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NIH, HHS fast-tracking point-of-care, pooled tech as way out of testing crunch

HHS and NIH spotlight aggressive push for point-of-care and pooled COVID-19 testing technologies

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The U.S. government is taking non-conventional paths to point-of-care and pooled technologies in its push to bulk up and speed up the country’s strained COVID-19 testing capacity.

In HHS’s case, the department is scrambling to patch together all available testing resources to meet surging demand. At NIH, a new program launched five days after federal funds became available is taking an aggressively streamlined approach that arguably models how translational research should have been conducted all along.

Both agencies put out communications this week that featured COVID-19 testing numbers, with HHS reporting capacity in the present and near-term, and NIH announcing the benchmarks its Rapid Acceleration of Diagnostics (RADx) program hopes to hit by year end.

HHS Assistant Secretary for Health Brett Giroir said in a press briefing Thursday that the U.S. is running 700,000 COVID-19 tests per day, and that projections indicate 51 million tests will be run in August and 65 million in September; 13 million and 20 million of those, respectively, are projected to be point-of-care tests.

Separately, in a New England Journal of Medicine report published Wednesday, NIH Director Francis Collins and colleagues provided a detailed look at the aims and progress of RADx, a competitive program launched in April with $1.5 billion to fuel development of rapid and easy-to-use diagnostics for SARS-CoV-2 infection, with a focus on meeting the needs of underserved populations.

RADx’s goal is to expand testing capacity so that by December, 6 million people -- or 2% of U.S. population -- can be tested per day, with additional tests in reserve.

"This program represents a dramatic expansion of the usual NIH mode of supporting research."

Special Report on the NIH RADx Initiative

HHS’s and NIH’s communications both also addressed testing speed.

Giroir said the average turnaround time for COVID-19 results is 4.27 days, up 0.8 days from June, -- the numbers exclude testing at the point-of-care and in local hospitals. In some cases, results are taking as long as two weeks.

He said the government is working to shrink that lag by setting up surge testing sites and other resources in COVID-19 hotspot areas, relieving some of the burden on commercial providers.

Giroir also invoked pooled testing -- a strategy in which multiple individuals’ samples are combined and tested at once -- as a route to conserving resources and speeding up the delivery of results, and said the approach stands to improve efficiency by 20-30%.

On July 18, FDA granted the first emergency use authorization (EUA) for a pooled COVID-19 test, with the caveat that the strategy is best deployed in populations with low rates of case prevalence -- a temporary status that can change in a matter of weeks (see “EUA for Pooled Test Points to Effect of Prevalence on Performance”).

The molecular test from Quest Diagnostics Inc. (NYSE:DGX) can be used on upper respiratory swabs from up to four people suspected to have COVID-19 by their healthcare provider; a negative result for the pool deems all four individuals COVID-19 negative, while a positive result requires each sample to be re-tested individually.

A second authorization for pooled testing came Friday, this time coupled with the first FDA authorization to use a test in asymptomatic populations.

These new indications for Laboratory Corp. of America Holdings (NYSE:LH)’s COVID-19 test, which was already authorized for use on individual samples from symptomatic individuals, allow it to be used on pools of five individuals’ swabs collected under professional observation. A prescription is still required to obtain the test.

And while RADx’s mission to develop widely accessible rapid tests means it is largely focusing on point-of-care technologies, the NIH authors also highlighted pooled tests run by centralized labs as a route to speedier population-level surveillance.

The government’s focus on new rapid testing strategies, coupled with the persistence of the COVID-19 crisis, means that investments in these technologies have a chance to lay the groundwork for swift responses to future outbreaks (see “Crisis Spurs Innovation in Rapid Diagnostics”).

Scarcity mindset

Limited test availability is shaping the U.S. government’s guidance to individuals and institutions.

On Wednesday, the CDC updated its recommendations on when mild and moderate COVID-19 patients can end isolation, replacing the recommendation to wait for a negative COVID-19 test with one based on the passage of time since onset of symptoms or receipt of a positive result.

The recommendation is grounded in the observation that recovered patients can test positive for COVID-19 long after they stop harboring replication-competent virus due to the persistence of SARS-CoV-2 RNA, but Giroir said it’s an example of the type of testing that’s being deprioritized to conserve resources.

To maximize testing access and speed in settings with high infection risk, HHS is turning to viral antigen tests -- immunoassays for viral proteins that are generally less sensitive than more commonly used tests for viral RNA, but cheaper and faster (see “A Test for the Utility of Antigen Testing”).

On July 14, the agency announced it would distribute rapid, point-of-care antigen tests from Quidel Corp. (NASDAQ:QDEL) and Becton Dickinson and Co. (NYSE:BDX) to nursing homes in hot-spot areas. The companies are the only two to receive EUA for COVID-19 antigen tests.

Giroir referenced modeling studies indicating tests that are less sensitive, but faster and administered more frequently, are more effective at catching COVID-19 than tests that detect lower levels of the virus but are administered less frequently and return results more slowly. The latter describes the most common form of COVID-19 testing -- reverse transcription polymerase chain reaction (RT-PCR) tests performed by centralized labs (see “COVID-19 Diagnostic Tech Tableau”).

He said testing scarcity is also leading government officials to support out-of-the-box solutions for surveillance of asymptomatic individuals, for example by colleges and universities.

Giroir doesn’t recommend schools spend resources testing everyone before letting them back on campus, because that strategy captures only a single point in time. Instead, he and other officials are encouraging colleges and universities to run routine surveillance testing, using “excess reagents” in campus research labs to run tests in pools of five samples.

Because these tests would be used for surveillance and not diagnosis, they wouldn’t require an EUA or a CLIA-certified lab, he said, citing CMS Administrator Seema Verma. If a pool of samples tests positive, all five samples would then be retested using an FDA-authorized diagnostic.

Testing scarcity is also leading government officials to support out-of-the-box solutions for surveillance of asymptomatic individuals.

Giroir said the government is seeking more scalable paths to widespread surveillance of asymptomatic populations through technologies developed by RADx and the Biomedical Advanced Research and Development Authority (BARDA) -- including undisclosed “ultra-low cost” point-of-care technologies -- that could make tens of millions more tests available per month.

Another way of conserving testing capacity in the run up to flu season is through multiplexed assays that detect both COVID-19 and influenza, avoiding competition for resources between the two kinds of tests.

A handful of multiplexed tests have received EUA, and Giroir said there are many more in the pipeline. “Everybody’s going down that pathway,” he said.

Giroir said high demand has forced labs to be flexible about what kits they use, noting tests from Roche (SIX:ROG; OTCQX:RHHBY) and Hologic Inc. (NASDAQ:HOLX) are in limited supply, and point-of-care molecular tests from the Cepheid Inc. unit of Danaher Corp. (NYSE:DHR) are being prioritized to rural and other underserved areas with limited access to centralized labs.

Radical plans

According to NIH’s report on RADx, “this program represents a dramatic expansion of the usual NIH mode of supporting research.”

Unlike the institute’s modus operandi of putting out calls for grant proposals, funding top projects and keeping tabs on progress from a distance, RADx is triaging and pressure testing technologies through their entire life cycle.

As of July 13, the program received more than 600 applications for the initiative’s RADx-tech program, a “shark tank”-like competition in which technologies are subjected to a series of increasingly stringent checkpoints. The winners are to be deployed -- on the order of millions of tests per week -- by end of summer or fall.

More than 200 applications have come from businesses with fewer than 50 employees, about 100 have come from academic laboratories, and over 50 have come from start-up companies that are less than a year old. Many applicants are preparing applications for EUA.

Technologies under consideration include CRISPR, lateral flow “dipsticks,” microfluidics systems, compact electronics, and smartphone-based reporting systems designed for non-experts. Applicants are also exploring a range of sampling strategies, including saliva, nasal swabs and oral swabs.

The top 15-20% of applications undergo a week-long intensive review process by a panel of experts (Phase 0).

Of these, 25-30% are selected for a month-long independent testing and validation process (Phase 1) through core facilities in the Point-of-Care Technologies Research Network (POCTRN), which is run by NIH’s National Institute of Biomedical Imaging and Bioengineering (NIBIB).

Technologies that make it through that gate will undergo clinical testing and scale-up (Phase 2), with “substantial financial assistance.”

At least 27 projects have made it into Phase 1, one of which is soon to enter Phase 2.

Tests that have already received EUA, are able to produce 20,000-100,000 units by the fall, and have infrastructure for rapid deployment are eligible for the initiative’s RADx-Advanced Technologies Platforms (RADx-ATP) program, which fast-tracks them into Phase 1 or 2.

RADx-ATP is also working to boost the output of high-capacity central labs with automated workflows, and labs capable of conducting pooled tests, including “massive pooling” strategies that track individual samples via molecular barcoding.

On the other end of the spectrum, promising new and repurposed technologies requiring more than six months of development are eligible for the RADx-rad program. Examples include biosensors to detect SARS-CoV-2 in breath, community-based surveillance through wastewater analysis, and host biomarkers to predict disease severity.

The initiative’s RADx-UP program aims to increase the accessibility and effectiveness of COVID-19 testing in underserved populations disproportionately affected by the pandemic, in particular non-Hispanic Black people, Hispanics, American Indians and Alaskan Natives.

RADx-UP aims to work with underserved communities across the country in “a series of interlinked, pragmatic implementation science projects.” The program will also research “social, ethical and behavioral issues” related to testing, such as the factors that influence a group’s willingness to be tested for SARS-CoV-2.

The report identified hurdles to RADx’s goals, including limitations on patient samples, manufacturing resources, and distribution infrastructure. It also pointed to the need for digital health platforms that link test results to electronic health records (EHRs), and make that information accessible to public health organizations.

“Connecting the pipes” between COVID-19 testing data and healthcare systems is one of the major objectives of the Reagan-Udall Foundation’s COVID-19 Diagnostics Evidence Accelerator (see “Accelerating the Fight against COVID-19 with Real-World Data on Tests”).

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