My Symptoms Young - a New Internet-based Programme for Young People With Persistent Physical Symptoms in Primary Care: Exploration of Effect and Health Literacy Characteristics Among Users

IDEA The research programme is an ambitious and dedicated effort aiming at the improvement of functioning and quality of life for young people with bodily distress. Bodily distress is a condition characterised by persistent physical symptoms (PPS) not explained by well-defined diseases. Over time, PPS can develop into a functional somatic disorder, with detrimental impact on the young person's everyday life and opportunities. Thus, early intervention is crucial, but at present, access to specialized treatment of PPS to young people in primary care is very limited.

The investigators have developed the internet-based self-help programme My Symptoms Young as a new digital solution for early intervention of bodily distress. The investigators have applied a high degree of user involvement (young people with PPS) in the development process and are now ready to test the possible impact of the resulting solution.

The present project will 1) test the impact of My Symptoms Young on young people (age 15-25 years) with PPS in primary care and 2) explore the influence of participants' health literacy (HL) and aspects of eHealth literacy (eHL) on their engagement with the programme and whether the level of HL and eHL modifies the impact. The latter might inform improvements regarding provision of adequate support for users with HL and eHL challenges.

BACKGROUND AND RATIONALE The decrease in mental well-being and the increase in distress among young people have become a critical public health concern. Young people with PPS such as pain and fatigue, which cannot be attributed to a specific well-defined disease, are common across various health care settings. Such symptoms are often an indicator of low mental well-being with different expressions of bodily distress, i.e. various physical responses to prolonged stress in susceptible individuals. PPS may cause school absence, high health-care costs, high medication use and low educational attainment. Additionally, PPS increases the risk of mental illnesses such as anxiety and depression. Furthermore, without intervention PPS may develop into severe functional somatic disorders (also classified as somatoform disorders in ICD-10/bodily distress disorder in ICD-11 or somatic symptom disorder in DSM-5), which often require resource-intensive specialized treatment in secondary care, including psychiatric settings.

Internet-based delivery methods allow for early provision of treatments otherwise only available in specialized care. The internet is prominent in young people's daily life and online resources e.g. mindfulness apps are publicly available but rarely target young people. Therefore, to address the treatment needs of youths (aged 15-25) with PPS in primary care, the investigators recently developed My Symptoms Young, a responsive application accessible via a web browser. Through user involvement, this internet-based intervention was redesigned from the existing My Symptoms programme for adults to meet the needs of young people. The content is mainly inspired by cognitive behavioral therapy and contains seven modules on symptom understanding, physical energy, resources and strains, values, thoughts, feelings, self-care, and in addition a closing module on relapse prevention. Furthermore, a module targeting close relatives is available to provide information and guide relatives on how to support participants to actively engage with the programme. Adherence is motivated by text message prompts 1-2 times a week. After a thorough usability evaluation My Symptoms Young is ready for the first clinical testing. However, the usability testing also revealed that some users can be challenged by understanding some of the provided information and exercises.

Health literacy (HL) may be an important precondition for young people's ability to engage with a treatment such as My Symptoms Young. Personal HL refers to individuals' ability to find, understand, and use information and services to inform health-related decisions and actions for themselves and others. Low HL has been linked to maladaptive health behavior and adverse illness perceptions in adults. In internet-based interventions active engagement depends not only on the abilities of the individual but also on the interaction between user and system as encompassed by the concept of eHealth Literacy (eHL). Thus, both HL and eHL characteristics in end users may be important to consider when testing and implementing a new eHealth intervention.

RESEARH AIMS, OVERALL STUDY DESIGN, AND METHODS Aim: To primarily test the possible effects of My Symptoms Young in young people with PPS.

Hypothesis: Symptom intensity and interference with daily activities will improve after the treatment with My Symptoms Young. The effect will be modified by levels of HL and aspects of eHL.

Study design: Open pilot study. Design and reporting will be in accordance with existing recommendations for non-randomized pilot studies.

Methods: 62 participants will receive questionnaires at three time points: Baseline (first login to the programme), End of Treatment (8 weeks after baseline) and 3 months after End of Treatment.

Primary outcomes will be symptom intensity and symptom interference with daily activities as measured by a numeric rating scale (NRS) ranging from 0 to 10. Secondary outcomes will reflect physical symptom burden, psychobehavioural features, health-related quality of life and satisfaction with the programme. HL and eHL measures at baseline will be applied as potential moderators of effect. Covariates will be participant sociodemographics, obtained at baseline, including data on age, gender, education, occupation/sick leave and self-reported chronic disease.

STUDY SETTING AND RECRUITMENT PROCEDURE The study is conducted in close collaboration with healthcare professionals (HCP) in primary care who are mostly likely to be in contact with young people with PPS in the early stage, namely general practitioners (GPs) and practicing pediatricians.

All recruiting HCPs will receive a guide outlining the information they must provide to participants during the recruitment process. Throughout the intervention, the referring HCP is fully responsible for the health care of the young person. Referral and participation will be documented in the participants' primary care medical journal. If participants experience physical or psychological challenges during the project, they are advised to contact the referring HCP, i.e. the responsible healthcare provider. This is also emphasized in the participant information.

RECRUITMENT PROCEDURE The recruitment procedure for the open pilot study can be divided in the following steps

1. Young people with PPS will be recruited by a HCP in primary care. The HCP will determine whether referral to the My Symptoms Young programme is relevant.
2. If the eligible participant is interested to learn more about the research project, the HCP will, with their approval, provide their Danish Personal Identification Number (CPR number) and contact information (phone/email) to the investigator group.
3. When the investigators receives information on the eligible participant, written information material will be sent to the eligible participant through a secure system (eBoks).
4. A research assistent from the investigator group will contact (via phone) the eligible participant, to schedule a video consultation.
5. During the video consultation, a research assistant from the investigator group will provide verbal information about the project. The eligible participant will receive a presentation of the programme and guidance on how to log in and will also have the opportunity to ask questions. Finally study eligibility will be re-assessed and confirmed by the researcher.
6. After ensuring that sufficient verbal information has been provided, informed consent will be obtained. Written consent forms will be collected electronically via a unique link to the consent form hosted on the secure web-based data collection platform, REDCap.
7. Once written consent is obtained, a research assistent from the investigator group will provide the participant with a login code (via e-Boks) to access the programme at www.mine-symptomer.dk. The research assistent will encourage the participant to log in to the programme within a few days.
8. The research assistent will notify the referring HCP about participation (via phone or email).
9. The HCP will then document the referral in the participant's medical journal.

When the participant has signed the consent form, they login to a web portal via the website and access the internet-based programme. The programme is secured by two-factor authentication. The participant login with an unique national electronic identifier (MitID) and a code subsequently provided by the app MitID. Finally, they will need to provide the code provided by the research assistent. At first login, the participant will need to complete a set of questionnaires before accessing the programme. When completed the participant receives access to the programme. The research assistent will follow up with participants by phone after one week if they have not logged into the programme and after three weeks if they have logged in but remained inactive. Participants can decide individually how long they wish to use the programme, but they are encouraged and recommended to engage actively at least twice a week for a minimum of 30 minutes.

The research assistent will contact all participants for an end-of-treatment interview (8 weeks after baseline). The interview will be conducted via telephone and will not be recorded. The aim will be to gather their overall feedback/comments on the programme, and to recommend that the participant engage in a follow-up consultation with their referring HCP. Additionally, participants will be reminded to complete the End of Treatment questionnaire (8 weeks after baseline), and the 3-months follow up questionnaire, which will be delivered via e-Boks.

DATA COLLECTION The study will make use of self-reported questionnaire data from the participating young person and data retrieved from the My Symptoms Young-programme. Participant questionnaires will be administered at baseline (first login to the programme), Endof Treatment (8 weeks after baseline) and 3 months follow-up after End of Treatment. Participant data from the internet-based programme will also be retrieved at End of Treatment (8 weeks after baseline).

Self-report questionnaires

Time points of questionnaire distribution:

Time point 1: Baseline (first login to the programme) Time point 2: End of Treatment (corresponding to 8 weeks after first login) Time point 3: 3-month follow-up after End of Treatment.

Data retrieved from the internet-based programme

The investigators will keep track of young person's eventually accepting and logging into the programme and describe their use of the programme. Their work is logged with regard to:

• Number of logins
• Number of days with login
• Number of modules visited
• Number of visits on every single "page" in the programme
• Number of exercises created using the provided tools.
• Total time spent in the programme
• Time spent per programme module.

INTERVENTION The development of the intervention My Symptoms Young and the subsequent evaluation follows the principles for complex interventions as suggested by the Medical Research Council (MRC-guideline) in 2021.

Development of the My Symptoms Young The current project has been preceded by an iterative development of the first prototype of the intervention supported by the Quality Improvement Committee for General Practice of the Region of Southern Denmark (Kvalitets- og Efteruddannelsesudvalget i Region Syddanmark), J.no.: 20/37140 and the joint regional fund under Danish Regions (Den fælles regionale pulje under Danske Regioner), J. no. EMN-2019-00852 1310643. My Symptoms Young is based on the existing My Symptoms programme for adults and is through user involvement and usability testing redesigned to meet the specific needs of young people.

The process involved a review of evidence on existing self-help interventions for young people with PPS, identification of specific user needs through a qualitative interview study with 11 young people with PPS and usability testing in the further development and refinement of the content of the self-help intervention. Specific modifications have included reduction and simplification of text, adaption of case stories to content relevant for the age group, more focus on suggesting involvement of the family and other close relatives in the programme content and exercises to get support and encouragement.

Content of 'My Symptoms Young' My Symptoms Young is an internet-based self-help programme developed specifically to young persons with moderate PPS seen in primary care. It is designed so the HCP can refer the young person to the programme, when the HCP finds it relevant according to the guiding in- and exclusion criteria.

The young person will get access to an advanced internet-based programme consisting of seven modules, a closing module on relapse prevention, and a module targeting close relatives plus four tools: don't break the chain, goal setting staircase, symptom registration and notebook for reflections. The seven modules target symptom understanding, physical energy, resources and strains, thoughts, feelings, values, and self-care. Participants will gradually gain access to the modules.

The module for close relatives is designed to inform them about the program's content and what participants will experience. It also provides advice and guidance for relatives to support participants in successfully completing the programme. The closing module targets questions for reflection on personal outcome, statistics on work in the programme, results on the Bodily Distress Syndrome (BDS) checklist and relapse prevention. The programme encourages young persons to work with various exercises throughout the different modules but with freedom to choose what to work with. Besides text and exercises, the programme also includes explanatory animations, audio files on case stories, audio files on brief meditations and videos on physical exercises.

ANALYSIS AND STATSTICS Descriptive analyses of participant characteristics, primary and secondary outcomes, and HL and aspects of eHL will be performed at baseline. Linear regression models will be used to analyze the potential changes in outcomes from pre-treatment to post-treatment and three months follow-up. Levels of HL and eHL, respectively, will be added as continuous scores in separate analyses to test their impact on outcomes. If feasible the analyses will be adjusted for sociodemographic characteristics and presence of chronic disease.

Sample size calculation: Sample size is based on a power analysis performed for the adult programme My Symptoms using the same primary outcome, i.e. symptom intensity: detecting a true change in the primary outcome with a probability of 80%, alpha level set at 0.05 and the correlation between measurements in the same individual at baseline and post-treatment assumed to be 0.7, a minimum sample size of 62 would be required, assuming a mean difference of 0.52 and a standard deviation of 0.14 (based on effects reported on eHealth treatment for adults with chronic pain).

ETHICS AND DATA PROTECTION The study will be conducted in accordance with the Declaration of Helsinki and has received approval from the Research Ethics Committee of the Central Denmark Region (reference no. 1-10-72-52-25).

The study has also been registered in the Central Denmark Region's internal research project register (reference no. 1-16-02-266-25) and in Aarhus University's record of processing activities in accordance with Article 30 of the General Data Protection Regulation (GDPR) (reference no. 2022-0367531, registration no. 3892).

All personal data will be processed in compliance with the GDPR and the Danish Data Protection Act, including Section 10, which regulates the processing of personal data for scientific research purposes. Participants will receive written information about the study, including how their personal data will be processed.

EXPECTED OUTCOMES Overall, the intervention is expected to improve the health of young persons with bodily distress in the form of PPS, their functioning and quality of life at an early stage, i.e. before the symptoms become chronic. As part of symptom assessment and management, the HCP will have to draw on physical examinations and potential biomedical investigations etc., but the current programme may both empower the young person and improve how the HCPs in primary care communicate with young people about PPS, hence have the potential to reduce the use of health care, improve symptom coping and illness perception.

The investigators expect the intervention to be able to reduce symptom intensity and interference with daily activities. Over time the investigators expect a reduce in health care use. Thus, part of the idea behind the programme is to move time-consuming information about symptoms from the consultation to the young person's home. Use of primary care may increase temporarily as seen in previous intervention studies, but use of secondary hospital-based health care is expected to decrease.

ADVERSE EVENTS There are no expected side effects or risks in participating in the study. Thus, there are no known harmful effects of internet-based self-help interventions to young people, neither short nor long-term. The disadvantage of participation is mainly the need to spend time with the programme and the scientific evaluation (questionnaires).