Testing Beliefs About Uncertainty in the Treatment of Generalized Anxiety Disorder

• Sponsor: Concordia University, Montreal (Other)
• Overall Status: Completed
• CT.gov ID: NCT01958788
• Collaborator: Canadian Institutes of Health Research (CIHR) (Other), Hopital du Sacre-Coeur de Montreal (Other)
• Enrollment: 7
• Location: 1
• Arm: 1
• Duration (Months): 15
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

Generalized Anxiety Disorder (GAD) is an anxiety disorder characterized by excessive and uncontrollable worry. Our research group has developed a cognitive-behavioural treatment (CBT) for GAD centered upon intolerance of uncertainty, a dispositional characteristic that arises from a set of negative beliefs about uncertainty and its consequences (Dugas & Robichaud, 2007). This CBT protocol has demonstrated good efficacy over four previous clinical trials: approximately 70% of participants fully remit from GAD following treatment and maintain these gains over extended follow-up periods. These results, while positive, do suggest that a substantial minority of individuals do not fully benefit from the existing treatment protocol. Across our randomized clinical trials, individuals who do not achieve diagnostic remission of GAD continue to endorse elevated levels of intolerance of uncertainty. This suggests that the current CBT protocol does not effectively reduce intolerance of uncertainty in some treated individuals. To address this, we have developed a modified version of the original CBT protocol that targets intolerance of uncertainty more directly. The goal of the current proposal is to determine whether this newly developed CBT protocol with fewer components can deliver comparable or superior GAD symptom reduction. A total of 7 participants with a primary diagnosis of GAD received the newly developed CBT protocol over 12 weekly sessions. Measures of GAD symptoms, psychopathology, and intolerance of uncertainty were administered at pre-, mid-, and post-treatment, as well as at 3- and 6-month follow-ups. The proposed study will provide information about the efficacy of this new CBT protocol in reducing GAD symptoms.

Condition or Disease	Intervention/Treatment	Phase
Generalized Anxiety Disorder	Behavioral: Cognitive-Behavioural Treatment	N/A

Detailed Description

Generalized anxiety disorder (GAD) is characterized by excessive and uncontrollable worry and anxiety. This common and debilitating anxiety disorder is associated with significant distress as well as substantial impairment in occupational, social, and daily functioning. As a result, effective treatment for GAD is essential. Several cognitive-behavioural treatment (CBT) protocols have been developed for GAD, including an efficacious treatment developed by our research group. This CBT protocol for GAD centres upon intolerance of uncertainty, a dispositional characteristic that arises from a set of negative beliefs about uncertainty and its consequences (Dugas & Robichaud, 2007). Previous research has shown that individuals with GAD demonstrate high intolerance of uncertainty, and that there are a number of potential pathways by which intolerance of uncertainty may lead to symptoms of GAD (see Dugas & Robichaud, 2007 for a review). Our CBT protocol targeting intolerance of uncertainty has demonstrated good efficacy across four published randomized clinical trials: approximately 70% of participants have fully remitted from GAD following treatment and have maintained these gains over extended follow-up periods. These results, while positive, do suggest that a substantial minority of individuals do not fully benefit from the existing treatment protocol. Across our randomized clinical trials, individuals who do not achieve diagnostic remission of GAD continue to endorse elevated levels of intolerance of uncertainty. This suggests that the current CBT protocol does not effectively reduce intolerance of uncertainty in some treated individuals. Additionally, the existing treatment protocol has 6 major components, utilizes a number of cognitive and behavioural techniques (including symptom monitoring, motivational interviewing, situational exposure, problem-solving training, and imaginal exposure), and requires at least 14 sessions to implement. Recent literature (e.g., Cougle et al., 2011) has suggested that there is increased need for parsimony and efficiency in CBT protocols. As a result, our research group is investigating new methods of targeting intolerance of uncertainty that demonstrate greater parsimony and efficiency.

Our previous CBT protocol for GAD targeted intolerance of uncertainty directly through situational exposure, and indirectly through motivational interviewing, problem-solving training, and imaginal exposure. In an effort to streamline and strengthen GAD treatment, the newly developed CBT protocol only targets intolerance of uncertainty directly. In this new CBT protocol, intolerance of uncertainty was targeted using behavioural experiments in which participants identified and tested out their beliefs about uncertainty. The extant literature suggests that behavioural experiments are an efficacious way to target the emotional, cognitive, and behavioural components of anxiety disorders and may be superior to habituation-based exposure paradigms (McMillan & Lee, 2010; Salkovskis et al., 2007).

The current study examined if a newly developed CBT protocol with fewer components could deliver comparable GAD symptom reduction. Seven (7) individuals with a primary diagnosis of GAD completed 12 sessions of CBT using a newly developed treatment protocol focusing exclusively on intolerance of uncertainty. The treatment consisted of 50-minute, weekly sessions targeting intolerance of uncertainty primarily via behavioural experiments. The three treatment components included: (1) psychoeducation and uncertainty awareness training; (2) testing beliefs about uncertainty (via behavioural experiments); and (3) relapse prevention. Measures of GAD symptoms, general psychopathology, and intolerance of uncertainty were administered at pre-, mid-, and post-treatment, as well as at 3- and 6-month follow-ups. Our main outcomes of interest were effect sizes (i.e., relative magnitude of change from pre-posttreatment, pretreatment to 6-month follow-up, and posttreatment to 6-month follow-up).

Study Design

• Study Type: Interventional
• Actual Enrollment: 7 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Challenging Uncertainty: Behavioural Experiments in the Treatment of Generalized Anxiety Disorder
• Study Start Date: Sep 1, 2013
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cognitive-Behavioural Treatment 12 sessions of cognitive-behavioral treatment targeting negative beliefs about uncertainty	Behavioral: Cognitive-Behavioural Treatment; 12 weekly sessions of individual cognitive-behavioural treatment (CBT) targeting intolerance of uncertainty.

Outcome Measures

Primary Outcome Measures

1. Clinician's Severity Rating (CSR) Scale of Anxiety Disorders Interview Schedule for DSM-IV (ADIS-IV) [Pretreatment to posttreatment (12 weeks) and 6-month Follow-Up]

   The CSR is a severity rating scale ranging from 0-8. Scores of 4 or greater represent clinically significant symptoms, whereas scores lower than 4 indicate subclinical symptoms. Lower scores represent improved outcome. This measure was used to evaluate change from baseline in the severity of GAD symptoms as assessed by the ADIS-IV, a semi-structured clinical interview for Axis I disorders.

Secondary Outcome Measures

1. Worry and Anxiety Questionnaire (WAQ) [Pretreatment to posttreatment (12 weeks) and 6-month Follow-Up]

   The WAQ is a questionnaire assessing self-reported symptoms of GAD. Scores range from 0 to 56, with higher scores indicating greater severity of self-rated GAD symptoms. The measure was used to assess change from baseline in self-reported GAD symptoms (WAQ).

2. Intolerance of Uncertainty Scale (IUS) [Pretreatment to posttreatment (12 weeks) and 6-month Follow-Up]

   The IUS is a self-report questionnaire assessing intolerance of uncertainty, or the tendency to view uncertainty and its consequences as negative. Scores range from 27 to 135, with higher scores representing greater intolerance of uncertainty. The IUS was used to assess change from baseline in self-reported intolerance of uncertainty.

3. Penn State Worry Questionnaire (PSWQ) [Pretreatment to posttreatment (12 weeks) and 6-month Follow-Up]

   The PSWQ is a self-report questionnaire assessing excessive and uncontrollable worry. Scores range from 16 to 80, with greater scores indicating greater worry. The PSWQ was used to evaluate change from baseline in self-reported worry.

4. GAD Safety Behaviours Questionnaire (GAD-SBQ) [Pretreatment to posttreatment (12 weeks) and 6-month Follow-Up]

   The GAD-SBQ is a self-report questionnaire assessing the tendency to use safety behaviours to cope with anxiety, such as reassurance-seeking and overpreparation. Scores range from 18 to 90, with greater scores indicating greater use of safety behaviours. The GA-SBQ was used to evaluate change from baseline in self-reported safety behaviours.

5. Beck Anxiety Inventory (BAI) [Pretreatment to posttreatment (12 weeks) and 6-month Follow-Up]

   The BAI is a self-report questionnaire assessing affective, cognitive, and somatic anxiety over the preceding week. Scores range from 0 to 63, with greater scores representing greater self-reported anxiety. The BAI was used to evaluate change from baseline in self-reported anxiety.

6. Beck Depression Inventory, 2nd Edition (BDI-II) [Pretreatment to posttreatment (12 weeks) and 6-month Follow-Up]

   The BDI-II is a self-report questionnaire assessing a variety of depressive symptoms, including low mood, anhedonia, and worthlessness. Scores range from 0 to 63, with greater scores indicating greater depressive symptoms. The BDI-II was used to evaluate change from baseline in self-reported depressive symptoms.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Primary diagnosis of GAD (as assessed by semi-structured clinical interviews)

• Score of 58 or greater on the (Intolerance of Uncertainty Scale)

• Willingness to keep medication status stable while participating in the study

Exclusion Criteria:

• Change in medication type or dose in 12 weeks before study entry

• Use of herbal products known to have central nervous system effects in the 2 weeks before study entry

• Evidence of suicidal intent

• Evidence of current substance abuse

• Evidence of current or past schizophrenia, bipolar disorder or organic mental disorder

• Current participation in other trials

• Concurrent psychotherapy during treatment phase of trial

• Evidence of anxiety symptoms due to a general medical condition

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Concordia University	Montreal	Quebec	Canada	H4B 1R6

Sponsors and Collaborators

• Concordia University, Montreal
• Canadian Institutes of Health Research (CIHR)
• Hopital du Sacre-Coeur de Montreal

Investigators

• Principal Investigator: Elizabeth A Hebert, M.A., Concordia University, Montreal

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Elizabeth A. Hebert, M.A., Ph.D. Candidate, Concordia University, Montreal
• ClinicalTrials.gov Identifier: NCT01958788
• Other Study ID Numbers: MOP-69066-620
• First Posted: Oct 9, 2013
• Last Update Posted: Feb 23, 2016
• Last Verified: Jan 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Elizabeth A. Hebert, M.A., Ph.D. Candidate, Concordia University, Montreal: Cognitive-behavioral treatment; Generalized anxiety disorder; Worry; Behavioral experiments; Safety behaviors; Anxiety
• Additional relevant MeSH terms: Disease; Anxiety Disorders

Study Results

Participant Flow

Recruitment Details	The study was approved by Human Research Ethics Committees of Concordia University and the Hôpital du Sacré-Coeur de Montréal. Participants self-referred to the Hôpital du Sacré-Coeur de Montréal anxiety clinic via advertisements placed in a local newspaper. Recruitment occurred between April 2013 to March 2014.

Arm/Group Title	Cognitive-Behavioural Treatment
Arm/Group Description	12 weekly sessions of individual cognitive-behavioural treatment (CBT) targeting intolerance of uncertainty via behavioural experiments.
Period Title: Overall Study
STARTED	7
COMPLETED	7
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Cognitive-Behavioural Treatment
Arm/Group Description	12 weekly sessions of individual cognitive-behavioural treatment (CBT) targeting intolerance of uncertainty via behavioural experiments
Overall Participants	7
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	7 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	5 71.4%
Male	2 28.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	7 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
Canada	7 100%

Outcome Measures

1. Primary Outcome

Title	Clinician's Severity Rating (CSR) Scale of Anxiety Disorders Interview Schedule for DSM-IV (ADIS-IV)
Description	The CSR is a severity rating scale ranging from 0-8. Scores of 4 or greater represent clinically significant symptoms, whereas scores lower than 4 indicate subclinical symptoms. Lower scores represent improved outcome. This measure was used to evaluate change from baseline in the severity of GAD symptoms as assessed by the ADIS-IV, a semi-structured clinical interview for Axis I disorders.
Time Frame	Pretreatment to posttreatment (12 weeks) and 6-month Follow-Up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cognitive-Behavioural Treatment
Arm/Group Description	12 weekly sessions of individual cognitive-behavioural treatment (CBT) targeting intolerance of uncertainty via behavioural experiments.
Measure Participants	7
Pretreatment ADIS-IV	5.5 (0.82)
Posttreatment ADIS-IV	3.14 (1.03)
6-month follow-up ADIS-IV	2.43 (1.90)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cognitive-Behavioural Treatment
	Comments	Pre-posttreatment effect size estimation using Cohen's d: a calculation of the relative magnitude of the effect from pretreatment to posttreatment
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Cohen's d effect size
	Estimated Value	2.06
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cognitive-Behavioural Treatment
	Comments	Pretreatment to 6-month follow-up effect size estimation using Cohen's d: a calculation of the relative magnitude of the effect from pretreatment to 6-month follow-up
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Cohen's d effect size
	Estimated Value	1.34
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Cognitive-Behavioural Treatment
	Comments	Posttreatment to 6-month follow-up effect size estimation using Cohen's d: a calculation of the relative magnitude of the effect from posttreatment to 6-month follow-up
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Cohen's d effect size
	Estimated Value	0.37
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Worry and Anxiety Questionnaire (WAQ)
Description	The WAQ is a questionnaire assessing self-reported symptoms of GAD. Scores range from 0 to 56, with higher scores indicating greater severity of self-rated GAD symptoms. The measure was used to assess change from baseline in self-reported GAD symptoms (WAQ).
Time Frame	Pretreatment to posttreatment (12 weeks) and 6-month Follow-Up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cognitive-Behavioural Treatment
Arm/Group Description	12 weekly sessions of individual cognitive-behavioural treatment (CBT) targeting intolerance of uncertainty via behavioural experiments.
Measure Participants	7
Pretreatment WAQ	38.36 (5.25)
Posttreatment WAQ	24.36 (9.06)
6-month follow-up WAQ	25.43 (6.42)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cognitive-Behavioural Treatment
	Comments	Pre-posttreatment effect size estimation using Cohen's d: a calculation of the relative magnitude of the effect from pretreatment to posttreatment
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Cohen's d effect size
	Estimated Value	1.32
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cognitive-Behavioural Treatment
	Comments	Pretreatment to 6-month follow-up effect size estimation using Cohen's d: a calculation of the relative magnitude of the effect from pretreatment to 6-month follow-up
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Cohen's d effect size
	Estimated Value	1.29
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Cognitive-Behavioural Treatment
	Comments	Posttreatment to 6-month follow-up effect size estimation using Cohen's d: a calculation of the relative magnitude of the effect from posttreatment to 6-month follow-up
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Cohen's d effect size
	Estimated Value	-0.15
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Intolerance of Uncertainty Scale (IUS)
Description	The IUS is a self-report questionnaire assessing intolerance of uncertainty, or the tendency to view uncertainty and its consequences as negative. Scores range from 27 to 135, with higher scores representing greater intolerance of uncertainty. The IUS was used to assess change from baseline in self-reported intolerance of uncertainty.
Time Frame	Pretreatment to posttreatment (12 weeks) and 6-month Follow-Up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cognitive-Behavioural Treatment
Arm/Group Description	12 weekly sessions of individual cognitive-behavioural treatment (CBT) targeting intolerance of uncertainty via behavioural experiments.
Measure Participants	7
Pretreatment IUS	85.71 (14.71)
Posttreatment IUS	55.00 (15.55)
6-month follow-up IUS	54.29 (12.30)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cognitive-Behavioural Treatment
	Comments	Pre-posttreatment follow-up effect size estimation using Cohen's d: a calculation of the relative magnitude of the effect from pretreatment to posttreatment follow-up
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Cohen's d effect size
	Estimated Value	1.72
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cognitive-Behavioural Treatment
	Comments	Pretreatment to 6-month follow-up effect size estimation using Cohen's d: a calculation of the relative magnitude of the effect from pretreatment to 6-month follow-up
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Cohen's d effect size
	Estimated Value	1.66
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Cognitive-Behavioural Treatment
	Comments	Posttreatment to 6-month follow-up effect size estimation using Cohen's d: a calculation of the relative magnitude of the effect from posttreatment to 6-month follow-up
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Cohen's d effect size
	Estimated Value	0.07
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Penn State Worry Questionnaire (PSWQ)
Description	The PSWQ is a self-report questionnaire assessing excessive and uncontrollable worry. Scores range from 16 to 80, with greater scores indicating greater worry. The PSWQ was used to evaluate change from baseline in self-reported worry.
Time Frame	Pretreatment to posttreatment (12 weeks) and 6-month Follow-Up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cognitive-Behavioural Treatment
Arm/Group Description	12 weekly sessions of individual cognitive-behavioural treatment (CBT) targeting intolerance of uncertainty via behavioural experiments.
Measure Participants	7
Pretreatment PSWQ	61.57 (6.00)
Posttreatment PSWQ	50.00 (8.25)
6-month follow-up PSWQ	51.14 (6.15)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cognitive-Behavioural Treatment
	Comments	Pre-posttreatment effect size estimation using Cohen's d: a calculation of the relative magnitude of the effect from pretreatment to posttreatment
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Cohen's d effect size
	Estimated Value	1.13
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cognitive-Behavioural Treatment
	Comments	Pretreatment to 6-month follow-up effect size estimation using Cohen's d: a calculation of the relative magnitude of the effect from pretreatment to 6-month follow-up
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Cohen's d effect size
	Estimated Value	1.06
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Cognitive-Behavioural Treatment
	Comments	Posttreatment to 6-month follow-up effect size estimation using Cohen's d: a calculation of the relative magnitude of the effect from posttreatment to 6-month follow-up
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Cohen's d effect size
	Estimated Value	-0.18
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	GAD Safety Behaviours Questionnaire (GAD-SBQ)
Description	The GAD-SBQ is a self-report questionnaire assessing the tendency to use safety behaviours to cope with anxiety, such as reassurance-seeking and overpreparation. Scores range from 18 to 90, with greater scores indicating greater use of safety behaviours. The GA-SBQ was used to evaluate change from baseline in self-reported safety behaviours.
Time Frame	Pretreatment to posttreatment (12 weeks) and 6-month Follow-Up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cognitive-Behavioural Treatment
Arm/Group Description	12 weekly sessions of individual cognitive-behavioural treatment (CBT) targeting intolerance of uncertainty via behavioural experiments.
Measure Participants	7
Pretreatment GAD-SBQ	47.00 (9.95)
Posttreatment GAD-SBQ	32.71 (5.53)
6-month follow-up GAD-SBQ	36.14 (5.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cognitive-Behavioural Treatment
	Comments	Pre-posttreatment effect size estimation using Cohen's d: a calculation of the relative magnitude of the effect from pretreatment to posttreatment
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Cohen's d effect size
	Estimated Value	1.41
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cognitive-Behavioural Treatment
	Comments	Pretreatment to 6-month follow-up effect size estimation using Cohen's d: a calculation of the relative magnitude of the effect from pretreatment to 6-month follow-up
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Cohen's d effect size
	Estimated Value	1.65
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Cognitive-Behavioural Treatment
	Comments	Posttreatment to 6-month follow-up effect size estimation using Cohen's d: a calculation of the relative magnitude of the effect from posttreatment to 6-month follow-up
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Cohen's d effect size
	Estimated Value	-0.70
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Beck Anxiety Inventory (BAI)
Description	The BAI is a self-report questionnaire assessing affective, cognitive, and somatic anxiety over the preceding week. Scores range from 0 to 63, with greater scores representing greater self-reported anxiety. The BAI was used to evaluate change from baseline in self-reported anxiety.
Time Frame	Pretreatment to posttreatment (12 weeks) and 6-month Follow-Up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cognitive-Behavioural Treatment
Arm/Group Description	12 weekly sessions of individual cognitive-behavioural treatment (CBT) targeting intolerance of uncertainty via behavioural experiments.
Measure Participants	7
Pretreatment BAI	23.71 (10.47)
Posttreatment BAI	9.86 (10.56)
6-month follow-up BAI	12.57 (12.12)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cognitive-Behavioural Treatment
	Comments	Pre-posttreatment effect size estimation using Cohen's d: a calculation of the relative magnitude of the effect from pretreatment to posttreatment
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Cohen's d effect size
	Estimated Value	1.64
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cognitive-Behavioural Treatment
	Comments	Pretreatment to 6-month follow-up effect size estimation using Cohen's d: a calculation of the relative magnitude of the effect from pretreatment to 6-month follow-up
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Cohen's d effect size
	Estimated Value	1.47
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Cognitive-Behavioural Treatment
	Comments	Posttreatment to 6-month follow-up effect size estimation using Cohen's d: a calculation of the relative magnitude of the effect from posttreatment to 6-month follow-up
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Cohen's d effect size
	Estimated Value	-0.56
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Beck Depression Inventory, 2nd Edition (BDI-II)
Description	The BDI-II is a self-report questionnaire assessing a variety of depressive symptoms, including low mood, anhedonia, and worthlessness. Scores range from 0 to 63, with greater scores indicating greater depressive symptoms. The BDI-II was used to evaluate change from baseline in self-reported depressive symptoms.
Time Frame	Pretreatment to posttreatment (12 weeks) and 6-month Follow-Up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cognitive-Behavioural Treatment
Arm/Group Description	12 weekly sessions of individual cognitive-behavioural treatment (CBT) targeting intolerance of uncertainty via behavioural experiments.
Measure Participants	7
Pretreatment BDI-II	14.71 (4.39)
Posttreatment BDI-II	4.00 (5.69)
6-month follow-up BDI-II	5.57 (5.16)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cognitive-Behavioural Treatment
	Comments	Pre-posttreatment effect size estimation using Cohen's d: a calculation of the relative magnitude of the effect from pretreatment to posttreatment
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Cohen's d effect size
	Estimated Value	2.08
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cognitive-Behavioural Treatment
	Comments	Pretreatment to 6-month follow-up effect size estimation using Cohen's d: a calculation of the relative magnitude of the effect from pretreatment to 6-month follow-up
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Cohen's d effect size
	Estimated Value	2.15
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Cognitive-Behavioural Treatment
	Comments	Posttreatment to 6-month follow-up effect size estimation using Cohen's d: a calculation of the relative magnitude of the effect from posttreatment to 6-month follow-up
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Cohen's d effect size
	Estimated Value	-0.55
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	9 months per participant (12 weeks treatment, 6-month follow-up)
Adverse Event Reporting Description	Participant's mental health status was assessed at pretreatment, midtreatment, posttreatment, 3-month follow-up, and 6-month follow-up.
Arm/Group Title	Cognitive-Behavioural Treatment
Arm/Group Description	12 weekly sessions of individual cognitive-behavioural treatment (CBT) targeting intolerance of uncertainty via behavioural experiments
All Cause Mortality
	Cognitive-Behavioural Treatment
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Cognitive-Behavioural Treatment
	Affected / at Risk (%)	# Events
Total	0/7 (0%)
Other (Not Including Serious) Adverse Events
	Cognitive-Behavioural Treatment
	Affected / at Risk (%)	# Events
Total	0/7 (0%)

Limitations/Caveats

Small sample size due to clinical case replication series design. This reduced statistical power and types of statistical analyses that could be conducted. Participants were homogeneous in ethnicity and language, which may limit generalizability.

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.