This cluster randomized controlled trial evaluates whether a person-centred, AI-supported Clinical Decision Support System (CDSS) can improve outcomes and cost-effectiveness in interdisciplinary rehabilitation for people with complex chronic pain. The CDSS is designed to assist clinicians in making personalized treatment decisions within standard interdisciplinary treatment (IDT). It has been developed using machine learning models trained on real-world data from over 100,000 patients in the Swedish Quality Registry for Pain Rehabilitation (SQRP), linked to several national registers, including the National Patient Register, the Prescribed Drug Register, the Social Insurance Agency database (MiDAS), and the Cause of Death Register. This enables individualized predictions of treatment outcomes, work ability, and healthcare utilization.

The trial includes 400 adult patients with chronic pain, enrolled at 20 IDT clinics randomized to either CDSS-supported or standard IDT. The study has three phases: feasibility, effectiveness, and implementation. The primary outcome is a patient-prioritized composite single-index of health-related well-being, based on domains such as pain, sleep, physical and mental health, emotional distress, and work ability. Patients prioritize these domains together with their clinical team, enabling a person-centred assessment. Secondary outcomes include HRQoL (EQ-5D, SF-36), emotional distress (HADS), and work ability (WAI), measured at baseline, post-treatment, 6- and 12-month follow-up.

A parallel mixed-methods process evaluation will examine implementation outcomes such as usability, clinician adherence, and workflow integration, using logs, surveys (e.g., S-NoMAD), and interviews. Normalization Process Theory guides the analysis. Cost-utility will be assessed using QALYs and ICERs from a societal perspective, with long-term projections using simulation models. Results will be reported in peer-reviewed publications.

This project consists of three integrated phases aimed at evaluating a machine learning-based Clinical Decision Support System (CDSS) to improve interdisciplinary rehabilitation for individuals with complex chronic pain. The evaluation encompasses feasibility, clinical effectiveness, cost-utility, and implementation in routine care. The results will be reported in multiple peer-reviewed scientific publications.

Phase 1: Development, validation, and feasibility By the end of 2025, the CDSS-developed in an ongoing project-will be ready for clinical testing. It is based on predictive models trained on registry-linked data from over 100,000 patients in the Swedish Quality Registry for Pain Rehabilitation (SQRP), linked to several national registers, including the National Patient Register, the Prescribed Drug Register, the Social Insurance Agency database (MiDAS), and the Cause of Death Register. The system provides personalized forecasts for treatment outcomes, long-term work ability, and healthcare use. A pilot cluster-RCT will be conducted at 10 clinics (5 patients per site) to evaluate feasibility outcomes such as recruitment, retention, usability, data completeness, and workflow fit. These will be assessed using structured surveys, usage data, and interviews. Outcome measures will be collected at baseline, immediately after the intervention (i.e., up to 18 weeks after baseline), and at 12-month follow-up. While a typical interdisciplinary rehabilitation program lasts 6-8 weeks, some clinics may extend the intervention up to 18 weeks (with less treatment occasions per week) due to their ordinary and existing treatment procedures at that specific clinic. Published results indicate however no significant differences in treatment outcomes based on such extended program duration (Tseli et al., 2020). No major changes to the CDSS algorithm or interface are planned during the trial.

Phase 2: Clinical effectiveness and health economic evaluation The full evaluation will be conducted through a non-registry-based cluster randomized controlled trial involving 400 patients across 20 interdisciplinary rehabilitation clinics. Outcomes will be analyzed using linear mixed-effects models adjusted for time, group, clustering, and covariates. The primary endpoint is at 12-month follow-up. Secondary outcomes will be assessed at baseline, up to 18 weeks after baseline (i.e., immediately post intervention), and at 6- and 12-month follow-up. Health economic analyses will include within-trial cost-utility evaluation (QALYs from EQ-5D and SF-36) and longer-term modelling using Markov or microsimulation methods. Both direct (healthcare) and indirect (productivity loss) costs will be included. Sensitivity analyses will address uncertainty and robustness.

Phase 3: Implementation research A mixed-methods process evaluation will examine real-world adoption, scalability, and sustainability. Data will include system logs (e.g., reach, fidelity), survey responses (S-NoMAD), and interviews with clinicians and decision-makers. Analysis is guided by Normalization Process Theory, focusing on coherence (understanding), cognitive participation (engagement), collective action (integration), and reflexive monitoring (clinical utility). This structure enables a rigorous, practice-oriented evaluation of AI support in pain rehabilitation, integrating clinical, economic, and implementation perspectives to guide responsible and scalable integration into healthcare.

Inclusion Criteria:

• Aged 18 to 67 years
• Diagnosed with chronic non-malignant pain persisting longer than 3 months
• Pain condition includes, but is not limited to: fibromyalgia, widespread pain, back pain, neck pain, or shoulder pain
• Eligible for and referred to interdisciplinary rehabilitation (IDT) at a participating clinic
• Willing and able to participate in digital assessment and follow-up procedures
• Able to communicate and complete study materials in Swedish
• Provides written informed consent

Exclusion Criteria

• Pain caused by malignancy or cancer-related treatment
• Pain caused by systemic diseases such as rheumatoid arthritis, lupus, or other autoimmune or inflammatory conditions
• Severe psychiatric conditions interfering with study participation (e.g., untreated psychosis or severe depression requiring immediate psychiatric care)
• Documented cognitive impairment limiting ability to understand study participation or complete self-reported measures
• Currently enrolled in another interventional clinical trial that may confound the outcomes of this study
• Not expected to remain in the clinic's follow-up system for the duration of the study

De-identified individual participant data (IPD) may be shared upon reasonable request, pending legal and ethical approval. The research team is currently reviewing the feasibility of data sharing under Swedish regulations (e.g., GDPR).

Individual participant data (IPD) and supporting documentation will be made available beginning 12 months after publication of the primary results. Access will be granted upon reasonable request and subject to approval by the principal investigator and relevant ethical and legal review, in accordance with Swedish data protection regulations (e.g., GDPR).

Access to de-identified individual participant data (IPD) and supporting documentation may be granted to qualified researchers affiliated with academic or healthcare institutions, for ethically approved research purposes. Requests must include a detailed research proposal and ethical approval from an appropriate Swedish or EU-recognized ethics review board. All requests will be reviewed by the principal investigator and the responsible data controller at the host institution. A data sharing agreement must be signed. Data access will be provided through secure transfer mechanisms, in full compliance with the Swedish Patient Data Act (PDL) and the General Data Protection Regulation (GDPR).