Decentralized trials that radically transform research: ICON

The decentralized testing approach arrived on the scene long before COVID-19, but after the onset of the pandemic, adoption caught fire and continued to accelerate. Isaac Rodriguez-Chavez, senior vice president of scientific and clinical affairs at ICON and responsible for scientific and medical affairs of the strategy for decentralized clinical trials, spoke with Outsourcing-Pharma about the history of clinical trials and how the decentralized testing format will likely continue to change the course of this story.

OSP: Please explain to us how the “modern” drug development paradigm has evolved over the past few decades, and perhaps ways it has not.

IRC: The current “modern” drug development paradigm is over 60 years old – and was built on analog and paper architecture. The result has been inefficient clinical trial practices that have failed to keep up with digital and technological innovations that have been rapidly deployed in healthcare delivery in recent years.

The undeniable need to improve human health and the quality of life has been the main driver of the evolution of traditional clinical trials. The first modern-era controlled clinical trial was conducted in 1747 for scurvy disease in sailors and progressed to the first randomized controlled trial to test streptomycin in pulmonary tuberculosis in the UK in 1946.

Since the mid-1900s, a series of regulatory, legal and ethical developments have taken placewhich framed clinical trials as they are 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 declaration of Helsinki in 1964
• the United States National Research Act of 1974 and the Belmont Report of 1979
• the International Conference on Harmonization which published the “Good Clinical Practice” (GCP) standards that 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 responsibilities.

OSP: Specifically, please talk about the rise of the decentralized testing model and the factors (i.e. the COVID pandemic, the 21st Century Cures Act, etc.) that have contributed to the increase in the use of DCTs.

IRC: Like many industries, the clinical research enterprise has been risk averse and reluctant to embrace remote activities. Modernization of clinical trials, driven by legislation such as the 21st Century Treatments Act and changes in healthcare delivery and the COVID-19 pandemic, have propelled the concept of Decentralized Clinical Trials (DCT) at the forefront of innovation in clinical research.

While DCTs experienced slow growth in the early 2000s and a compound annual growth rate of 7% from 2014 to 2019, their implementation soared to 77% due to the COVID-19 pandemic in the second half of the year. 2019 and 2020. Regulators have also enabled rapid adoption of the DCTon the ground by issuing guidance documents to enable proponents to implement DCT approaches during the COVID-19 pandemic, and they have expressed public interest in permanently adopting best practice business practices. remote test. The law on cures of the 21st centuryHas also served as a catalyst for modern test designs, indirectly including DCTs.

Overall, the field of clinical research is undergoing a historic and transformative shift towards continued implementation of DCT approaches in multiple therapeutic areas and in all phases of clinical trials. For example, Investigators expect a three-fold increase in remote participant interactions to persist after the pandemic, accompanied by aggressive adoption of DCT-related services and technology response.

OSP: Please tell us how the technology “architecture” (as you put it) that supports DCTs differs from that typically used for on-site testing.

IRC: The underlying technology architecture is at the heart of delivering DCTs to support remote engagement and data collection of clinical trial participants outside of the traditional clinical trial research site. While considerable attention has been paid to mobile and digital apps, participant apps, and remote participant monitoring (RPM) using medical grade digital health technologies (e.g. wearable devices) ), it is important to include a host of other technologies – enabled platforms needed to streamline the overall logistics of clinical trials.

Clearly, communication and mobile platforms, as well as digital health technologies (e.g., integrated wearable devices), are a critical component of hybrid and comprehensive DCT models enabling testing activities related to electronic consent. (eConsent), Electronic Signature (eSignature), Electronic Clinical Outcome Assessments (eCOA), Adhesion and Compliance of Investigational Medical Products (IMP), Telehealth Commitments, and Dose and Assessment Planning medical of IMP events.

However, additional technological solutions are also essential to streamline clinical trials using DCT approaches. The technological architecture must also support the acquisition, management and storage of test data linked to an electronic source (e-Source), automated electronic health records (EHR) and electronic capture mapping of data (EDC), interactive response technologies (IXRS), IMP dispatch direct to participants, and delivery of home nursing services.

OSP: As you mentioned, there are a large number of technological tools on which the DCT teams rely to conduct their studies. Have sites and sponsors generally found it difficult to integrate all of these tools and ensure that they work together and “talk” to each other in a transparent manner?

IRC: Advances in Traditional Clinical Trialshas been driven for more than a decade by the addition of communication technologies (e.g. smartphones, tablets and laptops) and digital health technologies (e.g. wearable devices and sensors), resulting in designs for ‘modern trials that include decentralized clinical trials (DCT).

Advances in innovative technological architectures increase the efficiency and productivity of DCTs for sponsors, sites, suppliers and participants. This is accomplished using new digitized health outcomes; adapt technologies to meet specific DCT needs and data flows; increase the comfort of participants; maintain the retention of participants from multiple geographic areas; expand access and engagement of diverse populations of different races and ethnicities, socio-economic strata and cultural backgrounds; and perform central site monitoring.

OSP: Could you please share some tips on how clinical research professionals performing 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 goal for maximizing efficiency and streamlining is to ensure that we can create an end-to-end ecosystem that connects all of these. solutions in a fluid and holistic manner. This modernized clinical research enterprise, made possible by a solid technological architecture, will improve overall medical product development times, while simultaneously taking advantage of the latest technological developments to optimize the collection and analysis of clinical data in real time.

Using cutting edge technology architecture to streamline the deployment of the DCT ecosystem will be the most significant change to our medical product development paradigm since its inception.

DCTs leverage a complex technology architecture to deliver end-to-end, end-to-end solutions that consist of multiple remote trial-related components and functions integrated by a multi-functional and interoperable mHealth platform. This is different from traditional testing, where only a few asynchronous technology-based point solutions can be implemented.

In fact, digital synchronicity and the integration of technology architecture are some of the major challenges that sponsors, investigators and sites face when implementing DCT approaches. Therefore, verification, validation, usability testing and proper justification of the technologies used in DCTs are essential prior to the conduct of testing to ensure robustness, reliability and proper operation.

OSP: Would you like to add something, on this subject, the future of DCTs or something else?

IRC: For industry to capitalize on the transition to DCTs, a cultural shift is needed with change management needed to embrace the digital world and new technology architecture ecosystems in all areas of product design and delivery. testing. These changes require buy-in from top management and should be incorporated into all levels of organizations.

In addition, and while much attention and effort is devoted to the technology ecosystems that support hybrid and full DCTs, all other components and areas that comply end-to-end, specific solutions for these assays require equal attention, planning and work. . A solid integration of multiple components into regulatory and legal frameworks with a clear communication plan that encompasses the data flow and participant health journeys is key to a successful DCT.

Despite this transformative change, traditional testing and DCTs have several things in common, including:

• scientific rigor in the design of the assays to ensure the validity and reproducibility of the results
• the main objective of testing the safety and efficacy of new medical products in phases I-III of clinical investigations
• sponsors, investigators and sites must comply with regulatory requirements regarding participant safety, data quality and clinical trial integrity.

The future of clinical research involves increased adoption of DCTs, which are here to stay with an increased level of digitization in innovative and complex technology architecture ecosystems to streamline efficiency, costs and delivery of new medical products. to continue to improve human health. It will also allow for a greater diversity of trial participants and a wider range of diseases to be treated. We are in a seismic transformation of clinical trials that will bring unprecedented opportunities.