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Prior et al

ProtocolA Web-Based Cognitive Bias Modification Intervention (Re-train
Your Brain) for Emerging Adults With Co-occurring Social Anxiety
and Hazardous Alcohol Use: Protocol for a Multiarm Randomized
Controlled Pilot Trial
Katrina Prior1, BSci(Psych)(Hons)/BCom, PhD; Elske Salemink2, MSc, PhD; Reinout W Wiers3,4, MSc, PhD; Bethany
A Teachman5, BPsych(Hons), PhD; Monique Piggott1, BPsych; Nicola C Newton1, BPsych(Hons), PhD; Maree
Teesson1, BSci(Psych)(Hons), PhD; Andrew J Baillie6, BSci(Psych)(Hons), MClinPsych, PhD; Victoria Manning7,
BSci(Psych)(Hons), MSc, PhD; Lauren F McLellan8, BPsych (Hons), MClinPsych, PhD; Alison Mahoney9, BPsych(Hons), DPsych(Clin), PhD; Lexine A Stapinski1, BPsych (Hons), MClinPsych, PhD
1

The Matilda Centre for Research in Mental Health and Substance Use, The University of Sydney, Sydney, Australia

2

Experimental Psychopathology Lab, Department of Clinical Psychology, Utrecht University, Utrecht, Netherlands

3

Addiction Development and Psychopathology (ADAPT) Lab, Department of Psychology, University of Amsterdam, Amsterdam, Netherlands

4

Center for Urban Mental Health, University of Amsterdam, Amsterdam, Netherlands

5

Department of Psychology, School of Arts and Sciences, University of Virginia, Virginia, VA, United States

6

Sydney School of Health Sciences, The University of Sydney, Sydney, Australia

7

Eastern Health Clinical School, Faculty of Medicine, Nursing & Health Sciences, Monash University, Melbourne, Australia

8

Centre for Emotional Health, Department of Psychology, Macquarie University, Sydney, Australia

9

Clinical Research Unit for Anxiety and Depression, St Vincent's Public Hospital, Sydney, Australia

Corresponding Author:
Katrina Prior, BSci(Psych)(Hons)/BCom, PhD
The Matilda Centre for Research in Mental Health and Substance Use
The University of Sydney
Level 6, Jane Foss Russell building (G02)
Sydney, 2006
Australia
Phone: 61 02 8627 9032
Email: katrina.prior@sydney.edu.au

Abstract
Background: Alcohol use and anxiety disorders commonly co-occur, resulting in a more severe clinical presentation and poorer
response to treatment. Research has shown that approach bias modification (ApBM) and interpretation bias modification (IBM)cognitive retraining interventions can be efficacious adjunctive treatments that improve outcomes for alcohol use and social
anxiety, respectively. However, the acceptability, feasibility, and clinical utility of combining ApBM and IBM programs tooptimize treatments among comorbid samples are unknown. It is also unclear whether integrating ApBM and IBM within eachtraining session or alternating them between each session is more acceptable and efficacious.
Objective: This paper describes the protocol for a randomized controlled pilot trial investigating the feasibility, acceptability,and preliminary efficacy of the Re-train Your Brain intervention—an adjunct web-based ApBM+IBM program—among a clinicalsample of emerging adults with hazardous alcohol use and social anxiety.
Methods: The study involves a three-arm randomized controlled pilot trial in which treatment-seeking emerging adults (18-30
years) with co-occurring hazardous alcohol use and social anxiety will be individually randomized to receive the Re-train Your
Brain integrated program, delivered with 10 biweekly sessions focusing on both social anxiety and alcohol each week, plus
treatment as usual (TAU; ie, the model of care provided in accordance with standard practice at their service; n=30); the Re-train
Your Brain alternating program, delivered with 10 biweekly sessions focusing on social anxiety one week and alcohol the next
week, plus TAU (n=30); or TAU only (n=30). Primary outcomes include feasibility (uptake, follow-up rates, treatment adherence,
attrition, and adverse events) and acceptability (system usability, client satisfaction, user experience, and training format preference).
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Secondary efficacy outcomes include changes in alcohol approach and interpretation biases, social anxiety, and alcohol use (eg,drinks per day, binge drinking, drinking motives, severity of dependence, and cravings). The primary end point will be posttreatment(6 weeks postbaseline), with a secondary end point at 3 months postbaseline. Descriptive statistics will be conducted for primary
outcomes, whereas intention-to-treat, multilevel mixed effects analysis for repeated measures will be performed for secondary
outcomes.
Results: This study is funded from 2019 to 2023 by Australian Rotary Health. Recruitment is expected to be completed by
mid-2022 to late 2022, with follow-ups completed by early 2023.
Conclusions: This study will be the first to evaluate whether an ApBM+IBM program is acceptable to treatment-seeking,emerging adults and whether it can be feasibly delivered via the web, in settings where it will ultimately be used (eg, at home).
The findings will broaden our understanding of the types of programs that emerging adults will engage with and whether the
program may be an efficacious treatment option for this comorbidity.
Trial
Registration:
AustralianNew
Zealand
Clinical
TrialsRegistry
ACTRN12620001273976;
https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=364131
International Registered Report Identifier (IRRID): PRR1-10.2196/28667(JMIR Res Protoc 2021;10(7):e28667) doi: 10.2196/28667
KEYWORDS
alcohol; anxiety; cognitive bias modification; interpretation bias; approach bias; emerging adults

Introduction
Background
Social anxiety and alcohol use disorders are highly prevalent[1] and frequently co-occur [2,3]. When they are comorbid with
one another, the presenting symptoms tend to be more severe
and associated with greater functional impairment than either
disorder in isolation [4,5]. This is likely because of the existenceof a bidirectional, self-perpetuating cycle, whereby ongoinginteractions between the disorders serve to maintain or
exacerbate symptoms of both conditions [4,6,7]. The
co-occurrence of social anxiety and alcohol use disorders canalso interfere with treatment and recovery, with evidence fromclinical trials showing that standard single-disorder treatments
are less effective for people with comorbid anxiety and alcoholuse [4,8-11].
Given the frequent co-occurrence of these disorders and the
additional complications that this comorbidity confers on theindividual (eg, physical and psychological health, relationships,
work, and education) and society (eg, social and economic costs)[4,5,12], it is essential to understand and modify factors that
contribute to the maintenance of these conditions. One suchfactor is implicit or automatically activated cognitive biases.
Although there are a variety of implicit cognitive biases
associated with social anxiety and alcohol use disorders, twoof the most common are alcohol approach biases (ie, thetendency for alcohol cues to induce an automatic and habitualapproach action [13,14]) and interpretation biases (ie, thetendency to interpret ambiguous stimuli, scenarios, and eventsin a negative manner [15-17]). Alcohol approach biases havebeen shown to contribute to heavy drinking and predict futurealcohol use among adults with an alcohol use disorder [14] andhave also been associated with relapse to alcohol following
treatment [18,19]. Interpretation biases have been linked to thedevelopment of anxiety symptoms and disorders, and themaintenance and severity of these conditions [20,21].

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Over the past two decades, several computer-based cognitive
training paradigms, known as cognitive bias modification(CBM), have been developed to reduce symptoms by modifying
a range of maladaptive implicit biases, including alcohol
approach and anxiety-related interpretation biases. Approach
bias modification (ApBM) is one of the most common types of
CBM programs trialed as an adjunctive treatment for alcohol
use disorders. It seeks to train adaptive alcohol-avoidance
tendencies by getting an individual to repeatedly push away
images of alcohol shown on a computer screen. Interpretation
bias modification (IBM) is one of the dominant CBM programs
for ameliorating anxiety symptoms, particularly social anxiety.
IBM directly targets negative interpretation biases by repeatedly
presenting individuals with emotionally ambiguous social
scenarios and training them to resolve the uncertainty in apositive or neutral (vs threatening) way [22]. Several large
randomized controlled trials (RCTs) among clinical samples
show particularly promising findings for ApBM and IBM
interventions, especially in instances where they are added as
an adjunct to standard evidence-based treatments, such as
cognitive behavioral therapy (as described in detail later)[23-28]. It is argued that this is likely because clients intreatment are typically motivated to change their thoughts andbehaviors, which may be a prerequisite for successful training
effects [29]. By adding CBM on top of conventional treatment
approaches, treatment not only is able to target conscious,
deliberate, and explicit negative thinking styles and behavioral
responses but can also target unhealthy habitual and implicit
processes [30-32]. Thus, a combination of these complementary
approaches further aids in the effectiveness of treatment on
clinical outcomes. In contrast, there has been mixed empiricalsupport for the efficacy of ApBM and IBM programs as
stand-alone interventions among nonclinical samples (eg, heavy
drinking university students) [29,33,34]. Meta-analyses thatsynthesize findings on efficacy from a mixture of clinical andnonclinical studies have produced similar inconclusive findings[34,35], perhaps as a result of the substantial heterogeneity instudy samples, designs, and methodologies [29,36].
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Several large RCTs [23-26] and reviews [29,37,38] haveprovided evidence in support of the beneficial effects of ApBM
when delivered to clinical samples in conjunction with standard
treatments. Notably, 3 studies in Germany showed that theprovision of 4-12 sessions of ApBM alongside treatment as
usual (TAU; eg, inpatient alcohol use treatment or
abstinence-oriented cognitive behavioral therapy) toalcohol-dependent adults was associated with significantly lower
alcohol consumption and 7%-13% reduced rates of relapse one
year later compared with patients who received TAU plus asham placebo training or TAU only [23,24,26]. One of thesestudies reported that the change in alcohol approach biases
mediated the change in relapse rates and a stronger approach
bias at baseline moderated ApBM effects [24], whereas anotherwas unable to replicate these effects [26]. Furthermore, a recent
multisite RCT conducted in Australia reported significant
improvements in abstinence rates among those given four
sessions of ApBM during inpatient detoxification (54%), relative
to sham control training (42%) [39]. A significant reduction inapproach bias was observed among those in ApBM but not in
the sham-training condition after training. Overall, ApBM has
shown fairly consistent promising effects in clinical contexts
and has since been added to German and (forthcoming)
Australian guidelines for treating alcohol-related disorders[40,41].
Clinical studies investigating the efficacy of IBM have shownthat training can promote the development of a positive
interpretive bias in socially anxious populations and that thesemodifications are associated with reductions in social anxiety
symptoms [27,28]. Although there are fewer clinical RCTs in
number relative to ApBM, one study in the United States foundthat adults diagnosed with generalized social anxiety disorder
who received 12 sessions of IBM experienced significantly
greater reductions in negative interpretations of ambiguous
scenarios, self-reported and clinician-rated social anxiety
symptoms, and rates of social anxiety disorder diagnosis (65%vs 13%) from pre- to postassessment, relative to a shamcontrol-training condition. Moreover, the effects on social
anxiety were sustained at the 3-month follow-up [27]. Similarly,
a pilot study found that the provision of four IBM sessions
combined with CBM for attentional biases to an outpatient
sample diagnosed with social or generalized anxiety disorder
was associated with significant reductions in both types ofcognitive bias and state and trait anxiety [28]. Studies
investigating the mechanism of change for these effects havereported that negative interpretation biases mediated therelationship between the training group and improvement insocial anxiety symptoms [27]. These findings are also supported
by a recent review of meta-analyses and a systematic review
and meta-analysis of CBM programs for anxiety, which bothconcluded that single- or multisession IBM training among
clinically diagnosed and subclinical samples can significantly
reduce threat-related interpretation biases [42] and reduce
anxiety levels compared with a sham training or waitlist control
condition [43].
A limitation to the clinical utility of ApBM and IBM
interventions to date is that they have predominantly been
restricted to the confines of a laboratory or clinic [44]. Despite
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Prior et al
this, internet delivery is a promising option for increasing thescalability and sustainability of these interventions. A handfulof published studies evaluating the effectiveness of web-based
ApBM and IBM have indicated that there is promise in thismode of delivery; however, additional studies are required tomake more definitive conclusions regarding their efficacy. For
instance, two studies in Europe provided evidence thatweb-based IBM training can significantly shift interpretations
from negative to positive [45,46], with one study showing
clinically significant improvement in social anxiety symptoms(eg, 48% of participants no longer met criteria for social anxiety
disorder after eight IBM sessions) [46]. Another study foundthat four sessions of web-based ApBM among
nontreatment-seeking problem drinkers were associated withimproved drinking outcomes across three active intervention
groups; however, this effect was also evident in the shamcontrol-training group [47]. The authors highlight that despite
their null findings, integrating web-based ApBM with more
traditional cognitive and motivational interventions may be key
to improving results and call for further research that combinesthese supplementary treatments. It is apparent that there is aneed for more studies of web-based CBM programs (particularly
ApBM) with clinical populations where there is a motivation
to change their thoughts and/or behaviors.
Overall, although the evidence base for the efficacy oflaboratory- and web-based ApBM and IBM is accumulating
for adults with singular disorders, their efficacy when delivered
to people with co-occurring social anxiety and alcohol use
problems remains largely unknown. To the authors’ knowledge,
only one RCT exists that examines the efficacy of an attentionbias–focused CBM program among a socially anxious,
alcohol-dependent adult sample (N=86) [48]. The findings
indicated that there were significant reductions in attentionalbiases, alcohol use disorder, and social anxiety symptoms inboth the intervention and control groups; however, no significant
between-group differences were identified for any symptom
measures. Given the interconnections between anxiety andalcohol use problems and the likely coexistence of approachand interpretation biases, a promising avenue that has not been
explored is the potential of combining existing effective ApBM
and IBM cognitive retraining protocols to optimize standard
treatments among comorbid anxiety-alcohol samples. Moreover,given the peak onset and disability associated with anxiety andalcohol use disorders occurs between adolescence and early
adulthood [49,50], the provision of a comorbidity-focused
ApBM+IBM training program at an earlier age (and earlier inthe course of their disorder) represents a promising opportunity
to intervene before problems become chronic and entrenchedin adulthood.
Addressing these gaps in the literature, the research teamcodeveloped a hybrid, web-based ApBM+IBM for emerging
adults with co-occurring hazardous alcohol use and social
anxiety (Re-train Your Brain), as a supplement to TAU for
anxiety and/or alcohol use. As trial repetition, boredom, anddisengagement are serious concerns for CBM training [28], it
deemed was important to assess attitudes toward this treatment
and adapt the program where necessary. In line with this, a study
was conducted to evaluate the acceptability of a beta version of
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the Re-train Your Brain program according to the perspectivesof clinicians and emerging adults with hazardous drinking andheightened social anxiety [51]. The results indicated that the
ApBM+IBM intervention was an acceptable adjunct totraditional evidence-based treatments with potential clinicalutility, a finding that mirrors previous CBM acceptability studies[52,53]. To enhance engagement, clinical utility, and intrinsic
motivation to complete the training, clinicians and emerging
adults suggested that the program should include a
psychoeducational and motivation enhancement-type module
before the first training session. In light of the aforementioned
issues surrounding boredom and disengagement from CBM
programs, it was considered possible that the format in which
the ApBM+IBM program is delivered might influenceengagement and outcomes. For instance, one delivery option
could be to integrate the ApBM and IBM components into eachtraining session (50:50 ratio) to provide variation in tasks withineach training session and reduce boredom. This may, in turn,result in better retention, engagement, and outcomes becauseof a shorter time being spent completing each repetitious task.
An integrated variation might also be especially beneficial
because it gives people practice shifting multiple cognitive
processes close in time, which likely better mimics the cognitive
flexibility needed in daily life (where a cue may require both
healthy alcohol-avoidance reactions and healthy interpretation
bias in a short space of time) as compared with more temporally
distant application of modified cognitive processes. It is equallypossible, however, that doing shorter bursts of the two types oftraining within each session may water down any potential
clinical effects. Another option could be to alternate the ApBM
and IBM training between sessions, thereby providing full-length
sessions of each type of training, although fewer in number toachieve the same treatment dose. Clinicians and emerging adults
were asked to rate the format they perceived would be most
preferable to end users of the program: (1) an integrated
program that combines shortened versions of both ApBM andIBM within each training session or (2) an alternating programthat provides ApBM in one training session and IBM in the
next, in an alternating pattern. The results indicated that there
was no consistent preference for the program format (8/15, 53%
vs 7/15, 47% for integrated and alternating, respectively), andfurther research is required to better understand the impact oftraining format on acceptability and efficacy outcomes. Overall,
the beta Re-train Your Brain ApBM+IBM program was wellreceived, and obtaining feedback from service providers andemerging adults was critical to ensuring that the program wasage-appropriate, engaging, and potentially useful for end users.
However, to date, no research has been conducted to evaluate
the feasibility of delivering this program, whether it is deemed
acceptable by people who complete the training, and how
efficacious it is in reducing the targeted cognitive biases,
hazardous drinking, and social anxiety symptoms.

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Aims
This paper describes the study protocol for a randomized
controlled pilot trial investigating the feasibility, acceptability,and preliminary efficacy of the Re-train Your Brainintervention—a web-based hybrid ApBM+IBM program—as
an adjunct to TAU for anxiety and/or alcohol use, comparedwith TAU only, among emerging adults with co-occurring
hazardous alcohol use and social anxiety disorder symptoms.
The Re-train Your Brain program will be delivered in two
formats (integrated or alternating) to ascertain which is preferredby emerging adults and whether one shows more promising
signs of efficacy.
It is hypothesized that the integrated and alternating Re-train
Your Brain ApBM+IBM programs will both be feasible toimplement and deemed acceptable by emerging adults. It ishypothesized that the integrated format will be rated as more
acceptable and engaging than the alternating format because of
the variation of tasks within each session (ie, less time will bespent on each task within each session, which may reduceboredom and disengagement often experienced because of therepetitive nature of each task). Although this is a pilot trial thatis not powered to detect clinically significant group-by-time
interaction effects, based on previous research, it is likely thatboth the integrated and alternating Re-train Your Brain programs
will result in trend improvements in cognitive biases, anxiety,and alcohol-related outcomes, relative to the control condition.
It is further hypothesized that greater effect sizes will beobserved in the integrated Re-train Your Brain intervention
group than in the alternating intervention group because of
greater levels of engagement with the program. The results will
be used to inform the design and power analysis of a future
definitive trial.

Methods
Setting and Trial Design
The study will be conducted nationally across Australia andwill involve a three-arm randomized controlled pilot trial inwhich eligible participants will be individually randomized toreceive (1) the integrated Re-train Your Brain program,delivered with 10 biweekly sessions focusing on both social
anxiety and alcohol each training (50:50 ratio) plus TAU for
anxiety and/or alcohol use (ie, the model of care provided inaccordance with standard practice at their service); (2) thealternating Re-train Your Brain program, delivered with 10
biweekly sessions focusing on social anxiety in one training
and alcohol in the next training in an alternating pattern plus
TAU; or (3) TAU only. The treatment dose in terms of totalintervention time will be the same for the two intervention
groups (groups 1 and 2). The primary end point will be theposttreatment assessment, conducted at 6 weeks following
baseline, with a secondary end point at 3 months postbaseline.
The study design is shown in Figure 1.

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Figure 1. Study design for the Re-train Your Brain pilot trial. ApBM: Approach Bias Modification; IBM: Interpretation Bias Modification; TAU:
treatment as usual.

Ethics Approval and Registration
The Re-train Your Brain pilot trial was prospectively registeredwith the Australian New Zealand Clinical Trials Registry(ACTRN12620001273976) and received ethical approval fromthe University of Sydney Human Research Ethics Committee(#2020/135).

ParticipantsParticipant Recruitment

Social Interaction Anxiety Scale-Short Form or ≥2 on the Social
Phobia Scale-Short Form [55]; (4) have access to the internet
via a laptop or PC and have a mouse-operable computer; (5) becurrently receiving psychological treatment from a healthprofessional for anxiety and/or alcohol use problems, forexample, psychologist, psychiatrist, mental health, or alcohol
or other drug counselor; and (6) be willing to complete all 10
ApBM+IBM sessions, if allocated to one of the active
intervention groups.

Young Australians (n=90) aged 18 to 30 years with harmful
alcohol use and heightened social anxiety symptoms who are
currently receiving psychological treatment will be recruited
into the study via an array of advertising methods, including
clinician referral, poster, and flyer advertisements (eg, in clinicalservices and universities), and online advertising via platforms,
such as Facebook, Twitter, and Google AdWords.

Individuals will be excluded because of the following reasons:inability or unwillingness to provide contact information (ie,phone and email); insufficient English literacy; active symptomsof psychosis, that is, a score of ≥3 on the Psychosis Screening
Questionnaire [56]; self-reported history of neurological diseaseor head injury with a loss of consciousness exceeding 30
minutes; self-reported intellectual disability or cognitive
impairment; and eyesight not normal or corrected to normal.

Inclusion and Exclusion Criteria

MeasuresTo be eligible, participants must (1) be Australians aged 18-30
years; (2) be currently reporting hazardous or harmful alcoholuse, that is, a score of ≥8 on the Alcohol Use Disorder
Identification Test [54]; (3) be currently experiencing at least
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Overview
Table 1 summarizes the schedule of assessments (including
measures used for primary and secondary outcomes andpotential moderators or covariates) and procedures over the
study period.

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Table 1. Schedule of assessments and procedures over the study period.
Assessments

Study period
Enrollment

Preallocation; t1 Intervention week(baseline)
1

2

3

4

5

Postallocation
t2 (6 weeks postbaseline)t2 (3 months postbaseline)✓✓

Enrollment
Informed consent✓aEligibility survey✓

Baseline survey✓

Cognitive assessments✓

Randomization✓

Interventions
✓

✓

✓

✓

✓

Group 2: Alternating ApBM+IBM
plus TAU

✓

✓

✓

✓

✓

Group 3: TAU (routine anxiety or
alcohol treatment)

✓

✓

✓

✓

✓

Group 1: Integrated ApBMb+IBMcdplus TAU

Assessments or measures
Primary outcomes
Treatment feasibility questions✓

Acceptability questions✓

System Usability Scale✓

Client Satisfaction Questionnaire✓

Treatment feedback questions✓✓

Postuser experience questions(intervention groups)

✓

✓

✓

✓

Secondary outcomes and covariates or moderator variables
Approach Avoidance Task

✓

✓

✓

Interpretation Recognition Task

✓

✓

✓

Comorbid Interpretation andExpectancy Biases

✓

✓

✓

✓

✓

✓

✓

✓

✓

Social Phobia Scale and Social ✓Interaction Anxiety Scale-Short
Forms
Patient Health Questionnaire-4✓

Alcohol Use Disorder Identifi- ✓cation Test
Timeline Follow Back

✓

✓

✓

Alcohol Craving Questionnaire–Short Form–Revised

✓

✓

✓

Severity of Alcohol Dependence Questionnaire

✓

✓

✓

Drinking Motives Questionnaire-Revised

✓

✓

✓

Weekly Social Anxiety andAlcohol Symptom questions
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✓

✓

✓

✓

✓

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Assessments

Prior et alStudy period
Enrollment

Preallocation; t1 Intervention week(baseline)
1aReadiness to Change Ruler✓

University of Rhode Island
Change Assessment✓

Psychological and pharmacological treatment

✓

2

3

4

5

Postallocation
t2 (6 weeks postbaseline)t2 (3 months postbaseline)

✓

✓

✓

✓

Denotes which assessments and/or measures were conducted at each time point.

b

ApBM: approach bias modification.

c

IBM: interpretation bias modification.

d

TAU: treatment as usual.

Primary Outcome Measures
Feasibility
The feasibility of the program will be assessed according to thepercentage of successfully recruited participants who agree toparticipate (ie, uptake), commence training, and decline
participation. At postintervention, feasibility will be measured
by the number of sessions completed; reporting of adverse
events via spontaneous reports in open-feedback questions or
to the study team or deterioration of social anxiety or alcohol
use symptoms (see Multimedia Appendix 1 [54,55,57-66] forfull details) [57,58]; and the proportion of participants who (1)complete the 10-session protocol (as a proportion of those whocommence at least one session of training, ie, treatment
adherence or compliance), (2) complete the mean optimum
number of six sessions, based on ApBM research [67], and (3)drop out before training is completed. Survey or cognitive
assessment follow-up rates will also be recorded as a measureof the feasibility of the RCT methodology at the 6-week and3-month time points.
Acceptability
Measures of acceptability and usability of the program will beassessed at postintervention (6-week postbaseline). The usabilityof the program will be assessed using the 10-item System
Usability Scale [68]. Items are rated on a 5-point Likert scaleranging from 1 (strongly disagree) to 5 (strongly agree). The
scores for each item are converted to a new number, ranging
from 0 to 4. A total score is then computed by summing theconverted item scores and multiplying this by 2.5, giving a rangeof 0 to 100. Higher values denote greater usability and higher
satisfaction with the program. Cut-off scores using a school
grade analogue have recently been suggested for interpretingthe scores (F=0-51.7; D=51.8-62.6; C=62.7-72.5; B=72.6-78.8;
and A=78.9-100), with a score over 68 being considered above
average [69]. Satisfaction with the program will be measured
by Client Satisfaction Questionnaire-8 [70]. Items are rated on
a 4-point Likert scale from 1 to 4, with total scores ranging from
8 to 32. Higher scores indicate greater client satisfaction.
Acceptability will also be assessed by 13 acceptability items(eg, how user-friendly, simple to use, logical, and engaging thetasks were), rated using a 5-point Likert scale from 0 (not at
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RenderXall) to 4 (very). The survey will also contain several open-ended
questions about the most or least helpful and enjoyable featuresof the program. To determine which intervention delivery modelis preferred, participants in the active intervention groups willcomplete four user experience questions after completing eachof the Re-train Your Brain sessions. The four items will assess
their motivation while training, how much they enjoyed thetraining, how much they liked the delivery format, and whether
they found the training simple and user-friendly, using a 5-point
Likert scale (from 0 not at all to 4 extremely).

Secondary Outcome Measures
Overview
The following measures will be assessed at baseline,
postintervention, and 3 months postbaseline (a more detailed
description and interpretation of scores are given in Multimedia
Appendix 1).
Cognitive Biases
Alcohol approach biases will be assessed using the Alcohol
Approach Task [13]. Participants are instructed to pull or push
a computer mouse (in place of a joystick, which is typicallyused in laboratory-based studies) in response to an irrelevant
feature of images (ie, the orientation as portrait or landscape)shown on a computer screen while ignoring the content of thepictures. Two categories of pictures are used: 20 alcoholic
beverages and 20 color- and shape-matched nonalcoholic
beverages. Each picture appears one by one in both landscapeand portrait formats in a quasi-random order (maximum 3
consecutive pictures of the same category or format). Contingent
upon a pull or push movement, the picture zooms in (becomeslarger on the screen to generate the subjective experience of an
approach behavior) or zooms out (becomes smaller on the screen
to give a sense of avoidance behavior). A correct response isfollowed by feedback, as indicated by a green ✓on the screen,whereas an incorrect response is followed with error feedback,as indicated by a red X. The task begins with 5 practice trials
showing empty rectangular frames in a landscape or portrait
format. Format movement assignments are counterbalanced(half of the participants pull pictures that came in landscapeformat and push portrait pictures, and half of the participantsreceived the opposite instruction). The images have been
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selected to represent the beverage type and brands mostcommonly consumed by this population, as documented in a
recent acceptability study [51]. Each image is repeated twice,
for a total of 80 trials.

3.

Social anxiety interpretation biases will be measured using theInterpretation Recognition Task [22,71]. The Interpretation
Recognition Task contains two parts: an encoding phase and arecognition test phase. During the encoding phase, participants
are asked to read a set of 10 ambiguous social scenarios
presented on a computer screen. Each scenario consists of a title
and three short sentences that are ambiguous in terms of valence.
In the final sentence, a word fragment is presented. After readinga scenario, participants are asked to complete the word fragment
as quickly as possible by pressing the spacebar when they knowwhat the word is. They then press the key corresponding to thefirst missing letter. Next, the participant is asked to answer yesor no to a question that measures comprehension of the story,
also followed by feedback (ie, correct or wrong). An exampleof the encoding phase is provided as follows:

Interpretation and expectancy biases for co-occurring social
anxiety and alcohol use will be assessed by the self-report
Comorbid Social Anxiety and Alcohol Interpretation Bias task[59]. Participants are presented with a set of eight ambiguoussocial scenarios, followed by three possible explanations forthe situation. Participants will rate the degree to which each of
the explanations would likely be true if they were in thatsituation (0 not at all likely to 8 extremely).

(Title): The evening class.
(Scenario): You’ve just started going to an evening class. The
instructor asks a question and no one in the group volunteers
an answer, so he looks directly at you. You answer the question,aware of how your voice must sound to the...
(Word fragment): oth-rs(Correct word): others(Comprehension question): Have you been going to the eveningclass for a long time?
(Response): No(Feedback): ✓ Correct answer
In the recognition test phase, participants are presented with theidentifying titles of each ambiguous scenario, together with fourinterpretations of each of the scenarios, presented one at a time.
Participants are asked to rate each summary statement
independently for their similarity in meaning to the original
scenario on a 4-point Likert scale from 1 (very different inmeaning) to 4 (very similar in meaning). The four summary
statements always contain one valid, positively valanced
interpretation (positive target); one valid, negatively valanced
interpretation (negative target); one positively valanced
statement that was not a possible interpretation of the original
scenario in that it did not correspond to the previously presented
ambiguity (positive foil); and one negatively valanced statementthat was not a possible interpretation of the original scenario(negative foil). Foils are included to assess any wider priming
effects, indicating a potential response bias for endorsing any
information of a certain emotional valence. Examples of thesummary statements that would be provided for the
aforementioned scenario are shown as follows:1.
2.

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Alcohol Use
Alcohol consumption (average drinks per day) and frequencyof binge drinking days (>5 standard drinks per drinking day) in
the past month will be assessed through a computerized versionof the Timeline Followback Procedure [60-62]. Hazardous
alcohol use will be assessed using the 10-item Alcohol Use
Disorder Identification Test [54]. Severity of alcohol dependence
will be assessed using the 20-item Severity of Alcohol
Dependence Questionnaire [63]. Alcohol cravings will beassessed using the 12-item Severity of Alcohol Craving
Questionnaire–Short Form–Revised. Motives for alcohol use
in the past month will be assessed through the 28-item Drinking
Motives Questionnaire-Revised [64]. To assess alcohol use
throughout the intervention period, all groups will be asked tocomplete the Timeline Followback twice per week [60-62].
Anxiety
Symptoms of social anxiety will be assessed using the shortforms of the Social Interaction Anxiety Scale and the Social
Phobia Scale [55]. Symptoms of depression and anxiety will beassessed using the 4-item Patient Health Questionnaire-4 [65].
To assess changes in social anxiety symptoms throughout theintervention period, all groups will be asked to complete theSocial Phobia Weekly Summary Scale [66] biweekly.
Covariates and Additional Variables
Sociodemographic characteristics will include age, sex, gender,
education, employment, country of birth, and primary mental
health or substance use concerns. Participants will also be asked
about any psychological and pharmacological treatment
received in the past 3 months (full details given in Multimedia
Appendix 1). Readiness and motivation to change will beassessed via a readiness ruler (eg, on a scale of 1-10, how readyare you to change your anxiety or drinking) and the University
of Rhode Island Change Assessment [72]. The frequency ofother drug use (cannabis, nonprescribed benzodiazepines, andpsychostimulants) will be assessed by the National Institute on
Drug Abuse quick screen [73], and sleep disturbance over the
past month will be assessed using the Pittsburgh Sleep Quality
Index [74].

Positive target: You answer the question, aware of others
listening attentively.
Negative target: You answer the question, aware of how
unsteady your voice sounds.

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4.

Positive foil: You answer the question and then realize whata good answer it is.
Negative foil: You answer the question but realize that you
have made a mistake.

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JMIR RESEARCH PROTOCOLSIntervention and Control Groups
Re-train Your Brain ApBM+IBM Intervention Groups
Overview
Both the integrated and alternating Re-train Your Braininterventions contain ApBM and IBM components, deliveredin addition to TAU. Participants in both groups will be asked
to complete 10 training sessions over a 5-week period. Twosessions will be available to complete each week, andparticipants will be given 1-week flexibility to complete all the
10 training sessions. Each training session will be of
approximately 20 minutes. In addition, as per previous trials[52], before the commencement of the first training session,
participants in both intervention groups will receive an online
psychoeducational and motivational interviewing–based module,
which was adapted from a previous efficacious online programfor anxiety and alcohol use [75]. The module provides
psychoeducation about anxiety and alcohol use, theinterrelationship between these problems, the existence ofautomatically activated cognitive biases, and the importance ofchanging these biases. It also explores participants’ reasons forchange, and aims to increase intrinsic motivation for (anddecrease ambivalence about) change, promotes autonomy andchange talk, helps participants set goals for what they hope toachieve by completing the training, enhances motivation to
train, and harnesses the individual’s capacity for change. The

Prior et al
ApBM and IBM components of the integrated and alternating
training programs are described later.
Alcohol ApBM Component
ApBM is a modified training version of the assessment Alcohol
Approach Task, in which participants pull or push a computer
mouse in response to the orientation of images (containing
alcoholic or nonalcoholic beverages), which zooms the image
in or out (Figure 2). For ApBM (unlike the Alcohol ApproachTask), 95% of the orientations used to implicitly train avoidance
behaviors will contain images of alcoholic beverages, whereas
the remaining 5% of frames will contain images of nonalcoholic
beverages (and vice versa for orientations used to train approach
behaviors). The required push-pull movements arecounterbalanced so that half of the participants pull picturesthat come in landscape format and push pictures in portrait
format, whereas the other half receive the opposite instruction.
Participants receive feedback in the form of a green tick or red
cross presented on-screen, with a corresponding smiley or sadface emoji. The presentation is repeated if the response isincorrect. To increase motivation, points are awarded for eachcorrect push-pull movement (+1). To familiarize participants
with the task requirements, a brief practice round involving fiveempty rectangular frames in landscape or portrait format will
be provided. The alcoholic and nonalcoholic images used inthis study were selected to represent the beverage types andbrands most commonly consumed by this population, as
documented in a recent acceptability study [51].

Figure 2. Example of Approach Bias Modification scenario to illustrate the training procedures.

Anxiety IBM Program Component
In IBM training, participants are trained to resolve ambiguoussocial scenarios with either positive or benign outcomes throughthe completion of a word fragment (Figure 3) [22]. Eachscenario consists of three lines that are ambiguous in terms of
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valence or emotional interpretation. The participants are
instructed to imagine or visualize themselves in each situation
described. One word of the story is presented as a word
fragment, which disambiguates the story in a positive or benign
way. Participants are asked to complete the fragment as quickly
as possible by pressing the spacebar when they know what the
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JMIR RESEARCH PROTOCOLS
word is and then to press the key corresponding to the missing
letter. The reaction times are recorded. The program continues
only when a correct response is provided. After this, acomprehension question appears that reinforces the assigned
meaning when the word fragment is completed. Participants
answer the question with a Yes or No response. They
subsequently receive feedback (a correct or wrong answer, witha corresponding smiley or sad face emoji) to reinforce thePrior et alinterpretation imposed by the word fragment. Points are awarded
for each correct letter (+1) and correct answer to thecomprehension question (+1). The social scenarios are translated
versions of those used in previous research [22,45,76], adapted
for this study’s target age range of 18-30 years and theAustralian context [51]. Three practice trials are given at theoutset of the IBM training component.

Figure 3. Example of Interpretation Bias Modification scenario to illustrate the training.

Delivery Formats of the Re-train Your Brain ApBM+IBM
Intervention
Group 1: Integrated ApBM+IBM Intervention, With Biweekly
Sessions Combining IBM and ApBM
Group 1 will receive 10 biweekly training sessions containing
shortened versions of both IBM and ApBM within each session(50:50 ratio) plus TAU. For the ApBM component, participants
will be presented with frames containing 10 images of alcoholic
beverages and 10 images of nonalcoholic beverages, in a random
order. Each alcoholic and nonalcoholic beverage is presented
three times, for a total of 60 image presentations. For the IBMcomponent, participants will be presented with three blocks of
10 social scenarios (ie, 30 scenarios per session; 300 across the
10 sessions). Each block will contain eight positive modification(induction) scenarios and two probe or irrelevant scenarios thathave either a positive or benign outcome, to make the induction
less obvious. Blocks are in a fixed order, but the order of the
scenarios within blocks is random for each participant.
Group 2: Alternating ApBM+IBM Intervention, With Biweekly
Sessions Alternating Between IBM and ApBM
Participants in group 2 will receive the same treatment dose asgroup 1; however, on alternating weeks, participants will receive
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RenderXeither ApBM or IBM (ie, each session will switch between
retraining alcohol or anxiety biases in an alternating pattern;
five ApBM and five IBM sessions) plus TAU. For each of thefive ApBM training sessions, participants will be presented with120 (rather than 60) alcoholic and nonalcoholic beverage images(20 alcoholic and 20 nonalcoholic, shown three times in random
order), and each of the five IBM sessions will provide 60
scenarios (rather than 30).

Control Group (Group 3: TAU Only)
The control group will receive TAU, which will be the modelof care provided in accordance with standard practices at theirservice. The focus of the psychological treatment will not belimited to the provision of treatment for anxiety and/or alcoholuse (ie, clients may be receiving treatment for other conditionsin addition to anxiety and/or alcohol use). No restrictions will
be placed on the type of psychological treatment or how longthe client has been receiving the treatment. Details regarding
the type, length, and focus of treatment will be ascertained
during the baseline and follow-up surveys and reported uponin the trial outcomes (more information given in Multimedia
Appendix 1). The decision to have few restrictions tied to thetreatment offered as part of TAU follows a desire to test the
CBM program in the context of real-world care and to evaluate
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JMIR RESEARCH PROTOCOLS
the adjunctive intervention with a deployment focus. This groupwill be offered the opportunity to receive the Re-train Your
Brain program (in whichever format is deemed preferable byparticipants) after all follow-up surveys and measurements aretaken at the 3-month assessment point.

Procedure
Study Procedure
All participants will be directed to the Re-train Your Brain
website, which contains detailed information about the study
and provides a direct link to the online participant information
statement and consent form. After providing consent,
prospective participants will complete a brief, 10-minute online
screening survey to determine eligibility. Eligible participants
will gain access to an online baseline survey, which will takeapproximately 30 minutes to complete. Participants will be
asked to provide their name, email, and postal address so thatthe research team may post them a computer mouse to completea cognitive assessment (note: as these assessments are reaction
time based, this will ensure consistency in mouse settings
between participants, such as pointer speed, etc) and send thema link to the alcohol approach and interpretation bias cognitive
assessment. Immediately following the cognitive assessment,
participants will be individually randomized by the study
website to receive the following: (1) the integrated Re-train
Your Brain intervention plus TAU (n=30), (2) the alternating
Re-train Your Brain intervention TAU (n=30), or (3) TAU only
(n=30). Participants in the Re-train Your Brain intervention
groups will be asked to complete a 30-minute motivational
interviewing or psychoeducation-based module, followed by
10 cognitive training sessions, delivered online twice per week
for 5 weeks (approximately 2-4 days apart). Participants will
be reminded of these training sessions via multiple reminder
calls, emails, and SMS text messages. As difficulty and boredom
are intrinsically part of these kinds of implicit interventions,participants will also receive 3-4 brief motivational enhancement
texts or emails over the 5-week program to normalize any
difficulties encountered in the training execution and reaffirm
their commitment to change. In addition, to maximize
engagement with the research trial, participants in all groups
will be asked to complete two weekly 5-minute assessments of
their anxiety and alcohol use symptoms, for which they will
receive a Aus $5 (US $3.80) e-gift voucher per occasion (10total), with an accumulated voucher (max Aus $50; US $37.70)
paid at the end of the treatment period.
All participants will be emailed a link to complete an online
survey and a (separate) cognitive assessment at postintervention(ie, 6 weeks postbaseline, to provide 1 week of flexibility in therate of training completion) and 3 months postbaseline. The
survey and cognitive assessments are expected to takeapproximately 45-60 minutes (combined) to complete at eachtime point. Consistent with previous online trials [77,78],
participants who complete both the online survey and cognitive
assessment will receive an Aus $30 (US $22.60) e-gift voucher
at each time point as reimbursement for their time participatingin the research. To minimize data attrition, the following
evidence-based strategies will be used [79,80]: (1) monetary
incentives for each assessment completed, (2) collection of
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Prior et almultiple sources of contact information (eg, email, mobile
number, and postal address), (3) user-friendly electronic survey
design that can be completed via multiple devices (eg, via
mobile phone), (4) personalized reminder messages (SMS text
messaging and email) to complete surveys or cognitive
assessments, and (5) a follow-up letter and telephone call tothose participants who do not respond. The intervention andcognitive assessments will be accessed via the study website
and run using JavaScript, whereas all online surveys will bedelivered via Qualtrics. The trial will be conducted inaccordance with the SPIRIT (Standard Protocol Items:
Recommendations for Interventional Trials) 2013 Statement
and CONSORT (Consolidated Standards of Reporting Trials)
guidelines.

Randomization
To avoid bias, participants will be individually randomized to
the Re-train Your Brain integrated group, the Re-train Your
Brain alternating group, or the control group (on a 1:1:1: basis)
via the trial website using a computer-generated randomization
sequence, which is concealed from the investigators. This
process removes the potential for researcher involvement.
Randomization will occur directly after the completion of theonline baseline cognitive assessment (Figure 1).

Statistical Analysis and Power Calculations
As this is a pilot trial, a formal power calculation is not required[81,82]. The pilot trial is essential to determine the expected
size of effect, which will be used to inform the sample size ofa future definitive RCT aiming to assess the efficacy of theRe-train Your Brain program. Rates of attrition will be used toindicate estimated follow-up rates in future trials. On the basisof several rules of thumb used to determine an appropriate
sample size for a pilot study [83-85], a sample size of 90 young
people (30 per arm) was selected to provide sufficient data on
the feasibility, acceptability, and preliminary efficacy of the
program, although we recognize that the scope of this pilot trial
does not allow for a fully powered test of efficacy. Data will becollated and analyzed using StataCorp data analysis software[86].
Descriptive statistics for primary and secondary outcomes will
be conducted based on frequencies and cross-tabulations.
Analyses for secondary (preliminary) efficacy outcomes will
use multilevel mixed effects analysis for repeated measures,
which is a flexible analytic approach for modeling change overtime using RCT data [87,88]. All models will use baseline
measurements as the reference point to estimate
participant-specific starting points and change over time. Theintervention condition will be represented by a dummy-codedvariable, and the condition by time interaction will be examined
to assess between-group differences in outcomes over time.
Analyses will be consistent with an intention-to-treat framework,with all randomized participants included in the analysis models,
regardless of training completion or loss to follow-up. Missing
data will be accommodated in these models using maximum
likelihood estimation. Preliminary models will be estimated,with model fit statistics examined to determine the mostappropriate model and covariance structure. Cohen d will becalculated from model-estimated marginal means and SEs to
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JMIR RESEARCH PROTOCOLS
determine the size of the effect between conditions at therelevant end point. In addition, effect sizes will be analyzed asa function of session completion (ie, completion of six or moretraining sessions, given that this has been identified as the mean
optimum number of ApBM sessions in past research [67]).

Results
Recruitment is expected to be completed by mid-2022 to late2022, with the 6-week and 3-month follow-ups to be completed
by early 2023. The results are expected to be submitted for
publication in 2023. The research team intends to present thefindings of this trial at professional seminars and national andinternational conferences. Only aggregated group data will bereported, and no individuals will be identified.

Discussion
Principal Findings
This paper presents the design of the Re-train Your Brain study,
a randomized controlled pilot trial seeking to evaluate thefeasibility, acceptability, and preliminary efficacy of a
10-session, web-based ApBM+IBM brain training program forhazardous alcohol use and social anxiety among young
Australians aged 18-30 years, when combined with TAU. To
the best of our knowledge, this is the first study to evaluate acomorbidity-targeted intervention of this kind, using a
cost-effective, web-based delivery method.

Strengths and Limitations
This study has several strengths. First, the intervention was
co-designed with emerging adults who have direct lived
experience of hazardous drinking and social anxiety andclinicians who have experience treating anxiety and/or alcohol
use concerns. This bottom-up approach, whereby emerging
adults and clinicians were involved in the development of themethodology and stimuli used within the intervention (eg, thealcoholic or nonalcoholic beverages used in ApBM and thescenarios included in IBM), was critical to ensuring that the
program is relevant, engaging, and useful for end users. This
codevelopment process also helps to ensure that the program
can be feasibly implemented and is responsive to the needs ofservice providers.
An additional strength of this study is the web-based deliveryof the interventions. The Re-train Your Brain intervention is
simple, inexpensive, and can be self-administered via theinternet without any specific skills or knowledge. This format
allows for easy and convenient access anywhere and at any time(eg, in the privacy of one’s home), thereby offering a larger
outreach and greater availability. It is also being investigatedin the setting in which it is most likely to be implemented, if
proven effective in a future RCT. On theoretical and practicalgrounds, incorporation of a web-based psychoeducational or
motivational enhancement-type module at the outset of training
will aid its efficacy and will also likely boost engagement anduser buy-in. It may also increase treatment adherence and reducestudy attrition. Thus, the web-based delivery of this program
has the potential to enhance clinical outcomes at a minimum
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Prior et al
cost in terms of time and effort for both patients and service
providers.
Finally, despite their high co-occurrence, to date, most CBM
programs have addressed anxiety and alcohol use in isolationof one another, with a few exceptions for attention bas
modification [48]. The current intervention is unique in that it
combines effective alcohol ApBM and anxiety IBM-focused
protocols to optimize standard treatments among a young
comorbid sample. Given the interconnections between anxiety
and alcohol use problems, whereby each disorder fuels the otherand impedes recovery from the other, it is possible thatcombining these programs will have incremental (or synergistic)
effects on anxiety and alcohol use outcomes in a vulnerable
group that responds poorly to standard treatments [10,89].
One of the main strengths of this study is also its main
limitation: that is, its web-based delivery. First, internet
interventions are conducted in a less-controlled homeenvironment that may pose several online distractions (eg, email
notifications) and offline distractions (eg, housemates or phone
calls), which have the potential to impact the study results.
Second, web-based interventions also have higher rates of
attrition compared with standard face-to-face treatments (eg,34.2% vs 24.6%, respectively) [90]. Further increasing the riskof attrition, CBM interventions are inherently repetitive and assuch are sometimes considered boring because of themonotonous nature of the tasks [28,91]. To help overcome theselimitations, at the start of each session, participants are remindedof the importance of conducting training in a quiet environment
where they can concentrate for a 20-minute block. To leverageon participants’ intrinsic motivation for change and maximize
their initial buy-in, a compelling rationale and motivational
enhancement module is provided at the outset of the program.
These components will set expectations about the purpose andnature of the intervention (eg, computerized and repetitive
training), which will likely enhance motivation to train and,thus, result in increased adherence and lower attrition. In
addition, multiple evidence-based strategies to minimize
treatment and study attrition will be used, such as monetary
incentives, email and SMS text messaging reminders, andexplanation of the importance of completing the sessions andfollow-up surveys to participants [79,80]. Taken together, thepossible threats presented by the web-based delivery of theintervention are outweighed by the possibilities and benefits it
may offer.
Furthermore, this study uses a control group that receives TAU
and zero training, rather than a control group that is matched
for both stimulus exposure (ie, time spent completing the ApBM
and IBM tasks) and response requirements. Shamcontrol-training groups are considered the optimal comparatorgroups for these reasons and because participants remain blindto their group allocation [92]. However, some research has
shown that there is no significant difference between
experimental and sham control groups (as both groups improve[33,92]), suggesting that sham training may in fact have an
active component rather than it being a neutral or placebotraining it is intended to be. This is particularly the case foronline trials and less so for laboratory-based trials [47]. Thisway, it is conceivable that both online-delivered sham and
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JMIR RESEARCH PROTOCOLS
experimental conditions represent placebo effects; however,this cannot be ruled out in a two-arm design (active vs control
training). Given that this study is a pilot trial with primary
outcomes focused on feasibility and acceptability (as opposed
to efficacy) and secondary outcomes on preliminary efficacy,
an active control group could mask any possible intervention
effects, and thus, a no-training group was selected as thecomparator. Indeed, in this study, priority was given to testing
two experimental varieties on top of TAU, as compared with
TAU. Future RCTs aiming to evaluate the clinical efficacy ofthis hybrid intervention may consider a different three-arm
design, comparing the ApBM+IBM intervention against bothan (active) sham-training control and a zero training control
condition (ie, TAU), and examine potential mediation effects
across the three conditions.

Prior et al

Conclusions and Implications
This world’s first hybrid ApBM+IBM training program
combines the best elements of efficacious ApBM training
programs for alcohol use problems and IBM for social anxiety
into a hybrid program for emerging adults who experience bothof these problems. This innovative program can be delivered
over the internet and can thereby maximize efficiency and scarce
resources and sustainably increase the intervention options forvulnerable populations at a low cost. Given the costs ofconducting an RCT, it is important to establish whether theRe-train Your Brain ApBM+IBM program is acceptable toemerging adults and whether it is feasible to deliver via theinternet, in settings where it will ultimately be used and easily
scaled to, including at home. The pilot trial findings willcontribute to understanding the types of programs that emerging
adults will engage with and whether there are signs of it being
an efficacious treatment option for this comorbidity.

Acknowledgments
This work was supported by Australian Rotary Health (salary support for KP from 2019-2023), as well as research support
provided by an early career researcher seed funding grant from the National Health and Medical Research Council Centre of
Research Excellence in the Prevention and Early Intervention in Mental Illness and Substance Use, two seed funding grants fromthe University of Sydney’s Lifespan Research Network, and a University of Sydney-Utrecht University Partnership Collaboration
Award. Australian Rotary Health, the Centre of Research Excellence in the Prevention and Early Intervention in Mental Illness
and Substance Use, the University of Sydney, and Utrecht University did not influence the design of the study or the writing of
the manuscript. The authors would like to thank Samuel Campbell from Turning Point for creating an initial version of theintervention and Netfront Digital Agency for setting up the study website and finalizing the development of the intervention.

Authors' Contributions
KP, ES, RWW, and LAS designed the study and obtained the funding support. KP and MP prepared the first draft of the manuscript.
ES and VM shared study documents and materials related to ApBM and IBM. All authors assisted with the methodologicalaspects of the trial and reviewed and contributed to the final manuscript.

Conflicts of Interest
The authors are the developers of the Re-train Your Brain web-based program.

Multimedia Appendix 1
A detailed description and interpretation of scores for primary and secondary outcome measures.
[DOCX File , 20 KB-Multimedia Appendix 1]

References
1.

2.

3.

4.
5.

Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. Lifetime prevalence and age-of-onset distributionsof DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005 Jun;62(6):593-602. [doi:10.1001/archpsyc.62.6.593] [Medline: 15939837]
Crome E, Grove R, Baillie AJ, Sunderland M, Teesson M, Slade T. DSM-IV and DSM-5 social anxiety disorder in theAustralian community. Aust N Z J Psychiatry 2015 Mar 13;49(3):227-235. [doi: 10.1177/0004867414546699] [Medline:
25122449]
Grant BF, Stinson FS, Dawson DA, Chou SP, Dufour MC, Compton W, et al. Prevalence and co-occurrence of substanceuse disorders and independent mood and anxiety disorders: results from the National Epidemiologic Survey on Alcoholand Related Conditions. Arch Gen Psychiatry 2004 Aug 01;61(8):807-816. [doi: 10.1001/archpsyc.61.8.807] [Medline:
15289279]
Smith JP, Randall CL. Anxiety and alcohol use disorders: comorbidity and treatment considerations. Alcohol Res
2012;34(4):414-431 [FREE Full text] [Medline: 23584108]
Schneier FR, Foose TE, Hasin DS, Heimberg RG, Liu S, Grant BF, et al. Social anxiety disorder and alcohol use disorderco-morbidity in the National Epidemiologic Survey on Alcohol and Related Conditions. Psychol Med 2010 Jun;40(6):977-988[FREE Full text] [doi: 10.1017/S0033291709991231] [Medline: 20441690]

https://www.researchprotocols.org/2021/7/e28667

XSL• FO
RenderX

JMIR Res Protoc 2021 | vol. 10 | iss. 7 | e28667 | p. 13(page number not for citation purposes)

JMIR RESEARCH PROTOCOLS
6.

7.
8.

9.

10.

11.
12.

13.

14.

15.
16.
17.

18.

19.

20.
21.

22.
23.

24.

25.

26.

27.

Stapinski LA, Rapee RM, Sannibale C, Teesson M, Haber PS, Baillie AJ. The clinical and theoretical basis for integrated
cognitive behavioral treatment of comorbid social anxiety and alcohol use disorders. Cogn Behav Pract 2015
Nov;22(4):504-521. [doi: 10.1016/j.cbpra.2014.05.004]
Stewart S, Conrod P. Anxiety disorder and substance use disorder co-morbidity: common themes and future directions. In:
Stewart S, Conrod P, editors. Anxiety and Substance Use Disorders. Boston: Springer; 2008:239-257.
Farris S, Epstein E, McCrady B, Hunter-Reel D. Do co-morbid anxiety disorders predict drinking outcomes in women withalcohol use disorders? Alcohol Alcohol 2012;47(2):143-148 [FREE Full text] [doi: 10.1093/alcalc/agr155] [Medline:
22215000]
Smith JP, Book SW. Comorbidity of generalized anxiety disorder and alcohol use disorders among individuals seeking
outpatient substance abuse treatment. Addict Behav 2010 Jan;35(1):42-45 [FREE Full text] [doi:10.1016/j.addbeh.2009.07.002] [Medline: 19733441]
Kushner MG, Abrams K, Thuras P, Hanson KL, Brekke M, Sletten S. Follow-up study of anxiety disorder and alcohol
dependence in comorbid alcoholism treatment patients. Alcohol Clin Exp Res 2005 Aug;29(8):1432-1443. [doi:10.1097/01.alc.0000175072.17623.f8] [Medline: 16131851]
Schellekens AF, de Jong CA, Buitelaar JK, Verkes RJ. Co-morbid anxiety disorders predict early relapse after inpatientalcohol treatment. Eur Psychiatry 2015 Jan;30(1):128-136. [doi: 10.1016/j.eurpsy.2013.08.006] [Medline: 24630346]
Hendriks SM, Spijker J, Licht CM, Hardeveld F, de Graaf R, Batelaan NM, et al. Long-term work disability and absenteeism
in anxiety and depressive disorders. J Affect Disord 2015 Jun 01;178:121-130. [doi: 10.1016/j.jad.2015.03.004] [Medline:
25805404]
Wiers RW, Rinck M, Dictus M, van den Wildenberg E. Relatively strong automatic appetitive action-tendencies in male
carriers of the OPRM1 G-allele. Genes Brain Behav 2009 Feb;8(1):101-106 [FREE Full text] [doi:10.1111/j.1601-183X.2008.00454.x] [Medline: 19016889]
Braunstein LM, Kuerbis A, Ochsner K, Morgenstern J. Implicit alcohol approach and avoidance tendencies predict futuredrinking in problem drinkers. Alcohol Clin Exp Res 2016 Sep;40(9):1945-1952 [FREE Full text] [doi: 10.1111/acer.13151][Medline: 27421061]
Amir N, Beard C, Bower E. Interpretation bias and social anxiety. Cogn Ther Res 2005 Aug;29(4):433-443. [doi:10.1007/s10608-005-2834-5]
Murphy R, Hirsch CR, Mathews A, Smith K, Clark DM. Facilitating a benign interpretation bias in a high socially anxious
population. Behav Res Ther 2007 Jul;45(7):1517-1529. [doi: 10.1016/j.brat.2007.01.007] [Medline: 17349970]
Klein AM, de Voogd L, Wiers RW, Salemink E. Biases in attention and interpretation in adolescents with varying levelsof anxiety and depression. Cogn Emot 2018 Nov;32(7):1478-1486. [doi: 10.1080/02699931.2017.1304359] [Medline:
28366048]
Schlauch RC, Stasiewicz PR, Bradizza CM, Coffey SF, Gulliver SB, Gudleski GD. Relationship between approach andavoidance inclinations to use alcohol and treatment outcomes. Addict Behav 2012 Jul;37(7):824-830 [FREE Full text] [doi:10.1016/j.addbeh.2012.03.010] [Medline: 22459327]
Field M, Di Lemma L, Christiansen P, Dickson J. Automatic avoidance tendencies for alcohol cues predict drinking after
detoxification treatment in alcohol dependence. Psychol Addict Behav 2017 Mar;31(2):171-179 [FREE Full text] [doi:10.1037/adb0000232] [Medline: 27935726]
Hirsch CR, Meeten F, Krahé C, Reeder C. Resolving ambiguity in emotional disorders: the nature and role of interpretationbiases. Annu Rev Clin Psychol 2016 Mar;12:281-305. [doi: 10.1146/annurev-clinpsy-021815-093436] [Medline: 27019398]
Stuijfzand S, Creswell C, Field AP, Pearcey S, Dodd H. Research Review: Is anxiety associated with negative interpretationsof ambiguity in children and adolescents? A systematic review and meta-analysis. J Child Psychol Psychiatry 2018
Nov;59(11):1127-1142 [FREE Full text] [doi: 10.1111/jcpp.12822] [Medline: 29052865]
Mathews A, Mackintosh B. Induced emotional interpretation bias and anxiety. J Abnorm Psychol 2000;109(4):602-615.
[doi: 10.1037/0021-843X.109.4.602]
Wiers RW, Eberl C, Rinck M, Becker ES, Lindenmeyer J. Retraining automatic action tendencies changes alcoholic patients'
approach bias for alcohol and improves treatment outcome. Psychol Sci 2011 Apr;22(4):490-497. [doi:10.1177/0956797611400615] [Medline: 21389338]
Eberl C, Wiers RW, Pawelczack S, Rinck M, Becker ES, Lindenmeyer J. Approach bias modification in alcohol dependence:
do clinical effects replicate and for whom does it work best? Dev Cogn Neurosci 2013 Apr;4:38-51 [FREE Full text] [doi:10.1016/j.dcn.2012.11.002] [Medline: 23218805]
Manning V, Staiger PK, Hall K, Garfield JB, Flaks G, Leung D, et al. Cognitive bias modification training during inpatientalcohol detoxification reduces early relapse: a randomized controlled trial. Alcohol Clin Exp Res 2016 Sep;40(9):2011-2019.
[doi: 10.1111/acer.13163] [Medline: 27488392]
Rinck M, Wiers RW, Becker ES, Lindenmeyer J. Relapse prevention in abstinent alcoholics by cognitive bias modification:clinical effects of combining approach bias modification and attention bias modification. J Consult Clin Psychol 2018
Dec;86(12):1005-1016. [doi: 10.1037/ccp0000321] [Medline: 30507226]
Amir N, Taylor CT. Interpretation training in individuals with generalized social anxiety disorder: a randomized controlled
trial. J Consult Clin Psychol 2012 Jun;80(3):497-511 [FREE Full text] [doi: 10.1037/a0026928] [Medline: 22250851]

https://www.researchprotocols.org/2021/7/e28667

XSL• FO
RenderX

Prior et al

JMIR Res Protoc 2021 | vol. 10 | iss. 7 | e28667 | p. 14(page number not for citation purposes)

JMIR RESEARCH PROTOCOLS
28.

29.

30.

31.

32.
33.

34.
35.
36.

37.
38.

39.

40.
41.
42.
43.

44.
45.

46.

47.
48.

49.

Brosan L, Hoppitt L, Shelfer L, Sillence A, Mackintosh B. Cognitive bias modification for attention and interpretation
reduces trait and state anxiety in anxious patients referred to an out-patient service: results from a pilot study. J Behav Ther
Exp Psychiatry 2011 Sep;42(3):258-264. [doi: 10.1016/j.jbtep.2010.12.006] [Medline: 21349242]
Wiers RW, Boffo M, Field M. What's in a trial? On the importance of distinguishing between experimental lab studies andrandomized controlled trials: the case of cognitive bias modification and alcohol use disorders. J Stud Alcohol Drugs 2018
May;79(3):333-343. [Medline: 29885138]
Bowler JO, Mackintosh B, Dunn BD, Mathews A, Dalgleish T, Hoppitt L. A comparison of cognitive bias modification
for interpretation and computerized cognitive behavior therapy: effects on anxiety, depression, attentional control, andinterpretive bias. J Consult Clin Psychol 2012 Dec;80(6):1021-1033 [FREE Full text] [doi: 10.1037/a0029932] [Medline:
22963595]White LK, Sequeira S, Britton JC, Brotman MA, Gold AL, Berman E, et al. Complementary features of attention bias
modification therapy and cognitive-behavioral therapy in pediatric anxiety disorders. Am J Psychiatry 2017 Aug
01;174(8):775-784 [FREE Full text] [doi: 10.1176/appi.ajp.2017.16070847] [Medline: 28407726]
Baert S, Koster EH, De Raedt R. Modification of information-processing biases in emotional disorders: clinically relevant
developments in experimental psychopathology. Int J Cogn Ther 2011 Jun;4(2):208-222. [doi: 10.1521/ijct.2011.4.2.208]
Boffo M, Zerhouni O, Gronau QF, van Beek RJ, Nikolaou K, Marsman M, et al. Cognitive bias modification for behavior
change in alcohol and smoking addiction: Bayesian meta-analysis of individual participant data. Neuropsychol Rev 2019
Mar;29(1):52-78 [FREE Full text] [doi: 10.1007/s11065-018-9386-4] [Medline: 30644025]
Cristea IA, Kok RN, Cuijpers P. Efficacy of cognitive bias modification interventions in anxiety and depression: meta-analysis.
Br J Psychiatry 2015 Jan 2;206(1):7-16. [doi: 10.1192/bjp.bp.114.146761] [Medline: 25561486]
Cristea IA, Kok RN, Cuijpers P. The effectiveness of cognitive bias modification interventions for substance addictions:a meta-analysis. PLoS One 2016;11(9):e0162226 [FREE Full text] [doi: 10.1371/journal.pone.0162226] [Medline: 27611692]
Grafton B, MacLeod C, Rudaizky D, Holmes EA, Salemink E, Fox E, et al. Confusing procedures with process whenappraising the impact of cognitive bias modification on emotional vulnerability. Br J Psychiatry 2017 Nov 2;211(5):266-271.
[doi: 10.1192/bjp.bp.115.176123] [Medline: 29092835]
Kakoschke N, Kemps E, Tiggemann M. Approach bias modification training and consumption: a review of the literature.
Addict Behav 2017 Jan;64:21-28. [doi: 10.1016/j.addbeh.2016.08.007] [Medline: 27538198]
Batschelet HM, Stein M, Tschuemperlin RM, Soravia LM, Moggi F. Alcohol-specific computerized interventions to altercognitive biases: a systematic review of effects on experimental tasks, drinking behavior, and neuronal activation. Front
Psychiatry 2019 Jan 9;10:871 [FREE Full text] [doi: 10.3389/fpsyt.2019.00871] [Medline: 31998146]
Manning V, Garfield JB, Staiger PK, Lubman DI, Lum JA, Reynolds J, et al. Effect of cognitive bias modification on early
relapse among adults undergoing inpatient alcohol withdrawal treatment: a randomized clinical trial. JAMA Psychiatry2021 Feb 01;78(2):133-140. [doi: 10.1001/jamapsychiatry.2020.3446] [Medline: 33146693]
Mann K, Hoch E, Batra A, Bonnet U, Günthner A, Reymann G, et al. [Guideline-oriented treatment of alcohol-relateddisorders]. Nervenarzt 2016 Jan;87(1):13-25. [doi: 10.1007/s00115-015-0022-8] [Medline: 26670021]
Haber P. Relapse prevention, aftercare, and long-term follow-up. In: Haber PS, Riordan BC, editors. The Guidelines for
the Treatment of Alcohol Problems. Canberra: Commonwealth Australia; 2021.
Jones EB, Sharpe L. Cognitive bias modification: a review of meta-analyses. J Affect Disord 2017 Dec 01;223:175-183.
[doi: 10.1016/j.jad.2017.07.034] [Medline: 28759865]
Fodor L, Georgescu R, Cuijpers P, Szamoskozi S, David D, Furukawa T. Efficacy of cognitive bias modification interventionsin anxiety and depressive disorders: a systematic review and network meta-analysis. Lancet Psychiatry 2020:A [FREE Fulltext] [doi: 10.1016/s2215-0366(20)30130-9]
Zhang M, Ying J, Song G, Fung DS, Smith H. Web-based cognitive bias modification interventions for psychiatric disorders:scoping review. JMIR Ment Health 2019 Oct 24;6(10):e11841 [FREE Full text] [doi: 10.2196/11841] [Medline: 31651410]
Salemink E, Kindt M, Rienties H, van den Hout M. Internet-based cognitive bias modification of interpretations in patientswith anxiety disorders: a randomised controlled trial. J Behav Ther Exp Psychiatry 2014 Mar;45(1):186-195. [doi:10.1016/j.jbtep.2013.10.005] [Medline: 24177146]
Brettschneider M, Neumann P, Berger T, Renneberg B, Boettcher J. Internet-based interpretation bias modification forsocial anxiety: a pilot study. J Behav Ther Exp Psychiatry 2015 Dec;49(Pt A):21-29. [doi: 10.1016/j.jbtep.2015.04.008][Medline: 26005201]
Wiers RW, Houben K, Fadardi JS, van Beek P, Rhemtulla M, Cox WM. Alcohol cognitive bias modification training forproblem drinkers over the web. Addict Behav 2015 Jan;40:21-26. [doi: 10.1016/j.addbeh.2014.08.010] [Medline: 25218067]
Clerkin EM, Magee JC, Wells TT, Beard C, Barnett NP. Randomized controlled trial of attention bias modification in a
racially diverse, socially anxious, alcohol dependent sample. Behav Res Ther 2016 Dec;87:58-69 [FREE Full text] [doi:10.1016/j.brat.2016.08.010] [Medline: 27591918]
Teesson M, Hall W, Slade T, Mills K, Grove R, Mewton L, et al. Prevalence and correlates of DSM-IV alcohol abuse anddependence in Australia: findings of the 2007 National Survey of Mental Health and Wellbeing. Addiction 2010
Dec;105(12):2085-2094. [doi: 10.1111/j.1360-0443.2010.03096.x] [Medline: 20707771]

https://www.researchprotocols.org/2021/7/e28667

XSL• FO
RenderX

Prior et al

JMIR Res Protoc 2021 | vol. 10 | iss. 7 | e28667 | p. 15(page number not for citation purposes)

JMIR RESEARCH PROTOCOLS
50.
51.

52.
53.

54.

55.

56.
57.
58.
59.

60.

61.

62.
63.
64.

65.
66.

67.

68.
69.
70.
71.
72.
73.

Lijster JM, Dierckx B, Utens EM, Verhulst FC, Zieldorff C, Dieleman GC, et al. The age of onset of anxiety disorders.
Can J Psychiatry 2017 Dec;62(4):237-246 [FREE Full text] [doi: 10.1177/0706743716640757] [Medline: 27310233]
Prior K, Salemink E, Wiers RW, Teachman BA, Piggott M, Newton NC, et al. Acceptability and co-development of an
online cognitive bias modification intervention for emerging adults with hazardous alcohol use and social anxiety: a mixed
methods study. Alcohol Clin Exp Res 2020 Nov 04;44(11):2283-2297. [doi: 10.1111/acer.14452] [Medline: 33146919]
Beard C, Rifkin LS, Silverman AL, Björgvinsson T. Translating CBM-I into real-world settings: augmenting a CBT-based
psychiatric hospital program. Behav Ther 2019 May;50(3):515-530. [doi: 10.1016/j.beth.2018.09.002] [Medline: 31030870]
Leung CJ, Fosuaah A, Frerichs J, Heslin M, Kabir T, Lee TM, et al. A qualitative study of the acceptability of cognitive
bias modification for paranoia (CBM-pa) in patients with psychosis. BMC Psychiatry 2019 Jul 23;19(1):225 [FREE Fulltext] [doi: 10.1186/s12888-019-2215-3] [Medline: 31337373]
Babor T, Higgins-Biddle J, Saunders J, Monteiro M. The Alcohol Use Disorders Identification Test, Guidelines for Use inPrimary Care. 2nd Ed. Geneva, Switzerland: World Health Organization - Department of Mental Health and Substance
Dependence; 2001.
Peters L, Sunderland M, Andrews G, Rapee RM, Mattick RP. Development of a short form Social Interaction Anxiety(SIAS) and Social Phobia Scale (SPS) using nonparametric item response theory: the SIAS-6 and the SPS-6. Psychol Assess
2012 Mar;24(1):66-76. [doi: 10.1037/a0024544] [Medline: 21744971]
Bebbington P, Nayani T. The psychosis screening questionnaire. Int J Methods Psychiatr Res 1995;5(1):11-19. [doi:10.1037/t30040-000]
Rozental A, Andersson G, Boettcher J, Ebert DD, Cuijpers P, Knaevelsrud C, et al. Consensus statement on defining andmeasuring negative effects of internet interventions. Internet Interv 2014 Mar;1(1):12-19. [doi: 10.1016/j.invent.2014.02.001]
Jacobson NS, Truax P. Clinical significance: a statistical approach to defining meaningful change in psychotherapy research.
J Consult Clin Psychol 1991 Feb;59(1):12-19. [doi: 10.1037//0022-006x.59.1.12] [Medline: 2002127]
Chow PI, Portnow S, Zhang D, Salemink E, Wiers RW, Teachman BA. Comorbid interpretation and expectancy bias insocial anxiety and alcohol use. Anxiety Stress Coping 2018 Nov;31(6):669-685 [FREE Full text] [doi:10.1080/10615806.2018.1521958] [Medline: 30235946]
Rueger SY, Trela CJ, Palmeri M, King AC. Self-administered web-based timeline followback procedure for drinking andsmoking behaviors in young adults. J Stud Alcohol Drugs 2012 Sep;73(5):829-833 [FREE Full text] [doi:10.15288/jsad.2012.73.829] [Medline: 22846247]
Pedersen ER, Grow J, Duncan S, Neighbors C, Larimer ME. Concurrent validity of an online version of the Timeline
Followback assessment. Psychol Addict Behav 2012 Sep;26(3):672-677 [FREE Full text] [doi: 10.1037/a0027945] [Medline:
22486334]
Sobell L, Sobell M. Timeline Follow-Back. In: Litten R, Allen J, editors. Measuring Alcohol Consumption. Totowa, New
Jersey: Humana Press; 1992:41-72.
Stockwell T, Murphy D, Hodgson R. The severity of alcohol dependence questionnaire: its use, reliability and validity. Br
J Addict 1983 Jun;78(2):145-155. [doi: 10.1111/j.1360-0443.1983.tb05502.x] [Medline: 6135435]
Grant VV, Stewart SH, O'Connor RM, Blackwell E, Conrod PJ. Corrigendum to “Psychometric evaluation of the five-factor
Modified Drinking Motives Questionnaire—Revised in undergraduates” [Addictive Behaviors 32/11 (2007) 2611–2632].
Addict Behav 2009 Dec;34(12):1073-1075. [doi: 10.1016/j.addbeh.2007.07.016]
Kroenke K, Spitzer RL, Williams JB, Löwe B. An ultra-brief screening scale for anxiety and depression: the PHQ-4.
Psychosomatics 2009;50(6):613-621. [doi: 10.1176/appi.psy.50.6.613] [Medline: 19996233]
Clark DM, Ehlers A, McManus F, Hackmann A, Fennell M, Campbell H, et al. Cognitive therapy versus fluoxetine ingeneralized social phobia: a randomized placebo-controlled trial. J Consult Clin Psychol 2003 Dec;71(6):1058-1067. [doi:10.1037/0022-006X.71.6.1058] [Medline: 14622081]
Eberl C, Wiers RW, Pawelczack S, Rinck M, Becker ES, Lindenmeyer J. Implementation of approach bias re-training inalcoholism-how many sessions are needed? Alcohol Clin Exp Res 2014 Feb 24;38(2):587-594. [doi: 10.1111/acer.12281][Medline: 24164417]
Brooke J. SUS: A 'quick and dirty' usability scale. In: Usability Evaluation in Industry. Boca Raton, Florida, United States:
CRC Press; 1996:6.
Sauro J, Lewis J. Quantifying the User Experience: Practical Statistics for User Research. San Francisco, MA: Morgan
Kauffman; 2012:1-312.
Larsen DL, Attkisson CC, Hargreaves WA, Nguyen TD. Assessment of client/patient satisfaction: development of a generalscale. Eval Program Plann 1979;2(3):197-207. [doi: 10.1016/0149-7189(79)90094-6] [Medline: 10245370]
Salemink E, van den Hout M. Validation of the "recognition task" used in the training of interpretation biases. J Behav
Ther Exp Psychiatry 2010 Jun;41(2):140-144. [doi: 10.1016/j.jbtep.2009.11.006] [Medline: 19962127]
McConnaughy EA, Prochaska JO, Velicer WF. Stages of change in psychotherapy: measurement and sample profiles.
Psychother: Theory, Res Pract 1983;20(3):368-375. [doi: 10.1037/h0090198]
Zgierska A, Amaza IP, Brown RL, Mundt M, Fleming MF. Unhealthy drug use: how to screen, when to intervene. J FamPract 2014 Sep;63(9):524-530 [FREE Full text] [Medline: 25353031]

https://www.researchprotocols.org/2021/7/e28667

XSL• FO
RenderX

Prior et al

JMIR Res Protoc 2021 | vol. 10 | iss. 7 | e28667 | p. 16(page number not for citation purposes)

JMIR RESEARCH PROTOCOLS
74.

75.

76.
77.

78.

79.

80.

81.
82.
83.
84.

85.

86.
87.
88.

89.

90.
91.
92.

Prior et al

Buysse DJ, Reynolds CF, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument forpsychiatric practice and research. Psychiatry Res 1989;28(2):193-213 [FREE Full text] [doi: 10.2196/12370] [Medline:
30977742]
Stapinski LA, Prior K, Newton NC, Deady M, Kelly E, Lees B, et al. Protocol for the inroads study: a randomized controlled
trial of an internet-delivered, cognitive behavioral therapy-based early intervention to reduce anxiety and hazardous alcohol
use among young people. JMIR Res Protoc 2019 Apr 12;8(4):e12370 [FREE Full text] [doi: 10.1016/0165-1781(89)90047-4][Medline: 2748771]
Salemink E, van den Hout M, Kindt M. Effects of positive interpretive bias modification in highly anxious individuals. J
Anxiety Disord 2009 Jun;23(5):676-683. [doi: 10.1016/j.janxdis.2009.02.006] [Medline: 19272750]
Deady M, Mills KL, Teesson M, Kay-Lambkin F. An online intervention for co-occurring depression and problematic
alcohol use in young people: primary outcomes from a randomized controlled trial. J Med Internet Res 2016 Mar 23;18(3):e71[FREE Full text] [doi: 10.2196/jmir.5178] [Medline: 27009465]
Day V, McGrath PJ, Wojtowicz M. Internet-based guided self-help for university students with anxiety, depression andstress: a randomized controlled clinical trial. Behav Res Ther 2013 Jul;51(7):344-351. [doi: 10.1016/j.brat.2013.03.003][Medline: 23639300]
Brueton VC, Tierney JF, Stenning S, Meredith S, Harding S, Nazareth I, et al. Strategies to improve retention in randomised
trials: a Cochrane systematic review and meta-analysis. BMJ Open 2014 Feb 04;4(2):e003821 [FREE Full text] [doi:10.1136/bmjopen-2013-003821] [Medline: 24496696]
Edwards PJ, Roberts I, Clarke MJ, Diguiseppi C, Wentz R, Kwan I, et al. Methods to increase response to postal andelectronic questionnaires. Cochrane Database Syst Rev 2009(3):MR000008. [doi: 10.1002/14651858.MR000008.pub4][Medline: 19588449]
Arain M, Campbell MJ, Cooper CL, Lancaster GA. What is a pilot or feasibility study? A review of current practice andeditorial policy. BMC Med Res Methodol 2010;10:67 [FREE Full text] [doi: 10.1186/1471-2288-10-67] [Medline: 20637084]
Thabane L, Ma J, Chu R, Cheng J, Ismaila A, Rios LP, et al. A tutorial on pilot studies: the what, why and how. BMC Med
Res Methodol 2010;10:1 [FREE Full text] [doi: 10.1186/1471-2288-10-1] [Medline: 20053272]
Julious SA. Sample size of 12 per group rule of thumb for a pilot study. Pharmaceut Statist 2005 Oct;4(4):287-291. [doi:10.1002/pst.185]
Whitehead AL, Julious SA, Cooper CL, Campbell MJ. Estimating the sample size for a pilot randomised trial to minimise
the overall trial sample size for the external pilot and main trial for a continuous outcome variable. Stat Methods Med Res
2016 Jun;25(3):1057-1073 [FREE Full text] [doi: 10.1177/0962280215588241] [Medline: 26092476]
Teare MD, Dimairo M, Shephard N, Hayman A, Whitehead A, Walters SJ. Sample size requirements to estimate key design
parameters from external pilot randomised controlled trials: a simulation study. Trials 2014 Jul 03;15(1):264 [FREE Fulltext] [doi: 10.1186/1745-6215-15-264] [Medline: 24993581]
Stata Statistical Software: Release 13. StataCorp LP, College Station, TX. 2013. URL: https://www.stata.com/support/faqs/
resources/citing-software-documentation-faqs/ [accessed 2021-06-24]
West B, Welch K, Galecki A. Linear Mixed Models: A Practical Guide Using Statistical Software, Second Edition. Boca
Raton, Florida, United States: CRC Press; 2014:1-440.
Gueorguieva R, Krystal JH. Move over ANOVA: progress in analyzing repeated-measures data and its reflection in papers
published in the Archives of General Psychiatry. Arch Gen Psychiatry 2004 Mar 01;61(3):310-317. [doi:10.1001/archpsyc.61.3.310] [Medline: 14993119]
Deady M, Teeson M, Mills K, Kay-Lambkin F, Baker A, Baillie A, et al. One person, diverse needs: living with mental
health and alcohol and drug difficulties. National Mental Health Commission’s Report Card on Mental Health and Suicide
Prevention - A Review of Best Practice Produced by the NHMRC Centre of Research Excellence in Mental Health andSubstance Use. 2013. URL: https://www.mentalhealthcommission.gov.au/getmedia/8bff246f-4ffd-4eda-9716-db8c19d8d01b/
One-person-diverse-needs-Living-with-a-mental-illness-as-well-as-the-challenges-from-difficulties-with-alcohol-and-drugs-use[accessed 2021-06-12]
Fernandez E, Salem D, Swift JK, Ramtahal N. Meta-analysis of dropout from cognitive behavioral therapy: magnitude,
timing, and moderators. J Consult Clin Psychol 2015 Dec;83(6):1108-1122. [doi: 10.1037/ccp0000044] [Medline: 26302248]
Beard C, Weisberg RB, Amir N. Combined cognitive bias modification treatment for social anxiety disorder: a pilot trial.
Depress Anxiety 2011 Nov;28(11):981-988 [FREE Full text] [doi: 10.1002/da.20873] [Medline: 21898705]
Blackwell SE. Clinical efficacy of cognitive bias modification interventions. Lancet Psychiatry 2020 Jun;7(6):465-467.
[doi: 10.1016/s2215-0366(20)30170-x]

Abbreviations
ApBM: approach bias modification
CBM: cognitive bias modification
CONSORT: Consolidated Standards of Reporting Trials
IBM: interpretation bias modification
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Prior et al

RCT: randomized controlled trial
SPIRIT: Standard Protocol Items: Recommendations for Interventional Trials
TAU: treatment as usual

Edited by G Eysenbach; submitted 10.03.21; peer-reviewed by A Klein, T Hammond, D Smith; comments to author 13.05.21; revised
version received 26.05.21; accepted 26.05.21; published 07.07.21
Please cite as:
Prior K, Salemink E, Wiers RW, Teachman BA, Piggott M, Newton NC, Teesson M, Baillie AJ, Manning V, McLellan LF, Mahoney
A, Stapinski LA
A Web-Based Cognitive Bias Modification Intervention (Re-train Your Brain) for Emerging Adults With Co-occurring Social Anxiety
and Hazardous Alcohol Use: Protocol for a Multiarm Randomized Controlled Pilot Trial
JMIR Res Protoc 2021;10(7):e28667
URL: https://www.researchprotocols.org/2021/7/e28667
doi: 10.2196/28667
PMID: 34255726©Katrina Prior, Elske Salemink, Reinout W Wiers, Bethany A Teachman, Monique Piggott, Nicola C Newton, Maree Teesson,
Andrew J Baillie, Victoria Manning, Lauren F McLellan, Alison Mahoney, Lexine A Stapinski. Originally published in JMIR
Research Protocols (https://www.researchprotocols.org), 07.07.2021. This is an open-access article distributed under the termsof the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
distribution, and reproduction in any medium, provided the original work, first published in JMIR Research Protocols, is properly
cited. The complete bibliographic information, a link to the original publication on https://www.researchprotocols.org, as wellas this copyright and license information must be included.

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