The Effect of Group Support Psychotherapy Delivered by Trained Lay Health Workers for Depression Treatment Among People with HIV in Uganda: Protocol of a Pragmatic, Cluster Randomized Trial

Background There is limited information on the effectiveness of task shifting of mental health services in populations with HIV. Objective This trial aims to evaluate the effectiveness of group support psychotherapy delivered by trained lay health workers to persons living with HIV (PLWH) with depression in primary care. Methods Thirty eligible primary care health centers across three districts were randomly allocated to have their lay health workers trained to deliver group support psychotherapy (intervention arm) or group HIV education and treatment as usual (control arm) to PLWH with depression. Treated PLWH will be evaluated at baseline, after the end of treatment, and at 6-month intervals thereafter for 2 years. Primary outcomes will be the difference in follow-up proportions of participants with Mini International Neuropsychiatric Interview criteria for major depression and difference in follow-up function scores of participants in the intervention and control arms 6 months after the end of treatment. Secondary outcomes will include measures of self-esteem, posttraumatic stress symptoms, social support, stigma, adherence to antiretroviral therapy, viral load, and number of disability days, asset possession indices, and cost-effectiveness data. Primary and secondary outcomes as well as subgroup analyses will be conducted at the individual level using multilevel random effects regression analyses adjusting for clustering in health centers. A process evaluation using mixed methods to assess acceptability, feasibility, fidelity, causal mediating processes, and contextual influences in the trial will be conducted. Results The trial has been approved by the Makerere College of Health Sciences School of Health Sciences Research Ethics Committee, the AIDS Support Organization, and the Uganda National Council of Science and Technology. A data and safety monitoring board has been put in place to monitor trial progress. A total of 1140 persons living with HIV have been recruited to the trial. An analysis of baseline and 6-month data is in progress. The results of this trial will not only be presented at national and international conferences but also submitted for publication in peer-reviewed journals and as a report to the funding agencies. Conclusions This cluster randomized trial will provide critical evidence to support culturally sensitive group-based psychotherapy for depression treatment in sub-Saharan Africa. Process evaluation outcomes will provide contextual information that health care and public health stakeholders can use to guide implementation decisions for their particular setting. Trial Registration Pan African Clinical Trials Registry (PACTR): 201608001738234; http://www.pactr.org/ATMWeb/ appmanager/atm/atmregistry?dar=true&tNo=PACTR201608001738234 (Archived by WebCite at http://www.webcitation.org/ 6vUAgAQlj)

all times to the PI and co-investigators to review.
The PI has constituted a data and safety monitoring board (DSMB) consisting of a Professor of Epidemiology, Professor of Bio-statistician, and an Associate Professor of HIV Psychiatry to assist in the independent review of data, in particular, data concerning accrual, drop-outs, protocol deviations and adverse events. The PI and co-investigators review adverse effects (AEs) individually in real-time and in aggregate on a monthly basis. The PI and coinvestigators review serious adverse events (SAEs), such as sudden deaths, attempted suicide in real-time and this is entered into the SAE forms and submitted to both the DSMB the research ethics committee for review. The PI ensures all protocol deviations, AEs, and SAEs are reported to the DSMB and relevant IRBs according to the applicable regulatory requirements.

Collection and Reporting of SAES and AES:
For this study, the following standard AE definitions are used: Adverse event: Any unfavorable and unintended sign or symptom associated with the participation in group support psychotherapy, regardless of whether it is considered related to the therapy. Serious Adverse Event: Any AE that results in any of the following outcomes: Death, Life-threatening, Event requiring inpatient hospitalization, Persistent or significant disability/incapacity. AEs are graded according to the following scale Mild: An experience that is transient, & requires no special treatment or intervention. The experience does not generally interfere with usual daily activities. Moderate: An experience that is alleviated with simple therapeutic treatments. The experience impacts usual daily activities. Severe: An experience that requires therapeutic intervention. The experience interrupts usual daily activities. If hospitalization (or prolongation of hospitalization) is required for treatment it becomes an SAE.
The study uses the following AE attribution scale: Not related: The AE is clearly not related to the study procedures (i.e., another cause of the event is most plausible and/or a clinically plausible temporal sequence is inconsistent with the onset of the event). Possibly related: An event that follows a reasonable temporal sequence from the initiation of study procedures, but that could readily have been produced by a number of other factors. Related: The AE is clearly related to the study procedures.
During participant recruitment, all participants received a suicide risk assessment and those with high suicide risk were not eligible to participate in the study. Group facilitators were asked to check in on participant's feelings and thoughts at the start of each group session with the aim of eliciting suicidal thoughts. Any suicidal thoughts were addressed in the group discussion. If a group member did not return for a session, a group member was tasked to check on the patient and report on his or her condition in the next meeting. SAEs and specific therapy-associated AEs are reported to the DSMB and the School of Health Sciences Research and Ethics Committee which is overseeing the study.

Management of Risks to Subjects
Expected AEs associated with this study would be suicide attempts due to lack of treatment response to the group support psychotherapy. During participant recruitment, all participants received a suicide risk assessment (Patterson et al's 1983 Evaluation of suicidal patients: the SAD PERSONS scale). Individuals with depression with high suicide risk were excluded from the study. Those with a low to moderate risk were included, their thoughts were assessed at every group meeting and care givers were asked to keep close watch on the affected individual. If suicidal thoughts were still present after 4 sessions of GSP or GHE, these individuals were referred to a mental health worker.
STOPPING RULES: Persistent suicide thoughts or attempt is the main adverse event and safety issue in the study. Previous studies that 15-20% of patients with depression commit suicide. The incidence of persistent suicide thoughts or attempt will be compared across treatment arms that is: Number of patients referred because of persistent suicide thoughts within 90-days of randomization and number of suicide attempts occurring within 90-days of randomization. If there is a significant difference between the two groups, the trial will be stopped at that point and all patents in the control group will receive group support psychotherapy. If there are no significant differences the trial continues until 6 months after the end of group support psychotherapy sessions.

Study governance structure
The Principle investigator which specifies terms of reference. The DSMB will assess the performance of overall study operations and any other relevant issues, including 1) Interim/cumulative data for evidence of study-related adverse events; 2) Interim/cumulative data for evidence of efficacy according to pre-established statistical guidelines, if appropriate; 3) Data quality, completeness, and timeliness; 4) Performance of individual centers; 5) Adequacy of compliance with goals for recruitment and retention; 6) Adherence to the protocol; and 7) Factors that might affect the study outcome (such as protocol violations, etc.)