A Digital Health App to Assess Decisional Capacity to Provide Informed Consent: Protocol for a Randomized Controlled Trial

Background Any study with human subjects must have a robust consent process to ensure that participants understand the study and can decide whether they want to be involved. Investigators must determine whether a potential study participant is able to make an informed decision and what modifications or supports are needed to maximize participation in decision making. A variety of approaches have been used to modify consent forms and the consent process to increase the research participants’ decisional capacity. This protocol describes a randomized controlled trial (RCT) of a digital health app to support decision making among individuals contemplating providing consent to participate in a clinical trial. Objective The objective of this RCT will be to determine if the use of a tablet-based app facilitates greater participation in and satisfaction with the consent process compared with standard practice and identify which individual factors are associated with better response to the decision aid. We hypothesize that the tablet-based version of the consent process will promote more informed decision making, including decisions that are more consistent with individual preferences and values expressed during qualitative data collection. Methods A two-arm RCT will be conducted in a sample of approximately 100 individuals with fragile X syndrome in their homes across the United States. Results Data analysis will be completed by late 2018. Conclusions By developing and testing a novel consent decision aid, we will have a better understanding of whether and how technological support can optimize the fit between the decisional capacity and the decisional process. Trial Registration ClinicalTrials.gov NCT02465931; https://clinicaltrials.gov/ct2/show/NCT02465931 (Archived by WebCite at http://www.webcitation.org/72Q3xJQAw) International Registered Report Identifier (IRRID) PRR1-10.2196/10360

yes: all primary outcomes were signi cantly better in intervention group vs control partly: SOME primary outcomes were signi cantly better in intervention group vs control no statistically signi cant difference between control and intervention potentially harmful: control was signi cantly 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? * Protocol paper, no  1a-i) Identify the mode of delivery in the title Identify the mode of delivery. Preferably use "web-based" and/or "mobile" and/or "electronic game" in the title. Avoid ambiguous terms like "online", "virtual", "interactive". Use "Internet-based" only if Intervention includes non-web-based Internet components (e.g. email), use "computer-based" or "electronic" only if o ine products are used. Use "virtual" only in the context of "virtual reality" (3-D worlds). Use "online" only in the context of "online support groups". Complement or substitute product names with broader terms for the class of products (such as "mobile" or "smart phone" instead of "iphone"), especially if the application runs on different platforms.
subitem not at all important 1 2 3 4 5 essential subitem not at all important 1 2 3 4 5 essential 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 brie y explain why the item is not applicable/relevant for your study "A Digital Health App" to Assess Decisional Capacity to Provide Informed Consent: Randomized Controlled Trial Protocol 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 brie y explain why the item is not applicable/relevant for your study Non-web-based components or co-interventions were not used 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 brie y explain why the item is not applicable/relevant for your study Target audience 1b) ABSTRACT: Structured summary of trial design, methods, results, and conclusions NPT extension: Description of experimental treatment, comparator, care providers, centers, and blinding status.
subitem not at all important 1 2 3 4 5 essential 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) Does your paper address subitem 1b-i? * Copy and paste relevant sections from the manuscript abstract (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "Objective: The objective of this RCT will be to determine if the use of a tablet-based app facilitates greater participation in and satisfaction with the consent process compared with standard practice and identify which individual factors are associated with better response to the decision aid. We hypothesize that the tabletbased version of the consent process will promote more informed decision making, including decisions that are more consistent with individual preferences and values expressed during qualitative data collection. Methods: A 2-arm RCT will be conducted in a sample of approximately 100 individuals with fragile X syndrome in their homes across the United States. Results: Data analysis will be completed in early 2018.
Conclusions: By developing and testing a novel consent decision aid, we will have a better understanding of whether and how technological support can optimize the t between the decisional capacity and the decisional process." subitem not at all important 1 2 3 4 5 essential 1b-iii) Open vs. closed, web-based (self-assessment) vs. face-toface assessments in the METHODS section of the ABSTRACT Mention how participants were recruited (online vs. o ine), 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 o ine trials, an open trial (open-label trial) is a type of clinical trial in which both the researchers and participants know which treatment is being administered. To avoid confusion, use "blinded" or "unblinded" to indicated the level of blinding instead of "open", as "open" in web-based trials usually refers to "open access" (i.e. participants can self-enrol). (Note: Only report in the abstract what the main paper is reporting. If this information is missing from the main body of text, consider adding it) Does your paper address subitem 1b-iii?
Copy and paste relevant sections from the manuscript abstract (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "Objective: The objective of this RCT will be to determine if the use of a tablet-based app facilitates greater participation in and satisfaction with the consent process compared with standard practice and identify which individual factors are associated with better response to the decision aid. We hypothesize that the tabletbased version of the consent process will promote more informed decision making, including decisions that are more consistent with individual preferences and values expressed during qualitative data collection. Methods: A 2-arm RCT will be conducted in a sample of approximately 100 individuals with fragile X syndrome in their homes across the United States.
Results: Data analysis will be completed in early 2018. Conclusions: By developing and testing a novel consent decision aid, we will have a better understanding of whether and how technological support can optimize the t between the decisional capacity and the decisional process." subitem not at all important 1 2 3 4 5 essential subitem not at all important 1 2 3 4 5 essential 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 brie y explain why the item is not applicable/relevant for your study Copy and paste relevant sections from the manuscript abstract (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "Objective: The objective of this RCT will be to determine if the use of a tablet-based app facilitates greater participation in and satisfaction with the consent process compared with standard practice and identify which individual factors are associated with better response to the decision aid. We hypothesize that the tabletbased version of the consent process will promote more informed decision making, including decisions that are more consistent with individual preferences and values expressed during qualitative data collection. Methods: A 2-arm RCT will be conducted in a sample of approximately 100 individuals with fragile X syndrome in their homes across the United States. Results: Data analysis will be completed in early 2018. Conclusions: By developing and testing a novel consent decision aid, we will have a better understanding of whether and how technological support can optimize the t between the decisional capacity and the decisional process." 2a-i) Problem and the type of system/solution Describe the problem and the type of system/solution that is object of the study: intended as standalone 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) subitem not at all important 1 2 3 4 5 essential Does your paper address subitem 2a-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "This study will be the rst systematic investigation of decisional capacity in FXS in which we develop and evaluate a decision aid with the intent of enhancing participation in the informed consent processes. METHODS 3a) Description of trial design (such as parallel, factorial) including allocation ratio Does your paper address CONSORT subitem 2b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "The primary research question was, "Does a tablet-based app facilitate greater participation in and satisfaction with the consent process compared with standard practice?" We hypothesize that the tablet-based version of the consent process will promote more informed decision making, including decisions that are more consistent with individual preferences and values expressed during qualitative data collection. The secondary research question was, "What individual factors, such as IQ, autism status, or executive function, are associated with better response to the decision aid?" We hypothesize that all individuals with FXS will bene t from the tablet-based version, but those with higher functioning levels may bene t the most. Potential advantages of a tablet-based approach to patient education include consistent content and delivery, active learning, privacy, potentially greater access than a human health educator, and potential cost-effectiveness [44]. We expect that the interactive nature of the app will foster greater involvement in the decision making, a sense of empowerment, greater self-e cacy, and more satisfaction." 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 brie y explain why the item is not applicable/relevant for your study "We will use a 2-arm, parallel-design, randomized control trial (RCT) with a 1:1 allocation ratio. Participants will be randomized into either the control or experimental group. As shown in Table 1, both groups will be exposed to the same informed consent content but delivered through different channels-a digital informed consent app (experimental) or paper informed consent or usual practice (control). The content of both versions of the informed consent describes the requirements for participating in a hypothetical clinical trial for a fake prescription drug for FXS. Both versions include IRB-required information (eg, study procedures, study duration, and compensation). The digital informed consent app does not meet all of the regulated technical requirements for electronic informed consent (ie, the signature component)." Does your paper address CONSORT subitem 3b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study There were no changes to eligibility criteria after initiation of the trial 3b-i) Bug xes, Downtimes, Content Changes Bug xes, Downtimes, Content Changes: ehealth systems are often dynamic systems. A description of changes to methods therefore also includes important changes made on the intervention or comparator during the trial (e.g., major bug xes or changes in the functionality or content) (5-iii) and other "unexpected events" that may have in uenced study design such as staff Does your paper address subitem 3b-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study There were no changes, xes, or downtime events during the trial.
Does your paper address CONSORT subitem 4a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "Eligibility will be determined by a person's scores on an initial assessment, which includes a standardized IQ and autism measure. Participants will be excluded if they receive a score of 30 on the IQ measure; receive a score between 31 and 40 on the IQ measure and have a diagnosis of autism with severe autism symptoms as noted on a standardized autism measure; or are determined to have other behavioral challenges that would preclude their inclusion (eg, mutism and severe aggression). These exclusion criteria cutoffs were established to ensure a minimal level of comprehension and adaptive behavior for the study; IQs of 35 are indicative of severe ID." 4a-i) Computer / Internet literacy Computer / Internet literacy is often an implicit "de facto" eligibility criterion -this should be explicitly clari ed.
Does your paper address subitem 4a-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Digital literacy at baseline was not a consideration during the trial.
subitem not at all important 1 2 3 4 5 essential 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. o ine), e.g., from an open access website or from a clinic, and clarify if this was a purely web-based trial, or there were face-to-face components (as part of the intervention or for assessment), i.e., to what degree got the study team to know the participant. In online-only trials, clarify if participants were quasi-anonymous and whether having multiple identities was possible or whether technical or logistical measures (e.g., cookies, email con rmation, phone calls) were used to detect/prevent these.
Does your paper address subitem 4a-ii? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "Each study session will occur in the individual's home and will be videotaped to allow subsequent coding of individual engagement in the decisional process.
Approximately 10 days prior to the visit, the participant or their primary caregiver will be sent the standard paper consent form for a hypothetical clinical trial. All participants, including parents and caregivers, will be informed that the clinical trial is hypothetical. Participants will be asked to review the consent form as they would any research consent form." 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. Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "In this study, the following 3 primary methods will be used for recruitment: recontacting families who have participated in prior longitudinal assessment studies conducted by the research team; recruiting through the FX research registry maintained by the University of North Carolina at Chapel Hill; and announcing the research on the National Fragile X Foundation website. We have been highly successful in recruiting FX study participants, including a large national survey of >1000 families [45] so anticipate few problems in recruiting an adequate sample." Does your paper address CONSORT subitem 4b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "Each study session will occur in the individual's home and will be videotaped to allow subsequent coding of individual engagement in the decisional process. Approximately 10 days prior to the visit, the participant or their primary caregiver will be sent the standard paper consent form for a hypothetical clinical trial. All participants, including parents and caregivers, will be informed that the clinical trial is hypothetical. Participants will be asked to review the consent form as they would any research consent form." 4b-i) Report if outcomes were (self-)assessed through online questionnaires Clearly report if outcomes were (self-)assessed through online questionnaires (as common in webbased trials) or otherwise.
subitem not at all important 1 2 3 4 5 essential 5) The interventions for each group with su cient details to allow replication, including how and when they were actually administered Does your paper address subitem 4b-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "On the day of the visit, parents and individuals with FXS who are their own legal guardian will be asked to complete a 5-to 10-minute pretest to assess their or their child's belief and attitudes about participating in clinical trials. Pretest items included questions such as participants' possible reasons for participating in clinical trials, the likelihood of participating, and whom they think should make the decision about enrolling in a trial (full list of domains in "Study Outcomes" section below). Participants will then complete either the experimental or control group informed consent procedure. Both the control and experimental groups will be asked the modi ed MacCAT examination items throughout the informed consent process to assess the decisional capacity. The questions are identical for each group. After the informed consent procedure, all participants will again be asked to complete the posttest questions about their beliefs and attitudes about clinical trials." 4b-ii) Report how institutional a liations are displayed Report how institutional a liations are displayed to potential participants [on ehealth media], as a liations with prestigious hospitals or universities may affect volunteer rates, use, and reactions with regards to an intervention.(Not a required item -describe only if this may bias results) Does your paper address subitem 4b-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Institutional a liations are not displayed in the intervention material.
subitem not at all important 1 2 3 4 5 essential 5-i) Mention names, credential, a liations of the developers, sponsors, and owners Mention names, credential, a liations of the developers, sponsors, and owners [6] (if authors/evaluators are owners or developer of the software, this needs to be declared in a "Con ict of interest" section or mentioned elsewhere in the manuscript).
Does your paper address subitem 5-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "Design and development of the intervention material and the principles that informed our approach are described elsewhere [42]. The FXS Decision Aid is a tablet-optimized, responsive Web app that delivers content through 3 major components as follows: scenario-based vignettes to present key concepts on clinical trials, informed consent, and other IRB-required material; quiz items to assess the decisional capacity based on the MacCAT-CR; and a tile sorting activity to provide a values clari cation exercise at the conclusion of each session. Material for the Decision Aid was developed using input from a multidisciplinary committee of experienced developmental or clinical psychologists, clinicians, and communication scientists, based on data from qualitative interviews conducted with caregivers and individuals with FXS. Technical activities were informed by an agile, user-centered design approach, existing literature on the principles of universal design, and best practices for developing decision aids. The DA was implemented in Hypertext Markup Language 5 using CreateJS libraries for integration of animated multimedia, audio narration, and active tasks. The user interface and user experience were optimized for iOS tablet-based deployment and support interaction through standard touchscreen gestural controls (eg, swipe, tap, drag, and pinch). A custom case management system enables event logging for each study participant, including case identi er, interaction speci cs, and session time stamps. Built-in app analytics report events via JavaScript Object Notation packets sent over Secure Hypertext Transfer Protocol to a data management service that logs events, storing data in an encrypted relational database. subitem not at all important 1 2 3 4 5 essential 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 brie y explain why the item is not applicable/relevant for your study Design and development of the intervention material and the principles that informed our approach are described elsewhere [42]. The FXS Decision Aid is a tablet-optimized, responsive Web app that delivers content through 3 major components as follows: scenario-based vignettes to present key concepts on clinical trials, informed consent, and other IRB-required material; quiz items to assess the decisional capacity based on the MacCAT-CR; and a tile sorting activity to provide a values clari cation exercise at the conclusion of each session. Material for the Decision Aid was developed using input from a multidisciplinary committee of experienced developmental or clinical psychologists, clinicians, and communication scientists, based on data from qualitative interviews conducted with caregivers and individuals with FXS. Technical activities were informed by an agile, user-centered design approach, existing literature on the principles of universal design, and best practices for developing decision aids. The DA was implemented in Hypertext Markup Language 5 using CreateJS libraries for integration of animated multimedia, audio narration, and active tasks. The user interface and user experience were optimized for iOS tablet-based deployment and support interaction through standard touchscreen gestural controls (eg, swipe, tap, drag, and pinch).
A custom case management system enables event logging for each study participant, including case identi er, interaction speci cs, and session time stamps.
Built-in app analytics report events via JavaScript Object Notation packets sent over Secure Hypertext Transfer Protocol to a data management service that logs events,

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 brie y explain why the item is not applicable/relevant for your study The intervention material was not updated during the trial.

5-iv) Quality assurance methods
Provide information on quality assurance methods to ensure accuracy and quality of information provided [1], if applicable.
Does your paper address subitem 5-iv?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Design and development of the intervention material and the principles that informed our approach are described elsewhere [42]. The FXS Decision Aid is a tablet-optimized, responsive Web app that delivers content through 3 major components as follows: scenario-based vignettes to present key concepts on clinical trials, informed consent, and other IRB-required material; quiz items to assess the decisional capacity based on the MacCAT-CR; and a tile sorting activity to provide a values clari cation exercise at the conclusion of each session. Material for the Decision Aid was developed using input from a multidisciplinary committee of experienced developmental or clinical psychologists, clinicians, and communication scientists, based on data from qualitative interviews conducted with caregivers and individuals with FXS. Technical activities were informed by an agile, user-centered design approach, existing literature on the principles of universal design, and best practices for developing decision aids. The DA was implemented in Hypertext Markup Language 5 using CreateJS libraries for integration of animated multimedia, audio narration, and active tasks. The user interface and user experience were optimized for iOS tablet-based deployment and support interaction through standard touchscreen gestural controls (eg, swipe, tap, drag, and pinch).
A custom case management system enables event logging for each study participant, including case identi er, interaction speci cs, and session time stamps.
Built-in app analytics report events via JavaScript Object Notation packets sent over subitem not at all important 1 2 3 4 5 essential 5-v) Ensure replicability by publishing the source code, and/or providing screenshots/screen-capture video, and/or providing owcharts of the algorithms used Ensure replicability by publishing the source code, and/or providing screenshots/screen-capture video, and/or providing owcharts of the algorithms used. Replicability (i.e., other researchers should in principle be able to replicate the study) is a hallmark of scienti c reporting.
Does your paper address subitem 5-v?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study

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 brie y explain why the item is not applicable/relevant for your study Design and development of the intervention material and the principles that informed our approach are described elsewhere [42].

5-vii) Access
Access: Describe how participants accessed the application, in what setting/context, if they had to pay (or were paid) or not, whether they had to be a member of speci c group. If known, describe how participants obtained "access to the platform and Internet" [1]. To ensure access for editors/reviewers/readers, consider to provide a "backdoor" login account or demo mode for reviewers/readers to explore the application (also important for archiving purposes, see vi).
Does your paper address subitem 5-vii? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Design and development of the intervention material and the principles that informed our approach are described elsewhere [42]. The FXS Decision Aid is a tablet-optimized, responsive Web app that delivers content through 3 major components as follows: scenario-based vignettes to present key concepts on clinical trials, informed consent, and other IRB-required material; quiz items to assess the decisional capacity based on the MacCAT-CR; and a tile sorting activity to provide a values clari cation exercise at the conclusion of each session. Material for the Decision Aid was developed using input from a multidisciplinary committee of experienced developmental or clinical psychologists, clinicians, and communication scientists, based on data from qualitative interviews conducted with caregivers and individuals with FXS. Technical activities were informed by an agile, user-centered design approach, existing literature on the principles of universal design, and best practices for developing decision aids. The DA was implemented in Hypertext Markup Language 5 using CreateJS libraries for integration of animated multimedia, audio narration, and active tasks. The user interface and user experience were optimized for iOS tablet-based deployment and support interaction through standard touchscreen gestural controls (eg, swipe, tap, drag, and pinch).
A custom case management system enables event logging for each study participant, including case identi er, interaction speci cs, and session time stamps.
Built-in app analytics report events via JavaScript Object Notation packets sent over Secure Hypertext Transfer Protocol to a data management service that logs events, Does your paper address subitem 5-viii? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Design and development of the intervention material and the principles that informed our approach are described elsewhere [42]. The FXS Decision Aid is a tablet-optimized, responsive Web app that delivers content through 3 major components as follows: scenario-based vignettes to present key concepts on clinical trials, informed consent, and other IRB-required material; quiz items to assess the decisional capacity based on the MacCAT-CR; and a tile sorting activity to provide a values clari cation exercise at the conclusion of each session. Material for the Decision Aid was developed using input from a multidisciplinary committee of experienced developmental or clinical psychologists, clinicians, and communication scientists, based on data from qualitative interviews conducted with caregivers and individuals with FXS. Technical activities were informed by an agile, user-centered design approach, existing literature on the principles of universal design, and best practices for developing decision aids. The DA was implemented in Hypertext Markup Language 5 using CreateJS libraries for integration of animated multimedia, audio narration, and active tasks. The user interface and user experience were optimized for iOS tablet-based deployment and support interaction through standard touchscreen gestural controls (eg, swipe, tap, drag, and pinch).
A custom case management system enables event logging for each study participant, including case identi er, interaction speci cs, and session time stamps. Built-in app analytics report events via JavaScript Object Notation packets sent over Secure Hypertext Transfer Protocol to a data management service that logs events, storing data in an encrypted relational database.

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 brie y explain why the item is not applicable/relevant for your study Design and development of the intervention material and the principles that informed our approach are described elsewhere [42]. The FXS Decision Aid is a tablet-optimized, responsive Web app that delivers content through 3 major components as follows: scenario-based vignettes to present key concepts on clinical trials, informed consent, and other IRB-required material; quiz items to assess the decisional capacity based on the MacCAT-CR; and a tile sorting activity to provide a values clari cation exercise at the conclusion of each session.

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 brie y explain why the item is not applicable/relevant for your study Design and development of the intervention material and the principles that informed our approach are described elsewhere [42]. The FXS Decision Aid is a tablet-optimized, responsive Web app that delivers content through 3 major components as follows: scenario-based vignettes to present key concepts on clinical trials, informed consent, and other IRB-required material; quiz items to assess the decisional capacity based on the MacCAT-CR; and a tile sorting activity to provide a values clari cation exercise at the conclusion of each session. Material for the Decision Aid was developed using input from a multidisciplinary committee of experienced developmental or clinical psychologists, clinicians, and communication scientists, based on data from qualitative interviews conducted with caregivers and individuals with FXS. Technical activities were informed by an agile, user-centered design approach, existing literature on the principles of universal design, and best practices for developing decision aids. The DA was implemented in Hypertext Markup Language 5 using CreateJS libraries for integration of animated multimedia, audio narration, and active tasks. The user interface and user experience were optimized for iOS tablet-based deployment and support interaction through standard touchscreen gestural controls (eg, swipe, tap, drag, and pinch).
A custom case management system enables event logging for each study participant, including case identi er, interaction speci cs, and session time stamps.
Built-in app analytics report events via JavaScript Object Notation packets sent over Secure Hypertext Transfer Protocol to a data management service that logs events, essential 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 brie y explain why the item is not applicable/relevant for your study Not applicable

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 standalone 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 de ned pre-speci ed primary and secondary outcome measures, including how and when they were assessed Does your paper address subitem 5-xii? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "Each study session will occur in the individual's home and will be videotaped to allow subsequent coding of individual engagement in the decisional process. Approximately 10 days prior to the visit, the participant or their primary caregiver will be sent the standard paper consent form for a hypothetical clinical trial. All participants, including parents and caregivers, will be informed that the clinical trial is hypothetical. Participants will be asked to review the consent form as they would any research consent form.
On the day of the visit, parents and individuals with FXS who are their own legal guardian will be asked to complete a 5-to 10-minute pretest to assess their or their child's belief and attitudes about participating in clinical trials. Pretest items included questions such as participants' possible reasons for participating in clinical trials, the likelihood of participating, and whom they think should make the decision about enrolling in a trial (full list of domains in "Study Outcomes" section below).
Participants will then complete either the experimental or control group informed consent procedure. Both the control and experimental groups will be asked the modi ed MacCAT examination items throughout the informed consent process to assess the decisional capacity. The questions are identical for each group. After the informed consent procedure, all participants will again be asked to complete the posttest questions about their beliefs and attitudes about clinical trials." subitem not at all important 1 2 3 4 5 essential Does your paper address CONSORT subitem 6a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "The following measures will be collected as part of the study protocol: time spent with decision aid or in discussion with research assistant; perceptions about reasons to participate in trials (eg, altruism; pre-and posttest item); likelihood of enrolling in a clinical trial (pre-and posttest item); the preferred level of involvement in the decision (pre-and posttest item); self-e cacy related to decision-making ability (pre-and posttest item); level of engagement in the decision-making process ) Any changes to trial outcomes after the trial commenced, with reasons 6a-ii) Describe whether and how "use" (including intensity of use/dosage) was de ned/measured/monitored Describe whether and how "use" (including intensity of use/dosage) was de ned/measured/monitored (logins, log le 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 "Pretest measures, the intervention or control condition, and posttest measures will all be conducted on the same day during an approximately 1-hour study session.
The pre-and posttest measures will take approximately 15 minutes to complete, and the control and intervention condition will last approximately 30 minutes. No additional follow-up is planned." 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? 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 brie y explain why the item is not applicable/relevant for your study Not applicable 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 brie y explain why the item is not applicable/relevant for your study "We have conducted a power analysis using a between-subjects design (ie, participants are randomized to the control or experimental group) to determine the recommended sample size. With a sample size of 70 (35 participants per group), we will have 90% power to detect an effect size of 0.75." https://docs.google.com/forms/d/e/1FAIpQLSfZBSUp1bwOc_OimqcS64RdfIAFvmrTSkZQL2-3O8O9hrL5Sw/viewform?hl=en_US&formkey=dGlKd2… 45/66 8a) Method used to generate the random allocation sequence NPT: When applicable, how care providers were allocated to each trial group 8b) Type of randomisation; details of any restriction (such as blocking and block size) Does your paper address CONSORT subitem 7b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Not applicable Does your paper address CONSORT subitem 8a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Your answer Does your paper address CONSORT subitem 8b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "We will use a strati ed, block randomization method to assign participants to the control or experimental group. Two strati cation variables will be used-verbal IQ score (3 levels) and age (2 levels). Age was selected as a randomizing variable because children and adolescents under 18 are not able to provide informed consent, only assent, as their parents are their legal guardians. Verbal IQ was selected as a second variable because we had a small sample size and wanted to control for any possible effects on the outcome variables. However, we could have also chosen to account for any possible group differences based on IQ through statistical analyses. Given that enrollment for the RCT will be done on a rolling basis, a 10-block, 2-group design will be used. Thus, we will randomize 10 participants at a time into either the control or experimental group. Furthermore, we will utilize a random number generator (www.randomizer.com) to make the assignments." 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 10) Who generated the random allocation sequence, who enrolled participants, and who assigned participants to interventions Does your paper address CONSORT subitem 9? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "We will use a strati ed, block randomization method to assign participants to the control or experimental group. Two strati cation variables will be used-verbal IQ score (3 levels) and age (2 levels). Age was selected as a randomizing variable because children and adolescents under 18 are not able to provide informed consent, only assent, as their parents are their legal guardians. Verbal IQ was selected as a second variable because we had a small sample size and wanted to control for any possible effects on the outcome variables. However, we could have also chosen to account for any possible group differences based on IQ through statistical analyses. Given that enrollment for the RCT will be done on a rolling basis, a 10-block, 2-group design will be used. Thus, we will randomize 10 participants at a time into either the control or experimental group. Furthermore, we will utilize a random number generator (www.randomizer.com) to make the assignments." Does your paper address CONSORT subitem 10? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Authors 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 subitem not at all important 1 2 3 4 5 essential 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 brie y explain why the item is not applicable/relevant for your study "Owing to the nature of the study, participants and data collectors were not blinded to the group assignment." 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".
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 brie y explain why the item is not applicable/relevant for your study "In the analyses, we will examine the effect of the app on the decisional capacity, controlling for sociodemographic characteristics and severity of delay. We will rst conduct bivariate analyses comparing the decisional capacity, decision-making preferences, and the likelihood of trial participation across the 2 study groups (tablet vs standard procedure), using chi-square tests for categorical outcomes and t tests for continuous outcomes. In addition, we will conduct multiple regression models to compare study outcomes by the study group after controlling for demographics and severity of developmental delay. Linear regression models will be conducted for continuous outcomes (eg, decisional capacity scores and preferences) and logistic regression models for categorical outcomes (eg, the likelihood of participating in a hypothetical trial). Within these models, we will test for interactions between study group and demographic characteristics to identify the differential impact of the intervention on particular subgroups. For example, testing an interaction between study group and severity of delay would allow us to determine whether the tabletbased intervention is more or less successful among more impaired participants." 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]).
12b) Methods for additional analyses, such as subgroup analyses and adjusted analyses Does your paper address subitem 12a-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "In the analyses, we will examine the effect of the app on the decisional capacity, controlling for sociodemographic characteristics and severity of delay. We will rst conduct bivariate analyses comparing the decisional capacity, decision-making preferences, and the likelihood of trial participation across the 2 study groups (tablet vs standard procedure), using chi-square tests for categorical outcomes and t tests for continuous outcomes. In addition, we will conduct multiple regression models to compare study outcomes by the study group after controlling for demographics and severity of developmental delay. Linear regression models will be conducted for continuous outcomes (eg, decisional capacity scores and preferences) and logistic regression models for categorical outcomes (eg, the likelihood of participating in a hypothetical trial). Within these models, we will test for interactions between study group and demographic characteristics to identify the differential impact of the intervention on particular subgroups. For example, testing an interaction between study group and severity of delay would allow us to determine whether the tabletbased intervention is more or less successful among more impaired participants." X26) REB/IRB Approval and Ethical Considerations [recommended as subheading under "Methods"] (not a CONSORT item) subitem not at all important 1 2 3 4 5 essential Does your paper address CONSORT subitem 12b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "In the analyses, we will examine the effect of the app on the decisional capacity, controlling for sociodemographic characteristics and severity of delay. We will rst conduct bivariate analyses comparing the decisional capacity, decision-making preferences, and the likelihood of trial participation across the 2 study groups (tablet vs standard procedure), using chi-square tests for categorical outcomes and t tests for continuous outcomes. In addition, we will conduct multiple regression models to compare study outcomes by the study group after controlling for demographics and severity of developmental delay. Linear regression models will be conducted for continuous outcomes (eg, decisional capacity scores and preferences) and logistic regression models for categorical outcomes (eg, the likelihood of participating in a hypothetical trial). Within these models, we will test for interactions between study group and demographic characteristics to identify the differential impact of the intervention on particular subgroups. For example, testing an interaction between study group and severity of delay would allow us to determine whether the tabletbased intervention is more or less successful among more impaired participants." Does your paper address subitem X26-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "Each study session will occur in the individual's home and will be videotaped to allow subsequent coding of individual engagement in the decisional process.
Approximately 10 days prior to the visit, the participant or their primary caregiver will be sent the standard paper consent form for a hypothetical clinical trial. All participants, including parents and caregivers, will be informed that the clinical trial is hypothetical. Participants will be asked to review the consent form as they would any research consent form."

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)

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 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 brie y explain why the item is not applicable/relevant for your study Not applicable Does your paper address CONSORT subitem 13a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Not applicable Does your paper address CONSORT subitem 13b? (NOTE: Preferably, this is shown in a CONSORT ow diagram) * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study 16-i) Report multiple "denominators" and provide de nitions Report multiple "denominators" and provide de nitions: Report N's (and effect sizes) "across a range of study participation [and use] thresholds" [1], e.g., N exposed, N consented, N used more than x times, N used more than y weeks, N participants "used" the intervention/comparator at speci c pre-de ned time points of interest (in absolute and relative numbers per group). Always clearly de ne "use" of the intervention.
Does your paper address subitem 16-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Not applicable 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).
Does your paper address subitem 16-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Not applicable 17a) For each primary and secondary outcome, results for each group, and the estimated effect size and its precision (such as 95% con dence interval) subitem not at all important 1 2 3 4 5 essential 17b) For binary outcomes, presentation of both absolute and relative effect sizes is recommended Does your paper address CONSORT subitem 17a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Not applicable 17a-i) Presentation of process outcomes such as metrics of use and intensity of use In addition to primary/secondary (clinical) outcomes, the presentation of process outcomes such as metrics of use and intensity of use (dose, exposure) and their operational de nitions is critical. This does not only refer to metrics of attrition (13-b) (often a binary variable), but also to more continuous exposure metrics such as "average session length". These must be accompanied by a technical description how a metric like a "session" is de ned (e.g., timeout after idle time) [1] (report under item 6a).
Does your paper address subitem 17a-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Not applicable Does your paper address CONSORT subitem 17b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Does your paper address subitem 19-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Not applicable 19-ii) Include qualitative feedback from participants or observations from staff/researchers Include qualitative feedback from participants or observations from staff/researchers, if available, on strengths and shortcomings of the application, especially if they point to unintended/unexpected effects or uses. This includes (if available) reasons for why people did or did not use the application as intended by the developers.
Does your paper address subitem 19-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Not applicable 22) Interpretation consistent with results, balancing bene ts and harms, and considering other relevant evidence NPT: In addition, take into account the choice of the comparator, lack of or partial blinding, and unequal expertise of care providers or centers in each group subitem not at all important 1 2 3 4 5 essential subitem not at all important 1 2 3 4 5 essential 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 brie y explain why the item is not applicable/relevant for your study

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 brie y explain why the item is not applicable/relevant for your study Despite the strength of the evaluation design and scalability, the major limitation of this study is the focus on assessing decision making to participate in a hypothetical clinical trial. Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Not applicable 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.

21-i) Generalizability to other populations
Does your paper address subitem 21-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Not applicable Does your paper address CONSORT subitem 23? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study This study has been registered with ClinicalTrials.gov (NCT02465931).
25) Sources of funding and other support (such as supply of drugs), role of funders X27) Con icts of Interest (not a CONSORT item) subitem not at all important 1 2 3 4 5 essential Does your paper address CONSORT subitem 24? * Cite a Multimedia Appendix, other reference, or copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Yes Does your paper address CONSORT subitem 25? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study The authors thank the individuals with FXS and their families who participated in this research study. This study was funded by a grant from the Eunice Kennedy Shriver National Institute for Child Health and Human Development (R01HD071987-01A1). The ndings and conclusions in this report are those of the authors and do not necessarily represent the o cial position of the National Institutes of Health.
X27-i) State the relation of the study team towards the system being evaluated In addition to the usual declaration of interests ( nancial or otherwise), also state the relation of the study team towards the system being evaluated, i.e., state if the authors/evaluators are distinct from or identical with the developers/sponsors of the intervention. yes no Other: STOP -Save this form as PDF before you click submit To generate a record that you lled in this form, we recommend to generate a PDF of this page (on a Mac, simply select "print" and then select "print as PDF") before you submit it.
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