Online randomised e-hypnotherapy for chronic pelvic pain study (REST): comparing e-hypnotherapy with relaxation and waitlist to improve pain, cost-effectiveness and biopsychosocial outcomes

Chronic or persistent pelvic pain (CPP) is a common and disabling health condition associated with poor health-related quality of life (HRQoL). 1 Although various definitions exist, recent European Association of Urology guidelines have adopted an inclusive approach that encompasses male and female anatomy of intermittent or constant pain between the hips and below the umbilicus for at least 3 months. 2 Pain can involve the anal, scrotal, bladder, prostate, perineal and vaginal/vulval regions, with and without obvious pathology. While prevalence rates vary due to different study designs, definitions of pelvic pain and the inclusion of female and/or male anatomy, it is estimated that CPP affects 15–34% of people worldwide. 3 4 CPP is associated with substantial personal and societal burden; endometriosis, a common form of CPP, alone costs up to $21 000 per woman each year in health, productivity and carer-related expenses, with a total estimated economic burden per year in Australia of $6.5 billion. 5 CPP can be highly disabling and stigmatising, severely impacting mental health, sexual function and HRQoL. 6 7 People with CPP are approximately five times more likely to experience depression and anxiety compared with the general population. 8 Pain and psychological health mutually influence each other and lead to worse treatment outcomes when co-occurring. 9 10 Although psychological interventions are recommended as part of a multidisciplinary treatment plan for CPP, 11 12 their efficacy remains unclear in treating the range of symptoms associated with CPP. Therefore, further definitive clinical trials investigating their efficacy are needed. 13 Hypnotherapy holds promise in addressing pain, and associated psychological distress, in CPP. 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. 14 Although not regarded as a replacement for medical care, hypnotherapy can be used as part of multidisciplinary pain management to improve pain, HRQoL and psychological distress. 15 16 Hypnotherapy is cost-effective, has few side effects and can be made easily accessible through online delivery, as opposed to analgesic medication. 16 One limitation, however, is the lack of comparison of hypnotherapy to active control groups to understand whether hypnotherapy works beyond the benefits of relaxation. 17 Well-designed control conditions that allow masking (ie, which aim to mimic the delivery, time and attention received by the intervention group, with only their content differing, allowing for blinding of participants to group allocation) are needed to provide high-level evidence of CPP hypnotherapy efficacy. A meta-analysis of 669 patients with chronic pain demonstrated that hypnotherapy reduced chronic pain outcomes compared with standard care (effect size=0.60), outperforming other psychological interventions (eg, biofeedback, cognitive-behavioural therapy, guided imagery and progressive muscle relaxation) for non-headache pain (effect size=0.46). 18 A systematic review of six trials found that hypnotherapy was associated with a 30% reduction in pelvic pain severity in individuals with irritable bowel syndrome (IBS) compared with psychotherapy and waitlist controls. 19 Although another recent systematic review and meta-analysis of nine studies of CPP unrelated to gastrointestinal conditions (four randomised controlled trials (RCTs) and five case series) found no significant differences in pain or QoL for hypnotherapy compared with controls, the results were limited due to a lack of standardised interventions, poor experimental design and limited inclusion of psychosocial outcomes. 17 In a recent feasibility and pilot study of prerecorded online hypnotherapy (hereon referred to as e-hypnotherapy), significant reductions were found in screening measures of anxiety and depression, and a non-significant reduction in pain, of a small to moderate effect size ( d =0.43), in patients who received e-hypnotherapy compared with waitlist (n=20 women with CPP). 13 Although underpowered to detect efficacy, by having shown improvements in anxiety and depression, this study demonstrates the importance of assessing a range of outcomes related to CPP, including psychological factors. In addition to potential efficacy, this study demonstrated the acceptability of e-hypnotherapy as an economical way of delivering hypnotherapy that addresses access barriers related to cost and availability of health professionals. 20 22 Emerging evidence indicates that e-hypnotherapy leads to improvements similar to hypnotherapy delivered by a therapist, either face-to-face or online. The need for such research has increased following the uptake of telehealth services due to the coronavirus pandemic. 22 Hasan et al 23 found that hypnotherapy for IBS delivered online and face-to-face both resulted in significant improvements in symptoms, HRQoL, anxiety and depression, with only slightly better outcomes for the face-to-face group. In a recent RCT of e-hypnotherapy (prerecorded, online) for cancer survivors (n=109), significant and moderate-to-large improvements in pain, anxiety, fatigue and sleep disturbance (effect sizes ranging from 0.44 to 0.88) were found. 24 Given that e-hypnotherapy appears to be effective, easily accessible and inexpensive, the development of e-hypnotherapy as an alternative telehealth-delivered treatment for improving CPP symptoms is warranted. Current guidelines recognise the importance of psychological approaches to address the complex needs of individuals with CPP. 2 However, significant knowledge gaps exist regarding effective treatment, including a lack of RCTs with methodological rigour that examine a range of outcomes, and the development of novel delivery mechanisms that increase access and uptake. This study addresses these gaps by evaluating an e-hypnotherapy programme that will be designed to allow personalisation and accessibility across geographic locations compared with a carefully designed relaxation condition that allows masking on a broad range of outcomes. Using an RCT design, the purpose of this study is to explore whether a 7-week e-hypnotherapy intervention (n=44), compared with active relaxation control (n=44) and waitlist control (n=44): Improves pain at 7 weeks post-randomisation (T2) and 6 (T3) and 12 (T4) months post-randomisation. Improves symptoms of psychological distress (anxiety, depression, stress), as well as HRQoL, pain catastrophising, self-efficacy, central sensitisation, somatic symptoms, fatigue, symptom bothersomeness and sleep at 7 weeks (secondary outcomes), 6 and 12 months post-randomisation. Is cost-effective (from both healthcare system and societal perspectives). Qualitative data will explore participants’ experiences immediately after the intervention and in long-term follow-up, as well as the opinions of eligible healthcare providers who will consider potential barriers/facilitators to ‘real-world’ implementation.

A parallel-group, investigator-blinded, RCT will be conducted. People diagnosed with CPP will be randomly allocated (1:1:1) to an e-hypnotherapy (intervention), relaxation (control group 1/active control) or waitlist (control group 2) group for 7 weeks. Randomisation will occur through computer-generated random sequences embedded in the online Qualtrics platform, ensuring allocation concealment, with no stratification. To ensure participants are blinded to group allocation, the programme materials for the intervention and active control group will be masked, where the delivery of active control aims to mimic the time and attention received by the intervention group. The study will be advertised as a hypnosis study (with two intervention groups and a waitlist group) to achieve masking. The statisticians and health economists performing the analyses will be blinded to group status. Participants in all groups will continue their usual medical care. The entirety of the study will be conducted virtually from October 2024 to January 2026. Study advertisement/ recruitment will occur through online platforms. The trial will be delivered via a dedicated website (Platform O). Screening and data collection will occur online via the survey platform Qualtrics. Interviews will be conducted via Zoom. Implementation will occur online via partnerships. A block randomisation sequence with variable block size will be embedded in Qualtrics for allocation concealment. Participants are unlikely to know the difference between the intervention and active control group, unless they have extensive experience with hypnotherapy. Previous exposure to hypnotherapy within the last 6 months will be an exclusion criterion, and participants will be asked if they thought they were in the hypnosis or relaxation group as part of a postintervention questionnaire to understand whether masking was achieved. At least 132 Australian adults living with CPP will be assigned across the three trial groups (at least 44 in each group). Inclusion criteria will include Self-reported chronic pelvic pain (Numerical Rating Scale (NRS)) * , with pain persisting for at least 3 months. At least mild psychological distress as indicated by a score of 16 or above on the Kessler Psychological Distress Scale (K10). At least 18 years of age. Capacity to provide informed consent. Currently residing in Australia. Not pregnant nor seeking to become pregnant in the next 7 weeks. English-speaking or sufficient level of English to understand the trial intervention, answer relevant questionnaires and participate in online intervention. *Chronic pelvic pain is defined as “chronic or persistent pain perceived in structures related to the pelvis of either men or women. It is often associated with negative cognitive, behavioral, sexual, and emotional consequences as well as with symptoms suggestive of lower urinary tract, sexual, bowel, pelvic floor, or gynecological dysfunction.” 2 Exclusion criteria will include Absence of pain as indicated by a score <3 on the pain NRS. Recent pelvic area surgery (within the past 3 months). Recent engagement in hypnotherapy (within the past 6 months). Dissociative experiences as indicated by a score of ≥2.5 on the Brief Dissociative Experiences Scale. High risk of harming self/suicide (psychological screening by qualified practitioner). Significant cognitive impairment (psychological screening by qualified practitioner). Severe mental illness and/or symptoms (bipolar I or II, schizophrenia, psychosis, post-traumatic stress disorder, borderline personality disorder; psychological screening by qualified practitioner). Substance use/dependence (psychological screening by qualified practitioner). Concurrent participation in other clinical trials. Inclusion criteria will include CPP-related healthcare provider (eg, doctor, nurse, specialist, psychologist, dietician, etc). Reside in Australia. At least 18 years of age. Proficient in English. There will be no exclusion criteria. Up to 40 trial participants who have completed the REST programme (20 hypnotherapy and 20 relaxation participants) will complete interviews at T2 (7 weeks), T3 (6 months) and T4 (12 months) post-intervention. Up to 15 CPP-related healthcare providers will also be interviewed at T4. Participants will be recruited using a variety of online advertising strategies. Advertisements will be published through CPP-related social media platforms (eg, Facebook). Participants will also be recruited through the help of consumer organisations (eg, Chronic Pain Australia). Services matching people interested in trials to existing trials, such as HealthMatch, will also be used. Further, recruitment may occur through CPP-related media, such as dedicated social media groups. Interested individuals will be instructed to follow a URL link which will take them to pre-screening questions, a plain language statement and consent form via Qualtrics. Once participants have passed prescreening and consent has been provided, they will undergo further eligibility screening for pain, psychological distress and dissociative symptoms via Qualtrics. If participants pass further screening, they will then be asked several questions relating to their mental health via Qualtrics in preparation for a phone call from a member of the clinical psychology team who will assess for relevant psychological exclusions, if participants are deemed eligible, they will be approved for participation in the study. Ineligible participants may be able to request an additional follow-up phone call from the study psychologist to receive further guidance on how and where to seek psychological support. They will also be encouraged to use external support services such as contacting their GP or LifeLine. Participants will be reimbursed for the time taken to complete study questionnaires ($20 gift card for completing T2 and two $10 gift cards for T3 and T4 questionnaires = $40 total) and follow-up interviews, if selected ($30 gift card ×3 follow-up interviews = $90 total). All adults experiencing CPP will be encouraged to apply (including women, men, transgender and gender diverse, non-binary and intersex people). The sample size was calculated for pain severity measured on the NRS (0–10) using the software GLIMMPSE, assuming a baseline mean of 6 and an SD of 2.2 in all groups. 13 At 7 weeks (post-treatment), we assumed a mean of 5.5 in the waitlist group, 5 in the relaxation group and 4.3 in e-hypnotherapy (a clinically meaningful reduction in mean pain score on the NRS is 1.74). Assuming a correlation between baseline and post-treatment of 0.75 and using the linear mixed effects models, a sample of 102 achieves 80% power (α=0.05; two-sided tests). Assuming 30% attrition, consistent with our pilot findings, we will recruit 132 participants across the three groups (44 in each group). Healthcare providers will also be recruited using the above strategies with the addition of word-of-mouth/snowballing techniques to recruit participants within study investigators’ contact networks. Participants randomised to e-hypnotherapy will have access to a 7-week online intervention which will include one pain education session and seven self-directed e-hypnotherapy modules ( figure 1 ). The e-hypnotherapy programme will include stages of hypnotic induction, deepening, suggestion and reorientation techniques. Hypnotic induction is the process of preparing the person to go into a state where they are focused and open to suggestion. Deepening extends the induction phase and suggestions involve the practice of giving direct or indirect instructions to the participants to help them resolve their presenting problem(s). Finally, reorientation techniques guide the participant from trance back into full awareness, particularly by refocusing their perceptions on their own body and the external environment. 25 Participants will be able to ‘choose their own adventure’ and be provided with a range of hypnotic induction, deepening, suggestion and reorientation techniques, including direct and indirect styles, visual and non-visual options, and mindfulness-based elements. Although the intervention allows personalisation of certain elements (eg, choice of imagery or script style), all modules contain core standardised therapeutic components targeting pain, coping and psychological well-being. They will also be able to choose a male or female voice.We will control for any potential variation in outcomes through the use of linear mixed models and sensitivity analyses, as well as monitoring engagement and content selection. To inform selection of recordings, participants will be provided with information in the form of written descriptions about the themes (eg, water or clouds) in each recording. Trigger warnings will also be provided (eg, “This script contains the mention of water pools and hot water. If any of these things trigger you in any way, then we recommend you select another script”). Participants will be able to choose the most appropriate combination of recordings based on their personal preferences and/or triggers. Participants will be asked to complete one module (approximately 40 min) per week for 7 weeks; however, they will have access to all modules throughout the 7 weeks, allowing for observation of natural use. Participants will be encouraged to practise/repeat modules throughout the 7 weeks and will receive weekly reminders and check-in emails. The specific goals of the intervention will vary for each person depending on their individual symptoms, severity of disease, expectations and motivations, life experience and what they want to achieve from the intervention. Engagement in the e-hypnotherapy programme will be monitored through study team check-in phone calls, occurring at two time points: weeks 3 and 7. Strategies to maximise engagement will include regular email reminders, open access to modules over the 7-week programme and an engaging and user-friendly platform. Treatment fidelity problems are not anticipated as the interventions will be prerecorded. Participants will be contacted to provide feedback if they do not engage or if they choose to withdraw from the study. Participants randomised to relaxation will have access to a 7-week online intervention which includes one pain education session and seven self-directed relaxation modules ( figure 2 ). The relaxation intervention will be designed as an active control to allow masking with the format, delivery and follow-up aiming to mimic the intervention group. The relaxation programme will include stages of non-hypnotic induction, relaxation and reorientation techniques. Like in the hypnosis programme, participants will be able to ‘choose their own adventure’ by selecting their choice of non-hypnotic induction and reorientation audio recordings, as well as prefer listening to a male or female voice. The relaxation materials will be designed symmetrically to the intervention, meaning they address the same overarching and specific themes and use the same tools and techniques where non-hypnotic versions are possible. Participation and adherence requirements and strategies to maximise adherence will mirror those in the intervention. Participants randomised to the waitlist control will be assigned to a waiting list and will be offered the e-hypnotherapy intervention following the collection of their 12-month follow-up data. A script development committee comprising clinicians and researchers with experience and qualifications in hypnotherapy will be formed and meet approximately eight times via videoconference to develop the hypnosis and relaxation scripts. Several induction, deepening, suggestion and reorienting scripts will be produced. Once drafted, scripts will be reviewed by a lived experience expert and a panel of hypnosis experts who will provide comments and feedback on content and validity, which will then be incorporated into final versions. The relaxation scripts will be developed symmetrically to hypnosis scripts. The key distinction between the hypnosis and relaxation conditions is that only the hypnosis modules contain direct or indirect suggestions intended to produce changes in pain perception, cognition or behaviour, delivered within an induction–deepening–suggestion–reorientation structure. 26 27 In contrast, the relaxation modules consist solely of passive relaxation instructions without therapeutic suggestions. The script development committee will also provide feedback on three additional documents: (1) a pain education script, which will comprise the first week of material for the hypnotherapy and relaxation interventions, but not for the waitlist condition; (2) a triage script, which will combine elements from e-hypnotherapy and placebo e-hypnotherapy in a way that preserves the subsequent masking of both interventions. The purpose of this script will be to detect any potential abreaction to the interventions prior to randomisation, and (3) a Frequently Asked Questions guide to hypnotherapy, orienting participants to hypnosis, safety and procedural instructions. Primary and secondary outcomes will be measured by participant completion of online questionnaires at baseline (preintervention), 7 weeks (postintervention), 6 and 12 months following the intervention (follow-up). Pain and the level to which participants are bothered by pain will be measured using NRS from 0 (‘no pain’) to 10 (‘worst pain possible’), 28 29 with high internal validity (α=0.84), 30 and qualitative questions (ie, in your own words, please describe your pain in the last week (eg, burning, stabbing, radiating)) across a variety of situations (eg, sexual activity, using bladder or bowels). Pain and functioning will be further measured using the Brief Pain Inventory, a nine-item self-report measure that assesses the severity of pain, including a pain body map, and extent of pain interference, with good validity and reliability (α=0.85 (intensity) and 0.88 (interference)). 31 Psychological symptoms will be measured with the Depression Anxiety Stress Scale-21, a 21-item self-report measure designed to assess symptoms of depression, anxiety and stress with high internal consistency (α=0.88 (depression), 0.82 (anxiety), 0.90 (stress) and 0.93 (total)) 32 and test–retest reliability (r=0.71–0.81 (depression), 0.74–0.81 (anxiety), 0.81–0.89 (stress) over 2 weeks). 32 HRQoL will be measured with the EQ-5D-5L which encompasses mobility, self-care, usual activities, pain/discomfort and mental health, with good reliability (weighted kappa of ≥0.61) and validity (α=0.79). 33 35 Fatigue will be measured with the Fatigue Symptom Inventory, which has 14 items to assess the severity, frequency and daily pattern of fatigue, as well as its perceived interference with HRQoL. The inventory has good reliability and validity (α=0.87–0.93). 36 Sleep quality will be measured with the Jenkins Sleep Scale, a four-item self-report scale that assesses the frequency and intensity of sleep difficulties and is recommended for use with chronic pain patients 37 and has demonstrated acceptable internal consistency (α=0.80) and excellent test–retest reliability (r=0.93). 38 Pain catastrophising will be measured with the Pain Catastrophizing Scale that assesses rumination, magnification and feelings of helplessness about pain; 39 it has been shown to have strong consistency (α=0.92) and test–retest reliability (ρ ≈ 0.88 (95% CI 0.83 to 0.93)). 40 Self-efficacy will be measured with the Pain Self-Efficacy Questionnaire, a 10-item self-report measure that assesses confidence in performing activities of daily living while experiencing pain; 41 it has strong internal consistency (α=0.94) and good test–retest reliability (Intraclass Correlation Coefficient (ICC) =0.82). 42 Central sensitisation will be measured using the Fibromyalgia Criteria-2016, a six-item measure of pain sites and symptoms, 43 with high internal consistency (α=0.904) and test–retest reliability (ICC=0.87) 44 Somatic symptoms will be measured using the Somatic Symptom Scale, an eight-item measure of somatic symptom burden with good internal consistency (α=0.76) and construct validity (correlations with depression (r = 0.57) and anxiety (r = 0.55)). 45 Health utilisation and cost data will be collected via a patient health service utilisation and employment questionnaire administered at baseline, 7 weeks, 6 and 12 months. The questionnaire has been developed specifically for the trial and will include questions on hospital same-day and overnight admissions, including procedures, length of stay, hospital attendance with no admission and community allied health visits related to pelvic pain and associated symptoms. Services Australia records will be retrieved with participant consent to determine medical services, investigations and pharmaceutical use over 12 months. Cost-effectiveness will be assessed through cost-consequences and cost–utility analyses from a societal perspective, using data from the Resource Use Questionnaire, employment questionnaire and Services Australia, with incremental cost-effectiveness ratios (eg, cost per additional responder for pain, psychological symptoms, QoL) and cost per quality-adjusted life-year (QALY) calculated at 12 months. For Australian contexts, since there are no validated healthcare utilisation questionnaires, we use an established questionnaire from prior studies by our health economics team. 46 This instrument includes productivity/absenteeism items aligned with Services Australia data and has demonstrated feasibility in comparable populations. Participants will also complete weekly measures throughout the programme to assess their experience of pain, module engagement and treatment satisfaction. Weekly symptom experience and the level to which participants were bothered by their symptoms will be measured using NRS and qualitative questions (eg, “In your own words, please describe your most bothersome symptoms over the last week?”). Further, participants will be asked to indicate any changes to medication/treatment of pelvic pain or any other condition(s). Participants will also be required to indicate whether they completed a module (‘yes’ or ‘no’) and their level of satisfaction with the module, from 0 (‘not at all satisfied’) to 4 (‘extremely satisfied’). They will have the option to provide additional qualitative feedback. Adverse events will be monitored across intervention groups throughout the trial. Safety data will be collected via email, Qualtrics and over the phone by a member of the study team. In addition to weekly check-in emails, participants will receive a check-in phone call by a member of the study team during weeks 3 and 7 of the intervention. Any adverse events reported will be followed up by a member of the study team with relevant qualifications, for example, psychologist. Semi-structured interviews will be conducted with participants from the hypnosis and relaxation groups (n=40) at 7 weeks, 6 and 12 months post intervention. Interviews will be aimed at understanding the participant experience, including perceived barriers and enablers to engagement and any meaningful change, along with feedback to inform ‘real-world’ implementation efforts. A sampling matrix representing women, men, transgender and non-binary people with various CPP conditions, from urban, rural and remote areas of Australia will be used to support diversity of voices. Postintervention semi-structured interviews will also be conducted with CPP-related healthcare providers (n=15) to inform potential barriers/facilitators to ‘real-world’ implementation. Descriptive statistics will be provided for baseline demographic and health-related data, satisfaction ratings, module completion rates, as well as participant recruitment and retention rates (and reasons for withdrawal). All quantitative statistical analyses will be conducted on an intention-to-treat basis. The intervention effect over 12 months on the primary outcome (pain) and other biopsychosocial outcomes will be estimated using linear mixed models. The models will include group, time (T1, T2, T3, T4), time by group interaction as fixed effects and participant as random effect. Economic data evaluation will involve cost-consequences analysis from a societal perspective and will compare the incremental costs to the full spectrum of outcomes via a series of cost-effectiveness ratios, for example, the incremental cost per additional responder for improvement in pain, psychological symptoms and QoL. A cost–utility analysis (cost per additional QALY) will also be conducted at 12 months. Intervention, healthcare, productivity and out-of-pocket costs will be estimated from the Resource Use Questionnaire, employment questionnaire and Services Australia data. Standardised economic evaluation techniques, including incremental analysis of mean differences, generalised linear modelling techniques 47 48 and bootstrapping, 49 50 to determine confidence intervals will be used. Qualitative data collected during semi-structured interviews with participants will be transcribed and analysed thematically, following the main procedural steps of Template Analysis. 51 People with CPP, and those involved in their care, are key stakeholders in this project, from planning through to implementation. Several peak bodies, including Chronic Pain Australia, Pain Australia, EndoHelp Foundation, Pelvic Pain Foundation of Australia and Western Alliance, which represents Victoria’s regional and remote communities in health science research, are important partners in this research. Any important protocol modifications will be promptly communicated to all relevant parties, including investigators, ethics committees and trial registries, in accordance with regulatory and institutional requirements. This study protocol received ethics approval in Australia from the Deakin University Human Research Ethics Committee (DUREC ref. 2024-080) and is prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12623000368639p). Participation is voluntary, and all participants will provide written informed consent before taking part. Written informed consent will be obtained from all participants. This study will also adhere to the Consolidated Standards of Reporting Trials statement. The findings from this trial will be disseminated through peer-reviewed journal publications and presented at national and international conferences relevant to chronic pelvic pain, hypnosis and mind–body interventions. Results will also be shared with key stakeholders, including consumer advocacy groups and healthcare providers, to inform future practice.

CPP includes several costly, common and challenging conditions, including endometriosis and IBS, impacting 15–34% of the population. 3 4 CPP is a highly disabling and stigmatising condition with a significant impact on HRQoL. 1 Effective treatment involves multidisciplinary care, including psychological therapies. Hypnotherapy, one treatment that is known to reduce pain and psychological distress, has shown promise in addressing some of the difficult symptoms of chronic pain conditions. 18 52 It theoretically differs from relaxation by using focused attention and suggestions for cognitive and physical behaviour change. Hypnotherapy modulates neural processes associated with pain intensity and unpleasantness, supporting its use for CPP where pain and distress are mutually influential. 13 Large well-designed RCTs with appropriate control groups and outcomes are needed, as is the development and testing of online hypnotherapy approaches. e-Hypnotherapy, involving online recorded hypnosis, is likely to address the scale of CPP in the community and overcome current barriers to access, where trained therapists are in demand. This study will examine whether an innovative version of e-hypnotherapy, involving ‘choose your own adventure’ technology to closely replicate the personalised and tailored aspects of face-to-face hypnotherapy, improves a range of biopsychosocial outcomes, including pain, psychological distress and QoL compared with relaxation and waitlist control groups. The cost-effectiveness of e-hypnotherapy will also be examined, and qualitative data will aid understanding of how e-hypnotherapy can be implemented in a real-world setting.