Co-designing, evaluating and implementing online supportive care for endometriosis in Australia: study protocol for the hybrid type 1 effectiveness, cost-effectiveness and implementation randomised controlled trial of the CodeEndo program

Endometriosis is a chronic condition involving the growth of tissue similar to the lining of the uterus on other organs, including the pelvic peritoneum, rectovaginal septum and ovaries. 1 2 In Australia alone, endometriosis is estimated to affect 11% of women and individuals presumed female at birth by the age of 44 years. However, it largely remains under-recognised due to the variability of symptoms, reliance on surgical diagnosis and the stigma surrounding menstruation. 2 3 Endometriosis also has a substantial societal burden, with 35 000 yearly hospitalisations in Australia and annual direct costs of $A9.7 billion nationwide, or $A30 000 per affected individual. 3 4 Key symptoms vary but often include pelvic pain, neuropathic pain, dysmenorrhoea, dyspareunia, dyschezia, dysuria and impaired fertility. 5 8 Gastrointestinal symptoms are also common, with >75% of individuals experiencing abdominal pain, diarrhoea, constipation or bloating. 9 13 Endometriosis can also be highly disabling and stigmatising, negatively impacting mental health and health-related quality of life (HRQoL), with common issues surrounding family planning, sexual functioning and finances. 14 16 Recent meta-analytic evidence (k=15) showed that 68% of people with endometriosis experience mild-to-severe psychological distress. 17 The aetiology of endometriosis is complex and is thought to involve multiple hormonal, neurological, immunological and inflammatory factors. 8 10 Diagnosis can take between 4 and 11 years, and usual care—comprising hormones and pain medication—is commonly associated with dissatisfaction and adverse effects, often resulting in treatment discontinuation. 6 14 18 19 Surgical management has an average wait time of 3 years and variable success rates, with studies showing rates of between 20% and 50% of individuals receiving repeat surgery within 10 years. 20 23 Importantly, pain and poor psychological health are known to influence one another and lead to worse treatment outcomes when co-occurring; therefore, addressing psychological health is important for modifying pain response and response to disease progression, as well as improving HRQoL. 24 28 Recognising the inadequacy of current biomedical approaches to endometriosis management and considering its complex psychosocial burden, the British National Institute for Health and Care Excellence (NICE), the Australian National Action Plan for Endometriosis (NAPE) and the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) recommend its interdisciplinary management, highlighting consumer-centred supportive care as an important area for future research. 29 31 Supportive care can be defined as biopsychosocial care provided to enhance quality of life for individuals with an illness or disease, or to address its symptoms and the side effects associated with its treatment. 32 Interdisciplinary management can be defined as a dynamic process involving two or more health professionals with complementary backgrounds and skills, sharing common health goals and exercising concerted physical and mental effort in assessing, planning or evaluating patient care. This is accomplished through interdependent collaboration, open communication and shared decision-making. 33 34 Due to lengthy wait times for endometriosis specialists for diagnosis and treatment and limited access to health services, online-delivered interdisciplinary supportive care can provide widely available and timely access to treatment from any location. Furthermore, the provision of such care, which can be self-directed by patients, using pre-recorded materials created by healthcare providers who are leaders in endometriosis management, allows patients the flexibility to engage with high-quality treatment resources at their own pace and fills a significant gap in service delivery. Given that current supportive care interventions are largely based on existing treatment protocols developed for non-chronic disease populations and considering the unique needs and concerns of those with endometriosis, guidelines suggest that such interventions be co-created with consumers for better engagement and health outcomes. 35 This is further evidenced by the findings of a recent mixed-methods study; the researchers concluded that there was an unmet need for holistic interdisciplinary care that is not just focused on pain, finding that close to 90% of the interviewed women with a diagnosis of endometriosis were using at least one complementary form of treatment. 35 The current study, therefore, proposes to provide a world-first online interdisciplinary supportive care program—CodeEndo—for people with a diagnosis of endometriosis. The CodeEndo program offers participants an array of modular supportive care interventions, including mindfulness, relaxation training, hypnotherapy, cognitive behavioural therapy (CBT), acceptance and commitment therapy (ACT), endometriosis-related psychoeducation, dietary education, yoga and physiotherapy information. These distinct interventions share the common goal of improving health and well-being from a biopsychosocial perspective by harnessing the power of self-management and are complementary when used together. Unlike treatment protocols that primarily target pain, the CodeEndo program offers a whole person approach to the supportive care of endometriosis, addressing multiple endometriosis symptoms and making it suitable for managing different symptom profiles. Mindfulness is commonly defined as ‘paying attention in a particular way, on purpose, in the present moment and non-judgmentally to the unfolding of experience moment by moment’, aiming to foster awareness of emotions, thoughts and behaviour to support self-regulation. 36 Similarly, ACT focuses on reducing the perceived need to eliminate, control or suppress unwanted thoughts or emotions (known as experiential avoidance) to foster a willingness to consciously experience the present moment, while remaining in contact with both positive and negative thoughts and emotions (known as psychological flexibility). 37 38 ACT aims to promote a commitment to engaging in value-driven life activities even in the presence of negative inner experiences. 37 38 CBT incorporates cognitive restructuring techniques designed to help individuals learn to identify and modify their negative thoughts, feelings and behaviours. 39 40 Hypnotherapy is characterised by focused attention, reduced peripheral awareness and enhanced capacity for suggestion, with hypnotic suggestions shown to influence brain areas associated with pain regulation. 41 Relaxation training aims to reduce perceived stress and muscle tightness by decreasing arousal of the sympathetic nervous system through various techniques, including progressive muscle relaxation, guided imagery and breathing exercises. 42 Yoga is a practice aimed at promoting physical and mental health and well-being through physical exercise, body awareness, breath exercises and meditation. 43 Physiotherapy makes use of techniques such as bodily positioning, mobilisation, resistance training and other physical exercises to improve mobility and reduce muscle tension and pain. Dietitians use their scientific understanding of food and nutrition to promote health, prevent disease and manage health conditions. 44 Dietitians provide personalised dietary counselling to individuals to optimise health across all life stages. Finally, psychoeducation provides accurate and evidence-based endometriosis-related information, including its nature, symptoms and treatment options. Although interdisciplinary supportive care for endometriosis is recommended, empirical evidence for its use is currently limited. For instance, evidence for the use of psychotherapy for endometriosis comes from a recent systematic review (k=10), which found that pain-focused psychological interventions, including mindfulness, relaxation training, CBT, ACT, psychoeducation and yoga, significantly reduced pain. The authors concluded that at least half of the studies were of good quality, recommending further research to strengthen findings. 45 Another similar systematic review (k=12) showed that supportive biopsychosocial care, including mindfulness, relaxation training, yoga and CBT combined with physical therapy, improved HRQoL, pain, anxiety, depression, stress and fatigue in endometriosis. 46 The authors concluded, however, that the methodological quality of the studies was low, warranting further investigation by future high-quality RCTs. Evidence for the use of dietary education, physiotherapy and hypnotherapy comes from other sources. For instance, a recent systematic scoping review (k=13) evaluating the breadth and quality of dietary interventions for endometriosis found specific dietary approaches (eg, the low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols or ‘FODMAP’ diet) show promising evidence in alleviating gastrointestinal symptoms and enhancing HRQoL, whereas for other approaches (eg, gluten-free diet) the evidence was limited. 47 Therefore, providing individuals with endometriosis with up-to-date dietary education is essential in facilitating informed decision-making about treatment pathways. Authors of a recent literature review examining the efficacy of physiotherapy for endometriosis concluded that physiotherapy may be effective at reducing pain and improving HRQoL; however, due to the limited number of studies available, the use of physiotherapy may be underestimated. 48 Given the high prevalence of bowel and bladder symptoms in endometriosis, and the potential for pelvic floor muscle physiotherapy to improve dyspareunia and chronic pelvic pain, the evaluation of physiotherapy for endometriosis is necessary. 10 49 Hypnotherapy also has strong evidence for use as a pain management tool to improve physical pain, HRQoL and psychological distress in chronic pain populations. 50 51 This is the first integrative model of care trial for endometriosis, incorporating psychological and mind-body approaches. Such approaches to supportive care are rare, but similar trials have been conducted for irritable bowel syndrome. 52 The nine intervention modules, co-created with consumers and healthcare providers, provide high-quality treatment resources tailored to the needs of those with a diagnosis of endometriosis. CodeEndo also has the potential to be cost-effective, reduce pressure on the healthcare system and decrease disparities in care for regional, rural, remote and lesbian, gay, bisexual, transgender, queer (or questioning), intersex and other populations. Considering the potential positive therapeutic benefits of online interdisciplinary supportive care for endometriosis, further evaluation through rigorous clinical trials is warranted. 5153 57 The primary hypothesis is that CodeEndo will improve HRQoL compared with the waitlist control (WLC), at both 8 weeks and 6 months post-randomisation. Therefore, the current study aims to investigate whether, for people with a diagnosis of endometriosis, those who participate in the 8-week CodeEndo program (n=176), compared with those on a WLC (n=176), the program: Improves HRQoL at 8 weeks post-randomisation (T2) and 6 months post-randomisation (T3); Improves psychological symptoms (anxiety, depression, stress), self-efficacy, menstrual symptoms, bladder symptoms, gastrointestinal symptoms, pain, fatigue, sleep, exercise, symptom bothersomeness and physical and mental well-being at 8 weeks post-randomisation (T2) and 6 months post-randomisation (T3); Is cost-effective, from both healthcare system and societal perspectives. Additionally, we will explore participants’ experiences of the intervention at 8 weeks post-randomisation (T2) and 6 months post-randomisation (T3), and the opinions of endometriosis healthcare providers to consider the potential barriers, facilitators and benefits to ‘real-world’ implementation.

This protocol has received ethics approval in Australia from the Deakin University Human Research Ethics Committee (DUHREC Ref: 2024-157) and has been prospectively registered with the Australian New Zealand Clinical Trial Registry (ANZCTR Ref: ACTRN12623000598684p). Written informed consent will be obtained from all participants. Participation in this study will be voluntary, and participants will be able to withdraw at any time. The study will also adhere to the CONSORT guidelines. Findings will be disseminated through peer-reviewed journal articles, reports and conference publications, and data may form part of a PhD thesis. The findings may also be published on the websites and social media platforms of relevant chronic pain organisations and networks. No identifiable participant data will be shared, published and/or presented. Study data may be shared in a de-identified form with an open or controlled access storage system during the publication process. Participants will be emailed a summary of trial results at the completion of the trial.

A hybrid type 1 effectiveness, cost-effectiveness and implementation randomised controlled trial (RCT) will be conducted. People diagnosed with endometriosis will be randomly allocated (1:1) to the CodeEndo program (intervention group) or to a WLC group for 8 weeks. This study design and choice of comparator is appropriate for a ‘real-world’ effectiveness trial, whereby all participants will continue to access their usual care as required throughout the duration of the trial. The planned 5-year study will commence in September 2023 with ethics and trial preparation and conclude in August 2028 with the completion of dissemination activities. This Australian study will be conducted online. Study advertisement and recruitment will occur through online platforms. The intervention will be delivered via a dedicated web-based research platform (Platform O, V.9.3). 58 Screening and data collection will occur online via the survey platform, Qualtrics. Qualitative interviews will be conducted via Zoom. Implementation will also occur online through a variety of pathways. A total of 352 adults diagnosed with endometriosis will be enrolled in the trial (176 allocated to each study group). Proof of endometriosis diagnosis (including a letter from a doctor, results of histology, operations reports, ultrasound scan or other similar medical document confirming a diagnosis) At least 18 years of age Living in Australia. Not currently pregnant. Proficient in English. The presence of psychological distress as indicated by a score of 16 or more on the Kessler Psychological Distress Scale (K10). 59 Recent endometriosis-related surgery (within the past 3 months). Currently participating in another research study related to pelvic pain, endometriosis or hypnotherapy. No psychological distress (screened via K10—score of 15 or below). Dissociative experiences as indicated by a score of 2.5 or above on the Brief Dissociative Experiences Scale. High risk of harming self/suicide (psychological screening by a qualified practitioner). Significant cognitive impairment (psychological screening by a qualified practitioner). Severe mental illness and/or symptoms, including bipolar I or II disorder, schizophrenia, psychosis, post-traumatic stress disorder or borderline personality disorder, as identified through psychological screening by a qualified practitioner. Substance use/dependence (psychological screening by a qualified practitioner). Following completion of the baseline questionnaire, consenting participants will be randomly assigned (1:1 ratio) to CodeEndo or WLC using a block randomisation sequence with variable block size via Qualtrics randomisation feature to guarantee allocation concealment. Blinding of the study group will not be possible for participants; outcome measures will be self-reported using online questionnaires with automatic reminders. Researchers will not be involved in data collection, nor will they have access to the randomisation sequence. Data analysts will be blinded to group status. Participants will be recruited using a variety of online strategies, including advertisements via endometriosis-related social media platforms (eg, Facebook, Instagram and X) and consumer organisations (eg, Endometriosis Australia, EndoHelp Foundation, EndoZone); matching services (eg, Healthmatch); media such as TV, radio or print and via endometriosis clinics. Interested individuals will be instructed to follow a URL link, which will take them to pre-screening questions, a plain language statement (PLS) and a consent form via Qualtrics (see online supplemental file 1 ). Once participants have passed pre-screening and consent has been provided, they will be required to undergo further eligibility screening via Qualtrics according to the eligibility criteria. If participants pass further eligibility screening, they will then be asked to upload evidence of their endometriosis diagnosis. Once their diagnosis has been confirmed by a member of the study team, participants will be asked several questions via Qualtrics related to their psychological health in preparation for a phone call from a member of the psychology team, who will assess them for relevant psychological exclusions and confirm eligibility. A Consolidated Standards of Reporting Trials (CONSORT) flow chart template is provided in online supplemental file 2 . Healthcare providers will be recruited using online advertisement and snowballing techniques. Interested individuals will be instructed to follow a URL link, which will take them to pre-screening questions, a PLS and consent form via Qualtrics. Once consent has been provided, participants will be automatically redirected to complete the demographic questionnaire. Once this is complete, participants will be contacted by a member of the study team to confirm eligibility for inclusion in the trial. CodeEndo is an 8-week individual online program that consists of nine interventions, including: mindfulness, relaxation training, hypnotherapy, CBT, ACT, psychoeducation, dietary education, physiotherapy information and yoga. Each intervention comprises sub-modules that consist of a mix of video, audio and written resources—as well as homework practices ( table 1 ). Participants will have access to all modules throughout the intervention and will be able to spend as little or as much time as they like accessing the CodeEndo program, allowing for observation of natural use. Participants will also be encouraged to practise (repeat) the modules. The specific goals of the intervention will vary for each person, depending on their individual symptoms, severity of disease, expectations, motivations, life experience and what they want to achieve from the intervention ( figure 1 ). A series of focus groups were conducted prior to the development of the CodeEndo program as the first part of the program’s co-design process, aiming to explore the perceptions of individuals with a diagnosis of endometriosis in terms of current usual care and available services, to gather feedback on CodeEndo intervention content and planned website structure, as well as to identify potential barriers to use and strategies to overcome the barriers. 60 The insights gathered from these groups were analysed and compiled into a report. Together with the latest body of evidence, the nine CodeEndo interventions were then iteratively developed by teams consisting of leading clinicians and researchers in the field of endometriosis, consumers with endometriosis and experienced consumer representatives. To maintain the highest possible standards, separate committees were formed for each intervention, composed of professionals specialising in specific intervention topics, ensuring that the interventions are developed with expert knowledge and care. Further to this, each intervention committee contained at least one expert from an alternative health discipline to provide their interdisciplinary input, for example, the hypnotherapy intervention committee consisted of hypnotherapists, a gastroenterologist and health and clinical psychologists. All intervention materials were reviewed and enhanced with practical recommendations by a consumer representative organisation, the EndoHelp Foundation, to ensure alignment with real-world needs and concerns of those with endometriosis. Additionally, two senior researchers with a lived experience of endometriosis (AM-W, SE) were tasked with reviewing all intervention materials to ensure they aligned with the unique needs of those with endometriosis and focus group recommendations. Participants randomised to the WLC group will be assigned to a waiting list for the duration of the intervention. At the end of the data collection period (6 months post-randomisation), participants in the WLC group will be offered access to the CodeEndo program. Primary, secondary and health economic outcomes will be measured by self-report online questionnaires via Qualtrics at T1 (baseline), T2 (8 weeks post-intervention) and T3 (6 months post-intervention). After completion of each questionnaire, participants will receive a $A10 gift voucher. The following data will be collected from all trial participants at T1, T2 and T3: HRQoL will be measured using the EQ-5D-5L and the endometriosis health profile (EHP): The EQ-5D-5L is a five-item, self-report measure of mobility, self-care, usual activities, pain/discomfort and mental health, with good reliability and validity. 61 62 The EHP is a 30-item, self-report measure of control and powerlessness, social support, emotional well-being and self-image and a further 23-item measure examining work life, relationships with children, sexual intercourse, the medical profession, treatment and infertility, with good reliability, validity and sensitivity to change. 63 64 Psychological health symptoms will be measured by the Depression Anxiety Stress Scale-21 (DASS-21). The DASS-21 is a 21-item, self-report measure of symptoms of depression, anxiety and stress with high internal consistency and test-retest reliability. 65 Self-efficacy will be measured by the Pain Self-Efficacy Questionnaire (PSEQ). The PSEQ is a 10-item, self-report measure of confidence in performing activities of daily living while experiencing pain, with high internal consistency, test-retest reliability and validity. 66 Menstrual symptoms will be measured by the Menstrual Symptoms Questionnaire (MSQ). The MSQ is a 24-item self-report measure of symptoms during and near menstruation with good internal consistency and high test-retest reliability. 67 Fatigue will be measured by the Fatigue Symptom Inventory (FSI). The FSI is a 14-item, self-report measure of fatigue, including its perceived severity, frequency and interference with daily functioning. The FSI has good reliability and validity. 68 69 Gastrointestinal symptoms will be measured by the Gastrointestinal Symptoms Rating Scale (GSRS). The GSRS is a 15-item self-report measure of gastrointestinal symptoms and bowel movements including reflux, abdominal pain, indigestion, diarrhoea and constipation. The GSRS has good reliability and validity. 70 Bladder symptoms will be measured by the Interstitial Cystitis Symptom (ICS) and Problem Index (PI). The ICS and PI are two four-item self-report measures of urinary and pain symptoms with good internal consistency, construct validity and test-retest reliability. 71 Sleep quality will be measured by the Jenkins Sleep Scale (JSS). The JSS is a four-item self-report scale that assesses the frequency and intensity of sleep difficulties with sound psychometric properties. 72 Exercise will be measured by the Brief Physical Activity Scale (BPAS). The BPAS is a six-item, self-report measure of frequency of exercise with good reliability and validity. 73 Pain—including severity, bothersomeness and presence during sexual activity, while using bladder or bowels, or during menstruation—will be measured using a series of Numerical Rating Scales (NRS), rated from 0 to 10. Physical and psychological well-being, as well as the most bothersome symptom, will be measured using a series of NRS, rated from 0 to 10. The following outcomes will be collected from participants at the end of each week over the 8-week intervention period: Changes to participants’ treatment or medication will be collected via open-ended qualitative questions. Pain—including severity, bothersomeness and presence during sexual activity, while using the bladder or bowels, or during menstruation—will be measured using a series of NRS, rated from 0 to 10. Physical and psychological well-being, as well as the most bothersome symptom, will be measured using a series of NRS, rated from 0 to 10. Participants who engage with the dietary education module will be invited to complete a 3-day, food record pre-module and post-module engagement. The food record has been specifically designed for the trial following best practice guidelines. 73 The study team dietitian will also provide a follow-up call to participants who complete the food record to ensure fullness and accuracy of data collected. The primary outcome for the cost-effectiveness analysis is the incremental cost-effectiveness ratio (ICER), calculated as the difference in costs divided by the difference in outcomes. 74 Intervention (CodeEndo program), healthcare, productivity and out-of-pocket costs will be estimated from the Consumer Resource Use and Employment Questionnaire, specifically developed for this trial. Detailed health service and pharmaceutical usage over a 6-month period from baseline will be measured using routinely collected Medicare Benefits Schedule and the Pharmaceutical Benefits Scheme data from Services Australia. After the 8-week intervention period, participants will be provided with optional ongoing access for a further 4 months to monitor engagement and satisfaction over time. Specifically, to assess engagement and satisfaction with the CodeEndo program, all trial participants will be asked to complete a series of questions at the end of each week over the 8-week intervention period, as well as at 6-month follow-up. Questions will include the frequency of module usage and level of satisfaction. Recruitment and retention rates (including reasons for withdrawal) will also be collected throughout the trial. In addition, the online platform used to deliver the CodeEndo intervention will have an in-built tracking system, which will automatically report on user engagement with the program. Trial participants will receive weekly well-being check-in emails, as well as a phone call from a member of the study team in weeks 1, 4 and 8 of the program to determine their safety and the occurrence of any adverse events. Any adverse events reported will be recorded and followed up by a member of the study team with relevant qualifications (ie, psychologist or other clinician). A dedicated trial manager will oversee and monitor the trial, with regular support from the principal investigator and from the broader investigator team as required. Routine data audits will be conducted throughout data collection to ensure data quality and security. Furthermore, a Data Safety Monitoring Board (DSMB) will be established, aligned with national guidelines. 75 The DSMB will consist of three members independent of the study investigators, including one statistician, to assess data validity and safeguard the interests of study participants. PASS software V.14.0.9 (NCSS, USA) was used. A sample of 246 participants (123 in each arm) achieves 80% power to detect a moderate standardised effect size of 0.36 in change between baseline and end of intervention for any of the study outcomes. 16 Data from the HaPPI trial (Healing Pelvic Pain Intervention, with three arms (CBT (n=41), yoga (n=39), education (n=43)); data analysis is in progress) showed effect sizes ranging between 0.2 and 0.5 for most of the outcomes when comparing CBT and education and for the DASS and some dimensions of the QoL scales when comparing yoga versus education. Our study is powered to detect effects that are comparable to those displayed by CBT or yoga alone in the same population. We anticipate that CodeEndo, a multi-component intervention that includes yoga and CBT, will have a larger impact on outcomes. Based on a 30% attrition rate identified in the HaPPI study, we aim to recruit 352 participants (176 per arm). Up to 40 trial participants who complete the CodeEndo program will be invited to participate in individual interviews at T2 (8 weeks; n=20) and T3 (6 months; n=20) post-intervention. Interviews will aim to understand the participant experience of the CodeEndo program, any meaningful change over time, perceived barriers and enablers to engagement and feedback to inform ‘real-world’ implementation efforts. A $A50 gift voucher will be provided to those who participate in an interview. As the interviews are qualitative in nature, a statistical power analysis is not required. Instead, sample size was guided by the information power concept proposed by Malterud et al for qualitative research. 76 Although the initial plan was to conduct focus groups with intervention participants, this was changed to individual interviews for two reasons: (i) the sensitive nature of conversations that may not be appropriate in a group format and (ii) anticipated logistical challenges of organising focus groups. This change was approved via ethics amendment by the Deakin University Human Research Ethics Committee (DUHREC Ref: 2024-157). Up to 15 endometriosis healthcare providers will be invited to participate in semi-structured interviews at T3 (6 months post-intervention) to inform potential barriers, facilitators and benefits to ‘real-world’ implementation of the CodeEndo program, after review of its content. A $A50 gift voucher will be provided to those who participate in the interview. The sample size was determined using the information power guidelines proposed by Malterud et al for qualitative research. 76 Endometriosis-related healthcare provider (eg, nurse, general practitioner, gynaecologist, psychologist, dietitian, physiotherapist). Reside in Australia. At least 18 years of age. Proficient in English. There will be no exclusion criteria. All quantitative statistical analyses will be conducted on an intention-to-treat basis. The intervention effect over 6 months on the primary outcome (QoL) and the other secondary biopsychosocial outcomes will be estimated using linear mixed models. The models will include group (intervention, WLC), time (T1, T2, T3) and time-by-group interaction effects. Generalised mixed models will be used for binary or categorical outcomes. Although mixed-effects models provide unbiased treatment effect estimates under the assumption of missing at random, 77 we will also consider multiple imputation as a sensitivity analysis. Qualitative survey questions and interview data will be transcribed and analysed thematically, following the procedure of template analysis. 78 A cost-consequences analysis will be conducted from a societal perspective, comparing the incremental costs and outcomes via a series of ICERs, for example, the incremental cost per additional responder. A cost-utility analysis will also be conducted at 6 months. Generalised linear modelling and bootstrapping will be used to estimate cost-effectiveness and CIs. 7479 81 Three-day food record data will be analysed for energy, macronutrients, micronutrients and FODMAP composition using FoodWorks Software, 82 incorporating bespoke FODMAP composition data, 83 to assess whether diet composition changed throughout the study. People with endometriosis, consumer advocacy groups and the healthcare providers involved in their care are key stakeholders in this project, from planning through to implementation. Several peak bodies, including EndoHelp Australia, EndoZone, Endometriosis Australia, Jean Hailes for Women’s Health, Western Alliance, Endometriosis Care Centre of Australia, Australasian Gynaecological Endoscopy and Surgery Society and Pelvic Pain Foundation Australia are important partners in this research. As described above, participants’ feedback about the intervention will be collected via qualitative interviews at T2 and T3. If efficacious, the CodeEndo program—an online delivered supportive care model of endometriosis—may be implemented into the current Australian healthcare system across metropolitan and regional areas. Partnerships with key stakeholders as outlined above will assist in the translation of the CodeEndo program into routine practice—leveraging their websites, newsletters, social media, public events and more. As a part of this study, a variety of implementation outcomes summarised in table 2 (further detailed in previous sections of this paper) will be measured throughout the trial period and used to inform future adaptations of the CodeEndo program, as well as to develop strategies for implementation and testing in future research. We will define constructs important for implementation success with respect to the users, stakeholders and context of the intervention, including adoption of the CodeEndo program. This staged approach ensures that CodeEndo is positioned for future implementation to benefit individuals with endometriosis.

In Australia alone, endometriosis affects 11% of people presumed female at birth by age of 44 years. It is a chronic health condition associated with pain, menstrual irregularities, infertility and gastrointestinal symptoms. 1 2 9 10 Endometriosis is also associated with significant economic and personal costs, with HRQoL adversely impacted. 34 14 16 Diagnosis can take up to 4–11 years, resulting in delayed care. 6 18 19 Usual care, comprising hormones, pain medication and surgery, can be associated with adverse effects, discontinuation and symptom recurrence. 18 20 The pathophysiology of endometriosis involves complex biochemical processes that appear to be worsened by contextual and psychological factors. 810 24 28 Research has shown that people with endometriosis experience significant psychosocial burden, including increased stress and psychological health comorbidities. For instance, meta-analytic evidence shows that 68% of individuals with endometriosis experience mild to high distress levels. 17 Common issues include painful sex, family planning, finances and stigmatisation. 14 16 Yet, there are limited consumer-driven evidence-based supportive care resources to ease these biopsychosocial burdens. 45 46 International and national guidelines such as NICE and RANZCOG, in addition to NAPE, now recommend the interdisciplinary management of endometriosis, to address the significant gap in integrated endometriosis care. 29 31 Although there is some evidence that supportive care for those with endometriosis may improve HRQoL and mental health, with the view to influence disease progression and modify pain perception, further high-quality research is recommended. 45 46 This world-first study will examine whether an online modular supportive care program—CodeEndo—that leverages a range of interdisciplinary interventions and targets holistic, biopsychosocial well-being improves endometriosis-related biopsychosocial outcomes compared with a WLC, with HRQoL as the primary outcome. The 8-week CodeEndo program provides an array of interdisciplinary approaches to choose from, including mindfulness, relaxation training, CBT, ACT, hypnotherapy, dietary education, physiotherapy information, yoga and endometriosis psychoeducation. Although CodeEndo has been developed with and for the Australian context, given the nature of the program (ie, online, self-directed, nine evidence-based modules), implementation with populations and healthcare settings beyond Australia is likely to be feasible. If CodeEndo is shown to be efficacious, there is potential for language and cultural adaptation, and broader international access and implementation to support people with endometriosis. CodeEndo will be co-created together with those with endometriosis, their healthcare providers and consumer advocacy groups. Uniquely, CodeEndo will be delivered online via a tailored web-based research platform and will be self-directed by participants through pre-recorded intervention modules, where participants can spend as long or as little as they like accessing the CodeEndo program. It will assist with overcoming accessibility barriers to care, including time, location and resource constraints, and will provide insight into which supportive care interventions are most sought after by consumers. The cost-effectiveness of CodeEndo will also be examined, and qualitative feedback will be provided from participants and their healthcare providers to support the implementation of CodeEndo into a real-world setting. Should this trial demonstrate the effectiveness of CodeEndo, the multidisciplinary research team is well-positioned to facilitate scale-up across relevant healthcare settings, and to leverage Australian government support and health policy change to sustain implementation.