Virtual Reality Relaxation for Patients With a Psychiatric Disorder: Crossover Randomized Controlled Trial

Background Virtual reality (VR) relaxation is a promising mental health intervention that may be an effective tool for stress reduction but has hardly been tested in clinical trials with psychiatric patients. We developed an easy-to-use VR self-management relaxation tool (VRelax) with immersive 360° nature videos and interactive animated elements. Objective To investigate the immediate effects of VR relaxation on negative and positive affective states and short-term effects on perceived stress and symptoms in patients with a psychiatric disorder, compared to standard relaxation exercises. Methods A randomized crossover trial was conducted in 50 patients receiving ambulatory treatment for anxiety, psychotic, depressive, or bipolar disorder. Participants were randomly assigned to start with VRelax or standard relaxation and used both interventions for 10 days at home. They completed 8 visual analog scales of momentary negative and positive affective states before and after each session. Global perceived stress and psychiatric symptoms were measured before and after both intervention periods. Treatment effects were analyzed with multilevel mixed model regression analyses and 2-way analysis of variance. Results Both VRelax and standard relaxation exercises led to a statistically significant immediate improvement of all negative and positive affective states. Compared to standard relaxation, VRelax resulted in a significantly greater reduction of total negative affective state (change 16.2% versus 21.2%; t1684=−2.02, 95% CI −18.70 to −0.28; P=.04). Specifically, VRelax had a stronger beneficial effect on momentary anxiety (t1684=−3.24, 95% CI −6.86 to −1.69), sadness (t1684=−2.32, 95% CI −6.51 to −0.55), and cheerfulness (t1684=2.35, 95% CI 0.51 to 5.75). There were no significant differences between short-term effects of the two treatments on global perceived stress and symptoms. Conclusions If the results of this trial are replicated and extended, VRelax may provide a much-needed, effective, easy-to-use self-management relaxation intervention to enhance psychiatric treatments. Trial Registration Netherlands Trial Register NTR7294; https://www.trialregister.nl/trial/7096

yes: all primary outcomes were significantly better in intervention group vs control partly: SOME primary outcomes were significantly better in intervention group vs control no statistically significant difference between control and intervention potentially harmful: control was significantly better than intervention in one or more outcomes inconclusive: more research is needed Anders: Approx. Percentage of Users (starters) still using the app as recommended after 3 months * Overall, was the app/intervention effective? * 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 offline 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.
Does your paper address subitem 1a-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 briefly explain why the item is not applicable/relevant for your study Yes. Title of the manuscript: "Virtual Reality stress reduction for patients with a psychiatric disorder: cross-over randomized controlled trial."

1a-ii) Non-web-based components or important co-interventions in title
Mention non-web-based components or important co-interventions in title, if any (e.g., "with telephone support").

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 briefly explain why the item is not applicable/relevant for your study No, the intervention is a self-management tool. subitem not at all important 1 2 3 4 5 essential 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 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 briefly explain why the item is not applicable/relevant for your study Yes. Title of the manuscript: "Virtual Reality stress reduction for patients with a psychiatric disorder: cross-over randomized controlled trial."

1b-i) Key features/functionalities/components of the intervention and comparator in the 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) https://docs.google.com/forms/d/e/1FAIpQLSfZBSUp1bwOc_OimqcS64RdfIAFvmrTSkZQL2-3O8O9hrL5Sw/viewform?hl=en_US&formkey=dG… 10/52 subitem not at all important 1 2 3 4 5 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 briefly explain why the item is not applicable/relevant for your study Yes.
Background: "We developed a virtual reality (VR) self-management relaxation tool with immersive 360o nature videos and interactive animated elements." Objective: "To investigate the immediate and short-term effects of VR relaxation (VRelax) on stress level, mood states and symptoms in patients with a psychiatric disorder, compared to standard relaxation exercises."

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) 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 briefly explain why the item is not applicable/relevant for your study Yes.
Self-management tool, i.e., without therapist: "We developed a virtual reality (VR) selfmanagement relaxation tool." "Participants were randomly assigned to start with VRelax or standard relaxation, and used both interventions for 10 days at home." 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 briefly explain why the item is not applicable/relevant for your study Yes.
Recruitment of participants among "patients receiving ambulatory treatment for anxiety, psychotic, depressive or bipolar disorder." 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)

INTRODUCTION 2a) In INTRODUCTION: Scientific background and explanation of rationale
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 briefly explain why the item is not applicable/relevant for your study The abstract reports that 50 patients were included. No further details of use/uptake/dropout in the abstract, this information is shown in Flowchart ( Figure 2) and Results section.

1b-v) CONCLUSIONS/DISCUSSION in abstract for negative trials
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. (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) Does your paper address subitem 1b-v?
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 briefly explain why the item is not applicable/relevant for your study Trial had positive results, i.e., significant differences on primary outcome between intervention and control condition. 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 briefly explain why the item is not applicable/relevant for your study VR: "VR exposure treatments have been developed for various psychological and psychiatric problems, including anxiety and psychosis [13]. The results of some preliminary VR studies that exposed participants to virtual natural experiences suggested that this is a promising approach for relaxation and stress reduction that requires further development [14,15]." Comparison: "Stress-reducing interventions such as breathing exercises, mental imagery, progressive muscle relaxation and mindfulness are commonly applied in routine mental health care. These interventions are effective for reducing anxiety, stress and sleeping problems [4,5], have some effects on level of depressive symptoms [6,7], and have hardly been investigated in patients with psychotic disorders [8]." 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 briefly explain why the item is not applicable/relevant for your study "We conducted a cross-over randomized controlled trial (RCT), comparing VRelax with standard relaxation exercises. We hypothesized that: 1. VRelax results in an immediate reduction of subjective stress and negative mood states and an immediate increase in positive mood states; and 2. VRelax is more efficacious than standard relaxation exercises for immediate stress reduction and improving mood states. Also, we explored short-term effects of VRelax on global perceived level of stress and psychiatric symptoms." 3b) Important changes to methods after trial commencement (such as eligibility criteria), with reasons subitem not at all important 1 2 3 4 5 essential 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 briefly explain why the item is not applicable/relevant for your study "The study was a randomized controlled cross-over trial with two stress-reducing interventions: 1) the VRelax relaxation app and 2) standard relaxation exercises. Study procedures are shown in Figure 1. After informed consent, participants were randomly assigned to either start with VRelax or standard relaxation exercises. After 10 days, they crossed over to the other intervention." 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 briefly explain why the item is not applicable/relevant for your study No changes made to methods.

3b-i) Bug fixes, Downtimes, Content Changes
Bug fixes, 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 fixes or changes in the functionality or content) (5-iii) and other "unexpected events" that may have influenced study design such as staff changes, system failures/downtimes, etc. [2].

4a) Eligibility criteria for participants
subitem not at all important 1 2 3 4 5 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 briefly explain why the item is not applicable/relevant for your study No technical problems or changes in content, software or hardware.
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 briefly explain why the item is not applicable/relevant for your study "Patients receiving ambulatory treatment for a depressive disorder, bipolar disorder, anxiety disorder or psychotic disorder were eligible for the study. The other inclusion criteria were: perceived stress, based on self-report or clinician report; age >18; and having a desktop computer or laptop computer at home. Exclusion criteria were: a diagnosis of substance use disorder; benzodiazepine use > 10 mg / day diazepam equivalent; diagnosis of epilepsy; and insufficient command of Dutch."

4a-i) Computer / Internet literacy
Computer / Internet literacy is often an implicit "de facto" eligibility criterion -this should be explicitly clarified. 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 briefly explain why the item is not applicable/relevant for your study Computer / Internet literacy was not needed. The intervention was developed in co-creation with patients, with explicit focus on user experiences. After a brief instruction, all participants were able to use it. No drop-outs because of computer literacy problems.
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. offline), e.g., from an open access website or from a clinic, and clarify if this was a purely webbased 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 quasi-anonymous and whether having multiple identities was possible or whether technical or logistical measures (e.g., cookies, email confirmation, phone calls) were used to detect/prevent these.
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 briefly explain why the item is not applicable/relevant for your study Patients were recruited from primary health care or specialized mental health care, were eligible if they were receiving treatment for a psychiatric disorder. Assessments before and after the interventions were done face-to-face. Pre/post session ratings were made by patients at home.
"Momentary mood states were assessed before and after each session, other measures were obtained at baseline (T0), after the first intervention period (T1) and after the second intervention period (T2)." subitem not at all important 1 2 3 4 5 essential 4b) Settings and locations where the data were collected 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.
Does your paper address subitem 4a-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 briefly explain why the item is not applicable/relevant for your study In the information materials and the informed consent procedure, patients were briefed about the potential added value of the VR relaxation tool and the relaxation exercises to their ongoing treatment. They were informed about the aim of the study, i.e., investigating if VR relaxation is effective for immediate stress reduction, in comparison to standard relaxation exercises. The cross-over study design was explained.
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 briefly explain why the item is not applicable/relevant for your study "Patients receiving ambulatory treatment for a depressive disorder, bipolar disorder, anxiety disorder or psychotic disorder were eligible for the study." Specific details of locations are not included in the manuscript. 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.
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 briefly explain why the item is not applicable/relevant for your study 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 briefly explain why the item is not applicable/relevant for your study The medical ethical committee regulations require to include which institution is conducting the research, in this case University Medical Center Groningen. Most participants were receiving treatment in this hospital.

5-i) Mention names, credential, affiliations of the developers, sponsors, and owners
Mention names, credential, affiliations of the developers, sponsors, and owners [6] (if authors/evaluators are owners or developer of the software, this needs to be declared in a "Conflict of interest" section or mentioned elsewhere in the manuscript).

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 briefly explain why the item is not applicable/relevant for your study "The 360o videos were created by Viemr, The Dolphin Swim Club and Atmosphaeres; the VRelax tool was developed in collaboration with University Medical Center Groningen (first author WV)." Conflicts of interest statement: "BL, RH and CvD: none declared. WV is co-founder and chief scientific officer of VRelax BV, the company that has developed the VR in collaboration with UMCG, and holds shares in VRelax BV. MJ is co-founder of VRelax BV and holds shares. Statistical analyses were independently checked by Dr. Klaas Wardenaar, statistician at University of Groningen, University Medical Center Groningen."

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. 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 briefly explain why the item is not applicable/relevant for your study Development history not reported in the manuscript. Website (https://vrelax.com/en/homeus/) is included in the manuscript, for more background information about the intervention / product.

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).
Does your paper address subitem 5-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 briefly explain why the item is not applicable/relevant for your study The VRelax version has not changed throughout the study period.

5-iv) Quality assurance methods
Provide information on quality assurance methods to ensure accuracy and quality of information 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 briefly explain why the item is not applicable/relevant for your study Not sure what to report here. Version of the intervention as used in the study will be preserved.

5-v)
Ensure replicability by publishing the source code, and/or providing screenshots/screen-capture video, and/or providing flowcharts of the algorithms used Ensure replicability by publishing the source code, and/or providing screenshots/screen-capture video, and/or providing flowcharts of the algorithms used. Replicability (i.e., other researchers should in principle be able to replicate the study) is a hallmark of scientific reporting.
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 briefly explain why the item is not applicable/relevant for your study Screenshots of the intervention are included in the manuscript. More information is provided on the website, including video materials.

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. 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 briefly explain why the item is not applicable/relevant for your study URL and screenshots are included in the manuscript. This version of the intervention will be preserved and archived.

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 specific 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).
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 briefly explain why the item is not applicable/relevant for your study "Participants received a VRelax set to take home, including Gear VR, smartphone and headphones. They were instructed to use the VRelax app at least once daily for 10 minutes. After 10 days, they returned the VR set to the study team." "As active control intervention, participants received headphones and a USB stick with audio tracks of guided meditation and progressive relaxation exercises. They could play the tracks on devices they had at home (desktop or laptop computer, or smartphone). They were instructed to use it at least once daily for 10 minutes. After 10 days, participants returned the headphones and USB stick to the study team." 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 briefly explain why the item is not applicable/relevant for your study "The VRelax tool (https://www.vrelax.com) was used with a Samsung Galaxy S6 or S7 smartphone, connected to a head mounted display, the Samsung Gear VR. Threedimensional audio was played with headphones. When VRelax was activated, the participant entered a white-walled waiting room. Pre-session measures (see section Measures) started automatically within the virtual waiting room. After completion of the pre-session measures, the walls of the waiting room disappeared, and the participant was standing on a beach, from which he/she could choose where to go. VRelax included the following environments: quiet beaches without interaction, a beach with interactive relaxation exercises (guided meditation and progressive muscle relaxation), a coral reef with an interactive game element of popping bubbles by looking at them, swimming underwater with wild dolphins, a drone flight over a river landscape, a mountain meadow with animals, another mountain scenery in the alps, a sea view from a cliff with an interactive music element, and a beach session of Tibetan singing bowl therapy (Figure 3). Participants navigated through the interconnected environments by looking at hotspots within their field of view, that were activated after two seconds." "As active control intervention, participants received headphones and a USB stick with audio tracks of guided meditation and progressive relaxation exercises. They could play the tracks on devices they had at home (desktop or laptop computer, or smartphone)."

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.
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 briefly explain why the item is not applicable/relevant for your study Participants were instructed were instructed to use VRelax / relaxation exercises at least 10 days, once daily for 10 minutes. For VRelax, frequency, time and duration of use, and journey within the app were logged.

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). 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 briefly explain why the item is not applicable/relevant for your study After a brief face to face instruction, there was no further human involvement during the interventions. Participants used these as self-management tools at home.
For routine application outside RCTs, online and printed instruction materials are prepared.

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).
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 briefly explain why the item is not applicable/relevant for your study No prompts or reminders to use the interventions were used.

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. 6a) Completely defined pre-specified primary and secondary outcome measures, including how and when they were assessed subitem not at all important 1 2 3 4 5 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 briefly explain why the item is not applicable/relevant for your study "All patients received regular treatment for their mental health problems throughout the study period. VRelax and standard relaxation were add-on interventions." 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 briefly explain why the item is not applicable/relevant for your study All primary and secondary outcome measures are described in detail in the method section of the manuscript, as well as when they were assessed. Not copied and pasted here. 6a-ii) Describe whether and how "use" (including intensity of use/dosage) was defined/measured/monitored Describe whether and how "use" (including intensity of use/dosage) was defined/measured/monitored (logins, logfile analysis, etc.). Use/adoption metrics are important process outcomes that should be reported in any ehealth trial.

Does your paper address subitem 6a-ii?
Copy and paste relevant sections from manuscript text "During VRelax sessions, it was automatically recorded in log files how long participants spent time in which environments." These data are reported in Table 2.
"Mean number of sessions were 9.4 (SD, 3.5; range 0-16 sessions) for relaxation exercises and 8.7 (SD, 4.4; range 0-24 sessions) for VRelax. VRelax log files showed that average time spent in VRelax video environments was 17 minutes (SD, 9.5) per session." subitem not at all important 1 2 3 4 5 essential 6b) Any changes to trial outcomes after the trial commenced, with reasons 7a) How sample size was determined NPT: When applicable, details of whether and how the clustering by care provides or centers was addressed 6a-iii) Describe whether, how, and when qualitative feedback from participants was obtained Describe whether, how, and when qualitative feedback from participants was obtained (e.g., through emails, feedback forms, interviews, focus groups).

Does your paper address subitem 6a-iii?
Copy and paste relevant sections from manuscript text Qualitative feedback was obtained at the end of VRelax treatment. Interviews were conducted about user experiences. These will be reported in a separate manuscript.
Does your paper address CONSORT subitem 6b? * 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 briefly explain why the item is not applicable/relevant for your study "The trial was registered prospectively in the Dutch trial register, number NTR 7294." No changes in outcomes have been made. subitem not at all important 1 2 3 4 5 essential 7b) When applicable, explanation of any interim analyses and stopping guidelines 8a) Method used to generate the random allocation sequence NPT: When applicable, how care providers were allocated to each trial group 7a-i) Describe whether and how expected attrition was taken into account when calculating the sample size Describe whether and how expected attrition was taken into account when calculating the sample size.

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 briefly explain why the item is not applicable/relevant for your study "As this was the first randomized VR stress-reduction intervention study with an active control condition, there was no estimation of effect size available. The sample size was determined at N=50, based on recommendations for a clinical pilot study [16,17]." 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 briefly explain why the item is not applicable/relevant for your study Not applicable.
8b) Type of randomisation; details of any restriction (such as blocking and block size) 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 Dit is een vereiste vraag 10) Who generated the random allocation sequence, who enrolled participants, and who assigned participants to interventions 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 briefly explain why the item is not applicable/relevant for your study "After informed consent, participants were randomly assigned to either start with VRelax or standard relaxation exercises." This was a cross-over RCT, all participants received both interventions. Randomization for order of interventions was done by an independent research coordinator of University Medical Center Groningen.

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 briefly explain why the item is not applicable/relevant for your study 1:1 randomization, no restrictions.
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 briefly explain why the item is not applicable/relevant for your study Jouw antwoord 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 briefly explain why the item is not applicable/relevant for your study Jouw antwoord 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).

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 briefly explain why the item is not applicable/relevant for your study Participants could not be blinded for order of interventions.
Research assistants / assessors could not be blinded either, because they had to give instructions and had to interview participants about their experiences after use. 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 11a-ii) Discuss e.g., whether participants knew which intervention was the "intervention of 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".
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 briefly explain why the item is not applicable/relevant for your study Participants were aware that VRelax was the intervention of interest. In the information consent materials, VR relaxation was presented as a new intervention. The comparator, relaxation exercises, is a well-known, commonly used 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 briefly explain why the item is not applicable/relevant for your study Both interventions were designed for stress reduction and relaxation. Thus, this RCT had an active control condition, with known effect on primary and secondary outcomes.

12b) Methods for additional analyses, such as subgroup analyses and adjusted analyses
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 briefly explain why the item is not applicable/relevant for your study We used intention-to-treat analyses for the statistical analyses. The multilevel regression analyses allow for missing data, which means that all available data are used, and no cases are dropped if they have incomplete data.

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]).
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 briefly explain why the item is not applicable/relevant for your study The multilevel regression analyses allow for missing data, which means that all available data are used, and no cases are dropped if they have incomplete data. We did not use imputation techniques for missing data. 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 briefly explain why the item is not applicable/relevant for your study We did not perform subgroup analyses. As it was a cross-over RCT, we did not have to adjust analyses.

X26-i) Comment on ethics committee approval
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 briefly explain why the item is not applicable/relevant for your study We do not have any comments on the procedure of the ethics committee approval.

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 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 briefly explain why the item is not applicable/relevant for your study Informed consent was obtained face to face, after written information, further oral explanation, and possibility to ask questions.

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)

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 briefly explain why the item is not applicable/relevant for your study Participants were instructed how to use the interventions, received oral and written information. Telephone numbers of the research team were included in the materials.
There were no risks expected, apart from mild cyber sickness. This was explained to participants, including advice what to do in case of nausea/dizziness. 13b) For each group, losses and exclusions after randomisation, together with reasons subitem not at all important 1 2 3 4 5 essential 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 briefly explain why the item is not applicable/relevant for your study A CONSORT flow diagram is included in the manuscript.
Does your paper address CONSORT subitem 13b? (NOTE: Preferably, this is shown in a CONSORT flow 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 briefly explain why the item is not applicable/relevant for your study A CONSORT flow diagram is included in the manuscript.

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 figures or tables demonstrating usage/dose/engagement.

Does your paper address subitem 13b-i?
Copy and paste relevant sections from the manuscript or cite the figure 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 briefly explain why the item is not applicable/relevant for your study A CONSORT flow diagram is included in the manuscript, including numbers of participants discontinuing the use of the interventions.
14a) Dates defining the periods of recruitment and follow-up subitem not at all important 1 2 3 4 5 essential 14b) Why the trial ended or was stopped (early) 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 briefly explain why the item is not applicable/relevant for your study "Fifty patients were enrolled in this study between 27 March and 17 December, 2018." 14a-i) Indicate if critical "secular events" fell into the study period Indicate if critical "secular events" fell into the study period, e.g., significant changes in Internet resources available or "changes in computer hardware or Internet delivery resources" 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 briefly explain why the item is not applicable/relevant for your study No significant events fell into the study period. Better hardware became available, but the same hardware was used throughout the study period. All participants had the same hardware and software.

15) A table showing baseline demographic and clinical characteristics for each group
NPT: When applicable, a description of care providers (case volume, qualification, expertise, etc.) and centers (volume) in each group subitem not at all important 1 2 3 4 5 essential 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 briefly explain why the item is not applicable/relevant for your study The trial ended because the planned number of participants was included.
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 briefly explain why the item is not applicable/relevant for your study See Table 1.

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.
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 briefly explain why the item is not applicable/relevant for your study See

16-i) Report multiple "denominators" and provide definitions
Report multiple "denominators" and provide definitions: 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 specific pre-defined time points of interest (in absolute and relative numbers per group). Always clearly define "use" of the intervention.
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 briefly explain why the item is not applicable/relevant for your study Details of use are provided: "One patient dropped out after randomization and did not start either condition, leaving 49 patients for analyses. ... Mean number of sessions were 9.4 (SD, 3.5; range 0-16 sessions) for relaxation exercises and 8.7 (SD, 4.4; range 0-24 sessions) for VRelax. VRelax log files showed that average time spent in VRelax video environments was 17 minutes (SD, 9.5) per session. Use of different VRelax environments is shown in Table 2."

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).
17a) For each primary and secondary outcome, results for each group, and the estimated effect size and its precision (such as 95% confidence interval) subitem not at all important 1 2 3 4 5 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 briefly explain why the item is not applicable/relevant for your study Analyses of the primary outcome were intention-to-treat. Only one participant had no data at all, drop-out before start of any treatment.
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 briefly explain why the item is not applicable/relevant for your study All reported primary and secondary outcomes include test statistics and 95% confidence intervals where appropriate.
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 definitions 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 defined (e.g., timeout after idle time) [1] (report under item 6a).
17b) For binary outcomes, presentation of both absolute and relative effect sizes is recommended 18) Results of any other analyses performed, including subgroup analyses and adjusted analyses, distinguishing pre-specified from exploratory 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 briefly explain why the item is not applicable/relevant for your study All reported primary and secondary outcomes include test statistics and 95% confidence intervals where appropriate.
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 briefly explain why the item is not applicable/relevant for your study No binary outcomes.
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 briefly explain why the item is not applicable/relevant for your study No other analyses performed.

18-i) Subgroup analysis of comparing only users
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).
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 briefly explain why the item is not applicable/relevant for your study We did not perform only users analyses.
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 briefly explain why the item is not applicable/relevant for your study "No serious adverse events occurred. Several participants reported cyber sickness, two stopped using VRelax because of nausea and dizziness. Mean total score on the cyber sickness questionnaire (SSQ), however, was lower rather than higher after VRelax compared to before VRelax, and similar before and after relaxation exercises (Table 4)."

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].

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 briefly explain why the item is not applicable/relevant for your study Qualitative data are not included in this manuscript, will be reported in a separate paper. 22-i) Restate study questions and summarize the answers suggested by the data, starting with primary outcomes and process outcomes (use) Restate study questions and summarize the answers suggested by the data, starting with primary outcomes and process outcomes (use).

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 briefly explain why the item is not applicable/relevant for your study "This randomized cross-over clinical trial found that VR relaxation immediately improved positive momentary mood states and reduced feelings of stress, anxiety and other negative mood states in patients who concurrently received ambulatory psychiatric treatment. VRelax had a stronger effect on momentary mood states than standard relaxation exercises, in particular on feeling anxious, down and cheerful. Psychiatric symptoms, measured over a ten-day period, improved somewhat in both conditions." 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 briefly explain why the item is not applicable/relevant for your study "If the results of this trial are replicated and extended, VR nature exposure may provide an effective stress-management intervention to support and enhance psychiatric treatments. Stress-management is a cornerstone of psychiatric therapies, but there is a dearth of effortless, pleasant and powerful stress self-management tools. Longer-term effects of VR relaxation on psychiatric symptoms and relapse prevention should be investigated, as well as cost-effectiveness. Also, integration of biofeedback and more interactive elements (e.g., breathing exercises) may increase efficacy of VRelax. Finally, a broader use of VR relaxation can be envisioned for people in need of distraction. For example, during unpleasant medical interventions, long isolated hospital stays or for bed-ridden (terminally) ill patients. VR applications are rapidly growing and may have a profound impact on the landscape of mental health interventions."

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. 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 briefly explain why the item is not applicable/relevant for your study Strengths and limitations: "As a consequence of the cross-over design, it was not possible to investigate the effects of VR relaxation on medium or long-term outcomes. It is conceivable that VR experiences have a longer-lasting impact than standard relaxation exercises because of the immersive character, or simply because people may find it easier to keep using VRelax than to keep doing relaxation exercises. We did not observe such a pattern during the short duration of this study. Patients used the interventions multiple times over a (double) ten-day period, with effect measures before and after each session. These frequent assessments and detailed longitudinal data increased real life ecological validity and reliability of the primary outcome measure, and increased statistical power of the study. A disadvantage was that patients had to reflect on their mood state immediately after relaxation sessions, which may have reduced the positive effects to some extent. Another limitation is that we did not measure physiological effects of VR relaxation, which would have been a valuable outcome measure and a possibility to study biological mechanisms of VR nature exposure. Relaxation therapy as well as nature exposure have been related to changes in physiological stress parameters, such as vagal tone, electroencephalography (EEG) alpha and theta waves, heart rate variability, blood pressure, gene expression and cortisol level [36,37]. Recent research of VR nature videos found that EEG event related potentials may be used as a marker of attention restoration [38]."

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 subitem not at all important 1 2 3 4 5 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 briefly explain why the item is not applicable/relevant for your study Implications and generalizibility: "If the results of this trial are replicated and extended, VR nature exposure may provide an effective stress-management intervention to support and enhance psychiatric treatments. Stress-management is a cornerstone of psychiatric therapies, but there is a dearth of effortless, pleasant and powerful stress self-management tools. Longer-term effects of VR relaxation on psychiatric symptoms and relapse prevention should be investigated, as well as cost-effectiveness. Also, integration of biofeedback and more interactive elements (e.g., breathing exercises) may increase efficacy of VRelax. Finally, a broader use of VR relaxation can be envisioned for people in need of distraction. For example, during unpleasant medical interventions, long isolated hospital stays or for bed-ridden (terminally) ill patients. VR applications are rapidly growing and may have a profound impact on the landscape of mental health interventions."

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.

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 briefly explain why the item is not applicable/relevant for your study We discussed one element of the RCT which may have negatively influenced the results: "Patients used the interventions multiple times over a (double) ten-day period, with effect measures before and after each session. These frequent assessments and detailed longitudinal data increased real life ecological validity and reliability of the primary outcome measure, and increased statistical power of the study. A disadvantage was that patients had to reflect on their mood state immediately after relaxation sessions, which may have reduced the positive effects to some extent."

OTHER INFORMATION
23) Registration number and name of trial registry 24) Where the full trial protocol can be accessed, if available 25) Sources of funding and other support (such as supply of drugs), role of funders 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 briefly explain why the item is not applicable/relevant for your study The trial was registered prospectively in the Dutch trial register, number NTR 7294.
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 briefly explain why the item is not applicable/relevant for your study The full research protocol has not been published online, but is described in the Dutch trial register, number NTR 7294. About the CONSORT EHEALTH checklist 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 briefly explain why the item is not applicable/relevant for your study "Funding for this study was provided by University Medical Center Groningen, Healthy Ageing grant, number CDO17.0014/2017-1/308. The authors wish to thank The Dolphin Swim Club for sharing the 360 degrees dolphin video and their contribution to the development of the VRelax tool. All statistical analyses were independently checked by Dr. Klaas Wardenaar, statistician at University of Groningen, University Medical Center Groningen."

X27-i) State the relation of the study team towards the system being evaluated
In addition to the usual declaration of interests (financial 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.
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 briefly explain why the item is not applicable/relevant for your study "BL, RH and CvD: none declared. WV is co-founder and chief scientific officer of VRelax BV, the company that has developed the VR in collaboration with UMCG, and holds shares in VRelax BV. MJ is co-founder of VRelax BV and holds shares. Statistical analyses were independently checked by Dr. As a result of using this checklist, did you make changes in your manuscript? * What were the most important changes you made as a result of using this checklist?
not applicable.
How much time did you spend on going through the checklist INCLUDING making changes in your manuscript *

hours
As a result of using this checklist, do you think your manuscript has improved? * I had submitted the manuscript before completing this checklist, but I am fam 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