ENDO-EVE: protocol for a multicenter mixed methods evaluation of a digitally enabled tiered care pathway for endometriosis

Background: Endometriosis is a common chronic gynecological disease associated with pain, impaired quality of life, reduced productivity, impaired fertility, and high healthcare costs. Diagnosis is often delayed because symptoms are normalized, structured assessment in outpatient gynecology is limited, and referral pathways to certified Endometriosis Centers (ECs) are poorly standardized. Care after referral is often fragmented, with insufficient coordination between outpatient gynecologists and ECs. Objective: ENDO-EVE evaluates whether a digitally enabled tiered care pathway can improve earlier identification, referral quality, coordinated care, and patient-reported outcomes (PROs) in routine practice. Methods: ENDO-EVE is a multicenter mixed-methods health services research project with two linked intervention components. Intervention 1 evaluates a structured referral pathway using a stepped-wedge cluster randomized trial across Halle, Heidelberg, and Tuebingen. A standardized symptom-oriented Endo-Assessment supports earlier identification and risk-informed referral of women with suspected endometriosis to certified ECs. The primary endpoint is the proportion of specialist-confirmed endometriosis among referred patients. Intervention 2 is a multicenter three-arm randomized controlled trial evaluating a digital support intervention after specialist assessment at a participating EC and confirmation of study eligibility. Participants are randomized to (1) usual care with assessment-only app, (2) app-based support, or (3) app-based support plus coach support. The digital companion includes remote symptom monitoring, longitudinal PRO collection, educational content, self-management support, reminders, event-triggered follow-up, and clinician-facing workflow integration. The primary endpoint is 12-week change in the SF-36 Physical Component