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Economic evaluation of the Target-D platform to match depression management to severity prognosis in primary care: A within-trial cost-utility analysis

Background Target-D, a new person-centred e-health platform matching depression care to symptom severity prognosis (minimal/mild, moderate or severe) has demonstrated greater improvement in depressive symptoms than usual care plus attention control. The aim of this study was to evaluate the cost-effectiveness of Target-D compared to usual care from a health sector and partial societal perspective across 3-month and 12-month follow-up. Methods and findings A cost-utility analysis was conducted alongside the Target-D randomised controlled trial; which involved 1,868 participants attending 14 general practices in metropolitan Melbourne, Australia. Data on costs were collected using a resource use questionnaire administered concurrently with all other outcome measures at baseline, 3-month and 12-month follow-up. Intervention costs were assessed using financial records compiled during the trial. All costs were expressed in Australian dollars (A$) for the 2018–19 financial year. QALY outcomes were derived using the Assessment of Quality of Life-8D (AQoL-8D) questionnaire. On a per person basis, the Target-D intervention cost between $14 (minimal/mild prognostic group) and $676 (severe group). Health sector and societal costs were not significantly different between trial arms at both 3 and 12 months. Relative to a A$50,000 per QALY willingness-to-pay threshold, the probability of Target-D being cost-effective under a health sector perspective was 81% at 3 months and 96% at 12 months. From a societal perspective, the probability of cost-effectiveness was 30% at 3 months and 80% at 12 months. Conclusions Target-D is likely to represent good value for money for health care decision makers. Further evaluation of QALY outcomes should accompany any routine roll-out to assess comparability of results to those observed in the trial. This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12616000537459).


Supplementary Text S1. Detailed description of Target-D interventions
All participants completed a brief eligibility screening survey on an iPad in their GP waiting room and were not required to disclose any information to the research assistant other than their willingness to complete this survey. The eligibility survey was integrated with the Target-D platform, consent form, randomisation schedule and baseline and follow-up measures in a purposebuilt website, accessible on any internet-enabled device. As part of the consent process, eligible patients were asked to enter an email address; if they were unable or unwilling to complete the baseline assessment and CPT using the iPad provided in the waiting room, they were emailed a link to do so on their own device at a time that was convenient to them. Research assistants followed up with non-responders via phone, text and/or email.

Intervention arm
After completing the clinical prediction tool, participants randomly allocated to the intervention arm received:  feedback on their responses;  an opportunity to set mental health priorities and reflect on the importance of addressing these priorities and their confidence in doing so; and  a management option matched to their predicted depressive symptom severity.
Together, these elements comprise the Target-D platform. The presentation of the platform was informed by the principles of motivational interviewing, 1 a psychologically-driven goal modelling approach, 2 and developed with input from end-users. 3 The CPT comprises the PHQ-9 plus eight additional items assessing sex, anxiety, general health, living situation and financial security. These additional items, as well as providing some predictive power over and above that provided by the PHQ-9, are included in recognition of the broader determinants of poor mental health. By taking a holistic approach to mental health rather than considering depressive symptoms alone, the intervention aims allow people to set priorities and engage with care options that are relevant to their needs. Recommended management options were displayed on screen immediately after completing the CPT and re-iterated in follow-up contact from the Target-D team (as described below). All participants also received an automated email encouraging them to speak with their GP regarding any concerns they may have about their mental health and providing contact details for community-based services (e.g., crisis support lines). Selected management options had RCT evidence of effectiveness for the appropriate level of depressive symptom severity, as described below; management and planned follow-up procedures for each prognostic group are described below.

Minimal/mild prognostic group
Participants in this group were recommended to use the myCompass program, an online, CBTbased, self-help resource comprising information, treatment modules, homework activities and mood tracking functions. 4 At the time of this study, information and mood tracking functions could be accessed on any internet-enabled device, although the treatment modules were computer-based.
Target-D participants were free to use myCompass as much or as little as they liked. They received an initial welcome email from the Target-D team providing the link to myCompass with a brief outline of what to expect on first log in and a follow-up telephone call from a research assistant to discuss their treatment recommendation and troubleshoot if needed. Up to four attempts at this call were made. Finally, participants in this group were sent an email one week after completing the CPT (or after all call attempts were exhausted) reminding them of the benefits of myCompass and encouraging them to register for the program if they hadn't already. Adherence was defined as completion of at least one module, as indicated by website analytics provided by the Black Dog Institute (who manage the myCompass program).

Moderate prognostic group
Participants in this group received a recommendation to use the This Way Up iCBT program (specifically, the Worry and Sadness course); a guided, linear program comprising six online lessons, homework activities and symptom monitoring. 5 Participants were free to complete as many or as few lessons as they wished and to access the course when, where and using the device that was convenient to them. They received an initial email from the study team with information about the program and advising that they would receive a separate email from This Way Up with a unique link providing them with free access to the course for 90 days.
Research assistants then contacted participants weekly via phone or email either until they completed Lesson Two or until four weeks after they were emailed their unique link, whichever came first. One phone call attempt was made at each scheduled contact, with a personalised email sent to non-responders (tailored to their progress through the program). When participants reported a worsening of depressive symptoms within This Way Up (≥ 5 points on the PHQ-9 from their previous assessment), an automated email was generated to both the Target-D team and the participant encouraging the participant to access further support. Adherence was defined as completion of all 6 lessons in the Worry and Sadness course, as indicated by website analytics provided by the This Way Up team at the University of New South Wales.

Severe prognostic group
Participants in this group were offered collaborative care, 6-9 described on the Target-D platform as an opportunity to work together with a specially trained nurse and their GP to identify options to improve their emotional health and wellbeing. Participants were offered up to eight structured appointments with the nurse over 12 weeks. The intervention aimed to improve outcomes by supporting participants' engagement in and ownership over their own health care by applying the principles of motivational interviewing. 1 A research assistant contacted participants allocated to this group via phone to discuss their treatment recommendation and schedule their first appointment with a Target-D nurse. Four call attempts were made, after which the participant was emailed a brief introduction to the collaborative care intervention and invited to get in touch with the study team to schedule an appointment. Participants were reminded of subsequent appointments via SMS from their Target-D nurse and could contact their nurse directly via SMS or phone to reschedule as required.
The collaborative care intervention was delivered by five female registered nurses with between 13 and 21 years of experience in a range of fields including primary, emergency and intensive care nursing. All nurses completed a 2-day training course on the background to Target-D and trial protocol (day 1; delivered by project manager) and an introduction to motivational interviewing techniques (day 2; delivered by registered psychologist). Nurses were assisted to put these techniques into practice through detailed procedure manuals and structured appointment templates which stepped through the process of developing a plan to improve participants' mental health. The template for appointment 1 was pre-populated with the priority areas the participant identified in the Target-D platform. This provided structure to their first interaction with the Target-D nurse and established a focus for the collaborative care intervention across the eight appointments, as follows: • Appointment 1: reflect on current situation, set goals relevant to each priority area and identify actions they could take to meet those goals.
• Appointments 2 -7: review progress, identify barriers to taking action and how these may be overcome • Appointment 8: review progress and identify additional supports required or actions to take after Target-D.
In order to facilitate rapport building, participants were encouraged to attend appointments in person at their general practice (particularly the first appointment) but this was not a requirement and they were free to meet with their nurse either over the phone or in person, according to individual preference. After each appointment, the Target-D nurse provided the participant with a copy of their plan (via email or in hard copy) to remind and support them with taking their intended actions that week. The nurse also provided a copy of the plan to the participant's GP and other professionals involved in the participant's mental health care. In supporting participants to develop their plan, Target-D nurses spent time outside the eight structured appointments to research appropriate services both within and external to the health system, discuss management options with GPs and other professionals and draft referrals for GPs. Target-D nurses were also able to contact both the project manager and registered psychologist for support and guidance as required; no additional strategies were employed to encourage fidelity to intervention delivery.
Adherence was defined as completion of eight appointments, as indicated by appointment logs completed by the nurses delivering the intervention. Nurse fidelity to the collaborative care model was assessed through review of written plans and appointment logs and of audio recordings conducted for a subset of appointments. This data are currently being analysed and will be reported separately.

Control arm
After completing the CPT, participants randomly allocated to the control arm did not receive symptom feedback, priority setting, or prognosis-matched treatment recommendations. Instead, they received usual care plus Target-D attention control (UC+) in the form of a telephone call from a trained research assistant to reiterate the importance of involvement in the trial, address questions and concerns as required and administer a brief structured interview about research participation.
Up to four attempts at contacting participants via phone were made, after which an email was sent encouraging the participant to contact the study team. All participants in this arm also received the automated email sent to the intervention arm providing information about community-based services and encouragement to speak to their GP about mental health concerns. They were free to continue accessing health services as usual throughout the duration of the trial.

$676
Base case. Applied to participants in the severe prognostic group of the intervention arm. † The true cost of the ThisWayUp 'Worry and Sadness' iCBT course is unknown. Patients are charged a nominal fee of A$56 which does not reflect the opportunity cost of the intervention. This fee is charged to incentivise program completion rather than to cover program costs. True cost will be higher.

Supplementary Text S4. Methods to cost health service use
Diagnostic tests and the majority of health professional visits were costed using a weighted average cost paid by the government for the specific service as derived from the Medicare Benefits Schedule (MBS) item reports. 14 In cases where health professionals do not receive reimbursement through an MBS item (e.g., counsellors, alcohol and drug workers), costs were estimated using an hourly wage rate (plus 30% on-costs). 15 Community services were costed using the national average hourly wage rate (plus 30% on-costs). 15

Supplementary Text S5. Analysis of missing data mechanisms
The mechanisms underlying missing responses for utility scores (i.e., health outcomes) and cost variables were analysed by: (1) investigating overall patterns of missing data; and (2) performing multivariate logistic regression analyses to determine if data missingness was related to other observed variables collected at baseline.
A summary of the top ten missing data patterns for utility and cost variables, at 3-month and 12-month follow-up, is presented in Table S5.1. Complete data were observed across 33% of study participants. A monotone missing pattern, which typically involves missing data caused by loss to follow up, was observed across 55% of participants. Of these, 37% had missing data across both follow-up periods and 18% had missing data at 12-month follow-up only. A nonmonotone missing pattern, where missing cases at 3-month follow-up provided subsequent data at 12-month follow-up, was observed across 6% of participants. Miscellaneous missing data patterns were observed across the remaining 6% of participants. were all significantly associated with missing utility responses. The results of the logistic regression analysing the relationship between missing cost responses and baseline variables are presented in Table S5. 3. Trial arm, clinic, age and having visited a psychiatrist/counsellor in the past 12 months were all significantly associated with missing cost responses. The results of the multivariate logistic regressions described above provide further evidence that missing utility/cost data are missing at random, given that missing responses were found to be associated with other sociodemographic variables collected at baseline. considered missing at random. The use of multiple imputation as a means of addressing missing data is valid when the underlying missing data mechanism is, at a minimum, deemed missing at random. If data were missing not at random, then this would lead to biased statistical inferences. The current study has incorporated the multiple imputation method to deal with missing utility/cost data as part of the statistical analysis. Based on the logistic regression analyses presented above, multiple imputation methods were used to impute missing utility/cost data, with adjustment for the following baseline covariates that were associated with missing utility/cost values: trial arm, gender, clinic, age, highest level of education and having visited a psychiatrist/counsellor in the past 12 months.