The decentralized trial approach arrived on the scene well ahead of COVID-19, but after the pandemic showed up adoption caught fire and has continued to accelerate. Isaac Rodriguez-Chavez—ICON’s senior vice president of scientific and clinical affairs, and head of scientific and medical affairs of strategy for decentralized clinical trials—spoke with Outsourcing-Pharma about the history of clinical trials, and how the decentralized trial format likely will continue changing the course of that history.
OSP: Please tell us about how the “modern” drug development paradigm has evolved in the past few decades, and maybe ways in which it hasn’t.
IRC: The current “modern” drug development paradigm is over 60 years old – and was built on an analog and paper architecture. The result has been inefficient clinical trial practices that have not kept up with the digital and technological innovations that have been rapidly deployed in healthcare delivery over the last several years.
The undeniable need to improve human health and quality of life has been the main driver for the evolution of traditional clinical trials. The first controlled clinical trial of the modern era was conducted in 1747 on scurvy disease in sailors and progressed to the first randomized control trial to test streptomycin in pulmonary tuberculosis in the UK in 1946.
Since the mid-1900s, a series of regulatory, legal, and ethical developments occurred that framed clinical trials as known today. These advances include:
- the Nuremberg Code in 1947
- the Universal Declaration of Human Rights in 1948
- the Kefauver-Harris amendments in 1962
- the Helsinki Declaration in 1964
- the US National Research Act of 1974 and Belmont Report of 1979
- the International Conference on Harmonization that published “Good Clinical Practice” standards (GCP) which are currently used for the ethical conduct of clinical trials.
The increased complexities of the clinical research enterprise have been progressively defined by expanded scientific, regulatory, legal, and ethical accountabilities.
OSP: Specifically, please talk about the rise of the decentralized trial model, and factors (i.e., the COVID pandemic, 21st Century Cures Act, etc.) that have helped drive the increase in the use of DCTs.
IRC: Like many industries, the clinical research enterprise has been risk-averse and reluctant to adopt remote activities. The modernization of clinical trials, driven by legislation such as the 21st Century Cures Act and changes in healthcare delivery and the COVID-19 pandemic, have propelled the concept of Decentralized Clinical Trials (DCT’s) to the forefront of clinical research innovation.
While DCTs experienced slow growth in the early 2000s and a 7% compound annual growth rate from 2014 to 2019, their implementation soared to 77% due to the COVID-19 pandemic in the second half of 2019 and 2020. Regulatory agencies have also enabled fast DCT adoption in the field by issuing guidance documents to allow sponsors to implement DCT approaches during the COVID-19 pandemic, and they have expressed public interest in embracing best practices from remote trial activities permanently. The 21st Century Cures Act also served as an enabler of modern trial designs, including indirectly DCTs.
Altogether, the clinical research field is experiencing a historical and transformative shift for a permanent implementation of DCT approaches in multiple therapeutic areas and in all phases of clinical trials. For instance, investigators expect that a threefold increase in remote participant interactions will persist after the pandemic accompanied by an aggressive adoption of DCT-related services and technology intervention.
OSP: Please tell us how the technology ‘architecture’ (as you put it) that supports DCTs differs from that typically used for onsite trials.
IRC: Central to the delivery of DCTs is the underlying technology architecture to support the remote engagement and data collection of clinical trial participants outside of the traditional clinical trial research site. While considerable focus has been placed on mobile and digital-based applications, participant-facing applications, and remote participant monitoring (RPM) using medical-grade digital health technologies (e.g., wearables), it is important to include a host of other technology-enabled platforms necessary to streamline overall clinical trial logistics.
Clearly, communication and mobile platforms, as well as digital health technologies (e.g., integrated wearable devices), are a core component of the hybrid and full DCT models enabling trial-related activities connected to electronic consent (eConsent), electronic signature (eSignature), electronic clinical outcome assessments (eCOAs), investigational medical product (IMP) adherence and compliance, telehealth engagements, and event IMP dosing and medical assessment scheduling.
However, additional technology solutions are also pivotal to streamlining clinical trials using DCT approaches. The technology architecture also needs to support trial-related data acquisition, management, and storage linked to an electronic source (e-Source), automated electronic health records (EHRs) and electronic data capture (EDC) mapping, interactive response technologies (IXRS), IMP direct-to-participant shipping, and the delivery of in-home health nursing services.
OSP: As you mention, there are a significant number of technology tools that DCT teams rely upon in running their studies. Have sites and sponsors typically experienced challenges in integrating all of these tools and making sure they work together and ‘talk’ to each other seamlessly?
IRC: The progress made in traditional clinical trials has been boosted for more than a decade by adding communication technologies (e.g., smartphones, tablets, and laptops) and digital health technologies (e.g., wearable devices and sensors), giving rise to modern trial designs that include decentralized clinical trials (DCTs).
Advances in innovative technology architectures are increasing the efficiency and productivity of DCTs for sponsors, sites, vendors, and participants. This is accomplished by using novel digitalized health outcomes; adjusting technologies to meet specific DCT needs and data flows; increasing participant convenience; sustaining participant retention from multiple geographies; expanding access and engagement of diverse populations from different races and ethnicities, socioeconomic strata, and cultural backgrounds; and conducting central monitoring of sites.
OSP: Could you please share some advice on how clinical research professionals running DCTs can work to ensure their technology is deployed and operated smoothly and efficiently?
IRC: As the DCT models and the technology that supports them continue to evolve, the next focus to maximize efficiency and streamlining is to ensure that we can create an end-to-end ecosystem that connects all of these solutions smoothly and holistically. This modernized clinical research enterprise enabled by a sound technology architecture will improve the overall medical product development timelines, while simultaneously taking advantage of the latest technological developments to optimize the collection and analysis of clinical data in real-time.
The use of state-of-the-art technology architecture to streamline the deployment of the DCT ecosystem will be the most impactful change to our medical product development paradigm since its inception.
DCTs rely on a complex technology architecture to deliver end-to-end and fit-for-purpose solutions, which consist of multiple trial-related remote components and functions integrated by a mobile health platform that is multifunctional and interoperable. This is different compared to traditional trials, in which only a few asynchronous technology-driven point solutions may be implemented.
In fact, digital synchronicity and integration of the technology architecture are some of the major challenges that sponsors, investigators, and sites experience when implementing DCT approaches. Hence, verification, validation, usability testing, and proper justification of the technologies used in DCTs are essential before trial conduct to ensure robustness, reliability, and smooth operations.
OSP: Is there anything you’d like to add—about this topic, the future of DCTs, or anything else?
IRC: For the industry to capitalize on the shift to DCTs, there is a necessary cultural shift with change management needed to embrace the digital world and novel technology architecture ecosystems in all areas of trial design and delivery. These changes require buy-in from senior leadership and should be integrated at all levels in organizations.
Additionally, and while a great deal of focus and efforts are put into the technology ecosystems that support hybrid and full DCTs, all other components and areas that conform end-to-end, specific solutions for these trials need equal attention, planning, and work. Sound integration of multiple components under regulatory and legal frameworks with a clear communication plan that embraces dataflow, and the health journeys of participants is key for a successful DCT.
Despite this transformative change, traditional trials and DCTs have multiple things in common, including:
- the scientific rigor in trial design to ensure validity and reproducibility of the results
- the main goal of testing the safety and efficacy of novel medical products in Phases I-III of clinical investigations
- the sponsors, investigators, and sites need to comply with regulatory requirements regarding participants’ safety and data quality, and integrity in clinical trials.
The future of clinical research entails increased adoption of DCTs, which are here to stay with an increased level of digitalization in innovative and complex technology architecture ecosystems to streamline efficiencies, cost, and the delivery of novel medical products to continue improving human health. This will also allow for increased diversity of trial participants and a wider range of diseases to be addressed. We are in a seismic transformation of clinical trials that will bring unprecedented opportunities.