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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

Date results information 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]

None.

Universal Trial Number (UTN)

U1111-1204-8675

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Anxiety disorders

Condition category

Condition code

Mental Health

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]

Treatment: Other

Intervention code [2]

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]

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]

Pre-treatment
Post-treatment (primary endpoint)
6-month follow-up

Primary outcome [2]

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]

Pre-treatment
Post-treatment (primary endpoint)
6-month follow-up

Primary outcome [3]

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]

Pre-treatment
Post-treatment (primary endpoint)
6-month follow-up

Secondary outcome [1]

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]

Pre-treatment
Week 5 (five weeks after commencing)
Post-treatment
6 month follow-up

Secondary outcome [2]

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]

Pre-treatment
Week 5 (five weeks after commencing)
Post-Intervention
6 month follow-up

Secondary outcome [3]

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]

Completed at program registration, and as a standard part of the online program, at the beginning of each session.

Secondary outcome [4]

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]

Post-treatment
6-month follow-up

Secondary outcome [5]

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]

At end of session 1.

Secondary outcome [6]

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]

Post-treatment

Secondary outcome [7]

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]

Pre-treatment
Post-treatment
6-month follow-up

Secondary outcome [8]

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]

Post-treatment

Secondary outcome [9]

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]

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?

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]

Charities/Societies/Foundations

Name [1]

Foundation for Children - Children's Financial Markets Trust

Address [1]

Foundation for Children
GPO Box 3655
Sydney NSW 2000

Country [1]

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]

University

Name [1]

Griffith University

Address [1]

Griffith University
Nathan campus
Kessels Rd., Nathan
QLD 4111

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

University of Southern Queensland Human Research Ethics Comittee

Ethics committee address [1]

University of Southern Queensland
Education City
Sinnathamby Blvd
Springfield Central
QLD 4300

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

02/03/2017

Approval date [1]

01/06/2017

Ethics approval number [1]

H17REA050

Summary

Brief summary

Anxiety affects 7% of young people & only 50% receive help. This project aims to test the feasibility of a new, stepped care, internet based Cognitive behavioural treatment (iCBT) model for youth anxiety utilising the BRAVE Program. Therapist supported iCBT demonstrates equivalent efficacy with face to face CBT, but cost and insufficient numbers of clinicians means therapist guided iCBT is often not available or unsuitable to reach large numbers of anxious youth. Self help iCBT (no therapist) offers one solution.

A national trial of BRAVE Self Help (>16,000 registrations in 2 years) showed meaningful anxiety reductions for youth completing the program. Many children failed to complete the treatment without support and not all were successfully treated. There is a need to identify models of care that can reach large numbers and provide appropriate support; such as a Stepped Care Model (SCM). Within a SCM, all young people would first receive the less intensive treatment. Those who have not responded well to the first step then receive a more intensive intervention.

In this project, all participants would first receive 5 sessions of self help iCBT (step 1; psychoeducation, skills acquisition). Those who respond will receive 5 more self help sessions (skill rehearsal & maintenance). Those who fail to respond after step 1 would `step up' to receive their remaining 5 iCBT sessions with therapist guidance (step 2). Pilot evidence supports the use of a SCM in high intensity face to face CBT for childhood anxiety. To date, no studies of SCMs for iCBT exist. If a SCM approach, using self help plus therapist guided iCBT is as effective as therapist guided iCBT alone, we will have identified a scalable, easily disseminated model that can produce clinical outcomes similar to standard clinical therapy. This particular project utilises a very simple form of therapist support, primarily delivered via emails from the therapist, which can be conducted anywhere, anytime. Therefore, a stepped care model of intervention where people step up to email therapist support presents a model of care that can be easily distributed and is not intrusive to young people.

Trial website

https://brave4you.psy.uq.edu.au/

Trial related presentations / publications

Public notes

Participants can register for the research trial at: https://brave4you.psy.uq.edu.au/
Participants who register for the program and meet eligibility criteria will be invited to participate.

Contacts

Principal investigator

Name

A/Prof Sonja March

Address

School of Psychology and Counselling, & Institute for Resilient Regions
University of Southern Queensland
Springfield Campus
37 Sinnathamby Blvd,
Springfield Central
QLD 4300

Country

Australia

Phone

+61 7 3470 4434

Fax

[email protected]

Contact person for public queries

Name

A/Prof Sonja March

Address

School of Psychology and Counselling, & Institute for Resilient Regions
University of Southern Queensland
Springfield Campus
37 Sinnathamby Blvd,
Springfield Central
QLD 4300

Country

Australia

Phone

+61 7 3470 4434

Fax

[email protected]

Contact person for scientific queries

Name

A/Prof Sonja March

Address

School of Psychology and Counselling, & Institute for Resilient Regions
University of Southern Queensland
Springfield Campus
37 Sinnathamby Blvd,
Springfield Central
QLD 4300

Country

Australia

Phone

+61 7 3470 4434

Fax

[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.	Type	Citation	Link	Email	Other Details	Attachment
14965	Informed consent form			[email protected]
14966	Ethical approval			[email protected]

Results publications and other study-related documents

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No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Stepped-care versus therapist-guided, internet-based cognitive behaviour therapy for childhood and adolescent anxiety: A non-inferiority trial.	2023	https://dx.doi.org/10.1016/j.invent.2023.100675

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

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