And I think, clearly, antigen tests are for diagnostic use. The goalposts of antigen vs. PCR testing are not different—“they test for different things” is a mischaracterization of what they do.
The way antigen tests are used, they are frequently used to check whether or not someone is infectious when attending a given event on the day after the test was taken. If a person is infected but there’s only were little virus in their upper respiratory system, they aren’t infectious so it’s less problematic when the test doesn’t detect that.
I somewhat like the distinction between “testing for infectiousness” and “testing for whether I have it” (especially from a public health, rather than personal healthcare, standpoint). “People want to go to parties so they want fast, even if slightly less sensitive, tests because sometimes they don’t really even care about their own health status, just whether they can reasonably party” is also a great reason to try to market the product (let party organizers or other organization police what tests they will accept or whether they will expect pre-testing), but the FDA needs to assess that sensitivity somehow. What is the standard for infectiousness that the FDA is going to use to have a second evaluation pathway if there really is a distinction with a difference here? Probably some indicator of the amount of infectious virus present. A plaque assay (yields plaque-forming units, PFU) would be great, counting infectious particles, but the test itself takes days, needs BSL-3 conditions, and is resource intensive in other ways as well. Don’t compare to PCR, compare to PFU...that’s even more demanding against would-be antigen test manufacturers. And PFU has a pretty strong relationship with Ct. Compare to PCR then!
People are rightly dissatisfied with the status quo and looking for someone to blame for the lack of tests, but the problem is not that the FDA compares to PCR, it’s the threshold they wanted. I know “evidence-based decision-making” is abused and gets a rap, but I don’t think effectively advocating for evidence-less decision-making will make us less wrong (in case that sounds too harsh, what was the alternative to PCR that was supposed to validate antigen testing for us?).
I know “evidence-based decision-making” is abused and gets a rap, but I don’t think effectively advocating for evidence-less decision-making will make us less wrong
The EU and the UK also have regulatory agencies that require evidence for accepting tests.
Assays should have a sensitivity of 90% or greater for subjects with a Ct < 25.
That means that the test has to has a sensisitivty of 90% for patients with “Very high viral load”
The world is bigger then the US. In a case like this it makes sense to look at other countries who have enough tests for everyone who wants instead of just declaring the task impossible.
This is again a threshold, not comparator, complaint. Ct values are generated by PCR. Instead of using a crosstab for all samples, this approach is to use a crosstab for a subset of samples with higher viral load. It’s reasonable! IIRC from a previous paper, this (90% of Ct<25) has a similar effect as just reducing the overall cutoff to (80% of all). It’s also reasonable to use studies from other countries or to follow other agencies, in either case the ones we think are credible, which is again about the evidence threshold. What I’ve been hammering on is that the idea these tests are so different that they’re noncomparable is not sensible.
The way antigen tests are used, they are frequently used to check whether or not someone is infectious when attending a given event on the day after the test was taken. If a person is infected but there’s only were little virus in their upper respiratory system, they aren’t infectious so it’s less problematic when the test doesn’t detect that.
I somewhat like the distinction between “testing for infectiousness” and “testing for whether I have it” (especially from a public health, rather than personal healthcare, standpoint). “People want to go to parties so they want fast, even if slightly less sensitive, tests because sometimes they don’t really even care about their own health status, just whether they can reasonably party” is also a great reason to try to market the product (let party organizers or other organization police what tests they will accept or whether they will expect pre-testing), but the FDA needs to assess that sensitivity somehow. What is the standard for infectiousness that the FDA is going to use to have a second evaluation pathway if there really is a distinction with a difference here? Probably some indicator of the amount of infectious virus present. A plaque assay (yields plaque-forming units, PFU) would be great, counting infectious particles, but the test itself takes days, needs BSL-3 conditions, and is resource intensive in other ways as well. Don’t compare to PCR, compare to PFU...that’s even more demanding against would-be antigen test manufacturers. And PFU has a pretty strong relationship with Ct. Compare to PCR then!
People are rightly dissatisfied with the status quo and looking for someone to blame for the lack of tests, but the problem is not that the FDA compares to PCR, it’s the threshold they wanted. I know “evidence-based decision-making” is abused and gets a rap, but I don’t think effectively advocating for evidence-less decision-making will make us less wrong (in case that sounds too harsh, what was the alternative to PCR that was supposed to validate antigen testing for us?).
The EU and the UK also have regulatory agencies that require evidence for accepting tests.
From https://ec.europa.eu/health/sites/default/files/preparedness_response/docs/covid-19_rat_common-list_en.pdf it seems that the alternative for using the straight comparison to PCR is:
That means that the test has to has a sensisitivty of 90% for patients with “Very high viral load”
The world is bigger then the US. In a case like this it makes sense to look at other countries who have enough tests for everyone who wants instead of just declaring the task impossible.
This is again a threshold, not comparator, complaint. Ct values are generated by PCR. Instead of using a crosstab for all samples, this approach is to use a crosstab for a subset of samples with higher viral load. It’s reasonable! IIRC from a previous paper, this (90% of Ct<25) has a similar effect as just reducing the overall cutoff to (80% of all). It’s also reasonable to use studies from other countries or to follow other agencies, in either case the ones we think are credible, which is again about the evidence threshold. What I’ve been hammering on is that the idea these tests are so different that they’re noncomparable is not sensible.