First, age 8-17 years. Second, a primary diagnosis according to the ROME-IV criteria of one of the FAPD subtypes—irritable bowel syndrome (IBS) or functional abdominal pain not otherwise specified (FAP-NOS) documented by the child’s regular pediatric physician [31]. The somatic evaluation includes recommended routine medical investigations, that is, growth, fecal calprotectin, and blood samples (TSH [thyroid stimulating hormone], total IgA [immunoglobulin A], IgA-tissue transglutaminase, complete blood count, C-reactive protein analysis, and liver enzymes). Third, stable dosage of regular FAPD-related medication such as laxatives, antidiarrheal medicines, or psychopharmacological medication during the past month.

First, another medical or psychiatric disorder that better explains the symptoms. Second, severe child psychiatric or social problems (eg, high level of suicidal ideation, school absence of more than 40% during the past month, or ongoing substance abuse). Third, ongoing psychological treatment. Fourth, insufficient language or computer skills (patients and parents). Fifth, severe family problems (eg, child maltreatment, parental substance abuse or severe psychiatric illness, and custody fight).

For this study, the Swedish ICBT programs were translated into Danish. The translation procedure was stepwise; first, a direct translation was performed by native Danish speakers familiar with the Swedish language; second, a mutual discussion of the Danish translation took place within the research group, including a discussion of problematic sentences or wordings; third, remaining issues were discussed with the Swedish authors, and a final consensus on the Danish translation was reached. This translation was reviewed by both a Danish language expert and a clinician with experience with the patient group to make further refinements. Finally, in the last step, the revised translation was reviewed again by the Danish research group for final adjustments.

The 4 distinct ICBT programs used in this study are targeted children (8-12 years), adolescents (13-17 years), and the parents of each group, respectively. The treatment lasts for 10 weeks and consists of 10 modules for children, adolescents, and parents of children (with a new module every week) and 5 modules for parents of adolescents (with a new module every other week). An overview of treatment content can be seen in Table 1. The programs include sections with videos, exercises, and quizzes designed to actively engage the child or adolescent in the treatment. Psychoeducation regarding FAPDs, detection of avoidance behavior, a brief mindfulness exercise called “SOL (Stop, observe, let go)” and graded repeated exposure exercises comprise some of the central components covered in the programs for both children and adolescents. The first modules of treatment introduce the above-mentioned concepts whereas later modules focus on repeated exposures. The purpose of “SOL” is Stopping, Observing how the stomach feels, and Letting go of the focus on the stomach and continuing with the activity. The parental programs emphasize supporting their child or adolescent’s exposure, decreasing attention to their child or adolescent’s abdominal symptoms, and prioritizing shared positive activities. Each module ends with planning of the homework assignments which are evaluated first thing in the next module.

The Danish versions of the ICBT programs were pretested in 2 children and 2 adolescents with biweekly feedback from the patients and parents on overall experience and content (telephone interviews performed by a research assistant). Minor modifications were performed, mainly in the adolescent program where the IBS treatment was adjusted to include IBS and FAP-NOS. Furthermore, the mindfulness exercise “SOL” was integrated in the adolescent program to further support the process of labeling thoughts and sensations.

All treatment elements are delivered through a web page specifically designed for this study (Figure 2). Each family will choose 1 primary parent to participate in the treatment at the assessment. All 4 treatment programs are supported by a therapist who provides written feedback after each module. The affiliated therapists will be psychologists and medical doctors with knowledge of CBT. They will receive weekly supervision from Danish specialists in CBT and further supervision from the Swedish research team, who developed and tested the original programs.

Children and adolescents will answer a daily short questionnaire (DSQ) throughout a pretreatment baseline period, randomized to last between 5 and 15 days, throughout the 10 weeks of treatment, and for a final 7-day follow-up period 3 months after treatment. The DSQ is an 8-item questionnaire, designed in line with the SCRIBE (Single-Case Reporting guideline In BEhavioural interventions) guidelines [32], addressing specific targets of the intervention, with items from different validated questionnaires for children and adolescents [32,33]. The full DSQ questionnaire is shown in Textbox 1. The primary outcome in the SCED study is the level of gastrointestinal symptoms assessed using 2 items from the Pediatric Quality of Life Inventory (PedsQL) Gastrointestinal Symptoms Questionnaire [34]. Secondary outcomes include illness worries, avoidance behavior, and level of pain acceptance as measured by the Visceral Sensitivity Index (VSI), irritable bowel syndrome behavioral response questionnaire (IBS-BRQ), and the Chronic Pain Acceptance Questionnaire – Adolescent Short Form (CPAQ-A8), respectively [35-37]. The items have been modified into questions concerning the last 24 hours and are rated on a 0-10 scale (“not at all” 0, “all the time” 10).

Cognitive biases will be assessed before and after treatment using a newly developed experimental design with a computerized web-based task: biases in youth toward gastrointestinal-related stimuli (BY-GIS) [38]. The BY-GIS task consists of a combination of a word task, which is a modified version of the Health Norms Sorting Task [39-41] and a picture task inspired by Gehrt et al [42]. The BY-GIS task is adapted to be appropriate for children and adolescents, featuring gastrointestinal-related stimuli (ie, words related to abdominal symptoms and pictures of food, leisure, and school situations). The BY-GIS task has 3 phases—encoding, free recall, and recognition. In the encoding phase, participants are asked to rate words and pictures presented to them. In the free recall phase, participants are instructed to recall as many words and pictures from the encoding phase as possible, and in the recognition phase, they are presented with words and pictures from the encoding phase along with new words and mirror images of the original pictures. They are then asked to mark which items have been presented to them before. The development, test, and full procedure of the BY-GIS task are described by Bjerre-Nielsen et al [38].

Interoception will be investigated before and after treatment using a psychophysical measure of cardiac interoception, that is, the heart rate discrimination (HRD) task, developed by Legrand et al [43]. During the HRD task, participants have their heart rate monitored using a pulse oximeter while they are presented with auditory and visual stimuli from a computer and answer questions about their sensations of heart rate and subjective confidence in their answers. Thereby, the interoceptive performance (psychometric threshold, slope, and reaction time) and the metacognitive performance (confidence) can be measured. In collaboration with researchers from the Center of Functionally Integrative Neuroscience at Aarhus University, the task was adapted for a younger age group and pretested in 3 children and adolescents. Adaptations consisted of shortening the test by reducing the number of repetitions of trials, as well as replacing written instructions about the conduction of the test with direct oral guidance from a research assistant.

For both studies in substudy 2, we will perform parallel studies on healthy controls. The BY-GIS task was already tested in 96 healthy controls [38], and the interoception test setup will be performed in 60 healthy controls (all aged 8-17 years).

To assess how parental distress, illness worry, and behavior impact the child’s overall treatment effects in various domains and treatment adherence, all participating parents and children or adolescents in the ICBT programs will answer extensive questionnaires before assessment (T1: baseline), halfway through treatment (T2: mid-treatment), at end of treatment (T3: end of treatment), and 3 months after the end of treatment (T4: follow-up; Figure 1). Furthermore, the number of completed treatment modules will be obtained from the treatment web page after the end of treatment. The specific measures to be used are shown in Table 2 and described subsequently.

Parental distress will be assessed by the Symptom Checklist-8, an 8-item subscale from the Symptom Checklist Revised-90, screening for emotional symptoms. Items are rated on a 5-point scale from 0 “not at all” to 4 “a whole lot,” with a total range from 0 to 32. Higher scores indicate more emotional distress [44,45].

Parental illness worries will be assessed by the Health Anxiety by Proxy Scale (HAPYS), a newly developed questionnaire assessing parents’ worries about their child’s health [46]. The questionnaire covers 26 items about health anxiety by proxy, rated on a 5-point scale (from 0 “not at all” or “never” to 4 “a whole lot” or “most of the time”), with a sum score range from 0 to 104. In addition, there are 6 items about the impact of the worries rated on a 4-point scale (from 0 “no” to 3 “yes, severely”), with a sum score range from 0 to 18. Higher scores indicate a high level of health anxiety by proxy and the impact of the anxiety, respectively. HAPYS is a valid measure of health anxiety by proxy with good psychometric properties, including high internal reliability and known-groups validity [47].

Parental illness behavior will be measured by the Adult Responses to Children’s Symptoms, which is originally a 29-item questionnaire [48]. In this study, 2 subscales (monitor and protect subscales) comprising 15 items will be used. Items are rated on a 5-point scale from 0 “never” to 4 “always” with a score range from 0 to 60. Higher scores indicate a higher degree of monitoring and protective responses [49,50].

Gastrointestinal symptoms will be assessed by PedsQL gastrointestinal symptoms [34]. This is a 9-item questionnaire assessing gastrointestinal symptoms related to functional or organic gastrointestinal diseases, during the past month, on a 5-point scale from 0 “never” to 4 “almost always.” Scores are reversed and transformed into a 0-100 scale, with high scores indicating greater quality of life. Pain intensity will be assessed by the Faces Pain Rating Scale – revised (FPS-R) [51]. The FPS-R score includes 6 pictures of faces, each showing an increasing amount of pain and scored on a 2-step scale between “no pain” (0) and “worst pain” (10). The scale is validated in children and adolescents and found to be sensitive to change [52].

Quality of life will be measured by the 23-item PedsQL [53], which is a widely used questionnaire to assess quality of life during the past month in children and adolescents. Items are scored on a 5-point scale from 0 “never” to 4 “almost always.” Scores are reversed and transformed into sum scores between 0 and 100, with high scores indicating higher quality of life.

Overall symptom load will be assessed by the Children’s Somatic Symptom Inventory. It measures somatic symptoms during the last 2 weeks using 24 items, rated on a 5-point scale from 0 “not at all” to 4 “a whole lot,” with a range in scores from 0 to 96. High scores indicate a high symptom load. The questionnaire is found to be reliable and psychometrically sound for children and adolescents with abdominal pain disorders [54].

Depressive symptoms will be measured using the Mood and Feelings Questionnaire Short. It comprises 13 items rated on a 3-point scale from 0 “not true” to 2 “true,” with a range from 0 to 26, where higher scores indicate more depressive symptoms. The questionnaire is found reliable for evaluating depressive symptoms in both clinical and community populations of children and adolescents [55,56].

Anxiety levels will be assessed with 2 different questionnaires—the Spence Children Anxiety Scale Short (SCAS-S) [57,58] for general anxiety, and the Visceral Sensitivity Index-Children (VSI-C) [35,59] for gastrointestinal-specific anxiety. SCAS-S contains 19 items which are answered on a 4-point scale from 0 “never” to 3 “always,” with a total range from 0 to 57, where higher scores indicate higher anxiety levels. The questionnaire is designed for use in children and adolescents, and the short version is validated for screening of anxiety levels in children and adolescents [58]. The VSI-C is a shortened child-adapted version of the VSI for adults [35], with 7 items answered on a 6-point scale from 0 “strongly disagree” to 5 “strongly agree,” with a range from 0 to 42, where higher scores indicate more GI-anxiety. It has been found reliable and valid in children and adolescents with FAPDs [60].

Avoidance and control behavior will be assessed by the IBS-BRQ–Child-adapted short version with 11 items, which is an adapted version of the IBS-BRQ for adults [36]. Items are rated on a 7-point scale from 0 “never” to 6 “always,” with scores ranging from 0 to 66, where higher scores indicate more avoidance. It has been validated for children and adolescents with FAPDs [60].

Illness perception will be assessed by the Brief Illness Perception Questionnaire [61,62], which is a 9-item questionnaire where 8 items are answered on an 11-point scale, and 1 item is an open-ended question. The total score range is 0-80, with higher scores indicating more severe illness perception.

Illness worries will be assessed by the Childhood Illness Attitude Scale with 11 items from the fear factor [63]. The questionnaire is developed and validated for children and adolescents. Items are answered on a 3-point scale from 0 “never” to 2 “most of the time,” with a total score range from 0 to 22, and higher scores indicate more illness worries.

Pain acceptance will be assessed by 2 items from the CPAQ-A8 [37]. One regarding pain willingness and one regarding activity engagement. They are both answered on a 5-point scale from 0 “never true” to 4 “always true,” the item on pain willingness is reversed scored, and higher scores then indicate higher pain acceptance.

Parents will provide information about school absence (hours last month) for children (aged 8-12 years) and about their work absence (days past month). Adolescents will provide information about their own school absence (hours last month).

Adverse events will be assessed by adolescents and parents of children using a binary (yes or no) question and an open-ended question to describe the potential event in detail.

Treatment satisfaction will be assessed by the Modified Experience of Service Questionnaire [64], which is a 13-item questionnaire with 10 items scored from “not true” to “certainly true” and 3 free-text items. The total score range is 0-20 with higher scores indicating a better experience with the treatment.