Optimizing Cognitive-behavioral Therapy for Social Anxiety Disorder Using the Factorial Design

Study Overview
=================
Brief Summary
-----------------
Social Anxiety Disorder (SAD) is characterized by a marked fear of negative evaluation in social situations. It is the third most common psychiatric disorder and highly disabling (American Psychiatric Association, 2000). Although effective treatments such as cognitive-behavioral therapy (CBT) are available, most individuals suffering from SAD do not seek and eventually find help, and even in the best available treatments, remission rates are below 50%. The overall aim of the project is to better understand and improve the efficacy of Internet-based CBT (ICBT) that has shown to be efficacious in many trials and that provide broad and low-threshold access to empirically supported treatments. Specifically the objectives of the study are: to investigate the active ingredients of ICBT for SAD by testing the main effects and interactions for the four main treatment components (i.e., psychoeducation, cognitive restructuring, attention training, and exposure); to investigate the effects of each treatment component on hypothesized change mechanisms, and to explore whether and which change mechanisms mediate the effect of the treatment components on symptom reduction. to investigate whether the specific mechanisms mediate the effect of the treatment components on primary and secondary outcomes.

Detailed Description
-----------------
Social Anxiety Disorder (SAD) is characterized by a marked fear of negative evaluation in social situations. It is the third most common psychiatric disorder and highly disabling. Although effective treatments such as cognitive-behavioral therapy (CBT) are available, most individuals suffering from SAD do not seek and eventually find help, and even in the best available treatments, remission rates are below 50%. The overall aim of the project is to improve the efficacy of Internet-based CBT (ICBT) that has shown to be efficacious in many trials and that provide broad and low-threshold access to empirically supported treatments. Specifically, the objectives of the study are: to investigate the active ingredients of ICBT for SAD by testing the main effects and interactions for the four main treatment components (i.e., psychoeducation, cognitive restructuring, attention training, and exposure); to investigate the effects of each treatment component on hypothesized change mechanisms (change of the knowledge of SAD, change on negative social cognitions, changes on self-focused attention, changes on social avoidance and use of safety behaviors), and to explore whether and which change mechanisms mediate the effect of the treatment components on symptom reduction. to investigate whether the specific mechanisms mediate the effect of the treatment components on primary and secondary outcomes. The study is a single-center, factorial trial with four experimental factors (treatment components, i.e., psychoeducation, cognitive restructuring, attention training, and exposure) each evaluated at two levels (presence vs. absence) resulting in 16 conditions. Recruitment: Participants will be recruited using reports in newspapers, through internet forums, social media (e.g., Facebook), and via our website (https://www.online-therapy.ch/) in German-speaking countries. Sampling: After checking the inclusion criteria, participants will be randomized with equal probability to one of the 16 conditions. The random allocation will be unknown to the investigators. In order to keep the sample sizes of the 16 conditions similar, the allocation list will be made using randomly permuted blocks. A total of 464 participants with a Diagnostic and Statistical Manual of Mental Disorders diagnosis of SAD will be included, with 29 patients being assigned to each of the 16 conditions. Assessment procedures: The primary outcome measure is change in symptoms of SAD at post-treatment, i.e., after 8 weeks. Secondary outcomes include sustaining change at follow up (6 months after baseline), changes in depressive symptoms, changes in general anxiety symptoms, changes in quality of life, adherence to treatment, treatment satisfaction, negative effects and changes of diagnosis of SAD. Furthermore, the hypothesized change mechanisms (change of the knowledge of SAD, change on negative social cognitions, changes in self-focused attention, changes in social avoidance and use of safety behaviors) will be assessed. Self-report measures are taken at pre-treatment (baseline), after 4 weeks (mid-treatment), after 8 weeks (post-treatment), and at 6 months after randomization (follow-up). Besides the self-report measures, a diagnostic interview will be conducted by phone at pre-treatment, eight weeks (posttreatment), and six months (follow-up). The structured M.I.N.I. Interview will be used. The interviews will be administered by advanced Master students in clinical psychology and psychotherapy supervised by the study team. Interrater reliability will be assessed on a subset of the cases. Treatment: The internet-based self-help program (Shyne, https://selfhelp1.psy.unibe.ch/shyne/) is based on the well-established cognitive-behavioral treatment of social anxiety by Clark and Wells and has been proven efficacious in previous studies. Shyne is accessed through a secure website, with each participant having a password-protected account. It consists of the following four treatment components: (1) psychoeducation (knowledge about SAD and its treatment); (2) cognitive restructuring (challenging dysfunctional social cognitions); (3) attention training (decrease of self-focused attention); and (4) exposure (decrease of avoidance of feared situations and safety behaviors). These treatment components will be offered in 16 different combinations. Data analysis: Primary analyses will be conducted on the Intention-To-Treat (ITT) sample (i.e., all randomized participants). The analyses are carried out on the basis of the intention-to-treat (ITT) approach using linear mixed models. In addition, but only secondary, completers analysis will be carried out. In order to test for main and interaction effects of treatment components on outcomes and change mechanisms across the time points of assessment, linear mixed models Analysis of Variance (ANOVA) or latent growth curve modelling will be used. Main effects and interactions will be based on aggregates across experimental conditions. Sensitivity analyses will explore the impact of the imputation of missing values. For binary outcome data (i.e., SAD diagnosis), a logistic regression model will be used. Furthermore, mediation analyses will be used to determine whether the hypothesized change mechanisms mediate the effect of the treatment components on primary and secondary outcomes. The mediation will be tested using an approach that allows multiple mediators in one model. In addition, potential moderation of the treatment components by various measured variables such as comorbid disorder, medication, the severity of SAD, age and sex will be investigated. Reporting will follow CONSORT E-Health standards.

Official Title
-----------------
Optimizing Cognitive-behavioral Therapy for Social Anxiety Disorder Using the Factorial Design: What Works Best and How Does it Work (OPTIMIZE)

Conditions
-----------------
Social Anxiety Disorder (Social Phobia)

Intervention / Treatment
-----------------
* Behavioral: Exposure
* Behavioral: Attention Training
* Behavioral: Cognitive Restructuring
* Behavioral: Psychoeducation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1. read the study information and sign informed consent; 2. are 18 years or older; 3. have access to the Internet, to a smartphone, PC or tablet; 4. have sufficient knowledge of German; 5. exceed predefined cut-off scores on one of the social anxiety measures (22 points on the Social Phobia Scale or 33 points on the Social Interaction Anxiety Scale; SPS & SIAS); 6. fulfil the diagnostic criteria of SAD according to the diagnostic telephone interview (the presence of other disorders does not result in exclusion if SAD is the primary diagnosis) 7. in the case of taking psychiatric medication, the treatment is stabilized (over one month) Exclusion Criteria: 1. they score 2 or higher on the suicide item of the PHQ-9 (Spitzer, 1999) or with active suicidal plans in the diagnostic telephone interview. 2. they have other comorbid psychiatric conditions that might be the main focus of clinical attention (e.g., psychotic symptoms, bipolar disorder, or other severe disorder) 3. they undergo another psychological treatment at the beginning of the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: The study is a single-center, factorial trial with four experimental factors (treatment components, i.e., psychoeducation, cognitive restructuring, attention training, and exposure) each evaluated at two levels (presence vs. absence) resulting in 16 treatment conditions.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: 1_Waiting List control<br>Randomized participants will only get the full intervention after study completion period (6 months since the randomization) | |
| Experimental: 2_Exposure only<br>Randomized participants will only get the Exposure component | Behavioral: Exposure<br>* Participants are instructed to plan and track in vivo exposures using an exposure diary. Participants are also instructed to reduce safety behaviors, which are overt or covert acts such as avoiding eye contact or rehearsing sentences to prevent a feared outcome.<br>|
| Experimental: 3_Attention Training only<br>Randomized participants will only get the Attention Training component | Behavioral: Attention Training<br>* Participants are trained to reduce self-focused and biased attention. Various audio exercises are introduced in which participants learn to intentionally direct the attention away from themselves (i.e., less private self-consciousness), and to be less alert to potentially dangerous external social stimuli (i.e., less public self-consciousness).<br>|
| Experimental: 4_Exposure + Attention Training<br>Randomized participants will get Exposure + Attention Training components | Behavioral: Exposure<br>* Participants are instructed to plan and track in vivo exposures using an exposure diary. Participants are also instructed to reduce safety behaviors, which are overt or covert acts such as avoiding eye contact or rehearsing sentences to prevent a feared outcome.<br>Behavioral: Attention Training<br>* Participants are trained to reduce self-focused and biased attention. Various audio exercises are introduced in which participants learn to intentionally direct the attention away from themselves (i.e., less private self-consciousness), and to be less alert to potentially dangerous external social stimuli (i.e., less public self-consciousness).<br>|
| Experimental: 5_Cognitive Restructuring only<br>Randomized participants will only get the Cognitive Restructuring component | Behavioral: Cognitive Restructuring<br>* Participants are instructed to identify and modify dysfunctional and negatively biased assumptions. It includes a thought diary to track negative beliefs in daily routine, alongside with exercises to formulate helpful and adaptive thoughts.<br>|
| Experimental: 6_Cognitive Restructuring + Exposure<br>Randomized participants will get Cognitive Restructuring + Exposure components | Behavioral: Exposure<br>* Participants are instructed to plan and track in vivo exposures using an exposure diary. Participants are also instructed to reduce safety behaviors, which are overt or covert acts such as avoiding eye contact or rehearsing sentences to prevent a feared outcome.<br>Behavioral: Cognitive Restructuring<br>* Participants are instructed to identify and modify dysfunctional and negatively biased assumptions. It includes a thought diary to track negative beliefs in daily routine, alongside with exercises to formulate helpful and adaptive thoughts.<br>|
| Experimental: 7_Cognitive Restructuring + Attention Training<br>Randomized participants will get Cognitive Restructuring + Attention Training components | Behavioral: Attention Training<br>* Participants are trained to reduce self-focused and biased attention. Various audio exercises are introduced in which participants learn to intentionally direct the attention away from themselves (i.e., less private self-consciousness), and to be less alert to potentially dangerous external social stimuli (i.e., less public self-consciousness).<br>Behavioral: Cognitive Restructuring<br>* Participants are instructed to identify and modify dysfunctional and negatively biased assumptions. It includes a thought diary to track negative beliefs in daily routine, alongside with exercises to formulate helpful and adaptive thoughts.<br>|
| Experimental: 8_Cognitive Restructuring + Attention Training + Exposure<br>Randomized participants will get Cognitive Restructuring + Attention Training + Exposure components | Behavioral: Exposure<br>* Participants are instructed to plan and track in vivo exposures using an exposure diary. Participants are also instructed to reduce safety behaviors, which are overt or covert acts such as avoiding eye contact or rehearsing sentences to prevent a feared outcome.<br>Behavioral: Attention Training<br>* Participants are trained to reduce self-focused and biased attention. Various audio exercises are introduced in which participants learn to intentionally direct the attention away from themselves (i.e., less private self-consciousness), and to be less alert to potentially dangerous external social stimuli (i.e., less public self-consciousness).<br>Behavioral: Cognitive Restructuring<br>* Participants are instructed to identify and modify dysfunctional and negatively biased assumptions. It includes a thought diary to track negative beliefs in daily routine, alongside with exercises to formulate helpful and adaptive thoughts.<br>|
| Experimental: 9_Psychoeducation only<br>Randomized participants will only get the Psychoeducation component | Behavioral: Psychoeducation<br>* Participants are delivered detailed evidence-based information on SAD with a focus on maintaining processes (e.g., the vicious circle of negative thoughts and emotions, cognitions, and behaviors associated with the maintenance of SAD). Based on the information provided, participants are encouraged to develop an individual model of their social anxiety symptoms.<br>|
| Experimental: 10_Psychoeducation + Exposure<br>Randomized participants will get the Psychoeducation + Exposure components | Behavioral: Exposure<br>* Participants are instructed to plan and track in vivo exposures using an exposure diary. Participants are also instructed to reduce safety behaviors, which are overt or covert acts such as avoiding eye contact or rehearsing sentences to prevent a feared outcome.<br>Behavioral: Psychoeducation<br>* Participants are delivered detailed evidence-based information on SAD with a focus on maintaining processes (e.g., the vicious circle of negative thoughts and emotions, cognitions, and behaviors associated with the maintenance of SAD). Based on the information provided, participants are encouraged to develop an individual model of their social anxiety symptoms.<br>|
| Experimental: 11_Psychoeducation + Attention Training<br>Randomized participants will get the Psychoeducation + Attention Training components | Behavioral: Attention Training<br>* Participants are trained to reduce self-focused and biased attention. Various audio exercises are introduced in which participants learn to intentionally direct the attention away from themselves (i.e., less private self-consciousness), and to be less alert to potentially dangerous external social stimuli (i.e., less public self-consciousness).<br>Behavioral: Psychoeducation<br>* Participants are delivered detailed evidence-based information on SAD with a focus on maintaining processes (e.g., the vicious circle of negative thoughts and emotions, cognitions, and behaviors associated with the maintenance of SAD). Based on the information provided, participants are encouraged to develop an individual model of their social anxiety symptoms.<br>|
| Experimental: 12_Psychoeducation + Attention Training + Exposure<br>Randomized participants will get the Psychoeducation + Attention Training + Exposure components | Behavioral: Exposure<br>* Participants are instructed to plan and track in vivo exposures using an exposure diary. Participants are also instructed to reduce safety behaviors, which are overt or covert acts such as avoiding eye contact or rehearsing sentences to prevent a feared outcome.<br>Behavioral: Attention Training<br>* Participants are trained to reduce self-focused and biased attention. Various audio exercises are introduced in which participants learn to intentionally direct the attention away from themselves (i.e., less private self-consciousness), and to be less alert to potentially dangerous external social stimuli (i.e., less public self-consciousness).<br>Behavioral: Psychoeducation<br>* Participants are delivered detailed evidence-based information on SAD with a focus on maintaining processes (e.g., the vicious circle of negative thoughts and emotions, cognitions, and behaviors associated with the maintenance of SAD). Based on the information provided, participants are encouraged to develop an individual model of their social anxiety symptoms.<br>|
| Experimental: 13_Psychoeducation + Cognitive Restructuring<br>Randomized participants will get the Psychoeducation + Cognitive Restructuring components | Behavioral: Cognitive Restructuring<br>* Participants are instructed to identify and modify dysfunctional and negatively biased assumptions. It includes a thought diary to track negative beliefs in daily routine, alongside with exercises to formulate helpful and adaptive thoughts.<br>Behavioral: Psychoeducation<br>* Participants are delivered detailed evidence-based information on SAD with a focus on maintaining processes (e.g., the vicious circle of negative thoughts and emotions, cognitions, and behaviors associated with the maintenance of SAD). Based on the information provided, participants are encouraged to develop an individual model of their social anxiety symptoms.<br>|
| Experimental: 14_Psychoeducation + Cognitive Restructuring + Exposure<br>Randomized participants will get the Psychoeducation + Cognitive Restructuring + Exposure components | Behavioral: Exposure<br>* Participants are instructed to plan and track in vivo exposures using an exposure diary. Participants are also instructed to reduce safety behaviors, which are overt or covert acts such as avoiding eye contact or rehearsing sentences to prevent a feared outcome.<br>Behavioral: Cognitive Restructuring<br>* Participants are instructed to identify and modify dysfunctional and negatively biased assumptions. It includes a thought diary to track negative beliefs in daily routine, alongside with exercises to formulate helpful and adaptive thoughts.<br>Behavioral: Psychoeducation<br>* Participants are delivered detailed evidence-based information on SAD with a focus on maintaining processes (e.g., the vicious circle of negative thoughts and emotions, cognitions, and behaviors associated with the maintenance of SAD). Based on the information provided, participants are encouraged to develop an individual model of their social anxiety symptoms.<br>|
| Experimental: 15_Psychoeducation + Cognitive Restructuring + Attention Training<br>Randomized participants will get the Psychoeducation + Cognitive Restructuring + Attention Training components | Behavioral: Attention Training<br>* Participants are trained to reduce self-focused and biased attention. Various audio exercises are introduced in which participants learn to intentionally direct the attention away from themselves (i.e., less private self-consciousness), and to be less alert to potentially dangerous external social stimuli (i.e., less public self-consciousness).<br>Behavioral: Cognitive Restructuring<br>* Participants are instructed to identify and modify dysfunctional and negatively biased assumptions. It includes a thought diary to track negative beliefs in daily routine, alongside with exercises to formulate helpful and adaptive thoughts.<br>Behavioral: Psychoeducation<br>* Participants are delivered detailed evidence-based information on SAD with a focus on maintaining processes (e.g., the vicious circle of negative thoughts and emotions, cognitions, and behaviors associated with the maintenance of SAD). Based on the information provided, participants are encouraged to develop an individual model of their social anxiety symptoms.<br>|
| Experimental: 16_full version (Psychoeducation + Cognitive Restructuring + Attention Training + Exposure)<br>Randomized participants will get the Psychoeducation + Cognitive Restructuring + Attention Training + Exposure components | Behavioral: Exposure<br>* Participants are instructed to plan and track in vivo exposures using an exposure diary. Participants are also instructed to reduce safety behaviors, which are overt or covert acts such as avoiding eye contact or rehearsing sentences to prevent a feared outcome.<br>Behavioral: Attention Training<br>* Participants are trained to reduce self-focused and biased attention. Various audio exercises are introduced in which participants learn to intentionally direct the attention away from themselves (i.e., less private self-consciousness), and to be less alert to potentially dangerous external social stimuli (i.e., less public self-consciousness).<br>Behavioral: Cognitive Restructuring<br>* Participants are instructed to identify and modify dysfunctional and negatively biased assumptions. It includes a thought diary to track negative beliefs in daily routine, alongside with exercises to formulate helpful and adaptive thoughts.<br>Behavioral: Psychoeducation<br>* Participants are delivered detailed evidence-based information on SAD with a focus on maintaining processes (e.g., the vicious circle of negative thoughts and emotions, cognitions, and behaviors associated with the maintenance of SAD). Based on the information provided, participants are encouraged to develop an individual model of their social anxiety symptoms.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change on social anxiety symptoms at post-treatment | Composite endpoint. Social anxiety symptoms are measured as the combined score of the Social Phobia Scale and the Social Interaction Anxiety Scale (SPS & SIAS; Mattick & Clarke, 1998). These instruments are complementary and used as one single measurement. They assess the fear of being judged by others during daily activities (SPS) and more general fears in social interaction (SIAS). The combined scale consists of 40 items and scores range from 0 (no social anxiety symptoms) to 160 (severe social anxiety symptoms). | Baseline, Mid-treatment (4 weeks after baseline), Post-treatment (8 weeks after baseline) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change on social anxiety symptoms at follow-up | Social anxiety symptoms are measured as the combined score of the Social Phobia Scale and the Social Interaction Anxiety Scale (SPS & SIAS; Mattick & Clarke, 1998). These instruments are complementary and used as one measurement. They assess the fear of being judged by others during daily activities (SPS) and more general fears in social interaction (SIAS). The combined scale consists of 40 items and scores range from 0 (no social anxiety symptoms) to 160 (severe social anxiety symptoms). | Baseline, Mid-treatment (4 weeks after baseline), Post-treatment (8 weeks after baseline), Follow-up (6 months after baseline) | 
| Change on the severity of depressive symptoms | Depressive symptoms will be measured by the Patient Health Questionnaire (PHQ-9; Spitzer et al., 1999). Scores range from 0 (no depressive symptoms) to 27 (severe depressive symptoms). | Baseline, Mid-treatment (4 weeks after baseline), Post-treatment (8 weeks after baseline), Follow-up (6 months after baseline) | 
| Change on the severity of general anxiety symptoms | Severity of anxiety symptoms will be measured by the Generalized Anxiety Disorder Scale (GAD-7; Spitzer et al., 2006). Scores range from 0 (no general anxiety symptoms) to 21 (severe general anxiety symptoms) | Baseline, Mid-treatment (4 weeks after baseline), Post-treatment (8 weeks after baseline), Follow-up (6 months after baseline) | 
| Change on quality of life | Quality of life will be measured by the Short-Form Health Survey-12 (SF-12; Ware et al., 1996). Scores range from 12 (high quality of life) to 53 (poor quality of life). | Baseline, Mid-treatment (4 weeks after baseline), Post-treatment (8 weeks after baseline), Follow-up (6 months after baseline) | 
| Level of satisfaction with the treatment | Treatment satisfaction will be measured by the Client Satisfaction Questionnaire (CSQ-8; Attkisson & Zwick, 1982), adapted to internet-based interventions. Scores range from 0 (not satisfied at all) to 24 (extremely satisfied). | Post-treatment (8 weeks after baseline) | 
| Negative effects of the treatment | Adverse effects on social, intrapersonal or work-related situations and whether they are attributed to the intervention will be measured on the 15 items Negative Effects of the Treatment scale (INEP; Ladwig et al., 2014). The scores range from - 39 (worse) to +18 (best), in which negative values indicate negative effects of the intervention | Mid-treatment (4 weeks after baseline), Post-treatment (8 weeks after baseline), Follow-up (6 months after baseline) | 
| Change on the diagnosis of social anxiety disorder | Diagnosis of social anxiety disorder will be assessed with M.I.N.I International Neuropsychiatric Interview for DSM-IV 6.0.0 (M.I.N.I; Sheehan et al., 1998). Possible diagnoses are absence or presence of SAD, current or past, generalized or specific, primary diagnosis (yes or no) | Baseline, Post-treatment (8 weeks after baseline), Follow-up (6 months after baseline) |