For effective rollout on a global scale, sponsors must address and develop a plan around known challenges including recruitment, sit adoption, and technology integration.
In the dynamic landscape of clinical research, decentralized clinical trials (DCTs) have emerged as a compelling proposition, poised to reshape conventional development programs by integrating digital technologies and remote data acquisition. Amidst the enthusiasm surrounding the advantages and efficiencies promised by DCTs, encompassing remote or hybrid trials, an imperative gap remains—the need for deeper understanding, agreement, and standardization of optimal practices and protocol. When executed thoughtfully, accounting for several factors, DCTs promise improved and more representative evaluations of treatment efficacy and benefits.
The successful execution of DCTs is contingent upon addressing various challenges. These challenges encompass participant recruitment, effective adoption and execution at trial sites, seamless technology integration, and navigating evolving regulatory requirements. To pave the way for an effective global rollout of DCT trials, it is incumbent on sponsors to meticulously address and develop comprehensive strategies around each of these pivotal aspects.
Recruitment, a challenge in nearly every clinical study, takes on a unique dimension in DCTs. DCTs, by their very nature, offer the distinct advantage of tapping into an expansive participant pool that transcends the limitations of traditional research site populations often confined by geographical boundaries. This opens the door to a diverse range of potential participants who might otherwise be excluded. However, the complexity lies in identifying, filtering, and screening individuals who fit a study’s criteria while ensuring that research sites, whether physical in hybrid trials or virtual in remote settings, do not become overwhelmed.
Addressing this challenge requires implementing tailored, study-specific, multi-channel recruitment strategies and establishing rigorous pre-screening and screening processes. Sponsors are presented with several options to tackle this challenge effectively. Recruitment strategies should harness the power of digital platforms and patient engagement tools to reach potential participants. Leveraging social media, online communities, and digital advertising can engage individuals who may not be found through conventional outreach methods. Collaboration with specialized healthcare providers and referral sites, partnering with patient advocacy groups, and disseminating targeted editorial content on prominent websites can bolster recruitment efforts.
Integrating real-world data sources such as electronic health records (EHRs) and electronic medical records (EMR) into the recruitment process can more accurately target individuals who meet a study’s specific criteria. To enhance pre-screening processes, sponsors can implement multi-level filtering mechanisms, employ intelligent site selection strategies, and conduct call-center-based assessments.
In addition, sponsors must prioritize aligning their DCT protocols with prevailing industry guidance on participant recruitment, including regulatory recommendations such as those provided by the FDA and the EMA on informed consent (and DCT). DCTs offer an opportunity to simplify the informed consent process by utilizing electronic consent forms and remote interactions. This approach can seamlessly integrate fully remote informed consent or electronically supported consent into a participant’s journey, spanning the various phases of the trial from initial introduction through to the trial results. By reducing barriers to participation in DCTs, this approach can expedite the recruitment process and enhance its efficiency.
Introducing a new system to support DCTs at fully remote and hybrid research sites begins with the crucial step of a site feasibility assessment and effective communication of the approach requirements. It’s essential to recognize that not all sites possess the necessary infrastructure or capabilities to accommodate DCTs or hybrid studies. Meticulous site selection is paramount, and initiatives aimed at facilitating DCT adoption should be included in the site contracting and payment processes to sustain the motivation and commitment of participating sites.
To streamline operations and minimize site burden, the systems implemented should be user-friendly and prioritize intuitiveness, requiring minimal integrations. Additionally, sites must be equipped with comprehensive participant training materials, ideally delivered through the system, and robust support mechanisms to engage study subjects actively. A dedicated support organization should also be readily available to assist sites in fulfilling their responsibilities within the DCT framework. Ideally, systems and training will be thoughtfully structured to minimize the need for extensive ongoing support, ensuring a smooth and efficient operation that enhances the overall effectiveness of DCTs.
Fully transitioning from paper to electronic instruments is necessary to implement quality clinical outcome assessments in DCTs. However, this shift represents just the initial phase, and several important decisions should be worked through.
First and foremost, the choice between ‘bring your own device’ (BYOD) and provisioned devices carries significant weight. While the latter may entail logistical and financial challenges, it provides greater control and support for all electronic clinical outcome assessment (eCOA) instruments. On the other hand, BYOD, which relies on participants’ using their own devices like smartphones, often yields more consistent adherence, as individuals are less likely to overlook or neglect their personal devices.
Addressing scheduling complexities and time dependencies is another critical aspect. DCTs necessitate support for various diaries and electronic patient-reported outcomes (ePRO) models, including on-demand entries, actions-triggered responses, and scheduled inputs. Implementing notifications, reminders, and alerts becomes imperative to ensure data quality, such as specifying windows during which eCOA input is accepted or identifying non-compliance with frequency requirements.
The ability to review and amend participant-entered source data, especially in the context of safety data, becomes essential. Additionally, efficient translation support within the same interface for local languages should be readily available to cater to a diverse participant pool.
Each of these decisions can significantly impact the quality of data collected and the level of participant engagement in clinical trials. Making informed choices at these junctures is essential to ensure the success and reliability of eCOA implementation in DCTs.
Integrating technology into DCTs is a multifaceted endeavor characterized by the need to manage inherent variability in study configurations, diverse data collection methods, and varying visit and data input structures. While technologies such as single sign-on and Application Programming Interfaces (APIs) serve as indispensable tools, the unique challenges encountered often demand tailored or customized solutions. Care must be taken to collaborate with technology providers capable of adapting their solutions to align with the needs of a specific protocol and, subsequently, who can offer expert guidance on deployment.
Ideally, a single technology solution capable of capturing and consolidating all relevant data in a single database should address most aspects necessary for DCTs. This approach minimizes the need to piece together disparate solutions and amalgamate data from various sources, streamlining the overall process.
Design integration also necessitates the incorporation of fundamental development principles, such as robust error handling and stringent data security measures. Equally important is the strategic decision-making concerning where integration should occur. This choice may involve integrating at the front-end/application level (e.g., for devices) or at the backend, which often hinges on the reliability of server connectivity.
Successful technology integration in DCTs requires a holistic approach that accounts for each study's intricacies and prioritizes data integrity, security, and connectivity throughout the trial’s lifecycle. Collaboration with adaptable technology partners and the pursuit of cohesive, end-to-end solutions contribute to the efficiency and effectiveness of DCT technology integration efforts.
Adopting new submission processes in Europe to streamline multi-country approvals through the Clinical Trials Information System (CTIS) represents a promising and progressive development in clinical research. Ethics committees, sponsor organizations, and local support entities like Contract Research Organizations (CROs) must understand the opportunities and legal complexities associated with these specific approaches. It should be noted that initial standards for digital methods often exceed those of traditional paper-based procedures, underscoring the significance of being well-informed and proactive in adapting to these changes.
Several key topics warrant in-depth discussion and consideration. These include the feasibility of enrolling participants without physical visits, innovative methods for participant identification, the acceptability of electronic signatures for informed consent, strategies to ensure investigator oversight is maintained in remote settings, participant safety within the framework of DCTs, techniques for monitoring subjects’ adherence to study protocols, and the legality surrounding the shipment of investigational medicinal products (IMPs) from central pharmacies.
These questions and challenges emphasize the need for collaborative efforts to establish clear guidelines and best practices within the evolving landscape of DCTs. As we navigate this dynamic terrain, it becomes increasingly evident that collective engagement and a commitment to adapting to these changing paradigms will be essential to advancement in the field.
DCTs represent a relatively new frontier in the realm of clinical development. As the demand for standardization and consistent protocols within this burgeoning field continues to rise, it becomes increasingly clear that industry-wide collaboration among influential stakeholders is not just desirable but essential to establishing robust best practices.
An illustration of this collaborative spirit is the recently inaugurated Trials@Home consortium. The consortium is embarking on a mission to explore the remarkable opportunities presented by relocating clinical trials from their traditional clinical setting to the immediate surroundings of trial participants. This ambitious initiative brings together various stakeholders, including academic institutions, small and medium-sized enterprises (SMEs), private foundations, and the European Federation of Pharmaceutical Industries and Associations (EFPIA). It also draws on the collective specialisms of experts from medicine, technology, regulation, and ethics.
At the heart of this consortium’s work lies the concept study known as RADIAL. This adaptive study spans six European countries and focuses on Type-2 diabetes, evaluating traditional, hybrid, and fully remote approaches. Notably, the initiative is adopting a foundational, end-to-end DCT technology.
The collective objective of the Trials@Home consortium is twofold. Firstly, it aims to nurture the development of actionable recommendations and innovative tools that can propel the adoption and seamless integration of DCTs into mainstream clinical research. Secondly, the project is set to explore the real-world application of these approaches across multiple countries, focusing on defining best practices and leveraging technology, as well as analyzing the relevant ethical, quality, and regulatory barriers.
In this pursuit, the study's primary endpoints are comparing associated costs, gauging patient retention rates, and assessing patient satisfaction levels across hybrid, remote, and traditional trial methodologies. Through this collaborative and innovative consortium, it is anticipated that valuable insights will emerge that will help shape the future landscape of clinical research.
DCTs present a substantial opportunity to introduce operational efficiency and enhance data collection for clinical trials. Yet, they also present significant challenges. Success relies on multiple factors, and expertise is vital for sponsors venturing into hybrid or remote practices. This expertise can be developed in-house or through partnerships with specialized third-party providers.
The potential for a transformative shift in clinical research is undoubted; however, the practical implementation of DCTs requires meticulous planning. Robust multi-channel recruitment strategies, site support, thoughtful integration of technology, and compliance with evolving regulations will be fundamental. With these considerations addressed, DCTs stand to enhance data quality in clinical trials significantly.
Karl Landert, Managing Director, DCT, Cambridge Cognition