By Deborah Borfitz
August 26, 2020 | Day two of the Next Generation Dx Summit was highlighted by a spirited panel discussion on the lessons learned during the pandemic, hosted by Columbia University’s Susan Hsiao. In the words of the University of Washington’s Alex Greninger, COVID-19 has brought “different levels of awful” to the pathology lab where personnel burnout is a recurring theme. On the other hand, reimbursement has doubled to $100 per test since the pandemic began. The uptick has “created a $30 billion industry overnight … and that dog hasn’t barked.” Jordan Laser with Northwell Health referenced unprecedented supply chain challenges making it necessary for him to validate seven different platforms just to meet the urgent testing need, while shortages have expanded from test kits and PPE to reagents and now consumables. Ongoing demand for samples, including saliva, prompted creation of a consortium for sharing across institutions that has only partially alleviated the scarcity, according to David Walt from Brigham & Women’s Hospital.
Clinical need dictates that hospitals embrace distributed testing where turnaround time is measured in hours, reserving centralized testing for outpatient settings where results (at least theoretically) can be produced in a day or two, Walt said. But he objects to the FDA using PCR as the gold standard, effectively preventing more predictive rapid antigen tests from being approved. Despite their lower sensitivity and specificity, a well-validated antigen test might be developed for at-home use that is affordable enough to be repeated twice a week by people in quarantine and be coupled with antibody testing. Laser advocated for evidence-based testing guidelines, noting the CDC recently recommended that asymptomatic patients with known exposure to the virus not be tested. For a small tradeoff in analytical sensitivity, Greninger noted, sample pooling has helped increase testing volume at the University of Washington. The need for serology tests will likely disappear once a COVID-19 vaccine transitions to clinical care, Laser predicted, which has been the case for other viruses excepting hepatitis B.
Ping Wang at the University of Pennsylvania provided some practical guidance on the development of next-generation diagnostics, including common barriers and checklists of questions developers need to ask themselves and that they can expect from clinicians, providers, and payers. Her point-of-care development efforts at Penn include a microbubbling digital assay powered by machine learning that in early testing has performed on par with many commercially available assays, as well as a urine-based fentanyl lateral flow assay test that has better sensitivity (100%) and specificity (99.5%) than most such marketed tests.
The challenges in testing for COVID-19 was the topic of a second panel discussion moderated by Nathan Ledeboer from the Medical College of Wisconsin, beginning with the maddening level of misinformation circulating on Facebook. Part of the remedy may be steering traffic to reliable sites hosted by the CDC and WHO, as well as educating friends and family about the scientific method and addressing their questions about the believability of PCR test results. Glen Hansen from Hennepin County Medical Center (Minneapolis) said a study is underway that could set the sensitivity barometer (e.g, concentration of RNA copies) against which future assays will be challenged. Researchers are also looking at reports of viral transmission during window periods for PCR testing that are producing false negatives.
For the next pandemic, early and widespread access to testing may require providing diagnostics manufacturers and laboratories with positive samples the moment a new virus emerges, said Matthew Binnicker with Mayo Clinic & Foundation. The panelists seemed to agree that the lack of a coordinated national response to COVID-19 contributed to assay rationing that disproportionately affected small community labs. Emily Crawford at Chan Zuckerberg Biohub favored the idea (featured in a recent article in The Atlantic) of creating a service corps to train young people, many of them currently unemployed, as much-needed lab workers. Jennifer Dien Bard reported that Children’s Hospital Los Angeles has been exploring a saliva-based test that has had results comparable to nasopharyngeal (NP) swabs. Saliva testing could be a way to make testing more available in some communities outside the hospital where a degree of error is defensible, said Hansen. If adopted as a screening tool, pointed out Binnicker, such tests may need more frequent repeating and only add to the processing backlog in labs.
Binnicker led one of several talk on the subject of diagnostic stewardship to reduce the overall cost of healthcare while improving its delivery. He described the team-based, data-driven approach taken by Mayo Clinic that includes an evidence-based ordering algorithm. Among the measures taken have been review of multiplex respiratory panels when orders originate with primary care or the emergency department, and a decision support tool and order entry system that underscore recommended tests. Mayo also discontinued serological testing for herpes after finding it had limited clinical utility, reducing lab expenses by $130,000 annually.
At a separate session on the topic, Christopher Doern at Virginia Commonwealth University made a strong case for taking commonsense steps with potentially big impact—for example, restrictions on repeat testing with NP swabs within seven days or making sure doctors know the results of a previously ordered Fungitell test when they go to order it a second time. The facility has also been a good diagnostic steward by consolidating on a single Lyme’s disease test, putting a dollar sign next to a high-cost testosterone test, selectively calling ordering physicians with critical test results, and giving patients some responsibility by posting results to a portal that links them to additional care.