Diagnostics Lab Meeting Summaries

This week’s Diagnostics Evidence Accelerator meeting consisted of 2 presentations:

1. A Systems Integrations Approach to Pandemic Response (Dr. Renee Wegryzn, Ginkgo Bioworks) 2. SHIELD Overview (Dr. Keith Campbell, FDA/CDRH)

A Systems Integrations Approach to Pandemic Response (Dr. Renee Wegryzn, Ginkgo Bioworks) Ginkgo Bioworks was founded in 2008 with the mission to make biology easier to engineer. Ginkgo Bioworks designs, builds, tests, and ferments organisms. They envision these tools will be used for therapeutics, biosurveillance, environmental sequencing, bioinformatics and a variety of other use cases. At the beginning of the pandemic, Ginkgo launched Concentric, a division of Ginkgo which would focus on Biosecurity. They used their platform to help manufacture vaccines and scale testing through different collaborations. Concentric by Ginkgo is positioned to enable the implementation and scaling of newly developed tests. Figure 1 shows their integrated pandemic response during the height of the pandemic. As a continued effort, Concentric by Ginkgo is layering on other population level surveillance such as waste water and air monitoring.

Full July Lab Summary

This week’s Diagnostics Evidence Accelerator meeting consisted of 2 presentations:

1. Real-world assessment of diagnostic and serologic testing of SARS-CoV-2 (Drs. Garrett Jenkinson and Benjamin Pollock, Yale-Mayo Clinic CERSI)

2. Steps Towards Laboratory Interoperability for RWD/RWE (Dr. Andrea Pitkus, University of Wisconsin-Madison) Real-world assessment of diagnostic and serologic testing of SARS-CoV-2 (Drs. Garrett Jenkinson and Benjamin Pollock, Yale-Mayo Clinic CERSI) Mayo Clinic, along with Yale University, through the Center for Excellence in Regulatory Science and Innovation (CERSI) program, identified patients who were diagnosed with COVID-19 at three Mayo Clinic sites and Yale University. These data were collected via the Mayo Clinic Laboratory Information System (LIS) (Figure 1) which is well integrated. However, with the different COVID-19 tests that were rolled out at the beginning of the pandemic, he LIS required significant IT staff efforts to keep up with all the tests administered and the constantly evolving testing landscape.

Full June Lab Summary

This week’s Diagnostics Evidence Accelerator meeting consisted of 3 presentations:

• Connecting the Pipes (Amar Bhat, Reagan-Udall Foundation for the FDA)

• IVD Sponsors’ RWD Needs for Test Development and Regulatory Purposes (Nate Carrington, Roche Diagnostics) • Introduction to Graphite Health (Dr. Stan Huff, Graphite Health)

• ONC TEFCA Recognized Coordinating Entity (Mariann Yeager, The Sequoia Project)

At the beginning of the Evidence Accelerator series, the community wanted to understand the interrelationship between diagnostics real-world performance and outcome assessment. The community stated that we need to be able to connect the pipes between diagnostic testing and outcome. The critical aspects for the FDA was knowing test manufacturer, type of test, collection date, result date and test result. Given that there are many types of data sources to help us fill the data gaps, reality shows that connecting all of the “data pipe” is challenging. Figure 1 shows the different sources of data. This led to increased discussion into understanding the steps need to improve the data flow for interoperability.

Full May Lab Summary

April's  Diagnostics Evidence Accelerator meeting consisted of 2 presentations:

1. Public-Private Partnerships for the Generation of Real-World Evidence (Nilay Shah, PhD, Delta Air Lines)

2. Decentralized, Rapid Molecular Disease Screening (Randy True, FloodLAMP Biotechnologies, PBC) Public-Private Partnerships for the Generation of Real-World Evidence (Dr. Nilay Shah, Delta Air Lines) Delta Airlines has approximately 90,000 employees with approximately 175,000 beneficiaries. They have a global footprint but 95% of the footprint in the US. Figure 1 shows the timeline of testing and vaccination administered to the Delta Airlines employees and beneficiaries.

Their COVID-19 mitigation strategies included distributing masks and administrating and distributing tests and vaccines. Delta Airlines has distributed 25 million+ masks (KN95, cloth, and surgical mask) to Delta employees and customers. They have distributed and administered 1 million+ tests (BinaxNOW rapid antigen test, Flowflex rapid antigen test, Quest laboratory PCR test, and onsite Rapid PCR test) and 300,000+ vaccine doses for employees, friends, and families. With the amount of masks, tests, and vaccines distributed, there was an opportunity to compare the effectiveness in a real-world setting. One diagnostic testing finding to note was that individuals that reported positive for a rapid antigen test, they would proceed to get a lab-based PCR test or an onsite rapid PCR test. The testing practice would provide confirmation of the individual being positive for COVID-19. Additional data can also be collected through an individual testing positive on a rapid antigen test but negative on a PCR test and negative on both rapid antigen and PCR test. With the different data collected on the tests, there were opportunities to explore the performance of the test options.

Full April Lab Summary

This week’s Diagnostics Evidence Accelerator meeting consisted of two presentations:

1. Totality of Evidence for the Evaluation of Repurposed Therapeutics for COVID-19 (Névine Zariffa, NMD Group and Jaap Mandema, Certara)

International COVID-19 Data Alliance (ICODA) unites international health research data to enable discoveries that benefit everyone, everywhere, by reducing the harm of COVID-19 and enable an efficient data response to future pandemics and other health challenges. The presentation focused on how real-world studies (RWS) and randomized controlled trials (RCT) are both necessary tools to understand the impact of the COVID-19 pandemic. Figure 1 lists the strengths and limitations of RWS and RCTs discussed during the presentation.

2. Genomic Surveillance for SARS-CoV-2 Variants (Molly Steele and Philip Shirk, CDC)

CDC has three sources of genomic surveillance data. The first one is National SARS-CoV-2 Strain Surveillance (NS3). This is a partnership with state public health laboratories and APHL. It contains approximately 3,000 random specimens per month, including additional priority specimens (novel variants, infections in vaccinated people). The second source is Contract Sequencing Data. This is a partnership with commercial diagnostic laboratories and conducts >10,000 sequences per week. The third source is Tagged Metadata from Sequence Repositories. Data from this leads to CDC guidance for surveillance sequences in GISAID/GenBank. State/local health departments, universities, and non-federally contracted diagnostic labs tag sequence metadata in public repositories. Figure 2 shows the data workflow.

Full March Lab Summary

Introduction to Diagnostics Evidence Accelerator Meeting #44

This week’s Diagnostics Evidence Accelerator meeting consisted of two presentation:

1. IICC Introduction (Serge Jonnaert, IVD Industry Connectivity Consortium and Ed Heierman, Abbott)

The IVD Industry Connectivity Consortium (IICC) began in 2009 with the mission to modernize connectivity between laboratory IT systems and analyzers, to standardize data workflows and make them more secure, but also to reduce the overall cost of deployment and support. The current members of this consortium are volunteers representing leading IVD companies such as Abbott Laboratories, Beckton Dickinson, BioMérieux, Roche Diagnostics, Siemens Healthcare Diagnostics. The goal of the consortium is to create and ensure adoption of an interoperable connectivity paradigm to reduce the complexity and variability of data exchange between IVD testing systems and healthcare informatics systems

2. Lab Data Interoperability Opportunities (Charles Halfpenny, Consultant, and Eric Crugnale, Sunrise Medical Laboratories)

This question and answer session looked at the different lab data interoperability opportunities that are connected to understanding the data flow four essential data elements (i.e., test name, specimen collected date, test result, and test result date). This session was moderated by Susan C. Winckler, the CEO of the FDA Foundation.

Full February Lab Summary

This week’s Diagnostics Evidence Accelerator meeting consisted of 2 presentation:

1. COVID-19 Test with Consumer-Collected Sample and Data Flow/Data Opportunities (Savitha Arokiamary, Amazon Dx, and Jim Daniel and Dr. Taha Kass-Hout, Amazon Web Services)

The public health reporting (PHR) team at Amazon Dx is responsible for reporting COVID-19 test results to all state public health leaders and reporting authorities. In order to achieve this, the team uses their internal reporting service engine where they established an electronic reporting process with all 50 states and DC. The electronic laboratory reporting (ELR) system is a transport mechanism used by the state agencies to share data, and in this case, the results of PCR- based COVID-19 testing. This reporting structure has three mechanism: Secure File Transfer Protocol (SFTP), Simple Object Access Protocol (SOAP) and Public Health Information Network Messaging System (PHINMS). Using the transport mechanisms, PHR shares the data via HL7, with the state reporting authorities. HL7 is a file type contains strings of data such as patients’ demographics and test information and collates into a single report. HL7 bridges the gap between the different health IT applications and allows the sharing of the data.

2. Funding Announcement (Reagan-Udall Foundation for the FDA)

As the pandemic has continued, the role of accurate and reliable SARS-CoV-2 diagnostics tests remain a critical component of the COVID-19 response. Some of the needs were assessed in Project One and we learned about important trends in sero-testing and performance of serological tests. Additionally, through Project One we learned a lot from our limitations such as the lack of interoperability to link manufacturer information with clinical and demographic data left us with a good deal of missing data on the actual test name and race. Therefore, the FDA Foundation is announcing a new program that can help us dig into the limitations from Project One.

The purpose of the funding is to

• Improve the use, interpretation, and performance of diagnostic tests as a means to:

                 • improve the medical products available to patients

                 • enable critical public health decision-making

• Expedite advances in knowledge regarding IVD performance, including strengths and limitations for use in different settings or subpopulations

• Enable a more rapid regulatory review process relative to current pre- and post-market data approaches • Increase knowledge of real-world performance of SARS-CoV-2 IVDs

• Inform a framework for IVD test developers to collect and analyze data for regulatory submission

• Can lead to regulatory submissions from SARS-CoV-2 IVD manufacturers for Emergency Use Authorization (EUA) or Full Market Approval (FMA)

Full January Lab Summary