Methods
comorbidity, posttraumatic stress disorder, anxiety, cognitive impairment, bipolar disorder, psychotic disorders, depression, obsessive–compulsive disorder
DISORDER, RECRUITMENT, REGRESSIONS, ADVERSE EFFECTS, SECONDARY, REMISSION, BLIND, PCP, REGRESSION
The methods of the study have been publishedAll participants were recruited in primary care clinics in urban areas, suburban locations, and rural areas across Ontario (Canada) with all study activities conducted remotely by phone from a central office in Toronto. All participants signed an informed consent form approved by the Research Ethics Board at the Centre for Addiction and Mental Health, Toronto, Ontario. The trial was registered on ClinicalTrials.gov (Identifier: NCT02345122) on January 26, 2015.The main inclusion criteria were age 18 years and older; receiving care at 1 of the participating clinics; self-referring or being referred by a PCP to the study because of depression, anxiety, or at-risk drinking; and ability to converse in English by telephone. The main exclusion criteria were lifetime diagnoses primarily reported by participants, including psychotic disorders, bipolar disorder, obsessive–compulsive disorder, or posttraumatic stress disorder; current substance use disorder other than alcohol use disorder; cognitive impairment with a score of 16 or above on the Blessed Orientation-Memory Concentration test (BOMC)Research Associates (RAs) administered by telephone to all participants a comprehensive assessment at baseline, 4, 8, and 12 months later using the Behavioral Health Laboratory (BHL) software.Participants assessed at baseline to have depression (defined as a PHQ-9 score ≥10), anxiety (defined as a GAD-7 score ≥10), or at-risk drinking (exceeding the Canadian Guidelines for safe drinking, which are based on the number of drinks or bingesParticipants randomized to tCC were assigned to a trained bachelor-level MHT (i.e., a “lay provider”During the initial weekly, then bi-monthly, and finally monthly phone calls, MHTs also helped CC participants to identify resources (e.g., apps and community-based services) and provided monitoring including the administration of the PHQ-9, GAD-7, or an inquiry about the number of drinks, as relevant. MHTs also monitored treatment adherence and adverse effects and provided continuing psychoeducation related to the participant's conditions and their treatment.The RAs assessed the participants randomized to eUC by phone with the same BHL software at the same time points. The results of these symptom assessments were e-faxed to PCPs, but no recommendations were provided. PCPs managed these participants as they saw fit. To maintain the blind, eUC participants were also contacted by an MHT after the completion of each assessment, and they were briefly informed about the results of their assessment and told that they would be contacted again in 4 months.The primary outcome measure was the change in PHQ-9 from baseline to 12 months in those presenting with depression (i.e., those with a PHQ-9 ≥10 at baseline). Because of the transdiagnostic recruitment strategy, preplanned secondary outcome measures included change in GAD-7 from baseline to 12 months in those presenting with anxiety (i.e., those with a GAD-7 score ≥10 at baseline); change in the number of weekly drinks from baseline to 12 months in those presenting with at-risk drinking (i.e., those exceeding the Canadian Guidelines for safe drinking at baseline); and the documentation of initiation and adequacy of antidepressant treatment using the Antidepressant Treatment History FormAdditional preplanned outcomes included change in health-related quality of life and functioning in the whole sample as measured by the VR-12; rates of response or remission for depression in the depression group (defined as PHQ-9 score <10 and <5, respectively) or for anxiety in the anxiety group (defined as GAD-7 score <10 and <5, respectively), and decrease in the number of weekly drinks to meeting the guidelines for safe drinking.The main analyses compared changes from baseline to 12 months between the 2 treatment groups with linear contrasts of estimated means for the 3 main outcome measures (i.e., PHQ-9, GAD-7, and number of drinks). Accounting for the clustering within subjects and sites, mixed models assessed changes in depression or anxiety scores and changes in health-related quality of life and functioning. Because of skewed distribution, a generalized estimating equation (GEE) assessed changes in the number of drinks. Both mixed models and GEE were specified with a time-by-group interaction, where time was considered categorical. Given the high rates of comorbidity, the 3 models adjusted for baseline PHQ-9 scores, GAD-7 scores, and number of drinks. A similar approach was used for the analysis of changes in VR-12 scores. Logistic regressions compared rates of remission, response, or safe drinking at 12 months in the 2 treatment groups. We used multiple imputation to impute missing values for response and remission at 12 months. Remission and response were the dependent variable of our logistic regression to look at treatment-group differences for these outcomes. A logistic regression assessed whether the proportion of participants reporting receiving treatment differed in the 2 treatment groups. Rates of initiation and adequacy of antidepressant treatment documented in health records were compared with Fisher tests. The analyses of response and remission rates were conducted using Mplus, and all other analyses using SAS System 9.4.We had planned to recruit a sample of 1,000 participants that should have provided enough power to detect any clinically meaningful effect of the intervention. Since we were able to randomize only half of this planned sample and a post-hoc power calculation is not statistically sound, we estimated the detectable effect size, given the size of our sample and the characteristics of our model. Considering 80% power and significance level of 0.05, the detectable effect size was a difference between treatment groups in changes from baseline to 12 months of 1.85 for the PHQ-9, 1.90 for the GAD-7, and 5.7 drinks per week. This calculation was conducted using our data and a series of 1,000 Monte Carlo simulations for each outcome with the R package SIMR.