Prognosis Prediction and Shared Decision Making for Personalised Anticoagulant Therapy after Unprovoked Venous Thromboembolism: The MORPHEUS project.

Background In patients with unprovoked venous thromboembolism (VTE), indefinite anticoagulation is recommended to prevent recurrence but may expose some patients to unnecessary long-term bleeding risk. Current clinical scores and biomarkers have limited discriminative performance, do not capture the time-dependent nature of VTE, and do not incorporate patients' perspectives or support shared decision-making. Objectives To develop and validate time-dependent, multicomponent risk prediction scores and socio-anthropological scales (TDMI) integrated in a shared decision-making process to optimise long-term anticoagulation management after unprovoked VTE. Patients/Methods MORPHEUS is an international, multidisciplinary research program conducted in eight European countries. The TDMI will combine clinical, biological, imaging, and pharmacological biomarkers with socio-anthropological scales reflecting patients' lived experiences, preferences, and perceptions of risk. Candidate components will be identified through systematic literature review, Delphi consensus, qualitative interviews with patients and physicians, and pooled analyses of large prospective European VTE cohorts including clinical outcomes, biobanks, and imaging data. Dynamic, multilevel, time-dependent prediction models for recurrent VTE and anticoagulant-related bleeding will be derived using advanced statistical and machine-learning approaches. The clinical effectiveness and acceptability of TDMI integrated in a shared decision-making process will be evaluated in a stepped-wedge cluster randomised trial enrolling 2,400 patients with a first unprovoked VTE. Expected results The TDMI is expected to improve individualized risk stratification, reduce unnecessary extended anticoagulation, lower bleeding complications, and improve patient satisfaction, treatment adherence, and quality of life. Conclusions The MORPHEUS project will support personalised anticoagulation decisions and improve long-term outcomes in patients after unprovoked VTE.