On May 5, 2022, we had an article in ONCLIVE on testing challenges in cancer patients (here), and on May 4, FDA announces approval of the second-ever biomarker test for Alzheimer's disease, a CSF test (here, here).
What connects these? Remarkably, the "14 day rule" for Medicare hospital inpatient and outpatient services.
The 14 Day Rule
The 14 Day Rule is actually an interaction between two different regulations. All hospital inpatient biopsies and tests are bundled to the DRG, unless ordered 14 days after discharge. All hospital outpatient biopsies and tests are also bundled to the hospital outpatient payment, per regulation 42 CFR 419.2(b)(17), unless there is an exception. Exceptions are created not at 419.2, but at an entirely different regulation, 42 CFR 414.510, the date of service rule. The main exception is for human DNA-RNA tests.
Tests on biospecimens that are not hospital-related (from physician office or a lab draw center) are always paid fee for service and not bundled.
The ONCLIVE article discusses the 14 day rule as a barrier for cancer testing. This is especially true for inpatient biopsies (such as tissue from a lung lobectomy, or a colectomy, or nephrectomy). Payment for genomics may be delayed more than 14 days - for example, 5 days while the patient recovers in the hospital, plus 14 days after discharge, = 19 days, and that's for ordering the test, allow more time for running the test and delivering it.
For a hospital outpatient biopsy (e.g. melanoma tissue), for most cancer tests the DNA-RNA rule applies and the biopsy can now be tested and paid separately right away.
CSF - Alzheimer Proteomics Test
The Alzheimer CSF test also bumps up into this rule, as I read it.
The Fujirebio "Lumipulse" Alzheimer test is a proteomic test, an ABeta 42/40 ratio, so it's not a DNA-RNA test. The main CSF lumbar puncture code is 62270, which ran about 80,000 services per year 2015-2019 (pre COVID). But, 44% of these tests are inpatient, and 35% are E.R. and another 10% are hospital outpatient. (That tallies about 90%). For proteomic tests, all of these hospital-associated CSF biospecimens collide with the 14 day rule. Only 10% of the 80,000 tests, or 8000 tests, were in a physician office which doesn't collide with the 14 day rule, and where the test can be billed immediately.
To my knowledge, there isn't yet a specific CPT code for "amyloid biomarker lab test," nor a PLA code for this test.
In 2020, coding was changed. 62270 continues, but over half of services now bill under the new code 62328, which is lumbar puncture including imaging guidance. The coding complexifies, but the 14 day rule applies the same.
The Fujirebio test had Breakthrough review at FDA, granted in February 2019.
Per FDA, "97% of individuals with Lumipulse G β-amyloid Ratio (1-42/1-40) positive results had the presence of amyloid plaques by PET scan and 84% of individuals with negative results had a negative amyloid PET scan." Detailed FDA summary-of-effectiveness usually appears weeks or even a few months after approval (clearance). This product went through De Novo review.
ADLT Not Possible
The test isn't eligible for ADLT status, since it's not a sole source test. Even if it got ADLT status as an FDA-cleared test, FDA-cleared ADLTs don't get exemption from 14 day rule, only MAAA-type ADLTs (see 414.510).
Amyvid PET History
FDA previously approved the Lilly Amyvid PET Amyloid biomarker (and later several other brands) in 2012 (and as a PMA approval as a drug), but CMS has "non-covered" it since 2013. (There's are some paid claims for approved clinical studies - here.)
So in summary, if you have Alzheimer's disease, you can't get a PET scan, you can't get an amyloid drug (Aduhelm), and it's darn hard to get a proteomic CSF test due to bundling.
I mentioned effects of this type of bundling on innovation in a recent article. This aspect of bundling is usually left out of articles on bundling (JAMA 2022 here).