The TREATMENT project: a Physical-Internet-enabled reference architecture for end-to-end visibility in direct-to-patient clinical trial logistics

Clinical trials are increasingly adopting decentralized and direct-to-patient delivery models, but these models intensify the need for auditable chain-of-custody, condition control, and coordinated execution across heterogeneous logistics actors. This paper presents TREATMENT as a Physical-Internet-enabled reference architecture for regulated direct-topatient clinical trial logistics. The contribution does not lie in standards adoption alone, but in the integration of connected logistics units, a neutral multi-tenant cooperation platform, a single-trace interoperability mechanism combining GS1 EPCIS 2.0 events and GS1 EDI documents, and an explicit milestone-driven rule-based logic for road–drone synchronization. The evaluation is structured around trace completeness, chain-of-custody integrity, documentevent correlation, telemetry timeliness, condition monitoring, route integrity, and intermodal synchronization. Results show complete capture of planned custody milestones, successful correlation of shipment documents and physical events across heterogeneous providers, nearreal- time telemetry availability, correct alert generation for conservation and route anomalies, and event-governed release of the downstream drone leg from validated upstream milestones. The paper also discusses transferability conditions, architectural limits, and the broader relevance of the approach for regulated multimodal healthcare logistics.