Gensichen 2009.

Methods	Randomized controlled trial
Participants	The study location was 74 small primary care practices in Hesse, Germany 35 practices, 310 participants were randomized to the intervention group and 39 practices, 316 participants were randomized to the control group The inclusion criteria were diagnosis of major depression with indication for any antidepressive treatment, age 18 to 80 years, access to a private telephone, ability to give informed consent, and ability to communicate in German The exclusion criteria were confirmed pregnancy, severe alcohol or illicit drug consumption, or acute suicidal ideation assessed by the family physician
Interventions	Intervention: CASE MANAGEMENT The intervention was in accordance with Chronic Care Model, which emphasizes proactive support for the patient by the entire practice team. One healthcare assistant from each practice assigned to the intervention group in 2 workshops (an 11‐hour and a 6‐hour workshop). This interactive training included information on depression, communication skills, telephone monitoring, and behavioral activation for the patient. The healthcare assistants contacted their patients by telephone twice a week in the first month and then once a month for the following 11 months. They monitored depression symptoms and adherence to medication by using the Depression Monitoring Context List. Healthcare assistants also encouraged patients to follow self management activities, such as medication adherence and activation for pleasant or social activities. The assistants provided this information to the family physician in a structured report that stratified the urgency of the contact by a robot scheme. Family physicians in both the intervention and control groups received training on evidence‐based depression treatment guidelines Control: USUAL CARE Patients in the control group were given usual care
Outcomes	The measures of adherence were a modified Morisky patient self report scale, in which patients are scored from 0 to 3 on the basis of their answers to the following 3 questions (coded higher values indicate higher adherence): Did you ever forget to take your medicine during the last 2 weeks? During the last 2 weeks, did you sometimes stop taking your medicine when you felt better? During the last 2 weeks, did you stop taking your medicine when you felt worse? This questionnaire was given to patients at 6 and 12 months The patient outcome was depression symptoms as the primary outcome, which was assessed by using the primary care–validated PHQ‐9. Each item is scored from 0 (not at all) to 3 (nearly every day), for a total score that ranges from 0 to 27 (high scores indicate more severe depression). Response (50% improvement in PHQ‐9 score) and remission status (PHQ‐9 score=5) were secondary outcomes. Data for the following secondary outcomes were also recorded: quality of life, patient assessment of chronic illness care, and medication adherence. Health‐related quality of life was measured by using the Medical Outcomes Study Short Form 36 (SF‐36) and the EuroQol‐5D. The SF‐36 allows the calculation of scores for physical health and mental health (range, 0 to 100; higher scores indicate better status). The EuroQol‐5D is a generic instrument that measures health‐related quality of life with a visual analog scale (range, 0 to 100; higher ratings indicate higher quality of life). The number of physical comorbid conditions was determined by counting the documented diagnoses from different diagnostic groups listed in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, and International Classification of Diseases, 10th Edition, excluding all psychiatric diagnoses in the patient record. Severity of chronic physical diseases was assessed by using the Chronic Disease Score, on the basis of prescription data from the patient record. All outcomes were assessed at 6 and 12 months
Notes	―
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer randomized. (pg 370) "The data safety and monitoring board stratified the practices according to the size of the city and performed computer‐based randomization. Patient random assignment status was nested within the practice status. The data safety and monitoring board was responsible for allocation concealment by keeping the randomization results in a secure database."
Allocation concealment (selection bias)	Low risk	Allocation concealment done. (pg 370) "The data safety and monitoring board stratified the practices according to the size of the city and performed computer‐based randomization. Patient random assignment status was nested within the practice status. The data safety and monitoring board was responsible for allocation concealment by keeping the randomization results in a secure database."
Selective reporting (reporting bias)	Unclear risk	Did not report some prespecified outcomes from the protocol of Beck Depression Inventory and days out of work
Other bias	Unclear risk	Some risk of bias noted by the author ‐ (pg 369) "Patients, health care assistants, family physicians, and researchers were not blinded to group assignment, and 12‐month follow‐up of patients was incomplete". However, overall risk of bias is unclear
Blinding of outcome assessment (detection bias) Adherence measure	High risk	(PRIMARY) SELF REPORT ‐ QUESTIONNAIRE ‐ Outcome assessors were not blind. (pg 370) "Because of the practice staff training required for the behavioral intervention, patients, health care assistants, family physicians, and researchers were not blinded to assignment once the trial was started."
Blinding of outcome assessment (detection bias) Patient outcome	High risk	(PRIMARY) DEPRESSION SYMPTOMS AND QUALITY OF LIFE QUESTIONNAIRES ‐ Outcome assessors were not blinded. (pg 370) "Because of the practice staff training required for the behavioral intervention, patients, health care assistants, family physicians, and researchers were not blinded to assignment once the trial was started."
Blinding of participants (performance bias) Adherence measure	High risk	(PRIMARY) SELF REPORT ‐ QUESTIONNAIRE ‐ Patients were not blind. (pg 370) "Because of the practice staff training required for the behavioral intervention, patients, health care assistants, family physicians, and researchers were not blinded to assignment once the trial was started."
Blinding of participants (performance bias) Patient outcome	High risk	(PRIMARY) DEPRESSION SYMPTOMS AND QUALITY OF LIFE QUESTIONNAIRES ‐ Patients were not blinded. (pg 370) "Because of the practice staff training required for the behavioral intervention, patients, health care assistants, family physicians, and researchers were not blinded to assignment once the trial was started."
Blinding of personnel (performance bias) Adherence measure	High risk	(PRIMARY) SELF REPORT ‐ QUESTIONNAIRE ‐ Study staff were not blind. (pg 370) "Because of the practice staff training required for the behavioral intervention, patients, health care assistants, family physicians, and researchers were not blinded to assignment once the trial was started."
Blinding of personnel (performance bias) Patient outcome	High risk	(PRIMARY) DEPRESSION SYMPTOMS AND QUALITY OF LIFE QUESTIONNAIRES ‐ Study staff were not blinded. (pg 370) "Because of the practice staff training required for the behavioral intervention, patients, health care assistants, family physicians, and researchers were not blinded to assignment once the trial was started."
Incomplete outcome data (attrition bias) Adherence measure	Unclear risk	(PRIMARY) SELF REPORT ‐ QUESTIONNAIRE ‐ Reasons for dropouts not noted, dropouts were not balanced across ‐ but not clear how this would have affected the results
Incomplete outcome data (attrition bias) Patient outcome	Unclear risk	(PRIMARY) DEPRESSION SYMPTOMS AND QUALITY OF LIFE QUESTIONNAIRES ‐ Reasons for dropouts not noted; dropouts were not balanced across groups, but unclear how this would have affected the results