In brief, a New York Times story today describes elite Manhattan hospitals - like Lenox Hill - charging $3000 for single COVID tests. They note that Congress requires COVID tests to be covered without a fee to the patient, but assert there is price gouging by some suppliers.
An interesting short open-access article in JAMA this week by Edara et al:
https://jamanetwork.com/journals/jama/fullarticle/2777898
Two findings. One, vaccinated persons (Moderna version) produced stronger neutralizing antibodies than either new or recent COVID patients. Second, the antibodies performed well regardless which of the four viruses was used in the cell culture system. Click to enlarge.
Note that in the left panel, a few hospital patients 10 days into their illness still had minimal detectable neutralizing antibodies (their dots sit at bottom in each column.) Note also that the convalescing patients (middle panel) were several months post infection, and expected to have gradually falling antibodies, whereas the Moderna patients (right panel) were exactly 2 weeks after their second injection, which might be the natural "peak antibody" timepoint.
As AMA prepares for its May 2021 CPT meeting, it has released the agenda of code proposals. Interested stakeholders can obtain a copy of the application packets by requested by April 15, and then, responding by April 22. AMA screens the requests to comment for being a validly involved stakeholder (e.g. not a journalist, not just curious, etc). For example, a competitor company is a valid stakeholder.
See the code proposal list here:
https://www.ama-assn.org/system/files/2021-03/cpt-panel-may-2021-agenda.pdf
It might be a bit scary for owners of Cat III codes that there are ~17 new applications for these codes, but I only counted 1 application to elevate a Cat III to a Cat I code and 17 applications for simple deletion of Cat III codes.
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Lab test items had an earlier comment cycle in the beginning of March (entry point here) to allow the comments be available for pre-May subgroups for lab tests (Molecular Pathology Advisory Group MPAG, Pathology Coding Caucus PCC.)
We periodically hear that too many genetic studies are overpopulated with people of white European backgrounds (e.g. here). This week, a paper by MGH's Alicia Martin et al. is the basis of a lead story by Christie Rizk at Genomeweb.
They [Martin et al.] further found that 1x sequencing was among the more affordable options, costing less and performing similarly to or better than commonly used lower-density arrays such as the Illumina GSA.They also noted that the GSA is composed of variants that are most common in European populations and so it's therefore not the most appropriate technology for studies of participants with primarily non-European ancestry.Aside from cost, low-coverage sequencing had several distinct advantages compared to GWAS arrays, particularly more accurate identification of genetic variation across the allele frequency spectrum in underrepresented populations.In the NeuroGAP-Psychosis data, the researchers found that 38 percent of common variants could not be imputed from the 1000 Genomes Phase III data, most likely because of a lack of eastern and southern African diversity in that panel.
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Three interesting readings came across my desk this weekend.
In December 2019, Congress delayed PAMA implementation by a year (and in Spring 2020, by an additional year). However, in return, Congress required the federal advisory body MedPAC to report on PAMA policy and issues by April 2021.
That day has come.
PAMA TOPIC is scheduled from 11:00am to 12:30pm on April 2 (ET).
MedPAC discussed lab pricing under PAMA in September 2020 (entry point here). Their discussion of lab pricing falls in the context of increased molecular pathology spending, in round numbers from $500M in 2017 to $1B in 2018 to $1.5B in 2020. Both OIG and MedPAC have pointed responsibilty to what they call "expensive tests." OIG here. In is annual multi-topic report to Congress earlier in March, MedPAC suggested Congress or CMS restrict telemedicine orders of expensive DME or lab tests, due to program vulnerabilities revealed by "Operation Double Helix." Operation Double Helix asserted there had recently been $2B of genetic test fraud, much of it by fly by night telemedicine orders. ("...fraudulent genetic cancer testing has resulted in charges in five federal districts against 35 defendants associated with dozens of telemedicine companies and cancer genetic testing laboratories.") For an example of a conviction of this type of telemarketing/telemedicine scheme after a 4-day trial, here.
The assertions about telemedicine misuse conflict with the complexity of genetic testing and the need for expertise (and, for commercial insurers, often preauthorization), which can often be provided by telemedicine by expert genetic counselors and physicians. See for example the highly legitimate acquisition of Trapelo's precision oncology services and platform by NeoGenomics last week - here. see also the alliance between Foundation Medicine and Informed DNA announced earlier this month - here.
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| Practically100% of 81408 Spending, 2019, in Novitas & FCSO MACs |
In December 2019 legislation, Congress delayed PAMA but required MedPAC to report on its implementation, options to streamline data collection. However, Congress added a phrase allowing MedPAC to also report on any issues it deemed relevant.
The PAMA delay is confusing. Originally, national lab prices from 1H2019 would be submitted to CMS in 1H2020 to set prices in 2021, 2022, 2023. Now, lab price data from 1H2019 will be submitted to CMS in 1H2022 to set prices in 2023, 2024, 2025.
Medicare has a unique type of provider (created by regulation not statute) called IDTF - Independent Diagnostic Testing Facility.
For example, this is how iRhythm is enrolled as a Medicare medical provider, as an "IDTF."
HeartFlow
One of the most innovative providers in cardiology imaging is HeartFlow, which provides sophisticated computed fractional flow reserve based on prior high resolution cardiac CT imaging. Website here.
As a cutting-edge innovator, Heartflow faced a series of problems with CMS that are a matter of public record.
I noticed that Noridian has a brand new pending LCD for HeartFlow which will be effective in April (L36615, A58097). Seeing those LCDs, it led me to as, Is HearFlow enrolled as an IDTF now?
Is Heartflow Enrolled as an IDTF now?
Start by finding the NPI Number
First, it's really easy to lookup an NPI number - you can google Heartflow and NPI, or go to a database.
The NPI for Heartflow is 1982019980.
What Doesn't Work
There's a CMS Physician Compare database that lets you look up whether a physician NPI is enrolled in Medicare, or a hospice, but this dataset doesn't include IDTF as a category to look up within.
https://www.medicare.gov/care-compare/?providerType=Physician&redirect=true
What Did Work
Support staff at Noridian pointed me to a public database called MEDPARD that gives LOTS of types of providers, many more than the prior link. Use this Noridian link:
http://norweb.noridian.com/medpard/main.aspx
Here, the drop down menu gives you all the physician specialties (hematologist, internal medicine, endocrinology), plus a plethora of institutional categories (hospital, hospice), plus... IDTF.
Select IDTF and select Northern California, and you get a list of 200 IDTFs, one of which is HeartFlow.
Bingo!
Footnotes
Misnamed? MEDPARD is "Medicare Participating Physician Directory," but as just indicated, it seems to be misnamed, in as much as it displays a large variety of provider types besides physicians.
Other MACs, Different Windows to MEDPARD. I may have been lucky with the Noridian webpage into MEDPARD; I tried to search the MEDPARD database at the NGS MAC for any IDTFs in Illinois and got "0" which seems unlikely.
I tried Novitas for Texas, but it required a county to be named in Texas, before initiating its Medpard search, and when I picked one by chance, it gave an error message.
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* Based on information I got via FOIA, these enrollment challenges between HeartFlow and Noridian continued past 2017 into 2018 or 2019.
VIDEOS POSTED:
Did you know that Los Angeles and Orange Counties are one of the top several investment zones for digital health? See the 4th Annual Digital Health Conference, sponsored by SoCalBio, the Southern California Biomedical Council.
The SoCalBio website is here.
The page for the digital health conference is here. As you scroll down, you'll see the full agenda.
The conference runs March 23, 24, 25 (Tuesday, Wednesday, Thursday). The three-day list of topics and speakers is pretty impressive.
I'm speaking on a panel on digital health policy and payers - 3 pm PT on Wednesday, March 24. Our topic is, "Digital Health - Regulatory and Reimbursement Issues to Watch." We'll have myself, Vivek Thakkar, Digital Health Program Director, Genentech; Rick Gannotta, Chief Healthcare Administrative Officer, Masimo; Evan Seigel, CEO, Ground Zero Pharmaceuticals; and the panel is moderated by Peter Blaisdell, Chair, SoCalBio Innovation Catalyst Program.
See a webinar convened by Dark Report on Thursday, March 25, 1 ET (10 PT):
"State of the Genetic Testing Marketplace--Getting Paid for All Your Lab's Genetic Test Claims: What's Changing, What's Not, What's Working Best."
Home page is here.
Registration page is here.
Discount code, GENTEST.
Trapelo Health is an interesting organization that aims to improve the patient experience for cancer patients, reducing complexity and making decisions more clear
Trapelo offers some interesting media collateral. (Email sign-up required).
I was on a call recently with a startup lab company that has a new technology it asserts will save money. The startup doesn't have any modeling or data yet, but was making the general argument that better diagnostics save money.
Do diagnostics save money? Well, sometimes yes, for sure, but not necessarily. I put together some citations and I'm logging them here.
Do Preventive Services Save Money?
On the topic of preventive services saving money, much has been written. In general, preventive services that are widely adoptive are at least cost effective (the cost in dollars per each life year saved), but not literally cost-saving. See a New England Journal article from 2008 here. See a 2012 Congressional Budget Office report (discussed in NEJM) here. See a 2018 Aaron Carroll article here.
Looking at imaging, mammography is beneficial, but likely not literally cost-saving, with costs per life year in the $10,000-$70,000 range (here, here).
For one example, when smoking prevention avoids a lung cancer death, that person lives on to die of something else - a stroke, colon cancer, Alzheimer's disease, and so on.
A CMS-funded study in 2019 seemed to show that 7 different colorectal cancer prevention strategies all saved money (at least a bit, a bit better than cost-neutral) against no-screening, but some of the more expensive methods were less effective (per this study) and ;ess cost-effective than less-expensive methods. So just because a method is more accurate and more expensive, it is not necessarily more cost-saving or more cost-effective. (I think this publication has had rebuttals; take it as a for-example).
Do Diagnostic Tests Save Money?
Sure, some do. See Pimentale 2016 for cost savings with better diagnosis of irritable bowel syndrome (here). See Pliakos 2018 on saving money with more rapid diagnosis of blood stream infections (here.)
But is that the big picture? If we want a general answer, we should probably turn to a comprehensive review. Fang, Neumann et al at Tufts did a 2011 comprehensive systematic review of diagnostic test cost effectiveness (here). Reviewing 141 studies, about 15% reported results that were literally cost-saving; others were "cost-effective." See figure, in which the left-most column is the number of the tests reported as "cost-saving:"
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| Fang et al. 2011 Fig 3 |
In J Clin Oncol in 2018, Wang et al. looked at numerous cost effectiveness studies of a 21-gene breast cancer recurrence test (here). They reported that they found a range of cost effectiveness values, critiqued the methodology of some reports, and reported that the two studies with the "worst" cost effectiveness (>$50,000 per life year), were "not" industry-funded. A few studies, but only a few out of 20 or so, reported "cost savings" per se.
Most recently, writing in Value in Health in 2021, Koldehoff et al. looking at the cost-effectiveness of genetic testing for breast and ovarian cancer risk (e.g. BRCA testing) - here. BRCA testing could run from being cost-saving to have a cost of $22,000 per life-year (QALY). In other settings, multi-gene testing ran from $15,000/QALY to $70,000/QALY, depending on scenarios and health care costs in selected countries.
Are diagnostic tests cost-saving? "It depends," and if you are depending on an insurer like BCBS to pay you a lot more, "because you are saving the payer billions in costs," they'll probably require some convincing.
The Personalized Medicine Coalition (PMC) and the consultancy Health Advances have published a landmark study on how U.S. medical systems are integrating (or failing to integrate) personalized medicine into their healthcare delivery and workflow.
The work was previewed at the November 2019 PMC annual meeting in Boston.
See the open access article at J Pers Med online here (PDF, 13 pp).
See the March 16, 2021 press release at PMC here.
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Each spring, MEDPAC releases a lengthy annual Report to Congress. This year it weighs in at 531pp.
Comments ran to mid April and CMS posted 97 comments on April 22 - here. Advamed comment here.
CMS will post final decision on MCIT by about May 15.
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On Friday, March 12, after market close, CMS announced it was delaying implementation of the Medicare Coverage for Innovative Technology (MCIT) program. The program, which was released as final by the Trump administration in mid-January, would provide 4 years of coverage for any devices cleared by the FDA as "breakthrough pathway" devices, from a start date of 3/15/2019. The regulation also "codified" longstanding CMS rules defining "reasonable and necessary" as a coverage criterion.
The delay was pre-posted as a PDF on March 12 and published in the Federal Register on March 17 published in the Federal Register on Wednesday, March 17. Home page for the new rule here. See the green box, "Submit A Formal Comment." PDF of rule here. Citation, 86 Fed Reg 14542-45. Comments due April 16.
The change is styled as a "60 day delay with comment period." The new implementation date, if nothing else changes, will be May 15 instead of March 15. Note that the regulations for MCIT have already, technically, been finalized for Code of Federal Regulations, all ready to launch (42 CFR 405.601ff). However, perhaps because of this new rule, the January "final regulations" for MCIT don't appear in the eCFR (here).
The publication today was not strictly "pro forma." The administration gives several types of concerns.
Operationalizing the Rule. For example, CMS notes the rule might be hard to operationalize, since it promises coverage "from the first day of FDA approval." I would have assumed, or the rule stated, that existing coding and payment rules apply, and if a new code was needed, it would take a few months and providers would have to hold claims. For example, NCDs are effective "the day they appear" but CMS often takes months to issue full-fledged codes or coding rules. On the other hand, if a device was bundled, it would be "covered" but without any net impact. CMS adds that as the implementation drew closer, it realized it had "underestimated" operational challenges.
Bruce's takeaway: I assumed "coverage" would be first-day but "claims" would take several months to implement, sometimes. But that has occurred in other situations. A lot of things might be "covered" but no added payment to a outpatient or inpatient bundle.
DME Rule. CMS also cites some overlapped with a proposed, but not finalized DME rule that appeared last fall.
Bruce's takeaway: I've read the DME rule and didn't see much conflict.
Volume. CMS notes that breakthrough device volume was estimated, in the rule, by CMS, at 2-5 devices per year. This made no sense to me, since a July 2020 publication had reported there were 200+ devices in the MCIT pathway already at that time. CMS cites public remarks by FDA in February 2021 that 400+ devices were in the breakthrough pathway. FDA here.
Bruce's takeaway: Yup, the CMS estimate of 2 devices a year seemed oddly low.
Bruce's takeaway: The FDA devices annual report page is worth seeing on its own.
Validation in the Elderly; first do no harm. CMS notes that some devices might not be well-validated in the elderly and there could be "patient protection issues" which would point toward non-coverage of the device.
Did your complaint get ignored? CMS notes that in the original public comments, some parties had asked for more details on implementation. CMS gives any negative stakeholders a chance to assert that their negative views were not properly discussed, aired, and dealt with in the CMS final rule.
The rule specifically cites criticisms that appeared in New York Times and Health Affairs.
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Footnotes.
Diagnostics Are In (for now). Whereas the August rule proposal had been ambiguous about Diagnostics coverage, the final rule in January made clear it applied to all FDA breakthrough devices, including diagnostic ones.
NEJM Article. After my original March 12 blog, I became aware of a March 10 paper in NEJM critical of MCIT, Rathi, Johnston et al. here.
This quarter, Medicare added a 9th test to its list of "ADLT" tests - advanced diagnostic laboratory tests. ADLTs are a specially defined type of lab test whose code is priced initially at its market list price (assuming it hadn't been previously priced on the CMS fee schedule) then annually repriced to its market median price.
The ninth test is Code 0239U, Foundation Medicine Liquid CDx test. It was approved 1/25/2021, with its "New ADLT Initial Period" to run 4/1/2021 to 12/31/2021. Prior to 4/1, the test is "contractor priced." The ADLT price will be $3,500.
Historical note - The initial paraffin-based FMI CDx test was the "first ADLT," with code 0037U, and granted ADLT initial pricing status from 7/1/2018 to 3/31/2019.
ADLT 0239U was applied-for July 2020, released October 2020, effective January 2021. The FDA approval was October 26, 2020 (here). It was an FDA "breakthrough" device. The 64 page safety summary P200006B is here. An additional November 6, 40 page safety summary P200016B is here, adding genes. (I believe that FDA has to issue new "P" PMA numbers rather than updating the original - ?). The ADLT application at CMS would have waited til the actual FDA approval dates, I think, at which point it was too late to make the deadline for a January 1 kickoff ADLT pricing date.
See the updated ADLT price list here:
https://www.cms.gov/files/document/advanced-diagnostic-laboratory-tests-under-medicare-clfs.pdf
Quirks of ADLT
The ADLT pricing process is driven by the creation of a CPT code. If a lab test has a CPT code (including a PLA code) that completes the annual new code pricing process before it completes the ADLT process, then the CLFS fee schedule price will apply rather than the rule regarding the new ADLT's list price. So usually, you want to time your code creation to ensure it will finish the ADLT pricing process before CMS handles the code through the traditional gapfill/crosswalk annual process.
Due to tricky ways that the ADLT regulation is written, the initial 9 month ADLT price will be the lowest price publicly available on the first day the test is available for ordering. For example, as I read it, if your price on Day One is $3000 list, $500 for uninsured patients, then your ADLT initial price will be $500.
On the other hand - as I read it - if your Day One price is $3000 list, and on Day Three you add a $500 uninsured price, only your Day One price is used to set the ADLT initial price at $3000.
See the regulation at 42 CFR 414.522, but paying extra-special attention to the definitions of the wording found there.
ADLT's are priced annually, based on reported market prices, but it's a slow process. As I understand it, for example, 1H2018 might be a claims collection period for the ADLT, 1Q2019 a reporting period, and January 1, 2020, the new ADLT price date. So it's annual, but slow.
Two ADLT prices have been reset downward by the PAMA annual process, with Myriad test 0172U Myriad My Choice CDx [FDA] dropping from $4040 initial to $3030, and Myriad test 0090 MyPath Melanoma dropping from $1950 to $1755.
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CMS releases new local contractor policies and articles on Thursday, and yesterday, MolDx released an article with the concise title, "Algorithm Definition." It's logged as CMS article A58650.
Find the link here:
I've cut-pasted the article in full within this blog. It has effective date, 3/11/2021.
Other Definitions of Algorithm
CMS also defines algorithm for a lab test by law at 42 CFR 414.502, but it's beyond my scope to assess if there's a meaningful difference between 414.502 and A58650. I've clipped the 414.502 definition at bottom.
AMA defines algorithm in the CPT code booking regarding MAAA tests - I've also clipped this at bottom.
International Group - Polygenic Risk Scores
In related news, The Clinical Genomics Resource Complex Disease Working Group has published a paper in Nature on defining polygenic risk scores. Nature here, Genomeweb here.
Palmetto MolDx Article Text:
This contractor defines an algorithm, as a distinct component of clinical laboratory processes, as follows:
An algorithm may be considered a clinically valuable and independent component of a laboratory process when ALL the following conditions are met:
Either be required for the analytical result, OR
If adjunct to the analytical result as a post-analytical process, the calculation itself must be independently found to be reasonable and necessary apart from the other components of the test.
Examples. [Note that examples 2,3,4 are of "non-algorithms".]
Log on to the Palmetto MolDx Diagnostics Exchange this week, and you'll see this splash screen:
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A few weeks ago, I had the chance to write and post a 25-page white paper on advanced genomics coding and reimbursement, focusing on the evolving position of PLA codes - here.
Looking at genome-wide services, like exome, genome, and cytogenomics, I noticed something unusual. There were at least three codes for germline (constitutional) cytogenomics using NGS, but there was no corresponding Category 1 CPT code. This is in contrast to various codes for pharmacogenetics, hereditary panels, exome or genome, where the PLA codes are at least related to an existing CPT code. IO was pulled back to this topic last week, when AMA posted proposed CPT codes for May 2021, and there is now a proposal for a low-pass NGS Category I code (here).
Interested parties can see the AMA CPT proposal here and follow instructions to request permission to comment by March 12.
Coding Today
There are several cytogenomics codes today, but all specify "microarray" cytogenomics as the technological method. These are 81228, 81229 (microarray with SNPs), and 81277 (tumor microarray), all designed to report chromosomal abnormalities rather than point mutations. They're priced by CMS at $900, $1160,. and $1160.
In the PLA world, there are codes for sequencing-based cytogenomics, of which I count at least three for germline tests, being 0012U (Mayo), 0156U (NY Genome Center), and 0209U (Perkin-Elmer). The Mayo code is priced by CMS at $2515, while the NYGC and Perkin codes are newer and still in the 2021 gapfill process at the MACs.
In 2020, ACMG published technical standards for interpretation and reporting of constitutional (germline) copy-number variants (Riggs et al.), and remark,
"Tremendous strides have been made in understanding the effects of copy-number variants (CNVs) in both affected individuals and the general population...continued broad implementation of array and next-generation sequencing–based technologies will expand the types of CNVs encountered in the clinical setting."
(I recall the first time I read a headline about NGS-based chromosome analysis 6 or 8 years ago, and in the interim it sounds like it's clearly come of age.)
New Publications
New to me is Chaubey et al., J Molec Diagn 22:823-40 (2020). This team at Perkin-Elmer assessed 409 cases for microarray and low pass genome sequencing for CNV, and suggest that NGS methods are economical at scale and potentially more accurate (depending on copy depth; they use 5X) than microarray. Find it open access here.
Chaubey et al. conclude,
Several cases with pathogenic CNVs were detected that were missed by CMA. This study demonstrates that LP-GS (5X GS) was able to reliably detect absence of heterozygosity, microdeletion/microduplication syndromes, and intragenic CNVs with higher coverage and resolution over the genome. Because of lower cost, higher resolution, and greater sensitivity of this test, our study in combination with other reports could be used in an evidence-based review by professional societies to recommend replacing CMAs.
A lab that is new to me is Gencove, whose website headline is "Industrial-scale genome sequencing." They cite collaborations with Broad, Coriell, and others. The website states, "Gencove’s low-pass sequencing platform is setting the new standard for high-throughput genomics research and diagnostics applications."
See a new open-access publication Li et al. using 0.5X and 1X LP-NGS and published in Genome Research, February 2021 - here. These authors summarize, "We conclude that low-pass sequencing plus imputation, in addition to providing a substantial increase in statistical power for genome wide association studies, provides increased accuracy for polygenic risk prediction at effective coverages of ~0.5× and higher compared to the Illumina Global Screening Array."
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Traditionally in tumors, we've used NGS to detect mutations or indels in 50 to 500 genes. Another aspect of tumor biology is "chromothripsis," the widespread disruption of chromosomal structure in some cancers. See a March 2021 paper in Nature by Shoshani et al. here. See a review on cell biology of chromothripsis by Kolb, 2021, here. See a new March 2021 paper in NEJM on the need for whole-genome sequencing in myeloid cancers, Duncavage et al., here. Put low-pass NGS (0.25X) together with chromothripsis in a myeloma paper from Belgium by Rengifo, 2021, here. Separately, see Zhao et al. 2021 on chrotin modification in cancer here.
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Update May 18, 2021. We've talked here about microarrays and low-pass NGS. Another entry in the field is "optical genome mapping" - OGM - not to be confused with OMG - see a review on Bionano's work in this space in Genomeweb, May 14, here.
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For a retrospective on how much we already knew on tumor chromosomes in 2003, see Albertson, 2003, Nature Genetics, here.
Very brief blog. On March 6, 2021, NYT published an excellent article with first-class graphics on the spread of COVID variants in the US. Multiple references to work performed under a federal contract by HELIX. In addition, the article references an online 24 page PDF (Feb 2021) from the Johns Hopkins Center for Health Security.
NYT here -
https://www.nytimes.com/interactive/2021/03/06/us/coronavirus-variant-sequencing.html
And Johns Hopkins 24 page PDF here -
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| JH PDF (Feb 2021) |
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| NYT Graphic - March 6 |
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| Take Home: B1117 Mostly 20% by March 3 In All These States |