Optimizing E-interventions for Alcohol Use: Do Common Factors Apply?
Phase: NA
Conditions: Alcohol Drinking in College
Sponsor: Wayne State University

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
 
 
 
 
 
Optimizing e-interventions for Alcohol Use: Do 
Common Factors Apply? 
NIAAA Grant Number: R21AA023660 
Principal Investigator: Emily R. Grekin, Ph.D. 
NIAAA Program Official: Brett Thomas Hagman 
Draft or Version Number: 1 
December 5, 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
1 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
 
 
STATEMENT OF COMPLIANCE 
 
The study will be conducted in accordance with the International Conference on 
Harmonisation guidelines for Good Clinical Practice (ICH E6), the Code of Federal 
Regulations on the Protection of Human Subjects (45 CFR Part 46), and the NIDCR 
Clinical Terms of Award. All personnel involved in the conduct of this study have 
completed human subject protection training. 
 
SIGNATURE PAGE 
 
The signature below constitutes the approval of this protocol and the attachments, and 
provides the necessary assurances that this trial will be conducted according to all 
stipulations of the protocol, including all statements regarding confidentiality, and 
according to local legal and regulatory requirements and applicable US federal 
regulations and ICH guidelines. 
 
Principal Investigator or Clinical Site Investigator: 
 
 
 
Signed: 
Date: 5-21-19 
Name: Emily R. Grekin, Ph.D. 
Title: Principal Investigator 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
2 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
TABLE OF CONTENTS 
PAGE 
STATEMENT OF COMPLIANCE ................................................................................................ 1 
TABLE OF CONTENTS .............................................................................................................. 2 
LIST OF ABBREVIATIONS ......................................................................................................... 4 
PROTOCOL SUMMARY ............................................................................................................. 5 
1 
INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE ......... 7 
1.1 
Background Information .......................................................................................... 7 
1.2 
Potential Risks and Benefits ................................................................................... 7 
1.2.1 Potential Risks .......................................................................................... 10 
1.2.2 Potential Benefits ...................................................................................... 10 
2 
OBJECTIVES ................................................................................................................... 11 
2.1 
Study Objectives/Outcome Measures ................................................................... 11 
2.1.1 Primary ...................................................................................................... 11 
2.1.2 Secondary ................................................................................................. 11 
3 
STUDY DESIGN .............................................................................................................. 12 
3.1 
Subject Inclusion/Exclusion Criteria ...................................................................... 15 
3.2 
Strategies for Recruitment and Retention .............................................................. 16 
3.3 
Treatment Assignment Procedures ....................................................................... 16 
3.3.1 Randomization Procedures ....................................................................... 16 
3.3.2 Masking Procedures (if applicable) ............................................................ 16 
3.4 
Subject Withdrawal ............................................................................................... 16 
3.4.1 Reasons for Withdrawal ............................................................................ 17 
3.4.2 Handling of Subject Withdrawals or Subject Discontinuation of Study 
Intervention ............................................................................................... 17 
3.5 
Premature Termination or Suspension of Study .................................................... 17 
4 
STUDY INTERVENTION .................................................................................................. 22 
4.1 
Study Behavioral or Social Intervention(s) Description .......................................... 22 
4.2 
Administration of Intervention ................................................................................ 23 
4.3 
Procedures for Training Interventionists and Monitoring Intervention Fidelity ........ 24 
5 
STUDY SCHEDULE ......................................................................................................... 25 
5.1 
Screening ............................................................................................................. 26 
5.2 
Enrollment/Baseline .............................................................................................. 26 
5.3 
Follow-ups (1 and 3 month visits) .......................................................................... 28 
6 
ASSESSMENT OF SAFETY ............................................................................................ 30 
6.1 
Specification of Safety Parameters ....................................................................... 30 
6.1.1 Unanticipated Problems ............................................................................ 30 
6.1.2 Adverse Events ......................................................................................... 30 
6.1.3 Serious Adverse Events ............................................................................ 30 
6.2 
Characteristics of an Adverse Event ..................................................................... 31 
6.2.1 Relationship to Study Intervention ............................................................. 31 
6.2.2 Expectedness of SAEs .............................................................................. 31 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
3 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
6.2.3 Severity of Event ....................................................................................... 31 
6.3 
Reporting Procedures ........................................................................................... 31 
6.3.1 Unanticipated Problem Reporting to IRB and NIAAA ................................. 32 
6.3.2 Serious Adverse Event Reporting to NIAAA .............................................. 32 
7 
STUDY OVERSIGHT ....................................................................................................... 35 
8 
STATISTICAL CONSIDERATIONS .................................................................................. 35 
8.1 
Study Hypotheses ................................................................................................. 36 
9 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS .................. 36 
10 
QUALITY CONTROL AND QUALITY ASSURANCE ........................................................ 39 
11 
ETHICS/PROTECTION OF HUMAN SUBJECTS ............................................................. 40 
11.1 
Ethical Standard ................................................................................................... 40 
11.2 
Institutional Review Board ..................................................................................... 40 
11.3 
Informed Consent Process .................................................................................... 40 
11.4 
Inclusion of Women and Minorities (Special Populations) ..................................... 41 
11.5 
Subject Confidentiality .......................................................................................... 41 
12 
DATA HANDLING AND RECORD KEEPING ................................................................... 42 
12.1 
Data Management Responsibilities ....................................................................... 42 
12.2 
Data Capture Methods .......................................................................................... 42 
12.3 
Data Entry ............................................................................................................. 42 
12.4 
Schedule and Content of Reports ......................................................................... 42 
12.5 
Study Records Retention ...................................................................................... 42 
12.6 
Protocol Deviations ............................................................................................... 43 
13 
PUBLICATION/DATA SHARING POLICY ........................................................................ 44 
14 
LITERATURE REFERENCES .......................................................................................... 45 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
4 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
LIST OF ABBREVIATIONS 
 
AE 
Adverse Event/Adverse Experience 
CFR 
Code of Federal Regulations 
CONSORT 
Consolidated Standards of Reporting Trials 
DSMB 
Data and Safety Monitoring Board 
eCRF 
Electronic Case Report Form 
FDA 
Food and Drug Administration 
FWA 
Federalwide Assurance 
HIPAA 
Health Insurance Portability and Accountability Act 
ICF 
Informed Consent Form 
IRB 
Institutional Review Board 
LC-MS/MS 
Liquid Chromatography-Tandem Mass Spectrometry 
MOP 
Manual of Procedures 
N 
Number (typically refers to subjects) 
NIAAA 
National Institute on Alcohol Abuse and Alcoholism, NIH, DHHS 
NIH 
National Institutes of Health 
PHI 
Protected Health Information 
PI 
Principal Investigator 
SAE 
Serious Adverse Event/Serious Adverse Experience 
SOP 
Standard Operating Procedure 
UP 
Unanticipated Problem 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
5 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
PROTOCOL SUMMARY 
 
Title: 
Optimizing e-interventions for Alcohol Use: Do Common 
Factors Apply? 
Objectives: 
Primary: The primary outcome will be mean drinks per day 
over the past 30 days (as measured at both 1 and 3-month 
follow ups). 
Secondary: Secondary outcome measures include past 
month heavy drinking days, alcohol-related consequences, 
and intention to reduce alcohol use. 
Population: 
Participants will be college students age 18 and older who 
meet heavy drinking criteria. 
Number of Sites: 
Wayne State University 
Description of 
Intervention: 
This R21 clinical trial planning grant proposes the 
development and preliminary validation of computer- 
delivered brief interventions in which empathy, use of a 
voice and use of an animated narrator are systematically 
manipulated using a factorial design. We will also 
manipulate the presence or absence of motivational content 
in order to examine possible interactions between common 
factors and specific motivational techniques. 
Study Duration: 
24 months 
Subject Participation 
Duration: 
3 months (there is a 1 month and 3 month post baseline 
follow-up) 
Estimated Time to 
Complete Enrollment: 
21 months 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
6 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
 
 
Principal 
Investigator: 
Emily R Grekin, PhD 
Wayne State University 
5057 Woodward Ave., 7th Floor Detroit, MI 48202 
(313) 577-2820; (313) 577-7636 (fax) 
grekine@wayne.edu 
NIAAA Program 
Official: 
Brett Thomas Hagman 
(301) 443-0638; (301) 443-8744 (fax) 
brett.hagman@nih.gov 
Institutions: 
Wayne State University 
Other Key 
Personnel: 
Steven Ondersma, Ph.D. 
Wayne State University 
Kari C Kugler, Ph.D. 
Pennsylvania State University 
Jennifer B. McClure, Ph.D. 
University of Washington 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
7 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
1 INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE 
 
1.1 
Background Information 
 
A. Brief Interventions for Alcohol Use 
Brief interventions for alcohol use have been effective in reducing drinking 
(O’Donnell et al., 2013; Tanner-Smith & Lipsey, 2015; Kohler & Hofmann, 2015; Larimer 
& Cronce, 2007). These interventions are particularly useful for the large percentage 
(i.e. 87%) of problem drinkers who do not want longer-term, more intensive treatments 
(SAMHSA, 2012). However, the public health impact of brief interventions has been 
severely impeded by implementation challenges, such as limitations in time, training, 
and willingness among providers (e.g., Hilbink et al., 2012). Further, positive overall 
findings in meta-analyses obscure the results of multiple rigorous efficacy trials showing 
no brief intervention effect on alcohol use (e.g., Maio et al, 2005). Both of these 
issues—the implementation challenges and the inconsistency in outcomes— 
suggest that changes are needed before brief alcohol interventions can meet 
their full potential. 
Technology offers exciting potential in both respects. Computer-delivered brief 
interventions (CDBIs) have consistently yielded small but significant effects in meta- 
analyses (e.g., Donoghue et al., 2014; Rooke et al., 2010; Webb et al., 2010). Further, 
they can be presented inexpensively, with perfect fidelity, and without the need for 
training or provider time. Finally—and most relevant to the present study—their 
replicability, flexibility, and modularity makes them an ideal platform for isolating the 
active ingredients that are associated with positive outcomes. Leveraging this capability 
could lead to optimized and increasingly effective CDBIs. Notably, however, 
surprisingly little research has used this approach to identify which elements of 
these multi-component interventions are most strongly associated with change. 
This R21 exploratory/developmental study therefore sought to identify active CDBI 
components, using a factorial design guided by the Multiphase Optimization Strategy 
(MOST; Collins et al, 2009; 2011), as well as by both Common Factors Theory 
(Norcross & Wampold, 2011) and Media Equation Theory (Nass & Moon 2000). 
B. The Potential for Dramatic Improvement: Common Factors Theory and 
Media Equation Theory 
Common Factors Theory suggests that therapist-delivered interventions vary in 
efficacy, not just as a function of their theoretical approach, but also with the 
characteristics of the therapist him or herself. Specifically, a set of common relationship 
factors (e.g., positive regard, empathy) has been clearly associated with therapy 
outcome (Norcross & Wampold, 2011). However, research has not examined whether 
attention to these factors in the context of a computerized intervention can similarly 
increase efficacy. 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
8 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
Media Equation Theory (Nass & Moon 2000) suggests that people automatically 
react to computers in social ways (e.g., they assign ‘personalities’ to computers, engage 
in impression management, respond to flattery, worry about ‘offending’ the computer, 
etc.). These data suggest that CDBIs have the potential to be effective, not just by 
providing information and/or skills training, but also by establishing a therapeutic 
‘relationship’ with a client based on qualities such as respect and empathy. 
To date, the idea of using a computer to develop a meaningful therapeutic 
relationship is in its infancy. It is unclear whether (1) making a CDBI more ‘humanlike’ 
(e.g., giving it a voice, adding an interactive narrator, etc.) or (2) imbuing it with 
facsimiles of common relationship factors (e.g. empathy, positive regard) will enhance 
its efficacy. The current study experimentally examined these questions by investigating 
whether four variables (common factors, voice, narrator, and presence of motivational 
content) increased the efficacy of a CDBI. In doing so, it not only fully leveraged the 
unique flexibility and modularity of CDBIs, allowing systematic manipulation of very 
specific elements; but was also the first study to systematically and experimentally 
examine common factors in CDBI research. 
II. Research Strategy: Innovation 
The current study includes a number of innovations, consistent with its status as an 
R21 exploratory/developmental application. Given that innovation and certainty are 
often partially incompatible, this exploratory research was designed to seek possible 
signals in an important new area, rather than to confirm effects that were already well- 
established. Key innovations included: 
 The proposed study was the first to experimentally evaluate the role of common 
factors in computer-delivered interventions. Findings from the field of Human- 
Computer interaction suggest that individuals (1) react to computers in a social 
manner, especially when they include a voice or other “human” characteristics; Nass 
& Moon, 2000), and (2) respond positively to relational behaviors (e.g., flattery, 
empathy) expressed by computers (Bickmore et al, 2005). The current study was the 
first to apply these findings in a therapeutic context, or to use them to inform brief 
intervention development. 
 The current study made use of unique technology. The software used in this study 
was highly interactive and individualized, and relied heavily on realistic interactions 
with a three-dimensional, animated narrator that could mimic the more 
conversational nature of person-delivered brief interventions. This narrator could 
speak, move, point, provide empathic reflections, and display emotional responses 
such as pleasure, surprise, sadness, and thoughtfulness. The uniquely interactive, 
lifelike nature of this software provides an ideal platform for examining common 
factors in CDBIs. 
 Following the Multiphase Optimization Strategy (e.g., Collins et al., 2011), the 
current study used a factorial design to test 16 combinations of 4 common factors 
(Collins, Dziak, & Li, 2009). Because each participant either received or did not 
receive each common factor, analyses of all factors utilized the entire sample and 
thus were fully powered with a relatively small N. This unique factorial design 
allowed us to test not only the main effects of the four factors under study (one of 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
9 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
which is consistent with Common Factors Theory, and two of which are consistent 
with Media Equation Theory), but also whether these factors interacted to result 
in better outcomes. 
 The current study evaluated common factors, voice, and narrator while also 
systematically varying the presence vs. absence of motivational content, by 
comparing it to very straightforward didactic material. This unique design element 
allowed us to examine the relative therapeutic contribution of specific motivational 
strategies, vs. simply providing information about the problem. These comparisons 
are particularly important given that (1) key components of brief motivational 
interventions (e.g., MI spirit, therapeutic alliance) have not been consistently 
associated with better outcomes (Bertholet et al, 2013), and (2) research-related 
consent, randomization, and/or assessment have been shown to have clear 
therapeutic effects (e.g., Ondersma et al, 2012). 
 The current study was the first to examine the role of common factors using random 
assignment to conditions involving different combinations of common factors. 
Virtually all existing common factors research is correlational. As a result, it is 
unclear whether certain clients elicit certain reactions from therapists (e.g., motivated 
clients may elicit more positive, empathic responses than unmotivated clients). 
Additionally, it is unclear whether common factors are the cause or the result of a 
successful therapy outcome (i.e., does empathy cause less alcohol use or does less 
alcohol use elicit more empathy). 
 
III. Research Strategy: Approach 
A. Investigators and Preliminary Studies 
The current application includes a team with extensive experience in all key 
elements of the proposed study: alcohol use among youth, CDBIs, and MOST factorial 
studies. The PI, Dr. Grekin, has a long-standing research program focusing on the 
development and maintenance of risky drinking among college students (Grekin et al, 
2005, 2006, 2012; Goudriaan et al 2011). She also has experience with brief 
motivational interventions (particularly Dr. Ondersma’s Computerized Intervention 
Authoring System – see below). She has conducted research examining (1) how state 
variables measured during a computer-delivered intervention are related to long-term 
substance use outcomes (Ondersma et al, 2011) and (2) how indirect screening can be 
used to facilitate substance use intervention without the need for self-report (Grekin et 
al, 2010). 
Co-Investigator Ondersma has over a decade of NIH-funded experience with 
computer-delivered brief interventions for substance use. A member of the Motivational 
Interviewing Network of Trainers, his e-interventions have placed great emphasis on 
facsimiles of empathy, optimism, and positive regard. The efficacy of these interventions 
has been supported in multiple randomized trials (Ondersma et al., 2005, 2007, 2012, 
2014; Naar-King et al., 2013; Schwartz et al., 2014). 
Dr. Jennifer McClure’s research focuses on high-reach interventions for substance 
use, primarily tobacco. Importantly, she is a leader with regard to use of the Multiphase 
Optimization Strategy (MOST) for computer-delivered interventions (e.g., see McClure 
et al., 2013), and, as such, will contribute important expertise and experience to the 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
10 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
proposed study. Dr. Kari Kugler will also contribute important expertise with 
MOST/factorial designs, particularly with respect to their analysis; she is a member of 
The Methodology Group at Penn State where MOST was developed. Dr. George Divine 
is a Senior Biostatistician at Henry Ford Hospital who has worked extensively on NIH- 
funded health services and clinical trials research. He provided consultation on data 
analysis and methods of handling non-normal count data. 
 
This work also benefitted greatly from specialized software developed under Co-I 
Ondersma’s previous awards. This software, called the “Computerized Intervention 
Authoring System,” or CIAS, was designed specifically to allow easy creation and/or 
modification of computer-delivered content, without the need for new programming. It 
was also designed to be as lifelike and synchronous as possible; it includes a three- 
dimensional animated character capable of over 50 specific actions that can talk, read 
each item for the participant, act as a guide throughout the process, and provide 
occasional comic relief. These capabilities allow CIAS to provide empathic and emotive 
reflections, and allow developers to imbue the narrator with a lifelike personality. These 
capabilities, however, can be easily and individually turned on or off—making CIAS 
ideal for the study of each characteristic/capability. Previous studies using CIAS- 
developed interventions have yielded extremely high ratings for acceptability and ease 
of use (e.g., Ondersma et al., 2005, 2014). 
Using the CIAS software described above, Dr. Ondersma has developed a standard 
brief, single session substance use intervention based on principles of motivational 
interviewing (Miller & Rollnick, 2002). This intervention involves three components; (a) 
decisional balance, in which participants answer questions about what they like/don’t 
like about drinking (e.g., “Right now, what would you say is the single biggest reason 
you drink?”) (b) normed feedback, in which participants are shown graphs that illustrate 
where their drinking falls in relation to others their age; and (c) goal-setting, in which 
participants have the option of indicating a change goal, and—if setting a goal—are 
helped to work through a specific change plan, including a menu of change options and 
referral to local treatment options. 
Further, since the initial submission of this application, Dr. Grekin has pilot 
tested high and low empathy versions of the intervention described above on 25 Wayne 
State undergraduates (all of whom met proposed study criteria; see below). Despite the 
small sample size, participants who were randomized to the high (versus low) empathy 
version scored significantly higher on 5 of 11 readiness to change items (e.g. ‘How likely 
are you to reduce your drinking in the next week?”). No other between-group 
differences were found. 
 
1.2 
Potential Risks and Benefits 
 
1.2.1 
Potential Risks 
 
There are no known significant risks to students from participating in this study. Some 
students may have concerns about the confidentiality of their answers, although they 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
11 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
will be assured of confidentiality as stated below. In addition, professional referrals may 
be made if students indicate that they are actively suicidal or experiencing significant 
psychological distress (though this will not be specifically assessed). Minor risks may 
include some discomfort from answering questions about alcohol use. 
 
1.2.2 
Potential Benefits 
 
Participants will benefit from increased understanding of psychological research. In 
addition, some participants may gain insight into factors which affect their alcohol use or 
may experience increased motivation to reduce their drinking. Upon publication, 
research findings will benefit society, generally, by increasing knowledge of the 
mechanisms underlying effective, computer-delivered interventions. 
 
OBJECTIVES 
 
1.3 
Study Objectives/Outcome Measures 
 
1.3.1 
Primary 
The primary outcome will be mean drinks per day over the past 30 days (as measured 
at both 1 and 3-month follow ups). Outcome data will be analyzed using ANCOVAs, 
factorial ordinal regression, or binary logistic regression, depending on each outcome’s 
distribution. The alpha level will be set at 5%. 
 
 
1.3.2 
Secondary 
Secondary outcome measures include past month heavy drinking days, alcohol-related 
consequences, and intention to reduce alcohol use. 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
12 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
3 STUDY DESIGN 
 
The purpose of this study was to develop a maximally effective computer-delivered brief 
intervention (CDBI) for reducing heavy alcohol use. To accomplish this we created 16 
different versions of a CDBI in which common factors, use of a voice, use of an 
animated narrator, and motivational content were systematically manipulated using a 
factorial design. Participants were 352 male and female undergraduate students at 
Wayne State University recruited either through the Psychology department ‘subject 
pool’ or through ads placed on the university’s website. Eligible students needed to 
meet NIAAA--defined binge or heavy drinking criteria. Heavy drinking criteria: More than 
3 (women)/4 (men) drinks per day, or more than 7 (women)/14 (men) drinks per week. 
Binge drinking criteria: more than 4 (women)/5 (men) drinks in a 2 hr. period. 
 
The study consisted of a baseline assessment (45 minutes, in lab), a 1-month follow-up 
assessment (10 minutes, online), and a 3-month follow-up assessment (30 minutes, 
online). During all three assessments, participants completed questionnaires assessing 
demographics, past-month alcohol use, alcohol-related consequences, heavy episodic 
drinking, and motivation to reduce drinking. During the baseline and the 3-month follow- 
up assessments, participants were given a Timeline Follow-Back Interview to assess 
past month alcohol use. Additionally, during the baseline assessment, participants 
completed a brief (15 minute), computer-delivered intervention aimed at reducing heavy 
drinking. This intervention has been used in multiple previous studies and is based on 
the principles of motivational interviewing. At the end of each session, participants were 
fully debriefed and compensated with either course credit or an Amazon gift card ($20 
gift card for the baseline session, $30 gift card for the 1-month follow-up, $40 gift card 
for the 3-month follow-up). 
 
The first step in the development phase was to create, using CIAS software, 16 
alternate versions of the motivational intervention described above. Alternate versions 
varied in the presence vs. absence of four factors (see Table 1). Two of the factors— 
use of a voice, and use of an animated narrator—involved “humanization” of the 
computer program which, according to the Media Equation Theory, will increase alliance 
with the software. The manipulation of common factors—operationalized as a 
combination of empathic reflection and expression of positive regard—allowed us to 
directly test the effects of common factors on CDBI outcomes. The fourth factor we 
manipulated was use of strategic motivational techniques, including decisional balance, 
normed feedback, and optional goal-setting. Notably, experimental conditions that did 
not contain motivational techniques could still include common factors, as the computer 
can make positive/empathic statements about the participant’s understanding of 
educational content (e.g., “I appreciate your efforts to understand this”). See Table 1, 
below. 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
13 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
 
Table 1. Four factors and preliminary operationalization of present/not present 
distinction 
Empathy 
Human 
voice 
Narrator 
Motivational 
strategies 
Present 
Non- 
judgmental 
reflections of 
responses; 
clear attempts 
to understand 
participant’s 
perspective 
A synthetic 
text to 
speech 
engine will 
read all 
content for 
the 
participant 
(questions 
will also 
appear on 
screen) 
An 
animated 
narrator 
capable of 
nodding, 
smiling, 
pointing, 
etc.; can 
either talk 
aloud or 
use a 
speech 
bubble 
Decisional 
balance, 
personalized 
normed 
feedback, 
and optional 
goal setting 
using a 
menu of 
options 
Example Drinking really 
helps you to 
relax. 
Not 
present 
No reflections 
or overt 
attempts to 
elicit 
participant’s 
perspective 
No use of 
voice 
No narrator 
Educational 
content only 
 
1. Participants: Participants were 352 students at Wayne State University in Detroit. 
Undergraduates are an ideal population for this first stage of testing, in that (1) they are 
at high risk for heavy alcohol use (e.g., 40% of college students report past 2-week 
binge drinking; O’Malley & Johnson, 2002); (2) they have been shown to reduce alcohol 
use in response to CDBIs (Carey et al, 2009; Larminer et al, 2007); and (3) their 
accessibility allows us to efficiently and preliminarily test the proposed hypotheses of 
this exploratory study. 
 
2. Recruitment: Participants were recruited in 1 of 2 ways. Some of the participants 
were recruited from the Wayne State Psychology department subject pool, which serves 
between 2400 and 2500 undergraduates each year. Students in the subject pool can 
sign up online to participate in research being conducted in the Wayne State 
psychology department. Students may sign up for as many studies as they choose and 
participation is typically compensated with course credit. In a typical year, 10-12 studies 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
14 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
actively recruit from the subject pool. 
Students in the subject pool were asked to complete a prescreen questionnaire 
before signing up for research studies. Six of the prescreen items assessed NIAAA- 
defined binge and heavy drinking criteria. Heavy drinking criteria: More than 3 
(women)/4 (men) drinks per day, or more than 7 (women)/14 (men) drinks per week. 
Binge drinking criteria: more than 4 (women)/5 (men) drinks in a 2 hr. period. Subject 
pool students who met either binge or heavy drinking criteria were e-mailed and invited 
to participate in the study. 
Students were also be recruited through advertisements posted on the Wayne 
State online portal “Pipeline.” Pipeline is viewed daily by virtually all of the 17,000 
undergraduates at Wayne State. Advertisements placed on Pipeline offered students 
who drank at least once per week the opportunity to participate in the study. Students 
who responded to the Pipeline advertisement were given a 3-minute phone screener to 
determine eligibility. All eligible students (recruited from either the subject pool or 
Pipeline) were told that participation would involve completing three brief alcohol use 
assessments and receiving information about how their alcohol use compares to others 
their age. Those who wished to participate were then signed up for a baseline session 
 
3. Baseline Laboratory Session: Participants were met in the lab by a research 
assistant. After providing consent, they completed (1) a computerized Timeline Follow- 
Back (TLFB) interview assessing past-month drinking, and (2) computerized 
questionnaires that assessed demographics, mean drinks per day in the past 30 days, 
past month alcohol consequences, and 
motivation to reduce alcohol use. After 
completing these measures, participants 
were randomized to a particular version 
of the intervention by the computer (352 
participants were assigned to 16 
conditions: see Table 2, right). Each 
condition lasted approximately 15 
minutes. Afterwards, participants 
completed post-intervention 
questionnaires assessing (1) motivation 
to reduce alcohol use, and (2) perceived 
degree of empathy and positive regard 
received from the intervention. At the 
end of the study, participants were debriefed and compensated with either course credit 
or a $20 Amazon gift card (participant’s choice). The entire baseline session took 
approximately 45 minutes (10 minutes for orientation and consent, 20 min. for 
questionnaires/ interviews, and 15 min. for the intervention). At the end of this session, 
participants were given instructions about their 1 and 3-month follow-up assessments. 
 
4. 1-Month Follow-Up Session (Online): One month post-intervention, participants 
were e-mailed a link to a brief (10 minute), secure online survey (using Qualtrix) which 
assessed mean drinks per day in the past 30 days, past month alcohol consequences, 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
15 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
and motivation to reduce alcohol use. Participants who completed the survey received 
either course credit or a $30 Amazon gift card (participant’s choice). 
 
5. 3-Month Follow-Up Session: Three months post-intervention, participants were e- 
mailed a link to a secure (30 minute) online survey (using Qualtrix). They completed all 
1-month follow-up measures, as well as a computerized TLFB interview assessing past- 
month drinking. At the end of the session, they were given either course credit or a $40 
Amazon gift card (participant’s choice). 
 
Measures 
Past Month Alcohol Use was assessed with two measures: (1) The Timeline Follow- 
Back interview (Sobell & Sobell, 1966), a highly reliable interview that uses a calendar 
and multiple procedures to aid retrospective reporting of substance use (Fals-Stewart et 
al, 2000) and (2) the 3-item Quantity/Frequency questionnaire (U.S. Dept. of Health and 
Human Services, 1995), a survey which assesses the quantity, frequency, and 
maximum number of drinks consumed in the past month. Past Month Alcohol 
Consequences was assessed using the Brief Young Adult Alcohol Consequences 
Questionnaire (Read et al, 2006), a well-validated questionnaire designed to assess 
high and low level drinking consequences commonly experienced by young adults. 
Motivation to Reduce Drinking was assessed with the Readiness to Change Scale 
(Sobell, 1996), a 4-item scale that assesses motivation and intention to reduce drinking. 
Intervention Empathy and Positive Regard were assessed with the The Participant 
Satisfaction Questionnaire (PSQ), a measure created for this study.  The PSQ 
assessed the degree to which participants perceived that the intervention was empathic 
and respectful. 
 
3.1 
Subject Inclusion/Exclusion Criteria 
 
Inclusion criteria 
 
Age 18 or older, currently enrolled in classes at Wayne State University, and 
meet NIAAA--defined binge or heavy drinking criteria. Heavy drinking criteria: More than 
3 (women)/4 (men) drinks per day, or more than 7 (women)/14 (men) drinks per week. 
Binge drinking criteria: more than 4 (women)/5 (men) drinks in a 2 hr. period 
 
Exclusion criteria 
 
Frank cognitive impairment, not able to communicate in English, or not currently 
enrolled at Wayne State University. 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
16 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
3.2 
Strategies for Recruitment and Retention 
Many techniques and communications were employed to orient each participant from 
enrollment to completion of participation after follow up appointments. This includes all 
of the correspondences described in the Correspondence Schedule, some of which are 
detailed here. 
 
3.3 
Treatment Assignment Procedures 
 
3.3.1 
Randomization Procedures 
 
Randomization was set up a priori using randomization.com to allow equal opportunity 
for participants to be placed in all 16 groups. All participants who screen eligible are 
randomized to one of sixteen conditions. In order to blind participants and research 
assistants 4 colors and 4 numbers were used to differentiate the 16 groups so that each 
group had one color and one number. The randomization list specified both the color and 
number to select for each participant. The PI and Project Coordinator monitor the 
randomization rate to ensure that equal numbers of participants are randomized to each 
condition. 
 
3.3.2 
Masking Procedures (if applicable) 
 
This is a blinded study, meaning that the research assistant collecting data is blinded to 
the participant’s randomization condition, but the PI and Project Coordinator have access 
to that condition. Participants are informed in the consent form that they will be randomly 
placed into one of the sixteen conditions. A prior randomization list of the sixteen 
conditions (broken down between 4 colors and 4 numbers) was generated before data 
collection began using the website randomization.com. The research assistant would 
select the appropriate color and number using the list for each participant after completing 
consent and before handing the participant the tablet. The correct assignment was then 
verified in the data when it was downloaded weekly. 
 
3.4 
Subject Withdrawal 
 
Participants are free to withdraw from the study without changing any present or future 
relationship with Wayne State University or any of its affiliates. The PI may withdraw 
participants as well. If the PI makes this determination, participants will be told. The 
decision is made only to protect participants health and safety, or because the participant 
did not follow instructions to take part in the study. 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
17 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
3.4.1 
Reasons for Withdrawal 
 
Participants are notified in the consent form that their participation is voluntary and that 
they may withdraw from the study at any time. Participants are not obligated to provide a 
reason for withdrawing, though suspected reasons might include the sensitive nature of 
certain questions, or a lack of available time to complete assessments. 
 
3.4.2 
Handling of Subject Withdrawals or Subject Discontinuation of Study 
Intervention 
If withdrawal occurs, this is noted on tracking spreadsheets so that the participant is no 
longer contacted. Subjects who unofficially withdraw due to loss to follow up are 
reported during progress reports. 
 
3.5 
Premature Termination or Suspension of Study 
 
An IRB shall have authority to suspend or terminate approval of research that is not being 
conducted in accordance with the IRB’s requirements or that has been associated with 
unexpected serious harm to subjects. Any suspension or termination of approval shall 
include a statement of the reasons for the IRB’s action and shall be reported promptly to 
the investigator, appropriate institutional officials, and to the Department or Agency Head. 
[45 CFR 46.113; 38 CFR 16.113 Suspension or Termination of Research.] 
 
To fulfill the regulatory requirements (as noted above), Wayne State University (WSU) 
has authorized the Institutional Review Board (IRB), the individual Institutional Review 
Boards (IRBs,Committees) and/or the Committee Chairs or the Assistant/Associate Vice 
President for Research (AVPR), to suspend or terminate a research project that is not 
being conducted in accordance with the IRB’s requirements and/or that may pose 
increased risks and/or unacceptable risks to the safety and welfare of human research 
subjects. Additionally, any of the above entities or individuals can suspend the human 
research activities of an investigator who has committed serious or continuing non- 
compliance in order to assess and/or remediate the problem(s). Suspension or 
termination would occur when there are issues of continuing or serious noncompliance 
with IRB and federal requirements, when the research is associated with unexpected 
serious harm to research participants, or when there are immediate serious issues 
involving participant safety. 
 
Key Definitions 
Committee – Refers to the individual IRBs at Wayne State University. 
Designee – A person appointed by the IRB Chair, acting on his/her behalf. 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
18 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
Confirmed Non-Compliance – Non-compliance (as defined below) that has been verified 
as a result of a for-cause audit or investigation. 
Continuing Non-Compliance – A repeated pattern of non-compliance with all federal 
regulations, including Veterans regulations and guidance, by an individual investigator or 
research staff member either on a single protocol or multiple protocols. 
Non-Compliance – The failure to comply with all federal regulations, including Veterans 
Administration regulations and guidance, state and local requirements, WSU Policy and 
determinations of the IRB. 
Serious Non-Compliance – The failure to comply with all federal regulations, including 
Veteran’s Administration regulations and guidance, state and local requirements, WSU 
Policy and determinations of the IRB that involve one or more of the following: 
 Harm to research participants; 
 Exposing research participants to a significant risk of substantive harm; 
 Comprising the privacy and confidentiality of research participants; 
 Damage caused to scientific integrity of the research data that has been collected; 
 Willful or knowing non-compliance on the part of the investigator; and 
 Adversely impacting ethical principles 
 
(See IRB Policy: “Identifying, Defining, and Managing Non-Compliance in Human 
Research” for specific examples). 
Suspension – A suspension occurs when the IRB Committee, IRB Chair, or AVPR places 
a temporary hold on the research that had been previously approved so that no new 
participants can be accrued, no research interventions may occur (unless necessary for 
the safety and well-being of the enrolled participants), and no follow-up can be conducted 
unless it is in the best interest of the participant and approved by the IRB. 
Termination of a previously approved protocol – Termination of a previously approved 
protocol occurs when the IRB Committee, IRB Chair, or AVPR withdraw approval or stop 
all research activity permanently. No new participants may be enrolled and no additional 
research interventions can occur. However, future follow-up may be conducted with the 
approval of the IRB to monitor the well-being and any potential risk to participants. 
Termination of activities that have never received prior review and approval – On the 
occasion when research activities have occurred that did not receive prior review and 
approval from the IRB, the IRB shall stop all such activities permanently. None of the data 
collected in this activity can be used in any future publication or presentation. 
Unexpected Problem – An unexpected problem is associated with any aspect of the 
research study that may involve not only risks to the participant enrolled in a research 
study, but to other individuals who may or may not be directly associated with the research 
study. Unexpected problems may occur in non-clinical (behavioral or social science) as 
well as clinical research studies (see IRB Policy and Procedure “Unexpected Problems 
Involving Risk to Participants” for an inclusive list of categories). 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
19 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
 
 
IRB Procedures 
Prior to, or during, the process of suspending or terminating a previously approved 
research protocol or research activities that have been conducted without prior approval, 
a for-cause audit will be conducted. The results of this audit will be provided to the AVPR, 
the IRB Chairs and Committee Members as a part of their decision to suspend and/or 
terminate a research protocol (see IRB Policy and Procedure “For-Cause Audit”). 
 
When other administrative groups within the University have suspended a research 
activity for an issue involving human participants, they are required to notify the IRB within 
5 business days. An investigation will be done and an audit may be conducted by the IRB 
as part of their decision to suspend and/or terminate the research protocol. These results 
of the above actions may range from corrective or educational measures for the 
researcher up to and including the termination of all research activities. Further, the IRB 
may suspend the approval of research projects at any time during an inquiry or 
investigation to assure the protection of human participants. 
 
Suspension of a Research Protocol 
When reviewing an unexpected problem, the IRB or IRB designee may determine that 
the protocol associated with the unexpected problem should be suspended. 
 
In addition, when there is concern that research is being conducted that is not in 
compliance with an approved research protocol, the IRB or IRB designee may suspend 
the research protocol until an internal audit has been completed. The completed audit 
report will be reviewed by the IRB, to determine whether or not to terminate the IRB 
approval. 
 
As an alternative to termination, the IRB may impose a suspension and/or remedial 
actions to bring the research activities into compliance with the IRB requirements and to 
reduce the risk to participants. When the IRB has determined that all remedial actions 
have been implemented, the IRB may withdraw the suspension and the research may 
resume. 
 
Termination of a Research Protocol 
A research protocol is terminated: 
 When a remedial action plan approved by the IRB has not been implemented; or 
 When the IRB determines that it is in the best interest of the research participants. 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
20 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
Due to safety issues and full disclosure (as outlined in the informed consent process), 
participants in the research must be notified in writing of all terminations. This notification 
must be approved by the IRB before it is sent to participants. A plan for safe withdrawal 
of participants from the research is required and should consider their rights and welfare, 
and must be submitted to the IRB for review and approval. If follow-up of the participants 
for safety and effectiveness reasons is permitted or required by the IRB, the participants 
should be informed after obtaining IRB review and approval of the notice. Any unexpected 
problems or other outcomes identified during follow-up should be reported to the IRB, the 
research study sponsor, and the FDA, if applicable. 
 
If the investigator wishes to resume a research protocol that has been terminated, it must 
be submitted as a new protocol. 
 
Terminating Research Activities Prior to IRB Review and Approval 
When research activities have occurred without prior review and approval, then all 
activities must cease immediately and the following process is followed: 
 The PI will be required to submit an Unexpected Problem Report/Form regarding 
the event; 
 A for-cause audit of all research documents will be conducted; 
 The investigator must verify in writing that none of the data will ever be used for 
research purposes in the future; 
 All paper documents and informed consent forms must be sent to the IRB office to 
be confiscated; 
 All computer files must be destroyed and a signed verification submitted by the PI; 
 Mandatory education of the investigator and research team will be conducted; 
 Appropriate University, IRB, Agency, and Sponsor entities will be notified. 
 
Reporting of All IRB Suspensions and/or Terminations 
The suspension and/or termination of IRB approval of a research protocol will be promptly 
reported to the investigator by courier within 24 hours and will include a written statement 
of the reasons for the IRB’s actions. 
 
When research has been suspended and/or terminated, the Associate Vice President for 
Research will report the suspension and/or termination to other appropriate Institutional 
Officials, Departmental Chairs or Deans and appropriate regulatory agencies (e.g., 
Offices for Human Research Protection, Food and Drug Administration, Veterans Affairs, 
Sponsor, etc.) within 60 days of the suspension or termination (see IRB Policy and 
Procedure “Reporting of Unexpected Problems, Suspensions and Terminations, and 
Serious and Continuing Non-Compliance and the Institutional Official’s Responsibilities”). 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
21 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
For VA requirements, in addition to reporting to ORO, the following offices must be 
notified: 
 The Privacy Office, when the report involves unauthorized use, loss, or disclosure 
of individually identifiable patient information. 
 The Information Security Officer when the report involves violations of information 
security requirements. 
 
PI Recourse 
The PI may request a meeting with the AVPR, IRB Committee or IRB Chair or designee 
regarding any decision to suspend and/or terminate a protocol. This should be 
accompanied by a written appeal. 
 
Disciplinary Action 
While the IRB shall have the authority to suspend and/or terminate a research protocol, 
or any of an investigator’s human research activities, all disciplinary action taken against 
an individual for being out of compliance with institutional policies regarding the protection 
of 
human 
participants, 
shall 
be 
the 
responsibility 
of 
the 
institution. 
The 
Associate/Assistant Vice President for Research shall be responsible for reporting the 
termination to other institutional officials (Department Chairs, Deans, the Provost, etc., as 
required) and to assist in taking appropriate institutional disciplinary action. 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
22 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
4 STUDY INTERVENTION 
 
4.1 
Study Behavioral or Social Intervention(s) Description 
 
Sixteen versions of the intervention were created by manipulating 4 factors (voice, 
narrator, common factors and MI content) in a full factorial design. In conditions with a 
voice, all content was read aloud to participants through headphones; in non-voice 
conditions, content was presented exclusively as text on screen. 
In conditions with a narrator, participants interacted with an animated, three-dimensional 
parrot who is capable of multiple specific actions (e.g., pointing, waving, yawning, etc.). 
The animated parrot was selected for his high likeability ratings in previous research 
(Ondersma, Chase, Svikis, Schuster, 2005) and the fact that (as a non-human 
character) he has no race or ethnicity. 
In high empathy conditions, participants were exposed to a series of non-judgmental 
reflections and statements of affirmation that were tailored to their individual responses 
(e.g., “You’ve felt really stuck” or “It sounds like you feel two ways about this”). In low 
empathy conditions, these reflections/affirmations were absent, but all other content 
was identical. We chose to focus on empathy, rather than other relationship factors, 
because the provision of empathy has consistently been associated with better therapy 
outcomes in meta-analyses (e.g. Elliot et al, 2011), and because it was relatively easy 
to operationalize with our software. 
In motivational strategy conditions, participants were presented with three specific 
strategies: (1) personalized normed feedback showing how the participant’s drinking 
compared to that of same-age peers; (2) decisional balance (i.e. weighing the pros and 
cons of drinking); and (3) an optional goal-setting component in which participants were 
given the choice to set a drinking reduction goal. Non-motivational strategy conditions 
provided straightforward, non-tailored didactic information about alcohol use. 
Research Design 
As noted above, the current study used a 2X2X2X2 factorial design to test 16 
combinations of the 4 CDBI factors described above (Collins et al, 2016). Factorial 
designs differ from 2-arm, randomized controlled trials (RCTs) in several ways. First, 
factorial designs randomly assign the entire sample to all levels of each independent 
variable. This allows each main effect to be powered based on the entire sample rather 
than a fraction of the sample (as with RCTs). This efficiency makes factorial designs 
ideal for optimization. Further, when it comes time for analysis, use of effect coding (-1, 
1) rather than dummy coding (0, 1) renders orthogonal all main and interaction effects, 
thereby increasing power for detection of interaction effects (Collins et al, 2016). 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
23 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
4.2 
Administration of Intervention 
 
The computerized intervention is delivered by a tablet with the aid of CIAS. This eliminates 
fidelity concerns because, pending no software glitches, packages are delivered the same 
way every time. At baseline lab visit after consent is complete, the RA sets up the 
participant on the tablet (selecting both the color and number listed next on the 
randomization list). Participants then use the tablet to complete both the assessment 
questions and the intervention. Pictures and intervention slides appear on-screen, as well 
as questions and response options. Feedback regarding satisfaction and change beliefs 
is collected by the tablet post-intervention. All data collected during tablet administration 
is transferred to the Wayne State server via an encrypted and protected transmission 
system. 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
24 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
4.3 Procedures for Training Interventionists and Monitoring Intervention 
Fidelity 
 
The intervention as described above does not require training interventionists or 
monitoring intervention fidelity in the traditional sense. Rather, the CIAS-authored 
intervention is delivered via the internet to the tablet computer for participants to interact 
and answer questions. CIAS is routinely checked for issues, though none have been 
found to date that were not easily fixed. Data is also analyzed for out-of-range values or 
entry errors monthly so that they may be identified, logged, and prevented in the future. 
This ensures an extremely high level of intervention fidelity and trial administration in 
general. 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
25 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
5 STUDY SCHEDULE 
 
 Day 1 
o Recruit into study 
o Confirm contact information 
o Emphasize follow-up and explain how links to surveys and payments will 
be emailed 
 
 1-month follow-up (emailed 1-5 times from 2 weeks before due date to 2 weeks 
after due date) 
o An email is sent with the survey link and a reminder of their participant ID. 
o Several emails are sent within the time frame (if necessary) to remind the 
participant 
o Once participant completes the following email is sent: 
Hello , 
Below you will find the claim code for your $30 Amazon Gift card. This is for the 
compensation for completing session 2 of the College Alcohol Study. Thank you for your 
patience. 
Gift Card Number: 
Claim Code: 
Thank you for your participation! 
Best, 
Grekin Lab 
 
 3-month follow-up (emailed 1-5 times from 2 weeks before due date to 2 weeks 
after due date) 
o An email is sent with the survey link and a reminder of their participant ID. 
o Several emails are sent (if necessary) within the time frame to remind the 
participant 
o Once participant completes the following email is sent: 
Hello , 
Below you will find the claim code for your $40 Amazon Gift card. This is for the 
compensation for completing session 3 of the College Alcohol Study. Thank you for your 
patience. 
Gift Card Number: 
Claim Code: 
Thank you for your participation! 
Best, 
Grekin Lab 
 
 At study completion 
 Participants are emailed a debriefing letter for the study and final 
gift card information 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
26 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
5.1 Screening and Recruitment 
 
Participants were 352 male and female undergraduate students at Wayne State 
University in Detroit (50.9% male; 50.9% Caucasian). 
 
Participants were recruited in 1 of 2 ways. Some participants were recruited from the 
Wayne State Psychology department subject pool, which serves between 2400 and 
2500 undergraduates each year. These students were asked to complete a prescreen 
questionnaire which assessed NIAAA-defined binge and heavy drinking criteria. Heavy 
drinking criteria: More than 3 (women)/4 (men) drinks per day, or more than 7 
(women)/14 (men) drinks per week. Binge drinking criteria: more than 4 (women)/5 
(men) drinks in a 2 hr. period. Subject pool students who met either binge or heavy 
drinking criteria were e-mailed and invited to participate in the study. 
 
A second group of students was recruited through advertisements posted on the 
Wayne State online portal “Pipeline.” Advertisements placed on Pipeline offered 
students who drank at least once per week the opportunity to participate in a study on 
“Undergraduate Alcohol Use.” Students who responded to the Pipeline advertisement 
were given a 3-minute phone screener to determine eligibility. 
 
All eligible students (recruited from either the subject pool or Pipeline) were told that 
participation involved completing three brief alcohol use assessments and receiving 
information about how their alcohol use compares to others their age. Those who 
wished to participate were then signed up for a baseline session. 
 
5.2 Enrollment/Baseline 
 
Participants meeting all eligibility criteria were given the opportunity to set up a baseline 
session. Upon arriving in the laboratory, participants completed a written consent form. 
The PI’s research assistants reviewed the consent form with participants and were 
available to answer any questions related to consent. A copy of the signed consent form 
was provided to participants. Names and phone numbers of both the PI and the Wayne 
State Institutional Review Board were provided in these consent forms. The original 
consent forms were kept in a locked file cabinet in the PI’s office, separate from all other 
data. 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
27 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
Brief Alcohol e-Intervention Study (MOST) 
 
Time started:  
 
Time end:  
 
 
  
 
Read Consent form with participant and had them provide signature. 
 
 
Answered all questions? 
Yes 
No 
 
Agreed to participate? 
Yes No 
 
Participant signed consent? Yes No 
(Retain signed consent for records) 
  
 
Checked Randomization Sheet and selected color and number for package 
(Green/Orange use one tablet-WITH SOUND; Yellow/Purple use another tablet- 
NO SOUND) 
*To turn off sound. Push down on Peedy. Select “Advanced Character 
Options.” Check “Display spoken output in word 
bubbles,” and uncheck “Play spoken audio.” 
  
   Begin CIAS intervention for participant and obtained CIAS ID (exit CIAS after you 
get the ID) 
CIAS ID#   
 
 
  
   Completed TLFB with participant in Qualtrics 
**PUT CIAS ID IN QUALTRICS 
 
  
   Reopen CIAS and begin intervention (enter the CIAS ID) 
*Always put first name in (for Green/Orange, may need to write 
phonetically; for Yellow/Purple, always write as spelled with capital letter 
at beginning) 
* Will need to hit “Next” on blank screen with “Screening” title 
 
  
 
Discussed follow-up and scheduled 3 month lab visit 
Date scheduled:   
 
  
 
Marked the Google calendar for session 2 and session 3 using CIAS ID # 
 
  
 
Gave SONA credits or Gift card (please circle) 
Gift card #   
 
 
  
 
Gave participant a copy of the consent form, flyer, and resource sheet 
*The resource sheet is only given to participants at the 3rd session 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
28 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
 
  
 
E-mailed initials, CIAS ID#s, and contact info to the grekinlab email, gift card number 
 
  
 
Update CIAS ID on the Google calendar 
 
 
5.3 
Follow-ups (1-month and 3-month) 
 
This study was designed to maximize the follow-up rate and therefore both follow-ups 
were administered online. One month post-intervention, participants were e-mailed a 
link to a brief (10 minute), secure online survey (using Qualtrics) which assessed mean 
drinks per day in the past 30 days, past month alcohol consequences, and motivation to 
reduce alcohol use. Participants who completed the survey received either course 
credit or a $30 gift card (participant’s choice). 
 
The 3-Month Follow-Up online survey (using Qualtrics) included all 1-month follow-up 
measures, as well as a computerized TLFB interview assessing past-month drinking. At 
the end of the session, Participants were given either course credit or a $40 gift card 
(participant’s choice). 
 
The gift cards were sent to participants’ email address after the project coordinator 
confirmed completion of the online survey. At the very end of the study, all participants 
were emailed a debriefing letter describing the study in more detail. 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
29 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
An Explanation of the College Alcohol Study 
 
Thank you for participating in the College Alcohol Study. We really appreciate your time and 
effort. Since you’ve just completed your last session, we want to explain to you what our study 
is about. 
 
As you know, drinking alcohol can be associated with both good things, like relaxation, and bad 
things, like health problems. As a result, many people have mixed feelings about whether they 
want to reduce their alcohol use. 
 
A number of different programs have been developed to help people better understand the pros 
and cons of drinking and decide whether it’s worth it to them to reduce their alcohol use. 
However, these programs can be very different from one another. Some programs are 
computerized (like the one you interacted with during your first visit), whereas others use an 
actual person. Programs can also differ in their content and presentation. Currently, it’s not 
clear which types of programs are most effective in helping people decide whether or not they 
want to change their drinking patterns. 
 
Participants in this study are exposed to 1 of 16 different versions of a computer program. 
These versions differ in a number of ways. For example, some contain a voice, or animated 
narrator, whereas, others ask participants to read text on the computer screen. Some versions 
contain a large number of empathic statements, whereas others are more neutral. The goal of 
the current study is to examine which of these 16 versions has the greatest effect on people’s 
decision to reduce - or not to reduce - their alcohol use 1 and 3 months later. 
 
We realize that many people are not interested in reducing their alcohol use. We also realize 
that some people want to reduce their alcohol use, but not right now. We’ve tried to design 
computer programs that take those facts into consideration and help participants clarify their 
own, individual goals. 
 
Again, we want to thank you for being in our study. Your participation will help us learn more 
about alcohol use among college students. If you have any questions, please feel free to 
contact use at grekinlab@wayne.edu or 313-577-9305. 
 
 
 
 
Emily Grekin, Ph.D. 
Associate Professor, Psychology 
Principal Investigator, College Alcohol Study 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
30 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
6 ASSESSMENT OF SAFETY 
 
During recruitment it is explained to the participant that this is a research study. They 
are also told the types of questions that will be asked and that they have the right to 
decline participation or withdrawal at any time. Participants are also explained the 
potential risk of distress due to the sensitive nature of the questions. The participant is 
explained their rights and what the study is clearly. 
 
6.1 Specification of Safety Parameters 
 
6.1.1 
Unanticipated Problems 
The Office for Human Research Protections (OHRP) considers unanticipated problems 
involving risks to subjects or others to include, in general, any incident, experience, or 
outcome that meets all of the following criteria: 
 
 unexpected in terms of nature, severity, or frequency given (a) the research 
procedures that are described in the protocol-related documents, such as the 
IRB-approved research protocol and informed consent document; and (b) the 
characteristics of the subject population being studied; 
 related or possibly related to participation in the research (“possibly related” 
means there is a reasonable possibility that the incident, experience, or outcome 
may have been caused by the procedures involved in the research); and 
 suggests that the research places subjects or others at a greater risk of harm 
(including physical, psychological, economic, or social harm) than was previously 
known or recognized. 
 
6.1.2 
Adverse Events 
An adverse event is any untoward or unfavorable medical occurrence in a human 
subject, including any abnormal sign (for example, abnormal physical exam or 
laboratory finding), symptom, or disease, temporally associated with the subject’s 
participation in the research, whether or not considered related to the subject’s 
participation in the research. 
 
6.1.3 
Serious Adverse Events 
A serious adverse event (SAE) is one that meets one or more of the following criteria: 
 
 Results in death 
 Is life-threatening (places the subject at immediate risk of death from the event 
as it occurred) 
 Results in inpatient hospitalization or prolongation of existing hospitalization 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
31 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
 Results in a persistent or significant disability or incapacity 
 
6.2 Characteristics of an Adverse Event 
 
6.2.1 
Relationship to Study Intervention 
To assess relationship of an event to study intervention, the following guidelines are 
used: 
 
1. Related (Possible, Probable, Definite) 
 
a. The event is known to occur with the study intervention. 
 
b. There is a temporal relationship between the intervention and event onset. 
 
c. The event abates when the intervention is discontinued. 
 
2. Not Related (Unlikely, Not Related) 
 
a. There is no temporal relationship between the intervention and event 
onset. 
 
b. An alternate etiology has been established. 
 
6.2.2 
Expectedness of SAEs 
The Study PI will be responsible for determining whether an SAE is expected or 
unexpected. An adverse event will be considered unexpected if the nature, severity, or 
frequency of the event is not consistent with the risk information previously described for 
the intervention. 
 
6.2.3 
Severity of Event 
The following scale will be used to grade adverse events: 
 
1. Mild: no intervention required; no impact on activities of daily living (ADL) 
 
2. Moderate: minimal, local, or non-invasive intervention indicated; moderate impact 
on ADL 
 
3. Severe: significant symptoms requiring invasive intervention; subject seeks 
medical attention, needs major assistance with ADL 
 
6.3 
Reporting Procedures 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
32 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
6.3.1 
Unanticipated Problem Reporting to IRB and NIAAA 
Incidents or events that meet the OHRP criteria for unanticipated problems require the 
creation and completion of an unanticipated problem report form. OHRP recommends 
that investigators include the following information when reporting an adverse event, or 
any other incident, experience, or outcome as an unanticipated problem to the IRB: 
 
 appropriate identifying information for the research protocol, such as the title, 
investigator’s name, and the IRB project number; 
 a detailed description of the adverse event, incident, experience, or outcome; 
 an explanation of the basis for determining that the adverse event, incident, 
experience, or outcome represents an unanticipated problem; 
 a description of any changes to the protocol or other corrective actions that have 
been taken or are proposed in response to the unanticipated problem. 
To satisfy the requirement for prompt reporting, unanticipated problems will be reported 
using the following timeline: 
 
 Unanticipated problems that are serious adverse events will be reported to the 
IRB and to NIAAA within 1 week of the investigator becoming aware of the event. 
 Any other unanticipated problem will be reported to the IRB and to NIAAA within 
2 weeks of the investigator becoming aware of the problem. 
 All unanticipated problems should be reported to appropriate institutional officials 
(as required by an institution’s written reporting procedures), the supporting 
agency head (or designee), and OHRP within one month of the IRB’s receipt of 
the report of the problem from the investigator. 
 
 
6.3.2 
Serious Adverse Event Reporting to NIAAA 
 
Procedures and timeline for reporting AEs to NIAAA. 
 
AEs will be reported to the NIAAA PO at least once per year as a part of the annual 
progress report. These reports will describe the event, when it occurred, the study arm 
of the participant, and the outcome/resolution. If there are no AEs in a given year, the 
report will include a statement to this effect. 
 
Procedures and timeline for reporting SAEs to NIAAA. 
 
SAEs, whether or not anticipated, will be reported to the NIAAA PO within 24 hours of 
the event by email. This 24 hour notification will include a brief explanation of the SAE 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
33 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
and when it occurred. A written follow up will be sent within 72 hours of the event. This 
written follow up will include information on the date of the event, what occurred, actions 
taken by project staff, planned follow up (if any), the intervention group/study arm of the 
affected participant, whether the event appears to be related to the intervention, and 
whether participant will continue in the study. 
 
Reporting of IRB actions to NIAAA. 
 
Follow-up reports to the NIAAA program official—made within 48 hours of IRB actions— 
will specify IRB actions related to study shut-down or changes. We will follow Wayne 
State University policy in the handling of all AEs and SAEs; see Appendix 1 for 
algorithm from the WSU IRB, which will be followed in all respects except with regard to 
unanticipated SAEs, which will be reported to NIAAA. 
 
Wayne State University Risk-Adverse Event Algorithm: 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
34 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
 
 
 
 
 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
35 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
7 STUDY OVERSIGHT 
 
The Principal Investigator was responsible for monitoring the safety and efficacy 
of the interventions, executing the Data and Safety Monitoring Plan (DSM), and 
complying with all reporting requirements. The PI will provide a DSM report to NIAAA 
on an annual basis, as part of the progress report. The DSM report will include the 
participants’ sociodemographic characteristics, expected versus actual recruitment 
rates, treatment retention rates, any quality assurance or regulatory issues that 
occurred during the past year, summary of adverse events (AEs) and serious adverse 
events (SAEs), and any actions or changes with respect to the protocol. The report will 
also include, when available, the results of any efficacy data analysis conducted. 
 
a. Data Monitoring Plan. Data was collected by researcher entry (interviews) or 
by direct participant entry (self-report) using secure technology (CIAS and Qualtrics; 
both of which use strong encryption and other data safety protocols). The codes that 
link participant names with study ID# were secured by the PI in a locked cabinet. All 
data was kept in the PI’s lab. 
The primary outcome was mean drinks per day over the past 30 days (as measured 
at both 1 and 3-month follow ups). Secondary outcome measures included past month 
heavy drinking days, alcohol-related consequences, and intention to reduce alcohol 
use. Outcome data was analyzed using ANCOVAs, factorial ordinal regression, or 
binary logistic regression, depending on each outcome’s distribution. The alpha level 
will be set at 5%. 
Data quality was facilitated by direct participant entry of most data directly into 
sophisticated data collection software, and use of double-entry for all data not entered 
directly by participants. Data quality was monitored regularly by Co-Investigator Beatty 
(at Wayne State), in concert with the PI and Co-Investigator. 
 
b.  Safety Monitoring Plan. For this study, we used the FDA definition of serious 
adverse events (SAEs). Any SAE, whether or not related to study intervention, will be 
reported to the IRB and NIAAA. 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 
a SAE, the participant will be monitored by the investigator via ongoing status 
assessment until (1) a resolution is reached (i.e., the problem requiring hospitalization 
has resolved or stabilized with no further changes expected); (2) the SAE is determined 
to be clearly unrelated to the study intervention; or (3) the SAE results in death. 
Outcomes of SAEs will be periodically reported to NIAAA. A summary of the SAEs that 
occurred during the previous year will be included in the annual progress report to 
NIAAA. 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
36 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
8 STATISTICAL CONSIDERATIONS 
 
8.1 Study Hypotheses 
 
Factorial designs differ from randomized trials in several ways. Perhaps most 
importantly, in factorial designs each participant either receives or does not receive 
each independent variable. This allows analysis of each factor to utilize the entire 
sample, which in turn allows each main effect to be powered based on the entire 
sample rather than a fraction of the sample (as with randomized clinical trials). This 
efficiency makes factorial designs ideal for pre-trial optimization. Further, use of effect 
coding (-1, 1) rather than dummy coding (0, 1) renders orthogonal all main and 
interaction effects, increasing power for detection of interaction effects (Collins, 2009). 
Although R21 studies are not typically fully powered, the current N of 352, presuming 
use of intent to treat analysis, provides 80% power to detect main/interaction effects of d 
≥ .3. 
Analyses will follow standard procedures for evaluating distributional assumptions, 
disproportionate or biased follow-up, and randomization success, and will utilize 
transformations and replacement of missing data using multiple imputation as 
appropriate. Primary analyses will evaluate main and interaction effects on mean 
drinks/day in the past 30 days, as measured by both the TLFB and the 
Quantity/Frequency Questionnaire. (Secondary analyses will similarly examine main 
and interaction effects on binge drinking days, drinking consequences, and pre-post 
changes in intention to reduce drinking.) A single 2X2X2X2X2 ANCOVA (or factorial 
ordinal/binary logistic regression, depending outcome distribution) will test the following 
hypotheses: 
 
 Hypothesis 1. There will be significant main effects on mean drinks/day for the 
two factors consistent with Common Factors Theory (empathy and positive 
regard). 
 Hypothesis 2. There will be significant main effects on mean drinks/day for the 
two factors consistent with the Media Equation Theory (voice and narrator). 
 Hypothesis 3. There will be significant main effects on mean drinks/day for 
motivational content. 
 Hypothesis 4. Mean drinks/day will be lower when one or more of the common 
factors (empathy, positive regard) is combined with a voice and/or a narrator. 
 Hypothesis 5. Mean drinks/day will be lower when motivational content is 
combined with one or more common factors and/or with voice/narrator. 
 
Following MOST guidelines (Collins et al, 2009), if intervention components (or 
combinations of components) are clearly effective, we will proceed to developing an 
optimized intervention. If intervention components show some effectiveness, we will 
conduct refining experiments to explore what form/dose of the components will 
maximize effects. If there are no significant main or interaction effects, we will conduct 
additional exploratory/developmental studies using new factors. 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
37 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
 
V. Research Strategy: Limitations and Design Considerations 
Given its status as an R21 application, this research aims to be innovative and to 
seek evidence of preliminary effects in an important area of research. Additionally, we 
note the following design considerations. 
1. Should we use college student participants? CDBIs for undergraduates generally 
contain the same content as those administered to clinical and community samples 
(e.g., normed feedback, change plan, etc; Larimer et al, 2007). Moreover, effect 
sizes for CDBIs in college vs. non-college samples do not differ (Portnoy et al, 
2008). This initial, exploratory study will allow us to recruit participants in high 
numbers and over a short time period. We will test for generalizability—which we 
expect to be present—in future studies. 
2. Are we under-powered? Our proposed sample (N=352) will give us marginally 
sufficient power (80% power to detect effects up to d=.3). However, R21 exploratory 
studies typically lack even marginally sufficient power; we see this as a large 
exploratory study rather than as an underpowered confirmatory study, with its size 
made possible by our intentional use of a readily available sample. 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
38 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
9 SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS 
 
Study staff will maintain appropriate medical and research records for this study, in 
compliance with ICH E6, Section 4.9 and regulatory and institutional requirements for 
the protection of confidentiality of subjects. Study staff will permit authorized 
representatives of NIAAA and regulatory agencies to examine (and when required by 
applicable law, to copy) research records for the purposes of quality assurance reviews, 
audits, and evaluation of the study safety, progress and data validity. 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
39 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
10 QUALITY CONTROL AND QUALITY ASSURANCE 
 
The accuracy with which data input matches data output using the software was 
exhaustively checked prior to beginning the trial (using sample protocols).We have 
never found data coding errors on the part of the software in all previous trials. Although 
no problems are expected given past experiences with this technology, any evidence of 
errors in data recording by the ACASI will result in dropping all participants since the 
last quality check. Data will be checked once per month for out of range values and 
other quality issues. Data from participants will be accessible only with appropriate 
passwords known only to the PI and project coordinator. 
 
The PI, the project manager, and the RA will meet regularly and review all data 
collection procedures, as well as recent data, to ensure that study procedures are being 
followed appropriately and all data are present. 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
40 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
11 ETHICS/PROTECTION OF HUMAN SUBJECTS 
 
11.1 
Ethical Standard 
 
The investigator will ensure that this study is conducted in full conformity with the 
principles set forth in The Belmont Report: Ethical Principles and Guidelines for the 
Protection of Human Subjects of Research, as drafted by the US National Commission 
for the Protection of Human Subjects of Biomedical and Behavioral Research (April 18, 
1979) and codified in 45 CFR Part 46 and/or the ICH E6. 
 
11.2 Institutional Review Board 
 
The Wayne State University Internal Review Board (IRB) oversees research to ensure 
the safe and ethical conduct of human participant research by all faculty, staff, and 
students of WSU. This includes reviews of proposed research, oversight committees, 
continuing oversight for compliance with regulations and policy, quality assurance, and 
education and training for investigators, staff, and committee members. The IRB is 
initially notified of proposed research prior to securement of funding and works with 
investigators to optimize study design, data collection, and associated consents and 
information sheets. After approval of study protocols, any changes must be submitted to 
the IRB via amendments. A yearly continuation is necessary so long as research is 
active; at this time, staff update the IRB of currently approved forms, enrollment figures, 
participant demographics, preliminary results (if applicable), and other pertinent 
information that allows the Board to determine study execution success and participant 
safety and protections. Upon discovering any adverse events, the Coordinator and PI 
are required to file a report with the IRB and perform any suggested response actions. 
Finally, the IRB assists staff in closing the study once data collection has been finalized. 
 
11.3 Informed Consent Process 
 
We will utilize written informed consent for those who meet all inclusion and exclusion 
criteria. This consent form will be summarized by the research assistant and also read, 
if the participant wishes. The consent form will describe the nature of the possible 
interventions, the kinds of questions that will be asked, follow-up procedures, the 
participant’s right to decline or quit at any time, and the possibility of distress as a result 
of some of the questions or material. Participants will also be told that their data will be 
identified by a code number only, with the only link between that code and their data 
being a single form kept locked in the PI’s office. Finally, although we will not ask any 
questions that might elicit reportable information in these areas, the consent form will 
clearly note the possible need to breach confidentiality should the investigators become 
aware of reportable information regarding child abuse, neglect, suicide risk, or infectious 
disease. 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
41 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
11.4 Inclusion of Women and Minorities (Special Populations) 
 
Participants will be 352 male and female undergraduate students at Wayne State 
University in Detroit. The majority of participants will be recruited from the Wayne State 
Psychology department subject pool which serves between 2400 and 2500 
undergraduates each year. Currently, the subject pool is 72% female, 40% Caucasian, 
19% African-American, 18% Arab, 13% Asian, 4% Multiracial, 3% Hispanic, and 3% 
‘Other.’ A subset of participants will also be recruited through advertisements posted on 
the Wayne State University webpage. The undergraduate population, as a whole, at 
Wayne State is 55% female, 53% Caucasian, 21% African-American, 8% Asian, 8% 
‘Unknown’ race/ethnicity, 5% Hispanic, 3% Multiracial, and 2% ‘Other.’ 
 
11.5 Subject Confidentiality 
 
 
Subject confidentiality is strictly held in trust by the investigators, study staff, and the 
sponsor(s) and their agents. This confidentiality is extended to cover testing of 
biological samples and any study information relating to subjects. 
 
The study protocol, documentation, data, and all other information generated will be 
held in strict confidence. No information concerning the study or the data will be 
released to any unauthorized third party without prior written approval of the sponsor. 
The authorized representatives of the sponsor may inspect all study documents and 
records required to be maintained by the investigator, including but not limited to, 
medical records (office, clinic, or hospital) for the study subjects. The clinical study site 
will permit access to such records. 
 
Breaches of confidentiality will be prevented in a number of ways. First, we will strictly 
separate identifying information and data, connecting them only via a linking table (with 
a hard copy kept in a locked file cabinet in the PI’s lab, and a password-protected 
electronic version kept on a secure WSU server). Old versions of the paper linking table 
will be shredded; the table will only be accessible by the PI and Project Coordinator. 
Second, breaches will also be prevented by encrypting all ACASI data in transit using 
AES-256 encryption (the highest level possible). Third, breaches will be prevented by 
further protecting saved data with extremely strong passphrases (combining capital 
letters, lowercase letters, and numbers, using at least 12 characters, and changing 
them monthly). Fourth, all study computers will be protected with a very strong 
passphrase. 
 
Should a breach be discovered, it will be reported within 24 hours to the WSU IRB and 
to NIAAA officials, followed by a written report within 72 hours. In addition to addressing 
and correcting the source of the breach, discussions with the IRB, the study DSMB, and 
NIAAA will determine whether study participants must be notified of the breach. 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
42 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
12 DATA HANDLING AND RECORD KEEPING 
 
12.1 Data Management Responsibilities 
Data collection and accurate documentation are the responsibility of the study staff 
under the supervision of the investigator. Unanticipated problems and adverse events 
must be reviewed by the investigator or designee. 
 
12.2 Data Capture Methods 
 
Most data will be collected using computer-based self-interview (ACASI) technology on 
a Tablet computer, with data being encrypted in transit and stored on a secure server; 
further, all data in the ACASI system will only be identified only with a non-identifying ID 
number for the participant. A single paper copy of the table linking this number to the 
participant’s name will be kept locked in a file cabinet in the PI’s lab, with a password 
protected electronic version stored on a secure WSU server with restricted access, such 
that only the PI and the Project Coordinator will have access to the server and to the 
passwords for the linking table file. The PI’s lab is kept locked, in a locked and alarmed 
secure building on campus. 
 
12.3 Data Entry 
Data entry for all self-report measures will be completed directly by the participant onto 
a tablet computer using the ACASI software. 
 
Regarding the ACASI: the accuracy with which data input matches data output will be 
exhaustively checked prior to beginning the trial, using sample protocols. (Note: we 
have never found data coding errors on the part of the software in all previous trials.) 
Further, we will test a randomly chosen sample protocol monthly following trial initiation. 
Although no problems are expected given past experiences with this technology, any 
evidence of errors in data recording by the ACASI will result in dropping all participants 
since the last quality check. In addition, data will be checked once per month for out of 
range values and other quality issues. All data will be accessible only with appropriate 
passwords known only to the PI and project coordinator. 
 
12.4 Schedule and Content of Reports 
PI, the project manager, and the RA will meet at least monthly while data collection is 
ongoing, to review all data collection procedures, as well as recent data, to ensure that 
study procedures are being followed appropriately and all data are present. 
 
12.5 
Study Records Retention 
Study records will be maintained for at least three years from the date that the grant 
federal financial report (FFR) is submitted to the NIH. 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
43 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
12.6 Protocol Deviations 
A protocol deviation is any noncompliance with the clinical study protocol, Good Clinical 
Practice, or Manual of Procedures requirements. The noncompliance may be on the 
part of the subject, the investigator, or study staff. As a result of deviations, corrective 
actions are to be developed by the study staff and implemented promptly. 
 
These practices are consistent with investigator and sponsor obligations in ICH E6: 
 
 Compliance with Protocol, Sections 4.5.1, 4.5.2, 4.5.3, and 4.5.4. 
 Quality Assurance and Quality Control, Section 5.1.1 
 Noncompliance, Sections 5.20.1 and 5.20.2. 
All deviations from the protocol must be addressed in study subject source documents 
and promptly reported to NIAAA and the local IRB, according to their requirements. 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
44 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
13 PUBLICATION/DATA SHARING POLICY 
 
This study will comply with the NIH Public Access Policy, which ensures that the public 
has access to the published results of NIH funded research. It requires scientists to 
submit final peer-reviewed journal manuscripts that arise from NIH funds to the digital 
archive PubMed Central upon acceptance for publication. 
 
This study also follows the policy that requires that all clinical trials be registered in a 
public trials registry such as ClinicalTrials.gov, which is sponsored by the National 
Library of Medicine. The Clinical Trials registration number for this study is 
NCT02952872. 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
45 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
14 LITERATURE REFERENCES 
 
Aalto, M., Pekuri, P. & Seppa, K. (2003). Obstacles to carrying out brief intervention for 
heavy drinkers in primary health care: A focus group study. Drug and Alcohol Review, 
22, 169-173. 
 
Barett-Lennard, G. T. (1978). The Relationship Inventory: Development and adaptation. 
Catalog of Selected Documents in Psychology 8 (68, MS #1732). 
 
Bertholet, N., Daeppen, J.B., Wietlisback, V., Fleming, M. & Burnand, B. (2005). 
Reduction of alcohol consumption by brief alcohol intervention in primary care: 
Systematic review and metaanalysis. Arch Intern Med,165, 986–995. 
 
Beich, A., Gannik, D., & Malterud, K. (2002). Screening and brief intervention for 
excessive alcohol use: qualitative interview study of the experiences of general 
practitioners. Bmj, 325, 870. 
 
Bertholet, N., Palfai, T., Gaume, J., Daeppen, J. & Saitz, R. (2013). Do brief alcohol 
motivational interventions work like we thinking they do? Alcoholism: Clinical and 
Experimental Research, 
 
Bien, T.H., Miller, W.R. & Tonigan, J. S. (1993). Brief interventions for alcohol problems: 
A review. Addiction, 88, 315-335. 
 
Bickmore, T., Gruber, A. & Picard, R. (2005). Establishing the computer–patient working 
alliance in automated health behavior change interventions. Patient Education and 
Counseling, 59, 21-30. 
 
Boucher, E.E., Harwood, H.J., Sacks, J.J., Simon, C.J. & Brewer, R.D. (2011). 
Economic costs of excessive alcohol use consumption in the U.S., 2006. American 
Journal of Preventative Medicine, 41, 516-524. 
 
Carey, K.B, Scott-Sheldon, L.A., Elliot, J.C., Bolles, J.R. & Carey, M.P. (2009). 
Computer-delivered interventions to reduce college student drinking: A meta-analysis. 
Addiction 104, 1807–1819. 
 
Collins, L.M., Baker, T.B., Mermelstein, R.J., Piper, M.E., Jorenby, D.E., Smith, S.S., 
Schlam, T.R., Cook, J.W., & Fiore, M.C. (2011). The Multiphase Optimization Strategy 
for engineering effective tobacco use interventions. Annals of Behavioral Medicine, 41, 
208-226. 
 
Collins, L.M., Dziak, J.R., & Li, R. (2009). Design of experiments with multiple 
independent variables: A resource management perspective on complete and reduced 
factorial designs. Psychological Methods, 14, 202-224. 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
46 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
Donoghue, K., Patton, R., Phillips, T., Deluca, P. & Drummond, C. (2014). The 
Effectiveness of Electronic Screening and Brief Intervention for Reducing Levels of 
Alcohol Consumption: A Systematic Review and Meta-Analysis. Journal of Medical 
Internet Research, 16, e142. 
 
Elliot, R., Bohart, A.C., Watson, J.C. & Greenberg, L.S. (2011). Empathy. 
Psychotherapy, 48, 43-49. 
 
Fals-Stewart, W., O'Farrell, T. J., Freitas, T. T., McFarlin, S. K., & Rutigliano, P. (2000). 
The timeline followback reports of psychoactive substance use by drug-abusing 
patients: psychometric properties. J Consult Clin Psychol, 68, 134-144. 
Farber, B.A. & Doolin, E.M. (2011). Positive Regard. Psychotherapy, 48, 58-64. 
Grekin, E.R. (2012). Perceived racism and alcohol consequences among african- 
american and Caucasian college students. Psychology of Addictive Behaviors, 26, 924- 
930 
 
Grekin, E.R., Brennan, P.A. & Hammen, C. (2005). Parental alcohol use disorders and 
child delinquency: The mediating effects of executive functioning and chronic family 
stress. Journal of Studies on Alcohol, 66, 14-22. 
 
Grekin, E.R. & Sher, K.J. (2006). Alcohol dependence symptoms among college 
freshmen: Prevalence, stability and person/environment interactions. Experimental and 
Clinical Psychopharmacology, 14, 329-338. 
 
Grekin, E.R., Svikis, D.S., Lam, P., Connors, V., LeBreton, J., Streiner, D.L., Smith, C. & 
Ondersma, S.J., (2010). Drug use during pregnancy: Validating the Drug Abuse 
Screening Test against physiological measures. Psychology of Addictive Behaviors, 24, 
719-723. 
 
Goudriaan, A., Grekin, E.R. & Sher, K.J. (2011). Decision making and response 
inhibition as predictors of heavy alcohol use: A prospective study. Alcoholism: Clinical 
and Experimental Research, 35, 1050-1057. 
 
Hilbink, M., Voerman, G., van Beurden, I., Penninx, B. & Laurant, M. (2012). A 
randomized controlled trial of a tailored primary care program to reverse excessive 
alcohol consumption. Journal of the American Board of Family Medicine, 25, 712-722. 
 
Hingson, R.W., Zha, W. & Weitzman, E.R. (2009). Magnitude of and trends in alcohol- 
related mortality and morbidity among U.S. college students ages 18-24, 1988-2005. 
Journal of Studies on Alcohol and Drugs, 16, 12-20. 
 
Johnston, L.D., O’Malley, P.M., Bachman, J.G. & Schulenberg, J.E. (2008). Monitoring 
the Future National survey results on drug use, 1975-2007: Volume 1, secondary school 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
47 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
students, (NIH Publication No. 08-6418A). Bethesda, MD: National Institute on Drug 
Abuse. 
 
Kaner, E.F, Beyer, F., Dickinson, H.O., Pienaar, E., Campbell, F., Schlesinger, C., 
Heather, N. Suanders, J. & Bernand, B.. (2007) Effectiveness of brief alcohol 
interventions in primary care populations. Cochrane Database of Systematic Reviews, 
Art. No.: CD004148. 
 
Kaner E, Dickinson, H., Beyer F, Pieneer, E., Schlesinger, C., Campbell, F., Saunders, 
J.B., Bernand, B. & Nick, H. (2009). The effectiveness of brief alcohol interventions in 
primary care settings: A systematic review. Drug and Alcohol Review, 28, 301–323. 
 
Kaplan B, Farzanfar R & Friedman R. (2003). Personal relationships with an intelligent 
interactive telephone Health behavior advisor system: a multimethod study using 
surveys and ethnographic interviews. Int J Med Inform, 71, 33–41. 
 
Kohler, S. & Hofmann, K. (2015). Can Motivational Interviewing in Emergency Care 
Reduce Alcohol Consumption in Young People? A Systematic Review and Meta- 
analysis. Alcohol and Alcoholism, 50, 107-117. 
 
Kypri, K., Langley, J. D., Saunders, J. B., & Cashell-Smith, M. L. (2007). Assessment 
may conceal therapeutic benefit: findings from a randomized controlled trial for 
hazardous drinking. Addiction, 102, 62-70. 
 
Laforge, R.G., Borsari, B. & Baer, J.S. (2005). The utility of collateral informant 
assessment in college alcohol research: Results from a longitudinal prevention trial. J 
Stud Alcohol, 66, 479-487. 
 
Larimer, M.E. & Cronce, J.M. (2007). Identification, prevention, and treatment revisited: 
Individual-focused college drinking prevention strategies 1999–2006. Addictive 
Behaviors 32, 2439–2468. 
 
Madras, B.K., Compton, W.M., Avula, D., Stegbauer, T., Stein, J. B. & Clark, H. W. 
(2009). Screening, brief interventions, referral to treatment (SBIRT) for illicit drug and 
alcohol use at multiple healthcare sites: Comparison at intake and 6 months later. Drug 
and Alcohol Dependence, 99, 280-295. 
 
Maio, R.F, Shope, J.T., Blow, F.C., Gregor, M.A., Zakrajsek, J.S., Weber, J.E. & 
Nypaver, M.M. (2005). A randomized controlled trial of an emergency department- 
based interactive computer program to prevent alcohol misuse among injured 
adolescents. Annals of Emergency Medicine 45, 420–429. 
 
McCambridge, J. & Kypri, K. (2011). Can Simply Answering Research Questions 
Change Behaviour? Systematic Review and Meta Analyses of Brief Alcohol Intervention 
Trials, PLOS ONE. 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
48 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
McCance-Katz, E.F. & Satterfield, J. (2012). SBIRT: A key to integrate prevention and 
treatment of substance abuse in primary care. The American Journal of Addictions, 21, 
176-177. 
 
McClure, J.B., Shortreed, S., Bogart, A., Derry, H., Riggs, K., St. John, J., Nair, V., & 
An, L. (2013). The effect of program design on engagement with an Internet-based 
smoking intervention: A randomized factorial trial. Journal of Medical Internet Research, 
15(3): e69. 
 
Miller, W. R., & Rollnick, S. (2002). Motivational Interviewing: Preparing People for 
Change (Second ed.). New York: Guilford. 
 
Mokdad, A.H., Marks, J.S., Stroup, D.F. & Gerberding, J.L. (2005). Actual causes of 
death in the United States, 2000. JAMA, 293, 298. 
 
Moyer A., Finney, J.W., Swearingen, C.E. & Vergun, P. (2002). Brief interventions for 
alcohol problems: a meta-analytic review of controlled investigations in treatment- 
seeking and non-treatment-seeking populations. Addiction, 97, 279-292. 
 
Naar-King, S., Outlaw, A. Y., Saar, M., Parsons, J. T., Belzer, M., MacDonnell, K., 
Tanney, M., Ondersma, S. J., & The Adolescent Medicine Network for HIV/AIDS 
Interventions (2013). Motivational Enhancement System for Adherence (MESA): Pilot 
Randomized Trial of a Brief Computer-Delivered Prevention Intervention for Youth 
Initiating Antiretroviral Treatment. Journal of Pediatric Psychology, 38, 638-48. 
 
Nass, C. & Moon, Y. (2000). Machines and mindlessness: Social responses to 
computers. Journal of Social Issues, 56, 81-103. 
 
Norcross, J.C. & Wampold, B.E. (2011). Evidence-Based Therapy Relationships: 
Research Conclusions and Clinical Practices. Psychotherapy, 48, 98-102. 
 
O’Donnell, A., Anderson, P., Newbury-Birch, D., Schulte, B., Schmidt, C., Reimer, J. & 
Kaner, E. (2013). The impact of brief interventions in primary health care: A systematic 
review of reviews. Alcohol and Alcoholism, 49, 66-78. 
 
O’Malley, P.M & Johnston, L.D. (2002). Epidemiology of alcohol and other drug use 
among American college students. Journal of Studies on Alcohol, Suppl 14, 23-39. 
 
Ondersma, S. J., Chase, S. K., Svikis, D. S., & Schuster, C. R. (2005). Computer-based 
brief motivational intervention for perinatal drug use. J Subst Abuse Treat, 28, 305-312. 
 
Ondersma, S. J., Grekin, E. R., & Svikis, D. (2011). The potential for technology in brief 
interventions, and during session prediction of computer-delivered brief intervention 
response. Substance Use & Misuse, 46, 77-86. 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
49 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
Ondersma, S. J., Svikis, D. S., Lam, P. K., Connors-Burge, V. S., Ledgerwood, D. M., & 
Hopper, J. A. (2012). A randomized trial of computer-delivered brief intervention and 
low-intensity contingency management for smoking during pregnancy. Nicotine Tob 
Res, 14(3), 351-360. 
 
Ondersma, S. J., Svikis, D. S., & Schuster, C. R. (2007). Computer-based brief 
intervention a randomized trial with postpartum women. Am J Prev Med, 32, 231-238. 
 
Ondersma, S.J., Svikis, D.S., Thacker, L.R., Beatty, J.R., & Lockhart, N. (2014). 
Computer-delivered screening and brief intervention (e-SBI) for postpartum drug use: A 
randomized trial. Journal of Substance Abuse Treatment, 46, 52-59 
 
Ondersma, S. J., Winhusen, T., & Lewis, D. F. (2012). Pre-treatment change in a 
randomized trial with pregnant substance-abusing women in community-based 
outpatient treatment. Contemp Clin Trials, 33, 1074-1079. 
 
Read, J.P., Kahler, C.W., Strong, D.R. & Colder, C.R. (2006). Development and 
Preliminary Validation of the Young Adult Alcohol Consequences Questionnaire. 
Journal of Studies on Alcohol, 67, 169-177. 
 
Reeves, B., & Nass, C. (1996). The Media Equation: How People Treat Computers, 
Television, and New Media Like Real People and Places. Cambridge University Press. 
 
Rooke, S., Thorsteinsson, E., Karpin, A., Copeland, J., & Allsop, D. (2010). Computer- 
delivered interventions for alcohol and tobacco use: a meta-analysis. Addiction, 105, 
1381-1390. 
 
Schwartz, R.P., Gryczynski, J., Mitchell, S.G., Gonzales, A., Moseley, A., Peterson, 
T.R., Ondersma, S.J., & O’Grady, K.E. (2014). Computerized v. in-person Brief 
Intervention for drug misuse: A randomized clinical trial. Addiction 
 
Sobell, L.C., Cunningham, J.A., Sobell, M.B., Agrawal, S., Gavin, D.R., Leo, G.I. & 
Singh, K.N. (1996). Fostering self-change among problem drinkers: A proactive 
community intervention. Addictive Behaviors, 21, 817-833. 
 
Sobell, L. C., & Sobell, M. B. (1996). Timeline FollowBack: A Calendar Method for 
Assessing Alcohol and Drug Use. Toronto, Ontario: Addiction Research Foundation. 
 
Substance Abuse and Mental Health Services Administration. (2012). Results from the 
2011 National Survey on Drug Use and Health. Rockville, MD: Office of Applied 
Studies, NSDUH Series H-44, HHS Publication No. (SMA) 12-4713. 
 
Tanner-Smith, E.E. & Lipsey, M.W. (2015). Brief alcohol interventions for adolescents 
and young adults: A systematic review and meta-analysis. Journal of Substance Abuse 
Treatment, 51, 1-18. 

Optimizing e-interventions for Alcohol Use: Do Common Factors Apply? 
Protocol 1 
Version 1 
12/5/2018 
50 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
 
 
U.S. Dept. of Health and Human Services, National Institute on Alcohol Abuse and 
Alcoholism. (1995). The physicians' guide to helping patients with alcohol problems. 
Bethesda, Md.: NIH publication no. 95–3769. 
 
VanBeurden, I., Anderson, P., Akkermans, R.P., Grol, R.P., Wensing, M. & Laurant, 
M.G. (2012). Involvement of general practitioners in managing alcohol problems: a 
randomized controlled trial of a tailored improvement programme. Addiction, 107, 1601- 
1611. 
 
Wampold, B. E. (2001). The great psychotherapy debate: Models, methods and 
findings. Mahwah, NJ. Erlbaum. 
 
Webb, T. L., Joseph, J., Yardley, L., & Michie, S. (2010). Using the internet to promote 
health behavior change: a systematic review and meta-analysis of the impact of 
theoretical basis, use of behavior change techniques, and mode of delivery on efficacy. 
J Med Internet Res, 12, e4. 
 
Wilk, A.L, Jensen, N.M. & Haviqhurst, T.C. (1997). Meta-analysis of randomized control 
trials addressing brief interventions in heavy alcohol drinkers. Journal of General 
Internal Medicine, 12, 274-283.