Clinical Effectiveness of Training for Awareness Resilience and Action (TARA) Compared to Standard Treatment for Adolescents and Young Adults With Depression, a Pragmatic Multi-center Randomised Controlled Superiority-trial
Phase: NA
Conditions: Depression in Adolescence, Depressive Disorder, Dysthymia and Chronic Depression
Sponsor: Umeå University

Clinical Effectiveness of Training for Awareness 
Resilience and Action Online Compared to 
Standard Treatment for Adolescents and Young 
Adults With Depression: Study Protocol and 
Analysis Plan for a Pragmatic, Multi-Center 
Randomized Controlled Superiority Trial 
 
NCT registration identifier: NCT04747340 
 
Study protocol revision, amendment 1.0 
 
Date: 2022-10-14 
 
 
 
 
__________________________________ 
 
Eva Henje, PI, on behalf of the TARA study-group 
 
 
 

Introduction 
 
As outlined in the study protocol (1): “We strive for full transparency throughout the study 
and any changes made to and/or deviations made from the protocol will be reported. Any 
modifications of the protocol including changes of study objectives, study design, participant 
population, sample size, study procedures, or significant administrative aspects will require a 
formal amendment to the protocol. The same applies to any changes of the protocol that may 
be a potential benefit, disadvantage or safety concern for the participants. Such amendments 
will be agreed upon by the study group, approved by the national ethical review board prior 
to implementation and notified to all study personnel involved.” 
 
Based on that intention and due to circumstances, that were not anticipated at the time of 
protocol publication we now officially make several changes to the study protocol. All 
changes have been agreed upon by the study group, reviewed and approved by the national 
ethical review board in Sweden (D.nr 2020-05734, D.nr. 2021-06418-02) and notified to all 
study personnel involved. 
 
Purpose 
 
The purpose of this amendment is to describe the revisions made to the study protocol for the 
clinical trial specified above.  
 
 
Implementation 
 
The changes outlined in the amendment will be implemented immediately from the time this 
document is published on clinicaltrials.gov. As the changes are considered minor and as only 
three groups (n=18) have been randomized thus far, we will not perform any separate 
analyses on the participants based on their inclusion before/after the implementation of the 
amendment. 
 
 
Revision history 
 
Revision to previous protocol version 1.0, published 11 October 2021 (1). 
Amendment 1.0, 8 October 2022: 
 
Change 
 
Rationale 
Affected protocol section 
Patients will be eligible for 
recruitment from the year 
they turn 15, not from the 
date they turn 15 as 
previously specified.  
To increase recruitment 
rates 
Eligibility 
Child and Adolescent 
psychiatry units and Youth 
Clinic units that belong to 
the same administrative 
Region will recruit and 
randomize and treat patients 
The units within the same 
administrative Region share 
staff and management 
personnel. Region-wide 
recruitment facilitates the 
recruitment process.  
Center and Participant 
Recruitment Procedure 

Region-wide and not locally 
as previously specified. In 
the analysis these Region-
wide centers (N=3-4) will be 
treated as one center each 
and not as several centers as 
previously specified. New 
randomization lists have 
been created using the same 
procedure as outlined 
previously. In the analysis, 
groups that have already 
been randomised will be 
treated as belonging to the 
larger center from within 
which they were recruited. 
A new data collection 
timepoint is introduced at 12 
months follow-up. Only 
self-rating will be performed 
at that timepoint using the 
scales Reynolds Adolescent 
Depression Scale 2nd edition, 
and Multidimensional 
Anxiety Scale for Children.  
More data will be collected 
for subsequent analysis of 
“other outcome measures”, 
and contact is maintained 
with the participants to 
reduce participant dropout at 
the 24-months follow up. 
Outcome Measures 
Analysis Plan 
The timepoint from which 
the calculated time to follow 
up (3-months, 6 months 
follow-up etc.) starts will be 
the time of treatment 
initiation in the TARA-arm 
and from randomization in 
the Standard Treatment arm.  
This was not previously 
defined.  
Assessments 
The cut-off at which 
participants may be 
recruited on CDRS-R-score 
only will be reduced from 
40 to 35. 
To increase recruitment 
rates. 
Eligibility 
Youth clinics will also post 
flyers with information 
about the study on their 
social media platforms.  
To increase recruitment 
rates from these centers 
specifically.  
Center and participant 
recruitment procedure.  
We will allow for the 
possibility of randomizing 
up to eight eligible 
individuals if eight have 
been recruited (instead of six 
as previously specified). 
To enable a reduction in 
waiting-times from 
recruitment to 
randomization.  
Randomization 

Consent from parents/legal 
guardians is no longer 
needed for individuals 
below 18 years of age.  
For participation not to be 
contingent upon cooperating 
caregivers.  
Eligibility 
Two new exploratory 
outcomes have been added 
and both are self-rated by 
the participant. The scales 
include: 1.) A self-made 
questionnaire with questions 
related to community-
aspects of TARA 
(administered at 3-, 6-, and 
24-months follow-up to 
TARA-arm participants 
only), and 2.) A checklist 
with questions regarding 
bullying and harassment in 
school, during leisure-time 
or on-line (administered at 
3-, 6-, and 24-months 
follow-up). 
Qualitative interviews with 
previous TARA-participants 
have highlighted 
community-aspects as 
important parts of the 
intervention. Previous 
questionnaires assessed 
trauma in a narrow way.  
Other outcome measures. 
 
 
References 
 
1. 
Ekbäck E, Granåsen G, Svärling R, Blomqvist I, Henje E. Clinical Effectiveness of 
Training for Awareness Resilience and Action Online Compared to Standard Treatment for 
Adolescents and Young Adults With Depression: Study Protocol and Analysis Plan for a 
Pragmatic, Multi-Center Randomized Controlled Superiority Trial. Front Psychiatry. 
2021;12:674583. 
 

 
Begränsad delning 
Clinical Effectiveness of Training for Awareness 
Resilience and Action Online Compared to 
Standard Treatment for Adolescents and Young 
Adults With Depression:  
Study Protocol and Analysis Plan for a Pragmatic, Multi-Center 
Randomized Controlled Superiority Trial 
 
 
NCT registration identifier: NCT04747340 
 
Study protocol revision, amendment 2.0 
 
Date: 2024-04-09 
 
 
 
 
Signature __________________________________ 
 
Eva Henje, PI, on behalf of the TARA study-group 
 
 
 

 
Begränsad delning 
Introduction 
 
As outlined in the study protocol (1): “We strive for full transparency throughout the study 
and any changes made to and/or deviations made from the protocol will be reported. Any 
modifications of the protocol including changes of study objectives, study design, participant 
population, sample size, study procedures, or significant administrative aspects will require a 
formal amendment to the protocol. The same applies to any changes of the protocol that may 
be a potential benefit, disadvantage or safety concern for the participants. Such amendments 
will be agreed upon by the study group, approved by the national ethical review board prior 
to implementation and notified to all study personnel involved.” 
 
Based on this intention and due to circumstances, that were not anticipated at the time of the 
protocol publication, we now officially make an amendment with some new changes to the 
study protocol. All changes have been agreed upon by the study group, reviewed and 
approved by the national ethical review board in Sweden (D.nr 2020-05734, D.nr. 2021-
06418-02, 2022-04979-02) and notified to all study personnel involved. 
 
Purpose 
 
The purpose of this amendment is to describe the revisions made to the study protocol for the 
clinical trial specified above.  
 
 
Implementation 
 
The changes outlined in the amendment will be implemented immediately from the time this 
document is published on clinicaltrials.gov. As the changes are considered minor, we will not 
perform any separate analyses on the participants based on their inclusion before/after the 
implementation of the amendment. 
 
 
Revision history 
 
Revision to previous protocol version 1.0, published 11 October 2021 (1). 
Amendment 1.0, 8 October 2022. 
 
 
Amendment 2.0, 9 April 2024: 
 
Change 
 
Rationale 
Affected protocol section 
Participants will be recruited 
to the primary care center in 
Region Västerbotten also 
from primary care units that 
are not youth clinics 
specifically. No additional 
pilot trial will be performed 
before their inclusion in the 
RCT.  
To increase recruitment 
rates and to recruit with a 
more even distribution 
across the age-range. The 
pilot trial step is not 
performed as all the 
implementation 
infrastructure is already in 
place.  
Center and participant 
recruitment procedure.  

 
Begränsad delning 
 
No MRI-scanning is 
performed 
A large neuroimaging study 
of TARA has been launched 
at University of California 
San Francisco 
(NCT05267340) 
Assessments.  
The main mixed effects 
model will include fixed 
effects for treatment 
allocation, RADS-2-score at 
T0, age, study center and 
sex. 
 
To avoid potential problems 
related to analyzing age as a 
dichotomous variable as 
previously suggested. The 
cut-off at 18 years of age is 
arbitrary and does not match 
cognitive and brain 
maturation processes.  
Analysis plan 
Additional professions are 
included as TARA-
facilitators: such as 
pharmacist, students of 
clinical psychology, public 
health scientist 
To widen the recruitment 
base for TARA facilitators, 
and to evaluate the 
feasibility of a broader 
facilitator population.  
TARA intervention 
protocol. 
 
 
 
 
 
 
 
 
References 
 
1. 
Ekbäck E, Granåsen G, Svärling R, Blomqvist I, Henje E. Clinical Effectiveness of 
Training for Awareness Resilience and Action Online Compared to Standard Treatment for 
Adolescents and Young Adults With Depression: Study Protocol and Analysis Plan for a 
Pragmatic, Multi-Center Randomized Controlled Superiority Trial. Front Psychiatry. 
2021;12:674583.