Authors: Richard S Creager, John Blackwood, Thomas Pribyl, Leda Bassit, Anuradha Rao, Filipp Frank, Wilbur Lam, Eric Ortlund, Raymond Schinazi, Alexander L Greninger, Mia Cirrincione, Dale Gort, Emily Kennedy, Adam Samuta, Megan Shaw, Brian Walsh, Eric Lai
Monitoring the genetic diversity and emerging mutations of SARS-CoV-2 is crucial for understanding the evolution of the virus and assuring the performance of diagnostic tests, vaccines, and therapies against COVID-19. SARS-CoV-2 is still adapting to humans and, as illustrated by B.1.1.7 (Alpha) and B.1.617.2 (Delta), lineage dynamics are fluid, and strain prevalence may change radically in a matter of months. The National Institutes of Healths Rapid Acceleration of Diagnostics (RADx) created a Variant Task Force to assess the impact of emerging SARS-CoV-2 variants on in vitro diagnostic testing. Working in tandem with clinical laboratories, the FDA, and the CDC, the Variant Task Force uses both in silico modeling and in vitro testing to determine the effect of SARS-CoV-2 mutations on diagnostic molecular and antigen tests. Here, we offer an overview of the approach and activities of the RADx Variant Task Force to ensure test performance against emerging SARS-CoV-2 lineages.
This Special Section of the IEEE Open Journal of Engineering in Medicine and Biology focuses on the major interrelated components of Rapid Acceleration of Diagnostics (RADxSM) Tech, a National Institutes of Health (NIH)-funded program launched on April 29, 2020 to accelerate development, validation, and commercialization of innovative point-of-care and home- based tests, as well as improvements to clinical laboratory tests, that can directly detect SARS-CoV-2, the virus that causes COVID-19. RADx Tech was implemented and coordinated by the Consortia for Improving Medicine with Innovation & Technology (CIMIT) in its role as the Coordinating Center for the Point-of-Care Technologies Research Network (POCTRN) in conjunction with the NIH and the four POCTRN Centers.
Likened to a mini-Manhattan Project by Sen. Lamar Alexander, and as described throughout this Special Section, RADx Tech has proven to be unprecedented in many aspects, including its mission and vision, budget, accelerated timeframe, scale, extent of cross-government agency collaboration and information exchange, and blending of best business/academic/investment practices, all of which came together despite significant constraints imposed by the pandemic.
This Special Section provides operational details for the key components and processes of RADx Tech that have proven to be vital to its success: software platforms that enabled the program’s infrastructure and processes (Collins et al.), the expert review panels (Tessier et al.), the unique facilitation provided to the funded applicants (Dempsey et al. and Robinson et al.), the POCTRN Cores that evaluated the technologies at the benchtop and in actual use (Nehl et al. and Gibson et al.), and the support for large-scale manufacturing and deployment of diagnostic tests (Walsh et al.). The final paper describes the impact of RADx Tech on future med-tech entrepreneurs and developers (DiMeo et al.).
On behalf of POCTRN and as Co-Principal Investigators for the POCTRN Coordinating Center, we are grateful to NIH leadership for their invaluable support and guidance, especially National Institute of Biomedical Imaging and Bioengineering director Bruce Tromberg and NIH director Francis Collins, and are privileged to present this collection of outstanding papers from a group of dedicated colleagues committed to serving our nation, which we humbly suggest represents a new paradigm for medical technology development and a validated model for the United States to use and adapt when challenged by another national healthcare emergency.
Authors: Paul Tessier, Michael K. Dempsey, John Collins, Steve Schachter
RADx SM Tech’s mission is to rapidly accelerate deployment of SARS-CoV-2 tests and could not utilize typical grant application and review processes that can run 4 to 6 months. Instead, RADx Tech leveraged methodologies developed by CIMIT and utilized by POCTRN as described further in this special issue. RADx Tech uses a multi-stage review with two review panels, a Viability Panel and a Steering Panel, that are supported by subject matter experts and a Deep Dive team. Members of the panels have extensive commercialization and business experience in addition to scientific and technical knowledge. The Viability Panel is responsible for assessing whether the proposal is a good fit with the RADx Tech Program and whether it should be recommended to move into a Deep Dive. Less detailed information is requested in the application than a typical SBIR application since the application is refined and details added during the Deep Dive. The Steering Panel reviews the results from the Deep Dive and decides whether to recommend further funding. Everyone on the Viability Panel and Steering Panel reviews every application, thereby providing consistency and context for the reviewers. Utilization of an “assess, improve, and then select” process with review panels comprised of highly experienced review panel members has resulted in improved timing, efficiency, and effectiveness of reviews and has the potential to be extensible beyond RADx Tech.
Authors: Michael K. Dempsey, Paul Tessier, John Collins, Elias Caro
The RADx SM Tech program was a unique funding and support mechanism to accelerate the market introduction of diagnostic tests for SARS-CoV-2, the virus that causes COVID-19. In addition to providing funding, the RADx Tech program provided unprecedented levels of non- monetary support. Applications were evaluated using a deep dive process which involved a 1- to 2-week intensive collaboration between the applicant and a team of experts from RADx Tech. The result of this deep dive was a very comprehensive understanding of the potential and risks associated with the proposed work, which was far beyond what can typically be understood in a written grant application. This detail allowed the deep dive team to provide a better-informed recommendation on how to proceed. In some instances, the recommendation was made to not fund the project; in other cases, the recommendation was made to provide the applicant with more funding or support to help maximize their probability of success. After the deep dive, the project moved to a Work Package 1 (WP1) phase that focused on further de-risking. The same RADx Tech team that conducted the deep dive also worked with the applicant through the WP1 phase of the program. This allowed for joint responsibility of the work with the common goal of rapid, successful product introduction.
Authors: Matthew L. Robinson, Charlotte Gaydos, Barbara Van Der Pol, Sally McFall, Yu-Hsiang Hsieh, William Clarke, Robert L. Murphy, Lea E. Widdice, Lisa R. Hirschhorn, Richard Rothman, Chad Achenbach, Claudia Hawkins, Adam Samuta, Laura Gibson, David D. McManus, Yukari C. Manabe
The NIH Rapid Acceleration of Diagnostics (RADx SM ) Tech Program was created to speed the development, validation, and commercialization of innovative point-of-care (POC) and home-based tests, and to improve clinical laboratory tests, that can directly detect SARS-CoV-2. Leveraging the experience of the Point-of-Care Technologies Research Network, a Clinical Review Committee (CRC) composed of clinicians, bioengineers, regulatory experts, and laboratorians was created to provide structured feedback to SARS-CoV-2 diagnostic innovators. The CRC convened 53 meetings with 49 companies offering SARS-CoV-2 tests in POC and reference laboratory formats as well as collection materials. The CRC identified common barriers to device design finalization including biosafety, workflow, result reporting, regulatory requirements, sample type, supply chain, limit of detection, lack of relevant validation data, and price-performance-use mismatch. Feedback from companies participating was positive.
Authors: Eric J. Nehl, Stacy S. Heilman, David Ku, David S. Gottfried, Sarah Farmer, Robert Mannino, Erika Tyburski, Julie Sullivan, Allie Suessmith, Leda Bassit, Janet Figueroa, Anna Wood, Traci Leong, Anuradha Rao, Beverly Rogers, Robert Jerris, Sunita Park, Mark D. Gonzalez, Jennifer K. Frediani, Claudia R. Morris, Joshua M. Levy, Nils Schoof, Maud Mavigner, John D. Roback, Kristen Herzegh, Natia Saakadze, Jess Ingersoll, Narayana Cheedarla, Andrew Neish, Bradley Hanberry, Christopher C. Porter, Annette M. Esper, Russell R. Kempker, Paulina A. Rebolledo, Pamela D. McGuinness, Frederick Balagadde, Rebecca Gore, Ainat Koren, Nira Pollock, Eugene J. Rogers, Karl Simin, Nathaniel S. Hafer, Mary Ann Picard, Chiara E. Ghezzi, David D. McManus, Bryan O. Buchholz, Christina A. Rostad, Viviana Clavería, Thanuja Ramachandra, Yun F. Wang, CaDeidre Washington, Cheryl Stone, Mark Griffiths, Ray Schinazi, Ann Chahroudi, Miriam B. Vos, Oliver Brand, Greg S. Martin, Wilbur A. Lam
Faced with the COVID-19 pandemic, the US system for developing and testing technologies was challenged in unparalleled ways. This article describes the multi-institutional, transdisciplinary team of the “RADx SM Tech Test Verification Core” and its role in expediting evaluations of COVID-19 testing devices. Expertise related to aspects of diagnostic testing was coordinated to evaluate testing devices with the goal of significantly expanding the ability to mass screen Americans to preserve lives and facilitate the safe return to work and school. Focal points included: laboratory and clinical device evaluation of the limit of viral detection, sensitivity, and specificity of devices in controlled and community settings; regulatory expertise to provide focused attention to barriers to device approval and distribution; usability testing from the perspective of patients and those using the tests to identify and overcome device limitations, and engineering assessment to evaluate robustness of design including human factors, manufacturability, and scalability.
Authors: Laura L. Gibson, Nisha M. Fahey, Nathaniel Hafer, Bryan Buchholz, Denise R. Dunlap, Robert L. Murphy, Chad Achenbach, Cheryl Stone, Rebecca Cleeton, Jared O’Neal, Jennifer K. Frediani, Miriam B. Vos, Oliver Brand, Risha Nayee, Leona Wells, Wilbur A. Lam, Greg S. Martin, Yukari C. Manabe, Matthew L. Robinson, John P. Broach, Jeffrey E. Olgin, Bruce Barton, Stephenie C. Lemon, Allison Blodgett, David D. McManus
The National Institutes of Health (NIH) launched the Rapid Acceleration of Diagnostics (RADx SM ) Tech initiative to support the development and commercialization of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) point-of-care test devices. The primary objective of the Clinical Studies Core (CSC) was to perform SARS-CoV-2 device studies involving diverse populations and settings. Within a few months, the infrastructure for clinical studies was developed, including a master protocol, digital study platform, data management system, single IRB, and multi-site partnerships. Data from some studies are being used to support Emergency Use Authorization of novel SARS-CoV-2 test devices. The CSC reduced the typical time and cost of developing medical devices and highlighted the impactful role of academic and NIH partnership in addressing public health needs at a rapid pace during a global pandemic. The structure, deployment, and lessons learned from this experience are widely applicable to future in vitro diagnostic device clinical studies.
Authors:Brian Walsh, Annette Hosoi, Manuel Kingsley, Susan Moreira, Sreeram Ramakrishnan, Paul Tessier, Nancy Gagliano
This paper explores how the approach, process, and learnings of the RADx SM Tech Deployment Core in its support of manufacturing, deployment, and implementation of medical technologies is creating a replicable model for the future. Initially, the key construct of the RADx Tech Deployment Core was helping companies manufacture, commercialize, and develop a digital infrastructure for the purpose of SARS-CoV-2 testing and reporting. However, the team and RADx Tech leadership soon realized that the larger infrastructure to deploy testing in non-clinical environments was nonexistent and that wrap-around services were required to build the necessary bridge between manufacturing and end users. Furthermore, the unique communities that required testing (e.g., manufacturing plants, transportation hubs, K-12 schools, etc.) had different infrastructure requirements and outsized needs for education and support around testing plan implementation. The Deployment Core, therefore, quickly scaled a team to help to complete the picture and provide guidance to end users and ultimately help shape public policy around a useful data model.
Authors: Andrew J. DiMeo, Chipo J. Afamefuna, Skyler J. Ward, Phil Weilerstein, Elias Caro, Max Germer, Alexander J. Carroll
There are many benefits of the RADx SM Tech initiative worth exploring beyond that of the current acceleration of diagnostic tests being developed and deployed to the nation. One of those benefits has been the impact on work readiness for recent biomedical engineering (BME) graduates who have been hired by RADx Tech as Assistant Project Facilitators (APFs) and to the students and faculty members on applicant teams. This paper includes a literature review of the current status of BME professional skills development in traditional academic and clinical settings. The organizational structure of RADx Tech teams is described, including how recent BME graduates are integral to the process. Opportunities are discussed on how the RADx Tech structural model can be leveraged to improve professional skills education. It is concluded that the RADx Tech organizational structure and process including APFs may be replicable. Further research is planned to explore its impact.
Authors: John M. Collins, Marshall R. Collins, Tamara McKenzie, Mark Marino
The RADx SM Tech initiative required a massive mobilization of the biomedical community. It was chartered with the extremely ambitious goal of rapidly developing and deploying innovative tests to detect people infected with the SARS-CoV-2 virus. It needed to do so at a scale and with urgency to get the country back to daily activities such as school and work as soon as possible. It required forming and supporting a diversity of teams with members from around the country and beyond. These teams collaborated in complex workflows that needed to be carefully monitored and tracked. This paper describes the key elements of the secure, web-based infrastructure that was configured to enable the efficient and effective operation of RADx Tech’s key processes and address its unique and urgent challenges. One such challenge was to manage the flow of applications through a multi-stage, interactive selection process (using the CoLab platform) and another was to support and facilitate the progress of projects selected for support and funding through an accelerated commercialization program (using the GAITS platform).