Reduction of Anxiety in People With Disabilities Through Dual Treatment: Digital CBT & NBHWC Coaching - A Randomized Clinical Trial

The Hamilton Anxiety Rating Scale (HAM-A) is a structured interview using 14 items, each rated from 0 ("not present") to 4 ("severe"). Scores range from 0 to 56. Analyses will use a mixed model for repeated measures (MMRM) in the Intent-to-Treat (ITT) population. The MMRM will model change from Baseline and Weeks 4 and 8 as repeated post-baseline measurements. The model will include fixed effects for treatment group, visit, treatment-by-visit interaction, study site, and Baseline HAM-A total score as a covariate. Within-participant correlation across repeated measurements will be modeled using an appropriate covariance structure. The primary treatment comparison will be the difference between treatment groups in least squares mean change from Baseline to Week 8. Statistical significance for the primary endpoint will be assessed based on the Week 8 treatment contrast from the MMRM. The estimated treatment difference, 95% confidence interval, and two-sided p-value will be reported.

The Hamilton Anxiety Rating Scale (HAM-A) is a structured interview assessing anxiety symptoms using 14 items, each rated from 0 ("not present") to 4 ("severe"). Scores range from 0 to 56. Change from Baseline to Week 12 in HAM-A total score will be analyzed using an MMRM analogous to that used for the primary endpoint. The model will include fixed effects for treatment group, visit, treatment-by-visit interaction, and study site, with Baseline Assessments HAM-A total score included as a covariate. Post-baseline assessments at Weeks 4, 8, and 12 will be included in the model. The treatment comparison of interest will be the between-group difference in least squares mean change from Baseline Assessments at Week 12. The estimated treatment difference, 95% confidence interval, and two-sided p-value will be reported.

The Clinical Global Impression for Improvement (CGI-I) is a evaluator-rated scale to assess how much a patient's illness has improved or worsened relative to baseline. It assesses overall clinical change based on a single item rated from 1 ("very much improved") to 7 ("very much worse"). CGI-I at Week 8 will be analyzed using an MMRM including fixed effects for treatment group, visit, treatment-by-visit interaction, and study site. Because CGI-I is not measured at baseline, no baseline covariate will be included in the model. Post-baseline assessments at Weeks 4 and 8 will be included. Although CGI-I is an ordinal endpoint, it will be analyzed as a continuous variable for this study. The treatment comparison of interest will be the between-group difference in least squares mean score at Week 8. The estimated treatment difference, 95% confidence interval, and two-sided p-value will be reported.

The Clinical Global Impression for Improvement (CGI-I) is a evaluator-rated scale to assess how much a patient's illness has improved or worsened relative to baseline. It assesses overall clinical change based on a single item rated from 1 ("very much improved") to 7 ("very much worse"). CGI-I at Week 12 will be analyzed using an MMRM including fixed effects for treatment group, visit, treatment-by-visit interaction, and study site. Because CGI-I is not measured at baseline, no baseline covariate will be included in the model. Post-baseline assessments at Weeks 4, 8 and 12 will be included. Although CGI-I is an ordinal endpoint, it will be analyzed as a continuous variable for this study. The treatment comparison of interest will be the between-group difference in least squares mean score at Week 8. The estimated treatment difference, 95% confidence interval, and two-sided p-value will be reported.

The Hamilton Anxiety Rating Scale (HAM-A) is a structured interview assessing anxiety symptoms using 14 items, each rated from 0 ("not present") to 4 ("severe"). Scores range from 0 to 56. HAM-A response at Week 8, defined as a reduction of at least 4 points from Baseline Assessments in HAM-A total score, will be analyzed using Week 8 data only. Participants without a Week 8 assessment will be classified as non-responders. Response rates will be summarized by treatment group and compared using Pearson's chi-square test. The between-group difference in response rate and its 95% confidence interval will also be provided.

The Hamilton Depression Rating Scale (HAM-D) is a structured interview assessing depression based on 17 items; 9 items range from 0 ("not present") to 4 ("severe") and 8 items range from 0 ("absent") to 2 ("severe"). Change from Baseline in HAM-D total score will be analyzed using an MMRM with the same general structure as that used for the primary endpoint. The model will include fixed effects for treatment group, visit, treatment-by-visit interaction, and study site, with Baseline Assessments HAM-D total score included as a covariate. Post-baseline assessments at Weeks 4 and 8 will be included. Estimated between-group differences in least squares mean change from baseline, with corresponding 95% confidence intervals and two-sided p-values, will be reported.

The Generalized Anxiety Disorder-7 (GAD-7) is a 7-item self-report measure of anxiety. Each item is rated on a 4-point Likert scale ranging from 0 ("not at all") to 3 ("nearly every day"), yielding total scores ranging from 0 to 21. Change from Pre-Screening in GAD-7 total score will be analyzed using an MMRM with the same general structure as that used for the primary endpoint. The model will include fixed effects for treatment group, visit, treatment-by-visit interaction, and study site, with Pre-Screening GAD-7 total score included as a covariate. Post-baseline assessments at Weeks 4 and 8 will be included. Estimated between-group differences in least squares mean change from baseline, with corresponding 95% confidence intervals and two-sided p-values, will be reported.