Simon 2011.

Methods	Randomized controlled trial
Participants	The study location was 9 primary care clinics in Bellevue, Burien, Everett, Olympia, Renton, Seattle, and Spokane, Washington, USA 106 participants were randomized to the intervention group and 102 participants were randomized to the control group The inclusion criteria were age 18 or older, filled a new antidepressant prescription from a participating primary care physician; did not fill any prescription for antidepressant medication in the prior 270 days; had a diagnosis of a depressive disorder associated with the prescription; was registered to use online messaging; and received no diagnosis of bipolar disorder or psychotic disorder nor any prescription for mood stabilizer or antipsychotic medication in the prior 2 years
Interventions	Intervention: CARE MANAGEMENT Intervention group received care management intervention in addition to usual care by the treating physician. The intervention was delivered online but the structure was similar to the telephone programs tested in earlier studies. After randomization, participants received a welcome letter describing the program and it contained general advice about the antidepressants medication and self care for depression. Monitoring contacts were scheduled 2, 6, and 10 weeks later. At each monitoring contact, there was an outreach message from the nurse containing a link to an online assessment. The assessment included the PHQ depression questionnaire and questions regarding use of antidepressant medication, side effects, and reasons for medication discontinuation. Those not responding were sent up to 2 reminder messages. For each assessment completed, an algorithm generated a suggested response based on PHQ depression score, current antidepressant use, and side effects. The care manager could tailor this suggested response using information in the medical record or in messages since the last contact. The care manager communicated with the treating physician using an electronic messaging system within the electronic medical record. In consultation with the physician, the care manager might facilitate follow‐up visits, support changes in medication, or facilitate referral for specialty care (including urgent referrals in case of suicidal ideation or severe symptoms). Each of the 3 care management contacts included this cycle: outreach message from the care manager, patient completion of online assessment, structured response from the care manager, and follow‐up communication with the patient and physician as needed. The care manager's messages to patients included brief support but no formal psychotherapy. Patients were free to send additional messages or telephone the care manager if needed. The care manager was expected to make outreach telephone calls in case of suicidal ideation or other urgent clinical need. All outgoing messages were in English. The care manager in this trial was a registered nurse with added certification in psychiatry and 15 years of experience in mental health Control: USUAL CARE Controls received usual care and did not receive any additional care other than what was normally available, which included follow‐up in primary care or specialty referral for psychotherapy or medication management. Online patient‐provider messaging was available to all patients in the usual care
Outcomes	The measures of adherence were electronic medical records checks for filled antidepressant prescriptions. Prescription refill data were used to assess 2 measures of antidepressant use: the total days dispensed AND receipt of a second antidepressant (indicating medication switch or combination) The patient outcomes were the SCL depression score and a single‐item rating of satisfaction with depression care on a 7‐point scale ranging from "very dissatisfied" to "very satisfied". Consistent with previous trials, comparison of satisfaction ratings considered the proportion "very satisfied". For all potential participants, computerized membership and medical records were used to examine demographic characteristics, and overall medical morbidity
Notes	―
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Random number generated. (pg 699) "Following the survey, each participant was randomly assigned to continued usual care or to the intervention program and was immediately notified of her/his assignment. Assignments were automatically generated by the survey database using a random number generator with no blocking or stratification. Treating physicians were not notified regarding study participation or group assignment, but (as described below) physicians of intervention group patients were later contacted by the care manager."
Allocation concealment (selection bias)	Unclear risk	No clear mention of allocation concealment. (pg 699) "Following the survey, each participant was randomly assigned to continued usual care or to the intervention program and was immediately notified of her/his assignment. Assignments were automatically generated by the survey database using a random number generator with no blocking or stratification. Treating physicians were not notified regarding study participation or group assignment, but (as described below) physicians of intervention group patients were later contacted by the care manager."
Selective reporting (reporting bias)	Unclear risk	No protocol available
Other bias	Unclear risk	(pg 703) "We should emphasize that these findings only apply to patients able and willing to communicate by online messaging. Nearly 80% of Americans have home internet access, 29 and surveys find high interest in e‐mail communication with health care providers. 30 Financial incentives authorized by the 2009 Recovery Act may further increase availability of online health communication, especially if those incentives define meaningful use of electronic records to include online patient–provider communication. 31 Nevertheless, disadvantaged populations may have less access to online health services. In our sample of patients starting antidepressant treatment, those not registered for online services more often lived in disadvantaged neighborhoods. Approximately half of those registered to use online services enrolled in this trial, compared to 60% to 65% participation in similar trials of telephone care management. Non‐participation may have reflected reservations about online depression follow‐up or reservations about participation in a clinical trial. Participation may have been greater if (as in previous trials of telephone interventions) the initial invitation had come from the patient's health care team rather than a researcher and was followed by vigorous telephone outreach. The overall completion rate for care management contacts was approximately 85% compared to 95% in previous telephone programs. Despite these lower completion rates, clinical benefits (considering all patients randomized) were similar. This study was conducted in an integrated health care system with shared records of medical and mental health care as well as established collaborative relationships between primary care and mental health providers. The efficiency and clinical benefit of this program might be difficult to replicate outside of an integrated system. Follow‐up in the usual care group was more intensive than in typical primary care practice, probably reflecting both above average follow‐up rates in this setting 2,5 and a greater likelihood of research participants to return for follow‐up. Testing this intervention among patients receiving above‐average follow‐up care could create a conservative bias (i.e. reduce the likelihood of showing a benefit)".
Blinding of outcome assessment (detection bias) Adherence measure	Unclear risk	(PRIMARY) PHARMACY REFILL DATA ‐ No mention of blinding, unclear if lack of blinding would influence outcome
Blinding of outcome assessment (detection bias) Patient outcome	Low risk	(PRIMARY) SCL DEPRESSION SCORE ‐ The surveys were filled out by the participants. "Approximately five months after randomization each participant in the care management and usual care groups received a message inviting participation in a research follow‐up survey" (pg 700). Thus, the data collectors would not influence this outcome measure
Blinding of participants (performance bias) Adherence measure	Low risk	(PRIMARY) PHARMACY REFILL DATA ‐ No mention of blinding; pharmacy refill objective and should not be influenced by patient blinding
Blinding of participants (performance bias) Patient outcome	High risk	(PRIMARY) SCL DEPRESSION SCORE ‐ Participants were not blinded to the study groups; subjective measure. "Following the survey, each participant was randomly assigned to continued usual care or to the intervention program and was immediately notified of her/his assignment." (pg 699)
Blinding of personnel (performance bias) Adherence measure	Unclear risk	(PRIMARY) PHARMACY REFILL DATA ‐ No mention of blinding; unclear if lack of blinding would influence outcome
Blinding of personnel (performance bias) Patient outcome	Unclear risk	(PRIMARY) SCL DEPRESSION SCORE ‐ The surveys were filled out by the participants. "Approximately five months after randomization each participant in the care management and usual care groups received a message inviting participation in a research follow‐up survey" (pg 700). Thus, the data collectors would not influence this outcome measure
Incomplete outcome data (attrition bias) Adherence measure	Low risk	(PRIMARY) PHARMACY REFILL DATA ‐ No incomplete data were identified. Figure 1 shows that all 106 from the intervention group and 102 from the control group were included in data analysis for health utilization. This could be because this outcome was measured from the electronic medical records, thus there might not have been any missing data
Incomplete outcome data (attrition bias) Patient outcome	Unclear risk	(PRIMARY) SCL DEPRESSION SCORE ‐ Unequal dropouts across groups; no reasons provided for dropouts