Preventing Risky Drinking in Veterans Treated With Prescription Opioids
Phase: NA
Conditions: Pain, Opiates, Alcohol Drinking
Sponsor: University of Pennsylvania

 
HRPP Accepted:  03-2015 
 
 
 
 
 
 
Page 1 of 39 
 
CMCVAMC SPECIFIC PROTOCOL SUMMARY 
Corporal Michael J. Crescenz Department of Veterans Affairs Medical Center (CMCVAMC) 
Institutional Review Board (IRB) 
 
 
 
Original Protocol Title: Preventing Risky Drinking in Veterans Treated With Prescription Opioids 
 
Renamed: Assisting Veteran in the Safe Use of Prescription Opioids 
 
NCT02709317 
 
Document date 03/08/2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
HRPP Accepted:  03-2015 
 
 
 
 
 
 
Page 2 of 39 
 
A. Protocol Title 
1. 
Full Protocol Title: Assisting Veterans in the Safe Use of Prescription Opioids 
 
2. 
Date of Protocol Summary and Version #: Date 03/08/2019; Version # 12 
 
B. Principal Investigator’s Full Name and Degree: James McKay, PhD 
 
C. Co-Investigator’s Full Name and Degree:  David Oslin, MD 
 
D. Financial Sponsor (Provide the name of the agency, organization, company or person providing 
funds for the research study.)  Department of Defense (DoD)  (U.S. Army Medical Research and 
Materiel Command) 
 
E. Grant (Provide the name of individual who holds the grant and the grant number, if applicable.) 
James McKay, 1 R01 DA037018-01 
 
F. Protocol Number (Provide the financial sponsor’s protocol number, if applicable.)     
 
G. Institution(s) responsible for the project: 
1. 
For single-site studies - CMCVAMC is the only institution involved.  Yes 
  No 
 
2. 
For multi-center studies. 
2.1. 
CMCVAMC is the Coordinating Center in which the PI is the lead investigator.  Yes 
  
No 
  N/A 
   
2.2. 
Provide the name of the Coordinating Center.  Yes 
  No 
  N/A 
 CMCVAMC 
2.3. 
List the name of the other sites involved.   VA Pittsburgh; University of Pennsylvania 
2.4. 
Provide the FWA numbers for each of the other sites involved.  00001282 (VA 
Pittsburgh); 00004028 (Penn) 
 
THE FOLLOWING INFORMATION MUST BE CMCVAMC-SPECIFIC, THAT IS, SPECIFIC TO WHAT 
WILL BE DONE WITH CMCVAMC-RECRUITED VETERANS. 
 
H. Background and Significance: (Describe succinctly and clearly the past findings which justify the 
plan for this project.  A summary of the relevant literature in the area of interest and reports of 
previous studies should be included.)    
1. 
Opioid Use in the Treatment of Pain 
The prevalence of chronic pain continues to increase in the United States causing 
individual suffering and contributing to morbidity, mortality and disability. It has been 
estimated that over 100 million Americans suffer from chronic pain.  In the Veteran 
population, improvements in battlefield medicine have resulted in large numbers of 
Veterans of Iraq and Afghanistan surviving injuries that in previous wars would have 
resulted in fatalities.  A substantial percentage of these Veterans experience clinically 
significant pain and many require treatment with opioid analgesics.  Clark et al. 
randomly selected and reviewed 300 charts of U.S. Veterans from a general medical 
population. They found that 50% of patients suffered from chronic pain and 
approximately 75% of the patients with chronic pain were prescribed at least one 
analgesic.  Although non-steroidal anti-inflammatory drugs were the most commonly 
prescribed class of analgesics, 44% of patients receiving an analgesic received opioids. 
Wu et al. have also reported a rise in the prevalence of opioid use in young Veterans.  
Within the VA, chronic pain management and thus opioid prescriptions are almost 
exclusively provided within the primary care program. 
 
2. 
Risky Alcohol Use in Returning Service Personnel and Veterans 
Alcohol misuse is the fourth leading cause of disability worldwide and is associated 
with increased mortality.  Alcohol is, after nicotine, the most frequently abused 
substance among Veterans.  The Veterans Health Study found that 12.1% of outpatients 

 
HRPP Accepted:  03-2015 
 
 
 
 
 
 
Page 3 of 39 
 
had alcohol-related problems, and more recent studies found that 11-14% of Veterans in 
primary care screened positive for hazardous alcohol use. Several studies among 
Veterans recently returning from Iraq have found prevalence of alcohol misuse ranging 
from 24-39%, likely reflective of the younger age cohort.  One other study found that of 
the OEF/OIF Veterans treated at VA hospitals in 2005, almost half screened positive on 
the AUDIT-C for likely risky/hazardous alcohol use. Alcohol misuse has tremendous 
individual and societal costs.  For instance, Veterans who reported drinking during the 
previous year and who had a positive alcohol screening test experienced a 1.6 fold 
higher mortality rate over the subsequent 5 years than did patients who screened 
negative.  
 
3. 
Effects of Risky Alcohol and Drug Use in Veterans Being Treated with Prescription 
Opioids 
Although opioids can be a safe and effective therapeutic agent for many patients 
suffering from chronic pain, they have many known adverse effects including 
gastrointestinal complaints, cardiac problems, hormonal changes, immunologic effects, 
sleep disorders, sedation, addiction, and overdose. Of particular concern, there has 
been a substantial increase in fatal poisonings involving opioid analgesics. For 
example, the number of opioid-related fatal poisonings tripled from 4,000 to 13,800 
deaths from 1999 through 2006 and approximately 40% of all deaths by poisoning in 
2006 involved opioids.  Opioid use is also associated with frequent use of emergency 
departments.   
 
Many of these opioid-related overdoses or adverse effects involved the use of other 
substances including alcohol and benzodiazepines. Central nervous system depressant 
drugs such as alcohol and benzodiazepines, when combined with opioids, have an 
additive or interactive pharmacological effect on respiratory depression that may lead 
to serious adverse effects including death. Data from the Drug Abuse Warning Network 
in 2010 revealed that pain relievers were involved in 23% of emergency department 
visits involving the ingestion of both that alcohol and prescription medicine. Based on 
epidemiological data, alcohol is implicated more frequently in opioid-related deaths 
than any other substance.  However, in 2006 approximately 50% of all opioid-related 
deaths in the US involved more than one substance, and benzodiazepines were found 
in 17% of these deaths. Also, benzodiazepines are frequent co-intoxicants in 
methadone-related deaths. These data highlight the importance of prevention of such 
adverse outcomes, which can be accomplished by screening patients receiving 
prescription opioids for risky/hazardous alcohol use, and providing interventions to 
those individuals who screen positive.  
 
Similar issues have been noted with regard to other substance use in patients receiving 
opioids to treat chronic pain.  In a recent national study of Veterans receiving opioid 
treatment for non-cancer pain, the strongest predictor of the development opioid 
abuse/dependence was a non-opioid substance use disorder.  However, research 
results have raised some concern about how well Veterans receiving opioid 
medications are being monitored for other substance use problems.  For example, Wu 
et al. found that nearly 80% of opioid prescriptions to young Veterans were given by 
primary care providers rather than pain specialists, and that only 31% of patients on 
chronic opioids had undergone urine drug testing to detect other drug use. 
 
4. 
Screening and Brief Interventions in the VA:  Current Practice 
In 2004, the VA Office of Quality and Performance (OQP) began requiring annual alcohol 
screening using the AUDIT-C.  Since implementation of this policy, medical record 
reviews conducted for the VA External Peer Review Program (EPRP) have shown that 
an average of 86% of patients are screened with the AUDIT-C.  The vast majority of this 
screening occurs within primary care.  In 2007, the VA implemented a performance 

 
HRPP Accepted:  03-2015 
 
 
 
 
 
 
Page 4 of 39 
 
measure to incentivize the conduct of brief interventions and referral after a positive 
screen.  This performance measure was temporarily associated with an increase in the 
delivery of brief interventions from a baseline of 5.5 % of Veterans who were screen 
positive getting a brief intervention to 29% after the implementation of the performance 
measure.  These low rates of brief intervention and referral contrast sharply with 
patients’ expressed desire for help.  In the VA Large Health Survey, only 12% of heavy 
drinkers and 17% of very heavy drinkers reported getting the help they needed (30). 
Similarly, the seven-site ACQUIP study showed that only 30% of VA patients with 
alcohol misuse reported receiving advice to decrease or stop drinking, despite the fact 
that 83% reported contemplating or taking steps to change their drinking.  Most 
recently concerns have been raised about the validity of screening done in clinical 
practice. As many as 61 percent of risky/heavy drinkers are not being identified by their 
clinicians, most likely because of improper screening techniques.  Moreover, there was 
substantial variation between VA facilities suggesting marked implementation problems 
with screening.  These data demonstrate that many patients with risky alcohol use are 
not receiving adequate diagnostic evaluations or preventive care to reduce their 
drinking.  These problems take on increased significance with VA patients receiving 
opioid prescriptions, because of the potential for harmful interactions between opioids 
and alcohol, which can be compounded by the co-ingestion of other drugs.  
 
To address some of these concerns, the VA is an industry leader in integrating a 
comprehensive set of services for mental health conditions in primary care.  At the 
CMCVAMC, this program is known as the “Behavioral Health Lab” or BHL.  During the 
last 5 years, there has been a complete reshaping of the VA’s primary care system so 
that today it is organized as Patient Aligned Care Teams (PACT) similar to medical 
home programs, a key characteristic of which is the integration of mental health 
services with primary care.  A driving force leading to the PACT model was the 
accumulation of evidence demonstrating that treating depression and alcohol misuse in 
the primary care setting within the VA leads to improved symptom-based outcomes, 
including reduced all-cause mortality.  VA wide, BHL programs have served Veterans in 
two million patient encounters in less than five years and are a central aspect of the 
interdisciplinary care in the PACT programs.  
 
The principles of the BHL program are to deliver patient-centered care while adhering to 
recommended treatment algorithms, modeled from the VA/DOD Depression Treatment 
Guidelines, including the use of structured assessments to facilitate care (instruments 
like the PHQ-9) at nearly every encounter.  At the CMCVAMC and nationally, the BHL 
program is guided by a set of training guides entitled, “Foundations for Integrated 
Care.”  The training program was recently released to the field and embodies the 
evidence base for care management and co-located collaborative care.  The goal of the 
program is to deliver care where the Veteran wants care and consistent with the 
resources needed to provide that care.  The BHL program is designed to be the 
principal point of entry for any Veteran seeking mental health care or who has screened 
positively on any mental health screening questionnaire including the AUDIT-C.  Thus, 
in general, the BHL program provides care to Veterans with milder disorders or those 
who need prevention services, while specialty care services are reserved for more 
complex or severe illness.  Specifically for alcohol misuse, the BHL program provides a 
structured brief intervention (it is VA policy for Veterans to be administered the AUDIT-
C and for anyone scoring a 5 or higher to be referred to BHL for clinical assessment).  
In reference to this proposal, the BHL program receives requests from the primary care 
team to conduct assessments and deliver brief interventions for Veterans who screen 
positive on the AUDIT-C.  Currently more than 300 Veterans are evaluated in the BHL 
per month with 25% screening positive for alcohol misuse.  This program will serve as 
the standard care arm of the study.  Despite advances in screening, we are well aware 
that not all Veterans who screen positive on the AUDIT-C are referred for follow-up care 

 
HRPP Accepted:  03-2015 
 
 
 
 
 
 
Page 5 of 39 
 
in the VA.  Indeed, Maust et al showed that Veterans with a positive AUDIT-C score were 
10 times less likely to be referred than Veterans who screen positive for depression or 
PTSD. 
 
February 2017 Amendment 
We amended the protocol to include subjects with a lower AUDIT score that would most 
likely NOT be referred by their Primary Care Provider (PCP) to the BHL for a Brief 
Intervention. However, as the National Institute on Alcohol abuse and Alcoholism 
(NIAAA) defines drinking while taking contraindicated medications as risky alcohol use: 
(https://www.niaaa.nih.gov/alcohol-health/overview-alcohol-consumption/moderate-
binge-drinking), and thus a BI is still warranted. For subjects enrolled in the study with 
a low AUDIT score, the study counselors will perform the BI. 
 
March 2018 Amendment 
We amended the protocol to eliminate the AUDIT score as part of our screening 
procedure.  BHL will refer individuals who are drinking and on opioids, but no longer on 
AUDIT C results. 
 
5. 
Research on Brief Interventions for Risky Alcohol Use  
Two recent reviews have indicated that brief interventions delivered in primary care are 
effective in reducing rates of risky/hazardous alcohol use.  However, two other reviews 
have indicated that brief interventions in primary care and other settings may not be 
effective for individuals with more severe alcohol problems.  A recent study in a sample 
of Veterans showed that providing patients who had screened positive for risky alcohol 
use with a web-based brief alcohol intervention in addition to brief alcohol counseling 
from a primary care provider did not improve drinking outcomes over the primary care 
provider only control condition.  However, several other studies have shown positive 
effects for web-based brief alcohol interventions in military samples.  
 
6. 
Beyond the Brief Intervention 
Although research on brief interventions (BIs) for risky alcohol use has generally 
shown positive results, several important gaps in evidence remain.  First, there is 
considerably less information on whether such interventions are effective with other 
substances.  Second, despite their efficacy, significant percentages of patients fail to 
respond to BIs.  There is essentially no research on what types of interventions might 
be efficacious and feasible with individuals who continue to drink at risky levels after 
receiving a BI.  Third, no studies have focused on the efficacy of BIs for risky alcohol 
use in patients receiving prescription opioids for pain.  
 
One possible approach for BI non-responders is to provide additional BI sessions.  
Only a small number of studies have compared a single session of BI to an extended 
version of the same or similar intervention in primary care patients.  Longabaugh et al. 
and Maisto et al. examined the impact of 1 and 2 additional sessions, respectively. 
Richmond et al. and Israel et al. tested the effect of 4 and 6 addition sessions, 
respectively, whereas Aalto et al. compared 2 and 6 additional sessions to a single 
session. The additional sessions in these studies were provided over periods ranging 
from a few days after the initial session up to 24 months later.  Results varied across 
these studies, with some showing positive effects for the extended intervention and 
others showing no positive effects.  However, none of these studies tested an adaptive 
approach to BIs, in which follow up after the BI is determined by the patient’s response, 
such as through the use of an algorithm directing additional sessions to individuals 
who did not respond to an initial session.    
 
In adaptive prevention and treatment interventions, the services provided to any given 
individual are tailored over time on the basis of response.  In a typical adaptive 

 
HRPP Accepted:  03-2015 
 
 
 
 
 
 
Page 6 of 39 
 
protocol, after an initial intervention, non-responders receive an augmented 
intervention or are switched to a new intervention.  The tailoring variable is usually a 
measure of the targeted symptom or behavior (e.g., risky drinking, depression, tumor 
markers), assessed regularly over some period of time. Adaptive interventions have 
several important advantages over conventional interventions. First, they provide 
guidelines for how to modify interventions for non-responders, to improve outcomes 
for this group. Second, they lower patient burden and overall cost by reducing 
unnecessary additional interventions for patients who respond to the initial 
intervention.   
 
7. 
Preventing Risky Drinking and Other Drug Use in Veterans on Prescription Opioids     
We have developed an adaptive intervention designed to reduce levels of risky drinking 
and other drug use, in Veterans receiving prescription opioids for chronic pain.  This 
patient-centered intervention provides integrated screening, brief intervention, 
monitoring, and extended prevention services that are delivered through a combination 
telephone calls, and text messages.  Moreover this intervention is ideally suited to be 
disseminated within the primary care/mental health initiatives for patient centered 
medical home teams.  The intervention is intended for Veterans who are receiving 
prescriptions for daily doses of opioids for pain and/or opioid replacement therapy; 
who also screen positive for risky/hazardous drinking. At the beginning of the 
intervention, a brief intervention (BI) is provided to reduce alcohol to safe levels, and a 
health screening is provided to flag other medication use that could interact negatively 
with opioid use (e.g., benzodiazepines).  Following administration of the BI, alcohol use 
is monitored for one month to determine whether the intervention has been effective.  
Veterans who reduce their drinking to non-hazardous levels will continue in a 
monitoring track, which consists of tailored text messages and brief monthly telephone 
contacts.  Veterans who continue to use alcohol at unsafe levels will instead be placed 
in a track that provides tailored text messages and more frequent telephone calls.  In 
addition to monitoring, these calls provide further prevention to help the Veteran 
reduce alcohol use to non-hazardous levels.  These services address motivational 
issues and identify more effective ways to cope with stress and other factors that 
trigger unsafe substance use. 
 
8. Rationale for Intervention Components 
a. 
Extended monitoring in responders.  BIs typically do not provide follow-up 
contacts, which raise questions about the need for ongoing monitoring in 
responders.  However, studies have indicated that Veterans receiving prescription 
opioids are at heightened risk for a number of adverse health outcomes, and would 
be at even higher risk if they were to resume hazardous drinking.  Brief monthly 
monitoring calls, supplemented by text messages, represent a low-burden, low-cost 
method to detect the resumption of hazardous alcohol use.  Providing monitoring 
over 12 months allows for the possibility that some Veterans will do well initially, 
but increase their use of alcohol at a later point, perhaps due to stressors related to 
the transition to civilian life, including family or employment problems.  If increased 
substance use occurs, additional prevention interventions can be delivered.   
b. 
Enhanced prevention efforts for non-responders.  Examination of results from BI 
studies suggests that 20-50% of participants who receive these interventions do 
not reduce alcohol use to non-hazardous levels, with a higher percentage of non-
responders among individuals who are also using drugs.  Very few of these 
individuals are appropriate for specialty addiction treatments which typically have 
an abstinence orientation and are designed for people with more severe substance 
use problems.  Therefore, additional prevention services are needed that are 
feasible to implement, of relatively low burden, and acceptable to Veterans.  The 
combination of text messages and brief prevention counseling provided via the 
telephone meets these requirements.  In our prior work (see below), we have 

 
HRPP Accepted:  03-2015 
 
 
 
 
 
 
Page 7 of 39 
 
demonstrated that it is possible to deliver interventions to increase motivation and 
coping abilities via relatively brief telephone calls, with good fidelity to treatment 
manuals.   These interventions directly address the factors that contribute to 
nonresponse to brief interventions—low motivation for change, low self-efficacy, 
and problems with coping with stressors that precipitate drinking episodes.   
c. 
Inclusion of text messaging (SMS) interventions.  Mobile interventions, specifically 
SMS interventions, are well suited for ongoing monitoring and prevention 
interventions for risky alcohol and drug use because they can be tailored to the 
individual through decision support features, are flexible enough to meet 
individuals in their natural environment, and can adapt to their current needs in 
real-time using ecological momentary assessment.  Numerous studies have shown 
that text messaging can improve outcomes across physical and mental health 
disorders. SMS interventions have been found to have small-to-moderate effects 
against no treatment controls with the largest effects being for smoking cessation 
and HIV medication adherence. In the largest SMS study to date, “txt2stop,” an SMS 
intervention for smoking cessation doubled quit rates in a sample of over 5,000 
individuals in the UK. 
 
Recent reviews suggest that the addition of text messaging and other prompts 
improves the effects of web-based interventions, highlighting the use of SMS as a 
component to enhance other interventions. Although messaging interventions may 
work via mechanisms similar to those of telephone-based interventions (e.g. by 
catching individuals in their natural environment, reaching people in the moment 
without a computer connection), they offer several unique benefits that can 
enhance phone-based interventions. Text messaging allows for increased 
confidentiality, invulnerability to missed calls, and convenient continual viewing of 
messages sent and received. Text messages are less intrusive than phone calls, 
expend less labor, and do not require the phone to be active (the message will be 
resent for several days until the phone is active. This is especially important as low 
income individuals may have their phones turned on and off due to difficulties in 
paying bills.  
 
SMS interventions have several other important features that warrant their 
integration into prevention models. First, messaging interventions inherit the 
benefits of computer-based interventions (e.g. low cost, standardized, 
individualized, adaptable and tailored, allowing for data collection) but there is no 
need for an internet connection or a computer. Second, unlike mobile applications 
(apps), SMS interventions do not require a smart phone, custom software 
programming for specific phones, or application updates, and are accessible on 
most phones, making the intervention significantly more accessible and 
generalizable than smart phone apps. Third, SMS-ready phones can perform nearly 
all of the functions of stand-alone ecological momentary assessment (EMA) 
devices without additional hardware or custom programming. There is an emerging 
literature on the using of text messaging to capture EMA data and results reveal 
outcomes similar to those of personal digital assistants (PDAs) and interactive 
voice response technology (IVR). Additionally, most studies have also indicated 
that SMS interventions are well accepted by participants as an intervention or 
adjunctive intervention and messaging is seen as more personal than that of other 
automated approaches.  Muench, Adams, McKay and Morgenstern found that only 
2 of the 125 individuals screened for a study of treatment for substance abuse did 
not have a mobile phone and all participants’ phones were SMS ready with 60% of 
participants having unlimited messaging plans. Interestingly, weekly SMS 
questions about appointment attendance were perceived to be as helpful to keep 
appointments as daily reminders highlighting the fact that minimal prompts may be 
all that is needed to reinforce change. 

 
HRPP Accepted:  03-2015 
 
 
 
 
 
 
Page 8 of 39 
 
 
In our previous work, we found that only 2 of the 125 individuals screened for a 
study of treatment for substance abuse did not have a mobile phone and all 
participants’ phones were SMS ready with 60% of participants having unlimited 
messaging plans 
 
9. 
Prior Studies.  We have conducted a series of studies that examined the efficacy of the 
telephone for the provision of follow-up care to individuals with risky drinking or 
substance use disorders.  The interventions that were evaluated in these studies were 
telephone care management for heavy drinkers in primary care, motivational 
interviewing for patients with alcohol or cocaine use disorders who failed to engage in 
or dropped out of treatment, and telephone continuing care for patients with alcohol or 
cocaine use disorders who had completed several weeks of addiction specialty care 
treatment.   
a. 
Telephone Care Management for Heavy Drinkers in Primary Care.  Helstrom and 
colleagues randomized Veterans who screened positive for risky/hazardous alcohol 
use in primary care to a standard session of brief advice from their primary care 
provider or to the brief advice plus 3 telephone care management (TCM) follow-up 
sessions at 3, 6, and 9 months.  At the 12-month follow-up, rates of risky/hazardous 
drinking were 51% in the TCM condition vs. 56% in the usual care condition (p= ns).  
The results of this study highlight the persistence of risky drinking in Veterans (i.e., 
almost 50% were still engaging in risky drinking after 12 months), and suggest that 
providing three follow-up prevention sessions is probably not adequate to decrease 
the rate of risky drinking in this population.    
b. 
Motivational Interviewing (MI) Delivered by Telephone.  We recently completed two 
studies in which patients with alcohol or cocaine use disorders who dropped out of 
treatment were provided with 1-2 telephone-based MI sessions in an effort to re-
engage them.  Half of the participants in these two studies were Veterans.  The MI 
sessions were audio recorded, and coded to assess the quality of the MI.  On 
average, MI fidelity as measured by the MITI met or exceeded “beginning 
proficiency” thresholds.  The skill level for MI-consistent strategies was at threshold 
level and the use of “fundamental” MI strategies and skill level was above threshold 
level.  Results indicated that MI designed to re-engage patients in their original 
treatment program produced better alcohol use outcomes than MI coupled with a 
menu of other treatment options.  
c. 
Telephone-Based Alcohol Disease Management Study.  We developed an 18-month 
telephone-based intervention, which we compared to standard care in 252 alcohol 
dependent patients who completed 3-4 weeks of outpatient treatment.  Telephone 
Monitoring and Counseling (TMC) consisted of 20-minute telephone calls that were 
provided weekly for 8 weeks, twice monthly for 10 months, and monthly for the final 
6 months.  Each call began with a 5-minute structured assessment of risks and 
protective factors, followed by Cognitive-Behavioral Therapy (CBT) techniques 
focused on developing coping responses to the most pressing problem identified in 
the assessment.  During the 18-month treatment period, rates of any alcohol use 
(OR= 1.88) and any heavy alcohol use (OR=1.74) were significantly higher in 
standard care (TAU) than in TMC.  Significant group x time interactions were 
obtained on the percentage days alcohol and heavy alcohol use, in which the 
advantage for TMC over TAU increased over time.  Subgroup analyses over the full 
24 month follow-up period showed effects favoring TMC over TAU on percent days 
drinking were greater in women (OR=0.47, p=.04) and those with prior treatments 
(OR= 0.59, p= .02); and in those with social networks that supported continued 
drinking (OR=0.44, p=.02) and low readiness to change (OR=0.53, p=.05) after 3 
weeks of IOP.  
d. 
Telephone-Based Cocaine Disease Management Study.  In a similar continuing care 
study with cocaine dependent patients (N=321), there were interactions between 

 
HRPP Accepted:  03-2015 
 
 
 
 
 
 
Page 9 of 39 
 
cocaine and alcohol use at baseline and the continuing care conditions (p= .03) on 
the primary outcome, a measure of abstinence from cocaine, other drugs, and heavy 
alcohol use (confirmed by urine toxicology tests).  In patients with any days of 
cocaine or alcohol use in the 30 days prior to baseline (i.e., the week prior to intake 
and the first 3 weeks of treatment), abstinence rates were higher in TMC than in 
TAU, with the treatment effect larger in those who had been drinking at baseline 
(OR=2.47, p= .007) than in those who had been using cocaine (OR=1.95, p= .04). 
Conversely, in patients with no days of cocaine or alcohol use in the 30 days prior to 
baseline, there were no treatment effects. Of note, incentivizing participation in the 
telephone sessions dramatically increased the number of sessions completed, but 
did not further improve outcomes.      
e. 
Summary of Findings from Our Research Program.  These studies demonstrate our 
ability to recruit large samples in a timely fashion, enroll Veterans who are engaging 
in risky drinking into research studies, deliver interventions over the telephone, and 
maintain high follow-up rates across periods as long as 24 months.  Three of these 
studies also provide evidence to support the effectiveness of enhanced or extended 
interventions for patients who do not evidence a good initial response to 
alcohol/drug treatment. 
 
I. 
Purpose of the Project: (Clearly provide the purpose of this research project.) In this application, 
we propose to test an integrated prevention intervention, designed to reduce rates of risky 
drinking in Veterans receiving prescription opioids for chronic pain management or opioid 
replacement therapy. For Veterans on opioid replacement therapy, they must have a chronic 
pain diagnosis.  This adaptive, patient-centered intervention provides integrated clinical 
assessment, brief intervention, monitoring, and extended prevention services delivered 
through a combination of telephone calls, and text messages. 
 
J. Describe the Research Questions or Hypotheses (that is, what questions are you trying to 
address by conducting the research.) 
1. Primary objective: To compare the effectiveness of a 12-month prevention intervention (PI) 
with a brief intervention only group (BIO) over an 18-month follow-up period, for Veterans 
treated with prescription opioids and who are engaging in risky/hazardous drinking, based 
on NIAAA guidelines.  
 
Hypothesis 1:  PI will produce better outcomes than BIO, as indicated by lower rates of 
risky/hazardous alcohol use across the follow-up period. 
2. Secondary objectives:  To examine secondary outcome measures, moderator effects, and 
mediation effects:  
 
Hypothesis 1:  PI will produce better outcomes than BIO on frequency of heavy 
drinking, biological measures of heavy drinking (i.e., GGT and CDT), urine toxicology 
tests to assess other drug use, depression, and pain.  
 
Hypothesis 2:  Rates of opioid overdoses will be lower in PI than in BIO  
 
Hypothesis 3:  Intervention effects will be greater in higher-risk Veterans, including 
those with higher prescription opioid dosages, co-occurring benzodiazepine use, poor 
social support, and low readiness for change.   
 
Hypothesis 4: Results favoring PI over BIO on risky drinking will be mediated by 
greater readiness for change, self-efficacy, and coping. 
 
K. Primary Outcome Variable(s): (Define the primary outcome variable(s) used to support the study 
objectives (e.g. if the objective is to show that treatment A is superior to treatment B in the treatment 
of subjects with essential hypertension, the primary outcome variable is blood pressure 
measurement.)   The primary outcome measure will be rates of risky drinking (i.e., more than 4 
drinks at any one sitting or more than 14 drinks/week for men; more than 2 drinks at any one 
sitting or more than 7 drinks/week for women) (5) within each follow-up period, as determined 
by the TLFB. 
 

 
HRPP Accepted:  03-2015 
 
 
 
 
 
 
Page 10 of 39 
 
L. Secondary Outcome Variable(s): (Define the secondary outcome variables. Such measured 
variables should also include the timing of measurement.)   Secondary outcomes in the study will 
be self-reported frequency of heavy drinking days (TLFB), biological measures of alcohol use 
(%dCDT and GGT), urine toxicology tests to assess other drug use, VA records of opioid 
overdoses, depression, and pain. 
 
M. Study Design and Methods: 
1. 
Is this a clinical trial?       
YES     
NO 
1.1. 
If yes, what type?  Check all that apply. 
  Phase I      
  Phase II          
  Phase III      
  Phase IV 
1.2. 
If yes, this study must be registered on Clinicaltrials.gov. 
 
2. 
Design 
2.1. 
What research methods will be used in the project?  Check all that apply. 
 Surveys/Questionnaires 
 Interviews           
 Audio Taping 
 Behavioral Observations 
 Chart Reviews    
 Video Taping 
 Focus Groups 
 Randomization 
 Double-Blind 
 Control Group 
 Placebo 
 Withhold/Delay Treatment 
 Specimen Collection 
 Deception 
 Telephone Survey 
 Other (Describe) 
 
 
2.2. 
Describe how randomization or other treatment assignment will be made. Veterans 
who meet criteria for participation will be randomly assigned to one of the two 
treatment conditions.  Urn randomization will be used to balance the groups on 
three factors: gender, benzodiazepine or other drug use, and age.  We will also be 
blocking on whether the person admits use or not when we do the randomization, 
so we get equal numbers of non-users in each condition.  Urn randomization is a 
kind of biased-coin randomization where probability of being assigned to a group 
decreases if the group is overrepresented and increases if the group is 
underrepresented. As the sample size increases, the randomization shifts from 
perfect balance to complete randomization. 
2.3. 
For retrospective research studies, provide the “look-back” period.  (e.g., December 1, 
1999 through December 31, 2008.) n/a 
 
3. 
Study Duration 
3.1. 
Provide the estimated length of time to enroll all subjects and complete the study. 2.5 
years of enrollment, but 5 years total for study start up, enrollment, completion, 
and analyses.  
3.2. 
Explain the expected duration of subject participation including any follow-up.18 
months for patients enrolled prior to 4/1/2019; 12 months for patients enrolled 
after 4/1/2019 
3.3. 
Specify the projected date of completion of the proposed study. 5 years from date of 
funding. 
 
4. 
Drug Information (If not applicable state, “Not Applicable.”) Not Applicable 
4.1. 
Specify if the drug or biological agent is:   
4.1.1. 
FDA approved       
4.1.2. 
Used for off-label purposes       
4.1.3. 
Not yet FDA approved.       
4.2. 
Include the FDA Investigational New Drug (IND) number for all non-FDA approved and 
off-label drugs, biological agents or nutritional supplements.  If not applicable state, “Not 
Applicable.”       
4.3. 
Provide all relevant information about the drug       
4.4. 
Explain any wash-out periods, rescue medications permitted and any type of 
medications not permitted while enrolled in the study.        
4.5. 
Describe blinding and un-blinding procedures.        

 
HRPP Accepted:  03-2015 
 
 
 
 
 
 
Page 11 of 39 
 
4.6. 
Include the dosage, route of administration, previous use, and the safety and efficacy 
information on any drug used for research purposes.       
4.7. 
Describe rationale for the dosage in this study.        
4.8. 
Justify why the risks are reasonable in relation to anticipated benefits and/or knowledge. 
      
4.9. 
Describe where drug preparation will be done.       
4.10. All drugs for CMCVAMC subjects must be dispensed through the VA investigational 
pharmacy.       
4.11. Describe where the study treatment will be administered.       
4.12. Describe plan for tracking a non-compliant treatment study subject.       
4.13. Summarize any pre-clinical data.       
4.14. Describe the process for the storage, security, dispensing and return of an 
investigational drug.       
 
5. 
Investigational Device (If not applicable state, “Not Applicable.”) Not Applicable 
5.1. 
The Investigational Device Exemption (IDE) number must be submitted for all significant 
risk devices and if an IDE exists for a non-significant device.       
5.2. 
Significant Risk or Non-significant Risk - If a device is not approved by the FDA, specify 
whether or not the sponsor has determined this device to be a “significant risk” or “non-
significant risk” as defined by the FDA.       
5.3. 
Provide all relevant information about the device.       
5.4. 
Describe blinding and un-blinding procedures.        
5.5. 
Specify if device is:   
5.5.1. 
FDA approved       
5.5.2. 
Used for off-label purposes       
5.5.3. 
Not yet FDA approved.       
5.6. 
Explain if the investigational device will be delivered and/or stored by the Principal 
Investigator or Pharmacy Services.        
5.7. 
Describe the process for the storage, security, dispensing and return of an 
investigational device.       
5.8. 
For research involving an investigational device, describe the SOP or plan for device 
control.       
5.9. 
Address how the device will be stored in such a way that only research staff associated 
with the protocol will have access to the device.       
5.10. Describe measures that will be put into place to ensure that the device will only be used 
in participants of this research protocol.       
 
N. Does this project involve international research?   
YES 
NO    
1. 
For further instructions refer to VHA Directive 2005-050, Requirements for Conducting VA-
Approved International Research Involving Human Subjects, Human Biological Specimens, or 
Human Data 
2. 
VHA Handbook 1200.05 definition of international research - VA international research is any 
VA-approved research conducted at international sites (not within the United States (U.S.), its 
territories, or Commonwealths); any VA-approved research using either human biological 
specimens (identified, de-identified, or coded) or human data (identified, de-identified, or 
coded) originating from international sites; or any VA-approved research sending such 
specimens or data out of the U.S. (see par. 56). NOTE: For the purposes of this Handbook, 
research conducted at U.S. military bases, ships, or embassies is not considered international 
research.  
 
O. Study Procedure 
1. 
Study Procedures 
Outline all study procedures - (If necessary, include a table or flow chart, showing the 
schedule of the procedures and interactions.  Distinguish between interventions that are 
experimental and carried out for research purposes vs. those that are considered 

 
HRPP Accepted:  03-2015 
 
 
 
 
 
 
Page 12 of 39 
 
standard of care. Routine procedures that are performed solely for research purposes 
should also be identified.) Recruitment for this study will happen in a few ways. For 
the majority of our potential participants, we will be using pharmacy records and 
reaching out by letter and phone call (Letter and phone script provided). We will 
use VA pharmacy records to identify Veterans who are currently being prescribed 
daily opioid medication for the treatment of chronic pain. Veterans already in 
treatment for alcohol use disorders (AUD) will then be excluded from the study. 
Veterans in treatment for opioid use disorders who are on a daily medication 
assisted regimen (i.e. OTP program) will be included as long as they have a 
chronic pain diagnosis and no AUD. For potentially eligible patients, we will send 
an encrypted email to the prescribing physicians (See email content below).   If a 
PCP objects to our intent to recruit their patient, we will not send that Veteran a 
letter.  If the clinician does not object to the study team contacting the potential 
subject we will contact potential subjects via letter to describe the research study 
and follow-up with a telephone call to invite them to participate (phone script 
provided). We respect the time of all the Veterans we are recruiting for this study. 
We want to ask these other questions because if we can clearly determine a 
Veteran is not eligible, we do not want to make them come in for a long 
consent/screening/baseline appointment and then be told they cannot participate. 
The Veteran may have to pay to take public transportation to the VAMC, or may 
be upset after completing the long first session and finding out they cannot 
participate. We want to limit unnecessary costs and agitation experienced by 
Veterans we are recruiting.  
There are a few potential outcomes of the screening call: 
 
If they are not eligible for the study and the Participant will not be 
contacted again. No referral or communication of results will be made.  If 
they are ineligible due to screening positive for a substance use disorder 
(by having 5 or more symptoms on the exclusion checklist), then they are 
drinking (or using) at too high a level and the results of this screening will 
be communicated to BHL for further clinical care. 
 
If they are not currently receiving mental health services at the MHC, and 
eligible: If Veteran decides to participate, a study counselor will complete 
the Brief Intervention only after participant has been consented to 
participate in the study and admits to any drinking. If the counselor 
determines their alcohol use is severe enough to necessitate more 
intensive treatment (i.e. inpatient treatment), the Veteran will be referred to 
the higher level of care and will be removed from our study. If Veteran 
decides not to participate, the technician will thank them for their time and 
end the call. A research note describing the outcome of screening call will 
be created in CPRS. 
 
If they are currently receiving mental health services at the MHC, and 
eligible: If Veteran decides to participate, a study counselor will complete 
the Brief Intervention only after participant has been consented to 
participate in the study. If Veteran decides not to participate or is later 
found to be ineligible, standard care through the MHC will continue as if 
he/she had never been contacted about the study. A research note 
describing the outcome of screening call will be created in CPRS. 
 
If they are not currently receiving mental health services at the MHC, and 
ineligible: A research note describing the outcome of screening call will be 
created in CPRS. 
 
If they are currently receiving mental health services at the MHC, and 
ineligible: Standard care will continue through the MHC as if the Veteran 
had never been referred to the study. A research note describing the 
outcome of screening call will be created in CPRS. 

 
HRPP Accepted:  03-2015 
 
 
 
 
 
 
Page 13 of 39 
 
 
It is possible through the course of receiving care at the CMCVAMC that a 
Veteran has received a BI in the past. However, this treatment could have 
occurred far enough in the past (i.e. greater than 3 months) that the BI 
would need to be repeated. As we cannot ensure a Veteran has received a 
recent (within the past 3 months) BI through the MHC, the study staff will 
perform the BI’s for those Veterans.  
 
If enrolled in the Opiate Treatment Program and eligible: If Veteran decides 
to participate, a study counselor will complete the Brief Intervention only 
after participant has been consented to participate in the study. If Veteran 
decides not to participate or is later found to be ineligible, standard care 
through the OTP will continue as if he/she had never been contacted about 
the study. A research note describing the outcome of screening call will be 
created in CPRS. 
 
If enrolled in the Opiate Treatment Program and ineligible: Standard care 
will continue through the OTP as if the Veteran had never been referred to 
the study. A research note describing the outcome of screening call will be 
created in CPRS. 
 
Encrypted email to prescribing clinician: 
 
Dear Dr. XX, 
 
One of your patients, XXX, may be eligible to participate in a study titled 
“Assisting Veterans in the Safe Use of Prescription Opioids.” Please see their 
information below. 
 
Name: <<Last>>, <<First>>, <<Middle>> 
Last 4: <<Last4>> 
 
Our recruitment entails sending Mr./Ms. XX a letter and then following up with 
him/her via phone one week later.  
 
If you have any questions or concerns please do not hesitate to contact the 
study’s principal investigator, James R McKay at james.mckay@va.gov 
 
Thank you, 
 
Margaret Lawlace 
 
Referrals from BHL 
In addition, we will take referrals from BHL.  BHL will refer subjects based on any 
alcohol and/or use of opioid.  If a Veteran expresses interest in our study to a 
member of the BHL team, study staff will be notified and will call the Veteran to 
further explain the study and perform a screening (phone script provided). 
 
In this scenario, there are a few potential outcomes of the screening call: 
 
If referred from the BHL and eligible: Results of screening call and 
patients’ decision to participate will be communicated to the BHL. A 
counselor from the study team will perform the Brief Intervention. If 
participant decides not to participate, services at the CMCVAMC will 
continue as if participant had never been referred to the study. A research 
note describing the outcome of screening call will be created in CPRS. 
 
If referred from the BHL and ineligible: Results of screening call and 
ineligibility to participate will be communicated to the BHL. Services at the 
CMCVAMC will continue as if participant had never been referred to the 

 
HRPP Accepted:  03-2015 
 
 
 
 
 
 
Page 14 of 39 
 
study. A research note describing the outcome of screening call will be 
created in CPRS. 
 
We will ask potential participants if they have texting capability during the initial 
phone screen. Cost of using the phone for texting and receiving calls will be 
covered by the participant but minimized as much as possible. In previous work, 
we found that only 2 of the 125 individuals screened for a study of treatment for 
substance abuse did not have a mobile phone and all participants’ phones were 
SMS ready with 60% of participants having unlimited messaging plans. 
 
For those who are potentially eligible following the phone screen (and interested 
in participating), the next step is coming to the VA for consent.  After consent, 
subjects will complete the first research visit. Final eligibility is determined after 
consent using the SCID and MINI. If after learning more about the study during the 
consenting process, the Veteran decides not to consent, or if they are ineligible 
following the SCID and MINI, then the Veteran will continue to receive services at 
the CMCVAMC to which they are eligible and entitled to. This could include 
services through the BHL or MHC. Similarly, Veterans can also elect to stop their 
participation in the study and can withdraw without penalty in writing using the 
revocation form at any time after they have consented to the study. In this case, 
their normal care at the CMCVAMC will continue. 
 
Veterans who meet criteria for participation will be randomly assigned to either 
receive the usual care (that which they would have gotten if they had not chosen 
to be in the study); or Prevention Intervention (PI).  
 
As a result of relaxing our inclusion criteria, it is likely that we will randomize 
Veterans who have not consumed alcohol in the past three months. For those 
Veterans, we will monitor their alcohol use during the research follow up visits at 
3, 6, and 9 months. If they report having a drink of alcohol, we will then begin 
which treatment arm they had been randomized to. If the Veteran does not report 
taking a drink prior to the 9 month follow up, they will simply continue with the 12 
and 18 month follow ups but will never have the Brief Intervention or Prevention 
Intervention. 
 
Brief Intervention (BI) 
Both groups will have received or will be scheduled to receive Brief Intervention 
(BI).  A brief intervention includes providing feedback linking the Veteran’s 
drinking to their health issues, in addition to providing education and advice 
about recommended drinking limits, and how to reduce alcohol use. In general, a 
BI involves increasing an individual’s insight about the risk of drinking on 
opiates, and how to cut down. However, each Veteran presents with a different 
situation, and thus the BI can be flexible in terms of content. Sometimes the BHL 
will send the NIAAA workbook “rethinking drinking” to a Veteran, sometimes they 
won’t. Sometimes a Veteran will get a follow up call, and sometimes they won’t. It 
depends on what the Veteran needs. So in terms of what exactly the research 
staff will do during BI’s, it will follow a similar structure to the BHL BI’s (raise 
insight, identify strategies on how to reduce) but the details on how to 
accomplish those goals will vary based on each Veteran’s individual situation. 
 
For Veterans not enrolled in the Mental Health Clinic (MHC), study staff will 
administer the BI since as a result of broadening our inclusion criteria these are 
individuals that would likely not be serviced by BHL. If during the baseline visit 
study staff determine that the Veteran’s drinking warrants a referral to the 
Behavioral Health Lab (BHL) then the BHL will administer the BI. For Veterans 

 
HRPP Accepted:  03-2015 
 
 
 
 
 
 
Page 15 of 39 
 
enrolled in the MHC, the study team will administer the BI. Study staff have 
worked with the BHL nurses and have all of their material and can perform BI 
according to standards set in the BHL protocol.  Study staff will get ongoing 
supervision from the BHL staff, to make sure that we are following their protocol. 
The research counselors are Masters level clinicians trained in recovery 
counseling and the administration of Brief Interventions. On average, BI’s take 
about 20 minutes, and will be done over the phone. Subjects will not be 
compensated for the BI done for study purposes. While not all BI’s require a 
follow up call, following the same procedures done by the BHL, the research staff 
providing the BI at times will complete one or two follow up calls one month after 
the initial BI, to check in on an individual’s progress. 
   
The reason why study staff needs to provide BI to subjects recruited from MHC is 
that BHL provides services to primary care patients.  Patients already using 
mental health specialty care are not typically referred back to BHL for 
interventions like BI. 
 
Brief Interventions for Pittsburgh Site 
Research counselors at the Crescenz VAMC in Philadelphia will perform all BI’s 
for Veterans recruited from the Pittsburgh site. These BI’s will follow the same 
structure as BI’s that occur at the Crescenz VA, they will be over the phone and 
take about 20 minutes to complete. 
 
Brief Intervention Only Group (BIO) 
This group only receives a Brief Intervention (BI) that is recommended in 
response to risky alcohol use. Participants in this group will have 6 study visits 
as described below. 
 
Prevention Intervention Group 
Participants in this group also will get a Brief Intervention. In addition, they will 
get text messages as described in the next section. 
 
PI Overview. We have designed an adaptive monitoring intervention, delivered 
primarily through text messages and brief telephone calls that can provide 
extended prevention services for Veterans engaging in risky/hazardous alcohol 
use. These services address motivational issues and identify more effective ways 
to cope with stress and other factors that trigger unsafe alcohol use. The 
intervention is adaptive in two ways. Veterans who reduce alcohol use to safe 
levels will be placed in a monitoring track, which consists of tailored text 
messages (see appendix which contains examples of text messages to be used) 
and brief monthly telephone contacts. Conversely, Veterans who continue to use 
alcohol at hazardous levels will instead be placed in a track that provides tailored 
text messages and more frequent telephone calls. In addition to monitoring, these 
calls provide further prevention/brief intervention services to help the Veteran 
reduce alcohol use to non-hazardous levels and reduce the use of 
benzodiazepines and other potentially hazardous drugs.  Phone calls will be 
audio recorded to ensure adherence of the Research prevention counselors to the 
manuals.  We will remind subjects that calls are being recorded and they can 
refuse the recording, but still participate in the research call. 
 
The Wellpass system will automatically send text messages to Veterans either 
within messaging windows or at specific days and/or times depending on the goal 
of the message (e.g. appointment reminder vs. motivational message vs. just-in-
time support for at-risk Veterans).  On average, Veterans will receive between 1-14 
tailored text messages per week, depending on whether they are reducing 

 
HRPP Accepted:  03-2015 
 
 
 
 
 
 
Page 16 of 39 
 
drinking to below risky levels. In addition to sending tailored messages as 
described above, the SMS system will conduct on average weekly ecological 
assessments. (Ecological assessments are research questionnaires that happen 
in the “real world.” Ours will entail text messages such as: “Have you met the 
goal you set for yourself over the past week? Please respond 1 (not at all), 2 
(somewhat) or 3 (mostly).” These are different from the motivational messages 
and are used to track progress and inform phone counseling sessions.)  Veterans 
who are having trouble meeting their goals will receive more assessment 
messages. Veterans who initially reduce alcohol use to safe levels and are 
therefore placed in the monitoring track will transfer over to the more intensive 
prevention track if their alcohol use increases to risky levels at some point in the 
12-month intervention. Veterans whose alcohol or drug use escalates to DSM-V 
moderate to severe substance use disorder levels will be given a referral to 
specialty care and their progress will be evaluated at regular follow-up visits. 
 
Although the research counselors will be able to alter the messaging frequency 
and scripts based on the progress of the Veteran, decision support rules based 
on change will help guide messaging content and frequency to reduce research 
counselor burden. The system will alert research counselors to reductions in 
motivation or other red flags that may indicate the Veteran needs more support 
and will include proactive “help messages” for Veterans in the moment, which 
will trigger just-in-time messages and system alerts. In addition, Veterans can 
decide on the minimum and maximum number of messages they wish to receive 
per week.  The text message conversations between our research counselors and 
the study participant will also be recorded and kept in an encrypted database. 
 
All participants will be using their own cell phones during their participation in the 
study. We will instruct participants to inform us if they lose/damage their phone. 
However, we will not replace Veterans’ personal cell phones. If data security is 
breached, we will follow VA and HIPAA mandatory disclosure procedures. If data 
is lost but not breached (e.g. to server malfunction), we will assess the situation 
and alert the study sponsor. 
 
Study visits: 
In addition to the intervention, all participants will be seen at 3, 6, 9, 12, and 18 
months post baseline for research follow ups. Participants enrolled after 4/1/2019 
will only be seen at 3, 6, 9, and 12 months post baseline for research follow ups. 
These will be done at the CMCVAMC and will take approximately 1.5 hours. The 
schedule of assessments (all of which are for research purposes only and not 
part of standard care) is as follows: SCID and MINI (B); Blood samples (%dCDT 
and GGT) (B and 18m); Time Line Follow-Back, SIP (B, 3, 6, 9, 12, 18); Drug urine 
toxicology tests (B, 3, 6, 9, 12, 18); Self-efficacy, Coping, Social Support, 
Readiness to Change, pain, depression, quality of life (B, 3, 6, 9, 12, 18). 
 
October 2015 Amendment 
Because of the potential subjects were concerned about the “integrated” aspect 
of the study and how it might influence their clinical care, we submitted an 
amendment to remove the integration of the study and leaving research notes 
summarizing their status will no longer be the default.  We have contacted the 
DoD about this change, and they are fine with it.  The “integrated” nature was not 
an important piece.  At a yearly progress meeting for DoD grant recipients, most 
of the other SUD related project have made it a point to NOT integrate their 
interventions with veterans¹s medical care, as it sharply reduces recruitment 
rates. 
 

 
HRPP Accepted:  03-2015 
 
 
 
 
 
 
Page 17 of 39 
 
We have randomized 7 subjects.  We will notify them of the change, and re-
consent them. 
 
January 2016 Amendment - An amendment to the protocol has been made adding 
two sites to the study, with the CMCVAMC being the coordinating site. We are 
adding VA Pittsburgh as well as recruiting veterans not seen by the CMCVAMC at 
the University of Pennsylvania site. These sites are being opened up to address 
the poor recruitment numbers at the CMCVAMC site. 
 
There is also a change to where the data is housed. Now instead of data being 
housed on a secure server in the VA, it is housed on a secure server at the 
University of Pennsylvania. An Off-Site Storage form is included. Additionally, the 
Penn/PVAMC MOU is included. 
 
Paper based data will ultimately be kept at the CMCVAMC. However, electronic 
data will be combined and stored at Penn. The direct data entry can be done at 
Pittsburgh, CMCVAMC, and Penn, as long as there is internet access. 
 
July 2016 Amendment – An amendment to the protocol has been made to change 
the server back to the secure server at the VA. The reason for this is an issue with 
software and being able to get through the VA firewall for data entry.  
 
Paper based data will ultimately be kept at the CMCVAMC. Electronic data for 
Pittsburgh and CMCVAMC will also be stored at the CMCVAMC. Penn data will be 
stored at Penn as there is no way to access the VA server from outside the VA. 
 
January 2017 Amendment - Previously Veterans had to score a four or greater 
(females 3 or great) on the AUDC during the initial phone screen to be eligible to 
participate in the study. We have lowered this threshold to a score of two, as this 
score can still be indicative of regular/heavy alcohol use that would place 
Veterans prescribed chronic opiates at risk.  
 
According the NIAAA, any alcohol use with contraindicated medications (like 
opiates) is considered risky:  
 
Certain people should avoid alcohol completely, including those who: 
 
Plan to drive a vehicle or operate machinery 
  
 
Take medications that interact with alcohol 
  
 
Have a medical condition that alcohol can aggravate 
  
 
Are pregnant or trying to become pregnant 
 
(https://www.niaaa.nih.gov/alcohol-health/overview-alcohol-
consumption/moderate-binge-drinking) 
 
Risky drinking will be ascertained during the AUDIT-C. Usually when 
administering the AUDIT-C, individuals will give vague answers (i.e. “every now 
and then”) that require follow up questions. For instance, if a Veteran affirms a 
period of time when they drank 6+ drinks in the past year, the interviewer could 
ask, “When was the last time that happened?” When asking about consumption 
the interviewer will be able to ascertain if the Veteran’s level of consumption 
meets this threshold (questions two and three) either with the Veteran’s initial 
response or with follow up questions. 

 
HRPP Accepted:  03-2015 
 
 
 
 
 
 
Page 18 of 39 
 
 
We have also included language on how this will affect standard care through the 
BHL. As Veterans will be referred with lower levels of alcohol use (but still risky), 
after BHL triage it is possible that these Veterans will not receive a brief 
intervention.  
 
Further, our business office is moving away from using petty cash to compensate 
research participants. Instead, we are switching to the Greenphire ClinCard 
system. ClinCard functions like a Visa debit card, and money can be loaded on to 
the card remotely by study staff. Our protocol has been updated to describe the 
system, how it functions, how Veterans will be paid.  
 
March 2018 Amendment- We are changing the name of the study to something 
that sounds less threatening to Veterans who may fear losing their opiate 
prescription if they admit to drinking alcohol. We plan to change it to "Assisting 
Veterans in the Safe Use of Prescription Opioids." 
 
Further, we plan to change the inclusion criteria to include Veterans on 
prescription opiates for chronic pain regardless of whether or not they admit to 
drinking alcohol.  
 
As part of broadening the inclusion criteria we plan to add a third group to the 
adaptive intervention. We will enroll and randomize the Veterans who do not 
admit to drinking and place them in a monitoring category where we continue to 
assess them and if they admit to consuming any amount of alcohol we would 
then transfer them to the treatment arm into which they had been randomized. 
This change is a significant change to the study but does not change the aims or 
outcomes and it does not increase the risk. It is a change supported by the DOD 
as a way to increase enrollment and reach veterans that we think may be less 
truthful about their alcohol use out of fear that they will have their opiate 
prescriptions taken away. 
 
Following up those who initially deny drinking will provide important data for the 
VA. The yearly AUDIT screening appears to be underestimating the numbers of 
vets who are drinking alcohol.  If our data indicate that a significant percentage of 
those who deny drinking at the start of the study end up reporting drinking later 
in the follow-up, it will be in indication that at risk patients (i.e., those on opioid 
meds) are at risk due to underreporting of their drinking, which could be an 
unintended consequence of the current VA policies. 
 
We also will no longer be using the AUDIT-C.  
 
Additionally, we have decreased the total n for the study to 150 from all sites. That 
is, 200 subjects from all sites being randomized (with 150 participants drinking 
and entering TX phase and 50 participants not drinking (25 at CMCVAMC and 25 
at Penn). 
 
Moreover, there is a personnel change. Max Stern is no longer a Research 
Coordinator on this study.  
 
Lastly, SenseHealth has changed its name to Wellpass and the TRC has moved 
its location to 3535 Market Street 
 
At the time of this amendment, the following number of subjects have been 
randomized at the following sites: 

 
HRPP Accepted:  03-2015 
 
 
 
 
 
 
Page 19 of 39 
 
 
CMCVAMC: 42 
Pittsburgh VA: 3 
University of Pennsylvania: 6 
 
1.1 
Explain if and how the follow-up of subjects will occur. Research follow up visits will 
occur at 3, 6, 9, 12, and 18 months post baseline. For participants enrolled after 
4/1/2019 research follow up visits will occur at 3, 6, 9, and 12 months post 
baseline. Participants will complete a locator form at baseline to assist the study 
team in scheduling future research visits. Subjects can fill out as much or as little 
of this form as they want to. 
1.2 
Describe where, how and who will be conducting study procedures.  Research staff 
will administer the questionnaires, interviews, and collect urine samples from 
participants. CMCVAMC lab staff will collect blood. 
1.4. 
If a survey study, specify the estimated amount of time that subjects will need to 
complete the questionnaires/tools.  Baseline assessments will take approximately 
2.5 hours and follow up visits will take approximately 1.5 hours. 
1.5. 
If a blood draw, specify the amount of blood to be drawn in milliliters and in 
teaspoonfuls or tablespoonfuls and specify how often and where the blood will be 
drawn. Blood will be drawn in the CMCVAMC lab on the third floor by CMCVAMC 
lab staff. Two tubes of blood (4 teaspoons or 20 mL) will be collected, one tube (2 
teaspoons) for disialo carbohydrate-deficient transferrin (%dCDT) testing and the 
other (2 teaspoons) for gamma-glutamyl transferase (GGT) testing. The 
CMCVAMC lab will conduct the GGT testing. The second tube of blood will be 
centrifuged and have the serum extracted by the TRC (Treatment Research 
Center) at the University of Pennsylvania who will then prepare the serum for 
shipping to the MUSC for the %dCDT testing.  
 
2. 
Data Collection (Include all questionnaires and survey tools with the submission.) 
2.1. 
Provide 
2.1.1. 
the mode of data collection, e.g. telephone, in-person, questionnaire, 
interviews, Data will be collected via paper and stored in locked cabinets 
in MIRECC., and by direct data entry into the intranet web-based system 
housed on the CMCVAMC server.  It will be set up on the CMCVAMC 
server (https://vhaphimulhl2.v04.med.va.gov/dmumain/), and accessed 
through the CMCVAMC intranet)  
2.1.2. 
the precise plan for how data is to be collected or acquired Data will be 
collected in a private location by research staff. Data collected via paper 
will be entered into the computer by a research technician, coordinator, 
counselor, or clinical liaison. Data collected directly onto the computer 
will be reviewed by the research staff. The data will be identified using a 
four digit subject id number.  Subject ID numbers are generated from 
order enrolled in the study, starting with 1001. 
2.1.3. 
exact location where data will be collected, MIRECC interview rooms, 2nd 
floor 
2.1.4. 
exact location where data entry will take place. MIRECC interview rooms, 2nd 
floor. 
2.1.5. 
the “title” of individual(s) collecting the data and analyzing the data, e.g. 
principal investigator, research coordinator. PI, co-investigator, research 
coordinator, research technicians, data analyst 
2.2. 
Provide a time line for each aspect of the study. In the first six months of funding, we 
will accomplish the following tasks. 
 
First, we will complete work with Dr. Muench and Wellpass to prepare the 
text-messaging system for the study, and finalize all manuals for the 
prevention intervention (PI).   Dr. Muench serves as a consultant for 

 
HRPP Accepted:  03-2015 
 
 
 
 
 
 
Page 20 of 39 
 
Wellpass during the creation of the content of the study’s text messages. 
He will not have access to other data regarding text messages or 
information provided by Veterans. 
 
Second, we will pilot test methods to identify Veterans with chronic pain 
who are receiving daily opioid medication through CMCVAMC pharmacy 
records, and the screening procedures to detect risky alcohol use in these 
individuals.  
 
Third, we will complete training for the two research counselors in PI, and 
identify and begin training a third research counselor. Enrollment of study 
participants will commence in month 7 and will be completed by the end of 
Y3, based on a conservative recruitment rate of 10 participants per month.  
Given the 18-month follow-up period, all follow-ups will be completed by 
month 6 of Y5, which would leave 6 months to complete and submit the 
main outcome papers.      
2.3. 
Chart/Records/Data Review (retrospective and/or prospective) 
2.3.1. 
Provide the planned or approximate number of charts/records/data to be 
accessed 
2.3.1.1. CMCVAMC       
2.3.1.2. Other site       
2.3.2. 
Does this protocol employ an Honest Broker?  
YES  
NO 
2.3.2.1. If yes, provide name of individual.       
2.3.2.2. If no, explain who will access the charts/records.       
2.3.2.3. Describe from what database charts/records/data will be accessed. 
      
 
3. 
Future Use of Data and Re-Contact, if applicable. N/A 
3.1. 
If any of the participant’s data are going to be retained after the study for future 
research, the following information must be provided to the participant: 
3.1.1. Where will the data be stored?       
3.1.2. Who will have access to the data?       
3.2. 
If the subject is going to be re-contacted in the future about participating in future 
research, this must be specified.  Describe the circumstances under which the 
participant would be re-contacted whether within the VA or outside the VA.       
3.2.1. 
If subjects will receive aggregate study results at the end of the study, the 
informed consent document must contain this information. 
 
4. 
Specimen Collection 
4.1. 
Give the source of all specimens and whether they were collected for research, 
treatment or diagnosis. Blood and urine will be collected for research purposes and 
will be labeled with Subject code and date sample was collected.  Results from 
both the urine and blood tests will not be part of the subject’s electronic CPRS 
medical record. 
4.2. 
State where specimens will be stored, secured and when discarded.  Urine will be 
stored, tested, and discarded as per the CMCVAMC lab protocol. Blood to be 
tested for GGT will be stored, tested, and discarded as per the CMCVAMC lab 
protocol. Blood to be tested for %dCDT will be walked from the CMCVAMC lab to 
the Treatment Research Center (TRC) lab at the University of Pennsylvania, 3535 
Market Street, where it will be centrifuged and the serum extracted. The serum 
will be stored until enough samples are collected to send to the Medical 
University of South Carolina (MUSC). 
4.3. 
Explain how destruction of samples will be substantiated.  MUSC will provide 
notification of the destruction of samples. 
 
P. Genetic Testing, if applicable 

 
HRPP Accepted:  03-2015 
 
 
 
 
 
 
Page 21 of 39 
 
1. 
Explain if the study is looking for an association between a genetic marker and a specific 
disease or condition, but at this point it is not clear if the genetic marker has predictive value. 
       
1.1. 
The uncertainty regarding the predictive value of the genetic marker is such that studies 
in this category will not involve participant counseling. 
1.2. 
Describe if the study is based on the premise that a link between a genetic marker and 
a specific disease or condition is such that the marker is clinically useful in predicting 
the development of that specific disease or condition.        
1.3. 
Will the subject be notified of the results and the provision for genetic counseling?  
 Yes   
 No  
 N/A 
1.3.1. 
If yes, explain further.        
1.4. 
If biological specimens are used in this protocol, please respond to the following 
questions by checking the appropriate box:  
 
YES NO N/A 
a. Does the project involve genetic testing? 
 
 
   
b. Will specimens be kept for future, unspecified use? 
 
 
 
c. Will samples be made anonymous to maintain confidentiality?  
(Instructions: Note:  If there is a link, it is not anonymous.  Coding 
is not anonymous. 
 
 
 
d. Will specimens be destroyed after the project-specific use is 
completed? 
 
 
 
e. Will specimens be sold in the future? 
 
 
 
f. 
Will subjects be paid for their specimens now or in the future? 
 
 
 
g. Will subjects be informed of the results of the specimen 
testing? 
 
 
 
h. Are there any implications for family members based on 
specimen testing results? (If yes, they may be participants.) 
 
 
 
i. 
Will subjects be informed of results obtained from their DNA? 
 
 
 
1.5. 
Will specimens be de-identified?  
YES        
NO 
 N/A 
1.5.1. 
If yes, please describe the procedures to be used.   
1.5.2. 
Include at what point in the process the specimens will be de-identified.   
1.6. 
Describe what measures will be taken to minimize the following risks from breaches of 
confidentiality and privacy resulting from participating in THIS aspect of the research 
project:   
1.6.1. 
physical 
1.6.2. 
psychological  
1.6.3. 
financial  
1.6.4. 
social   
1.6.5. 
legal harm  
 
Q. Banking of Collected Specimens 
1. 
Will collected specimens be banked?  
YES   
NO   
N/A 
1.1. 
IF BANKING SPECIMENS, IT MUST BE AT AN APPROVED VA REPOSITORY. (For 
additional information, contact the IRB office.) 
1.2. 
If yes, specify the location where specimens will be banked.        
1.3. 
Explain how destruction of banked samples will be substantiated.       
 
R. Subject Recruitment (characteristics of the study population) 
1. 
Provide the planned or targeted enrollment at: 
1.1. 
CMCVAMC -   115 (90 undergoing treatment and 25 just being followed and not 
undergoing one of the treatment groups) 
1.2. 
Other sites -  60  (10 at VA Pittsburgh; 50 at Penn) 
1.3. 
Not applicable; chart review or use of previously collected data - 
 
 

 
HRPP Accepted:  03-2015 
 
 
 
 
 
 
Page 22 of 39 
 
2. 
Screening and/or Eligibility Requirements -  Inclusion/exclusion criteria are the same for 
screening before and after consent, however, some assessments used to determine 
final eligibility (such as the SCID and the MINI) are only administered once the Veteran 
comes to the lab (which occurs after a positive phone screen) 
2.1. 
Describe and provide justification for:  
2.1.1. 
Inclusion criteria: To be eligible for participation, Veterans must: (1) 
currently be receiving daily treatment with a prescription opioid for 
chronic pain, OR receive a daily prescription for opiate replacement 
therapy and have a chronic pain diagnosis; (2) be between the ages of 18 
and 75; (3) have a cell phone capable of receiving text messages; (4) and 
be willing to be in a study where they might receive text messages.  
 
If at some point during follow-up research visit, if a subject admits to 
drinking they will move on to the treatment arm that they were 
randomized to upon entry into the study. 
 
2.1.2. 
Exclusion criteria: Veterans will not be eligible if they: (1) meet DSM-V 
criteria for a moderate to severe alcohol or drug disorder (with the 
exception of nicotine abuse/dependence); (2) have a current psychotic 
disorder severe enough to require inpatient treatment; or (3) are 
participating in alcohol use treatment at the VA or elsewhere (with 
exception of screening and brief intervention at the VA); (4) are currently 
on palliative care or are being treated with opioids for cancer-related 
pain.  
 
2.2. 
List all screening and/or eligibility requirements. To be eligible for participation, 
Veterans must: (1) currently be receiving daily treatment with a prescription 
opioid for chronic pain OR receive a daily prescription for opiate replacement 
therapy and have a chronic pain diagnosis; (2) be between the ages of 18 and 75; 
(3) have a cell phone capable of receiving text messages; (4) and be willing to be 
in a study where they might receive text messages. Veterans will not be eligible if 
they: (1) meet DSM-V criteria for a moderate to severe alcohol use disorder (with 
the exception of nicotine abuse/dependence); (2) have a current psychotic 
disorder severe enough to require inpatient treatment; (3) are participating in 
AUD treatment at the VA or elsewhere (with exception of screening and brief 
intervention at the VA); or (4) are currently on palliative care or are being treated 
with opioids for cancer-related pain.  
 
2.3. 
Explain any special test or evaluations potential subjects may have to undergo before 
they are actually determined to be eligible for the study. The SCID and MINI will be 
administered to ensure that potential subjects do not meet DSM criteria for 
moderate to severe alcohol or drug disorders (except nicotine) or have a current 
psychotic disorder severe enough to require inpatient treatment.  If this is found 
during the research, we will refer the patient via a “warm hand-off” to either Dr.  
Oslin, co-investigator, or Dr. DePhilippis, clinical liaison. 
 
2.4. 
Not Applicable; subjects not recruited; chart review.  
 
 
3. 
If applicable, indicate what populations will be targeted for recruitment as participants. 
Check all that apply.   
Males 
 
Females 
 
Inpatients 
 
Outpatients 
 
VA Employees 
 

 
HRPP Accepted:  03-2015 
 
 
 
 
 
 
Page 23 of 39 
 
Non-English Speaking** 
 
Veteran Family members*** 
 
Non-Veterans*** 
 
Other (Specify) 
 
Not Applicable, chart review 
 
3.1. 
**For non-English speaking subjects - If an investigator proposes to use a participant 
population that does not speak or read English, a copy of the translated document, as 
well as the English version, needs to be forwarded to the IRB for approval.  Translator 
certification is also required.       
3.2. 
***If non-Veterans will be recruited for this study, explain why sufficient Veterans are not 
available to participate in the project [VHA Handbook 1200.5, paragraph 16a]. Veteran’s 
spouses/partners, caregivers, etc. are considered non-Veterans for the purposes of this 
study.            
3.3. 
***Has approval to recruit non-Veterans been received from the ACOS/R&D and 
Medical Center Director?   
3.3.1. 
 Not Applicable 
3.3.2. 
 Pending (Non-Veteran forms should be used. IRB office will obtain approval 
from ACOS/R&D and Medical Center Director.) 
 
4. 
Does this project target a specific race or ethnic group as participants?  
YES  
 NO    
If yes, check all that apply. 
 Race 
 
 
Ethnicity 
 
American Indian or Alaskan Native 
 
 
Hispanic or Latino 
 
Asian 
 
 
Not Hispanic or Latino 
 
Black or African American 
 
 
Other 
 
Native Hawaiian or other Pacific 
Islander 
 
 
 
 
Black, not of Hispanic origin 
 
 
 
 
White, not of Hispanic origin 
 
 
 
 
Other 
 
 
 
 
4.1. 
Provide justification why this/these group(s) was/were chosen.       
 
5. 
What is the age range of participants?  Check all that apply. 
Children (Under 18) Requires Waiver from CRADO (VHA 
Directive 2001-028, Research Involving Children) 
 
Young Adults (18-21) 
 
Adults (22-65) 
 
Seniors (Over 65) 
 
Over 89 
 
Not Applicable, chart review 
 
 
6. 
Are there specific reasons why certain populations (i.e., age, gender or ethnic groups) 
are excluded as participants?   
YES   
NO    
N/A 
6.1. 
If yes, specify reasons.       
 
7. 
Does the project require enrollment of the following classes of participants? 
 
YES 
NO 
a. Employees 
 
 
b. Individuals with impaired decision making capability 
 
 
c. Pregnant women 
 
 
d. Economically and/or educationally disadvantaged persons 
 
 
e. Prisoners 
 
 
f. 
Illiterate, limited, or no English language proficiency 
 
 
g. Terminally ill patients 
 
 

 
HRPP Accepted:  03-2015 
 
 
 
 
 
 
Page 24 of 39 
 
7.1. 
If applicable, what is the justification for including any of the above classes of 
participants in the project?        
7.2. 
If the project requires enrolling any of the above classes of participants describe any 
project-specific measures or special considerations, steps, or safeguards to ensure that 
these individuals are adequately protected.        
 
8. 
Describe the exact plan how subjects will be identified and recruited for the study. Refer to 
procedures section for details about recruitment. 
 
9. 
Discuss methods, e.g., referrals from physician offices, clinics, programs, or through 
advertisements and brochures. We will be using VISTA records to identify Veterans on 
daily opioids. We will notify their prescribing physician in order to contact the Veteran 
about the study. We will then send a letter to the Veteran telling the Veteran about the 
study. We will also accept referrals from the BHL. 
9.1. 
If using a clinic, be specific about who will identify the potential subject and how that 
information will be transmitted to the research staff.  
9.2. 
If snowball method will be used, discuss the process and how the first individuals will be 
recruited. n/a 
9.3. 
Describe how information will be disseminated to subjects, e.g. handouts, brochures, 
flyers and advertisements (include all recruitment materials with this submission). 
Potential participants will be sent a letter about the study. We will then follow the 
letter up with a telephone call. Because we are concerned that when we state the 
full name of the study, Veterans would worry that we are trying to take their 
opiate prescriptions away due to alcohol use, we do not include the title of the 
research project in the letter or phone calls.  We state only that it is a research 
project for Veterans prescribed opiates for chronic pain. 
9.4. 
Non-Veteran participants will be given a copy of the Notice of Privacy Practices. 
NOTE: 
 Every non-Veteran should sign VA form 10-0483, Acknowledgement of the Notice of 
Privacy Practices (ANOP) 
 Once the ANOP is signed, the research study staff must send the non-Veteran's name 
to the CMCVAMC Privacy Officer via encrypted e-mail.  The signed ANOP must be 
kept in the research study binder. 
 If an oral informed consent is used, the NOP should be sent to the non-Veteran via 
postal mail.  In addition, the research study staff must write a Note-to-File that the 
NOP was sent to the non-Veteran. 
 
10. 
Informed Consent 
10.1. Informed Consent will not be sought. 
 
10.2. Written informed consent from participants. 
 
10.3. Written informed consent from participants’ legally authorized representative (LAR) as 
required by VA policy and/or applicable state laws. 
 
10.4. Request Waiver of Documentation of Informed Consent 
 
10.5. List the title of the key personnel involved in the following activities: 
10.5.1. Person Obtaining Consent 
10.5.1.1. 
Provide the title(s) of individual(s) Research Coordinator, 
Research Technician, Research Counselor, Co-investigator 
and clinical liaison. 
10.5.1.2. 
Type of training received to perform this process HIPAA, CITI, 
Human Subjects, and consent training from PI. 
10.5.2. Pre-Recruitment Screening (the use of medical records and other data bases 
to determine populations and individuals eligible for the study), Research 
Coordinator, Research Technician, Research Counselor 

 
HRPP Accepted:  03-2015 
 
 
 
 
 
 
Page 25 of 39 
 
10.5.3. Recruitment Process (the process in which individuals are contacted and first 
introduced to the study and to the possibility of participating as subjects), 
Research Coordinator, Research Technician, Research Counselor 
10.5.4. Informed Consent Process (the process by which recruited subjects are fully 
informed about participating in the study and then formally give their voluntary 
consent for participating), Research Coordinator, Research Technician, 
Research Counselor 
10.5.5. Screening of Recruited Subjects (those activities in the protocol in which a 
final determination of eligibility of prospective subjects is made during the early 
phases of the study, using laboratory data, inclusion and exclusion criteria, and 
other person-specific information), Research Coordinator, Research 
Technician, Research Counselor 
10.5.6. Include the breakdown of each individual’s responsibilities: 
10.5.6.1. 
Principal Investigator, Monitor data and patient safety, ensure 
adequate training of personnel, review SAEs. 
10.5.6.2. 
Co-Principal Investigator, train research counselors on 
integrating intervention notes into CPRS and communicate 
with providers in the system, review SAEs in the absence of 
the PI, provide clinical assistance if a participant starts to 
decompensate in a research visit or if a patient reveals they 
are a threat to themselves or others. Co-investigator will 
also help obtain consent. 
10.5.6.3. 
Research Coordinator, ensure appropriate procedures are 
being followed for recruitment and consenting process, 
keep regulatory binder up to date; monitor accuracy of data 
collected and communicate with PI if there are any 
problems, communicate with IRB, recruitment, consenting, 
send informed consents and HIPAA authorizations to HIMS 
for scanning of documents, complete research visits. 
10.5.6.4. 
Additional research staff by title,  
Research Technicians – recruit, consent, send informed 
consents and HIPAA authorizations to HIMS for scanning of 
documents, perform research visits, schedule follow ups.  
 
Research Counselors – Recruit, consent, complete initial 
research visits (baseline), provide assessment, brief 
interventions, telephone monitoring and counseling phone 
calls, and monitor text messages.   
 
The clinical liaison will be monitoring the phone calls made 
by the research counselors to ensure adherence to the 
manual. Additionally, the clinical liaison will be able to 
obtain consent in the event the two research technicians are 
unavailable. The clinical liaison will also have the authority 
to refer participants to the ARU (alcohol response unit) for a 
higher level of care, if needed.   
 
Our research counselors are Masters level clinicians trained 
in recovery counseling and the administration of Brief 
Interventions. Our counselors received their training on how  
to administer a BI from clinicians within the BHL.  
10.6. Will informed consent be obtained from potential subjects prior to determining eligibility?         
YES     
NO     
N/A 
10.6.1. If no, provide justification and a HIPAA Waiver of Individual Authorization for 
Disclosure of Protected Health Information.  We will be using pharmacy 

 
HRPP Accepted:  03-2015 
 
 
 
 
 
 
Page 26 of 39 
 
records to identify Veterans who are prescribed opioids for chronic pain. 
This will be done prior to obtaining consent. Potential participants will 
answer screening questions prior to consent.  This is a tool used in the 
clinics that we will use as an initial screening tool.  The results of the 
screening will be coded to safeguard each Veteran’s PII/PHI. A 
spreadsheet located on our secured study drive will be used to pair 
Veteran data to the code. Potentially eligible participants who then sign a 
consent form will undergo more in-depth screening to determine 
eligibility for randomization. 
10.7. Define when a subject is enrolled into the study, e.g. after the subject signs the 
informed consent or after randomized to treatment. A subject is enrolled once they 
have been randomized.  
10.8. Describe:  
10.8.1. The process when informed consent will be obtained and protecting patients’ 
privacy. Consent will be obtained at the first research visit.  
10.8.2. Any waiting period between informing the prospective participant and obtaining 
consent. The Veteran will be told of the study via letter.  After the letter is 
sent potential subjects will receive a telephone call. However, obtaining 
consent will not occur until after the Veteran completes the VA’s 
standard alcohol assessment and some other screening questions over 
the phone.  
10.8.3. Steps taken to minimize the possibility of coercion or undue influence. 
Veterans will be explained clearly as to what is standard of care and what 
is research. They will be reminded over and over that research is 
voluntary. The consent will be reviewed at each research follow up visit 
as consenting is a process and not a one-time event.  
10.9. Provide the language  
10.9.1. used by those obtaining consent The language suggested by the VA 
consent template will be used. 
10.9.2. understood by the prospective participant or the legally authorized 
representative  It is assumed that the reading level understood by the 
population is 8th grade as that is considered the average reading level 
understood by Americans. 
10.10. Provide location where informed consent will be obtained. MIRECC interview rooms. 
 
11. 
Waiver or Alteration of Informed Consent Requirements/Waiver of Requirement to 
Obtain Documentation of Informed Consent 
11.1. Are you requesting a waiver or alteration of informed consent? (Check all that apply) 
11.1.1. No 
 
11.1.2. Yes; provide justification. 
        
11.1.3. Yes; for recruitment purposes only.   
 
11.2. Are you requesting a waiver to obtain documentation of informed consent? 
11.2.1. No 
 
11.2.2. Yes; provide justification. 
 
 
S. Compensation (The amount of compensation may not constitute an undue inducement to participate in 
the research.) 
1. 
Summarize any financial compensation that will be offered to subjects. Veterans that complete 
the baseline assessment prior to 4/1/2019 will be compensated $75, then $50 for each 
follow up research visit completed. Veterans that complete the baseline assessment 
after 4/1/2019 will be compensated $75 for the baseline visit, then $50 for the follow up 
research visits at 3, 6, and 9 months, then $75 for the final 12 month research follow up 
visit. 
 

 
HRPP Accepted:  03-2015 
 
 
 
 
 
 
Page 27 of 39 
 
2. 
Provide the schedule for compensation. Veterans that complete the baseline assessment 
will be compensated $75, then $50 for each follow up research visit completed (3 month, 
6 month, 9 month, 12 month, and 18 month). Veterans who are enrolled after 4/1/2019 
will be compensated $75 for the baseline visit, then $50 for the follow up research visits 
at 3, 6, and 9 months, then $75 for the final 12 month research follow up visit. 
2.1. 
Per study visit or session. $50 to $75 as described. 
2.2. 
Total amount for entire participation. $325 for participants enrolled prior to 4/1/2019; 
$300 for participants enrolled after 4/1/2019 
 
3. Explain how compensation will be provided via cash, voucher, gift card, etc.  Participants will be 
paid with the Greenphire ClinCard system. Participants will receive a card like a debit card 
(called a ClinCard), and money will be added after each study visit by study staff. Funds 
added to the card should be available immediately, however in some cases it may take 1 
business day.  The Veterans will sign and date a receipt when they receive the ClinCard 
that details how much they were compensated and that it was for research. Details of the 
research participation are not included in order to protect Veteran privacy. The receipt 
also does not contain mention that the participant was a Veteran. A copy of the receipt will 
be kept in the MIRECC office. The original paper copy will be secured in a locked cabinet 
in the PI’s offices at 3535 Market Street. The cabinets reside in a locked room, and entry to 
the offices is restricted by an ID card scanner. Another copy of the receipt will be sent to 
the Penn Office of the Treasurer, where it will be secured in a locked cabinet.  
 
4. If financial compensation will be prorated, explain the process.  Subjects will be paid after each 
completed assessment 
 
5. Not Applicable - 
 
 
T. Withdrawal/Early Withdrawal 
1. 
Describe how and when a subject may withdrawal from the study. A participant may 
withdraw at any time by simply indicating to anyone in the research team that they no 
longer wish to participate. Subjects will be provided with the Revocation of HIPAA 
Authorization form. 
 
2. 
Provide procedures for the orderly termination of participation by the participant and if any 
consequences would result from early withdrawal from the study.  Upon the participant 
informing us they no longer wish to participate, they will be removed from active status 
on the study. There are no consequences to early withdrawal. 
 
3. 
Explain if survival data is required.  If so, clarify how data will be obtained. N/A 
 
4. 
Not Applicable; subjects not recruited; chart review.  
 
 
U. Risk/Benefit Assessment 
1. 
Potential Study Risks 
1.1. 
Describe and assess all of the following risks that may be associated with the research: 
1.1.1. 
Physical There is a small chance of mild pain and swelling where the 
needle enters the skin and vein, bruising, infection and possibly fainting 
during the blood draws at baseline and 18 months. Texting (reading and 
sending) while driving may potentially lead to automobile accidents and 
bodily injury. 
1.1.2. 
Psychological There is a small chance that talking about their personal 
history can be embarrassing and/or lead to psychological discomfort. 
1.1.3. 
Social There is slight risk of embarrassment in terms of coming to the 
MIRECC suite for the research as MIRECC is geared towards research 
with mental illness and the stigma associated with mental illness. 

 
HRPP Accepted:  03-2015 
 
 
 
 
 
 
Page 28 of 39 
 
1.1.4. 
Economic There is no foreseeable economic risk to participation. 
1.1.5. 
Monetary The Veteran will not have to pay for treatment or participation 
but will need to pay for transportation to get to the research visits. 
1.1.6. 
Legal There is no foreseeable legal risk associated with the research. In 
Pennsylvania it is illegal to text while driving. 
1.1.7. 
Loss of confidentiality In all research, indeed in all situations, there is a risk 
of a loss of confidentiality. For instance, if the participant does not have a 
password on their phone, anyone could pick up their phone and be able 
to read their confidential messages. This is of incredible importance to 
the research team and confidentiality will be closely guarded.  We will 
guard participants’ information through secure servers (for web-based 
data) and in locked cabinets in with the MIRECC suite (for paper-based 
data). In addition, there is the risk that a person authorized to access the 
text messages might use them for an unauthorized purpose or disclose 
them to an unauthorized party. 
1.1.8. 
Assess the likelihood and seriousness of such risks. Low. 
1.1.9. 
Other N/A 
1.2. 
Specify what steps will be taken to minimize these risks. Research staff is trained in 
the proper use and storage of confidential information as well as not to disclose 
information over the phone. Research staff is also trained in proper interviewing 
methods and how to handle delicate questions (such as questions regarding 
PTSD, etc). We have clinicians on hand at the VA who can speak with any Veteran 
who has experienced discomfort as a result of the research visit. We will attempt 
to schedule research visits on days that the Veteran has another appointment 
scheduled to minimize travel costs. Participants will be reminded of the risk of 
texting while driving and will affirm that they will not engage in this behavior with 
their signature on the consent form. 
1.3. 
If methods of research create potential risks, describe other methods, if any, that were 
considered and why they will not be used.       
1.4. 
If chart review, breach of confidentiality is always a concern.  Specify what steps will be 
taken to minimize these risks.        
 
2. 
Potential Study Benefits 
2.1. 
Assess the potential benefits to be gained by the individual subject, as well as benefits 
that may accrue to society in general as a result of the planned work.  The project will 
yield considerable information on whether a prevention intervention can help 
Veterans who are receiving prescription opioids daily and engaging in risky 
drinking reduce their drinking to below risky levels and sustain those 
improvements for 18 months.  Information will also be obtained regarding 
moderators and mediators of intervention effects that are obtained. This 
information will be of direct value to VA treatment providers who are working with 
Veterans on prescription opioids and trying to reduce their risk for poor 
outcomes.  Ultimately, the availability of effective prevention interventions will 
benefit Veterans on prescription opioids who are engaging in risky drinking.  
2.2. 
If the subject does not receive any direct benefit, then it must be stated here and in the 
consent form.  The subject may not receive any direct benefit from the study. 
 
3. 
Alternate Procedures 
3.1 
Describe the alternatives available to the subject outside the research context.  The 
alternative is VA’s usual care which includes a brief intervention aimed at 
reducing drinking.  
3.2 
If none, state that the alternative is not to take part in this research study at all.       
 

 
HRPP Accepted:  03-2015 
 
 
 
 
 
 
Page 29 of 39 
 
V. Data and Safety Monitoring Board (DSMB) or Data Monitoring Committee (DMC) (All Phase III 
studies are required to have a DSMB.  However, the IRB has the right to require a DSMB with any 
study.) 
1. 
Will an independent DSMB or DMC oversee the project?  
YES     
NO 
N/A 
2.1. If yes, please provide contact information for the DSMB or DMC or Coordinating Center 
Representative and attach a copy of the charter. 
              
Name:                                              
Phone Number:        
             
Title:                                                     
E-mail:        
 
2. 
If a DSMB or DMC will not monitor this study, who will monitor this study? Check all that 
apply. 
 
 
 Principal Investigator 
 
 
 Sponsor  
 
 
 VA Cooperative Studies Program 
 
 
 Safety monitoring committee 
 
W. Data Monitoring (Monitoring plans describe how a monitor, independent of the study team, regularly 
inspects study records to ensure the study is adhering to the study protocol and applicable research 
regulations and CMCVAMC requirements.  Monitoring plans do not necessarily require the use of an 
independent Data and Safety Monitoring Board (DSMB).  Such independent boards are usually 
reserved for high-risk phase I studies, or large, multi-center phase III trials.  Federally funded studies 
may require the use of an independent DSMB.)   
1. 
Describe the data monitoring plan. (All protocols must have a data monitoring plan 
appropriate for the potential risks and the complexity of the study.)  Data will be collected using 
standardized forms and will only be identified with the study’s ID of the participant. The 
codes that link the name of the participant and the study ID will be kept confidential by 
the project coordinator in a secured cabinet at CMCVAMC. Most of the study data will be 
entered directly into databases as it is collected, via an intranet-based data entry system 
at the CMCVAMC.    Data forms that are not amenable to web-based data entry will be 
entered by the research staff, and discrepancies will be corrected by a supervisor, 
based on source documents. The quality of the data will be monitored once per month. 
The study’s statistician will analyze the data, using SAS and SPSS software.   
 
The primary outcome measure will be rates of risky drinking (i.e., more than 4 drinks at 
any one sitting or more than 14 drinks/week for men; more than 2 drinks at any one 
sitting or more than 7 drinks/week for women) within each follow-up period (e.g., months 
1-3, 4-6, 7-9, 10-12, 13-18), as determine by the TLFB. Secondary outcomes in the study 
will be self-reported frequency of heavy drinking days (TLFB), biological measures of 
alcohol use ((%dCDT and GGT), urine toxicology tests to assess other drug use, VA 
medical records of opioid overdoses, depression, and pain.  Outcome data will be 
analyzed using mixed effect regressions for continuous and categorical data (i.e., SAS) 
and various packages to examine mediation effects (i.e., MPlus).  The alpha level for the 
primary outcome will be set at 5%.  
 
Data quality will be monitored by random inspection of the completed forms by the 
research coordinator and any problems detected will be discussed with the PI.  The 
Research prevention counselors will receive standardized training on the interventions, 
which are all manualized.  Adherence to the manuals will be monitored using audiotapes 
and individual supervision provided by the clinical coordinator.  If drift is observed the 
counselors will be re-trained.  
 
Blind interim analyses of the data will be conducted at two points when 50 and 75% of 
the sample has been accrued. If the results show statistically overwhelming significant 
differences between groups, the study will be stopped (or one of the conditions 
stopped). 

 
HRPP Accepted:  03-2015 
 
 
 
 
 
 
Page 30 of 39 
 
 
2. 
Describe how protocol deviations, adverse events, serious adverse events, breaches of 
confidentiality, unanticipated adverse device effect (UADE), and unanticipated or 
unexpected problems will be reported to the CMCVAMC IRB and sponsor.  (Refer to the 
CMCVAMC IRB Standard Operating Procedure (SOP) Manual for reporting guidelines.)  In this 
study we will use the FDA definition of serious adverse events (SAEs).  SAEs will be 
systematically assessed at each clinic visit. Any SAE, whether or not related to study 
intervention, will be reported to the IRB and DoD. The initial SAE report will be followed 
by submission of a completed SAE report to both institutions.  In the event that a 
participant either withdraws from the study or the investigator decides to discontinue a 
participant due to SAE, the participant will be monitored by the investigator via ongoing 
status assessment until either a resolution is reached (i.e., the problem requiring 
hospitalization has resolved or stabilized with no further changes expected), the SAE is 
determined to be clearly unrelated to the study intervention, or the SAE results in death.  
Unanticipated problems involving risk to volunteers or others, serious adverse events 
related to participation in the study and all volunteer deaths related to participation in 
the study should be promptly reported by phone (301-619-2165), by e-mail 
(hsrrb@amedd.army.mil), or by facsimile (301-619-7803) to the U.S. Army Medical 
Research and Materiel Command’s Office of Research Protections, Human Research 
Protections Office. A complete written report should follow the initial notification. In 
addition to the methods above, the complete report can be sent to the U.S. Army Medical 
Research and Materiel Command, ATTN: MCMR-RPH, 504 Scott Street, Fort Detrick, 
Maryland 21702-5012. 
 
Additionally, SAE’s, protocol deviations, breaches of confidentiality and unanticipated 
or unexpected problems will be reported to the VA IRB within five days of discovery. 
2.1. 
Describe the management of information obtain that might be relevant to participant 
protections such as: 
2.1.1. 
Unanticipated problems involving risks to subjects or others – These will be 
reported to IRB within five days of discovery just as SAEs. 
2.1.2. 
Interim results – Will be report these at continuing review. 
2.1.3. 
Protocol modifications – Will be proposed to the IRB and practices will not 
change until the modifications are approved by the IRB. 
 
3. 
If applicable, define the plan for subjects if research shows results such as: 
3.1. 
Depression If depression appears to be an issue for a participant, and they are not 
already receiving treatment, the research staff will consult with Dr. Oslin for a 
consult with the participant and a possible referral.  
3.2. 
Suicide Participants who indicate any suicidal ideation will be evaluated by Dr. 
Oslin, Dr. Kranzler, or Dr. DePhilippis at the CMCVAMC. 
3.3. 
Abuse It is anticipated that the Veterans in our study will be engaging in alcohol 
or drug abuse. Dr. Oslin will be consulted in the event there is significant change 
to the Veterans’ use status. If the Veteran is in danger in terms of physical abuse 
or someone else is in danger due to the Veteran abusing them, Dr. Oslin will be 
consulted and the appropriate actions will be taken.  
 
4. 
Statistical Analysis 
4.1. 
Include statistical power calculations and the assumptions made in making these 
calculations. We consider the primary hypothesis of risky alcohol use, which 
compares PI and BIO groups on five repeated binary outcomes. We use the 
sample size formulae of Diggle et al. We expect to have a 20% dropout rate by 
month 18, and to see a risky drinking rate of 30%. On the assumption of a within 
subject correlation of 0.3 (resp. 0.4, 0.5), our sample size of 150 per group 
provides 80% power for a main effect difference of 30% versus 20% (resp. 30% 
versus 19%, 30% versus 18%) for the BIO versus PI groups. 

 
HRPP Accepted:  03-2015 
 
 
 
 
 
 
Page 31 of 39 
 
 
March 2018 Amendment:  Our original power analysis in the grant was very 
conservative, as it took into account multiple outcome measures and moderation 
and mediation analyses.  We had our statistician re-run the analyses, focusing on 
the main effect treatment group comparison with the primary outcome measure.  
If we calculate sample size needed to have 80% power to find a 15- percentage 
point difference in rates of risky drinking between the two conditions (e.g., 35% 
control condition vs. 20% experimental condition on risky drinking rate), we need 
a total of 136 to 162 veterans (depending on different estimates of the correlation 
between the outcome measure at different follow-up points).  If the effect is 
slightly larger (e.g., 20 percentage point difference), we only need 72 to 84 
veterans in total.  Therefore, with a combination of the new design we are 
confident that we will reach a sample size that will be sufficient to at least 
examine our primary outcome measure. 
 
4.2. 
Define plans for data and statistical analysis, including key elements of the statistical 
plan, stopping rules and endpoints.  
a. 
Primary objective: The responses for the primary hypothesis comprise 
five repeated binary measurements per participant indicating risky 
alcohol use over the follow-up points. Our main analyses will use mixed 
effects logistic regression models to compare the two groups on the 
rates of risky alcohol use. We expect that linear and quadratic trends will 
account for the patterns of use across time. If residual analyses suggest 
significant lack of fit, we will examine more general time trends using 
spline specifications. The main explanatory variable will be a binary 
factor indicating intervention group, together with terms for time trends, 
and for group by time interactions, if appropriate. Based on analyses of 
similar data, we expect that a random intercept model, possibly with an 
autoregressive repeated measures structure, should provide a good fit to 
the covariance structure of the repeated measures, although we will 
examine more general specifications, if necessary. The estimated 
regression coefficients for the group variable, and possibly for group by 
time interactions, will address our primary hypothesis. We will test 
whether estimated coefficients are different from zero, and will report 
estimates and approximate 95% confidence intervals.  
b. 
Secondary outcomes. For Hypothesis 1, we will use the same type of 
mixed effects logistic regression models as described above to compare 
the groups on urine toxicology tests for use of drugs other than alcohol. 
The frequency of heavy drinking is a count response, so we will use 
mixed effects Poisson regression models to compare two groups on the 
number of heavy drinking days in a week. The models will allow for over 
dispersion by including estimation of a variance inflation factor or, if this 
is insufficient, by considering mixed effects negative binomial regression 
models. Some subjects have more days without heavy drinking than 
would be expected under a Poisson model. To account for this, we will fit 
mixed effects zero inflation models. If levels of heavy drinking are too low 
even for zero-inflation models, we will compare the intervention groups 
on the absence or presence of any heavy drinking days in a week, using 
mixed effects logistic regression models. Measures of depression and 
pain, and biological measures of alcohol use, will be continuously 
distributed, and will be compared across the groups using mixed effects 
linear regression models, after transformation of these responses to 
approximate normality. The explanatory variables, time trends, and 
covariance structure for these secondary analyses will be chosen as 
described for the primary hypothesis. 

 
HRPP Accepted:  03-2015 
 
 
 
 
 
 
Page 32 of 39 
 
 
We will follow a similar approach for testing Hypothesis 2, using data 
generated by electronic medical records to count the number of opioid 
overdoses for each participant through the course of the trial. We expect 
low rates of OD, so we will compare the groups on the rates of having an 
OD via a logistic regression model. If the numbers of OD are sufficiently 
high, we will compare the groups using Poisson or Negative Binomial 
models for the total number of OD per participant across the trial.  
c. 
Moderator analyses.  We will address Hypothesis 3 using moderator 
analyses extending the analyses described above. The models will be 
extended to include the main effect of measures of high risk status, 
including higher prescription opioid doses, co-occurring benzodiazepine 
use, poor social support, and low readiness for change, together with the 
interaction effect of these terms with the intervention group factor. If the 
inclusion of a given interaction term in a model yields significantly better 
model fit, this provides evidence for moderation. Data plots and the 
estimated regression coefficients for the intervention, the moderator, and 
their interaction will explain the nature of the moderating effect. 
d. 
Mediation analyses. We will address Hypothesis 4 through mediation 
analyses, with changes in readiness for change, self-efficacy, and coping 
as mediators. Here, we will follow the methods described in (105) First, to 
address the time course of these mediators separately from outcome, we 
will use the same mixed effects model approach described above. 
Second, to address whether these mediators predict later risky alcohol 
use, we will conduct a further series of mixed effects model analyses, 
using lagged versions of the mediator variables as time-varying 
covariates, together with the intervention and the other explanatory 
variables described above. We expect that the intervention effects on the 
mediators and on the outcomes will occur gradually over time, so we will 
use a latent growth curve mediation model to address the joint behavior 
across time. As suggested by MacKinnon, we will also examine the fit of 
other types of models, to obtain a more complete assessment of the 
intervention’s direct and indirect effects on outcomes. 
e. 
Missing values. The mixed effects models will provide valid estimates of 
treatment efficacy if the missing data meet the ignorable missingness 
assumption. We will conduct further analyses to assess the sensitivity of 
our inferences to possible violations of this assumption. First, we will 
use pattern mixture models (104), defining a categorical variable 
describing the main patterns of missing data, and including it as a main 
effect and interaction effect with intervention group in the modes for 
primary outcomes. Significant differences in the estimated intervention 
effects across levels of the pattern variable suggest one type of non-
ignorable missingness. Second, shared parameter models (104) assume 
that the repeated responses and repeated binary indicators of 
missingness have possibly correlated random effects, and significant 
correlation indicates possible non-ignorability. Finally, semiparametric 
regression models (106) use inverse probability weighting to extend the 
validity of GEE models, and provide a different type of sensitivity 
analysis for the mixed effects models. All three approaches require 
certain model assumptions, so we will compare the results of the 
analyses over a range of such assumptions.     
 
X. Privacy and Confidentiality (Privacy refers to persons and to their interest in controlling the access 
of others to themselves.) (Confidentiality refers to protecting information from unauthorized disclosure 
or intelligible interception.) (Investigator should contact the Privacy Officer for additional details.) 

 
HRPP Accepted:  03-2015 
 
 
 
 
 
 
Page 33 of 39 
 
1. 
Indicate the type of data that will be received by the Principal Investigator.  Check all 
that apply. 
1.1. 
 De-identified – Without any identifiers that could link the data to a specific 
participant.  (Contact Privacy Officer for assistance.  If data is coded, it is not 
considered de-identified.) 
1.2. 
 Identified – Linked to a specific participant by identifiers sufficient to identify          
participants.  (See HIPAA and Common Rule Criteria for list of identifiers.) 
1.3. 
 Coded – Linked to a specific subject by a code rather than a direct identifier. If coded 
is checked, specify:  
1.3.1 
Explain who will maintain the link or code.  The research coordinator will 
maintain the link/code.  Codes will be assigned during the initial 
screening phone call. The spreadsheet linking Veteran data to the code 
will be located on our secure study drive. Thus all data collected from 
screening onward will be protected by the code. 
1.3.2 
Describe who will have access to the link or code. Research staff will have 
access to the codes. 
1.3.3 
Provide exact details for how the data is coded. Participants will have a 
subject identification number that is a four digit number. We will use 
numbers sequentially, beginning with 1001.  
 
2. 
Does the project require the use of existing Protected Health Information (PHI) from a 
database, medical records, or research records?  
YES     
NO    
N/A 
2.1. 
If yes, 
2.1.1. 
Specify the source of the existing PHI VISTA Pharmacy and MHA records. 
(The Mental Health Assistant (MHA) is a software package for VistA. MHA 
was developed to create an effective and efficient tool for mental health 
clinicians and their patients to use for the administration and scoring of 
assessment instruments and interviews that are not available elsewhere 
in CPRS or VistA) 
2.1.2. 
Indicate the specific data elements/identifiers (e.g., name, address, phone 
numbers, etc.) on the below table. Name, address, phone number, opiate 
prescription status.  
2.2. 
If the study uses an existing database/data warehouse, 
2.2.1. 
Provide a description of the database/data warehouse.        
2.2.2. 
Make clear who is responsible for maintaining it.       
2.2.3. 
Cite any relevant Standard Operating Procedures (SOP) for the database/data 
warehouse.         
2.2.4. 
Provide a copy of the SOP.    
 
3. 
Will PHI be collected prior to obtaining informed consent?  
YES     
NO    
N/A 
3.1. 
If yes, complete and provide a HIPAA Waiver of Individual Authorization for Disclosure 
of Protected Health Information with this submission. 
 
4. 
HIPAA Identifiers - Indicate the PHI that will be collected from project participants 
directly or indirectly. 
4.1. 
 Name 
 
4.2. 
 All geographic subdivisions smaller than a State, including street address, city, 
county, precinct, zip code, and their equivalent geocodes, except for the initial three 
digits of a zip code if, according to the current publicly available data from the Bureau of 
the Census 
4.3. 
  All elements of dates (except year) for dates directly related to an individual, and all 
ages over 89 and all elements of dates (including year) indicative of such age, except 
that such ages and elements may be aggregated into a single category of age 90 or 
older.  
4.3.1. 
 Birth Date 
 
 Date of Death 

 
HRPP Accepted:  03-2015 
 
 
 
 
 
 
Page 34 of 39 
 
4.3.2. 
 Discharge date 
 Admission date 
4.3.3. 
 Appointment Dates 
 Other Dates (e.g. lab tests, x-rays, MRI, etc.)       
4.4. 
 Telephone numbers 
 
4.5. 
 Fax numbers 
4.6. 
 Electronic mail addresses 
 
4.7. 
 Social Security/Medical Record Number 
4.8. 
 Health plan beneficiary numbers 
 
4.9. 
 Account Numbers 
4.10. 
 Certificate/license numbers 
4.11. 
 Vehicle identifiers and serial numbers, including license plate numbers 
4.12. 
 Device identifiers and serial numbers 
4.13. 
 Web universal resource locators (URLS) 
4.14. 
 Internet protocol (IP) address numbers 
4.15. 
 Biometric identifiers, including fingerprints, voiceprints, audio recordings 
4.16. 
 Full-face photographic images and any comparable images 
4.17. 
 Any other unique identifying number, characteristic, or code 
4.18. 
 Personal and Family History 
 
4.19. 
 History and Physical Examination 
 Progress Notes 
4.20. 
 Discharge Summary(ies) 
 
 Photographs, videotapes, other  images 
4.21. 
 X-Ray 
 
 HIV (testing or infectious disease) records 
4.22. 
 Diagnostic/Laboratory tests 
 
 Sickle cell anemia 
4.23. 
 Drug Abuse Information 
 
 Behavioral Health notes 
4.24. 
 Alcoholism or Alcohol Use 
 
 Operative Reports 
4.25. 
 Billing records 
 
 Medication List 
4.26. 
 Health Summary Reports  
 
 Anatomic Pathology Report 
4.27. 
Other Records:       
 
5. 
Will participants be contacted from existing PHI?  
YES    
NO    
N/A 
5.1. 
If yes, clearly explain how participants will be contacted (NOTE: this would be the same 
information as listed under section R.8 identification and recruitment of subjects).  We 
will use VA VISTA pharmacy records to identify Veterans who are currently being 
prescribed daily opioid medication for the treatment of chronic pain. Veterans 
already in addiction treatment will then be excluded from the study. For the 
remaining patients, the prescribing physicians will be contacted, and notified of 
our intention to contact the patient to tell him/her about the research study. We 
will then contact patients via letter to describe the research study and follow-up 
with a telephone call to invite them to participate.  
 
Most often, the BHL refers Veterans to the study team who are engaging in risky 
drinking, but without the symptomology or levels of consumption that would 
warrant a referral to a higher level of care, such as the ARU. If during the triage 
assessment the BHL software flags a Veteran for risky drinking, but not a referral 
to a higher level of care, then the technician will refer them to the study team.  
 
6. 
Provide the titles of the exact individuals who will have access to the collected data.  PI, 
Research Coordinator, Research Technicians, Data Analyst, Co-Investigator, and 
Clinical Liaison  
6.1. 
Explain why these individual will have access to this data.  The PI has access for data 
safety monitoring. The research coordinator will be collecting and monitoring the 
data for adherence/accuracy/safety. The Research Technicians will be collecting 
the data and answering any queries that come up. 
 
Y. Information Security  (Contact the Information Security Officer for additional assistance regarding 
confidentiality (storage/security) of research data.) 
1. 
Provide the precise plan how data is to be collected or acquired (repeat the same information 

 
HRPP Accepted:  03-2015 
 
 
 
 
 
 
Page 35 of 39 
 
as listed under “Data Collection” section of this form.  Data will be collected in a private 
location by research staff. Data collected via paper will be entered into the computer by 
the researcher. Data collected directly onto the computer will be reviewed by the 
research staff. The data will be identified using a four digit subject id number. Phone 
calls between study participants and research counselors will be recorded using a 
digital recorder. The audio files created from these recordings will be stored on the VA 
server (https://vhaphimulhl2.v04.med.va.gov/dmumain/). 
 
January 2016 amendment to change data storage location: Due to a system failure of the 
MIRECC DMU at the VA, an amendment to this ongoing protocol was made to change 
where data was stored (as detailed above and in below sections that describe data 
storage).  This is being done with the input from the ISO and PO, and under the current 
PENN-VA MOU on data storage (even though there is a separate PENN component to 
our study). The need to use the DMU at Penn is critical because  the DMU provides more 
oversight and protection over the safety and integrity of the data, being able to capture 
every entry and any changes made. It also keeps the data on a highly secured server to 
protect not only against hacking, but against catastrophic loss of data. 
 
We will re-consent current subjects. 
 
We also note that there was no data loss to due to the VA DMU failure. 
 
July 2016 Amendment – An amendment to the protocol has been made to change the 
server back to the secure server at the VA. The reason for this is an issue with software 
and being able to get through the VA firewall for data entry.  
 
2. 
Provide a listing of the exact research data that will be stored, including but not limited to 
signed, original informed consent and HIPAA authorization forms, case report forms, etc.  
Consents, HIPAA authorization, CRFs, blood and urine results, recordings from 
counseling phone calls.  Being entered into DMU will be: dates of research visits, 
responses to questionnaires and interviews, as well as urine specimen and blood test 
results. 
 
3. 
Indicate how project’s research data (original and all copies) will be stored and provide 
corresponding security systems.  Consents will be kept in binders in locked cabinets 
within the MIRECC suite at CMCVAMC. Paper Case Report Forms will be kept in a locked 
drawer in a locked office separate from the consents. All data will be entered into a web-
based data entry system on a VA server.  In addition, if a Veteran is in the PI condition 
and has consented to audio recording of their counseling session, we will be using 
digital recorders to capture the call, and then we will save the audio files of the call to 
the server (https://vhaphimulhl2.v04.med.va.gov/dmumain/). 
 
4. 
Provide exact location where research data (original and all copies) will be stored and secured.   
Data will be stored in the MIRECC Suite, 2nd floor of Bldg 2. Veteran contact data for 
follow up and tracking purposes will be kept on the research server “McKay – PI with 
Vets.” 
 
5. 
Explain how data is to be transported or transmitted from one location to another.  Phone 
numbers and participant id numbers will be transmitted to Wellpass through their 
website (www.wellpass.com) which will be accessed using a secure CMCVAMC 
computer and network. Participant id numbers, serum samples, session dates, and 
blood test results will be transferred to/from MUSC via a password-protected 
spreadsheet on an encrypted USB device.  Data stored on DMU can be entered from the 
location at which the data is collected. It is transmitted via internet portal. 

 
HRPP Accepted:  03-2015 
 
 
 
 
 
 
Page 36 of 39 
 
5.1. 
Informed Consent discloses PHI transported or transmitted off-site.  
YES  
NO  
N/A 
5.2. 
HIPAA Authorization discloses entities to whom PHI will be transported or transmitted.  
YES  
NO  
N/A 
5.2.1. 
List all entities or individuals outside CMCVAMC to whom data is to be 
disclosed, and the justification for such disclosure and the authority. Blood 
samples will be sent to MUSC for analysis and will be coded as well. 
Wellpass (the company that created the SMS text messaging portion of 
the intervention) will have PHI – telephone numbers – of people 
randomized to receive the intervention. The Greenphire ClinCard system 
collects and uses PHI to pay participants. 
5.3. 
If yes, list the exact data that will be transmitted.  Blood samples with session dates 
and times and subject ID numbers will be sent to MUSC. Wellpass will receive 
phone numbers in order to conduct the text messaging portion of the 
intervention. 
5.4. 
If yes, explain how data will be protected during transmission outside of CMCVAMC.  
Data will be coded with a four digit number.   The link to the code will remain at 
the VA and not used during data analysis 
5.5. 
Off-site, provide exact location University of Pennsylvania, 3535 Market Street, 
Philadelphia, PA 19104; Medical University of South Carolina, 67 President Street, 
Charleston, SC 29425; Wellpass, 175 Varick Street, Floor 6, New York, NY; 
Greenphire, 1012 W. 8th Avenue, King of Prussia, PA, 19406  10014 (If off-site, 
attach at least one of the following.) 
5.5.1. 
Data Use/Transfer Agreement 
YES    
NO    
N/A 
5.5.2. 
Off-Site Storage/Transfer of Research Data 
YES    
NO    
N/A 
5.5.3. 
Memorandum of Understanding 
YES    
NO    
N/A 
5.5.4. 
(Note: VA data disclosed to a non-VA investigator at an academic affiliate for 
research purposes needs to be approved by the Under Secretary of Health or 
designee.) 
 
6. 
List who is to have access to the data and how they are to access it (anyone who has access 
to the data is responsible for its security).  PI, co-PI, research coordinator, research 
technician, research counselor, data analyst 
 
7. 
Describe who is to have access and be responsible for the security of the information (e.g., the 
Coordinating Center, the statistician, and PI who has ultimate responsibility).  PI, co-PI, 
research coordinator, research technician, research counselor, clinical liaison, data 
analyst 
 
8. 
Provide mechanisms used to account for the information.  There is an electronic record of 
changes to the data that is stored in the web-based CMCVAMC DMU system. The 
research coordinator will be responsible for the day-to-day keeping of the information. 
 
9. 
Give security measures that must be in place to protect individually identifiable information if 
collected or used.  PII will be kept locked at the MIRECC Suite, Building 2. 
 
10. 
How and to whom a suspected or confirmed loss of VA information is to be reported.    
10.1. The Investigator will notify the Information Security Officer, Privacy Officer, IRB, 
Associate Chief of Staff for Research and Research Compliance Officer within 
one hour of a suspected or confirmed loss of VA information. 
 
11. 
Identify any circumstances that may warrant special safeguards to protect the rights and 
welfare of subjects who are likely to be vulnerable including, but not limited to, those subjects 
who may be susceptible to coercion or undue influence, and describe appropriate actions to 
provide such safeguards.  N/A 

 
HRPP Accepted:  03-2015 
 
 
 
 
 
 
Page 37 of 39 
 
 
12. 
Electronic PHI will be stored on the following: 
12.1. CMCVAMC desktop computer with password protection and/or encryption. 
YES  
NO  
N/A 
12.1.1. 
If yes, identify where the desktop is located.       
12.2. CMCVAMC secure server.  
YES  
NO  
N/A 
12.2.1. 
If yes, identify the CMCVAMC server. MIRECC research server “McKay - PI 
with Vets” https://vhaphimulhl2.v04.med.va.gov/dmumain/ 
12.2.2. 
External drive that is password protected and/or encrypted.  
YES  
NO  
N/A 
12.2.2.1. If yes, identify the external drive.       
12.3. Off-Site server 
YES  
NO  
N/A (If off-site, attach at least one of the following.) 
12.3.1. 
Provide exact location and the name of the off-site server 
12.3.2. 
Data Use/Transfer Agreement 
YES  
NO  
N/A 
12.3.3. 
Off-Site Storage/Transfer of Research Data 
YES 
NO 
N/A 
12.3.4. 
Memorandum of Understanding 
YES    
NO    
N/A 
 
13. 
Explain how data is to be transported or transmitted from one location to another.  Phone 
numbers and participant id numbers will be transmitted to Wellpass via a password-
protected spreadsheet on an encrypted USB device. Participant id numbers, serum 
samples, session dates, and blood test results will be transferred to/from MUSC via a 
password-protected spreadsheet on an encrypted USB device. Electronic research data 
will be transmitted to the VA server via a web-based data entry system on the VA’s 
intranet. 
 
14. 
Informed Consent discloses PHI transported or transmitted off-site.  
YES  
NO  
N/A 
 
15. 
HIPAA Authorization discloses entities to whom PHI will be transported or transmitted.  
YES 
NO  
N/A 
 
16. 
List all entities or individuals outside CMCVAMC to whom data is to be disclosed, and the 
justification for such disclosure and the authority. Blood samples will be sent to MUSC for 
analysis and will be coded as well. Wellpass (the company that created the SMS text 
messaging portion of the intervention) will also have PHI – telephone numbers – of 
people randomized to receive the intervention. The Greenphire ClinCard system collects 
and uses PHI to pay participants. 
 
17. 
Clarify what protection exists for a database.  The web-based DMU system is double 
password protected and on a secure VA server. 
17.1. Data is stored: 
17.1.1. 
With identifiers - 
YES   
NO 
17.1.2. 
Coded - 
YES   
NO 
17.1.3. 
De-Identified -  
YES   
NO 
17.1.4. 
Provide the exact list of identifiers that will be stored. Dates of research 
visits 
 
18. 
Describe the plan for protecting research data from improper use or disclosure.  All staff will 
be sufficiently trained on the proper use of data and how to guard against improper use 
or disclosure. 
18.1. The Investigator must notify the Information Security Officer, Privacy Officer, IRB, 
Associate Chief of Staff for Research and Research Compliance Officer within one hour 
of the improper use or disclosure. 
 
19. 
Is there a plan to apply for a Certificate of Confidentiality?  
YES    
NO    
N/A 

 
HRPP Accepted:  03-2015 
 
 
 
 
 
 
Page 38 of 39 
 
19.1. If yes, provide a copy of the certificate with this application or to the IRB Office as soon 
as received.   
 
20. 
Record Retention:   
20.1. The required records, including the investigator’s research records, must be retained 
until disposition instructions are approved by the National Archives and Records 
Administration and are published in VHA's Records Control Schedule (RCS 10-1).  VHA 
Handbook 1200.05 §26.h  
20.2. Until a schedule for local research records is published, ALL records including 
identifiers must be retained.” ORO/ORD Guidance on Informed Consent Form 
Modifications Addressing VA Record Retention Requirements (July 23, 2009)  
20.3. If there are additional procedures for record retention, explain further.  N/A 
 
Z. Qualification of the Investigators 
1. 
Provide a description of the qualifications of each investigator/co-investigator and their specific 
role in the study.   
 
James McKay, PhD, PI: Dr. James McKay is a Professor of Psychology in Psychiatry at the 
University of Pennsylvania. He is the Director of the Penn Center on the Continuum of Care in 
the Addictions, and the Director of the CMCVAMC Center of Excellence in Substance Abuse 
Treatment and Education (CESATE). Dr. McKay received a Ph.D. from Harvard University, and 
completed a clinical psychology internship at McLean Hospital and a postdoctoral fellowship in 
treatment outcome research at Brown University.  
 
He is the recipient of an Independent Scientist (K02) Award from the NIDA, as well numerous 
research grants from NIDA and NIAAA, including a new NIAAA-funded Center on Adaptive 
Treatment for Alcoholism. He is also the author of “Treating Substance Use Disorders with 
Adaptive Continuing Care” (2009; American Psychological Association). 
 
Dr. McKay’s work has included evaluations of continuing care treatments for alcohol and 
cocaine use disorders, evaluations of the ASAM placement criteria, development of adaptive 
interventions for substance use disorders, and the identification of factors over time that predict 
relapse following substance abuse treatment.  
 
His current research efforts are focused on the development and evaluation of flexible 
approaches to the management of addiction, which include the use of the telephone to provide 
extended continuing care and incorporate adaptive algorithms and the client’s preferences in 
the selection of treatment interventions. 
 
Dr. McKay’s role in the study is as the ultimate responsible party that the research and 
intervention is done as described, that data integrity is upheld, and that the safety of 
participants is upheld. It is also the responsibility of the PI to ensure adequate personnel is 
working on the study and that each has adequate training to perform their duties. 
 
David Oslin, MD, co-PI: Dr. David Oslin is Associate Professor of Psychiatry at the 
CMCVAMC and the University of Pennsylvania Medical Center. Dr. Oslin is the Director of the 
VISN 4 Mental Illness, Research, Education, and Clinical Center (MIRECC) and the Associate 
Chief of Staff for Behavioral Health at the CMCVAMC. The MIRECC and Behavioral Health 
Laboratory support research on comorbidity and integrated care, respectively, and facilitate a 
number of research projects for post-doctoral fellows and faculty. Dr. Oslin is the author of over 
80 research publications and 31 chapters, books, or editorials. 
 
Dr. Oslin’s research interests include studies access to behavioral health intervention care, 
treatment outcomes for addictive disorders, and pharmacogenetics of addiction treatment. 

 
HRPP Accepted:  03-2015 
 
 
 
 
 
 
Page 39 of 39 
 
Specific projects include an adaptive treatment study of naltrexone to develop strategies for 
maintenance treatment and for non-response to treatment.  
 
Two studies examine endophenotypes associated with alcohol craving, subjective high and 
intoxication. Two other studies explore improving access to treatment for alcohol misuse with a 
focus on brief interventions and care management services.  
 
Additionally, Dr. Oslin continues research on the implementation and dissemination of evidence 
based practices for integrating primary and mental health care. 
 
For those participants who choose to allow research information to be entered into CPRS, Dr. 
Oslin will be responsible for training research counselors on integrating intervention notes into 
CPRS and communicate with providers in the system, review SAEs in the absence of the PI, 
and provide clinical assistance if a participant starts to decompensate in a research visit or if a 
patient reveals they are a threat to themselves or others. 
 
2. 
If applicable, the Principal Investigator must identify a qualified clinician to be responsible for all 
study related healthcare decisions. David Oslin, MD. 
 
3. 
PI should submit a current, dated CV with each new initial review.