Preventing Depression in Adults With Subthreshold Depression: Health-Economic Evaluation Alongside a Pragmatic Randomized Controlled Trial of a Web-Based Intervention

Background Psychological interventions for the prevention of depression might be a cost-effective way to reduce the burden associated with depressive disorders. Objective To evaluate the cost-effectiveness of a Web-based guided self-help intervention to prevent major depressive disorder (MDD) in people with subthreshold depression (sD). Methods A pragmatic randomized controlled trial was conducted with follow-up at 12 months. Participants were recruited from the general population via a large statutory health insurance company and an open access website. Participants were randomized to a Web-based guided self-help intervention (ie, cognitive-behavioral therapy and problem-solving therapy assisted by supervised graduate students or health care professionals) in addition to usual care or to usual care supplemented with Web-based psycho-education (enhanced usual care). Depression-free years (DFYs) were assessed by blinded diagnostic raters using the telephone-administered Structured Clinical Interview for DSM-IV Axis Disorders at 6- and 12-month follow-up, covering the period to the previous assessment. Costs were self-assessed through a questionnaire. Costs measured from a societal and health care perspective were related to DFYs and quality-adjusted life years (QALYs). Results In total, 406 participants were enrolled in the trial. The mean treatment duration was 5.84 (SD 4.37) weeks. On average, participants completed 4.93 of 6 sessions. Significantly more DFYs were gained in the intervention group (0.82 vs 0.70). Likewise, QALY health gains were in favor of the intervention, but only statistically significant when measured with the more sensitive SF-6D. The incremental per-participant costs were €136 (£116). Taking the health care perspective and assuming a willingness-to-pay of €20,000 (£17,000), the intervention’s likelihood of being cost-effective was 99% for gaining a DFY and 64% or 99% for gaining an EQ-5D or a SF-6D QALY. Conclusions Our study supports guidelines recommending Web-based treatment for sD and adds that this not only restores health in people with sD, but additionally reduces the risk of developing a MDD. Offering the intervention has an acceptable likelihood of being more cost-effective than enhanced usual care and could therefore reach community members on a wider scale. Trial registration German Clinical Trials Register: DRKS00004709; http://www.drks.de/DRKS00004709 (Archived by WebCite at http://www.webcitation.org/6kAZVUxy9)

Manuscript tracking number * If this is a JMIR submission, please provide the manuscript tracking number under "other" (The ms tracking number can be found in the submission acknowledgement email, or when you login as author in JMIR. If the paper is already published in JMIR, then the ms tracking number is the four-digit number at the end of the DOI, to be found at the bottom of each published article in JMIR) no ms number ( 1a-i) Identify the mode of delivery in the title Identify the mode of delivery. Preferably use "web-based" and/or "mobile" and/or "electronic game" in the title. Avoid ambiguous terms like "online", "virtual", "interactive". Use "Internet-based" only if Intervention includes non-web-based Internet components (e.g. email), use "computer-based" or "electronic" only if of�ine products are used. Use "virtual" only in the context of "virtual reality" (3-D worlds). Use "online" only in the context of "online support groups". Complement or substitute product names with broader terms for the class of products (such as "mobile" or "smart phone" instead of "iphone"), especially if the application runs on different platforms. subitem not at all important essential Does your paper address subitem 1a-ii?
Copy and paste relevant sections from manuscript title (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study NA.

1a-iii) Primary condition or target group in the title
Mention primary condition or target group in the title, if any (e.g., "for children with Type I Diabetes") Example: A Web-based and Mobile Intervention with Telephone Support for Children with Type I Diabetes: Randomized Controlled Trial   1  2  3  4  5 subitem not at all important essential Does your paper address subitem 1a-iii? * Copy and paste relevant sections from manuscript title (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "adults with subthreshold depression" 1b) ABSTRACT: Structured summary of trial design, methods, results, and conclusions NPT extension: Description of experimental treatment, comparator, care providers, centers, and blinding status.

METHODS section of the ABSTRACT
Mention key features/functionalities/components of the intervention and comparator in the abstract. If possible, also mention theories and principles used for designing the site. Keep in mind the needs of systematic reviewers and indexers by including important synonyms. (Note: Only report in the abstract what the main paper is reporting. If this information is missing from the main body of text, consider adding it) 1 2 3 4 5 subitem not at all important essential Does your paper address subitem 1b-i? * Copy and paste relevant sections from the manuscript abstract (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "a web-based guided self-help intervention (i.e. cognitivebehavioural therapy and problem-solving therapy assisted by supervised graduate students or health care professionals) in addition to usual care or to usual care supplemented with web-based psycho-education (enhanced usual care)"

1b-ii) Level of human involvement in the METHODS section of the ABSTRACT
Clarify the level of human involvement in the abstract, e.g., use phrases like "fully automated" vs. "therapist/nurse/care provider/physician-assisted" (mention number and expertise of providers involved, if any). (Note: Only report in the abstract what the main paper is reporting. If this information is missing from the main body of text, consider adding it) 1 2 3 4 5 subitem not at all important essential Does your paper address subitem 1b-ii?
Copy and paste relevant sections from the manuscript abstract (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "assisted by supervised graduate students or health care professionals" clinic or a closed online user group (closed usergroup trial), and clarify if this was a purely web-based trial, or there were face-to-face components (as part of the intervention or for assessment). Clearly say if outcomes were self-assessed through questionnaires (as common in web-based trials). Note: In traditional of�ine trials, an open trial (open-label trial) is a type of clinical trial in which both the researchers and participants know which treatment is being administered. To avoid confusion, use "blinded" or "unblinded" to indicated the level of blinding instead of "open", as "open" in web-based trials usually refers to "open access" (i.e. participants can self-enrol). (Note: Only report in the abstract what the main paper is reporting. If this information is missing from the main body of text, consider adding it) 1 2 3 4 5 subitem not at all important essential Does your paper address subitem 1b-iii?
Copy and paste relevant sections from the manuscript abstract (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "Participants were recruited from the general population via a large statutory health insurance company and an open access website" "Depression-free years (DFYs) were assessed by blinded diagnostic raters using the telephone-administered Structured Clinical Interview for DSM-IV Axis Disorders at 6-and 12-month follow-up, covering the period to the previous assessment. Costs were self-assessed through a questionnaire." 1b-iv) RESULTS section in abstract must contain use data Report number of participants enrolled/assessed in each group, the use/uptake of the intervention (e.g., attrition/adherence metrics, use over time, number of logins etc.), in addition to primary/secondary outcomes. (Note: Only report in the abstract what the main paper is reporting. If this information is missing from the main body of text, consider adding it) 1 2 3 4 5 subitem not at all important essential Does your paper address subitem 1b-iv?
Copy and paste relevant sections from the manuscript abstract (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "In total, 406 participants were enrolled in the trial. T he mean treatment duration was 5.84 (SD 4.37) weeks. On average, participants completed 4.93 of 6 sessions." Conclusions/Discussions in abstract for negative trials: Discuss the primary outcome -if the trial is negative (primary outcome not changed), and the intervention was not used, discuss whether negative results are attributable to lack of uptake and discuss reasons. subitem not at all important essential Does your paper address subitem 2a-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "Currently, major depressive disorder (MDD) is the single most important cause of years lived with disability (YLD) [1] and is further associated with substantial economic costs for society [2]. In high-income countries, the 12-month prevalence of MDD is estimated at 5•1% [3] with an annual incidence rate of 3% [4]." "Meta-analyses provide evidence for the effectiveness of psychological interventions to prevent first onsets and recurrences in depression [7][8][9]." "Using the Internet to provide community members with effective preventive interventions is currently viewed as a potentially cost-effective way of scaling up preventive interventions [12,13]." "Here we will evaluate the cost-effectiveness and cost-utility of such an indicated preventive intervention among self-selected members 2a-ii) Scienti�c background, rationale: What is known about the (type of) system subitem not at all important essential Does your paper address subitem 2a-ii? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "Especially indicated prevention, targeting subthreshold symptoms of an emerging depression, appears to be particularly effective [8]." "Elsewhere we reported the primary outcomes with respect to progression to MDD at 12 months [14]." "To the best of our knowledge, no randomised controlled trial has investigated the cost-effectiveness of a web-based guided self-help intervention to prevent the onset of diagnosed MDD."

2b) In INTRODUCTION: Speci�c objectives or hypotheses
Does your paper address CONSORT subitem 2b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "Here we will evaluate the cost-effectiveness and cost-utility of such an indicated preventive intervention among self-selected members from the community suffering from subthreshold depression." METHODS 3a) Description of trial design (such as parallel, factorial) including allocation ratio Does your paper address CONSORT subitem 3a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "We conducted a health-economic evaluation with a 12-month time horizon from a societal and public health care perspective alongside a 2-armed pragmatic randomised controlled trial in Germany (allocation ratio 1:1) to establish the cost-effectiveness and cost-utility of an indicated web-based guided self-help intervention in conjunction to usual care for people with subthreshold depression as compared to enhanced usual care (i.e., web-based psychoeducation in addition to treatment as usual)." 3b) Important changes to methods after trial commencement (such as eligibility criteria), with reasons Does your paper address CONSORT subitem 3b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study NA since no changes have been made.

3b-i) Bug �xes, Downtimes, Content Changes
Bug �xes, Downtimes, Content Changes: ehealth systems are often dynamic systems. A description of changes to methods therefore also includes important changes made on the intervention or comparator during the trial (e.g., major bug �xes or changes in the functionality or content) (5-iii) and other "unexpected events" that may have in�uenced study design such as staff changes, system failures/downtimes, etc. subitem not at all important essential Does your paper address subitem 3b-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study NA, no bug fixes, no changes in functionality or content.

4a) Eligibility criteria for participants
Does your paper address CONSORT subitem 4a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "Inclusion criteria were: (a) age 18 and above, (b) subthreshold depression (Centre for Epidemiological Studies Depression Scale (CES-D) ≥ 16) as having some depressive symptoms not meeting the diagnostic criteria for a full-blown DSM-IV major depressive disorder as assessed by the telephone-administered Structured Clinical Interview for DSM-IV (SCID), (c) Internet access, and (d) informed consent. Exclusion criteria included (a) meeting DSM-IV criteria for bipolar disorder or psychotic disorder, (b) having a history of a major depressive disorder in the past six months based on Kupfer's model [16], (c) currently receiving psychotherapy for any kind of mental health problem, (d) being on a waiting list for psychotherapy, (e) having received psychotherapeutic treatment in the past six months, and (g) showing a significant suicidal risk (item 9 of the Beck Depression Inventory > 1)."

4a-i) Computer / Internet literacy
Computer / Internet literacy is often an implicit "de facto" eligibility criterion -this should be explicitly clari�ed.
1 2 3 4 5 subitem not at all important essential Does your paper address subitem 4a-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study Computer / Internet literacy was not an inclusion criterion in this study.
4a-ii) Open vs. closed, web-based vs. face-to-face assessments: Open vs. closed, web-based vs. face-to-face assessments: Mention how participants were recruited (online vs. of�ine), e.g., from an open access website or from a clinic, and clarify if this was a purely web-based trial, or there were face-to-face components (as part of the intervention or for assessment), i.e., to what degree got the study team to know the participant. In online-only trials, clarify if participants were quasianonymous and whether having multiple identities was possible or whether technical or logistical measures (e.g., cookies, email con�rmation, phone calls) were used to detect/prevent these. subitem not at all important essential Does your paper address subitem 4a-ii? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "Participants were recruited from March 2013 to March 2014 from the general population via a large German health insurance company and through newspaper articles, on-air media, and related websites." "Inclusion criteria were: (a) age 18 and above, (b) subthreshold depression (Centre for Epidemiological Studies Depression Scale (CES-D) ≥ 16) as having some depressive symptoms not meeting the diagnostic criteria for a full-blown DSM-IV major depressive disorder as assessed by the telephone-administered Structured Clinical Interview for DSM-IV (SCID)" "MDD was assessed according to DSM-IV criteria as assessed by the telephone-administered SCID [19,20] at 6-and 12-month follow-up covering the period to the previous assessment." "T he research staff conducting SCID interviews were not otherwise 4a-iii) Information giving during recruitment Information given during recruitment. Specify how participants were briefed for recruitment and in the informed consent procedures (e.g., publish the informed consent documentation as appendix, see also item X26), as this information may have an effect on user self-selection, user expectation and may also bias results. 4b) Settings and locations where the data were collected Does your paper address CONSORT subitem 4b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "Self-report measures were collected at baseline, post-treatment, 6and 12-month follow-up using a secured online-based assessment system (AES, 256-bit encrypted). T he SCID interviews at baseline, 6and 12-month follow-up were conducted by telephone." 4b-i) Report if outcomes were (self-)assessed through online questionnaires Clearly report if outcomes were (self-)assessed through online questionnaires (as common in web-based trials) or otherwise.
subitem not at all important essential Does your paper address subitem 4b-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "Self-report measures were collected at baseline, post-treatment, 6and 12-month follow-up using a secured online-based assessment system (AES, 256-bit encrypted). T he SCID interviews at baseline, 6and 12-month follow-up were conducted by telephone." 4b-ii) Report how institutional af�liations are displayed Report how institutional af�liations are displayed to potential participants [on ehealth media], as af�liations with prestigious hospitals or universities may affect volunteer rates, use, and reactions with regards to an intervention.(Not a required item -describe only if this may bias results) subitem not at all important essential Does your paper address subitem 4b-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study Relevant logos of universities involved in the study and the EU logo (study was financed by EU regional development fund) were presented on the information leaflet for participants.

5)
The interventions for each group with suf�cient details to allow replication, including how and when they were actually administered

5-i) Mention names, credential, af�liations of the developers, sponsors, and owners
Mention names, credential, af�liations of the developers, sponsors, and owners [6] (if authors/evaluators are owners or developer of the software, this needs to be declared in a "Con�ict of interest" section or mentioned elsewhere in the manuscript). subitem not at all important essential Does your paper address subitem 5-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "T he web-based intervention, called GET.ON Mood Enhancer, is an online multimedia interactive intervention consisting of six sessions. Each session takes about 30 minutes to complete, but the amount of time spent on a session varies among users." ". T he intervention is based on behavioural activation and problemsolving therapy. An emphasis was placed on homework assignments to integrate newly acquired skills into daily life. T herefore, participants had the option to receive a set of about 42 standardised text-messages supporting them to integrate the learned techniques into their lives. Participants were also supported by an online-trainer, who provided written feedback after each session. T he total time a trainer spent per participant was approximately three hours." "T he intervention was developed by trained psychologists and therapists at the Leuphana University."

5-ii) Describe the history/development process
Describe the history/development process of the application and previous formative evaluations (e.g., focus groups, usability testing), as these will have an impact on adoption/use rates and help with interpreting results.
subitem not at all important essential Does your paper address subitem 5-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "T he intervention was developed by trained psychologists and therapists at the Leuphana University." Prior to conducting the RCT (n=406) we performed a pilot feasibility study (n=10) (not published).

5-iii) Revisions and updating
Revisions and updating. Clearly mention the date and/or version number of the application/intervention (and comparator, if applicable) evaluated, or describe whether the intervention underwent major changes during the evaluation process, or whether the development and/or content was "frozen" during the trial.
Describe dynamic components such as news feeds or changing content which may have an impact on the replicability of the intervention (for unexpected events see item 3b).
subitem not at all important essential Does your paper address subitem 5-iii?
CONSORT-EHEALTH (V 1.6.1) -Submission/Publication Form https://docs.google.com/forms/d/e/1FAIpQLSfZBSUp1bwOc_OimqcS6... indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "T he content of the intervention was frozen during the trial."

5-iv) Quality assurance methods
Provide information on quality assurance methods to ensure accuracy and quality of information provided [1], if applicable.
subitem not at all important essential Does your paper address subitem 5-iv?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study Trained psychologists, therapists and researchers designed and administered the study. A research coordinator supervised the study and was responsible for quality assurance and ensured accuracy and quality of the data.

5-v)
Ensure replicability by publishing the source code, and/or providing screenshots/screencapture video, and/or providing �owcharts of the algorithms used Ensure replicability by publishing the source code, and/or providing screenshots/screen-capture video, and/or providing �owcharts of the algorithms used. Replicability (i.e., other researchers should in principle be able to replicate the study) is a hallmark of scienti�c reporting.
subitem not at all important essential Does your paper address subitem 5-v?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study Screenshots of the intervention have been published elsewhere: Psychother Psychosom 84 (6): 348-358.

5-vi) Digital preservation
Digital preservation: Provide the URL of the application, but as the intervention is likely to change or disappear over the course of the years; also make sure the intervention is archived (Internet Archive, webcitation.org, and/or publishing the source code or screenshots/videos alongside the article). As pages behind login screens cannot be archived, consider creating demo pages which are accessible without login.
subitem not at all important essential Does your paper address subitem 5-vi?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study

5-vii) Access
Access: Describe how participants accessed the application, in what setting/context, if they had to pay (or were paid) or not, whether they had to be a member of speci�c group. If known, describe how participants obtained "access to the platform and Internet" [1]. To ensure access for editors/reviewers/readers, consider to provide a "backdoor" login account or demo mode for reviewers/readers to explore the application (also important for archiving purposes, see vi).
subitem not at all important essential Does your paper address subitem 5-vii? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "Participants created their own password to access the intervention." "Trial participants used the intervention free of charge." 5-viii) Mode of delivery, features/functionalities/components of the intervention and comparator, and the theoretical framework subitem not at all important essential Does your paper address subitem 5-viii? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "Web-based guided self-help intervention T he web-based intervention, called GET.ON Mood Enhancer, is an online multimedia interactive intervention consisting of six sessions. Each session takes about 30 minutes to complete, but the amount of time spent on a session varies among users. Participants were advised to carry out at least one, preferably two lessons per week. T he mean treatment duration was 5.84 (SD 4.37) weeks. On average, participants completed 4.93 of 6 sessions [14]. T he intervention was developed by trained psychologists and therapists at the Leuphana University. Participants created their own password to access the intervention. Trial participants used the intervention free of charge. T he intervention is based on behavioural activation and problem-solving therapy. T he content of the intervention was frozen during the trial. An emphasis was placed on homework assignments to integrate newly acquired skills into daily life. T herefore, participants had the option to receive a set of about 42 standardised text-messages supporting them to integrate the learned techniques into their lives. Participants were also supported by an online-trainer, who provided written feedback after each session. T he total time a trainer spent per participant was approximately three hours. Trained and supervised graduate students and health care professionals provided guidance. Further details about the intervention can be found in the study protocol [15].
Enhanced usual care Participants in the control condition got access to an online psychoeducational intervention, which was based on the German S3-Guideline/National Disease Management Guideline Unipolar Depression [17]. It informed participants about evidence-based treatments of depression should symptoms deteriorate. We thus mimicked and enhanced usual care because we provided patients with information that they may not always be offered thoroughly by their GP. Similar psycho-educational interventions have been shown to be effective in reducing depressive symptoms and is therefore suggested as a first-line intervention for early manifestations of depression in the primary care setting [18]. Participants could go

5-ix) Describe use parameters
Describe use parameters (e.g., intended "doses" and optimal timing for use). Clarify what instructions or recommendations were given to the user, e.g., regarding timing, frequency, heaviness of use, if any, or was the intervention used ad libitum.
subitem not at all important essential Does your paper address subitem 5-ix?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "Participants were advised to carry out at least one, preferably two lessons per week."

5-x) Clarify the level of human involvement
Clarify the level of human involvement (care providers or health professionals, also technical assistance) in the e-intervention or as co-intervention (detail number and expertise of professionals involved, if any, as well as "type of assistance offered, the timing and frequency of the support, how it is initiated, and the medium by which the assistance is delivered". It may be necessary to distinguish between the level of human involvement required for the trial, and the level of human involvement required for a routine application outside of a RCT setting (discuss under item 21 -generalizability).
subitem not at all important essential Does your paper address subitem 5-x?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "Participants were also supported by an online-trainer, who provided written feedback after each session. T he total time a trainer spent per participant was approximately three hours. Trained and supervised graduate students and health care professionals provided guidance."

5-xi) Report any prompts/reminders used
Report any prompts/reminders used: Clarify if there were prompts (letters, emails, phone calls, SMS) to use the application, what triggered them, frequency etc. It may be necessary to distinguish between the level of prompts/reminders required for the trial, and the level of prompts/reminders for a routine application outside of a RCT setting (discuss under item 21 -generalizability). subitem not at all important essential Does your paper address subitem 5-xi? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "Participants were also supported by an online-trainer, who provided written feedback after each session and monitored adherence to the intervention. In case of non-adherence, online-trainers sent up to three reminders."

5-xii) Describe any co-interventions (incl. training/support)
Describe any co-interventions (incl. training/support): Clearly state any interventions that are provided in addition to the targeted eHealth intervention, as ehealth intervention may not be designed as stand-alone intervention. This includes training sessions and support [1]. It may be necessary to distinguish between the level of training required for the trial, and the level of training for a routine application outside of a RCT setting (discuss under item 21 -generalizability. subitem not at all important essential Does your paper address subitem 5-xii? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "All study participants had unrestricted access to care-as-usual (CAU). CAU for subthreshold depression entails visits to the GP, but no treatment provided by mental health specialists. If depressive symptoms deteriorate, the German S3-Guideline/National Disease Management Guideline Unipolar Depression recommends psychotherapy and the prescription of antidepressant medication [17]. In our pragmatic study we did not interfere in CAU. Instead, we maintained a naturalistic CAU condition to represent current clinical practice as far as possible. It should also be noted that health care use was measured in detail (see Measures), implying that we now can describe CAU in great detail (see Table 1)." 6a) Completely de�ned pre-speci�ed primary and secondary outcome measures, including how and when they were assessed Does your paper address CONSORT subitem 6a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "T he main outcome in the cost-effectiveness analysis was depression-free years (DFYs). DFYs were based on the number of depression-free weeks up to the onset of a major depressive episode within the 12-month follow-up period. MDD was assessed according to DSM-IV criteria as assessed by the telephone-administered SCID [19,20] at 6-and 12-month follow-up covering the period to the previous assessment. Time to onset of MDD was assessed as accurately as possible using the Life Chart method as developed by Lyketsos [21]." "Quality-adjusted life years (QALYs) were used as the outcome in the cost-utility analysis. QALYs were based on the EQ-5D-3L (EuroQol [22]) and SF-6D (a subset of items of the SF-12v1 [23]). T he EuroQoL and the SF-12 were assessed at baseline, post-treatment (6 weeks), and 6-and 12-month follow-up." 6a-i) Online questionnaires: describe if they were validated for online use and apply CHERRIES items to describe how the questionnaires were designed/deployed subitem not at all important essential Does your paper address subitem 7a-i?
Copy and paste relevant sections from manuscript title (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "T he study was powered to demonstrate a risk reduction of 10% between study conditions as statistically significant in a survival analyses with α<0.05 (2-tailed), a power of (1-β)=0.80 using survival analysis and accounting for a 20% dropout (calculated using PASS 12). However, the study was not powered to statistically test differences in health economic outcomes. T herefore, we took a probabilistic decision-making approach for our health economic interferences [36]."

7b) When applicable, explanation of any interim analyses and stopping guidelines
Does your paper address CONSORT subitem 7b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study NA.

8a) Method used to generate the random allocation sequence
NPT: When applicable, how care providers were allocated to each trial group Does your paper address CONSORT subitem 8a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "Randomisation took place at individual level and was conducted centrally by an independent statistician not otherwise involved in the study using an automated computer-generated random numbers table." 8b) Type of randomisation; details of any restriction (such as blocking and block size) Does your paper address CONSORT subitem 8b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "Block randomisation, of size two, was used to ensure equal sample sizes across both conditions. Details about the randomisation procedure can be found elsewhere [14]." 9) Mechanism used to implement the random allocation sequence (such as sequentially numbered containers), describing any steps taken to conceal the sequence until interventions were assigned Does your paper address CONSORT subitem 9? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "Randomisation took place at individual level and was conducted centrally by an independent statistician not otherwise involved in the study using an automated computer-generated random numbers table. Block randomisation, of size two, was used to ensure equal sample sizes across both conditions. Details about the randomisation procedure can be found elsewhere [14]." 10) Who generated the random allocation sequence, who CONSORT-EHEALTH (V 1.6.1) -Submission/Publication Form https://docs.google.com/forms/d/e/1FAIpQLSfZBSUp1bwOc_OimqcS6...

enrolled participants, and who assigned participants to interventions
Does your paper address CONSORT subitem 10? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "Randomisation took place at individual level and was conducted centrally by an independent statistician not otherwise involved in the study using an automated computer-generated random numbers table. Block randomisation, of size two, was used to ensure equal sample sizes across both conditions. Details about the randomisation procedure can be found elsewhere [14]." 11a) If done, who was blinded after assignment to interventions (for example, participants, care providers, those assessing outcomes) and how NPT: Whether or not administering co-interventions were blinded to group assignment 11a-i) Specify who was blinded, and who wasn't Specify who was blinded, and who wasn't. Usually, in web-based trials it is not possible to blind the participants [1, 3] (this should be clearly acknowledged), but it may be possible to blind outcome assessors, those doing data analysis or those administering co-interventions (if any). 1 2 3 4 5 subitem not at all important essential Does your paper address subitem 11a-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "Study participants were not masked to their treatment allocation because of the nature of the intervention. SCID interviewers were, however, unaware of participants' randomisation status. Steps taken to maintain blinding are described in detail elsewhere [14]. In case of evidence for blinding breakdown, the interviewer was changed to the second outcome interview. T he research staff conducting SCID interviews were not otherwise involved in the study." interest" and which one was the "comparator" Informed consent procedures (4a-ii) can create biases and certain expectations -discuss e.g., whether participants knew which intervention was the "intervention of interest" and which one was the "comparator". 1 2 3 4 5 subitem not at all important essential Does your paper address subitem 11a-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "Study participants were not masked to their treatment allocation because of the nature of the intervention."

11b) If relevant, description of the similarity of interventions
(this item is usually not relevant for ehealth trials as it refers to similarity of a placebo or sham intervention to a active medication/intervention) Does your paper address CONSORT subitem 11b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study NA.
12a) Statistical methods used to compare groups for primary and secondary outcomes NPT: When applicable, details of whether and how the clustering by care providers or centers was addressed CONSORT-EHEALTH (V 1.6.1) -Submission/Publication Form https://docs.google.com/forms/d/e/1FAIpQLSfZBSUp1bwOc_OimqcS6...
Does your paper address CONSORT subitem 12a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study

"Evaluation of clinical outcomes
We reported all analyses in accordance to the CONSORT statement [37]. Data were analysed on an intention-to-treat basis meaning that all participants were included in the analyses as randomised. To this end, we used Cox proportional hazard regression analyses to test differences in time to onset of MDD (in weeks) between intervention and control group.

Costs
Missing costs data were imputed using the regression imputation procedure in Stata version 13 [38], but we did not impute hospitalisation costs because only three participants (0.7%) were hospitalised during the 12-month follow-up period leading to instable imputations. T herefore, we re-assessed the impact of hospitalisation costs on outcomes in a sensitivity analysis. Mean total costs were estimated by multiplying the units of resource use with corresponding unit cost prices. Cumulative costs for each participant over the full 12-month follow-up period were estimated by calculating the area under the curve (AUC) of linearly interpolated costs. Differences in mean total costs between intervention and control groups were estimated using 2,500 bootstrap replications."

12a-i) Imputation techniques to deal with attrition / missing values
Imputation techniques to deal with attrition / missing values: Not all participants will use the intervention/comparator as intended and attrition is typically high in ehealth trials. Specify how participants who did not use the application or dropped out from the trial were treated in the statistical analysis (a complete case analysis is strongly discouraged, and simple imputation techniques such as LOCF may also be problematic [4]).
1 2 3 4 5 subitem not at all important essential Does your paper address subitem 12a-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "Missing costs data were imputed using the regression imputation procedure in Stata version 13 [38], but we did not impute hospitalisation costs because only three participants (0.7%) were hospitalised during the 12-month follow-up period leading to instable imputations." 12b) Methods for additional analyses, such as subgroup analyses and adjusted analyses Does your paper address CONSORT subitem 12b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "Sensitivity analyses We tested the robustness of the outcomes of the main analysis in sensitivity analyses. Firstly, the EQ-5D-3L might suffer from ceiling effects when measuring QALY changes in people with mild conditions. T herefore, we did plan to also measure SF-6D QALYs, which have been reported to be more sensitive to QALY changes in milder conditions such as subthreshold depression [27]. Secondly, we assessed the impact of in-patient care on the ICER because in-patient care is one of the main cost drivers and was surrounded by much uncertainty since only three hospital admissions occurred in the whole sample (3/406 = 0.7%). Such outliers (driving costs in the control condition) could lead to misleading results and these costs

X26) REB/IRB Approval and Ethical Considerations [recommended as subheading under "Methods"] (not a CONSORT item)
X26-i) Comment on ethics committee approval 1 2 3 4 5 subitem not at all important essential Does your paper address subitem X26-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "T he study was approved by the medical ethics committee of the University of Marburg (reference number AZ 2012-35K)."

x26-ii) Outline informed consent procedures
Outline informed consent procedures e.g., if consent was obtained of�ine or online ( subitem not at all important essential Does your paper address subitem X26-ii? Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study Participants could send the signed informed consent form via post or e-mail.

X26-iii) Safety and security procedures
Safety and security procedures, incl. privacy considerations, and any steps taken to reduce the likelihood or detection of harm (e.g., education and training, availability of a hotline) 1 2 3 4 5 subitem not at all important essential Does your paper address subitem X26-iii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "Exclusion criteria included: (...) (g) showing a significant suicidal risk (item 9 of the Beck Depression Inventory > 1)." Besides, trained psychologist were available via telephone and email to increase safety and secruity.

RESULTS
13a) For each group, the numbers of participants who were randomly assigned, received intended treatment, and were analysed for the primary outcome NPT: The number of care providers or centers performing the intervention in each group and the number of patients treated by each care provider in each center Does your paper address CONSORT subitem 13a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "In total, 406 participants were enrolled in the study (NINT = 202; NCT R = 204). At post treatment, 366 participants (90.1%) were still participating. At 6-and 12-month follow-up, 325 (80.1%) and 286 (70.4%) participants completed the questionnaires, respectively. T he CONSORT flowchart (of the participants through the trial) can be found elsewhere [14]." "Data were analysed on an intention-to-treat basis meaning that all participants were included in the analyses as randomised." 13b) For each group, losses and exclusions after randomisation, together with reasons Does your paper address CONSORT subitem 13b? (NOTE: Preferably, this is shown in a CONSORT �ow diagram) * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "In total, 406 participants were enrolled in the study (NINT = 202; NCT R = 204). At post treatment, 366 participants (90.1%) were still participating. At 6-and 12-month follow-up, 325 (80.1%) and 286 (70.4%) participants completed the questionnaires, respectively. T he CONSORT flowchart (of the participants through the trial) can be found elsewhere [14]."

13b-i) Attrition diagram
Strongly recommended: An attrition diagram (e.g., proportion of participants still logging in or using the intervention/comparator in each group plotted over time, similar to a survival curve) or other �gures or tables demonstrating usage/dose/engagement. subitem not at all important essential Does your paper address subitem 13b-i?
Copy and paste relevant sections from the manuscript or cite the �gure number if applicable (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study See Multimedia Appendix.
14a) Dates de�ning the periods of recruitment and follow-up Does your paper address CONSORT subitem 14a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "In total, 406 participants were included in the study. Participants were recruited from March 2013 to March 2014 from the general population via a large German health insurance company and through newspaper articles, on-air media, and related websites." 14a-i) Indicate if critical "secular events" fell into the study period Indicate if critical "secular events" fell into the study period, e.g., signi�cant changes in Internet resources available or "changes in computer hardware or Internet delivery resources" 1 2 3 4 5 subitem not at all important essential Does your paper address subitem 14a-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study NA.
Does your paper address CONSORT subitem 14b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study NA.

15) A table showing baseline demographic and clinical characteristics for each group
NPT: When applicable, a description of care providers (case volume, quali�cation, expertise, etc.) and centers (volume) in each group Does your paper address CONSORT subitem 15? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study

15-i) Report demographics associated with digital divide issues
In ehealth trials it is particularly important to report demographics associated with digital divide issues, such as age, education, gender, social-economic status, computer/Internet/ehealth literacy of the participants, if known.
subitem not at all important essential Does your paper address subitem 15-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study 16) For each group, number of participants (denominator) included in each analysis and whether the analysis was by original assigned groups 16-i) Report multiple "denominators" and provide de�nitions Report multiple "denominators" and provide de�nitions: Report N's (and effect sizes) "across a range of study participation [and use] thresholds" [1], e.g., N exposed, N consented, N used more than x times, N used more than y weeks, N participants "used" the intervention/comparator at speci�c pre-de�ned time points of interest (in absolute and relative numbers per group). Always clearly de�ne "use" of the intervention.
1 2 3 4 5 subitem not at all important essential Does your paper address subitem 16-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study All analyses were based on intention-to-treat meaning that all randomised participants were included in the analyses.

16-ii) Primary analysis should be intent-to-treat
Primary analysis should be intent-to-treat, secondary analyses could include comparing only "users", with the appropriate caveats that this is no longer a randomized sample (see 18-i).
1 2 3 4 5 subitem not at all important essential Does your paper address subitem 16-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "Data were analysed on an intention-to-treat basis meaning that all participants were included in the analyses as randomised." 17a) For each primary and secondary outcome, results for each group, and the estimated effect size and its precision (such as 95% con�dence interval) Does your paper address CONSORT subitem 17a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study Since this is an economic evaluation: "From a societal perspective, the intervention resulted in a greater mean health benefit (0.12 DFY gained) achieved at higher mean total costs (€134; £114) as compared to enhanced CAU." "T he ICER based on the QALY gains showed a small health benefit (0.01 QALYs gained) for higher mean costs (€134 from a societal perspective and €135 from a health care perspective)."

17a-i) Presentation of process outcomes such as metrics of use and intensity of use
In addition to primary/secondary (clinical) outcomes, the presentation of process outcomes such as metrics of use and intensity of use (dose, exposure) and their operational de�nitions is critical. This does not only refer to metrics of attrition (13-b) (often a binary variable), but also to more continuous exposure metrics such as "average session length". These must be accompanied by a technical description how a metric like a "session" is de�ned (e.g., timeout after idle time) [1] (report under item 6a).
subitem not at all important essential Does your paper address subitem 17a-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study NA since we report on an economic evaluation.
17b) For binary outcomes, presentation of both absolute and relative effect sizes is recommended Does your paper address CONSORT subitem 17b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study NA since we report an economic evaluation.
18) Results of any other analyses performed, including subgroup analyses and adjusted analyses, distinguishing pre-speci�ed from exploratory Does your paper address CONSORT subitem 18? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "Sensitivity analyses Using the SF-6D resulted in a greater incremental QALY gain in favour of the intervention group (0.70 QALY, SD= 0.08) as compared to the control group (0.67 QALY, SD = 0.07), which was statistically significant (t(404) = -4.40, P < 0.001). T his agrees with available evidence that the EQ-5D suffers from a ceiling effect in less severe diseases [40]. At a WT P of €20,000 for gaining one QALY the probability of being cost-effective was 84% (societal perspective) and 99% (health care perspective). Hospital costs were higher in the control group so excluding these costs resulted in higher ICERs (Table 2). From a societal perspective and at a WT P of €20,000, the intervention's probability of being cost-effective then became 53%."
A subgroup analysis of comparing only users is not uncommon in ehealth trials, but if done, it must be stressed that this is a self-selected sample and no longer an unbiased sample from a randomized trial (see 16-iii).
1 2 3 4 5 subitem not at all important essential Does your paper address subitem 18-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study NA since we report on an economic evaluation.

19) All important harms or unintended effects in each group
(for speci�c guidance see CONSORT for harms) Does your paper address CONSORT subitem 19? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study NA.

19-i) Include privacy breaches, technical problems
Include privacy breaches, technical problems. This does not only include physical "harm" to participants, but also incidents such as perceived or real privacy breaches [1], technical problems, and other unexpected/unintended incidents. "Unintended effects" also includes unintended positive effects [2].
1 2 3 4 5 subitem not at all important essential Does your paper address subitem 19-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study NA.

19-ii) Include qualitative feedback from participants or observations from staff/researchers
Include qualitative feedback from participants or observations from staff/researchers, if available, on strengths and shortcomings of the application, especially if they point to unintended/unexpected effects or uses. This includes (if available) reasons for why people did or did not use the application as intended by the developers. subitem not at all important essential Does your paper address subitem 19-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study NA since we report on an economic evaluation.

22) Interpretation consistent with results, balancing bene�ts and harms, and considering other relevant evidence
NPT: In addition, take into account the choice of the comparator, lack of or partial blinding, and unequal expertise of care providers or centers in each group 22-i) Restate study questions and summarize the answers suggested by the data, starting with primary outcomes and process outcomes (use) CONSORT-EHEALTH (V 1.6.1) -Submission/Publication Form https://docs.google.com/forms/d/e/1FAIpQLSfZBSUp1bwOc_OimqcS6...
Restate study questions and summarize the answers suggested by the data, starting with primary outcomes and process outcomes (use). subitem not at all important essential Does your paper address subitem 22-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "Our study was set out to evaluate the cost-effectiveness and cost-utility of a web-based guided self-help intervention to prevent the onset of major depressive disorder (MDD) in adults suffering from subthreshold depression in comparison to usual care enhanced with web-based psycho-education. Main outcomes were depression-free life years (DFYs) and quality adjusted life years (QALYs).
Significantly more depression-free years (DFYs) were gained in the intervention group as compared to the control group. T he probability that the intervention is deemed to be cost-effective depends on the willingness-to-pay (WT P) for a depression-free year. At a WT P of €1,500, €5,000 and €20,000 the likelihood was 52%, 76% and 99%, respectively, suggesting that a WT P of €1,500 and above for gaining a DFY would make the intervention cost-effective. While these DFY health gains were not mirrored in EQ-5D QALY gains, they were observed in SF-6D QALY gains with the latter being more sensitive to change in milder conditions such as subthreshold depression and therefore not suffering as much from a ceiling effect as the EQ-5D does.
[27] If society would be willing to pay €20,000 (£17000) for gaining a QALY, the probability of being cost-effective will be 64% for gaining an EQ-5D QALY and 84% for gaining a SF-6D QALY. "

22-ii) Highlight unanswered new questions, suggest future research
Highlight unanswered new questions, suggest future research. 1 2 3 4 5 subitem not at all important essential Does your paper address subitem 22-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "Future studies should thus clarify whether web-based guided self-help interventions are cost-effective both for the prevention of first depression onset and the prevention of recurrence." 20) Trial limitations, addressing sources of potential bias, imprecision, and, if relevant, multiplicity of analyses

20-i) Typical limitations in ehealth trials
Typical limitations in ehealth trials: Participants in ehealth trials are rarely blinded. Ehealth trials often look at a multiplicity of outcomes, increasing risk for a Type I error. Discuss biases due to non-use of the intervention/usability issues, biases through informed consent procedures, unexpected events.
subitem not at all important essential Does your paper address subitem 20-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study Limitations to the trial have been described in detail elsewhere: JAMA 315 (17): 1854-1863.
Here we report limitations specific to the economic evaluation: "T his study has some limitations. Firstly, the time horizon of this study was limited to 12 months. Secondly, we did not assess lifetime history of MDD at baseline and therefore we cannot be sure if we prevented first-ever onsets of MDD or MDD recurrences. Future studies should thus clarify whether web-based guided self-help interventions are cost-effective both for the prevention of first depression onset and the prevention of recurrence. T hirdly, costs were assessed with the help of self-reports and may suffer from underreporting. However, the structured questionnaire used in the current study can be considered as valid instrument for recall periods up to 3 months [46]. Finally, participants in this trial differed from the general population as they were better educated and predominately female. Conclusions might therefore not be safely generalised to other population segments. T hat said, the present trial is likely to have good ecological validity because we used the same open recruitment strategy that is routinely used for recruiting people from the general population for web-based interventions as applied in real practice. T herefore we expect that the sample on which our 21) Generalisability (external validity, applicability) of the CONSORT-EHEALTH (V 1.6.1) -Submission/Publication Form https://docs.google.com/forms/d/e/1FAIpQLSfZBSUp1bwOc_OimqcS6...

trial �ndings
NPT: External validity of the trial �ndings according to the intervention, comparators, patients, and care providers or centers involved in the trial

21-i) Generalizability to other populations
Generalizability to other populations: In particular, discuss generalizability to a general Internet population, outside of a RCT setting, and general patient population, including applicability of the study results for other organizations 1 2 3 4 5 subitem not at all important essential Does your paper address subitem 21-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "Conclusions might therefore not be safely generalised to other population segments. T hat said, the present trial is likely to have good ecological validity because we used the same open recruitment strategy that is routinely used for recruiting people from the general population for web-based interventions as applied in real practice. T herefore we expect that the sample on which our study was based is representative for the population of future users of this preventive intervention."

21-ii) Discuss if there were elements in the RCT that would be different in a routine application setting
Discuss if there were elements in the RCT that would be different in a routine application setting (e.g., prompts/reminders, more human involvement, training sessions or other co-interventions) and what impact the omission of these elements could have on use, adoption, or outcomes if the intervention is applied outside of a RCT setting. 1 2 3 4 5 subitem not at all important essential Does your paper address subitem 21-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study We conducted a pragmatic randomised controlled trial thus mimicking routine care in our trial.

23) Registration number and name of trial registry
Does your paper address CONSORT subitem 23? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study German Clinical Trial Registry Identifier: DRKS00004709 24) Where the full trial protocol can be accessed, if available Does your paper address CONSORT subitem 24? * Cite a Multimedia Appendix, other reference, or copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study T he study protocol has been previously published: Buntrock, C., et al. (2014). "Evaluating the efficacy and cost-effectiveness of web-based indicated prevention of major depression: design of a randomised controlled trial." BMC psychiatry 14: 25.

25)
Sources of funding and other support (such as supply of drugs), role of funders Does your paper address CONSORT subitem 25? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "Funding was received from the European Union (project number: EFRE: CCI 2007DE161PR001) and the BARMER GEK (German statutory health insurance company). T he funders did not have a role in study design; data collection, analysis the interpretation of results or the decision to publicise the study results."

X27) Con�icts of Interest (not a CONSORT item)
X27-i) State the relation of the study team towards the system being evaluated In addition to the usual declaration of interests (�nancial or otherwise), also state the relation of the study team towards the system being evaluated, i.e., state if the authors/evaluators are distinct from or identical with the developers/sponsors of the intervention. subitem not at all important essential Does your paper address subitem X27-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie�y explain why the item is not applicable/relevant for your study "T he Leuphana University, Lueneburg, has the exploitation rights of the intervention. T he authors will not have a share in any possible license revenues from the Leuphana University Lueneburg. DE, MB, SN, and DL are stakeholders of the "Institute for Online Health Trainings", a company aiming to transfer scientific knowledge related to the present research into routine health care. T his institute licenses the intervention under study from the Leuphana University, Lueneburg, to provide the intervention within routine preventive services of health insurance companies in Germany. T he foundation of such an institute to disseminate findings and products from the research project was the primary aim of the European Union for funding the presented research. At the time of planning, conducting, and evaluating the study, the institute did not yet exist."

About the CONSORT EHEALTH checklist
As a result of using this checklist, did you make changes in your manuscript? * yes, major changes yes, minor changes no What were the most important changes you made as a result of using this checklist?
Description of the web-based intervention.
How much time did you spend on going through the checklist INCLUDING making changes in your manuscript *

4hrs
As a result of using this checklist, do you think your manuscript has improved? * yes no Sonstiges: Would you like to become involved in the CONSORT EHEALTH group?
This would involve for example becoming involved in participating in a workshop and writing an "Explanation and Elaboration" document yes no Sonstiges: Any other comments or questions on CONSORT EHEALTH 1) It would be really helpful to have the opportunity to safe entries and come back later to complete the form.
2) You asked to generate a PDF of this form but you only explain to Mac users how to do it. It would be much appreciated to extend the explanation to non-Mac users! 3) For economic evaluations: Ask authors to complete the CHEERS checklist as this is more appropriate even if a web-based intervention is evaluated.

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