CMS has a current NCD for biomarker CRC screening, using 74% sensitivity and 90% specificity as a benchmark. This means you pick up about 3/4 of cancers (relative to colonoscopy) and you send about 10 patients per 100 to a false positive based colonoscopy.
Here I expand on a prior blog and show the two new CMS options graphically.
We can show the statistical space on a probability chart. The vertical axis is specificity (and also shows "FP per 100"). The horizontal axis is the inverse of sensitivity. It also shows "cancers missed per 100." The IDEAL PLACE to be is the far upper left corner.
Since the required conditions are expressed as ≥, the look like an x,y point but define a rectangular solution space. Any given clinical trial will represent a point with a cloud for SD (such as 90% spec +-2, 85% spec +- 3).
Here is the current solution space, ≥ 74 SENS, ≥ 90 SPEC, using green:
- Bin A: SENS ≥90, SPEC≥87
- Bin B: SENS ≥ 79, SPEC ≥ 90
Here's Bin A in yellow:
And here's bin B in blue:
The argument for an efficiency frontier can be shown on this last graph. Admittedly, the void space caused between the two bin options is not too big, since one option uses 90% specificity and the other the slightly different 87% specificity. Basically, CMS is willing to go a little lower on specificity below 90% (thus sending a few extra patients to FP colonoscopy), as long as the same has at least 90% SENS, much more stringent than the old 74% sens [green dash line].
Still, if you look at the closeness to the ideal point, if CMS happily allows a test with performance "A" and one with performance "B," it should be reasonable to allow a test with performance "C."
Of course, any two dimensional chart is incomplete with regard to the policy questions. The charts just trade-off false positives and false negatives as you migrate away from the ideal point of 100% SENS, 100 SPEC at upper left. In fact, you don't probably get closer to the top left, but rather, as you move LEFT (fewer and fewer missed cases) you probably also move DOWN (more and more false positives).
And the debate isn't just between colonoscopy first or biomarker first. There are millions of people who get no testing now, certainly not colonoscopy, but also not stool-handling tests. So the blue space (or the far right dotted green space0 may be picking up 60%, 70%, 75%, of cancers in patients who otherwise get NO screening, a collateral public health issue. While - CMS is also thinking about reverse-migration, will someone planning on a 100% sensitive colonoscopy picking up precancers pivot to a 90% sensitive biomarker test...
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They say they are not reconsidering FIT, where there are different brands and different studies and a fairly wide range of reported data, some on the new chart, some too far to the right.
