The COVID-19 pandemic has sparked some innovation in testing, but not all that innovation has made it to market. Michael Mina, an assistant professor of epidemiology at the Chan School of Public Health at Harvard University, said on an Aug. 7 conference call that the U.S. FDA’s “archaic view” of testing is impeding the use of paper strip tests he said would turn the tide in the effort to contain the pandemic.

A recent blog at the Harvard Global Health Institute said much of the emphasis on testing revolves around the question of accuracy. This position reflects an emphasis on ensuring that carriers of the SARS-CoV-2 virus don’t return to work, where the virus would bloom. Mina is described as a proponent of a test that could be provided to hundreds of millions at a cost of $1 each, but the blog cites “pushback from those who believe it would be irresponsible” to allow a test that would yield a large absolute number of false negatives.

Mina said on the conference call, “we keep trying to take [molecular] diagnostic tests and use them for public health surveillance,” an approach he said does little more than increase the bottleneck effect already in play at the labs that process those tests. Because of the turn-around times involved, such tests will do little to break the chain of transmission, even if contact tracing efforts were well situated and executed.

The better approach, Mina said, would be to “use cheap tests that are highly accurate to detect someone at the moment they are transmitting.” This would allow individuals to act to avoid further transmission, an action they cannot take when in the dark about their status.

Even if such a test were available to only a slight majority of a population, it would halt most transmission, and a vaccine would not be as desperately needed. “The holdup is that they’re defined as diagnostic test,” Mina said, and when compared to molecular testing via polymerase chain reaction testing, these inexpensive tests appear to be wildly inaccurate.

Mina said there is a national movement to have this type of rapid test redefined as a public health tool for breaking transmission rather than as a diagnostic. If the federal government stood up something analogous to Operation Warp Speed for this kind of test, “we wouldn’t need a vaccine tomorrow. We could buy ourselves years of time” for much less than is being spent now, he said.

‘Whole new way of thinking’ is needed

“We’re allowing red tape and this archaic view of testing” to allow the virus to run free, Mina said, adding, “it takes a whole new way of thinking” at federal government agencies to realize the benefit of such an approach to pandemic testing. Mina said transmission could be cut by 90%-95% within a few weeks if such a test were made sufficiently widely available.

Mina said he is frustrated by the FDA’s response to the situation. “It’s insane that we have something that could stop an epidemic, and there is no clear path to legally distribute these tests” because of the diagnostic label. The FDA is already struggling to keep up with the applications it has received under the emergency use authorization (EUA) program, and since this type of test cannot be marketed without violating the law and the regulation, “it’s illegal to save lives right now.”

The EUA process might be reasonably jettisoned, Mina said, particularly given that lab-developed tests needn’t go through the same process as test kits that are commercially distributed.

“We’re just continuing to be stuck in this regulatory landscape that was never designed for a public health emergency,” he said, adding that the federal government agencies involved are “treating it as though it’s just another day.” Several of these test strips are in trial, but even a small manufacturer could turn out a million of them each week. “The government should be recognizing the potential for these tools as a core technology,” Mina said, and invite the National Institutes of Health and other agencies along with manufacturers to develop and push this approach to market.

“There is a groundswell of support at the federal level” for this approach, Mina said, adding that he has heard from members of the House and Senate along with several governors. Still, the CMS and FDA are reluctant to make the needed regulatory changes, but he said White House senior adviser Jared Kushner is aware of these tests. It may be necessary to push the case at the Oval Office, Mina said. “Otherwise, we’re stuck in this limbo where no one feels this is their problem.”

While it is difficult to accelerate vaccine and drug research, Mina said, “this is something we can actually do at warp speed.”

Concerns over diagnostic test accuracy also increasing

Despite the recent emphasis on surveillance testing, there is also concern about the accuracy of diagnostic testing as described in an editorial appearing Aug. 6 in the New England Journal of Medicine. The authors, which include Aaron Kesselheim of Harvard University Medical School, argue that current diagnostic tests are insufficient for even diagnostic use, let alone for any other purposes.

The authors said the FDA has allowed reverse transcriptase polymerase chain reaction (RT-PCR) tests onto the market when the sponsor establishes the candidate test’s agreement with an authorized PCR test. They said the use of contrived samples or known positive samples can lead to overestimates of test sensitivity, given that swabs may not acquire infected material in routine use.

They cite a preprint review of five studies of nearly 960 subjects that individually returned a false negative rate ranging from 2% to 29%. While the quality of the underlying studies was uneven, the evidence thus derived “raises concerns about frequent false negative RT-PCR results.”

A reasonable estimate of the sensitivity of a typical PCR test for the SARS-CoV-2 virus may be closer to 70%, but when the pre-test probability of infection is in the range of 50%, such a sensitivity could yield a negative rate of 23%, which they said is “far too high to safely assume someone is uninfected.” The authors recommended that the FDA require the developer to disclose test sensitivity and specificity at the time of marketing authorization.

Another recommendation is that stakeholders and federal government agencies establish a threshold for ruling out infection “for a variety of clinical situations.” Given that such a threshold “is a value judgment, public input will be crucial.”

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