The present study aims to develop a reference model that integrates Digital Twins (DTs) and Business Process Management (BPM) to enhance the efficiency and effectiveness of clinical trials. To achieve this, a five-step method was employed: (1) a collaborative workshop with Clinical Research Center (CRC) managers, scientists, and principal investigators (PIs); (2) validation of stakeholder needs; (3) conceptualization of a DT use case; (4) development of a synergetic reference model; and (5) evaluation of this model with a clinical research specialist. The results identified key business needs from various stakeholders, proposed a DT solution to address these needs, and created a reference model that integrates BPM and DT perspectives. This integrated approach addresses challenges such as ensuring continuous and interoperable data capture, motivating systematic data collection, and facilitating data transfer between CRCs, thus improving stakeholder satisfaction in clinical trials. The developed reference model and the identified research challenges provide a foundation for future research and practical implementation of DTs and BPM in clinical trials. This study advances the field by bridging DT and BPM frameworks, offering a comprehensive approach to managing clinical trial processes, and demonstrating the significant potential of these technologies to improve clinical research efficiency and effectiveness.