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Trial registered on ANZCTR


Registration number
ACTRN12618001415291
Ethics application status
Approved
Date submitted
20/08/2018
Date registered
24/08/2018
Date last updated
21/10/2022
Date data sharing statement initially provided
7/02/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Using Stepped Care in Internet-Based Cognitive Behaviour Therapy for child and adolescent anxiety
Scientific title
A Randomised Controlled Trial of Stepped Care, Internet-Based Cognitive Behaviour Therapy for child and adolescent anxiety
Secondary ID [1] 293253 0
None.
Universal Trial Number (UTN)
U1111-1204-8675
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anxiety disorders 305417 0
Condition category
Condition code
Mental Health 304697 304697 0 0
Anxiety

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Both conditions will receive the BRAVE-ONLINE program, which includes 10 online sessions of approximately 45-minute duration, completed once per week. BRAVE includes evidence-based anxiety management strategies such as recognition of physiological symptoms, relaxation, coping self-talk, cognitive restructuring, graded exposure, and self-reinforcement. Sessions comprise visually appealing pages, reading material, question/answer exercises, games, quizzes and homework. There are different versions of the program for children (aged 8-12 years) and adolescents (aged 13-17 years). Participants receive automated email reminders of session availability, reminding of overdue sessions and reinforcing progress.

Intervention Arm 1- Stepped-Care Internet-Cognitive Behavioural Therapy (SC-iCBT) with email therapist assistance.

Participants in this intervention arm will receive BRAVE-ONLINE as above, using a stepped-care version of the program. SC-iCBT will include all BRAVE-ONLINE components but incorporates 2 steps, namely (i) self-help iCBT and (ii) therapist guided iCBT. Step 1 (self-help) will be delivered to all SC participants and will include 5 sessions of low-intensity, self-directed iCBT (low intensity = no therapist support, participants complete program on their own).

‘Non-responders’ after Step 1 will progress to step 2, therapist-guided iCBT. Therapist support will include a brief phone introduction to their therapist (max 10 minutes) after session five, and one 30-minute phone call after session 5 (children) and 6 (adolescents) where the therapist assists the participant to refine their exposure hierarchy (developed in the previous session) and assist in planning the implementation of this exposure hierarchy. It will also include weekly emails from the therapist to the participant after completion of each of the remaining 5 sessions. In these one-way emails, the therapist will review participant responses, provide reinforcement of effort and correct misdirected responses. All therapists will be provided with template email responses to guide their responses and are asked to focus only on key elements of the treatment program. These have been generated by the lead investigator for each of the programs. Therapists will be asked to spend a maximum of 15 minutes per week on generating email responses. In this study, therapists will hold a minimum of 4-years training in Psychology.
In terms of treatment fidelity, therapists are required to keep a record of the number of minutes spent each week on sending emails and the phone calls, to provide a check of the treatment provided. Further, a random sample of 10% of email responses will be examined by the lead investigator to check adherence to template email responses.

Step 1 ‘responders’ will continue to receive the remaining five sessions of the self-help program (no therapist support provided) until the post-intervention assessment.
‘Responders’ will continue to be monitored, receiving automatic email alerts with referral recommendations if they demonstrate a return to clinical levels of anxiety, but will not receive additional therapist contact. ‘Non-responders’ will be defined as any participant who has not demonstrated a reduction into the non-elevated range, based on sex-standardised means (based on a large normative youth sample; and our previous large self-help trial) on the CAS-8 at mid-intervention. ‘Responders’ will be identified as participants who have demonstrated a reduction in anxiety by mid-intervention, to within the non-elevated range. This ‘step-up’ point was determined based on empirical evidence from our trial of BRAVE Self-Help which indicated that changes of this nature on the CAS-8 by Session 5 are representative of a positive response to the program and achieved by a significant proportion of the participants.

Participants will be able to access the online program beyond post-treatment, although no therapist support will be provided beyond this point.
Intervention code [1] 299584 0
Treatment: Other
Intervention code [2] 312208 0
Behaviour
Comparator / control treatment
Intervention Arm 2- Standard, therapist-guided internet-based cognitive-behavior therapy (TG-iCBT).

TG-iCBT will include all BRAVE-ONLINE components, delivered with therapist support including; an introductory phone call prior to treatment (10 minutes), personalised therapist emails (using templates) sent at the completion of each session (reinforcing effort and correcting misdirected responses), and a mid-point telephone call (30 minutes) to discuss exposure hierarchy development and implementation.
Therapists will be asked to spend a maximum of 15 minutes per week on generating email responses. In this study, therapists will hold a minimum of 4-years training in Psychology.

Participants will be able to access the online program beyond post-treatment, although no therapist support will be provided beyond this point.
Control group
Active

Outcomes
Primary outcome [1] 303972 0
The primary outcome measure is clinician severity rating relating to the primary anxiety disorder.
Clinician rating of symptom severity for the primary anxiety diagnosis is determined from information obtained in the diagnostic interview, and rated on a 0-8-point scale. Diagnostic status and severity will be determined via a "blind", independent clinical diagnostic interview for anxiety disorders and clinician severity rating of diagnosis using Anxiety Disorders Interview Schedule: Child version (ADIS-C).
Timepoint [1] 303972 0
Pre-treatment
Post-treatment (primary endpoint)
6-month follow-up
Primary outcome [2] 303973 0
A second primary outcome will be diagnostic status: free of primary anxiety disorder.

In this outcome, diagnostic status will be defined as whether or not the participant is free of their primary anxiety disorder.

Diagnostic status will be determined via a "blind", independent clinical diagnostic interview for anxiety disorders and clinician severity rating of diagnosis using Anxiety Disorders Interview Schedule: Child version (ADIS-C)
Timepoint [2] 303973 0
Pre-treatment
Post-treatment (primary endpoint)
6-month follow-up
Primary outcome [3] 307177 0
Diagnostic status: free of all anxiety disorders

In this outcome, diagnostic status will be defined as whether or not the participant is free of all anxiety disorders.

Diagnostic status will be determined via a "blind", independent clinical diagnostic interview for anxiety disorders and clinician severity rating of diagnosis using Anxiety Disorders Interview Schedule: Child version (ADIS-C).
Timepoint [3] 307177 0
Pre-treatment
Post-treatment (primary endpoint)
6-month follow-up
Secondary outcome [1] 340562 0
Spence Children's Anxiety Scale- Child and Parent Version (SCAS-C&P)

This measure will be completed by parents and children and provides a comprehensive anxiety symptom assessment. The total anxiety score will be used as a secondary outcome measure and to corroborate ‘step-up’ decisions at mid-intervention.
Timepoint [1] 340562 0
Pre-treatment
Week 5 (five weeks after commencing)
Post-treatment
6 month follow-up
Secondary outcome [2] 340563 0
Child Health Utility 9 Index (CHU9-D)

This measure assesses nine domains of general health in children, including: Worried, Sad, Pain, Tired, Annoyed, School Work, Sleep, Daily Routine, and Activities and will be used to inform the economic evaluation.
Timepoint [2] 340563 0
Pre-treatment
Week 5 (five weeks after commencing)
Post-Intervention
6 month follow-up
Secondary outcome [3] 340564 0
Children's Anxiety Scale-8 (CAS-8)

This is a brief 8-item anxiety scale to assess total anxiety severity. Participants with elevated pre-treatment scores (completed at program registration) will be invited to complete the diagnostic interview.
Timepoint [3] 340564 0
Completed at program registration, and as a standard part of the online program, at the beginning of each session.
Secondary outcome [4] 340583 0
Therapy adherence.
This data will be automatically generated through the program and will include the number of prescribed sessions and activities completed throughout the program.
Timepoint [4] 340583 0
Post-treatment
6-month follow-up
Secondary outcome [5] 341130 0
Treatment expectancy
Treatment expectancy will be assessed after randomisation and at the end of session 1 through a 5-item questionnaire developed by the team in earlier studies (March et al. 2009; Spence et al. 2006).
Timepoint [5] 341130 0
At end of session 1.
Secondary outcome [6] 341131 0
Treatment satisfaction/acceptability by children and adolescents will be assessed at post-treatment with an, 8-item questionnaire developed by the team in earlier studies (March et al. 2009; Spence et al. 2006).
Timepoint [6] 341131 0
Post-treatment
Secondary outcome [7] 341132 0
Overall adaptive functioning as assessed via the Children's Global Assessment Scale. (CGAS: Schaffer et al., 1983).
The CGAS provides a single global rating of functioning, assigned to the youth by the independent, interviewing clinician, on a scale of 0 to 100, where lower scores indicate poorer functioning. A rating is given based on the child or adolescent's most impaired level of general functioning for the specified time period by selecting the lowest level which describes his/her functioning on a hypothetical continuum of health-illness, benchmarked against anchor points in a descriptive glossary. This assessment will be based on information obtained in the diagnostic interview.
Timepoint [7] 341132 0
Pre-treatment
Post-treatment
6-month follow-up
Secondary outcome [8] 350981 0
Therapist satisfaction.
The Program satisfaction questionnaire will also will also be amended for use by therapists to assess therapist acceptability of the intervention.
Timepoint [8] 350981 0
Post-treatment
Secondary outcome [9] 350982 0
Economic evaluation:
The economic evaluation will assess the relative Cost Effectiveness (CEA) of TG-iCBT compared to SC-iCBT using cost data based on program development costs, maintenance of web-based infrastructure, and therapist delivery time. Any other program provision costs (including non market costs) will be captured and any additional incurred healthcare costs will be calculated using social values (Medicare rebate values). Calculation of mean values of both arms of the study will occur for comparison purposes with 95% confidence intervals obtained.
The patient net benefits from both treatment arms will be measured by obtaining their Health Related Quality of Life (HRQoL) over the same time period, collected via the CHU9. The Australian value set for adolescents will be used to score the CHU9 to convert HRQoL into Quality Adjusted Life Years (QALYs). All costs and QALYs will be converted to present values and the Incremental Cost-Effectiveness Ratio estimated. Sensitivity analysis will be undertaken where necessary, most likely in changes to treatment costs.
Timepoint [9] 350982 0
Post-treatment
6-month follow-up

Eligibility
Key inclusion criteria
Children and adolescents will be included in the study if they meet diagnostic criteria for a primary diagnosis of anxiety (social anxiety disorder, specific phobia, separation anxiety disorder, generalised anxiety disorder) with a clinical severity rating (CSR) of at least 4 (on a 0-8 scale). Comorbidity with other disorders will be permissible as long as the anxiety disorder is considered primary. Participants with comorbid depression will be excluded if the depression is severe (rated 6 or higher on an 8-point scale). Families must have access to a suitable computer and the internet, and be willing to participate in the study.
Minimum age
8 Years
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
As the internet program requires a minimum reading age of 8 years, children with an identified intellectual handicap or learning disability will not be included. Children with a pervasive developmental disorder will also be excluded. For ethical reasons pertaining to the danger of potential self-harm, youngsters with clinical levels of depression (Clinician Severity Rating of 6 or higher on a 0-8 scale on the ADIS-C/P) will not be included in the program and will be referred elsewhere for assistance.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation will concealed by using sealed opaque envelopes. The randomisation sequence will be determined by the first investigator who will provide the sealed envelopes to the assessors.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Stratified random assignment will be used controlling for participant age (child, teen), and an allocation ratio of 1:1 to treatment conditions.
Simple randomisation will be employed using a randomisation table created by computer sequence generation.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
This is a non-inferiority randomised controlled trial. The margin of non-inferiority was set at d=.20 (raw Effect Size), with the lower bound of the confidence interval not exceeding d=.40.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
We will aim to recruit between 50-75 participants per condition, which will provide sufficient power for a feasibility test of the primary outcome variable.

All analyses will be performed using SPSS. Per recommendations for non-inferiority trials (Scott, 2009; Piaggio et al. 2006), analyses will be conducted both using an intent-to-treat (ITT) and per-protocol (PP) approach. The latter is desirable in non-inferiority trials as protection from an increase in type I error risk; ITT analysis is more likely to narrow the difference between treatments and yield a non-inferior result. The continuous primary and secondary outcome data will be analysed using mixed model, hierarchical linear modelling, nested within treatment groups, taking time as a within subjects and group as a between subjects effect. Sensitivity analysis will assess the effects of attrition.

A one-sided 97.5% confidence interval will be applied as recommended for non-inferiority trials (Scott, 2009; Piaggio et al. 2006). Presence of anxiety diagnosis will be examined and reported using chi-square analyses. Effect sizes will be calculated for each measure and within each intervention condition to evaluate the level of clinically significant change at post-intervention and 6-month follow-up.

For the economic evaluation, this study will assess the relative Cost Effectiveness (CEA) of TG-iCBT compared to SC-iCBT using cost data. The patient net benefits from both treatment arms will be measured by obtaining their Health Related Quality of Life (HRQoL) over the same time period, collected via the CHU9. The Australian value set for adolescents will be used to score the CHU9 to convert HRQoL into Quality Adjusted Life Years (QALYs). All costs and QALYs will be converted to present values and the Incremental Cost-Effectiveness Ratio estimated. Sensitivity analysis will be undertaken where necessary, most likely in changes to treatment costs. The CEA will allow determination of whether the SC-iCBT intervention leads to a decrease in treatment costs compared to the TG-iCBT intervention.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
27/08/2018
Actual
3/09/2018
Date of last participant enrolment
Anticipated
13/12/2019
Actual
5/09/2019
Date of last data collection
Anticipated
14/08/2020
Actual
6/06/2020
Sample size
Target
130
Accrual to date
Final
137
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC

Funding & Sponsors
Funding source category [1] 297884 0
Charities/Societies/Foundations
Name [1] 297884 0
Foundation for Children - Children's Financial Markets Trust
Country [1] 297884 0
Australia
Primary sponsor type
University
Name
University of Southern Queensland
Address
USQ Springfield
37 Sinnathamby Blvd,
Springfield Central
QLD 4300
Country
Australia
Secondary sponsor category [1] 296934 0
University
Name [1] 296934 0
Griffith University
Address [1] 296934 0
Griffith University
Nathan campus
Kessels Rd., Nathan
QLD 4111
Country [1] 296934 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298932 0
University of Southern Queensland Human Research Ethics Comittee
Ethics committee address [1] 298932 0
Ethics committee country [1] 298932 0
Australia
Date submitted for ethics approval [1] 298932 0
02/03/2017
Approval date [1] 298932 0
01/06/2017
Ethics approval number [1] 298932 0
H17REA050

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 78698 0
A/Prof Sonja March
Address 78698 0
School of Psychology and Counselling, & Institute for Resilient Regions
University of Southern Queensland
Springfield Campus
37 Sinnathamby Blvd,
Springfield Central
QLD 4300
Country 78698 0
Australia
Phone 78698 0
+61 7 3470 4434
Fax 78698 0
Email 78698 0
[email protected]
Contact person for public queries
Name 78699 0
Sonja March
Address 78699 0
School of Psychology and Counselling, & Institute for Resilient Regions
University of Southern Queensland
Springfield Campus
37 Sinnathamby Blvd,
Springfield Central
QLD 4300
Country 78699 0
Australia
Phone 78699 0
+61 7 3470 4434
Fax 78699 0
Email 78699 0
[email protected]
Contact person for scientific queries
Name 78700 0
Sonja March
Address 78700 0
School of Psychology and Counselling, & Institute for Resilient Regions
University of Southern Queensland
Springfield Campus
37 Sinnathamby Blvd,
Springfield Central
QLD 4300
Country 78700 0
Australia
Phone 78700 0
+61 7 3470 4434
Fax 78700 0
Email 78700 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified data pertaining to primary and secondary outcomes may be shared. De-identified data will be shared with researchers under circumstances where the researchers have appropriate ethics approvals and appropriate research questions.
When will data be available (start and end dates)?
Data will only become available after all data has been analysed and results published from the trial. This includes both primary research questions, secondary research questions and those arising from the study later. These dates are to be determined.
Available to whom?
This de-identified data may be available to other researchers who hold suitable ethical clearance and wish to collaborate with the investigator team.
Available for what types of analyses?
The de-identified data may be available for review and meta-analytic purposes or other anlayses on request.
How or where can data be obtained?
The data can be obtained from the primary investigator at [email protected]


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
14965Informed consent form  [email protected]
14966Ethical approval  [email protected]



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseStepped-care versus therapist-guided, internet-based cognitive behaviour therapy for childhood and adolescent anxiety: A non-inferiority trial.2023https://dx.doi.org/10.1016/j.invent.2023.100675
N.B. These documents automatically identified may not have been verified by the study sponsor.