Telehealth-Based Psychoeducation for Caregivers: The Family Intervention in Recent-Onset Schizophrenia Treatment Study

Background Schizophrenia is a lifelong illness that requires long-term treatment and caregiving. Family psychoeducation (FP) has been shown to lessen caregiver burden, improve caregiver functioning, and improve outcomes in patients. However, the impact of FP delivered specifically to caregivers on patient outcomes has not been well explored, particularly for early schizophrenia. Furthermore, there is a lack of research examining the benefits of telehealth-based psychoeducation for caregivers on either patient or caregiver outcomes. Objective The Family Intervention in Recent-Onset Schizophrenia Treatment (FIRST) study is a randomized controlled trial of patients with schizophrenia spectrum disorders and their caregivers, which is designed to evaluate the effect of telehealth-based, caregiver-focused, study-provided psychoeducation versus usual care (UC) on patient treatment failure (TF). The impact of study-provided psychoeducation on caregiver burden is also investigated. Methods Eligible patients and their designated caregivers were randomly assigned to either the study-provided psychoeducation (≤16 sessions of telehealth-based psychoeducation over 6 months) or UC group, stratified by antipsychotic treatment (paliperidone palmitate or oral antipsychotic). The major TF events (ie, psychiatric hospitalization or intervention, arrest or incarceration, and suicide attempts) were assessed at 3, 6, and 12 months after baseline. A proportional means model using mean cumulative function was used to assess between-group differences in the mean cumulative number of TF events over 12 months. Caregiver burden was assessed using the Involvement Evaluation Questionnaire and 12-item Short Form Health Survey. Results A total of 148 pairs of participants were enrolled in the study, of whom 96 (64.9%) patients and 94 (63.5%) caregivers completed the 12-month follow-up. The mean number of sessions in the study-provided psychoeducation group was 7.7 (SD 5.9). No differences were observed between the study-provided psychoeducation and UC groups in patient outcomes (rates of TF: 70% vs 67%; P=.90) or measures of caregiver burden (assessment of caregiver distress and physical and mental health). However, post hoc analyses revealed lower relapse rates in patients who received paliperidone palmitate than in those who received oral antipsychotics at all time points. Although the FIRST study did not meet the primary end point, several key lessons were identified to inform future caregiver-focused, telehealth-based FP interventions. Lack of study-provided psychoeducation, focus on caregiver-only intervention, difficulties with enrollment, and caregiver–treatment team coordination may have affected the outcomes of the FIRST study. Conclusions Key insights from the FIRST study suggest the potential importance of supporting sufficient caregiver engagement; communication between clinicians, patients, and family members regarding treatment plans; and solidifying the relationship between clinicians providing psychoeducation to the caregiver and patient treatment team. Trial Registration ClinicalTrials.gov NCT02600741; http://clinicaltrials.gov/ct2/show/NCT02600741

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 Other: 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; "Telehealth-Based Psychoeducation"

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 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; "Recent Onset Schizophrenia"

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) 1b-iii) Open vs. closed, web-based (self-assessment) vs. face-to-face assessments in the METHODS section of the ABSTRACT Mention how participants were recruited (online vs. offline), e.g., from an open access website or from a 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 offline 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) 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 Your answer 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) 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 Yes; "A total of 148 pairs of participants were enrolled in the study, of whom 96 (65%) patients and 94 (64%) caregivers completed the 12-month follow-up. The mean number (SD) of sessions in the SPPE group was 7.7 (5.9). No differences were observed between the SPPE and UC groups in patient outcomes (rates of TF; 70% vs 67%; P=.90) or measures of caregiver burden (assessment of caregiver distress and physical and mental health). However, post hoc analyses revealed lower relapse rates in patients who received paliperidone palmitate compared with those who received oral antipsychotics at all time points. Although the FIRST study did not meet the primary endpoint, several key lessons were identified to inform future caregiver-focused, telehealth-based FP interventions. Lack of SPPE, focus on caregiver-only intervention, difficulties with enrollment, and caregivertreatment team coordination may have impacted the outcomes of the FIRST study."

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 Yes; "Key insights from the FIRST study suggest the potential importance of supporting sufficient caregiver engagement, communication between clinicians, patients, and family members regarding treatment plans, and solidifying a relationship between clinicians providing psychoeducation to the caregiver and patient treatment team." Describe the problem and the type of system/solution that is object of the study: intended as stand-alone intervention vs. incorporated in broader health care program? Intended for a particular patient population? Goals of the intervention, e.g., being more cost-effective to other interventions, replace or complement other solutions? (Note: Details about the intervention are provided in "Methods" under 5) 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 briefly explain why the item is not applicable/relevant for your study Yes; "Schizophrenia is a complex, lifelong illness that typically develops in young adults [1] and requires long-term treatment and caregiving, which is frequently provided by family members [2,3]. Caregivers often find that caring for a loved one with schizophrenia is difficult, and struggle with social isolation, financial burden, and physical and emotional exhaustion [4,5]. Family psychoeducation (FP), a guideline-recommended complement to pharmacologic treatment for schizophrenia, has been shown to lower burden and improve functioning in caregivers; it can also lead to improved patient outcomes, including lower rates of relapse and hospitalization [6][7][8][9][10][11] METHODS 3a) Description of trial design (such as parallel, factorial) including allocation ratio 3b) Important changes to methods after trial commencement (such as eligibility criteria), with reasons 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 Yes; "The Family Intervention in Recent-Onset Schizophrenia Treatment (FIRST) study (NCT02600741) was designed to evaluate the impact of FP given specifically to caregivers on outcomes of patients with a schizophrenia spectrum disorder under their care and family burden. In the FIRST study, FP was delivered using MyHealios (a DBA of Healios, Inc.), a telehealth-based study-provided psychoeducation (SPPE) and skills training intervention. MyHealios was developed to incorporate common components of efficacious caregiveroriented FP interventions during the patients' early phase of illness; the FP program was individualized to each caregiver to include education about schizophrenia and its treatment and skills training to improve communication, problem-solving, and coping [21][22][23]. MyHealios sessions were clinician-led, interactive, and online, enabling caregivers to access a professional service from home. This publication reports the primary findings of FIRST and outlines other key learnings from the study." 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 Yes; "FIRST (NCT02600741) was a randomized controlled trial of patients with schizophrenia spectrum disorders and their caregivers that was conducted to evaluate the overall effect of caregiver-focused SPPE and skills training compared with UC on the number of treatment failure (TF) events in patients ( Figure 1)." 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 Your answer 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 Yes; "Study participants were patients with diagnoses of schizophrenia, schizoaffective disorder, or schizophreniform disorder aged 18-35 years who were receiving paliperidone palmitate or oral antipsychotics as prescribed by their clinician. Participants must have had ≥1 TF within 6 months of screening, defined as a psychiatric hospitalization, intensive outpatient psychiatric treatment or partial hospitalization, psychiatric emergency department visit, crisis center visit, mobile crisis unit intervention, arrest/incarceration, or suicide attempt. Caregivers were individuals who provided the patient with assistance and care. They could be members of the immediate or extended family, friends, neighbors, or significant others. Caregivers were included if they were ≥18 years old, had verbal interaction with the patient ≥2 times a week, had internet access, and had not received formal psychoeducation in the past 12 months."

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 subitem not at all important 1 2 3 4 5 essential 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.
https://docs.google.com/forms/d/e/1FAIpQLSfZBSUp1bwOc_OimqcS64RdfIAFvmrTSkZQL2-3O8O9hrL5Sw/viewform?hl=en_US&formkey=dGlKd2… 20/59 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 Yes; "Caregivers randomly assigned to SPPE were invited to attend up to 16 virtual sessions of MyHealios, a telehealth-based FP and skills training program for caregivers of patients with schizophrenia over a 6-month period. Each caregiver was assigned a trained and certified masters-level clinician who was independent from, and had no communication with, the patient's UC team. All MyHealios clinicians received formal training and a training manual; they also underwent a certification process to conduct FP sessions. Routine supervision was provided to MyHealios clinicians, and fidelity measures ensured reliable and standard implementation of the intervention. Study investigators were not associated with MyHealios and received formal training through an investigator meeting and other trainings provided by the sponsor. The MyHealios clinicians worked with the caregivers through live virtual sessions on a one-on-one basis throughout the program. Each virtual session was 40 minutes in length and was conducted online at a time convenient for the caregiver. The web interface included live video of both the caregiver and clinician as well as a chat window to facilitate communication and caregiver participation in interactive activities. The number of sessions and topics delivered were determined jointly by the caregiver and clinician, with the teaching information and skills individually tailored to the caregiver. During each session, the caregiver presented problems that arose from caring for the patient and elaborated with specific examples. The clinician offered training and guidance on appropriate methods to manage the problems identified. Sessions were planned to occur weekly at the beginning of the program and decrease in frequency over the next 6 months as participants learned how to apply the skills in their day-to-day lives. Three modules were identified for initial completion by all caregivers (engagement and goal setting; communications; problem solving and goal achievement). Caregivers could then elect to complete any of the other modules in any order (coping; relapse prevention; delusions; low levels of activity; schizophrenia; anxiety; bipolar disorder; hallucinations; crisis identification and management; alcohol and drugs; depression; engaging the treatment team; treatment adherence)." 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

Your answer
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 Yes; "The study sites were 31 community mental health centers in the United States that provided routine clinical care to patients with schizophrenia." subitem not at all important 1 2 3 4 5 essential 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 Yes; "Assessments, including of TF events, were evaluated at baseline and at 3, 6, and 12 months. Patient illness self-management was evaluated with the self-reported Illness Management and Recovery (IMR) scale [25]. This self-reported scale contains 15 questions, each of which is answered on a 5-point Likert scale with higher scores indicating better recovery status. The IMR total score (range 15-75) is derived as the sum of the 15 item scores. Severity of psychotic symptoms was rated with the Clinical Global Impression of Severity (CGI-S) scale [26] by a member of the patient's treatment team (not a family clinician) who was not masked to treatment assignment. The CGI-S rating scale rates the severity of a participant's psychotic condition based on a 7-point global assessment of symptom severity from 1 (normal, not ill) to 7 (most extremely ill). Caregiver-reported assessments were conducted at the same times as patient assessments. The Involvement Evaluation Questionnaire (IEQ) [27] was used to measure caregiver distress and the 12-item Short-Form Health Survey (SF-12) [28] was used to measure overall perceived physical health (physical component score [PCS]) and mental health (mental health component score [MCS]). The IEQ is designed to measure the consequences of caregiving on family members and friends of patients with schizophrenia. All items are scored on a scale of 0 (never) to 4 (always) and the total score ranges from 0 to 108. Higher IEQ scores indicate higher levels of caregiver burden. The SF-12 is a self-administered 12-item questionnaire designed to cover eight domains of functional health status and well-being: physical functioning, role limitations due to physical health problems, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. These scales are scored from 0 to 100, with higher scores indicating better health. A 1-week recall period was used for PCS and MCS." 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 Your answer

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 Your answer

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 Your answer

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 Your answer

5-iv) Quality assurance methods
Provide information on quality assurance methods to ensure accuracy and quality of information provided [1], if applicable.
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 Your answer 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 Your answer

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 Your answer

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-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 Yes; "The number of sessions and topics delivered were determined jointly by the caregiver and clinician, with the teaching information and skills individually tailored to the caregiver. During each session, the caregiver presented problems that arose from caring for the patient and elaborated with specific examples. The clinician offered training and guidance on appropriate methods to manage the problems identified."

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 Your answer

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 Your answer 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 Not applicable to the study

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. 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 Not applicable to the study ). The IEQ is designed to measure the consequences of caregiving on family members and friends of patients with schizophrenia. All items are scored on a scale of 0 (never) to 4 (always) and the total score ranges from 0 to 108. Higher IEQ scores indicate higher levels of caregiver burden. The SF-12 is a self-administered 12-item questionnaire designed to cover eight domains of functional health status and well-being: physical functioning, role limitations due to physical health problems, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. These scales are scored from 0 to 100, with higher scores indicating better health. A 1-week recall period was used for PCS and MCS." 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

Your answer
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 to the study 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 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 Yes; "After screening, caregivers were randomly assigned 1:1 to SPPE or UC, stratified by patient antipsychotic treatment (paliperidone palmitate or oral antipsychotic; Figure 1)." 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 Not applicable to the study 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 Once eligibility criteria were confirmed at the baseline visit, the site randomized the patient/caregiver using the Parexel Interactive Web Response System (IWRS). Receipt of the Randomization and group assignment was then sent electronically to Site and Healios via the Parexel IWRS.
10) Who generated the random allocation sequence, who enrolled participants, and who assigned participants to interventions 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 subitem not at all important 1 2 3 4 5 essential 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 Once eligibility criteria were confirmed at the baseline visit, the site randomized the patient/caregiver using the Parexel Interactive Web Response System (IWRS). Receipt of the Randomization and group assignment was then sent electronically to Site and Healios via the Parexel IWRS.
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 Not applicable to the study

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) 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

Your answer
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 subitem not at all important 1 2 3 4 5 essential 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 Yes; "The primary efficacy endpoint was the mean cumulative number of TF events experienced by patients over the 12-month study period. A proportional means model using the mean cumulative function was used to assess the between-group difference in the mean cumulative number of TF events over 12 months. The mean cumulative function, as a function of time, was defined as the expected (mean) number of TF events in a given time interval since study day 1. Mean cumulative function for recurrent events and Kaplan-Meier (for time to first event) analyses were performed for overall TF due to any event and for TF due to each of the events specified in the definition of TF. For secondary outcomes, changes from baseline to 3, 6, and 12 months in IEQ, IMR, SF-12, and CGI-S scores were analyzed using mixed-model repeated-measures methodology with terms for study group, time, study group-by-time interaction, and baseline score. Additionally, treatment-emergent adverse events (TEAEs) were presented by treatment group (defined by the antipsychotic medication at baseline: paliperidone palmitate or oral antipsychotics ). The TF rate in the control group was assumed to be 0.50 based on a previous study with a similar endpoint [29]. The effect size in terms of risk ratio of 0.60 was obtained from a metaanalysis of 18 randomized controlled studies examining the effect of face-to-face psychoeducation for caregivers on similar endpoints [30]."

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]). 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 Yes; "The study protocol was approved by an institutional review board and conducted in accordance with the Declaration of Helsinki and consistent with Good Clinical Practices and applicable regulatory requirements. Patients and/or their legally acceptable representatives provided written informed consent."

x26-ii) Outline informed consent procedures
Outline informed consent procedures e.g., if consent was obtained offline or online (how? Checkbox, etc.?), and what information was provided (see 4a-ii). See [6] for some items to be included in informed consent documents.

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 Yes; "Patients and/or their legally acceptable representatives provided written informed consent."

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)

13b) For each group, losses and exclusions after randomisation, together with reasons
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

Your answer
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 Yes; "A total of 170 patient-caregiver pairs were screened in the study, and 151 were randomly assigned to SPPE or UC; of these, 148 patient-caregiver pairs were included in the all-randomized analysis set (SPPE, n=73; UC, n=75; Figure 2)."

14a) Dates defining the periods of recruitment and follow-up
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 Yes; "Ninety-six of 148 (65%) patients and 94 of 148 (64%) caregivers completed 12 months of follow-up; 52 of 148 (35%) patients and 54 of 148 (36%) caregivers discontinued participation before 12 months (Figure 2)."

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 Yes; Figure 2 is the attrition diagram 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 Yes; "The study was initiated on July 24, 2015, and completed on July 5, 2018"; Figure 1 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

Your answer
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 Yes; "Due to difficulties in study enrollment, recruitment was discontinued before the target enrollment of 300 pairs was met, resulting in underpowered statistical analyses."

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 No; the study team did not consider digital divide issues in planning the protocol.

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 Yes; "A total of 170 patient-caregiver pairs were screened in the study, and 151 were randomly assigned to SPPE or UC; of these, 148 patient-caregiver pairs were included in the all-randomized analysis set (SPPE, n=73; UC, n=75; Figure 2). Ninety-six of 148 (65%) patients and 94 of 148 (64%) caregivers completed 12 months of follow-up; 52 of 148 (35%) patients and 54 of 148 (36%) caregivers discontinued participation before 12 months ( Figure 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) 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

Your answer
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 Yes; "Eighty-nine TF events occurred during the study, 44 (70%) in SPPE and 45 (67%) in UC. TF rates were not associated with baseline CGI-S scores and did not differ between the SPPE and UC groups (P=.90) ( Figure 4A). Most TF events were due to psychiatric hospitalization (n=61, 69%) or psychiatric emergency department visits (n=13, 15%). Post hoc analyses also showed lower relapse rates in patients who received paliperidone palmitate compared with those who received oral antipsychotics at all time points ( Figure  4B). Caregiver IEQ total scores, SF-12 PCS and MCS scores, and patient IMR total scores and CGI-S scores all improved from baseline to the follow-up assessments for both the SPPE and UC groups (Table 4). However, there were no statistically significant differences in change from baseline between groups at any timepoints (P>.05 for all comparisons). Similar decreases from baseline in HRU at months 6 and 12 were observed in the SPPE and UC groups." 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).

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

Your answer
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 Not applicable to the study 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 Yes; "Exploratory post hoc analyses were performed to investigate whether higher levels of caregiver participation in the SPPE intervention were associated with improved patient TF outcomes. There was no significant difference in mean number of TF due to any event between caregivers who received more than eight sessions versus the overall UC group (36% vs 37%; P=0.757). In the SPPE group, TF rates were notably higher in patients whose caregivers received at least one session compared with patients of caregivers who received 15 to 16 sessions (77% [10/13] vs 33% [4/12]) ( Table 3)."

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 Your answer 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 Yes; "Of 148 patients, 84 reported at least 1 TEAE during the study (Multimedia Appendix 2). No TEAEs were considered related to study-specific procedures. Three deaths were reported (1 suicide, 1 drug overdose, and 1 cerebral hemorrhage), all in the UC group; none were considered related to trial-specific procedures. Safety in the paliperidone palmitate group was consistent with the known safety profile of paliperidone palmitate in adults, with no new events identified [31][32][33]."

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-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 Your answer

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 Your answer 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). 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 Yes; "No differences were observed over the 12-month study period between the SPPE and UC groups in either patient outcomes (treatment failures such as relapse, illness management, change in clinical functioning) or caregiver outcomes (burden, physical and mental health functioning), with both groups showing significant improvement. This study aimed to fill a gap in the evidence base for FP by providing information on the effects of FP delivered specifically to caregivers using a telehealth-based platform. FP programs share several common characteristics, but can vary considerably in length, setting, and content [34]. Although the results of this study did not show a benefit of the FP intervention at the level of exposure reached, consideration of the study limitations and additional key insights is important for continued development of efficacious telehealth FP interventions."

22-ii) Highlight unanswered new questions, suggest future research
Highlight unanswered new questions, suggest future research.

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 briefly explain why the item is not applicable/relevant for your study Your answer 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 Yes; "Studies of caregiver-directed psychosocial interventions with positive outcomes have typically been longer (mean of 57 weeks) and have provided more overall sessions (mean of 28 sessions) than the present study [30]. The duration of the SPPE program was also shorter than the minimum duration of nine months recommended for FP by some experts [8,34]. However, other factors may have also played a role in the null results. Among the caregivers assigned to SPPE, 26% received either 0 or 1 session of the intervention, and findings of exploratory analyses suggest that the relatively low level of participation in SPPE may have contributed to the negative findings. Furthermore, for caregivers who were engaged in SPPE, the psychoeducational modules that focused on relapse prevention, schizophrenia, and treatment adherence were received by fewer than 50% of caregivers, despite the relevance of these topics to coping with a recent TF experienced by a family member. caregivers. Baseline characteristics of caregivers in the FIRST study may help identify caregivers likely to sufficiently engage with a telehealth-based SPPE intervention and those who may need additional support to fully engage. In a post hoc analysis of the SPPE group comparing baseline characteristics of caregivers receiving ≤8 sessions with those receiving >8 sessions (Multimedia Appendix 1), caregivers who received >8 sessions were more likely to be older and the parent of the individual with schizophrenia. Furthermore, except for the IEQ subscale score of "worrying," the baseline IEQ total and subscale scores were lower among those who received >8 sessions, indicating lower caregiver burden. It is possible that caregivers with higher burden may have been too distressed to engage in the program, regardless of the convenience of internet-based access to interventions and dropped out early. As noted earlier, caregivers who discontinued participation within the first 12 months of the FIRST study were also more likely to be nonparent relatives with poorer health (Table  1). This finding may help future researchers develop "adherence to treatment" strategies that may improve attendance, engagement, and continuous caregiver involvement. Another limitation of the study was that the sample size was smaller than intended, which may have impacted the ability to draw specific conclusions. Additionally, patients were eligible for enrollment only if they had experienced at least one TF within 6 months of screening, indicating a high degree of clinical severity, and the observed TF rate in the FIRST study was higher than expected for comparable studies with similar sample sizes. The recovery period following a TF event (eg, psychiatric hospitalization) may be a particularly vulnerable period that requires an additional level of support not examined in this study to facilitate better outcomes. Furthermore, the median age of patients in the FIRST study was 25.0 years, indicating that they were also early in the course of their illness. Typically, many patients have difficulty accepting their diagnosis [41] and experience high levels of stress, mood symptoms, and suicidal ideation during early illness [6]. The risk of relapse is very high during this period and can predict disease progression [6]. Implementing effective interventions early to prevent repeated relapses may reduce associated declines in cognition and functioning [6]. The SPPE intervention was delivered across many study sites [31], which differed in standard services provided for both the SPPE and UC groups. Another limitation of the implementation of the SPPE intervention is that the clinician provided by MyHealios was not a member of the treatment team, so progress in the program was not integrated with patient care. This also precluded the ability of the clinician to relay potentially important clinical information learned from the caregiver to the treatment team about changes in the patient's condition (eg, emergence of early signs of relapse, treatment nonadherence). The results of this study coincide with a critical moment for telehealth interventions. Although telehealth interventions were only used by 8% of Americans in 2019, engagement with telehealth has grown dramatically in acceptance amidst the COVID-19 pandemic [42,43]. For example, in one community mental health authority in Michigan (Network180), the rates of telehealth services increased from 5% before the pandemic to 84% during the peak of the pandemic in 2020 [44]. Additionally, many mental health professionals have recommended the ethical use of telehealth interventions to provide continued support and care to patients and caregivers throughout the pandemic rather than in-person interventions, noting that telehealth support can be just as effective and may result in fewer missed visits [45][46][47]. Insights on best practices for virtual delivery of mental health interventions are critically needed and new models are under development [48]. Further research using FP methods, taking the lessons learned from the FIRST study into account, is warranted."

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 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 Your answer 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. 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

Your answer
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 Yes; "FIRST (NCT02600741) was a randomized controlled trial of patients with schizophrenia spectrum disorders and their caregivers that was conducted to evaluate the overall effect of caregiver-focused SPPE and skills training compared with UC on the number of treatment failure (TF) events in patients (Figure 1)...Further details of the study design can be accessed at the ClinicalTrials.gov page for the FIRST study [24]." 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 Yes; "Further details of the study design can be accessed at the ClinicalTrials.gov page for the FIRST study [24]." https://docs.google.com/forms/d/e/1FAIpQLSfZBSUp1bwOc_OimqcS64RdfIAFvmrTSkZQL2-3O8O9hrL5Sw/viewform?hl=en_US&formkey=dGlKd2… 56/59 25) Sources of funding and other support (such as supply of drugs), role of funders

X27) Conflicts of Interest (not a CONSORT item)
subitem not at all important 1 2 3 4 5 essential 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 Yes; "This study was funded by Janssen Scientific Affairs, LLC."

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.