July 21, 2022 | The COVID-19 pandemic is ushering in an era of self-testing that has been at least a decade in the making. Mayo Clinic researchers first demonstrated in a study published in 2012 that patients on their own are just as good as healthcare professionals in testing for the flu (Mayo Clinic Proceedings, DOI: 10.1016/j.mayocp.2012.02.011) and subsequently that the same holds true for group A strep testing involving patient- or parent-collected pharyngeal swabs (Journal of Clinical Microbiology, DOI: 10.1128/JCM.02500-14).
Despite the evidence—not to mention the cost and inconvenience of a trip to the doctor’s office—it took a public health crisis to finally convince most clinicians that the benefits of self-swabbing with an at-home test kit outweigh any of the potential problems, according to infectious disease specialist Frank R. Cockerill III, M.D., founding partner of Trusted Health Advisors and former chair of laboratory medicine and pathology at Mayo as well as CEO of its medical labs. The worry was that people might accidentally harm themselves in the testing process or be unable to follow the instructions for use or read the test strip, all of which are at best unlikely and at worst disingenuous.
If testing is done by a healthcare professional, it can cost patients potentially hundreds of dollars between the office visit and specimen collection and processing fees, Cockerill points out. At-home tests, on the other hand, are generally available at local retail pharmacies for less than $10.
Cockerill helped coordinate the swift development and execution of one of the first clinical studies of self-swabbing for COVID-19 infection in the U.S., in collaboration with the Bill & Melinda Gates Foundation, Quest Diagnostics, and the Everett Clinic in Seattle (now a part of Optum-UnitedHealthcare) where Yuan-Po Tu, M.D. is an internal medicine specialist (New England Journal of Medicine, DOI: 10.1056/NEJMc2016321). The study resulted in one of the earliest Food and Drug Administration (FDA) emergency use self-testing methods for COVID-19.
Some of the key players in that effort will be participating in a panel discussion on self-testing at the upcoming Next Generation Dx Summit. They are Karen A. Heichman, Ph.D., deputy director of the Gates Foundation; Elizabeth M. Marlowe, Ph.D., senior scientific director and head of R&D infectious diseases and immunology at Quest Diagnostics Nichols Institute; Raquel M Martinez, Ph.D., director of system and core lab in clinical and molecular microbiology at Geisinger Health System; and Nicole Zitterkopf, Ph.D., vice president of the laboratory service line advancement team at Optum.
Joining them will be Jack Jeng, M.D., chief medical officer of Hone Health who formerly served in the same position at Scanwell. Cockerill helped Scanwell develop an at-home lateral flow test for COVID-19 that is paired with a smartphone camera to analyze and interpret results. The technology was sold to Becton Dickinson (BD) last fall.
At the time Cockerill was approached for his expertise in 2020, he had only recently come out of retirement for a second time after his startup company, Analyte Health, was sold. Analyte Health offered direct-to-consumer testing for sexually transmitted diseases (STDs) through telehealth providers. In a matter of months, Seattle would become the epicenter of the COVID pandemic and make self-testing the only plausible way to expand testing at the population level, he says.
The first COVID outbreak in a U.S. nursing home, with many dead, was raising alarms in the region—including fear of exposure by going to a bricks-and-mortar site for testing, says Cockerill. The Gates Foundation was already supporting self-swabbing in Seattle for the flu, so Heichman suggested extending the support to also cover SARS-CoV-2.
Cockerill’s role was to serve as the “matchmaker,” bringing all these great institutions together, he says. “Within a few days, we had over 500 patients self-swab.”
In the NEJM study, the team showed that the sensitivities of tongue, nasal, and mid-turbinate samples collected by the patients were 89.8%, 94.0%, and 96.2%, respectively, when compared to healthcare workers doing pharyngeal swabs at outpatient facilities within the Puget Sound area of Washington, he notes. All samples were submitted to Quest Diagnostics for PCR testing.
Bolstered by this finding, Cockerill then began working with Quest Diagnostics to get FDA Emergency Use Authorization for self-testing. “Almost simultaneously around the country, a lot of other folks used the study to say, ‘We can do this,’” he says. “With crisis comes opportunity.”
At-home COVID tests are of course now ubiquitous, he adds, among them BinaxNOW (Abbott) and BD Veritor. Current iterations of lateral flow tests are easy to use.
To gain EUA by the FDA, the manufacturer of a self-testing kit needs to provide evidence of reliability in the hands of patients, says Cockerill. Although no formal template had existed for SARS-CoV-2 EUAs, his early experience in the U.S. was that observed self-collection and self-testing (e.g., by an online physician) was required.
Before long, however, multiple studies emerged showing patients did just as well with rapid self-testing whether observed or unobserved, he continues. Regulatory expectations regarding sample collection and testing performance or observation by a healthcare professional therefore went away.
The reality is that everyone isn’t comfortable with self-testing, at least initially, says Cockerill. “It is like riding a bike; the first time you’re going to have some mess-ups, but once you learn how to do it, it comes naturally.”
The big problem with self-testing now is that results aren’t being entered into public health databases, Cockerill says. Epidemiologists consequently have less of an idea of what the true occurrence rate of disease is in a population than when in-clinic testing is being done.
One topic up for discussion at the forthcoming conference session is what panelists see as the single most important advance in diagnostic testing that has occurred with the COVID-19 pandemic. From Cockerill’s perspective, the answer is easy—"self-swabbing and self-testing,” he says. The potential for a variety of at-home tests, from STDs to cancer, is likely to be highlighted.
As for the pluses of self-swabbing for respiratory viruses, it can happen at scale and at a much lower cost during a pandemic, remarks Cockerill. On the minus side, “some people are better with their hands than others.” While the first at-home swab tests were complex, they are now highly intuitive to use, and are often used repeatedly, he quickly adds.
Studies have yet to establish if self-swabbing provides adequate specimen or if the practice is universally applicable to all viruses. Microbiologists may wonder if it can be used for different strains of COVID, or more back-of-the-throat respiratory tract infections such as the flu, says Cockerill.
Other collection methods don’t stack up particularly well against swabbing. Saliva is difficult to work with in the lab, and the aesthetics of spitting into a tube and having some of it run down the side is unappealing. Breath tests for conditions like a Helicobacter pylori infection have returned good results, but “it has not been studied enough to convince me that it is a replacement [for conventional diagnostics].”
Specimen collection is also complicated with breath tests, since they involve breathing into a bag or tube, he adds. Tests generally need to be done close to the instrument, meaning in a lab certified under the Clinical Laboratory Improvement Amendments (CLIA).
Another hot topic up for discussion by the panelists is what has been learned from the FDA’s EUA process for COVID testing, and if the approach can be applied for validating any laboratory-developed test as has been proposed by the agency, says Cockerill. “The nice thing about EUA is that it is relatively fast [e.g., 30 days] compared to the FDA [approval] pathway. The negative thing is that it is only issued during a certain ‘public emergency’ time interval, and it can be removed.”
Perhaps all FDA approval pathways will begin to adopt a “more streamlined approach,” as has been accomplished with EUAs during COVID, without obviating proper validation, Cockerill says. The “ongoing threat” from the FDA that laboratory-developed tests will be subject to new standards and restrictions has everyone nervous, he adds, but if the experience resembles how the agency has handled EUAs “maybe it won’t be so bad.”
The next big advance in diagnostic testing, as it relates to self-collection and self-testing, will be “an expansion to other diseases, especially sexually transmitted diseases,” he predicts, referencing a portable, disposable, CLIA-waived PCR product of Visby (a company he consults for) that involves self-swabbing. It’s a first—and it is proving more sensitive than the lateral flow tests that have been used for COVID.
Each of the panelists will be bringing their unique perspective and experience to the conversation, Cockerill says. Heichman, a laboratory medicine physician, helped with self-testing for the flu in the Seattle area. Marlowe was involved with testing Quest Diagnostic’s PCR test and subsequent EUA submission. Martinez can provide insights on Geisinger’s “comprehensive streamlined approach” to COVID testing. Zitterkopf can speak to speeding the enrollment of UnitedHealthcare patients and the rapid turnaround on getting institutional review board approval to launch the trial. Jeng brings his background in at-home COVID testing, as well as unique technical components including smartphone use.