Decentralized clinical trials (DCTs) often rely on a complex integration of diverse technological components in their effort to move trial activities to a participant’s own and surrounding environment. These trial setups are typically modular, combining hardware and software solutions from various vendors to create customized systems that support remote study conduct. In addition to conventional trial technologies, DCTs increasingly incorporate tools such as wearable sensors, remote monitoring devices, study smartphone applications, and online platforms [5, 16, 19]. These innovations, while enhancing data collection [13] and potentially participant adherence [8, 12] also introduce new challenges. They often require higher levels of technological literacy and readiness from participants, clinical research associates (CRAs), and clinical site personnel, who must be equipped to handle troubleshooting and system navigation [2]. As a result, sponsor-provided technical support for sites, CRAs, and participants is essential and differs significantly from that in conventional clinical trials. It must cover a broad range of needs, including hardware functionality, software compatibility, user access management, and system maintenance: Frequent challenges related to hardware, software, and user access have been reported by Valdez et al. [18], whereas Perez et al. [11] highlight challenges around authentication and platform compatibility. In addition, maintaining independence from specific browsers or operating systems necessitates a continuous need for system updates and adaptation [11]. Effective support in this context relies heavily on clearly defined communication protocols – such as real-time chat, ticketing systems, and collaborative document sharing – and well-maintained, accessible documentation [7, 15]. In other studies, telehealth implementations have demonstrated the importance of training, iterative system development, and active clinician involvement to overcome technology-related challenges [1, 17]. Valdez et al. [18] describe common technical issues managed through a service desk model, addressing hardware, software, and access concerns. Several studies emphasize the importance of timely access to study-related data for investigators, clinicians, and data managers, alongside streamlined document workflows [14, 15]. Timely and accurate responses to technical queries are critical, as delays can disrupt study procedures [6, 11]. Training and preparation for site staff are equally important [1, 17], and dedicated resources should be allocated to manage the increased support demand [6]. Furthermore, ongoing quality monitoring and iterative development based on user feedback are vital for refining systems over time [11, 15]. Across multiple studies [11, 14, 15, 17], usability and intuitive interface design are consistently identified as key factors influencing technology adoption and user satisfaction.

Various models of support have been implemented in DCTs, ranging from 1) real-time human support [7, 18], to 2) asynchronous systems such as ticketing services and help desks [11, 15]. The latter document the use of electronic portals that streamline sponsor–investigator communication but can also raise usability concerns.

Support approaches are categorized into real-time human interaction, asynchronous human support, electronic communication platforms, structured technology training, and data management tools. These services may be organized through centralized models, such as unified ticketing systems and electronic portals, or distributed frameworks involving service desks with real-time or on-demand support. Integration with clinical workflows is a recurring theme and emphasizes the need for support systems to align with the routine practices of both participants and staff [14, 15, 17].

To accompany the RADIAL trial [19], conducted as part of the Trials@Home project, the aim was to design, implement, and test a technology support system addressing the key DCT-related challenges described above and to evaluate it in a real-world clinical setting. The RADIAL support system included an asynchronous ticketing system for issue tracking, scheduled on-demand human support, and an online wiki-style knowledge base (KB) that provided stakeholder-specific training materials. To better understand RADIAL’s requirements for a helpdesk and the solution implemented, both Trials@Home and RADIAL are described in the following.

The objective of the Trials@Home initiative is to identify opportunities for conducting clinical trials closer to the participant’s everyday environment. The project is driven by the goal of transforming the design and conduct of clinical trials. The aim is to develop and pilot standards, tools, and recommendations to guide the future definition of DCTs in practice. Innovative approaches should minimize participant burden, eliminate geographical constraints, and improve study data reliability.

A patient-centric design enables participants to contribute to research from their home, thereby alleviating logistical and time-related stress associated with on-site visits. The integration of cutting-edge digital health technologies (DHTs), including mobile medical devices and a customized mobile study app, enables remote data collection. These devices allow continuous, real-world monitoring, generating datasets that more accurately reflect the intervention’s effectiveness in everyday settings while also promoting participant engagement and adherence. The relocation of most or all trial activities to participant’s homes supports greater inclusivity and equitable access to clinical trials.

Trials@Home employs a co-creative multi-stakeholder approach, with the overarching goal of establishing a network of clinical investigators, engineers, and participants, that fosters seamless collaboration. Ultimately, by blending existing and novel techniques for use in DCTs, the Trials@Home research aims to validate these concepts in a proof-of-concept trial, called RADIAL.

RADIAL, an acronym for Remote And Decentralised Innovative Approaches to cLinical trials, is a European proof-of-concept trial that aims to assess the feasibility and acceptability of conducting future clinical trials from participants’ homes rather than at clinical (research) centers. RADIAL investigated the feasibility of DCT models by comparing fully remote and hybrid designs with a conventional approach. The evaluation focuses on scientific and operational dimensions, including participant recruitment, retention, diversity, satisfaction, and cost, alongside safety oversight, treatment adherence, and data quality. The secondary objective examines whether therapeutic efficacy of Insulin Glargine 300 U/mL, a long-acting insulin intended for individuals with Type 2 diabetes mellitus, is maintained across trial arms with varying degrees of decentralization. Consequently, the trial aims to respond to a methodological research question independent of commercial interests. [19]

Participants were recruited from multiple sites across the United Kingdom, Poland, Spain, Italy, Denmark, and Germany. The treatment period lasted 24 weeks. A bring-your-own-device (BYOD) methodology restricted to smartphones was employed, with all other devices supplied by the trial.

Using onsite recruitment methods, 100 participants were recruited into Part A, comprising the conventional and hybrid treatment arms. Participants in the conventional study format experienced primarily onsite trial interactions, while the hybrid arm involved a combination of home nurse visits and on-site visits. Exemplifying the full potential of DCTs, the fully decentralized treatment arm was carried out entirely remotely, with participants conducting all trial activities from their homes. Eight participants were recruited online and engaged solely with decentralized trial elements (remote arm, Part B). These include remote consenting, home nursing visits, remote monitoring of compliance with the study protocol through DHTs (smart injection cap, app for participant-reported outcomes and medical events), direct-to-participant shipping of medication and study materials, and self-conducted blood finger-prick at home. A complete overview of recruitment numbers and activities is available in a separate publication [10]. All elements of the support system (KB, ticketing system) were available to all clinical site personnel and CRAs at all participating trial sites, independent of their actual recruitment into the study arms.

In consideration of the RADIAL trial’s design, the integration of three arms with different levels of decentralization (conventional site-based, hybrid, remote) demonstrates the necessity for a technology support system capable of adapting to each arm [5].

The BYOD approach further increases the level of effort required to ensure that participants can install, access, and configure all study-related technologies on their own devices without losing valuable participant-reported data, thereby ensuring adherence to the study protocol.

A thorough examination of the technology framework diagram (Fig. 1) reveals that the remote arm of the RADIAL trial alone involves multiple systems and data flows. In the context of RADIAL, as is often the case in other DCTs, technology solutions are provided by multiple hardware and software vendors, each with varying levels of integration. This fragmentation requires a comprehensive and well-coordinated technical support system that oversees the study in its entirety and ensures seamless operation across all components. The involvement of multiple stakeholders, in the RADIAL case, a consortium including the sponsor, study teams, participants, vendors, and site users from different countries adds further complexity, making a structured and well-governed technical support system even more critical to successful DCT operations.

Overview of systems for the remote arm of the Trials@Home proof-of-concept trial RADIAL. RTSM, Randomization and Trial Supply Management System; IMP, Investigational Medicinal Product; EDC, Electronic Data Capture system; ICF Informed Consent Form; ePROs, electronic Patient-Reported Outcomes; (S)AEs, (Serious) Adverse Event Reports; SMPGs, Self-Measured Plasma Glucose; HbA1c, glycated hemoglobin

A sophisticated technology support system is therefore pivotal for ensuring the safety, quality, and validity of DCTs, while minimizing participant and site burden. In addition, analyzing helpdesk requests, as well as solutions and processing time can help to determine and further enhance the acceptability of future DCTs.

This paper presents the setup and evaluation of the implemented support system for the RADIAL proof-of-concept trial, detailing its operational processes and performance outcomes. By analyzing data from the ticketing system, the most frequently encountered issue types during the trial were identified to estimate the effectiveness of the support model. Insights from the RADIAL experience, aligned with the literature and emerging technological trends, are synthesized into a set of functional and operational recommendations.