it will be 
available in time. The only completely effective method for preventing subsequent OOD is successful 
treatment of the underlying opioid use disorder (OUD). Receiving medication assisted treatment (MAT) for 
OUD (e.g., methadone- or buprenorphine-maintenance) significantly reduces the likelihood of OOD.15-18 
However, in addition to the barriers of waiting lists and the costs of MAT, inaccurate perceptions of MAT – 
including myths about its side effects and lack of efficacy – also prevent some individuals with OUD from 
entering treatment.19, 20 Currently there are no published secondary prevention interventions to help patients 
who have experienced a non-fatal OOD enter OUD treatment. 


TTIP-PRO Protocol Version 4.1 – 11/8/17  
 
 
 
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A primary goal of TTIP-PRO is to address negative, inaccurate perceptions of MAT in order to encourage 
individuals with OUD to enter a MAT program. Research suggests that individuals experiencing a recent 
non-fatal OOD may be amenable to entering treatment.21 Specifically, 26% of injection drug users 
experiencing a non-fatal OOD sought treatment for their addiction within 30 days of the event and 75% of 
those patients enrolled in treatment.21 Seeking treatment was significantly more likely when someone spoke 
to the patient about addiction treatment.21 Thus, engaging individuals with a relatively recent OOD in a MAT 
program should be an achievable goal. In addition to using MAT to reduce OOD risk, it has been proposed 
that educating opioid abusers about OOD risk factors could reduce OOD rates.17, 22 While several studies 
have demonstrated that education can significantly increase knowledge,23, 24 the impact on risk reduction 
behavior is typically not assessed. 25 In addition, there can be a disconnect between knowledge and behavior, 
with individuals knowingly engaging in behaviors that can increase OOD risk.26  
 
In order to maximize the potential impact of TTIP-PRO on risk reduction behavior, particularly on entering a 
MAT program, the creation of TTIP-PRO was guided by the elaboration likelihood model (ELM) of 
persuasion.27, 28 The ELM posits that people process persuasive information through two routes: central, in 
which the material is actively considered, and peripheral, in which the material is given only superficial 
consideration. Information that is processed centrally and found to be convincing and valuable results in a 
positive attitude change that is relatively long lasting and predictive of behavior. Communication that is 
processed by the peripheral route results in attitudes that are susceptible to further change and not predictive 
of behavior. Conditions that increase the likelihood of information being centrally processed and leading to a 
positive attitude change (e.g., that MAT would be beneficial) include: 1) the material is seen as personally 
relevant; 2) the information can be readily understood; and 3) the source of the information is considered 
credible. TTIP-PRO was designed to maximize each of these conditions.  
 
1) Personally Relevant: Research suggests that the individuals targeted in TTIP-PRO, that is, those recently 
experiencing an OOD, are more likely to find information about OOD and the benefits of MAT personally 
relevant compared to individuals with OUD who have not recently overdosed. McGregor and colleagues17 
found that a significantly greater proportion of individuals experiencing an OOD within the prior 6 months 
estimated that a future OOD was likely (56%) compared to those who had experienced an OOD more than 6 
months ago (16%) and to individuals with OUD who had never experienced an OOD (14%). In applying 
ELM to health promotion messages, a key recommendation is to use tailored messaging to increase the 
relevance of the information to intervention recipients.29 Thus, TTIP-PRO provides tailored feedback to a 
given individual based on his/her OOD risk factors and knowledge about OOD and MAT. 2) Easy to 
Understand: To enhance patients’ understanding of the information provided in TTIP-PRO, information is 
provided both verbally and in writing to facilitate multimodal learning. The verbal component helps ensure 
that low literacy is not a barrier to understanding, as does careful attention to reading level for the written 
component. 3) Credible: To provide a credible source of information, all information has a solid empirical 
basis and is delivered by a peer interventionist, who has personal experience with OUD and OOD. Peer 
interventionists are typically perceived as highly credible and can provide personal knowledge that facilitates 
active learning through a shared experiential process.30  
 
Our conceptual model of TTIP-PRO’s mechanisms of change is provided in Fig.1. The measures for the four 
hypothesized mediators (i.e., fear of treatment, self-efficacy for quitting, desire to quit using drugs, and 
knowledge about OOD) can be found in section 1.4 (study assessments). According to ELM, information 
will be processed centrally, and have the most impact, to the degree that the information is seen as personally 
relevant and from a credible source; our measure of this, the Helpfulness of Peer Intervention (HOPI) is 
described in section 1.4 (study assessments); we hypothesize that the HOPI score will be a moderator of the 
mediator-outcome relationships.  
 
 
 


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C. PRELIMINARY STUDIES 
 
Our development and initial testing of the TTIP-PRO intervention is described by Winhusen et al.31 In brief, 
we conducted a pre-post study to assess TTIP-PRO-content acceptability and software performance. Two 
Peer Interventionists, who were abstinent from illicit opioids, enrolled in MAT at the UC Addiction Sciences 
Division (ASD) program, and had experience with OOD, were enrolled and trained to provide the TTIP-PRO 
intervention. Recruitment letters were sent to patients treated for OOD at the University of Cincinnati 
Medical Center (UCMC) emergency department (ED) within the prior 8 months. Eight patients received 
TTIP-PRO and completed pre/post assessment. Peer Interventionists reported high satisfaction with TTIP-
PRO. There were no performance issues with the TTIP-PRO-software. All participants rated TTIP-PRO as 
“very helpful” and their OOD knowledge increased significantly, with 69.9% correct responses pre-TTIP-
PRO and 93.6% post-TTIP-PRO.  
 
D. INVESTIGATOR EXPERIENCE 
Drs. Winhusen, Lyons, and Wilder worked together on the initial testing of TTIP-PRO.31 Drs. Winhusen and 
Lyons were site co-investigators for a prior clinical trial that tested screening, brief intervention, referral, and 
treatment (SBIRT) in the 
ED and participants were 
followed up for 12 months 
(NIDA’s Clinical Trials 
Network SMART-ED 
trial32). Dr. Winhusen is a 
licensed clinical 
psychologist and one of the 
foremost experts in 
conducting multi-site 
addiction clinical trials in 
clinical practice settings. 
Specifically, Dr. Winhusen 
has been the national PI of 
five33-37, and Co-PI of a 
sixth38, multi-site trials in 
NIDA’s Clinical Trials 
network (CTN) since 2001. 
Within the past five years, Dr. Winhusen has overseen the successful implementation of 13 clinical trials at 7 
community treatment sites, located in 5 states. In addition to serving as a co-investigator for the NIDA CTN 
SMART-ED trial, Dr. Lyons helped to lead a successful CDC-funded randomized trial of a brief-intervention 
to prevent risky driving and drinking practices in ED patients.39  Dr. Wilder is a board-certified addiction 
psychiatrist with expertise in opioid overdose prevention via naloxone distribution to patients in OUD 
treatment. She helped develop the Cincinnati VA Overdose Education and Naloxone Distribution (OEND) 
Program. Additionally, Dr. Wilder has previous experience in the development and dissemination of peer 
interventions, specifically facilitation of psychiatric advance directives.40 Dr. Wilder developed the initial 
peer training manual employed by the state of Virginia41 and was instrumental in identifying barriers to 
implementation of the intervention.42  
 
 


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E. METHODS 
1.0 Study Design 
1.1 Overview of study design 
 
Following finalization of the Peer Interventionist training materials (described below in section 3.0), a pilot 
efficacy trial will be completed. This pilot study is a randomized controlled intent-to-treat (ITT) clinical trial. 
Potential participants will be recruited through various methods, which include but are not limited to 
advertisements, flyers, and word-of-mouth. Approximately eighty eligible participants will be randomized in 
a 1:1 ratio to the control condition (Information and NARCAN® Nasal Spray kit) or to the experimental 
condition (TTIP-PRO in addition to the elements provided in the control condition). All participants will 
complete a follow-up phone call approximately 3-weeks post-randomization, during which process measures 
will be completed, and in-person visits at approximately 3, 6-, and 12-months following enrollment. 
 
1.2 Number of sites and participants 
This is a single site study; all data will be collected at the University of Cincinnati. This project includes two 
types of participants: 1) the participants who may receive the TTIP-PRO intervention, referred to as 
participants, and 2) the participants who will serve as Peer Interventionists. Participants will be recruited to 
develop training audio files until 4 training tapes are obtained; all of these “training” participants will receive 
the TTIP-PRO intervention. Approximately 80 participants will be randomized into the pilot efficacy trial. 
Approximately 15 Peer Interventionists will participate. 
 
1.3 Study eligibility 
This project includes two types of participants: 1) the participants who may receive the TTIP-PRO 
intervention, referred to as participants, and 2) the participants who will serve as Peer Interventionists.  
 
1.3.1 Participants 
All potential participants will be recruited through various methods, which include but are not limited to 
advertisements, flyers, and word-of-mouth. Eligible participants will meet all inclusion, and no exclusion 
criteria:  
 
Inclusion Criteria: 
1. Report having been treated for an OOD within the past 6 months;  
2. Age 18 years or older; 
3. Scores “high risk” for heroin and/or non-medical use of prescription opioids on the NIDA modified 
ASSIST (i.e., ≥ 27);  
4. Be able to understand the study, and having understood, provide written informed consent in  
English;  
5. Access to a phone (for TTIP-PRO intervention and phone follow-up);  
6. Be willing to have their intervention audio recorded and rated if randomized to TTIP-PRO; 
7. Have an opioid-positive baseline/screening urine drug screen. 
 Exclusion Criteria:  
1. In the judgment of the investigator, would not be expected to complete the study protocol (e.g., due to 
relocation from the clinic area, probable incarceration, etc.)  
2. Current engagement in addiction treatment; 
3. Residence more than 40 miles from the location of follow-up visits; 
4. Inability to provide sufficient contact information (must provide at least 2 reliable locators); 
5. Prior participation in the current study. 


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1.3.2 Peer Interventionists 
All potential Peer Interventionists will be recruited primarily by word of mouth from a UC ASD (UC 
Health/UCPC) MAT (i.e., receiving methadone or buprenorphine) clinic. For individuals early in recovery or 
struggling with recovery and/or other issues, interacting with active users could increase their risk of relapse. 
Our Peer Interventionist eligibility criteria are designed to select only those whose recovery is sufficiently 
stable to mitigate this risk. 
 
 Inclusion Criteria:  
1. Age 18 years or older;  
2. Enrolled in UC ASD (i.e., UC Health/UCPC) MAT program;  
3. Enrolled in a MAT program for at least one year; 
4. Report being abstinent from illicit opioids for at least one year;  
5. Report having experienced, witnessed, and/or lost a family member or friend to an overdose.  
Exclusion Criteria:  
1. Unwilling to sign a release of information (ROI) to allow research staff to confirm pertinent 
eligibility criteria and to monitor clinical status with UC ASD (i.e., UC Health/UCPC) MAT clinical 
staff; 
2. Clinical staff from their program have significant concerns about their participation;  
3. Unwilling to have their sessions audio recorded and assessed by a TTIP-PRO trainer;  
4. Specific plan to leave the UC ASD (i.e., UC Health/UCPC) MAT program within the next 6 months. 
 
1.4 Study assessments 
 
1.4.1 Participant Measures  
 
Primary outcome measure. Entered MAT (Yes/No) – The determination of whether the participant 
enrolled in a MAT program within the 12-month follow-up will be based on participant self-report, 
confirmed by clinic records, obtained with the proper release of information (ROI) from the participant.  
 
Secondary outcome measures. Opioid overdose (Yes/No)–Determination of whether the participant 
experiences an OOD within 12-month follow-up will be based on participant self-report. 
 
Opioid use will be assessed with the Timeline Follow-back (TLFB) procedure43, 44 and urine drug screens 
(UDS). At each assessment point, the TLFB will be used to assess self-reported substance use for the 28 days 
prior to the visit. The rapid UDS will include screens for substances of abuse. Urine samples will be 
collected using temperature monitoring and the validity of urine samples will be checked with the use of a 
commercially available adulterant test.  
 
Process measures.  Barriers to Treatment Inventory (BTI) - This 25-item Likert-scale questionnaire has 
seven internally consistent subscales relating to Absence of Problem, Negative Social Support, Fear of 
Treatment, Privacy Concerns, Time Conflict, Poor Treatment Availability, and Admission Difficulty.45, 46  
The Fear of Treatment subscale will be evaluated as a mediator of TTIP-PRO’s efficacy (see Fig. 1). 
 
Thoughts about abstinence (TAA) - Participants’ commitment to abstinence from illicit substances will be 
assessed with the TAA.47 This measure assesses the participant’s desire to quit, expected success in quitting 
and estimated difficulty in avoiding relapse. Both desire to quit and expected success in quitting will be 
evaluated as mediators (see Fig. 1). 


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The Opioid Overdose and Treatment Awareness Survey (OOTAS). The OOTAS assesses knowledge about 
OOD and MAT and is comprised of four sections: 1) OOD risk factors; 2) signs of an OOD; 3) how to 
respond to an OOD; and 4) myths about MAT. The total OOTAS score will be evaluated as a mediator of 
TTIP-PRO’s efficacy (see Fig. 1). 
  
The Helpfulness of Peer Intervention (HOPI) – The creation of TTIP-PRO was guided by the ELM which 
posits that material seen as personally relevant and from a credible source will be centrally processed, 
resulting in a positive attitude change that is relatively long lasting and predictive of behavior.27, 28 
Otherwise, the information will be processed by the peripheral route and will result in attitudes that are 
susceptible to further change and not predictive of behavior.27, 28 Thus the degree to which the information 
provided in TTIP-PRO is seen as personally relevant and from a credible source will likely moderate the 
mediator-outcome relationship (see Fig. 1).  Because there are no published assessments of these qualities, 
we created the HOPI. The HOPI is a 12-item assessment in which each statement is rated on a 5-point Likert 
scale (1=strongly disagree; 5=strongly agree). TTIP-PRO is assessed on two subscales: 1) personally 
relevant and 2) credible. According to ELM,27, 28 likability and credibility are the principal components of 
source credibility and so the credible subscale focuses on the participant’s perceptions of the Peer 
Interventionist. The total HOPI score will be tested as a moderator of the mediator-outcome relationships 
(see Fig. 1); two versions of the HOPI will be used – one for participants randomized to TTIP-PRO and one 
for those randomized to the control condition, which will assess the degree to which participants found the 
materials provided to be personally relevant and credible. 
 
Other measures.  
 
Demographics -This assessment includes questions about the participant’s ethnicity, age, and sex. 
 
The Personal Opioid-Overdose Risk Survey (PORS) The PORS assesses an individual’s OOD risk factors. It 
only includes risk factors for which there is documented evidence and scoring for each item is based on the 
strength of the evidence that the factor increases risk.31  
 
NARCAN® Nasal Spray kit Utilization - Determination of whether the participant utilizes the kit within 12-
month follow-up will be based on participant self-report. 
 
1.4.2 Peer Interventionist Assessments 
 
Demographics -This assessment includes questions about the Peer Interventionist’s ethnicity, age, and sex. 
 
Peer Volunteer Experience Questionnaire (PVEQ) – The PVEQ was developed by Dennis and colleagues to 
obtain feedback from peer volunteers delivering an intervention for post-partum depression.48 Three sections 
of the PVEQ are relevant for TTIP-PRO and will be used to obtain feedback on: 1) the training and 
certification process; 2) interactions with participants; and 3) the personal effects of being a Peer 
Interventionist (e.g., benefits and drawbacks of being a Peer Interventionist). An additional item will be 
included to assess the Peer Interventionist’s satisfaction with his/her experience, rated on a 5-point scale (1-
very dissatisfied, 2-dissatisfied, 3-neither satisfied or dissatisfied, 4- satisfied, 5-very satisfied).  
 
Global Health will be assessed with the PROMIS 10-item measure for Global Health, which briefly but 
comprehensively assesses physical, mental, and social health; this is a reliable (Cronbach's α > 0.80) measure 
with demonstrated construct validity.49 The interventionists will complete this measure, used to assess 
positive and negative outcomes, prior to being assigned participants (baseline), every 4 months during the 
approximately 14 month enrollment period, and after the last TTIP-PRO intervention has been provided. 


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1.4.3 Collection and reporting of adverse events (AEs) and serious adverse events (SAEs) 
In general, the risks associated with trials employing behavioral interventions are presumed minimal relative 
to those evaluating pharmacologic interventions. Based on the TTIP-PRO acceptability study the risk from 
TTIP-PRO is low.31 Still, for the present trial, the population studied may possibly be at higher risk given the 
nature of the disorder and the population. Thus, the following events, which are not defined as SAEs, will be 
tracked on an AE CRF for participants and Peer Interventionists: 
 
1. Suicidal ideation 
2. Homicidal ideation 
 
In addition, the following events will be tracked on an AE CRF for the Peer Interventionists: 
 
1. Discharge from MAT program for any reason 
2. Illicit opioid use  
3. Other clinical deterioration as reported by clinic staff 
 
For TTIP-PRO, which is a behavioral trial, the RA is primarily responsible for assessing the occurrence of 
AEs/SAEs with oversight by the Study Medical Monitor and PI. For Participants, the RA will query about 
how s/he has been feeling since the last visit (i.e., at the follow-up phone call in week 3 and in-person visits 
at 3, 6-, and 12-months following enrollment). For Peer Interventionists, the RA will query about how s/he 
has been feeling following the delivery of each TTIP-PRO intervention.  All AEs/SAEs occurring during the 
course of the clinical trial will be collected, documented, and reported by the investigator or sub-
investigators in accordance with reporting requirements. Dr. Lyons or the designated study physician will 
assess the severity, causality and outcome of all AEs and SAEs. It will also be Drs. Lyons’, Winhusen’s, and 
Wilder’s responsibility to manage all AEs and SAEs and to make referrals for appropriate care, as necessary. 
All SAEs will be reported to the University of Cincinnati Institutional Review Board and the NIDA project 
officer within 72 hours of their discovery. All subject information will be de-identified when reporting 
serious adverse events.  
 
1.5 Randomization Plan  
Eligible participants will be randomized in a 1:1 ratio to the control or experimental arms. The randomization 
sequence will be unknown to the research staff. 
 
2.0 Study Treatments 
 
2.1 Control condition 
 
All randomized participants will receive the following information: 1) SAMHSA’s “Opioid Overdose 
Prevention Toolkit: Safety Advice for Patients and Family Members” and “Recovering from Opioid 
Overdose”; 2) SAMHSA’s “Medication-Assisted Treatment for Opioid Addiction: Facts for Families and 
Friends”; and 3) a list of local methadone and buprenorphine treatment providers. They will also receive a 
NARCAN® Nasal Spray kit. The NARCAN® Nasal Spray kit is approved by the FDA for reversing OODs 
and has a favorable side-effects profile. 
 
 


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2.2 TTIP-PRO  
 
An overview of TTIP-PRO, as evaluated in this pilot trial, is provided in Fig. 2. A full description of the 
development and initial testing of TTIP-PRO is described in Winhusen et al.31 TTIP-PRO consists of two 
parts: 1) an information packet which includes three reports (“Personal Overdose Risk Factors Report”; 
“Medication Assisted Treatment (MAT) Report”; and the “Opioid Overdose Information Report”) generated 
from the participant’s responses to two surveys and information about how to access treatment at a UC ASD 
(UC Health/UCPC) MAT program;  2) a 20-minute telephone intervention delivered by Peer 
Interventionists. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Information Collected to Tailor the Intervention. The Personal Opioid-Overdose Risk Survey (PORS). The 
PORS assesses an individual’s OOD risk factors. It only includes risk factors for which there is documented 
evidence and scoring for each item was based on the strength of the evidence that the factor increases risk. In 
order to tailor the questions to reference only the type(s) of opioids used by a given individual, there are 
three versions of the PORS, one for heroin-only users, one for prescription opioid-only users and one for 
those who use both heroin and prescription opioids.31 The Opioid Overdose and Treatment Awareness 
Survey (OOTAS). The OOTAS assesses knowledge about OOD and MAT; like the PORS, there are three 
versions of the OOTAS to reflect the type(s) of opioids used. The OOTAS is comprised of four sections: 1) 
OOD risk factors; 2) signs of an OOD; 3) how to respond to an OOD; and 4) myths about MAT. The first 3 
sections include only evidence-based items supported by a recent literature review, while items for the 4th 
section are based on both a literature review and on input from the medical staff of the UC-affiliated 
methadone program.  
 
 The TTIP-PRO Computer Program. The TTIP-PRO data entry and report-generation system has been 
programmed into REDCap, a software toolset and workflow methodology for collection and management of 
clinical research data. After an operator enters all relevant information for a particular patient (type of opioid 
used, responses to the PORS and OOTAS questions), the TTIP-PRO system automatically generates three 
Figure 2. Overview of the Tailored Telephone Intervention Delivered by Peers to Prevent Recurring Opioid-Overdoses 
 
1. Information collected to tailor the intervention: 
-Opioids used: heroin, prescription opioids, both 
-The Personal Opioid-Overdose Risk Survey (PORS) 
-The Opioid Overdose and Treatment Awareness  
  Survey (OOTAS) 
2. TTIP-PRO computer program generates: 
-Personal Overdose Risk Factors Report 
-Medication Assisted Treatment (MAT) Report 
-Opioid Overdose Information Report 
3. The patient is given information packet: 
-Personal Overdose Risk Factors Report 
-Medication Assisted Treatment (MAT) Report 
-Opioid Overdose Information Report 
-Information about how to enter MAT at the UC ASD 
 
 
Key TTIP-PRO Characteristics 
-Designed for individuals with opioid use disorder and a  
  recent opioid overdose 
-Delivered by a Peer Interventionist – someone who has  
  been illicit opioid-abstinent for at least a year, is enrolled in 
  MAT, and has experience with opioid overdose 
-Intervention content tailored to each patient 
-TTIP-PRO computer program automatically generates  
  tailored feedback 
 
 
TTIP-PRO Goal: decrease recurring opioid overdoses 
-Encourage enrollment in MAT by: 
     -providing an opportunity to discuss MAT with a                
      successful MAT patient 
     -education about common MAT myths 
     -increasing patient awareness of risk for another  
      overdose 
 
-Increase knowledge about opioid overdoses and  
  appropriate response 
4. Peer Interventionist completes the telephone 
intervention 
-Introduces self as someone who has personal  
  experience with overdose, now successful in MAT 
-Answers questions about information packet 
-Shares treatment experiences and encourages  
  engagement in treatment 


TTIP-PRO Protocol Version 4.1 – 11/8/17  
 
 
 
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reports: 1) “Personal Overdose Risk Factors Report”; 2) “Medication Assisted Treatment (MAT) Report”; 
and 3) the “Opioid Overdose Information Report.” Sample reports for a fictional heroin-only user are 
provided in Appendix A. The TTIP-PRO Information Packet. To help prepare the participant for the peer-
delivered telephone component, each participant receives a packet with the three reports along with 
information on how to enroll in treatment at a UC ASD MAT program. Peer Interventionist Call. The Peer 
Interventionists will be provided with a full-set of information related to the three reports so that they can 
answer participant questions during the call. The primary goal of the call is for the Peer Interventionist to 
initiate an open exchange of information about MAT (e.g., the Peer Interventionist sharing her/his 
experiences etc.). The Peer Interventionists are reminded that although the goal is to encourage the 
participant to enter treatment, it is important to be accepting and supportive if the participant is not currently 
interested in MAT.  
 
3.0 TTIP-PRO Training, Certification, and Monitoring 
 
3.1 Finalizing Training Materials 
 
A training manual was created and utilized for the TTIP-PRO acceptability study; the Peer Interventionists 
provided positive feedback about the manual (i.e., provided the essential information succinctly)31 and, thus, 
we plan to use a version of this manual updated for the present project (e.g., to reference training tapes and 
other materials not available in the original project, less focus on the TTIP-PRO generated reports and more 
on an open exchange of information about MAT). Two important elements missing from the acceptability 
study, which will be established for the present project, are: 1) training files and 2) an assessment of inter-
rater reliability for the competence measure.  
 
3.2 Approach for developing training materials  
 
1. Creating training files. The training files will include 4 mock interventions (1 video, 3 audio) and 4 audio 
recorded interventions with patient volunteers. The 4 mock interventions will be created by ASD staff 
members acting as patients/interventionists. The mock interventions will include examples of well-done and 
poorly-done interventions. Since the intervention is delivered via telephone, the intervention for the training 
files (with the exception of the video file) will be delivered by phone and will be recorded using a 
combination of an in-ear microphone and a digital voice recorder. MAT patients meeting criteria to serve as 
a Peer Interventionist and passing certification will be recruited to create 4 audio training files with patient 
volunteers. Patient volunteers will be recruited from the UCMC ED and will meet the eligibility criteria 
outlined above (section 1.3) with the additional requirement of agreeing to have their audio recorded 
intervention used for training purposes.  
 
2. Inter-rater reliability. Two TTIP-PRO trainers who have been intimately involved with creating TTIP-
PRO will rate two training files. Inter-rater reliability will be measured by intraclass correlation coefficients 
(ICCs).50, 51 An ICC in the range of .75 - 1.0 reflects excellent agreement.51  If the ICC is less than .75 then 
clarifications will be made to the competence assessment and the trainers will rate two additional training 
files. This process will be repeated until an ICC greater than .75 is achieved. It is anticipated that the 8 
training files will be sufficient for establishing reliability but, if needed, additional training files will be 
created and rated. 
 
 
 


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3.3 Training and Certification of Peer Interventionists 
Potential Peer Interventionists will need to complete training and certification prior to being assigned 
participants. The process of becoming a certified Peer Interventionist includes the following: 
 
1. Reading the TTIP-PRO Peer Interventionist Manual  
 
2. Attending a training session on the TTIP-PRO Intervention 
 
3. Completing a practice intervention with the assigned trainer.  
 
4. Completing a blank copy of the OOTAS – the trainee needs to get at least 90% of the questions 
correct to “pass.” The OOTAS may be taken more than once. 
 
5.  Successfully completing a “mock” intervention. This entails providing the intervention to a person 
who is not a patient. The trainee’s performance will be rated by the trainer using a 3-point scale (1-
Meets expectations, 2-Needs improvement, 3-Expectations not met and additional training required). 
To be certified, the trainee needs to receive a “1” on at least 5 of the 6 abilities assessed: 
 
1. Ability to provide information while maintaining a conversational tone 
2. Ability to successfully complete the intervention within 20 minutes  
3. Ability to listen 
4. Sufficient familiarity with correct information about OOD and MAT to answer the 
participant’s questions 
5. Ability to remain non-judgmental and encouraging 
6. Ability to avoid confrontation 
 
 
 
3.4 Fidelity and Adherence Monitoring 
 
All TTIP-PRO interventions will be audio recorded and rated for adherence/fidelity using the same 
assessment as that used for certification. Any instance of falling below certification criteria will result in 
additional training or discontinuation from the trial depending on the nature of the problematic performance.  
 
 


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4.0 Study Procedures 
 
4.1 Schedule of Assessments and Procedures 
 
Table 1 provides an overview of the participant procedures and assessments. Table 2 provides an overview 
of the assessments that involve the Peer Interventionists.  
 
Table 1. Overview of Study Assessments and Procedures for Study Participants 
Assessment/Procedure 
Scr/Base/ 
Random 
TTIP-PRO 
Intervention 
3 WK 
FU call 
3 Mo 
FU 
visit 
6 Mo 
FU 
visit 
12 Mo 
FU 
visit 
Completed by 
ASD RA 
Peer  
Interventionist 
ASD 
RA 
ASD 
RA 
ASD 
RA 
ASD 
RA 
Screening Assessments 
 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
Releases of information 
X 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
NIDA modified ASSIST 
X 
 
 
 
 
 
Efficacy Measures 
 
 
 
 
 
 
MAT Entry Tracking 
 
 
 
X 
X 
X 
Opioid Overdose Tracking 
 
 
 
X 
X 
X 
Urine drug screen 
X 
 
 
X 
X 
X 
Time line follow-back 
X 
 
 
X 
X 
X 
Safety Measures 
 
 
 
 
 
 
Adverse Events  
 
 
X 
X 
X 
X 
Process Measures 
 
 
 
 
 
 
HOPI 
 
 
X 
 
 
 
OOTAS 
X 
 
X 
 
 
 
Barriers to Treatment 
X 
 
X 
 
 
 
Thoughts about abstinence 
X 
 
X 
 
 
 
Other Assessments 
 
 
 
 
 
 
Locator Information Form 
X 
 
 
X 
X 
 
PORS 
X 
 
 
 
 
X 
Utilization of NARCAN® 
 
 
 
X 
X 
X 
Interventions 
 
 
 
 
 
 
Provision of OOD and MAT 
information and NARCAN® 
Nasal Spray kit (all participants) 
X 
 
 
 
 
 
TTIP-PRO Intervention 
 
~ 2 weeks 
post-enroll 
 
 
 
 
Compensation 
$50 
 
$20 
$50 
$50 
$50 
 
 
 


TTIP-PRO Protocol Version 4.1 – 11/8/17  
 
 
 
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Table 2: Peer Interventionist Assessments  
Assessment 
Purpose 
Collection Schedule 
Demographics and eligibility 
Document Peer Interventionist study 
eligibility 
Screening/enrollment 
The OOTAS –Peer 
Interventionist Certification 
Helps to ensure intervention quality  
During certification 
Rating of TTIP-PRO sessions 
Helps to ensure intervention quality 
During certification and 
throughout the trial 
Peer Volunteer Experience 
Questionnaire (PVEQ) 
To obtain feedback on providing 
TTIP-PRO 
End of study participation 
PROMIS 10-item measure 
for Global Health 
To assess physical, mental, and social 
health 
Screening/enrollment and 
every 4 months during 
participation in pilot trial 
Adverse Events 
Safety 
After every TTIP-PRO session 
 
 
4.2 Study Schema 
 
The study schema is provided in Figure 3. 
4.3 Recruitment and Retention 
 
4.3.1 Recruitment. Potential 
participants will be recruited 
through various methods, which 
include but are not limited to 
advertisements, flyers, and word-
of-mouth. Potential candidates will 
complete a pre-screen assessment 
and those who are potentially 
eligible and interested will be 
invited to sign informed consent 
and complete screening/baseline.   
 
4.3.2 Retention. Strategies to 
maximize retention will include 
reminder phone calls prior to 
scheduled appointments and 
follow-up phone calls and, if 
needed, certified letters to 
participants missing a visit. 
Participants will also be 
reimbursed up to $220 for their time and travel. Peer Interventionists will be provided with a study cell 
phone for use in delivering TTIP-PRO and for staying in contact with research staff regarding scheduled and 
completed interventions. Peer Interventionists will be compensated $40 for completing training/certification, 
and $20 for each participant for whom they provide the intervention. 
 
 
 
Figure 3. Study Schema 
Potentially eligible participants recruited through advertisements, flyers, 
and word-of-mouth complete a pre-screen assessment 
Interested and potentially eligible participants sign informed consent, 
complete screening/baseline, and are randomized 
TTIP-PRO group 
Informational materials, TTIP-PRO 
information packet, and NARCAN® 
Nasal Spray kit provided; Peer 
Interventionist call scheduled 
Control group 
Informational materials and 
NARCAN® Nasal Spray kit 
Peer Interventionist completes call with 
participant within ~ 2 weeks of enrollment 
Research follow-up phone call to assess putative mediators and moderator 
during ~ study week 3  
Research follow-up visits at 3, 6, and 12 months post-enrollment  


TTIP-PRO Protocol Version 4.1 – 11/8/17  
 
 
 
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5.0 Data Storage and Analysis 
 
5.1 Data Storage and Confidentiality 
To maintain participant confidentiality, study records and data will be stored in compliance with the 
International Conference on Harmonization (ICH) guidelines.  Participant records will be held confidential 
by the use of study codes in the study database, secure storage of any documents that have participant 
identifiers, and secure computing procedures for entering and transferring electronic data. No identifying 
information will be disclosed in reports, publications or presentations. Information collected for this study 
will be kept in a locked secure location accessible only to research staff and authorized personnel directly 
involved with this study.  
 
5.2 Data Analysis 
All analyses will be completed on the ITT sample using SAS (SAS Institute, Inc.). Statistical tests will be 
conducted at a 5% Type I error rate (two-sided) for all measures. It has been recommended that effect sizes 
be provided rather than using the Bonferroni procedure to adjust for multiple-comparisons; thus, effect sizes 
and 95% confidence intervals (CI’s) will be computed for each treatment effect. For each efficacy analysis, 
demographic/baseline characteristics and length of time since last OOD will be selected for inclusion in the 
model using the corrected Akaike Information Criterion (AICC) as the optimizing criterion. For missing 
data, multiple imputation methods will be used and the resulting model compared to the non-imputed model. 
Participant Analyses-The primary hypothesis, that a significantly greater proportion of TTIP-PRO, relative 
to control, participants will enter MAT within 12-month follow-up will be tested using a logistic regression 
(a generalized linear model with a logistic link). Secondary analyses. The key secondary hypothesis, that a 
significantly lower proportion of TTIP-PRO, relative to control, participants will have a recurring OOD 
within 12-month follow-up will be tested using a logistic regression (a generalized linear model with a 
logistic link). The secondary hypothesis that TTIP-PRO, relative to control, participants will have a 
significantly greater reduction in illicit opioid use will be tested using two outcomes, one based on self-report 
and the other on UDS results. The proportion of self-reported use days will be treated as a binomial variable 
and regressed using logistic mixed model regression (random-intercept generalized mixed-model regression 
with a logistic link function). UDS results (positive for illicit opioids vs. not positive), will be treated as a 
binary variable which will also be regressed using logistic mixed-model regression. For both outcomes, the 
effects of interest will be treatment and treatment-by-time interaction.  
 
Power: A pilot study necessitates a limited sample size, and is more useful for showing feasibility than 
providing an effect size estimate. The proportion of patients who will enroll in a MAT program is unknown 
for both the TTIP-PRO and control group. Thus, we based the estimated proportions on a recent randomized 
trial comparing buprenorphine administration during medical hospitalization and linkage to office-based 
buprenorphine post-discharge to buprenorphine detoxification. In that study, the linkage patients were more 
likely to enter office-based buprenorphine treatment (72.2%) compared to the detox group (11.9%). The 
linkage condition was much more intensive than TTIP-PRO and, thus, it is expected that the TTIP-PRO 
enrollment rate will be considerably less than that observed for the linkage group. Assuming that 12% of our 
control group enrolls in MAT, and a total sample size of 80, we would have 80% power using a two-tailed 
test and α =.05 to detect a TTIP-PRO effect for a MAT enrollment rate of ≥ 39%. In our SBIRT trial, our 12-
month follow-up rate was 78%. If 78% of participants complete the 12-month follow-up (n=62) in the 
proposed trial, we would have 80% power (assuming 12% engagement for the control group, a two-tailed 
test, and α =.05) to detect a TTIP-PRO effect for a MAT enrollment rate of ≥ 46%. 
 
Peer Interventionist Analyses - The hypotheses related to the Peer Interventionists will be tested with 
descriptive statistics. The proportion of Peer Interventionists: 1) attending the training who complete training 
and certification within the expected 4-hour timeframe and 2) who report being satisfied or very satisfied 
with their experience as a Peer Interventionist will be calculated.  


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Analyses for Exploratory Aims- E1 – Testing the validity of the HOPI and PORS. The HOPI was designed 
to include two subscales (i.e., personally relevant; credible). Factor analyses will be used to determine if the 
HOPI does, in fact, yield two factors corresponding to the intended subscales. Since the HOPI uses Likert-
scale variables, the factor analysis will be based on polychoric correlation. A logistic generalized linear 
model regression will be used to test the PORS score as a predictor of 1 year OOD rates. The strength of 
predictive validity will be expressed both as the estimated odds ratio and by area under a ROC curve.   
 
E2 – Testing the conceptual model of TTIP-PRO’s mechanisms of change. The purpose of the analyses 
described here is to explore the degree to which our conceptual model is consistent with the obtained study 
results. Using all ITT data, we will perform mediation analysis (empirically estimating 95% confidence 
intervals via bootstrapping) to test three mediation relationships: 1. fear-of-treatment, expected-success, and 
desire-to-quit as joint mediators of the effect of TTIP-PRO on engagement-in-MAT, 2. desire-to-quit, 
expected-success, and engagement-in-MAT as joint mediators of the effect of TTIP-PRO on level-of-opioid-
use, and 3.  knowledge-of-opioid-overdose and level-of-opioid-use as joint mediators of the effect of TTIP-
PRO on whether there is an opioid overdose recurrence. We will test whether helpfulness-of-the-intervention 
(HOPI) respectively moderates the effects of fear-of-treatment, expected-success, desire-to-quit, and 
knowledge-of-opioid-overdose. We will perform logistic regression when engagement-in-MAT and 
overdose-recurrence are outcomes and logistic mixed-model regression when opioid use is the outcome.  
6.0 Study completion time 
An individual participant’s period of time for participation and study completion is approximately 12 
months. For an individual Peer Interventionist, the time for participation and completion in the pilot trial is 
approximately 16 months, which includes the time needed for training and certification and for providing 
TTIP-PRO sessions during the approximately 14-month enrollment period. It is expected that two Peer 
Interventionists will help to develop the training materials and also participate in the pilot trial; their time of 
participation and study completion may take up to 24 months. The present project will take less than 3 years 
to complete.   
 
 
F. HUMAN SUBJECTS 
A detailed data and safety monitoring plan (DSMP), which has been approved by the study sponsor (NIDA) 
is provided in Appendix B.  
 
Prisoner Status-  Due to the illegality of illicit opioid use, many potential participants are likely meet the 
definition of prisoner (e.g., being in jail or prison, detained in other facilitates as an alternative to criminal 
prosecution or incarceration, being on probation or parole, being under house arrest or electronic monitoring, 
etc.). This trial would, thus, be challenging to conduct without allowing the participation of individuals who 
meet the definition of a prisoner. All randomized participants will receive direct benefit from participating in 
this trial by receiving: 1) the NARCAN® Nasal Spray kit, which could save their lives if they experience 
another opioid overdose; 2) information about opioid overdose and substance abuse treatment. For 
individuals who are, or become during the course of their participation, prisoners, study participation will 
have no effect on the participant’s criminal case, release or parole from jail or prison, or probation case. 
 
 
G. RISK/BENEFIT ASSESSMENT 
 
This project includes two types of participants: 1) the participants who may receive the TTIP-PRO 
intervention, referred to as participants, and 2) the participants who will serve as Peer Interventionists.  


TTIP-PRO Protocol Version 4.1 – 11/8/17  
 
 
 
Page 18 of 39 
 
 
Risks associated with the TTIP-PRO intervention. TTIP-PRO consists of two parts: 1) an information packet 
which includes three reports (“Personal Overdose Risk Factors Report”; “Medication Assisted Treatment 
(MAT) Report”; and the “Opioid Overdose Information Report”) generated from the participant’s responses 
to two surveys and information about how to be access treatment at a UC ASD (UC Health/UCPC) MAT 
program; 2) a 20-minute telephone intervention delivered by Peer Interventionists. The Peer Interventionists 
interact with the study participants only on the phone, not in person, and, thus, physical safety is not a 
concern. The phone intervention may last up to 20 minutes during which the Peer Interventionist will answer 
the participant’s questions about the information packet reports, with the potential answers being highly 
scripted, and an exchange of information between the Peer Interventionist and participant about MAT.  
 
 
 
Potential risks of TTIP-PRO for participants include: 1) breach of confidentiality and 2) improper 
administration of the intervention by the Peer Interventionist. The Peer Interventionists will be provided with 
the first name and phone number of the participants assigned to them in a secure manner. As part of their 
training, the Peer Interventionists will be instructed on methods for maintaining confidentiality. Several steps 
will be taken to ensure proper administration of the intervention. First, all Peer Interventionists must 
complete a 4-hour training and certification before being assigned study participants as described in section 
3.3. Second, all interventions will be audio recorded and rated for adherence/fidelity using the same 
assessment as that used for certification. Any instance of falling below certification criteria will result in 
additional training or discontinuation from the trial depending on the nature of the problematic performance.  
 
 
 
Potential risks of TTIP-PRO for Peer Interventionists include: 1) breach of confidentiality and 2) increased 
risk of relapse. In order to diminish the possibility of the participants discovering PHI about the Peer 
Interventionists, a study cell phone, rather than the Peer Interventionist’s personal cell phone will be used; 
this will avoid the potential for the participant obtaining the Peer Interventionist’s phone number and then 
using the number to determine information about the Peer Interventionist (i.e., name, address). The Peer 
Interventionists will be exposed to active users during the 20 minute telephone intervention. As noted above, 
for individuals early in recovery or struggling with recovery and/or other issues, interacting with active users 
could increase the risk of relapse. Our Peer Interventionist eligibility criteria are designed to select only those 
individuals whose recovery is sufficiently stable to mitigate this risk. The consent form will clearly delineate 
relapse as a potential risk. The potential Peer Interventionist will need to agree to an ongoing exchange of 
information between the research team and his/her treatment providers in order to monitor his/her clinical 
status. Dr. Winhusen and her research team are co-located with the clinic staff for the UC ASD MAT 
program and interact on a daily basis; the clinic staff will be instructed to inform the research team of any 
deterioration in the Peer Interventionist’s functioning. In the event of clinical deterioration, the clinic’s multi-
disciplinary team will develop a treatment plan, which may include the Peer Interventionist’s discontinuation 
from study participation. Peer Interventionists will be compensated $40 for completing training/certification, 
and $20 for each participant for whom they provide the intervention. Peer Interventionists will not be 
compensated with cash, which could potentially be used to purchase illicit opioids but, rather, with a prepaid 
debit card.   
 
Risks associated with study participation. Breach of confidentiality: As with any study, there is a potential 
risk of loss of confidentiality. To maintain confidentiality, study records and data will be stored in 
compliance with the International Conference on Harmonization (ICH) guidelines.  Participant/Peer 
Interventionist records will be held confidential by the use of study codes in the study database, secure 
storage of any documents that have participant identifiers, and secure computing procedures for entering and 
transferring electronic data. No identifying information will be disclosed in reports, publications or 
presentations. Information collected for this study will be kept in a locked secure location accessible only to 
research staff and authorized personnel directly involved with this study. Finally, a Certificate of 
Confidentiality will be obtained for the study. Emotional Discomfort: The participants may experience some 


TTIP-PRO Protocol Version 4.1 – 11/8/17  
 
 
 
Page 19 of 39 
 
emotional discomfort from answering sensitive and/or personal questions. Participants may experience 
embarrassment in answering questions about their knowledge of MAT and OOD. The participants/Peer 
Interventionists can choose to not answer questions that they find to be too uncomfortable and will be 
reminded that study participation is completely voluntary. NARCAN® Nasal Spray kit. This medication has 
a very favorable side-effects profile. However, there have been rare cases in which using naloxone to reverse 
an OOD has resulted in vomiting, sweating, shaking, tachycardia, elevated blood pressure, seizures, 
pulmonary edema, ventricular dysrhythmias, rapid pulmonary edema, and cardiac arrest. 
 
Benefits. The results of the present pilot study are unlikely to have a direct substantial societal impact. 
However, promising pilot results would be used in support of a larger trial to test the efficacy of the TTIP-
PRO in reducing the recurrence of opioid overdoses. Should that project yield promising results, the benefits 
to individuals and to society could be substantial. Both the study participants and the Peer Interventionists 
may directly benefit from study participation in that they will receive information about risks for overdose, 
the signs of overdose, how to respond to an overdose, and factors that can reduce the risk of an overdose. 
The study participants may also benefit from receiving a NARCAN® Nasal Spray kit. Consequently, the 
risk/benefit ratio is favorable and conduct of the research well justified. 
 
 
H. PAYMENT 
 
Participants will also be reimbursed up to $220 for their time and travel. Peer Interventionists will be 
provided with a study cell phone for use in delivering TTIP-PRO and for staying in contact with research 
staff regarding scheduled and completed interventions. Peer Interventionists will be compensated $40 for 
completing training/certification, and $20 for each participant for whom they provide the intervention. 
Payments will be provided via a prepaid debit card. 
 
 
I. SUBJECT COSTS 
There are no subject costs for participating in this study. 
 
 
J. CONSENT FORMS 
 
Attached 
 
 
 
 


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Circumstances of recent heroin overdose and links to knowledge of overdose risk factors. Drug and 
Alcohol Dependence. 2006;84(3):223-230. 
27. 
Cacioppo JT, Petty RE. The elaboration likelihood model of persuasion. Advances in Consumer 
Research. 1984;11:673-675. 
28. 
Petty RE, Cacioppo JT. The elaboration likelihood model of persuasion. In: Berkowitz L, ed. 
Advances in Experimental Social Psychology. San Diego, CA: Academic Press; 1986:123-205. 
29. 
Petty RE, Barden J, Wheeler SC. The elaboration likelihood model of persuasion: Developing health 
promotions to produce sustained behavior change. In: DiClemente RJ, Crosby RA, Kegler M, eds. 
Emerging theories in health promotion practice and research. San Francisco, CA: Jossey-Bass; 
2009:185-214. 
30. 
Solomon P. Peer support/peer provided services underlying processes, benefits, and critical 
ingredients. Psychiatr Rehabil J. Spring 2004;27(4):392-401. 
31. 
Winhusen T, Theobald J, Lewis D, Wilder CM, Lyons MS. Development and initial testing of a 
tailored telephone intervention delivered by peers to prevent recurring opioid-overdoses (TTIP-PRO). 
Health Educ Res. Apr 2016;31(2):146-160. 
32. 
Bogenschutz MP, Donovan DM, Mandler RN, et al. Brief Intervention for Patients With Problematic 
Drug Use Presenting in Emergency Departments: A Randomized Clinical Trial. JAMA Intern Med. 
Sep 1 2014. 
33. 
Winhusen TM, Brigham GS, Kropp F, et al. A randomized trial of concurrent smoking-cessation and 
substance use disorder treatment in stimulant-dependent smokers. J Clin Psychiatry. Apr 
2014;75(4):336-343. 
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Winhusen TM, Kropp F, Lindblad R, et al. Multisite, randomized, double-blind, placebo-controlled 
pilot clinical trial to evaluate the efficacy of buspirone as a relapse-prevention treatment for cocaine 
dependence. J Clin Psychiatry. Jul 2014;75(7):757-764. 
35. 
Winhusen T, Lewis D, Adinoff B, et al. Impulsivity is associated with treatment non-completion in 
cocaine- and methamphetamine-dependent patients but differs in nature as a function of stimulant-
dependence diagnosis. J Subst Abuse Treat. May-Jun 2013;44(5):541-547. 
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Winhusen TM, Somoza EC, Brigham GS, et al. Impact of attention-deficit/hyperactivity disorder 
(ADHD) treatment on smoking cessation intervention in ADHD smokers: a randomized, double-
blind, placebo-controlled trial. J Clin Psychiatry. Dec 2010;71(12):1680-1688. 
37. 
Winhusen T, Kropp F, Babcock D, et al. Motivational enhancement therapy to improve treatment 
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Kelly BC, Liu T, Zhang G, Hao W, Wang J. Factors related to psychosocial barriers to drug treatment 
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Dennis CL. Breastfeeding peer support: maternal and volunteer perceptions from a randomized 
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Appendix A: Examples of TTIP-PRO-generated reports for fictional patient 
 
1.0 Example of a “Personal Overdose Risk Factors Report” for a fictional heroin user 
 
  


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2.0 Example of a “Medication Assisted Treatment (MAT) Report” for a fictional heroin user 
 
 
 


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3.0 Example of an “Opioid Overdose Information Report” for a fictional heroin user 
 
 


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Appendix B: Data Safety and Monitoring Plan (DSMP) 
 
 
 
 
 
 
 
 
Data and Safety Monitoring Plan  
 
1 R34 DA040862-01 
 
A Tailored, Peer-delivered Intervention to Reduce Recurring Opioid Overdoses  
 
PI: Theresa Winhusen, PhD, University of Cincinnati 
 
Medical Monitor: Michael Lyons, MD, University of Cincinnati 
 
 
October 27, 2017 
 


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I.   
SUMMARY OF PROTOCOL 
1. Brief description of the protocol: This project will further develop and test the Tailored Telephone Intervention 
delivered by Peers to Prevent Recurring Opioid Overdoses (TTIP-PRO), an intervention to facilitate entry into 
medication assisted treatment (MAT) for individuals experiencing a non-fatal opioid overdose (OOD). 
Specific aims are to: 1) Finalize the Peer Interventionist training materials (Stage IA); and 2) Conduct pilot 
testing in preparation for a full-scale clinical trial (Stage IB). Approximately 80 adults, who have been treated 
for an OOD within the past 6 months, will be randomized into the pilot study. Participants randomized to the 
control condition will receive contact information about local MAT programs, SAMHSA information about 
OOD and about MAT, and a NARCAN® Nasal Spray kit; all of which will be provided during the enrollment 
visit. Participants randomized to the experimental condition will receive TTIP-PRO in addition to the elements 
provided in the control condition. TTIP-PRO consists of two parts: 1) an information packet which includes 
three reports (“Personal Overdose Risk Factors Report”; “Medication Assisted Treatment (MAT) Report”; and 
the “Opioid Overdose Information Report”) generated from the participant’s responses to two surveys and 
information about how to access treatment at a UC ASD (UC Health/UCPC) MAT program; 2) a 20-minute 
telephone intervention delivered by Peer Interventionists. The TTIP-PRO intervention will be provided within 
2 weeks of the enrollment visit. All participants will complete a follow-up phone call in week 3 and in-person 
visits at 3, 6-, and 12-months following enrollment. Exploratory analyses will test our conceptual model of 
TTIP-PRO’s mechanisms of change and the validity of two assessments developed for TTIP-PRO.  
 
2. Primary and secondary outcome measures: Enrollment in MAT (Yes/No) within the 12-month follow-up 
period is the primary outcome measure. Secondary outcomes include experiencing an OOD (Yes/No) within 
the 12-month follow-up and change in opioid use, as measured by the Timeline Follow-back (TLFB) 
procedure and urine drug screens (UDS), between baseline and 12-month follow-up.  Process measures 
include: Barriers to Treatment Inventory- the Fear of Treatment subscale will be evaluated as a mediator of 
TTIP-PRO’s efficacy. Thoughts about abstinence will assess desire to quit illicit opioid use and expected 
success in quitting, which will be evaluated as mediators. The Opioid Overdose and Treatment Awareness 
Survey (OOTAS) assesses knowledge about OOD and MAT; the total OOTAS score will be evaluated as a 
mediator of TTIP-PRO’s efficacy. The Helpfulness of Peer Intervention (HOPI) will assess the degree to 
which participants perceived TTIP-PRO to be personally relevant and credible; the total score will be tested as 
a moderator. Peer Interventionist Measures include: 1) the Peer Volunteer Experience Questionnaire (PVEQ) 
will be used to obtain feedback from peer volunteers delivering TTIP-PRO; and 2) the PROMIS 10-item 
measure for Global Health. 
 
3. Inclusion/exclusion criteria: 
This project includes two types of participants: 1) the participants who may receive the TTIP-PRO 
intervention, referred to as participants, and 2) the participants who will serve as Peer Interventionists. 
 
Participants 
All potential participants will be recruited through various methods, which include but are not limited 
to advertisements, flyers, and word-of-mouth. Eligible participants will meet all inclusion, and no 
exclusion criteria:  
 
Inclusion Criteria: 
1) Report having been treated for an OOD within the past 6 months; 
2) Age 18 years or older; 
3) Scores “high risk” for heroin and/or non-medical use of prescription opioids on the NIDA  


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                            modified ASSIST (i.e., ≥ 27);  
4) Be able to understand the study, and having understood, provide written informed consent in  
    English;  
5) Access to a phone (for TTIP-PRO intervention and phone follow-up);  
6) Be willing to have their intervention audio recorded and rated if randomized to TTIP-PRO; 
7) Have an opioid-positive baseline/screening urine drug screen. 
 
  
 
Exclusion Criteria:  
1) In the judgment of the investigator, would not be expected to complete the study protocol (e.g., due  
    to relocation from the clinic area, probable incarceration, etc.);  
2) Current engagement in addiction treatment; 
3) Residence more than 40 miles from the location of follow-up visits; 
4) Inability to provide sufficient contact information (must provide at least 2 reliable locators); 
5) Prior participation in the current study. 
 
Peer Interventionists 
All potential Peer Interventionists will be recruited primarily by word of mouth from a UC Addiction 
Sciences Division (ASD) Medication Assisted Treatment (MAT) clinic (i.e., methadone or buprenorphine). 
For individuals early in recovery or struggling with recovery and/or other issues, interacting with active users 
could increase their risk of relapse. Our Peer Interventionist eligibility criteria are designed to select only those 
whose recovery is sufficiently stable to mitigate this risk. 
 
 Inclusion Criteria:  
1) Age 18 years or older;  
2) Enrolled in UC ASD (i.e., UC Health/UCPC) MAT program;  
3) Enrolled in a MAT program for at least one year;  
4) Report being abstinent from illicit opioids for at least one year;  
5) Report having experienced, witnessed, and/or lost a family member or friend to an overdose.  
 
Exclusion Criteria:  
1) Unwilling to sign a release of information (ROI) to allow research staff to confirm pertinent 
eligibility criteria and to monitor clinical status with UC ASD (i.e., UC Health/UCPC) MAT clinical 
staff; 
2) Clinical staff from their program have significant concerns about their participation;  
3) Unwilling to have their sessions audio recorded and assessed by a TTIP-PRO trainer.  
4) Specific plan to leave the UC ASD (i.e., UC Health/UCPC) MAT program within the next 6 months 
 
 
4. Sample size: Participants: Approximately 38 participants will be recruited to develop training audio files (Aim 
1) Approximately 80 participants will be randomized into the pilot efficacy trial.  
Peer Interventionists: Approximately 15 Peer Interventionists will participate.                                                              
 
II. TRIAL MANAGEMENT  


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1. List of participating enrolling clinics or data collection centers: All participants will be recruited by the 
University of Cincinnati Addiction Sciences Division (ASD). This is a single site study; all data will be 
collected at the University of Cincinnati. 
2. Projected timetable: This is a three-year study. Finalizing the Peer Interventionist training materials (Aim 1) 
will be accomplished within Year 1 as will the pre-initiation tasks for the pilot clinical trial. Conducting the 
trial, completing data analyses, and writing the final report will be accomplished during years 1.5 – 3. 
3. Target population distribution: Our planned enrollment is based on the demographics of the populations from 
which we will be recruiting. Of the 102 participants, we anticipate enrolling 34 (33%) females and 68 (67%) 
males, 9 (9%) black or African American, 1 (1%) American Indian/Alaska Native, and 92 (90%) white 
participants.  Additionally, we will enroll 1 (1%) Latino or Hispanic and 101 (99%) not Latino or Hispanic. Of 
the 15 Peer Interventionists, we anticipate enrolling 14 (93%) females and 1 (7%) males, 1 (7%) black or 
African American, and 14 (93%) white.  Additionally, we will enroll 15 (100%) not Latino or Hispanic. 
III.  DATA MANAGEMENT AND ANALYSIS  
1. Data acquisition and transmission: All data will be acquired from participant interviews, clinic records, or urine 
drug screens. All research staff will be trained in Good Clinical Practice (GCP) guidelines. All data will be de-
identified. Only research staff members directly involved with the study will have access to identifying 
information for the participants and Peer Interventionists. TTIP-PRO interventions will be audio recorded 
using a combination of an in-ear microphone and a digital voice recorder for fidelity monitoring. Recordings 
will be provided as MP3 or other digital format sound files to the TTIP-PRO trainers in person or via a secure 
electronic data repository provided by UC (“Box at UC”) which has an encrypted area for this purpose.  
 2. Data entry methods: All de-identified demographic and clinical data will be managed in REDCap, a software 
toolset and workflow methodology for collection and management of clinical research data developed by 
Vanderbilt University, in collaboration with institutional partners including the University of Cincinnati 
Academic Health Center. Only the necessary study personnel will have access to the database. Case report 
forms (CRFs) that are more complex, including Timeline Follow-back (TLFB) and tracking of treatment and 
OOD, which will entail transcription from medical records, will first be completed on paper and then entered 
into the electronic database. All other CRFs will be direct data entry, with paper versions used only if there are 
technical issues with the database. Any data entered from a paper CRF will be double entered by two separate 
research staff members and compared to ensure the integrity of the information. 
 
3. Data analysis plan: All analyses will be completed on the ITT sample using SAS, Version 9.4 (SAS Institute, 
Inc.). Statistical tests will be conducted at a 5% Type I error rate (two-sided) for all measures. It has been 
recommended that effect sizes be provided rather than using the Bonferroni procedure to adjust for multiple-
comparisons; thus, effect sizes and 95% confidence intervals (CI’s) will be computed for each treatment effect. 
For each efficacy analysis, demographic/baseline characteristics and length of time since last OOD will be 
selected for inclusion in the model using the corrected Akaike Information Criterion (AICC) as the optimizing 
criterion. For missing data, multiple imputation methods will be used and the resulting model compared to the 
non-imputed model. 
Participant Analyses-The primary hypothesis, that a significantly greater proportion of TTIP-PRO, relative to 
control, participants will enter MAT within 12-month follow-up will be tested using a logistic regression (a 
generalized linear model with a logistic link). Secondary analyses. The key secondary hypothesis, that a 
significantly lower proportion of TTIP-PRO, relative to control, participants will have a recurring OOD within 
12-month follow-up will be tested using a logistic regression (a generalized linear model with a logistic link). 
The secondary hypothesis that TTIP-PRO, relative to control, participants will have a significantly greater 


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reduction in illicit opioid use will be tested using two outcomes, one based on self-report and the other on UDS 
results. The proportion of self-reported use days will be treated as a binomial variable and regressed using 
logistic mixed model regression (random-intercept generalized mixed-model regression with a logistic link 
function). UDS results (positive for illicit opioids vs. not positive), will be treated as a binary variable which 
will also be regressed using logistic mixed-model regression. For both outcomes, the effects of interest will be 
treatment and treatment-by-time interaction.  
 
Power: A pilot study necessitates a limited sample size, and is more useful for showing feasibility than 
providing an effect size estimate. The proportion of patients who will enroll in a MAT program is unknown for 
both the TTIP-PRO and control group. Thus, we based the estimated proportions on a recent randomized trial 
comparing buprenorphine administration during medical hospitalization and linkage to office-based 
buprenorphine post-discharge to buprenorphine detoxification. In that study, the linkage patients were more 
likely to enter office-based buprenorphine treatment (72.2%) compared to the detox group (11.9%). The 
linkage condition was much more intensive than TTIP-PRO and, thus, it is expected that the TTIP-PRO 
enrollment rate will be considerably less than that observed for the linkage group. Assuming that 12% of our 
information-only control group enrolls in MAT, and a total sample size of 80, we would have 80% power 
using a two-tailed test and α =.05 to detect a TTIP-PRO effect for a MAT enrollment rate of ≥ 39%. In our 
SBIRT trial, our 12 month follow-up rate was 78%. If 78% of participants complete the 12 month follow-up 
(n=62) in the proposed trial, we would have 80% power (assuming 12% engagement for the control group, a 
two-tailed test, and α =.05) to detect a TTIP-PRO effect for a MAT enrollment rate of ≥ 46%. 
 
Peer Interventionist Analyses - The hypotheses related to the Peer Interventionists will be tested with 
descriptive statistics. The proportion of Peer Interventionists: 1) attending the training who complete training 
and certification within the expected 4-hour timeframe and 2) who report being satisfied or very satisfied with 
their experience as a Peer Interventionist will be calculated.  
 
   
Analyses for Exploratory Aims- E1 – Testing the validity of the HOPI and PORS. The HOPI was designed to 
include two subscales (i.e., personally relevant; credible). Factor analyses will be used to determine if the 
HOPI does, in fact, yield two factors corresponding to the intended subscales. Since the HOPI uses Likert-
scale variables, the factor analysis will be based on polychoric correlation. A logistic generalized linear model 
regression will be used to test the PORS score as a predictor of 1 year OOD rates. The strength of predictive 
validity will be expressed both as the estimated odds ratio and by area under a ROC curve.   
 
E2 – Testing the conceptual model of TTIP-PRO’s mechanisms of change. The purpose of the analyses 
described here is to explore the degree to which our conceptual model is consistent with the obtained study 
results. Using all ITT data, we will perform mediation analysis (empirically estimating 95% confidence 
intervals via bootstrapping) to test three mediation relationships: 1. fear-of-treatment, expected-success, and 
desire-to-quit as joint mediators of the effect of TTIP-PRO on engagement-in-MAT, 2. desire-to-quit, 
expected-success, and engagement-in-MAT as joint mediators of the effect of TTIP-PRO on level-of-opioid-
use, and 3.  knowledge-of-opioid-overdose and level-of-opioid-use as joint mediators of the effect of TTIP-
PRO on whether there is an opioid overdose recurrence.  We will use the data from participants receiving 
TTIP-PRO to test whether helpfulness-of-the-intervention (HOPI) respectively moderates the effects of fear-
of-treatment, expected-success, desire-to-quit, and knowledge-of-opioid-overdose. We will perform logistic 
regression when engagement-in-MAT and overdose-recurrence are outcomes and logistic mixed-model 
regression when opioid use is the outcome.  
 
IV. QUALITY ASSURANCE 
 
 
1.   Procedures in place to ensure the validity and integrity of the data: A modified version of a training manual 
developed for an earlier acceptability study of TTIP-PRO will be utilized. Two important elements missing 
from the acceptability study, which will be established for the present project, are: 1) training files and 2) an 
assessment of inter-rater reliability for the competence measure. The training files will include 4 mock 
interventions (1 video, 3 audio) and 4 audio recorded interventions with patient volunteers. Two TTIP-PRO 
trainers will rate two training files. Inter-rater reliability will be measured by intraclass correlation coefficients 


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(ICCs). If the ICC is less than .75 then clarifications will be made to the competence assessment and the 
trainers will rate two additional training files. This process will be repeated until an ICC greater than .75 is 
achieved. All TTIP-PRO sessions will be rated for providing fidelity and adherence by one of the two TTIP-
PRO trainers. Potential Peer Interventionists will need to complete training and certification prior to being 
assigned participants. 
 
2.  Procedures to guarantee the accuracy and completeness of the data during data collection, entry, transmission 
and analysis: Assessments programmed in REDCap will use validation rules, integrity checks, and hard stops 
as needed to ensure that data are as complete and accurate as possible. The RA will check any data collected 
by paper source for completeness. As previously described, all data entered from a paper source will be 
double-entered and checked for consistency by REDCap.  
V. REGULATORY ISSUES 
1.   Reporting of AEs/ SAEs to the IRB, NIDA, and the FDA: All SAEs will be reported to the IRB and NIDA 
within 72 hours of their discovery. This is a behavioral study and so FDA reporting is not required. We will 
use FDA criteria for SAEs (i.e., an adverse event that results in any of the following outcomes; death, life 
threatening, requires hospitalization, initial or prolonged, results in disability, congenital anomaly, requires 
intervention to prevent permanent impairment or damage, or other significant medical event); OOD will be 
treated as an SAE. Dr. Lyons or the designated study physician will assess the severity, relatedness, and 
outcome of each AE and SAE. It will also be Drs. Lyons’, Winhusen’s, and Wilder’s responsibility to manage 
all AEs and SAEs and to make referrals for appropriate care, as necessary. All participant information will be 
de-identified when reporting SAEs. All AEs and SAEs will be reported to and reviewed by the DSMB at the 
time of their standard meeting, except when Dr. Lyons or the designated study physician thinks that the SAE is 
very severe and/or may require a protocol amendment. In that case, Dr. Winhusen may request an ad hoc 
review by the DSMB. All AEs and SAEs will be entered into a database that is de-identified and password 
protected to ensure confidentiality.  
 
2.   Reporting of IRB action to NIDA: All communications with and actions of the IRB will be kept in a regulatory 
binder specific for this study. Any protocol changes, amendments, or deviations will be submitted to the IRB 
and NIDA and the IRB’s actions will then be reported to NIDA. Any other IRB actions (including annual re-
approvals and correspondence related to DSMB reports) will be submitted to NIDA. 
 
3. Report of changes or amendments to the protocol: All changes and amendments to the protocol will be 
submitted to the IRB and NIDA. Only after IRB and NIDA approvals are granted will the changes and 
amendments be implemented.  
4. Trial stopping rules: Individual study participants will be informed of their right to discontinue study 
participation at any time during the study. The PI/Medical Monitor may discontinue a participant or Peer 
Interventionist’s trial participation if deemed clinically appropriate. The DSMB may recommend study 
termination based on review of site performance or safety and efficacy data. NIDA has the right to discontinue 
the investigation at any time. 
 
          
 
5. Disclosure of conflict of interest: The investigators and members of the data safety and monitoring board 
(DSMB) have no conflicts of interest.  
VI. TRIAL SAFETY 


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1.  Potential risks and benefits for participants: This project includes two types of participants: 1) the 
participants who may receive the TTIP-PRO intervention, referred to as participants, and 2) the participants who will 
serve as Peer Interventionists.  
 
 
 
Risks associated with the TTIP-PRO intervention. TTIP-PRO consists of two parts: 1) an information packet 
which includes three reports (“Personal Overdose Risk Factors Report”; “Medication Assisted Treatment 
(MAT) Report”; and the “Opioid Overdose Information Report”) generated from the participant’s responses to 
two surveys and information about how to be access treatment at a UC ASD (UC Health/UCPC) MAT 
program; 2) a 20-minute telephone intervention delivered by Peer Interventionists. The Peer Interventionists 
interact with the study participants only on the phone, not in person, and, thus, physical safety is not a concern. 
The phone intervention may last up to 20 minutes during which the Peer Interventionist will answer the 
participant’s questions about the information packet reports, with the potential answers being highly scripted, 
and an exchange of information between the Peer Interventionist and participant about MAT. 
 
 
 
 
 
Potential risks of TTIP-PRO for participants include: 1) breach of confidentiality and 2) improper 
administration of the intervention by the Peer Interventionist. The Peer Interventionists will be provided with 
the first name and phone number of the participants assigned to them in a secure manner. As part of their 
training, the Peer Interventionists will be instructed on methods for maintaining confidentiality. Several steps 
will be taken to ensure proper administration of the intervention. First, all Peer Interventionists must complete 
a 4-hour training and certification before being assigned study participants. For certification, a TTIP-PRO 
trainer will rate the trainee’s performance on a mock intervention. The trainer will use a 3-point scale (1-Meets 
expectations, 2-Needs improvement, 3-Expectations not met and additional training required). To be certified, 
the trainee needs to receive a “1” on at least 5 of the 6 abilities assessed: 1) Ability to provide information 
while maintaining a conversational tone; 2) Ability to successfully complete the intervention within 20 
minutes; 3) Ability to listen; 4) Sufficient familiarity with correct information about OOD and MAT to answer 
the participant’s questions; 5) Ability to remain non-judgmental and encouraging; and 6) Ability to avoid 
confrontation. Second, all interventions will be audio recorded and rated for adherence/fidelity using the same 
assessment as that used for certification. Any instance of falling below certification criteria will result in 
additional training or discontinuation from the trial depending on the nature of the problematic performance.  
 
 
 
 
 
Potential risks of TTIP-PRO for Peer Interventionists include: 1) breach of confidentiality and 2) increased 
risk of relapse. In order to diminish the possibility of the participants discovering PHI about the Peer 
Interventionists, a study cell phone, rather than the Peer Interventionist’s personal cell phone will be used; this 
will avoid the potential for the participant obtaining the Peer Interventionist’s phone number and then using 
the number to determine information about the Peer Interventionist (i.e., name, address). The Peer 
Interventionists will be exposed to active users during the 20 minute telephone intervention. As noted above, 
for individuals early in recovery or struggling with recovery and/or other issues, interacting with active users 
could increase the risk of relapse. Our Peer Interventionist eligibility criteria are designed to select only those 
individuals whose recovery is sufficiently stable to mitigate this risk. The consent form will clearly delineate 
relapse as a potential risk. The potential Peer Interventionist will need to agree to an ongoing exchange of 
information between the research team and his/her treatment providers in order to monitor his/her clinical 
status. Dr. Winhusen and her research team are co-located with the clinic staff for the UC ASD MAT program 
and interact on a daily basis; the clinic staff will be instructed to inform the research team of any deterioration 
in the Peer Interventionist’s functioning. In the event of clinical deterioration, the clinic’s multi-disciplinary 
team will develop a treatment plan, which may include the Peer Interventionist’s discontinuation from study 
participation. Peer Interventionists will be compensated $40 for completing training/certification, and $20 for 
each participant for whom they provide the intervention. Peer Interventionists will not be compensated with 
cash, which could potentially be used to purchase illicit opioids but, rather, with a prepaid debit card.   
 
 
 
Risks associated with study participation. Breach of confidentiality: As with any study, there is a potential 
risk of loss of confidentiality. To maintain confidentiality, study records and data will be stored in compliance 
with the International Conference on Harmonization (ICH) guidelines.  Participant/Peer Interventionist records 
will be held confidential by the use of study codes in the study database, secure storage of any documents that 
have participant identifiers, and secure computing procedures for entering and transferring electronic data. No 


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identifying information will be disclosed in reports, publications or presentations. Information collected for 
this study will be kept in a locked secure location accessible only to research staff and authorized personnel 
directly involved with this study. Finally, a Certificate of Confidentiality will be obtained for the study. 
Emotional Discomfort: The participants may experience some emotional discomfort from answering sensitive 
and/or personal questions. Participants may experience embarrassment in answering questions about their 
knowledge of MAT and OOD. The participants/Peer Interventionists can choose to not answer questions that 
they find to be too uncomfortable and will be reminded that study participation is completely voluntary. 
NARCAN® Nasal Spray kit. This medication has a very favorable side-effects profile. However, there have 
been rare cases in which using naloxone to reverse an OOD has resulted in vomiting, sweating, shaking, 
tachycardia, elevated blood pressure, seizures, pulmonary edema, ventricular dysrhythmias, rapid pulmonary 
edema, and cardiac arrest. 
 
Benefits. The results of the present pilot study are unlikely to have a direct substantial societal impact. 
However, promising pilot results would be used in support of a larger trial to test the efficacy of the TTIP-PRO 
in reducing the recurrence of opioid overdoses. Should that project yield promising results, the benefits to 
individuals and to society could be substantial. Both the study participants and the Peer Interventionists may 
directly benefit from study participation in that they will receive information about risks for overdose, the 
signs of overdose, how to respond to an overdose, and factors that can reduce the risk of an overdose. The 
study participants may also benefit from receiving a NARCAN® Nasal Spray kit. Consequently, the 
risk/benefit ratio is favorable and conduct of the research well justified. 
 
2. Collection and reporting of AEs and SAEs: In general, the risks associated with trials employing behavioral 
interventions are presumed minimal relative to those evaluating pharmacologic interventions. Based on the 
TTIP-PRO acceptability study the risk from TTIP-PRO is low. Still, for the present trial, the population 
studied is a vulnerable population and possibly at higher risk given the nature of the disorder and the 
population. Thus, the following events, which are not defined as SAEs, will be tracked on an AE CRF for 
participants and Peer Interventionists: 
 
1. Suicidal ideation 
2. Homicidal ideation 
In addition, the following events will be track on an AE CRF for the Peer Interventionists: 
 
1. Discharge from MAT program for any reason 
2. Illicit opioid use  
3. Other clinical deterioration as reported by clinic staff 
For TTIP-PRO, which is a behavioral trial, the RA is primarily responsible for assessing the occurrence of 
AEs/SAEs with oversight by the Study Medical Monitor and PI. For Participants, the RA will query about how 
s/he has been feeling since the last visit (i.e., at the follow-up phone call in week 3 and in-person visits at 3, 6-, 
and 12-months following enrollment). For Peer Interventionists, the RA will query about how s/he has been 
feeling following the delivery of each TTIP-PRO intervention.  All AEs/SAEs occurring during the course of 
the clinical trial will be collected, documented, and reported by the investigator or sub-investigators in 
accordance with reporting requirements. Dr. Lyons or the designated study physician will assess the 
severity, causality and outcome of all AEs and SAEs. It will also be Drs. Lyons’, Winhusen’s, and Wilder’s 
responsibility to manage all AEs and SAEs and to make referrals for appropriate care, as necessary. All SAEs 
will be reported to the University of Cincinnati Institutional Review Board and the NIDA project officer 
within 72 hours of their discovery. All subject information will be de-identified when reporting serious adverse 
events.  
 
3.  Management of SAEs or other study risks: Please refer to Section VI. 1. for management of study risks.  
VII.  TRIAL EFFICACY 


TTIP-PRO Protocol Version 4.1 – 11/8/17  
 
 
 
Page 39 of 39 
 
1. Plans for interim analysis of efficacy data: There will be no interim analysis of efficacy data by the 
investigators. However, the DSMB (see below, Section IX, 5) will monitor efficacy data and provide 
recommendations regarding whether the study should continue without modification or with modification or 
be terminated.  
VIII.  DSM PLAN ADMINISTRATION 
1. Responsibility for data and safety monitoring: Drs. Winhusen, Lyons, and Wilder will be responsible for the 
clinical management and safety monitoring of the study participants and Peer Interventionists.  
2. Frequency of DSM reviews: The study protocol will be reviewed by the DSMB before recruitment starts. 
Efficacy and AE/SAE data will be reviewed by the DSMB every six months for the duration of the trial. The 
DSMB reports will be submitted to the IRB and NIDA. Additionally, annual reports will be sent to the IRB for 
re-approval of the study. SAEs will be reported and reviewed by the DSMB at the time of their meeting, 
except when Dr. Lyons or the designated study physician thinks that the SAE is very severe and/or may 
require a protocol amendment. In that case, Dr. Winhusen may request an ad hoc review by the DSMB. Each 
SAE will be reported in writing at the time of occurrence (within 72 hours) to the IRB and NIDA.  
3. Content of DSM report: The DSM report will include a brief description of the trial and any changes made to 
the trial. Additionally, we will report baseline sociodemographic characteristics, including age, gender, and 
race of the subjects screened and randomized.  We will also report retention rates and the disposition for all 
study participants and Peer Interventionists. Finally, any quality assurance issues, regulatory issues, AEs and 
SAEs will be included in the report. After review of the data, the DSM report will make recommendations 
about whether the trial should continue with or without modifications or be terminated.   
IX.  DSM BOARD (DSMB) PLAN 
1. Members and affiliation:  Members for the DSMB will include: 1. Marepalli Rao, PhD, Professor, University of 
Cincinnati College of Medicine, who has extensive expertise in data analysis for clinical trials. 2. Shawn Ryan, 
MD, MBA who is an emergency medicine physician at the University of Cincinnati Medical Center. 3. Darcelia 
Plott, MD, staff Psychiatrist at the Cincinnati Veterans Medical Center, who is board certified in both Internal 
Medicine and Addiction Medicine.  
 
2. Frequency of meetings: The DSMB will meet before recruitment starts, and then every six months. The PI may 
request an ad hoc review more frequently if protocol amendments are needed. 
 
3. Conflict of interest: The DSMB members report no conflicts. 
 
4. Protection of confidentiality:  All participant data will be de-identified prior to review by the DSMB to maintain 
participant confidentiality. Only participant ID number, gender, age, and race will be provided to the DSMB. 
 
5. Monitoring activities (initial and ongoing study review): The DSMB will review the protocol prior to participant 
enrollment and will provide recommendations for any protocol changes in order to maximize safety or efficacy 
assessments. The DSMB will then formally meet before recruitment starts, then at a minimum of every 6 months 
during the course of the study. The DSMB will review the disposition of all study participants and reasons for 
study drop-out. The DSMB will also review all SAEs. Dr. Welge, the project statistician, will be responsible for 
providing updated safety data to the DSMB prior to each meeting. The DSMB will provide a written report of their 
recommendation as to whether the study should continue, be modified, or should be terminated.  
 
6. Communication plan to IRB and NIDA: Dr. Winhusen, in conjunction with the DSMB, will be responsible for 
making certain that the DSMB files their report to the IRB as well as to the sponsor (NIDA) of the study.  
 

ICF_000.pdf: 
A Tailored, Peer-delivered Intervention to Reduce Recurring Opioid 
Overdoses 
 
NCT02922959 
 
Consent approval date: 8/8/2018 
 


IRB #: 2016-6635 
 
 
 
Approved:  
8/8/2018 
Do Not Use After: 
8/7/2019 
 
 
 
 
 
Page 2 of 13 
 
UNIVERSITY OF CINCINNATI - Medical 
CONSENT TO PARTICIPATE IN A RESEARCH STUDY 
Participant Consent 
 
Study Title: A Tailored, Peer-delivered Intervention to Reduce Recurring Opioid Overdoses 
 
UC IRB Study #:  
Sponsor Name: The National Institute on Drug 
Abuse (NIDA) 
 
Investigator Information: 
Theresa Winhusen, PhD 
513-310-0442 
Principal Investigator Name 
 
 
Telephone Number 24 hr Emergency Contact 
 
Subject Name: ______________________________ Date of Birth: _____/_____/____ 
 
 
INTRODUCTION:  
 
A biomedical or health-related research study is performed to answer specific questions about 
a disease.    
 
Before you agree to participate in this research study, it is important that you be told the 
purpose, procedures, benefits, risks, discomforts, and precautions of the research. You 
should also be told what alternative procedures are available to you if you do not participate in 
the research study.  The informed consent document is a written summary of this information. 
Be sure to ask questions while you read this consent document and ask questions if there is 
anything that you do not understand.   
 
Your participation in this research study is entirely voluntary.  
 
You may choose either to take part or not to take part in this research study. If you decide to 
take part, you may decide to leave the study at any time. Leaving the study will not result in 
any penalty or loss of benefits to you.  
 
The researcher and sponsor of this study do not promise that you will receive any benefits 
from this study. 
 
 WHY IS THIS RESEARCH BEING DONE?  
 
The purpose of this research study is to compare two approaches to reducing the risk of 
future opioid overdoses in individuals experiencing a non-fatal opioid overdose. The first 
approach entails providing the individual with a NARCAN® kit, which can be used to help 
reverse an opioid overdose, and written information about overdose and substance use 
disorder treatment. The second approach expands upon the first approach by also providing a 
telephone, peer-based intervention to the individual. 


IRB #: 2016-6635 
 
 
 
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WHY HAVE YOU BEEN ASKED TO TAKE PART IN THIS RESEARCH STUDY?  
 
You are being asked to take part in this research study because you are at least 18 years old 
and you report having been treated for an opioid overdose in the last 6 months. 
 
 
 HOW LONG WILL YOU BE IN THE RESEARCH STUDY?  
 
You will be in the research study for approximately 12 months. It will take about 2.5 years 
before all volunteers have finished and the study is complete. 
 
The researcher may decide to take you off this research study at any time. Reasons for 
withdrawal may include study funding being stopped or your failing to follow important 
instructions given by the investigator. 
 
You may withdraw from the study at any time. If you decide to stop participating in the study, 
we encourage you to talk to the research team first. Another reason to tell the researcher that 
you are thinking about stopping is to discuss what follow-up care and testing could be most 
helpful to you. 
 
You may be contacted in the future by representatives of the University of Cincinnati who are 
interested in asking you survey questions about your participation in this research study. If 
you choose to participate in the survey, your responses will be used for quality assurance 
purposes only. 
 
 
WHO IS CONDUCTING THE RESEARCH STUDY?  
 
The person in charge of this research study is Theresa Winhusen, PhD of the University of 
Cincinnati (UC) Department of Psychiatry and Behavioral Neuroscience – Addiction Sciences 
Division.  There may be other people on the research team helping at different times during 
the study. 
 
Medical monitoring for the study is provided by Michael Lyons, MD. 
 
 
HOW MANY PEOPLE WILL TAKE PART IN THE RESEARCH STUDY?  
 
About 80 people will take part in this study at UC Addiction Sciences Division. 
 
 


IRB #: 2016-6635 
 
 
 
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WHAT IS INVOLVED IN THE RESEARCH STUDY?  
 
1.  SCREENING/BASELINE 
If you decide to volunteer and sign this consent form, you will start screening procedures that 
help us to see whether or not this study is suitable for you.  Screening procedures will take 
approximately 1 hour and 15 minutes to complete. The things that will happen during screening 
are done only for this research study and are not part of any other routine healthcare you may 
receive. For screening, you will be asked to: 
• Answer questions about your alcohol and drug use, about things that can increase the 
risk of overdose, knowledge about overdose risk, and your knowledge, interest in, and 
barriers to getting treatment; 
• Answer basic questions about your gender, race, and ethnicity; 
• Provide contact information for people who can help us locate you in the future and sign 
a release of information for them 
• Provide a urine sample to screen for drug use. 
 
If after completing the screening process you are found to be eligible, this means that you can 
take part in the study if you choose to do so.  If you are found to be ineligible, this means that 
you cannot take part in the study.  Either way, you will receive $50 for your time and effort for 
completing the entire screening process. 
 
2.  RANDOMIZATION 
If you are eligible and agree to take part in the study, you will be "randomized" into one of the 
study groups described below. Randomization means that you are put into a group completely 
by chance. It is like flipping a coin. 
 
If you are randomized to the control condition, you will receive contact information about local 
Medication Assisted Treatment (MAT) programs, educational information about Opioid 
Overdose (OOD) and about MAT, and a NARCAN® Nasal Spray kit; all of which will be 
provided during the enrollment visit. 
 
If you are randomized to the experimental condition, you will receive contact information about 
local MAT programs, educational information about OOD and about MAT, and a NARCAN® 
Nasal Spray kit; all of which will be provided during the enrollment visit. You will receive a set 
of three personalized reports, and you will be scheduled to receive the Tailored Telephone 
Intervention delivered by Peers to Prevent Recurring Opioid Overdoses (TTIP-PRO) 
intervention within about 2 weeks following your enrollment into the study.   
 
3.  TTIP-PRO  
If you are randomized to the experimental condition, you will receive the TTIP-PRO 
intervention which consists of two parts: 1) a 30-minute telephone intervention delivered by a 
trained Peer Interventionist; and 2) a set of three personalized reports, including a report on 
your personal risk factors for experiencing another OOD.  The call will be recorded and stored 
long enough for an expert trainer to review the call for quality assurance purposes, after which 
the file will be deleted.  
 


IRB #: 2016-6635 
 
 
 
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 4.  FOLLOW UP 
You will complete a follow-up phone call in week 3 with research staff and in-person follow-up 
visits with research staff at 3, 6-, and 12-months following enrollment, regardless of how you 
are randomized. 
  
Follow-up Phone Call 
The week 3 phone call will last approximately 25 minutes. You will be asked to complete an 
interview to assess your knowledge about overdose risk, your interest in treatment, barriers to 
getting treatment, how you have been feeling since your enrolled in the study, and your 
feedback on the intervention you received following randomization.   
 
In-Person Visits 
You will be asked to come for follow-up visits 3, 6, and 12 months following your enrollment into 
the study.  At each of these visits you will be asked to: 
• complete questionnaires and interviews about how you have been feeling since the last 
study contact, your recent alcohol and drug use, whether or not you have had any 
additional overdoses, whether or not you have enrolled in MAT for opioid use disorder, 
and whether the NARCAN® Nasal Spray kit you received was used to help reverse an 
overdose; 
• provide releases of information for medical records to confirm enrollment in MAT; 
• provide a urine sample to screen for drug use. 
 
At the month 3 and month 6 follow-up visits, you will also be asked to confirm/update information 
for people who can help us locate you in the future. 
 
At the month 12 follow-up visit, you will also be asked to complete a questionnaire about your 
personal overdose risk. 
 
Each follow-up visit will last approximately 40 minutes. 
 
If you are currently or become a prisoner (including being in jail or prison, being on probation 
or parole, or being under house arrest or electronic monitoring), we would still like to find out 
how you are doing. Therefore, if necessary, we will make an effort to collect follow-up data from 
you over the phone or in person.  Please note that your continued participation, in this event, 
will have no effect on your criminal case, or release or parole from jail or prison, or probation 
case. 
 
WHAT ARE THE RISKS AND DISCOMFORTS OF THE RESEARCH STUDY?  
 
Breach of confidentiality: As with any study, there is a potential risk of loss of confidentiality. 
To maintain confidentiality, all study records and data will be secured, and information 
collected by the study will not be shared with your healthcare provider(s). Additionally, as 
described below, a Certificate of Confidentiality has been obtained for the study.  
 


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Emotional Discomfort: You may also experience some emotional discomfort from answering 
sensitive and/or personal questions. You may experience embarrassment in answering 
questions about your knowledge of MAT and opioid overdose. You can choose to not answer 
questions that you find to be too uncomfortable, or you may choose to withdraw from the 
study if you find participation too stressful. 
 
Improper administration of the intervention by the Peer Interventionist:  The Peer 
Interventionists will be provided with your first name and your phone number in a secure 
manner. As such, there is a chance of improper administration of the intervention. In order to 
prevent this, we will train and grade the Peer Interventionist candidates before allowing them 
to perform the intervention(s). 
 
Side Effects of NARCAN® Nasal Spray: 
NARCAN® Nasal Spray is an FDA-approved medication indicated for the emergency 
treatment of known or suspected opioid overdose. The primary side effect of NARCAN® is 
sudden opioid withdrawal symptoms. In someone who has been using opioids regularly, 
opioid withdrawal symptoms can happen suddenly after receiving NARCAN® Nasal Spray 
and may include the following: 
 
 
 
Body aches 
Diarrhea 
Increased heart rate 
Fever 
Runny nose 
Sneezing 
Goose bumps 
Sweating 
Yawning 
Nausea or vomiting 
Nervousness 
Restlessness or Irritability 
Shivering or trembling 
Stomach cramping 
Weakness 
Increased blood pressure 
 
 
 
ARE THERE BENEFITS TO TAKING PART IN THE RESEARCH STUDY?  
If you agree to take part in this research study, there may not be a direct medical benefit to 
you. We hope the information learned from this research study will benefit other opioid 
overdose patients in the future. You may directly benefit from study participation in that you 
will receive information about risks for overdose, the signs of overdose, how to respond to an 
overdose, and factors that can reduce the risk of an overdose. You may also benefit from 
receiving a NARCAN® Nasal Spray kit. 
 
WHAT OTHER CHOICES FOR CARE ARE THERE?  
You may choose not to participate in this study. Choosing not to participate will not result in 
any penalty or loss of benefits to you. 
 
WHAT IS A CERTIFICATE OF CONFIDENTIALITY?  
To further protect your privacy, the researchers have obtained a Certificate of Confidentiality 
from the Department of Health and Human Services (DHHS). With this certificate, the 
researchers may not disclose information (for example by court order or subpoena) that may 
identify you in any federal, state, or local civil, criminal, administrative, legislative, or other 


IRB #: 2016-6635 
 
 
 
Approved:  
8/8/2018 
Do Not Use After: 
8/7/2019 
 
 
 
 
 
Page 7 of 13 
proceedings. Disclosure will be necessary, however, upon request of DHHS for audit or 
program evaluation purposes.  
 
A Certificate of Confidentiality does not prevent you from voluntarily releasing information 
about yourself or your involvement in this research.  
 
Even with the Certificate of Confidentiality, if the investigator learns about abuse of a child or 
elderly person or that you intend to harm yourself or someone else, or about certain 
communicable diseases, they will report that to the proper authorities. If keeping information 
private would immediately put you or someone else in danger, the researchers would release 
information to protect you or another person.  
 
AVAILABILITY OF INFORMATION 
You will receive a copy of this signed and dated consent form.  
 
You will be told about any new information from this or other studies that may affect your 
health, welfare, or willingness to stay in this study. 
 
WHAT ARE YOUR COSTS TO BE IN THIS STUDY?  
You will not be charged for assessments related to this study. However, you and/or your third 
party payer (insurance, Medicaid, etc.) will still be responsible for costs related to substance 
use treatment and other healthcare costs not directly associated with this study. 
 
WILL YOU BE PAID TO PARTICIPATE IN THIS RESEARCH STUDY?  
If you receive payments for being a part of this research study, you may be asked to complete 
an Internal Revenue Service (IRS) form. The amount you receive may count as income and 
may affect your income taxes. Your social security number will be required to complete the 
IRS form. 
 
You will be paid up to $220 for your time and travel costs related to taking part in this study.   
Payments will be made to you with a prepaid debit card. The payment will be loaded onto 
your card within one business day of the completion of your visit.  A schedule of the payments 
is below: 
 
Visit 
Amount 
Enrollment/Randomization 
$50  
Week 3 Follow-up Call 
$20  
3-Month Follow-up Visit 
$50  
6-Month Follow-up Visit 
$50  
12-Month Follow-up Visit 
$50  
TOTAL 
$220  
 
Details of the system are explained on an additional information sheet. 
 


IRB #: 2016-6635 
 
 
 
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WHAT COMPENSATION IS AVAILABLE IN CASE OF INJURY? 
In the event that you become ill or injured from participating in this research study, emergency 
medical care will be provided to you. The National Institute on Drug Abuse OR the University 
of Cincinnati will decide on a case by case basis whether to reimburse you for your out of 
pocket health care expenses.  
 
WHAT ARE YOUR RIGHTS AS A PARTICIPANT?  
You may choose either to take part or not to take part in this research study. If you decide to 
take part, you may decide to leave the study at any time. Leaving the study will not result in 
any penalty or loss of benefits to you.  
 
The investigators will tell you about new information that may affect your health, welfare, or 
willingness to stay in this study.  
 
If you have questions about the study, you will have a chance to talk to one of the study staff 
or your regular doctor. Do not sign this form unless you have had the chance to ask questions 
and have received satisfactory answers.  
 
Nothing in this consent form waives any legal rights you may have nor does it release the 
investigator, the sponsor, the institution, or its agents from liability for negligence.  
 
HOW WILL INFORMATION ABOUT YOU BE KEPT PRIVATE AND CONFIDENTIAL?  
Every effort will be made to maintain the confidentiality of your medical and research records 
related to this study. Agents of the University of Cincinnati, and the sponsoring company, the 
National Institute on Drug Abuse (NIDA), the monitor, the auditor, the Institutional Review 
Board (IRB), and other regulatory authority(ies) will be granted direct access to your original 
medical and research records for verification of research study procedures or study data 
without violating your confidentiality, to the extent permitted by the applicable laws and 
regulations. By signing this consent form, you or your legally authorized representative are 
authorizing such access. The data from the study may be published; however, you will not be 
identified by name. Your identity will remain confidential unless disclosure is required by law. 
  
Authorization to Use and Disclose Health Information  
A federal regulation known as the Privacy Rule gives you certain rights concerning the privacy 
of your health information. Researchers covered by this regulation are required to get your 
authorization (permission) to use and disclose (share with others) any health information that 
could identify you. You should have received a Notice of Privacy Practices when you received 
health care services here.  If not, let us know and a copy will be given to you.  
 
If you sign this informed consent form, you are giving permission for the use and disclosure of 
your health information for purposes of this research study. You do not have to give this 
permission. Your health care outside of the study, payment for your health care, and your health 
care benefits will not be affected if you choose not to sign this form.  However, if you do not 
sign this form, you will not be able to participate in the study.  
  
 
 


IRB #: 2016-6635 
 
 
 
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Who Will Use and Disclose My Health Information? The study doctor and research staff (the 
study team) may use your health information to conduct, review, and determine the results of 
the study. The study team may also use your information to prepare reports or publications 
about the study. However, your name will not appear in any report or publication without your 
permission.   
  
What Health Information will be Used and Disclosed? The study team will record your 
medical history, the treatment you receive, and the results of examinations and tests done 
during the study on study forms. Representatives from the groups identified below may need to 
look at your medical records to make sure that the information on the study forms is correct or 
that the study was conducted properly. Your medical records may include other health 
information about you and may include documents that directly identify you.  Reviews like that 
will take place at the study center or where the medical records are stored and can take place 
after the study is over.  
  
Who Will Receive My Health Information? Your study information or medical records (as 
described above) or both may be shared with the following people or groups:  
  
• The study sponsor or its representatives, including companies it hires to provide study-
related services   
• UC Institutional Review Board and any other committees responsible for overseeing 
the research 
• Staff of the UC Human Research Protection Program 
• Federal and State agencies, such as the Department of Health and Human Services 
(DHHS), the National Institutes of Health (NIH), and other US and non-US government 
bodies that oversee or review research 
 
Will My Information be Protected by the Privacy Rule After it is Disclosed to Others?   
UC and UC Health are required by the Privacy Rule to protect your health information. After 
your information is shared with others, such as the study sponsor, it may no longer be protected 
by the Privacy Rule. The people who receive this information could use it in ways not discussed 
in this form and could disclose it to others. The sponsor will use and disclose your information 
only for research or regulatory purposes or to prepare research publications.  In addition to 
using it for this study, the sponsor may reanalyze the study data at a later date or combine your 
information with information from other studies for research purposes not directly related to this 
study. The goal of any such research would be to learn more about drugs, devices or diseases 
or to help design better studies in the future. When using your information in these ways, the 
sponsor may share it with regulatory authorities, other researchers, its business partners, or 
companies it hires to provide research-related services.   
  
What Happens if I Leave the Study Early?  If you stop participating in the study early for any 
reason, the study team will tell the sponsor why. If the study team asks you to come to any 
more study visits and you agree, the study team will send the sponsor information from those 
visits as well.  All information collected about you may continue to be used and disclosed.  
  
Will My Authorization Ever Expire?  This Authorization does not have an expiration date.  


IRB #: 2016-6635 
 
 
 
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 Page 10 of 13 
The study team may need to correct or provide missing information about you even after your 
study participation is over and a review of your medical records may also take place after the 
study is over.  
  
May I Take Back My Authorization? You have the right to take back (revoke) your 
Authorization at any time by writing to the person in charge of this research study whose 
information is listed on the front of this form.  If you revoke your Authorization, the study team 
will not collect any new health information about you.  However, they can continue to use and 
disclose any already-collected information if that is necessary for the reliability of the study.  The 
sponsor can also still keep and use any information that it has already received. If you revoke 
your Authorization, you can no longer continue to participate in the study.  
  
May I Look At My Study Information? You have a right to see and make copies of your 
medical records. However, to ensure the validity of the study, you will need to wait to see your 
study records until the study is completed.  
 
 
WHO DO YOU CALL IF YOU HAVE QUESTIONS OR PROBLEMS?  
If you have questions, concerns, complaints and/or suggestions about this research study or 
to report a research-related injury, please contact the researcher Theresa Winhusen, PhD at 
513-310-0442 or a member of her staff.  
 
Please call the University of Cincinnati Institutional Review Board at 513-558-5259 (Monday – 
Friday 8 am to 5 pm) if you:  
• Think the research has hurt you.  
• Have general questions about giving consent or your rights as a research participant in 
this research study. 
• Have questions, concerns, complaints and/or suggestions about the research.  
• Cannot reach the research team or you want to talk to someone else. 
 
To report complaints or concerns to an independent agency in an anonymous and confidential 
manner, please call the Research Compliance Hotline at 1-800-889-1547.  


IRB #: 2016-6635 
 
 
 
Approved:  
8/8/2018 
Do Not Use After: 
8/7/2019 
 
 
 
 
 Page 11 of 13 
Comprehension Quiz 
 
 
1.  My participation in this study is entirely voluntary. 
 
 
 
T 
F 
 
2. I may be randomly assigned to be contacted by a Peer Interventionist. 
T 
F 
 
3. My participation in this study will last for approximately 12 months.  
T 
F 
 
4. If randomized, I will be given a NARCAN® nasal spray kit. 
 
 
T 
F 
 
5. This procedure is guaranteed to stop me from overdosing again. 
 
T 
F 


IRB #: 2016-6635 
 
 
 
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8/8/2018 
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 Page 12 of 13 
UNIVERSITY OF CINCINNATI - Medical 
CONSENT TO PARTICIPATE IN A RESEARCH STUDY 
 
Study Title: A Tailored, Peer-delivered Intervention to Reduce Recurring Opioid Overdoses 
 
UC IRB Study #:  
Sponsor Name: National Institute on Drug 
Abuse (NIDA) 
 
Investigator Information: 
Theresa Winhusen, PhD 
513-310-0442 
 
Principal Investigator Name 
 
 
Telephone Number 24 hr Emergency Contact 
 
I have read or someone has read to me, this Informed Consent Document which describes 
the purpose and nature of this research. I have had time to review this information and have 
been encouraged to ask questions. If I do not participate or if I discontinue my participation, I 
will not lose any benefits or any legal rights.  My participation in this research is completely 
voluntary. I have received (or will receive) a copy of this signed and dated form for my records 
and future reference. I have been given the information about the use and disclosure of my 
health information for this research study.   
 
I give my consent to participate. 
 
I authorize the release of information concerning treatment relating to drug abuse to the parties 
listed in the authorization section of this consent for the purposes described above.  
 
 
 
 
Participant   
 
 
 
 
 
 
Date  
 
PERSON OBTAINING CONSENT 
I have read this form to the participant and/or the participant has read this form. An 
explanation of the research was given and questions from the participant were solicited and 
answered to the participant’s satisfaction. In my judgment, the participant has demonstrated 
comprehension of the information.  
 
 
 
Signature and Title of Person Obtaining  
 
 
Date  
Consent and Identification of Role in the Study 
 


IRB #: 2016-6635 
 
 
 
Approved:  
8/8/2018 
Do Not Use After: 
8/7/2019 
 
 
 
 
 Page 13 of 13 
Please indicate below whether you want us to notify your primary care physician or your 
specialist of your participation in this study. 
 
____I want the researcher to inform my primary care physician/specialist of my participation 
in this study. 
___ I do not want the researcher to inform my primary care physician/specialist of my 
participation in this study. 
___I do not have a primary care physician/specialist. 
___The researcher is my primary care physician/specialist. 
 
 
_____________________________________________________________________ 
Participant   
 
 
 
 
 
Date