Study setting 9
The study setting is a digital treatment environment (ENYOY). The Dutch participants will be recruited via Dutch the @ease centers in Amsterdam and Maastricht, plus via social media. The physical study site is the Amsterdam UMC, though most of the interviews with participants, measures, and conversation and measurements will take place online, partly because of the current COVID-19 pandemic.
Eligibility criteria 10
- Age 16-25, and with METC approval possibly at a later stage in the study age 12-25
- Help-seeking for mental health concerns in stages 1a or 1b
- Being able and willing to consent
- Mental disorder in clinical stages 2-4
- Acute risk of self-harm requiring urgent intervention (i.e., suicidal ideation with a current plan and intent to enact this plan)
The interventions will be supported by expert mental health and peer moderators to ensure the safety of the intervention and to directly support participants with moderation, chats and referral to other forms mental health care if needed.
Who will take informed consent? 26a
Once a young person shows interest in the study, the participant information and informed consent forms will be sent. The project staff will inform if this information is received, and after one week the young person will be asked if he/she has any questions, and wants to participate. If a young person wants to participate, an intake will take place to determine if the ENYOY platform would be helpful for the young person, or if other care is needed. If there is a match, within one week a research assistant from the project staff will obtain informed consent before the baseline measurements take place.
Intervention description 11a
The Australian MOST+ platform is based on evidence-based modules for mental health complaints, e.g. Cognitive Behavioral Therapy and mindfulness. Each participant will start on the platform with the ‘onboarding’ process. This is a process where clinical presenting issues and character strengths of the individual will be measured (based on Seligman’s positive psychology framework (47, 48) aligned with the empirically supported VIA questionnaire(49, 50)), following which the algorithm of the platform makes an individual tailored treatment journey suggestion for that person. The project group will consider the following modules (building blocks) of the MOST+ platform for translation and adaptation in the Netherlands:
- Guided therapy journeys: A program of engaging evidence-based therapy (Mindfulness-Based Cognitive Therapy, Cognitive Behavioral Therapy, Meta-Cognitive Therapy, and Social-Cognition strategies) tailored to young person’s needs by automated processes and ENYOY therapists. For example, programs for social anxiety challenges, worrying or depressive symptoms where themed content can be curated to needs of individual. Transdiagnostic processes are found in the domains of attention, memory/imagery, thinking, reasoning and behavior. Activities within a therapy journey entail:
- Reflective Actions: Behavioral or cognitive experiments to improve the ability to notice thought processes in order to build insight and self-awareness of these processes.
- Regular Actions: Assist the young person trial learnings in real-world contexts, hereby generalizing adaptive coping strategies and behaviors (increasing self-efficacy and challenging cognitions via experiments)
- Therapy Comics: Comics that offer an engaging, powerful and accessible means of understanding mental ill health challenges. Narratives offer young people new ways of negotiating the challenges of mental illness.
- Talking Points: Subjects that provide young people with an opportunity to share their effective coping strategies. This encourages social problem solving and peer modeling/learning
- Strength-Based Actions: Actions to assist the young person use their innate character strengths to overcome mental health challenges. Helps young person utilize their strengths (rather than emphasis on alleviating symptoms)
- Myth Busters: Information to help challenge internal stigma and help normalize and validate young people’s experiences
- Inspirational quotes
- Fun Facts: Facts to provide psychoeducation on a particular topic, which can also assist with de-stigmatizing particular experiences
- Personalized therapy toolkit: A personal library of young person’s therapy work and favorite strategies. Therapy activities that are helpful are automatically saved to the toolkit, and young people can save content in their toolkit.
- Safe online social network: A moderated virtual support network of other young people with a shared experience of mental health problems, there to support young persons if and when they need it on their recovery journey
- Professional online support: A base wrap-around support from online peer workers and ENYOY therapist.
In summary the ENYOY platform will contain:
- peer-to-peer online social networking;
- individually tailored interactive psychosocial interventions;
- involvement of expert mental health and peer moderators to ensure the safety of the intervention and to directly support participants with moderation, chats, and referrals to other forms of health care if needed.
Concerning clinical safety, the MOST+ safety protocol builds on the excellent track record of the Australian group managing 24/7 available digital social media interventions safely (51). Manual and automated procedures will be followed. Firstly, information related to clinical risk (posts or messages) will be screened twice daily by therapists. Secondly, MOST+ incorporates an automatic alert system which detects information consistent with increased risk of suicide (via automated monitoring of self-harm-related terms posted in the social feed using previously validated approaches; (51). Any detected increased risk will activate the safety protocol. The therapist will conduct a telephone risk assessment and, where necessary, implement one or more of the following procedures: i) inform the treating clinician (if relevant); ii) inform nominated emergency contact; iii) liaise with suitable emergency services. Additional safety features include a reporting function for users and visible 24/7 emergency numbers. This safety protocol has been approved by three ethics committees and successfully implemented in four pilot studies and two ongoing RCTs (52). Concerning ICT safety, the platform has been adjusted to European laws and safety standards together with a privacy officer.
Criteria for discontinuing or modifying allocated interventions 11b
If mental health complaints of a participant worsen, e.g. develop into stage 2 or above (see introduction), together with the participant the assigned clinical moderator and ENYOY team will look into finding more intensive care. This does not exclude them per se from the platform and current study; they can have additional help and still participate. The form and intensity of additional care will be logged. Following discontinuation, treatment will be offered on a “need for care-clinician’s choice” basis according to existing clinical practice guidelines. Wherever possible, subjects who discontinue the study prior to 12 months from entry will be followed with full regular assessments as per the subjects who continue with the protocol treatment.
Strategies to improve adherence to interventions 11c
The adherence to the platform is continually measured by the platform itself. The clinical moderators have access to usage data as well as the percentage of the personal pathway completed. With the weekly check-up they have with each participant, this will be discussed. In weekly supervision sessions among clinical-, peer moderators, and supervisors adherence of participants will be discussed, and thought about ways to improve when found low.
Relevant concomitant care permitted or prohibited during the trial 11d
All other forms of care, co-interventions, are permitted during the trial. Co-interventions will be registered with the treatment document sheet, and could be used for explorative analysis.
Data will be collected digitally using CASTOR at baseline and after 3, 6 and 12 months.
- Psychological Distress assessed with the Kessler Psychological Distress Scale (K10, (43))
- Social and Occupational Functioning Assessment Scale (SOFAS, (44))
- A measure that assesses empowerment, psychosocial functioning, quality of life, hope and recovery as well as mental symptoms of young people aged 12-25 years (42, 53). The positive health instrument of Huber (http://www.ipositivehealth.com/) qualifies for this purpose but young people commented that the language should be adjusted to better match their age group. There is also an app version of the positive health questionnaire, a method of assessment that is more appealing to young people. The Youth Panel, Huber and the project-group will revise the instrument and validate it in the current study. Mrs. Huber is already involved in the project.
- Stress biomarkers with a smart-watch. Participating clients who are interested will receive a smart-watch that continuously monitors relevant physiological markers of stress during 3 weeks. Available technology (e.g. the TIQ watch E2) is validated, and can measure heart rate variability. In this way, both incidental and cumulative stress can be validly assessed in a naturalistic setting. The participants will receive a short introduction for use about the watch. They can check their stress under different circumstances to discover the relationship between their activities and stress. The watch could also be used during their visits to the ENYOY site to measure the changes in stress level during exercises on the platform, such as mindfulness exercises, self-compassion elements and the anxiety program.
- “Websites journeys” of visitors (number of visits, number of selected activities etc.) will be collected. The website journeys will be anonymously logged under a system generated ID number and session number.
- Open questions asked in an digital online meeting (using MS teams) regarding usability, user friendliness, accessibility, acceptability, connection among peers, and contribution of the platform. The focus will lie on subjective meaning-giving and context, thereby focusing on the individual. The experience and interpretation of the participants will be explored. The presented results will form descriptions and insights into the core constructs, and help improve the ENYOY platform further.
Participant timeline 13
For the participant timeline, see figure below. During the 12 months, participants can use the platform as much as needed.
Sample size 14
Rickwood et al (2015a (31)) reported significant change (effect size Cohen’s d>.5) in the K10 and SOFAS between their first and last Headspace service ratings. In Australia over one-third of Headspace clients had significant improvements in psychological distress (K10; (43)) and a similar proportion in psychosocial functioning (SOFAS; (44)). Sixty percent of clients showed significant improvement on one or both measures. These outcomes were derived from face-to-face services, however similar effects are suspected since a similar framework will be used. Using a paired samples t-test with 80% power and an alpha of 0.01, we would need a sample of 43 subjects to find similar results. Drop-out rates for digital treatment interventions for young people with beginning mental health complaints have been found to range between 2 and 73% (54). Inclusion of 125 subjects in the study would give us ample power to investigate our main hypothesis.
Due to the COVID-19 crisis, there are now too few face-to-face appointments and intakes in the Headspace and other participating centers. Therefore, young people will be recruited via social media and websites for young people as well. Young people aged 12-25 years who show interest will receive an online intake via a secured environment (MS Teams). They will be assessed for the in- and exclusion criteria and demographic variables will be collected. When eligible, a second appointment will take place, where the informed consent can be signed, the first measurements take place (see flow diagrams above), and an account for the platform will be set up.
Data collection and management
Plans for assessment and collection of outcomes 18a
To determine eligibility, a clinical interview and screening will take place. In intervision with a team of psychologist the operationalization of the clinical staging model will (1) be used to determine the stage of mental health problems.
The data on T0, T1, T2 and T3 will be collected in CASTOR, which enables safety and anonymous storing of outcomes. The research team will be trained in how to collect the measures (questionnaires) and in how to use CASTOR.
The K10 is an instrument measuring psychological distress using 10 questions. Strong psychometric qualities have been found (43).
The Social and Occupational Functioning Scale (SOFAS) rates the social and occupational functioning of individuals. It is different from the Global Assessment of Functioning (GAF) known from the DSM-IV since it does not take into account psychological symptoms, and does take into account impairments due to a general medical conditioning. It is usually used for the evaluation of the current time period (44). The SOFAS has a good reliability and validity (55).
The Positive Health Instrument is an instrument that assesses empowerment, psychosocial functioning, quality of life, hope and recovery as well as mental symptoms. The instrument is relatively new and still being researched (53). Overall good reliability was found; the validity has not been researched yet (56).
Plans to promote participant retention and complete follow-up 18b
Participants will receive financial compensation for their time (9 euros per hour) and travel costs will be fully reimbursed at the end and completion of all measurements. All deviations form protocol will be reported.
Data management 19
Upon enrolment, participants will receive a participant number. In a document saved with a password on a protected computer environment the key will be saved. All data will be stored using solely the participant number. As mentioned before, CASTOR will be used for safe storage. All research assistants will be trained to promote safety, and data quality. Random check-ups by other research assistants will be done to assure data is saved correctly. Moreover, data will always be processed by two research assistants, to promote accurateness.
As stated above, the personal information of participants will be stored separately from the data of the research, and is only accessible for the selected research staff, with a password. Moreover, potential participants will get a screening number, using the same process of separate data form personal information. If a young person is interested in participation, he/she can send an email to a protected mailbox, thereby ensuring safety also in the shown interest. Only the research team has access to the mailbox. After the trial the data will be deidentified and saved for 15 years, in the controlled environment.
Statistical methods for primary and secondary outcomes 20a
The study has a longitudinal cohort design. Following Rickwood et al (31) frequencies of each primary presenting concern will be calculated, and age group and sex differences will be assessed by X2 analyses with Bonferroni correction for multiple comparisons. Changes in social functioning (SOFAS) and psychological stress (K10) measures over time will be analyzed in two ways (57). First, repeated measures multivariance analysis of cavariance (MANCOVA) will be used to assess aggregate changes over time in K10 and SOFAS scores according to time point. Time on the platform, therapy pathway complement, number of visits to the ENYOY platform, age group and/or sex will be used as covariates. The statistical relationship between K10 and SOFAS scores will be expressed as a Pearson product-moment correlation coefficient. Differences between the characteristics of clients who provide follow-up data and those who did not will be analyzed by logistic regression. Second, significant change, reliable change and clinically significant change scores will be calculated for the K10 and SOFAS data, as increasingly conditional indicators of change. The criterion for significant change is a moderate effect size (0.5) or greater for the degree of change. The reliable change index (RCI) (indicating reliable improvement or decline) and clinically significant change index (CSI) (cut-off point at which the person is more likely to belong to a non-clinical rather than a clinical population) will be determined using Jacobson and Truax’s method (58). For the K10 scores, the RCI will be estimated as a 7-point change using reliability coefficients reported for a normative group (age group, 16–24 years) in the 2007 National Survey of Mental Health and Wellbeing (59), and will calculated individually on the sample. Using the same norms, the CSI cut-off is estimated to 23 points. For the SOFAS data, an RCI score of 10 will be used (31). Positive health and stress bio markers outcome measures will be analyzed using regression analysis and an MANCOVA to investigate relationships between stress biomarkers, symptoms, empowerment, hope, quality of life and recovery longitudinally. Time on the platform, therapy pathway complement, number of visits to the ENYOY platform, age group and/or sex will be used as covariates. Explorative analyses can be used to research the effect of additional received treatments. Finally, 10 participants will be asked additional questions concerning usability, user friendliness, accessibility, acceptability, connection among peers, and contribution of the platform. The transcripts firstly will be coded using open methods by labeling and merging synonyms, this to ensure data reduction. Secondly the labels will be categorized by axial coding, thereby resulting in systematic arrangement. Finally, selective coding will be done to couple the research question to the central constructs.
Interim analyses 21b
An interim analysis will be conducted to investigate safety and usefulness in participants aged 16-25. If so, inclusion of those aged 12-15 will be considered. In accordance to section 10, subsection 4, of the WMO, the sponsor will suspend the study if there is sufficient ground that continuation of the study will jeopardise subject health or safety. The sponsor will notify the accredit METC without undue delay of a temporary halt including the reason for such an action. The study will be suspended pending a further positive decision by the accredited METC. The investigator will take care that all subjects are kept informed.
Methods in analysis to handle protocol non-adherence and any statistical methods to handle missing data 20c
Multiple imputation (MI) will be used to handle missing data.
Plans to give access to the full protocol, participant level-data and statistical code 31c
Participant-level dataset and statistical code can only be shared upon official request with METC permission. The study protocol will be published and will thereby be accessible.
Oversight and monitoring
Adverse event reporting and harms 22
The safety protocol will be consulted in the case of serious adverse events and adverse events. All serious adverse events and adverse events will be categorized, recorded and reported to sponsor, local trial site, clinical trials unit (CTU), and trial oversight committees. The investigator will report all SAEs to the sponsor without undue delay after obtaining knowledge of the events. The sponsor will report the SAEs through the web portal ToetsingOnline to the accredited METC that approved the protocol, within 15 days after the sponsor has first knowledge of the serious adverse reactions.
All AEs will be followed until they have abated, or until a stable situation has been reached. Depending on the event, follow up may require additional tests or medical procedures as indicated, and/or referral to the general physician or a medical specialist.
SAEs need to be reported till end of study within the Netherlands, as defined in the protocol.
Plans for communicating important protocol amendments to relevant parties (e.g. trial participants, ethical committees) 25
Amendments are changes made to the research after a favorable opinion by the accredited METC has been given. All amendments will be notified to the METC that gave a favorable opinion. All parties (e.g. investigators, participants, researchers, financers) will receive updates on changes.
Dissemination plans 31a
The results of scientific research involving human subjects must be disclosed unreservedly and there are no objections on this regard. The participants can request to receive the results of the study. Moreover presentations for the general public, and other healthcare professionals will take place in order to make found results accessible.